From 09644fb5e2ccb4ba9c4288fdac3f3323be39e98e Mon Sep 17 00:00:00 2001 From: Susheel Varma Date: Fri, 14 Jun 2024 00:49:49 +0000 Subject: [PATCH] Commit new papers --- data/covid/ack-preprints.csv | 30 +- data/covid/papers.csv | 68 +- data/papers.csv | 482 +-- data/papers.json | 7594 +++++++++++++++++----------------- 4 files changed, 4087 insertions(+), 4087 deletions(-) diff --git a/data/covid/ack-preprints.csv b/data/covid/ack-preprints.csv index 622b768e..ce0ba2a9 100644 --- a/data/covid/ack-preprints.csv +++ b/data/covid/ack-preprints.csv @@ -71,8 +71,8 @@ PPR607058,https://doi.org/10.2139/ssrn.4082927,Waning of mRNA Boosters after Hom PPR471508,https://doi.org/10.1101/2022.03.22.22271707,Vitamin D Supplements for Prevention of COVID-19 or other Acute Respiratory Infections: a Phase 3 Randomised Controlled Trial (CORONAVIT),"Jolliffe DA, Holt H, Greenig M, Talaei M, Perdek N, Pfeffer P, Vivaldi G, Maltby S, Symons J, Barlow NL, Normandale A, Garcha R, Richter AG, Faustini SE, Orton C, Ford D, Lyons RA, Davies GA, Kee F, Griffiths CJ, Norrie J, Sheikh A, Shaheen SO, Relton C, Martineau AR.",,No Journal Info,2022,2022-03-23,Y,,,,"

ABSTRACT

OBJECTIVES

To determine whether population-level implementation of a test-and- treat approach to correction of sub-optimal vitamin D status (25-hydroxyvitamin D [25(OH)D] <75 nmol/L) influences risk of all-cause acute respiratory infection (ARI) or coronavirus disease 2019 (COVID-19).

DESIGN

Phase 3 open-label randomised controlled trial (CORONAVIT) utilising trials-within-cohorts (TwiCs) methodology.

SETTING

United Kingdom.

PARTICIPANTS

6200 adults aged 16 years or older, who were not already taking vitamin D supplements at baseline.

INTERVENTIONS

Offer of a postal finger-prick test of blood 25(OH)D concentration with provision of a 6-month supply of higher-dose vitamin D (3200 IU/day, n=1550) or lower-dose vitamin D (800 IU/day, n=1550) to those with blood 25(OH)D concentration <75 nmol/L, vs. no offer of testing or supplementation (n=3100). Follow-up was from 17 th December 2020 to 16 th June 2021.

MAIN OUTCOME MEASURES

The primary outcome was the proportion of participants experiencing at least one doctor- or swab test-confirmed ARI of any cause. Secondary outcomes included the proportion of participants developing swab test-confirmed COVID-19. Logistic regression was used to calculate odds ratios and associated 95% confidence intervals.

RESULTS

Of 3100 participants offered 25(OH)D testing, 2958 (95.4%) accepted, and 2690 (86.8%) had 25(OH)D <75 nmol/L and were sent vitamin D supplements (1356 higher-dose, 1334 lower-dose). 76 (5.0%) vs. 87 (5.7%) vs. 136 (4.6%) participants in higher-dose vs. lower-dose vs. no offer groups experienced at least one ARI of any cause (odds ratio [OR] for higher-dose vs. no offer 1.09, 95% CI 0.82-1.46; lower-dose vs. no offer 1.26, 0.96-1.66). 45 (3.0%) vs. 55 (3.6%) vs. 78 (2.6%) participants in higher-dose vs. lower-dose vs. no offer groups developed COVID-19 (OR for higher-dose vs. no offer 1.13, 0.78-1.63; lower-dose vs. no offer 1.39, 0.98-1.97).

CONCLUSIONS

Among adults with a high baseline prevalence of sub-optimal vitamin D status, implementation of a population-level test-and-treat approach to vitamin D replacement did not reduce risk of all-cause ARI or COVID-19.

TRIAL REGISTRATION

ClinicalTrials.gov no. NCT04579640

SUMMARY BOX

What is already known on this topic?

Vitamin D metabolites support innate immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other respiratory pathogens. Sub-optimal vitamin D status (25-hydroxyvitamin D <75 nmol/L) associates with increased susceptibility to all-cause acute respiratory infections (ARI) and coronavirus disease 2019 (COVID-19). Phase 3 randomised controlled trials of vitamin D to prevent COVID-19 have not yet reported.

What this study adds

This phase 3 randomised controlled trial, including 6200 participants, shows that implementation of a population-level test-and-treat approach to oral vitamin D replacement at a dose of 800 IU or 3200 IU per day did not reduce risk of all-cause ARI or COVID-19 among adults with a high baseline prevalence of sub-optimal vitamin D status.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2022/06/24/2022.03.22.22271707.full.pdf; doi:https://doi.org/10.1101/2022.03.22.22271707; html:https://europepmc.org/article/PPR/PPR471508; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR471508&type=FILE&fileName=EMS149098-pdf.pdf&mimeType=application/pdf PPR530169,https://doi.org/10.1101/2022.08.08.22278532,Clinical effectiveness of SARS-CoV-2 booster vaccine against Omicron infection in residents and staff of Long-Term Care Facilities: a prospective cohort study (VIVALDI),"Stirrup O, Shrotri M, Adams NL, Krutikov M, Nacer-Laidi H, Azmi B, Palmer T, Fuller C, Irwin-Singer A, Baynton V, Tut G, Moss P, Hayward A, Copas A, Shallcross L.",,No Journal Info,2022,2022-08-09,Y,,,,"

Background

Successive SARS-CoV-2 variants have caused severe disease in long-term care facility (LTCF) residents. Primary vaccination provides strong short-term protection, but data are limited on duration of protection following booster vaccines, particularly against the Omicron variant. We investigated effectiveness of booster vaccination against infections, hospitalisations and deaths among LTCF residents and staff in England.

Methods

We included residents and staff of LTCFs within the VIVALDI study ( ISRCTN 14447421 ) who underwent routine, asymptomatic testing (December 12 2021-March 31 2022). Cox regression was used to estimate relative hazards of SARS-CoV-2 infection, and associated hospitalisation and death at 0-13, 14-48, 49-83 and 84 days after dose 3 of SARS-CoV-2 vaccination compared to 2 doses (after 84+ days), stratified by previous SARS-CoV-2 infection and adjusting for age, sex, LTCF capacity and local SARS-CoV-2 incidence.

Results

14175 residents and 19973 staff were included. In residents without prior SARS-CoV-2 infection, infection risk was reduced 0-83 days after first booster, but no protection was apparent after 84 days. Additional protection following booster vaccination waned, but was still present at 84+ days for COVID-associated hospitalisation (aHR: 0.47, 0.24-0.89) and death (aHR: 0.37, 0.21-0.62). Most residents (64.4%) had received primary course of AstraZeneca, but this did not impact on pre- or post-booster risks. Staff showed a similar pattern of waning booster effectiveness against infection, with few hospitalisations and no deaths.

Conclusions

Booster vaccination provides sustained protection against severe outcomes following infection with the Omicron variant, but no protection against infection from 3 months onwards. Ongoing surveillance for SARS-CoV-2 in LTCFs is crucial.

Summary

The COVID-19 pandemic has severely impacted residents in long-term care facilities (LTCFs). Booster vaccination provides sustained moderate protection against severe outcomes, but no protection against infection was apparent from around 3 months onwards. Ongoing surveillance in LTCFs is crucial.",,pdf:https://discovery.ucl.ac.uk/id/eprint/10162662/1/ofac694.pdf; doi:https://doi.org/10.1101/2022.08.08.22278532; html:https://europepmc.org/article/PPR/PPR530169; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR530169&type=FILE&fileName=EMS152512-pdf.pdf&mimeType=application/pdf PPR350007,https://doi.org/10.1101/2021.05.27.21257032,How immunity from and interaction with seasonal coronaviruses can shape SARS-CoV-2 epidemiology,"Waterlow NR, van Leeuwen E, Davies NG, Flasche S, Eggo RM, CMMID COVID-19 working group.",,No Journal Info,2021,2021-05-31,Y,,,,"We hypothesised that cross-protection from seasonal epidemics of human coronaviruses (HCoVs) could have affected SARS-CoV-2 transmission, including generating reduced susceptibility in children. To determine what the pre-pandemic distribution of immunity to HCoVs was, we fitted a mathematical model to 6 years of seasonal coronavirus surveillance data from England and Wales. We estimated a duration of immunity to seasonal HCoVs of 7.3 years (95%CI 6.8 - 7.9) and show that, while cross-protection between HCoV and SARS-CoV-2 may contribute to the age distribution, it is insufficient to explain the age pattern of SARS-CoV-2 infections in the first wave of the pandemic in England and Wales. Projections from our model illustrate how different strengths of cross-protection between circulating coronaviruses could determine the frequency and magnitude of SARS-CoV-2 epidemics over the coming decade, as well as the potential impact of cross-protection on future seasonal coronavirus transmission.

Significance statement:

Cross-protection from seasonal epidemics of human coronaviruses (HCoVs) has been hypothesised to contribute to the relative sparing of children during the early phase of the pandemic. Testing this relies on understanding the pre-pandemic age-distribution of recent HCoV infections, but little is known about their dynamics. Using England and Wales as a case study, we use a transmission model to estimate the duration of immunity to seasonal coronaviruses, and show how cross-protection could have affected the age distribution of susceptibility during the first wave, and alter SARS-CoV-2 transmission patterns over the coming decade.",,doi:https://doi.org/10.1073/pnas.2108395118; doi:https://doi.org/10.1101/2021.05.27.21257032; html:https://europepmc.org/article/PPR/PPR350007; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR350007&type=FILE&fileName=EMS126822-pdf.pdf&mimeType=application/pdf -PPR712319,https://doi.org/10.21203/rs.3.rs-3209706/v1,The cost of primary care consultations associated with long COVID in non-hospitalised adults: a retrospective cohort study using UK primary care data,"Tufts J, Guan N, Zemedikun D, Subramanian A, Gokhale K, Myles P, Williams T, Marshall T, Calvert M, Matthews K, Nirantharakumar K, Jackson L, Haroon S.",,No Journal Info,2023,2023-08-14,Y,,,,"

Background:

The economic impact of managing long COVID in primary care is unknown. We estimated the costs of primary care consultations associated with long COVID and explored the relationship between risk factors and costs. Methods Data were obtained on non-hospitalised adults from the Clinical Practice Research Datalink Aurum primary care database. We used propensity score matching with an incremental cost method to estimate additional primary care consultation costs associated with long COVID (12 weeks after COVID-19) at an individual and UK national level. We applied multivariable regression models to estimate the association between risk factors and consultations costs beyond 12 weeks from acute COVID-19. Results Based on an analysis of 472,173 patients with Covid-19 and 472,173 unexposed individuals, the annual incremental cost of primary care consultations associated with long COVID was £2.44 per patient and £23,382,452 at the national level. Among patients with COVID-19, a long COVID diagnosis and longer-term reporting of symptoms were associated with a 43% and 44% increase in primary care consultation costs respectively, compared to patients without long COVID symptoms. Older age, female sex, obesity, being from a white ethnic group, comorbidities and prior consultation frequency were all associated with increased primary care consultation costs. Conclusions The costs of primary care consultations associated with long COVID in non-hospitalised adults are substantial. Costs are significantly higher among those diagnosed with long COVID, those with long COVID symptoms, older adults, females, and those with obesity and comorbidities.",,doi:https://doi.org/10.21203/rs.3.rs-3209706/v1; html:https://europepmc.org/article/PPR/PPR712319; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR712319&type=FILE&fileName=EMS187055-pdf.pdf&mimeType=application/pdf PPR450800,https://doi.org/10.1101/2022.02.03.22270365,Post-peak dynamics of a national Omicron SARS-CoV-2 epidemic during January 2022,"Elliott P, Eales O, Bodinier B, Tang D, Wang H, Jonnerby J, Haw D, Elliott J, Whitaker M, Walters CE, Atchison C, Diggle PJ, Page AJ, Trotter AJ, Ashby D, Barclay W, Taylor G, Ward H, Darzi A, Cooke GS, Chadeau-Hyam M, Donnelly CA.",,No Journal Info,2022,2022-02-06,Y,,,,"

Background

Rapid transmission of the SARS-CoV-2 Omicron variant has led to the highest ever recorded case incidence levels in many countries around the world.

Methods

The REal-time Assessment of Community Transmission-1 (REACT-1) study has been characterising the transmission of the SARS-CoV-2 virus using RT-PCR test results from self-administered throat and nose swabs from randomly-selected participants in England at ages 5 years and over, approximately monthly since May 2020. Round 17 data were collected between 5 and 20 January 2022 and provide data on the temporal, socio-demographic and geographical spread of the virus, viral loads and viral genome sequence data for positive swabs.

Results

From 102,174 valid tests in round 17, weighted prevalence of swab positivity was 4.41% (95% credible interval [CrI], 4.25% to 4.56%), which is over three-fold higher than in December 2021 in England. Of 3,028 sequenced positive swabs, 2,393 lineages were determined and 2,374 (99.2%) were Omicron including 19 (0.80% of all Omicron lineages) cases of BA.2 sub-lineage and one BA.3 (0.04% of all Omicron) detected on 17 January 2022, and only 19 (0.79%) were Delta. The growth of the BA.2 Omicron sub-lineage against BA.1 and its sub-lineage BA.1.1 indicated a daily growth rate advantage of 0.14 (95% CrI, 0.03, 0.28) for BA.2, which corresponds to an additive R advantage of 0.46 (95% CrI, 0.10, 0.92). Within round 17, prevalence was decreasing overall (R=0.95, 95% CrI, 0.93, 0.97) but increasing in children aged 5 to 17 years (R=1.13, 95% CrI, 1.09, 1.18). Those 75 years and older had a swab-positivity prevalence of 2.46% (95% CI, 2.16%, 2.80%) reflecting a high level of infection among a highly vulnerable group. Among the 3,613 swab-positive individuals reporting whether or not they had had previous infection, 2,334 (64.6%) reported previous confirmed COVID-19. Of these, 64.4% reported a positive test from 1 to 30 days before their swab date. Risks of infection were increased among essential/key workers (other than healthcare or care home workers) with mutually adjusted Odds Ratio (OR) of 1.15 (95% CI, 1.05, 1.26), people living in large compared to single-person households (6+ household size OR 1.73; 95% CI, 1.44, 2.08), those living in urban vs rural areas (OR 1.24, 95% CI, 1.13, 1.35) and those living in the most vs least deprived areas (OR 1.34, 95% CI, 1.20, 1.49).

Conclusions

We observed unprecedented levels of infection with SARS-CoV-2 in England in January 2022, an almost complete replacement of Delta by Omicron, and evidence for a growth advantage for BA.2 compared to BA.1. The increase in the prevalence of infection with Omicron among children (aged 5 to 17 years) during January 2022 could pose a risk to adults, despite the current trend for prevalence in adults to decline. (Funded by the Department of Health and Social Care in England.)",,pdf:https://www.medrxiv.org/content/medrxiv/early/2022/02/06/2022.02.03.22270365.full.pdf; doi:https://doi.org/10.1101/2022.02.03.22270365; html:https://europepmc.org/article/PPR/PPR450800; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR450800&type=FILE&fileName=EMS143530-pdf.pdf&mimeType=application/pdf +PPR712319,https://doi.org/10.21203/rs.3.rs-3209706/v1,The cost of primary care consultations associated with long COVID in non-hospitalised adults: a retrospective cohort study using UK primary care data,"Tufts J, Guan N, Zemedikun D, Subramanian A, Gokhale K, Myles P, Williams T, Marshall T, Calvert M, Matthews K, Nirantharakumar K, Jackson L, Haroon S.",,No Journal Info,2023,2023-08-14,Y,,,,"

Background:

The economic impact of managing long COVID in primary care is unknown. We estimated the costs of primary care consultations associated with long COVID and explored the relationship between risk factors and costs. Methods Data were obtained on non-hospitalised adults from the Clinical Practice Research Datalink Aurum primary care database. We used propensity score matching with an incremental cost method to estimate additional primary care consultation costs associated with long COVID (12 weeks after COVID-19) at an individual and UK national level. We applied multivariable regression models to estimate the association between risk factors and consultations costs beyond 12 weeks from acute COVID-19. Results Based on an analysis of 472,173 patients with Covid-19 and 472,173 unexposed individuals, the annual incremental cost of primary care consultations associated with long COVID was £2.44 per patient and £23,382,452 at the national level. Among patients with COVID-19, a long COVID diagnosis and longer-term reporting of symptoms were associated with a 43% and 44% increase in primary care consultation costs respectively, compared to patients without long COVID symptoms. Older age, female sex, obesity, being from a white ethnic group, comorbidities and prior consultation frequency were all associated with increased primary care consultation costs. Conclusions The costs of primary care consultations associated with long COVID in non-hospitalised adults are substantial. Costs are significantly higher among those diagnosed with long COVID, those with long COVID symptoms, older adults, females, and those with obesity and comorbidities.",,doi:https://doi.org/10.21203/rs.3.rs-3209706/v1; html:https://europepmc.org/article/PPR/PPR712319; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR712319&type=FILE&fileName=EMS187055-pdf.pdf&mimeType=application/pdf PPR486653,https://doi.org/10.1101/2022.04.21.22274152,"Health care use attributable to COVID-19: A propensity matched national electronic health records cohort study of 249,390 people in Wales, UK","Kennedy J, Parker M, Seaborne M, Mhereeg M, Walker A, Walker V, Denaxas S, Kennedy N, Katikireddi S, Brophy S.",,No Journal Info,2022,2022-04-27,Y,,,,"

Background

To determine the extent and nature of changes in infected patients healthcare utilization, we studied healthcare contact in the 1-4 weeks and 5-24 weeks following a COVID-19 diagnosis compared to propensity matched controls.

Methods

Survival analysis was used for time to death and first clinical outcomes including clinical terminology concepts for post-viral illness, fatigue, embolism, respiratory conditions, mental and developmental conditions, fit note, or hospital attendance. Increased instantaneous risk for the occurrence of an outcome for positive individuals was quantified using hazard ratios (HR) from Cox Regression and absolute risk was quantified using relative risk (RR) from life table analysis.

Results

Compared to matched individuals testing negative, surviving positive community-tested patients had a higher risk of post-viral illness (HR: 4.57, 95%CI: 1.77-11.80, p=0.002), fatigue (HR: 1.47, 95%CI: 1.24-1.75, p<0.001) and embolism (HR: 1.51, 95%CI: 1.13-2.02, p=0.005) at 5-24 weeks post-diagnosis. In the four weeks after COVID-19 higher rates of sick notes were being issued for community-tested (HR: 3.04, 95%CI: 0.88 to 10.50, p<0.079); the risk was reduced after four weeks, compared to controls. Overall healthcare attendance for anxiety, depression was less likely in those with COVID-19 in the first four weeks (HR: 0.83, 95%CI: 0.73-1.06, p=0.007). After four weeks, anxiety, depression is less likely to occur for the positive community-tested individuals (HR: 0.87, 95%CI: 0.77-1.00, p=0.048), but more likely for positive hospital-tested individuals (HR: 1.16, 95%CI: 1.00-1.45, p=0.053). Although statistical associations between positive infection and post-infection healthcare use are clear, the absolute use of healthcare is very.

Conclusions

Community COVID-19 disease is associated with increased risks of post-viral illness, fatigue, embolism, depression, anxiety and respiratory conditions. Despite these elevated risks, the absolute healthcare burden is low. Either very small proportions of people experience adverse outcomes following COVID-19 or they are not presenting to healthcare.

Trial registration

Data held in SAIL databank are anonymised and therefore, no ethical approval is required. All data in SAIL has the permission from the relevant Caldicott Guardian or Data Protection Officer and SAIL-related projects are required to obtain Information Governance Review Panel (IGRP) approval. The IGRP approval number for this study is 1259.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2022/04/27/2022.04.21.22274152.full.pdf; doi:https://doi.org/10.1101/2022.04.21.22274152; html:https://europepmc.org/article/PPR/PPR486653; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR486653&type=FILE&fileName=EMS144659-pdf.pdf&mimeType=application/pdf PPR445332,https://doi.org/10.1101/2022.01.21.22269651,"Pre-COVID-19 pandemic health-related behaviours in children (2018-2020) and association with being tested for SARS-CoV-2 and testing positive for SARS-CoV-2 (2020-2021): a retrospective cohort study using survey data linked with routine health data in Wales, UK","Marchant E, Lowthian E, Crick T, Griffiths L, Fry R, Dadaczynski K, Okan O, James M, Cowley L, Torabi F, Kennedy J, Akbari A, Lyons R, Brophy S.",,No Journal Info,2022,2022-01-22,Y,,,,"

ABSTRACT

Objectives

Examine if pre-COVID-19 pandemic (prior March 2020) health-related behaviours during primary school are associated with i) being tested for SARS-CoV-2 and ii) testing positive between 1 March 2020 to 31 August 2021.

Design

Retrospective cohort study using an online cohort survey (January 2018 to February 2020) linked to routine PCR SARS-CoV-2 test results.

Setting

Children attending primary schools in Wales (2018-2020), UK who were part of the HAPPEN school network.

Participants

Complete linked records of eligible participants were obtained for n=7,062 individuals. 39.1% (n=2,764) were tested (age 10.6±0.9, 48.9% girls) and 8.1% (n=569) tested positive for SARS-CoV-2 (age 10.6±1.0, 54.5% girls).

Main outcome measures

Logistic regression of health-related behaviours and demographics were used to determine Odds Ratios (OR) of factors associated with i) being tested for SARS-CoV-2 and ii) testing positive for SARS-CoV-2.

Results

Consuming sugary snacks (1-2 days/week OR=1.24, 95% CI 1.04 – 1.49; 5-6 days/week 1.31, 1.07 – 1.61; reference 0 days) can swim 25m (1.21, 1.06 – 1.39) and age (1.25, 1.16 – 1.35) were associated with an increased likelihood of being tested for SARS-CoV-2. Eating breakfast (1.52, 1.01 – 2.27), weekly physical activity ≥ 60 mins (1-2 days 1.69, 1.04 – 2.74; 3-4 days 1.76, 1.10 – 2.82, reference 0 days), out of school club participation (1.06, 1.02 – 1.10), can ride a bike (1.39, 1.00 – 1.93), age (1.16, 1.05 – 1.28) and girls (1.21, 1.00 – 1.46) were associated with an increased likelihood of testing positive for SARS-CoV-2. Living in least deprived quintiles 4 (0.64, 0.46 – 0.90) and 5 (0.64, 0.46 – 0.89) compared to the most deprived quintile was associated with a decreased likelihood.

Conclusions

Associations may be related to parental health literacy and monitoring behaviours. Physically active behaviours may include co-participation with others, and exposure to SARS-CoV-2. A risk versus benefit approach must be considered given the importance of health-related behaviours for development.

STRENGTHS AND LIMITATIONS

Investigation of the association of pre-pandemic child health-related behaviour measures with subsequent SARS-CoV-2 testing and infection. Reporting of multiple child health behaviours linked at an individual-level to routine records of SARS-CoV-2 testing data through the SAIL Databank. Child-reported health behaviours were measured before the COVID-19 pandemic (1 January 2018 to 28 February 2020) which may not reflect behaviours during COVID-19. Health behaviours captured through the national-scale HAPPEN survey represent children attending schools that engaged with the HAPPEN Wales primary school network and may not be representative of the whole population of Wales. The period of study for PCR-testing for and testing positive for SARS-CoV-2 includes a time frame with varying prevalence rates, approaches to testing children (targeted and mass testing) and restrictions which were not measured in this study.",,pdf:https://cronfa.swan.ac.uk/Record/cronfa59234/Download/59234__25266__d2f92161119b4ae1a476e79b52b4a724.pdf; doi:https://doi.org/10.1101/2022.01.21.22269651; html:https://europepmc.org/article/PPR/PPR445332; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR445332&type=FILE&fileName=EMS142585-pdf.pdf&mimeType=application/pdf PPR570165,https://doi.org/10.1101/2022.11.11.22282217,"Digital ethnicity data in population-wide electronic health records in England: a description of completeness, coverage, and granularity of diversity","Pineda-Moncusí M, Allery F, Delmestri A, Bolton T, Nolan J, Thygesen J, Handy A, Banerjee A, Denaxas S, Tomlinson C, Denniston AK, Sudlow C, Akbari A, Wood A, Collins GS, Petersen I, Khunti K, Prieto-Alhambra D, Khalid S.",,No Journal Info,2022,2022-11-11,N,,,,"

Background

The link between ethnicity and healthcare inequity, and the urgency for better data is well-recognised. This study describes ethnicity data in nation-wide electronic health records in England, UK.

Methods

We conducted a retrospective cohort study using de-identified person-level records for the England population available in the National Health Service (NHS) Digital trusted research environment. Primary care records (GDPPR) were linked to hospital and national mortality records. We assessed completeness, consistency, and granularity of ethnicity records using all available SNOMED-CT concepts for ethnicity and NHS ethnicity categories.

Findings

From 61.8 million individuals registered with a primary care practice in England, 51.5 (83.3%) had at least one ethnicity record in GDPPR, increasing to 93·9% when linked with hospital records. Approximately 12·0% had at least two conflicting ethnicity codes in primary care records. Women were more likely to have ethnicity recorded than men. Ethnicity was missing most frequently in individuals from 18 to 39 years old and in the southern regions of England. Individuals with an ethnicity record had more comorbidities recorded than those without. Of 489 SNOMED-CT ethnicity concepts available, 255 were used in primary care records. Discrepancies between SNOMED-CT and NHS ethnicity categories were observed, specifically within “Other-” ethnicity groups.

Interpretation

More than 250 ethnicity sub-groups may be found in health records for the English population, although commonly categorised into “White”, “Black”, “Asian”, “Mixed”, and “Other”. One in ten individuals do not have ethnicity information recorded in primary care or hospital records. SNOMED-CT codes represent more diversity in ethnicity groups than the NHS ethnicity classification. Improved recording of self-reported ethnicity at first point-of-care and consistency in ethnicity classification across healthcare settings can potentially improve the accuracy of ethnicity in research and ultimately care for all ethnicities.

Funding

British Heart Foundation Data Science Centre led by Health Data Research UK.

Research in context

Evidence before this study

Ethnicity has been highlighted as a significant factor in the disproportionate impact of SARS-CoV-2 infection and mortality. Better knowledge of ethnicity data recorded in real clinical practice is required to improve health research and ultimately healthcare. We searched PubMed from database inception to 14 th July 2022 for publications using the search terms “ethnicity” and “electronic health records” or “EHR,” without language restrictions. 228 publications in 2019, before the COVID-19 pandemic, and 304 publications between 2020 and 2022 were identified. However, none of these publications used or reported any of over 400 available SNOMED-CT concepts for ethnicity to account for more granularity and diversity than captured by traditional high-level classification limited to 5 to 9 ethnicity groups.

Added value of this study

We provide a comprehensive study of the largest collection of ethnicity records from a national-level electronic health records trusted research environment, exploring completeness, consistency, and granularity. This work can serve as a data resource profile of ethnicity from routinely-collected EHR in England.

Implications of all the available evidence

To achieve equity in healthcare, we need to understand the differences between individuals, as well as the influence of ethnicity both on health status and on health interventions, including variation in the behaviour of tests and therapies. Thus, there is a need for measurements, thresholds, and risk estimates to be tailored to different ethnic groups. This study presents the different medical concepts describing ethnicity in routinely collected data that are readily available to researchers and highlights key elements for improving their accuracy in research. We aim to encourage researchers to use more granular ethnicity than the than typical approaches which aggregate ethnicity into a limited number of categories, failing to reflect the diversity of underlying populations. Accurate ethnicity data will lead to a better understanding of individual diversity, which will help to address disparities and influence policy recommendations that can translate into better, fairer health for all.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2022/11/11/2022.11.11.22282217.full.pdf; doi:https://doi.org/10.1101/2022.11.11.22282217; html:https://europepmc.org/article/PPR/PPR570165; doi:https://doi.org/10.1101/2022.11.11.22282217 @@ -103,8 +103,8 @@ PPR467856,https://doi.org/10.1101/2022.03.10.22272177,The Omicron SARS-CoV-2 epi PPR372315,https://doi.org/10.1101/2021.07.16.21260651,Evaluating discharges and readmissions using a COVID Virtual Ward model: a retrospective data study assessing patient outcomes and the likely staffing commitment,"Gallier S, Atkin C, Reddy-Kolanu V, Parekh D, Zou X, Evison F, Ball S, Sapey E.",,No Journal Info,2021,2021-07-20,Y,,,,"

Background

COVID-19 has placed a catastrophic burden on acute hospitals. In an attempt to reduce admissions and enable safe early discharge, a COVID virtual ward (CVW) care pathway has been supported by NHS England. This includes discharging people who meet objective criteria based on acuity scores and oxygen saturations, with pulse oximeters and daily phone calls for up to 14 days. Observational studies have reported the safety of this system, but without describing the outcomes from usual care.

Methods

A retrospective study using routinely collected health data from all adults with a confirmed positive severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) swab result between 1 st June 2020 and 31 st Jan 2021 who attended the Emergency Department or Acute Medical Unit at QEHB, which does not have a CVW service. Criteria for CVW were applied using data from the first 24 hours of presentation to hospital and subsequent health outcomes were included for 28 days, including re-presentation, re-admission, ITU escalation and death. Results were compared to reported studies based in secondary care.

Results

During the study period, 26,127 patients presented to QEHB hospital. 2301 had a positive SARS-CoV-2 swab. Of these, 1730 (75.2%) did not meet the criteria for the CVW and 571 (24.8%) did. Of the 571, 325 (56.9%) were discharged home within 24 hours and 246 (43.1%) were admitted for 24 hours or longer. Those admitted were older, with increased co-morbidities, 80.9% required hospital-supported acute therapies after the first 24 hours and 10.6% died. Of the 325 discharged, 44 were readmitted (13.5%), 30 (9.2%) with COVID-related symptoms, 5 (1.5%) required ITU and 1 patient (0.3%) died. These results were comparable to published studies with a CVW service.

Discussion

In the current study, discharging patients without a CVW did not confer a greater risk of re-presentation, re-admission, ITU escalation or death. The majority of patients who remained in hospital despite meeting the CVW criteria did so for the provision of treatments or acute assessments. It remains uncertain whether a CVW delivers improvements in hard outcomes, and further research is needed.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2021/07/20/2021.07.16.21260651.full.pdf; doi:https://doi.org/10.1101/2021.07.16.21260651; html:https://europepmc.org/article/PPR/PPR372315; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR372315&type=FILE&fileName=EMS131153-pdf.pdf&mimeType=application/pdf PPR530735,https://doi.org/10.1101/2022.08.08.22278576,Outcome of COVID-19 in hospitalised immunocompromised patients: an analysis of the WHO ISARIC CCP-UK prospective cohort study,"Turtle L, Thorpe M, Drake TM, Swets M, Palmieri C, Russell CD, Ho A, Aston S, Wootton DG, Richter A, de Silva TI, Hardwick HE, Leeming G, Law A, Openshaw PJ, Harrison EM, Baillie JK, Semple MG, Docherty AB, ISARIC4C investigators.",,No Journal Info,2022,2022-08-11,Y,,,,"

Background

Immunocompromised patients may be at higher risk of mortality if hospitalised with COVID-19 compared with immunocompetent patients. However, previous studies have been contradictory. We aimed to determine whether immunocompromised patients were at greater risk of in-hospital death, and how this risk changed over the pandemic.

Methods

We included patients >=19yrs with symptomatic community-acquired COVID-19 recruited to the ISARIC WHO Clinical Characterisation Protocol UK. We defined immunocompromise as: immunosuppressant medication preadmission, cancer treatment, organ transplant, HIV, or congenital immunodeficiency. We used logistic regression to compare the risk of death in both groups, adjusting for age, sex, deprivation, ethnicity, vaccination and co-morbidities. We used Bayesian logistic regression to explore mortality over time.

Findings

Between 17/01/2020 and 28/02/2022 we recruited 156,552 eligible patients, of whom 21,954 (14%) were immunocompromised. 29% (n=6,499) of immunocompromised and 21% (n=28,608) of immunocompetent patients died in hospital. The odds of in-hospital mortality were elevated for immunocompromised patients (adjOR 1.44, 95% CI 1.39-1.50, p<0.001). As the pandemic progressed, in-hospital mortality reduced more slowly for immunocompromised patients than for immunocompetent patients. This was particularly evident with increasing age: the probability of the reduction in hospital mortality being less for immunocompromised patients aged 50-69yrs was 88% for men and 83% for women, and for those >80yrs was 99% for men, and 98% for women.

Conclusions

Immunocompromised patients remain at elevated risk of death from COVID-19. Targeted measures such as additional vaccine doses and monoclonal antibodies should be considered for this group.

Funding

National Institute for Health Research; Medical Research Council; Chief Scientist Office, Scotland.",,pdf:https://www.pure.ed.ac.uk/ws/files/343951294/journal.pmed.1004086.pdf; doi:https://doi.org/10.1101/2022.08.08.22278576; html:https://europepmc.org/article/PPR/PPR530735; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR530735&type=FILE&fileName=EMS152614-pdf.pdf&mimeType=application/pdf PPR673302,https://doi.org/10.1101/2023.06.08.544212,Towards Pandemic-Scale Ancestral Recombination Graphs of SARS-CoV-2,"Zhan SH, Ignatieva A, Wong Y, Eaton K, Jeffery B, Palmer DS, Murall CL, Otto SP, Kelleher J.",,No Journal Info,2023,2023-06-08,Y,,,,"Recombination is an ongoing and increasingly important feature of circulating lineages of SARS-CoV-2, challenging how we represent the evolutionary history of this virus and giving rise to new variants of potential public health concern by combining transmission and immune evasion properties of different lineages. Detection of new recombinant strains is challenging, with most methods looking for breaks between sets of mutations that characterise distinct lineages. In addition, many basic approaches fundamental to the study of viral evolution assume that recombination is negligible, in that a single phylogenetic tree can represent the genetic ancestry of the circulating strains. Here we present an initial version of sc2ts, a method to automatically detect recombinants in real time and to cohesively integrate them into a genealogy in the form of an ancestral recombination graph (ARG), which jointly records mutation, recombination and genetic inheritance. We infer two ARGs under different sampling strategies, and study their properties. One contains 1.27 million sequences sampled up to June 30, 2021, and the second is more sparsely sampled, consisting of 657K sequences sampled up to June 30, 2022. We find that both ARGs are highly consistent with known features of SARS-CoV-2 evolution, recovering the basic backbone phylogeny, mutational spectra, and recapitulating details on the majority of known recombinant lineages. Using the well-established and feature-rich tskit library, the ARGs can also be stored concisely and processed efficiently using standard Python tools. For example, the ARG for 1.27 million sequences—encoding the inferred reticulate ancestry, genetic variation, and extensive metadata—requires 58MB of storage, and loads in less than a second. The ability to fully integrate the effects of recombination into downstream analyses, to quickly and automatically detect new recombinants, and to utilise an efficient and convenient platform for computation based on well-engineered technologies makes sc2ts a promising approach.",,pdf:https://www.biorxiv.org/content/biorxiv/early/2023/06/08/2023.06.08.544212.full.pdf; doi:https://doi.org/10.1101/2023.06.08.544212; html:https://europepmc.org/article/PPR/PPR673302; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR673302&type=FILE&fileName=EMS177195-pdf.pdf&mimeType=application/pdf -PPR599577,https://doi.org/10.21203/rs.3.rs-2349826/v1,"COVID-19 Vaccination in Pregnancy: The Impact of Multimorbidity and Smoking Status on Vaccine Hesitancy, a Cohort Study of 25,111 Women in Wales, UK","Mhereeg M, Jones H, Kennedy J, Seaborne M, Parker M, Kennedy N, Akbari A, Zuccolo L, Azcoaga-Lorenzo A, Davies A, Nirantharakumar K, Brophy S.",,No Journal Info,2023,2023-01-18,Y,,,,"

Background:

Multimorbidity and pregnancy are two risk factors for more severe outcomes after a SARS-CoV-2 infection, thus vaccination uptake is important for pregnant women living with multimorbidity. This study aimed to examine the impact of multimorbidity, smoking status, and demographics (age, ethnic group, area of deprivation) on vaccine hesitancy among pregnant women in Wales using electronic health records (EHR) linkage. Methods This cohort study utilised routinely collected, individual-level, anonymised population-scale linked data within the Secure Anonymised Information Linkage (SAIL) Databank. Pregnant women were identified from 13 th April 2021 to 31 st December 2021. Survival analysis was utilised to examine and compare the length of time to vaccination uptake in pregnancy by multimorbidity and smoking status, as well as depression, diabetes, asthma, and cardiovascular conditions independently. Variation in uptake by; multimorbidity, smoking status, and demographics was examined jointly and separately for the independent conditions using hazard ratios (HR) from the Cox regression model. Results Within the population cohort, 8,203 (32.7%) received at least one dose of the COVID-19 vaccine during pregnancy, with 8,572 (34.1%) remaining unvaccinated throughout the follow-up period, and 8,336 (33.2%) receiving the vaccine postpartum. Women aged 30 years or older were more likely to have the vaccine in pregnancy. Those who had depression were slightly but significantly more likely to have the vaccine compared to those without depression (HR = 1.08, 95% CI 1.03 to 1.14, p = 0.02). Women living with multimorbidity were 1.12 times more likely to have the vaccine compared to those living without multimorbidity (HR = 1.12, 95% CI 1.04 to 1.19, p = 0.001). Vaccine uptakes were significantly lower among both current smokers and former smokers compared to never smokers (HR = 0.87, 95% CI 0.81 to 0.94, p < 0.001 and HR = 0.92, 95% CI 0.85 to 0.98, p = 0.015 respectively). Uptake was also lower among those living in the most deprived areas compared to those living in the most affluent areas (HR = 0.89, 95% CI 0.83 to 0.96, p = 0.002). Conclusion Younger women, living without multimorbidity, current and former smokers, and those living in the more deprived areas are less likely to have the vaccine, thus, a targeted approach to vaccinations may be required for these groups. Women living with multimorbidity are slightly but significantly less likely to be hesitant about COVID-19 vaccination when pregnant.",,pdf:https://bmcinfectdis.biomedcentral.com/counter/pdf/10.1186/s12879-023-08555-8; doi:https://doi.org/10.21203/rs.3.rs-2349826/v1; html:https://europepmc.org/article/PPR/PPR599577; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR599577&type=FILE&fileName=EMS163297-pdf.pdf&mimeType=application/pdf PPR303184,https://doi.org/10.1101/2021.03.26.21254391,Vaccine effectiveness of the first dose of ChAdOx1 nCoV-19 and BNT162b2 against SARS-CoV-2 infection in residents of Long-Term Care Facilities (VIVALDI study),"Shrotri M, Krutikov M, Palmer T, Giddings R, Azmi B, Subbarao S, Fuller C, Irwin-Singer A, Davies D, Tut G, Bernal JL, Moss P, Hayward A, Copas A, Shallcross L.",,No Journal Info,2021,2021-03-26,Y,,,,"

Background

The effectiveness of SARS-CoV-2 vaccines in frail older adults living in Long-Term Care Facilities (LTCFs) is uncertain. We estimated protective effects of the first dose of ChAdOx1 and BNT162b2 vaccines against infection in this population.

Methods

Cohort study comparing vaccinated and unvaccinated LTCF residents in England, undergoing routine asymptomatic testing (8 December 2020 - 15 March 2021). We estimated the relative hazard of PCR-positive infection using Cox proportional hazards regression, adjusting for age, sex, prior infection, local SARS-CoV-2 incidence, LTCF bed capacity, and clustering by LTCF.

Results

Of 10,412 residents (median age 86 years) from 310 LTCFs, 9,160 were vaccinated with either ChAdOx1 (6,138; 67%) or BNT162b2 (3,022; 33%) vaccines. A total of 670,628 person days and 1,335 PCR-positive infections were included. Adjusted hazard ratios (aHRs) for PCR-positive infection relative to unvaccinated residents declined from 28 days following the first vaccine dose to 0·44 (0·24, 0·81) at 28-34 days and 0·38 (0·19, 0·77) at 35-48 days. Similar effect sizes were seen for ChAdOx1 (aHR 0·32 [0·15-0·66] and BNT162b2 (aHR 0·35 [0·17, 0·71]) vaccines at 35-48 days. Mean PCR cycle threshold values were higher, implying lower infectivity, for infections ≥28 days post-vaccination compared with those prior to vaccination (31·3 vs 26·6, p<0·001).

Interpretation

The first dose of BNT162b2 and ChAdOx1 vaccines was associated with substantially reduced SARS-CoV-2 infection risk in LTCF residents from 4 weeks to at least 7 weeks.

Funding

UK Government Department of Health and Social Care.

Research in Context

Evidence before this study

We conducted a systematic search for studies which evaluated SARS-CoV-2 vaccine effectiveness in residents of long-term care facilities (LTCFs) published between 01/01/2020 and 11/03/2021. We used variations of search terms for “COVID-19” AND “vaccine effectiveness” OR “vaccine efficacy” AND “care homes” OR “long term care facilities” OR “older people” on Ovid MEDLINE and MedRxiv. We identified one pre-print article regarding LTCFs in Denmark, which reported that a single dose of BNT162b was ineffective against SARS-CoV-2 infection in residents, however, participants received the second vaccine dose 24 days following the first dose on average, which is likely to be too soon to capture the protective effects of a single vaccine dose. Additionally, we identified two pre-print reports of studies evaluating vaccine effectiveness against symptomatic infection and hospitalisation amongst older adults in the community. The first of these found 81% vaccine effectiveness against COVID-19-related hospitalisation at 28-34 days following a single dose of BNT162b or ChAdOx1 in ≥80-year-olds. The second of these found vaccine effectiveness against symptomatic infection of 60% at 28-34 days and 73% at 35+ days following a single dose of ChAdOx1 in ≥70-year-olds. No studies were identified that focused on the effectiveness of a single vaccine dose against infection amongst LTCF residents at more than 4 weeks post-vaccination, a particularly important question in the context of the UK policy decision to extend the dose interval beyond 3 weeks.

Added value of this study

We conducted a prospective cohort study of 10,412 residents aged ≥65 years, from 310 LTCFs across England, to investigate the protective effect of the first dose of the ChAdOx1 and BNT162b vaccines against SARS-CoV-2 infection in frail older adults. We retrieved results from routine monthly PCR testing, as well as outbreak and clinical testing for SARS-CoV-2, thereby capturing data on asymptomatic as well as symptomatic infections, which we linked to vaccination records. We estimated vaccine effectiveness to be 56% (19-76%) at 28-34 days, and 62% (23-81%) at 35-48 days following a single dose of ChAdOx1 or BNT162. Our findings suggest that the risk of SARS-CoV-2 infection is substantially reduced from 28 days following the first dose of either vaccine and that this effect is maintained for at least 7 weeks, with similar protection offered by both vaccine types. We also found that PCR cycle threshold (Ct) values, which are negatively associated with the ability to isolate virus, were significantly higher in infections occurring at ≥ 28days post vaccination compared to those occurring in the unvaccinated period, suggesting that vaccination may reduce onward transmission of SARS-CoV-2 in breakthrough infections. To the best of our knowledge, our findings constitute the first real-world evidence on vaccine effectiveness against infection for ChAdOx1, in any age group. We can also infer that both vaccines are effective against the B.1.1.7 variant, because our analysis period coincided with the rapid emergence of B.1.1.7 in England during the second wave of the pandemic.

Implications of all the available evidence

Our findings add to the growing body of evidence on the protective effect of the BNT162b vaccines in residents of LTCFs and demonstrate the effectiveness of ChAdOx1 in this vulnerable population. Evaluating single-dose vaccine efficacy has become increasingly important in light of extended dosing intervals that have been implemented in order to maximise vaccine coverage across high-risk groups. Further work is required to evaluate the effectiveness of the first vaccine dose after 8-12 weeks, as well as following the second dose, and to evaluate the long-term impact of vaccination on SARS-CoV-2 infection, transmission and mortality in LTCFs. This will inform policy decisions regarding the ongoing need for disease control measures in LTCF such as visitor restrictions, which continue to have a detrimental impact on the wellbeing of residents, their relatives, and staff. Supplementary material attached.",,pdf:http://www.thelancet.com/article/S1473309921002899/pdf; doi:https://doi.org/10.1101/2021.03.26.21254391; html:https://europepmc.org/article/PPR/PPR303184; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR303184&type=FILE&fileName=EMS120994-pdf.pdf&mimeType=application/pdf +PPR599577,https://doi.org/10.21203/rs.3.rs-2349826/v1,"COVID-19 Vaccination in Pregnancy: The Impact of Multimorbidity and Smoking Status on Vaccine Hesitancy, a Cohort Study of 25,111 Women in Wales, UK","Mhereeg M, Jones H, Kennedy J, Seaborne M, Parker M, Kennedy N, Akbari A, Zuccolo L, Azcoaga-Lorenzo A, Davies A, Nirantharakumar K, Brophy S.",,No Journal Info,2023,2023-01-18,Y,,,,"

Background:

Multimorbidity and pregnancy are two risk factors for more severe outcomes after a SARS-CoV-2 infection, thus vaccination uptake is important for pregnant women living with multimorbidity. This study aimed to examine the impact of multimorbidity, smoking status, and demographics (age, ethnic group, area of deprivation) on vaccine hesitancy among pregnant women in Wales using electronic health records (EHR) linkage. Methods This cohort study utilised routinely collected, individual-level, anonymised population-scale linked data within the Secure Anonymised Information Linkage (SAIL) Databank. Pregnant women were identified from 13 th April 2021 to 31 st December 2021. Survival analysis was utilised to examine and compare the length of time to vaccination uptake in pregnancy by multimorbidity and smoking status, as well as depression, diabetes, asthma, and cardiovascular conditions independently. Variation in uptake by; multimorbidity, smoking status, and demographics was examined jointly and separately for the independent conditions using hazard ratios (HR) from the Cox regression model. Results Within the population cohort, 8,203 (32.7%) received at least one dose of the COVID-19 vaccine during pregnancy, with 8,572 (34.1%) remaining unvaccinated throughout the follow-up period, and 8,336 (33.2%) receiving the vaccine postpartum. Women aged 30 years or older were more likely to have the vaccine in pregnancy. Those who had depression were slightly but significantly more likely to have the vaccine compared to those without depression (HR = 1.08, 95% CI 1.03 to 1.14, p = 0.02). Women living with multimorbidity were 1.12 times more likely to have the vaccine compared to those living without multimorbidity (HR = 1.12, 95% CI 1.04 to 1.19, p = 0.001). Vaccine uptakes were significantly lower among both current smokers and former smokers compared to never smokers (HR = 0.87, 95% CI 0.81 to 0.94, p < 0.001 and HR = 0.92, 95% CI 0.85 to 0.98, p = 0.015 respectively). Uptake was also lower among those living in the most deprived areas compared to those living in the most affluent areas (HR = 0.89, 95% CI 0.83 to 0.96, p = 0.002). Conclusion Younger women, living without multimorbidity, current and former smokers, and those living in the more deprived areas are less likely to have the vaccine, thus, a targeted approach to vaccinations may be required for these groups. Women living with multimorbidity are slightly but significantly less likely to be hesitant about COVID-19 vaccination when pregnant.",,pdf:https://bmcinfectdis.biomedcentral.com/counter/pdf/10.1186/s12879-023-08555-8; doi:https://doi.org/10.21203/rs.3.rs-2349826/v1; html:https://europepmc.org/article/PPR/PPR599577; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR599577&type=FILE&fileName=EMS163297-pdf.pdf&mimeType=application/pdf PPR506599,https://doi.org/10.1101/2022.06.15.22276423,How acceptable is rapid whole genome sequencing for infectious disease management in hospitals? Perspectives of those involved in managing nosocomial SARS-CoV-2,"Flowers P, McLeod J, Mapp F, Stirrup O, Blackstone J, Snell LB, Peters C, Thomson E, Holmes A, Price J, Partridge D, Shallcross L, de Silva TI, Breuer J.",,No Journal Info,2022,2022-06-16,Y,,,,"

Structured summary

Background

Whole genome sequencing (WGS) for managing healthcare associated infections (HCAIs) has developed considerably through experiences with SARS-CoV-2. We interviewed various healthcare professionals (HCPs) with direct experience of using WGS in hospitals (within the COG-UK Hospital Onset COVID-19 Infection (HOCI) study) to explore its acceptability and future use.

Method

An exploratory, cross-sectional, qualitative design employed semi-structured interviews with 39 diverse HCPs between December 2020 and June 2021. Participants were recruited from five sites within the larger clinical study of a novel genome sequencing reporting tool for SARS-CoV-2 (the HOCI study). All had experience, in their diverse roles, of using sequencing data to manage nosocomial SARS-CoV-2 infection. Deductive and inductive thematic analysis identified themes exploring aspects of the acceptability of sequencing.

Findings

The analysis highlighted the overall acceptability of rapid WGS for infectious disease using SARS-CoV-2 as a case study. Diverse professionals were largely very positive about its future use and believed that it could become a valuable and routine tool for managing HCAIs. We identified three key themes ‘1) ‘Proof of concept achieved’; 2) ‘Novel insights and implications’; and 3) ‘Challenges and demands’.

Conclusion

Our qualitative analysis, drawn from five diverse hospitals, shows the broad acceptability of rapid sequencing and its potential. Participants believed it could and should become an everyday technology capable of being embedded within typical hospital processes and systems. However, its future integration into existing healthcare systems will not be without challenges (e.g., resource, multi-level change) warranting further mixed methods research.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2022/06/16/2022.06.15.22276423.full.pdf; doi:https://doi.org/10.1101/2022.06.15.22276423; html:https://europepmc.org/article/PPR/PPR506599; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR506599&type=FILE&fileName=EMS146081-pdf.pdf&mimeType=application/pdf PPR471516,https://doi.org/10.1101/2022.03.23.22272804,Waning effectiveness of BNT162b2 and ChAdOx1 COVID-19 vaccines over six months since second dose: a cohort study using linked electronic health records,"Horne EM, Hulme WJ, Keogh RH, Palmer TM, Williamson EJ, Parker EP, Green A, Walker V, Walker AJ, Curtis H, Fisher L, MacKenna B, Croker R, Hopcroft L, Park RY, Massey J, Morley J, Mehrkar A, Bacon S, Evans D, Inglesby P, Morton CE, Hickman G, Davy S, Ward T, Dillingham I, Goldacre B, Hernán MA, Sterne JA.",,No Journal Info,2022,2022-03-23,Y,,,,"

Summary

Background

The rate at which COVID-19 vaccine effectiveness wanes over time is crucial for vaccination policies, but is incompletely understood with conflicting results from different studies.

Methods

This cohort study, using the OpenSAFELY-TPP database and approved by NHS England, included individuals without prior SARS-CoV-2 infection assigned to vaccines priority groups 2-12 defined by the UK Joint Committee on Vaccination and Immunisation. We compared individuals who had received two doses of BNT162b2 or ChAdOx1 with unvaccinated individuals during six 4-week comparison periods, separately for subgroups aged 65+ years; 16-64 years and clinically vulnerable; 40-64 years and 18-39 years. We used Cox regression, stratified by first dose eligibility and geographical region and controlled for calendar time, to estimate adjusted hazard ratios (aHRs) comparing vaccinated with unvaccinated individuals, and quantified waning vaccine effectiveness as ratios of aHRs per-4-week period. The outcomes were COVID-19 hospitalisation, COVID-19 death, positive SARS-CoV-2 test, and non-COVID-19 death.

Findings

The BNT162b2, ChAdOx1 and unvaccinated groups comprised 1,773,970, 2,961,011 and 2,433,988 individuals, respectively. Waning of vaccine effectiveness was similar across outcomes and vaccine brands: e.g. in the 65+ years subgroup ratios of aHRs versus unvaccinated for COVID-19 hospitalisation, COVID-19 death and positive SARS-CoV-2 test ranged from 1.23 (95% CI 1.15-1.32) to 1.27 (1.20-1.34) for BNT162b2 and 1.16 (0.98-1.37) to 1.20 (1.14-1.27) for ChAdOx1. Despite waning, rates of COVID-19 hospitalisation and COVID-19 death were substantially lower among vaccinated individuals compared to unvaccinated individuals up to 26 weeks after second dose, with estimated aHRs <0.20 (>80% vaccine effectiveness) for BNT162b2, and <0.26 (>74%) for ChAdOx1. By weeks 23-26, rates of SARS-CoV-2 infection in fully vaccinated individuals were similar to or higher than those in unvaccinated individuals: aHRs ranged from 0.85 (0.78-0.92) to 1.53 (1.07-2.18) for BNT162b2, and 1.21 (1.13-1.30) to 1.99 (1.94-2.05) for ChAdOx1.

Interpretation

The rate at which estimated vaccine effectiveness waned was strikingly consistent for COVID-19 hospitalisation, COVID-19 death and positive SARS-CoV-2 test, and similar across subgroups defined by age and clinical vulnerability. If sustained to outcomes of infection with the Omicron variant and to booster vaccination, these findings will facilitate scheduling of booster vaccination doses.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2022/03/23/2022.03.23.22272804.full.pdf; doi:https://doi.org/10.1101/2022.03.23.22272804; html:https://europepmc.org/article/PPR/PPR471516; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR471516&type=FILE&fileName=EMS149099-pdf.pdf&mimeType=application/pdf PPR415631,https://doi.org/10.1101/2021.11.03.21265877,REACT-1 round 15 interim report: High and rising prevalence of SARS-CoV-2 infection in England from end of September 2021 followed by a fall in late October 2021,"Chadeau-Hyam M, Eales O, Bodinier B, Wang H, Haw D, Whitaker M, Walters CE, Atchison C, Diggle PJ, Page AJ, Ashby D, Barclay W, Taylor G, Cooke G, Ward H, Darzi A, Donnelly CA, Elliott P.",,No Journal Info,2021,2021-11-03,Y,,,,"

Background

The third wave of COVID-19 in England coincided with the rapid spread of the Delta variant of SARS-CoV-2 from the end of May 2021. Case incidence data from the national testing programme (Pillar 2) in England may be affected by changes in testing behaviour and other biases. Community surveys may provide important contextual information to inform policy and the public health response.

Methods

We estimated patterns of community prevalence of SARS-CoV-2 infection in England using RT-PCR swab-positivity, demographic and other risk factor data from round 15 (interim) of the REal-time Assessment of Community Transmission-1 (REACT-1) study (round 15a, carried out from 19 to 29 October 2021). We compared these findings with those from round 14 (9 to 27 September 2021).

Results

During mid- to late-October 2021 (round 15a) weighted prevalence was 1.72% (1.61%, 1.84%) compared to 0.83% (0.76%, 0.89%) in September 2021 (round 14). The overall reproduction number (R) from round 14 to round 15a was 1.12 (1.11, 1.14) with increases in prevalence over this period (September to October) across age groups and regions except Yorkshire and The Humber. However, within round 15a (mid- to late-October) there was evidence of a fall in prevalence with R of 0.76 (0.65, 0.88). The highest weighted prevalence was observed among children aged 5 to 12 years at 5.85% (5.10%, 6.70%) and 13 to 17 years at 5.75% (5.02%, 6.57%). At regional level, there was an almost four-fold increase in weighted prevalence in South West from round 14 at 0.59% (0.43%,0.80%) to round 15a at 2.18% (1.84%, 2.58%), with highest smoothed prevalence at subregional level also found in South West in round 15a. Age, sex, key worker status, and presence of children in the home jointly contributed to the risk of swab-positivity. Among the 126 sequenced positive swabs obtained up until 23 October, all were Delta variant; 13 (10.3%) were identified as the AY.4.2 sub-lineage.

Discussion

We observed the highest overall prevalence of swab-positivity seen in the REACT-1 study in England to date in round 15a (October 2021), with a two-fold rise in swab-positivity from round 14 (September 2021). Despite evidence of a fall in prevalence from mid- to late-October 2021, prevalence remains high, particularly in school-aged children, with evidence also of higher prevalence in households with one or more children. Thus, vaccination of children aged 12 and over remains a high priority (with possible extension to children aged 5-12) to help reduce within-household transmission and disruptions to education, as well as among adults, to lessen the risk of serious disease among those infected.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2021/11/03/2021.11.03.21265877.full.pdf; doi:https://doi.org/10.1101/2021.11.03.21265877; html:https://europepmc.org/article/PPR/PPR415631; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR415631&type=FILE&fileName=EMS138032-pdf.pdf&mimeType=application/pdf @@ -130,8 +130,8 @@ PPR607583,https://doi.org/10.1101/2023.01.24.23284916,"Real-world effectiveness PPR605877,https://doi.org/10.2139/ssrn.4065552,Impact of Dexamethasone and Remdesivir on Neurological Complications during COVID-19,"Grundmann A, Wu C, Hardwick M, Baillie JK, Openshaw P, Semple MG, Böhning D, Pett S, Michael B, Thomas RH, Galea I.",,No Journal Info,2022,2022-04-12,N,,,,"Importance: Neurological complications are common following acute COVID-19, causing significant morbidity with health economic consequences. However, no treatment studies in COVID-19 focussing on neurological complications have been published to date.

Objective: Does treatment with either remdesivir, dexamethasone or both reduce the risk of neurological complications in adult patients hospitalised with COVID-19?

Design and setting: COVID-19 neurological complications, and remdesivir and dexamethasone use, were studied in adults admitted to hospitals in the UK with COVID-19, using data from the International Severe Acute and emerging Respiratory Infection Consortium (ISARIC) WHO Clinical Characterisation Protocol UK (CCP-UK, study registration ISRCTN66726260). Treatment allocation was non-blinded and performed by reporting clinicians. A propensity scoring methodology was used to correct for confounding between treatment groups.

Participants: 89,297 patients aged 18 years and older with laboratory confirmed SARS-CoV-2 infection were eligible for inclusion. Patients requiring supplemental oxygen at any point during admission (n=64,088) were defined as having severe COVID-19, as per WHO criteria. Patients were excluded if they received a dose of any SARS-CoV-2 vaccine or contracted COVID-19 in hospital.

Exposures: Treatment with remdesivir, dexamethasone or both was assessed against standard of care.

Main outcome(s) and measure(s): A neurological complication (stroke, seizure, meningitis/encephalitis or any other neurological complication) occurring at the point of death, discharge, or resolution of the COVID-19 clinical episode.

Results: The median age of patients was 71 (IQR, 56 to 82). 56% were identified as male and 71% were of white ethnicity. 4,408 patients (4.7%) developed neurological complications. In patients with severe COVID-19, neurological complications were associated with increased mortality (OR 1.36, 95% CI 1.25 to 1.47), intensive care admission (OR 1.54, 95% CI 1.41 to 1.6), likelihood of worse self-care on discharge (OR 3.79, 95% CI 3.36 to 4.26) and an increased time to recovery (9.65 days, 95% CI 7.12 to 12.17 days). Treatment with dexamethasone (n=21,129), remdesivir (n=1,428) and both treatments combined (n=10,846) in severe COVID-19 were associated with a reduced incidence of neurological complications; OR 0.76 (95% CI 0.69 to 0.83); OR 0.68 (95% CI 0.51 to 0.90); OR 0.54, (95% CI 0.47 to 0.61) respectively.

Conclusions and relevance: Treatment with dexamethasone, remdesivir or both in patients hospitalised with COVID-19 was associated with reduced neurological complications in an additive manner, such that the greatest benefit was observed in patients who received both drugs together. The potential of these treatments to reduce neurological disability is of urgent importance to patients, healthcare systems and public health bodies.
",,doi:https://doi.org/10.2139/ssrn.4065552; html:https://europepmc.org/article/PPR/PPR605877; doi:https://doi.org/10.2139/ssrn.4065552 PPR242379,https://doi.org/10.2139/ssrn.3687378,COVID-19 in Patients with Hepatobiliary and Pancreatic Diseases in East London: A Single-Centre Cohort Study,"Ullah AZMD, Sivapalan L, Chelala C, Kocher HM.",,No Journal Info,2020,2020-10-19,Y,,,,"Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causing COVID-19 in patients with pre-existing hepatobiliary and pancreatic (HPB) conditions is not clearly understood.

Methods: In a single-centre retrospective cohort study (Barts Health NHS Trust, East London), linked primary, secondary and tertiary care electronic health records for patients diagnosed newly or with pre-existing HPB diseases since 2008 till March 6, 2020 were interrogated to identify COVID-19 cases between February 12 and June 12, 2020. We conducted risk analyses to identify the effect of demographics, comorbidities and associated medication use, and lifestyle factors and with appropriate adjustment for gender, ethnicity, age group and HPB diagnoses on COVID-19 incidence and mortality.

Findings: Some 212 (1·4%) of 15586 patients with existing HPB conditions had confirmed diagnosis of COVID-19, with an increased risk for men (Relative Risk (RR)=1.59 [95% CI 1·21–2·09]) and Black ethnicity (RR= 2·2 [1·5–3·18]) amongst demographic features. The increased risk for South Asian ethnicity, patients with pre-existing non-malignant pancreatic or liver conditions, and age>70 years seemed to be due to underlying comorbidities in these particular groups. Each additional comorbidity increased the risk of infection by 60%. Both current and past substance mis-users were at more risk of COVID-19 (RR= 2·5 [1·58–4·05] and 3.65 [1·81–7], respectively). The high risk associated with past smokers was largely associated with co-existing respiratory or cardiovascular diseases; surprisingly current smokers were associated with a lower risk of infection (RR=0·58 [0·35–0·93]). HPB patients on current or past Vitamin D treatment were at increased risk of COVID-19 (RR= 2·26 [1·6–3·12] and 2·55[1·55–3·95], respectively). Black ethnicity was at increased mortality risk (RR=2.4 [1·35–3·48]). COVID-19 patients with a pre-existing kidney condition had a higher risk of death (RR=2·13 [1·16–3·55]), particularly when accompanied with an acute episode of renal complications (RR=2·74 [1·32–5·13]).

Interpretation: In a large multi-ethnic population-based study of HPB patients, male gender, Black ethnicity, medical co-morbidities, and substance mis-use independently posed a higher risk of acquiring COVID-19. Particular attention should be paid to patients with a pre-existing kidney disease to further renal insult to prevent fatality.

Funding: The study is conducted under an umbrella study, focusing on the epidemiology of pancreatic and other hepatobiliary cancers in East London, funded by Medical Research Council UK as a UKRI/Rutherford Fellowship to ADU. No additional funding has been received for this study.

Declaration of Interests: All other authors declare no competing interests.

Ethics Approval Statement: The EL-PaC-Epidem study was approved by the East of England - Essex Research Ethics Committee (19/EE/0163; May 17, 2019) and supported by the NHS Confidentiality Advisory Group for collecting and processing confidential patient information without consent (19/CAG/0219; January 17, 2020).",,doi:https://doi.org/10.2139/ssrn.3687378; html:https://europepmc.org/article/PPR/PPR242379 PPR601887,https://doi.org/10.2139/ssrn.4052647,Using National Electronic Health Records for Pandemic Preparedness: Validation of a Parsimonious Model for Predicting Excess Deaths Among Those With COVID-19,"Mizani MA, Dashtban M, Pasea L, Lai A, Thygesen JH, Tomlinson C, Handy A, Mamza JB, Morris T, Khalid S, Zaccardi F, Macleod MJ, Torabi F, Canoy D, Akbari A, Berry C, Bolton T, Nolan J, Khunti K, Denaxas S, Hemingway H, Sudlow C, Banerjee A, CVD-COVID-UK Consortium.",,No Journal Info,2022,2022-03-08,N,,,,"Background: Throughout the pandemic, research, public health, and policy emphasised prediction and surveillance of excess deaths, which have mostly occurred in older individuals with underlying conditions, highlighting importance of baseline mortality risk, infection rate (IR) and pandemic-related relative risk (RR). We now use national, pre- and post-pandemic electronic health records (EHR) to develop and validate a model incorporating these factors for prediction of excess deaths.

Methods: In development (Clinical Practice Research Datalink) and validation (NHS Digital Trusted Research Environment) cohorts in primary and secondary care EHR in England, we included 3·8 million and 35·1 million individuals aged ≥30 years, respectively. For model development, we predicted excess deaths using baseline one-year all-cause mortality risk and assumed RR=3 and IR=10%. For model validation, we observed number of excess deaths from March 2020 to March 2021. We used baseline mortality risk, IR and RR (assumed and observed) to predict excess deaths related to COVID-19.

Findings: Among individuals with at least one high-risk condition, baseline (pre-pandemic) 1-year mortality risk at one year was 4·46% (95% CI 4·41–4·51) and 3.55% (3.54-3.57) in development and validation cohorts, respectively. In our original published model, we predicted 73,498 COVID-19 deaths over 1 year for the population of England. From 1st March 2020 to 1st March 2021, there were 127,020 observed excess deaths. Observed RR was 4·34 (4·31-4·38, 95% CI) and IR was 6·27% (6·26-6·28, 95%CI). In the validation cohort, predicted excess deaths over one year were 100,338 compared with the observed 127,020 deaths with a ratio of predicted to observed excess deaths of 0.79. We found that vaccination had a negligible effect on overall RR or IR between 1st December 2020 and 1st March 2021, compared to the likely effect of under-reported COVID-19 cases from the pre-vaccination period.

Interpretation: We show that a simple, parsimonious model incorporating baseline mortality risk, one-year infection rate and relative risk of the pandemic can be used to predict excess deaths. Our analyses show that EHR could inform pandemic planning and surveillance, despite limited use in emergency preparedness to-date. Although infection dynamics are important in prediction of morbidity and mortality, future models should take greater account of underlying conditions and their associated risks.

Funding Information: The British Heart Foundation Data Science Centre (grant No SP/19/3/34678, awarded to Health Data Research (HDR) UK) funded co-development (with NHS Digital) of the trusted research environment, provision of linked datasets, data access, user software licences, computational usage, and data management and wrangling support, with additional contributions from the HDR UK data and connectivity component of the UK Government Chief Scientific Adviser’s National Core Studies programme to coordinate national Covid-19 priority research. Consortium partner organisations funded the time of contributing data analysts, biostatisticians, epidemiologists, and clinicians. AB, MAM, MHD and LP were supported by research funding from AstraZeneca. AB has received funding from the National Institute for Health Research (NIHR), British Medical Association, and UK Research and Innovation. AB, SD and HH are part of the BigData@Heart Consortium, funded by the Innovative Medicines Initiative-2 Joint Undertaking under grant agreement No 116074. K.K. is supported by the National Institute for Health Research (NIHR) Applied Research Collaboration East Midlands (ARC EM) and NIHR Lifestyle BRC.

Declaration of Interests: JBM and TM are employees of AstraZeneca. KK is chair of the ethnicity subgroup of the Independent Scientific Advisory Group for Emergencies (SAGE) and director of the University of Leicester Centre for Black Minority Ethnic Health. KK and AB are trustees of the South Asian Health Foundation (SAHF). CS is Director of the BHF Data Science Centre. All other authors report no competing interests.

Ethics Approval Statement: Approval for the study in CPRD was granted by the Independent Scientific Advisory Committee (20_074R) of the Medicines and Healthcare products Regulatory Agency in the UK in accordance with the Declaration of Helsinki. The North East-Newcastle and North Tyneside 2 research ethics committee provided ethical approval for the CVD- COVID-UK research programme (REC No 20/NE/0161).
",,doi:https://doi.org/10.2139/ssrn.4052647; html:https://europepmc.org/article/PPR/PPR601887; doi:https://doi.org/10.2139/ssrn.4052647 -PPR698319,https://doi.org/10.1101/2023.07.25.23293143,The Cost of Keeping Patients Waiting: Retrospective Treatment-Control Study of Additional Healthcare Utilisation for UK Patients Awaiting Elective Treatment Following COVID-19,"James C, Denholm R, Wood R.",,No Journal Info,2023,2023-07-27,Y,,,,"

Objective

The COVID-19 pandemic has led to increased waiting times for elective treatments in many countries. This study seeks to address a deficit in the literature concerning the effect of long waits on the wider consumption of healthcare resources.

Methods

We carried out a retrospective treatment-control study in a healthcare system in South West England from 15 June 2021 to 15 December 2021. We compared weekly contacts with health services of patients waiting over 18 weeks for treatment (‘Treatments’) and people not on a waiting list (‘Controls’). Controls were matched to Treatments based on age, sex, deprivation and multimorbidity. Treatments were stratified by the clinical specialty of the awaited treatment, with healthcare usage assessed over various healthcare settings. T-tests assessed whether there was an increase in healthcare utilisation and bootstrap resampling was used to estimate the magnitude of any differences.

Results

A total of 44,616 patients were waiting over 18 weeks (the constitutional target in England) for treatment during the study period. Evidence suggests increases (p < 0.05) in healthcare utilisation for all specialties. Patients in the Cardiothoracic Surgery specialty had the largest increase, requiring 17.9 [4.3, 33.8] additional contacts with secondary care and 17.3 [-1.1, 34.1] additional prescriptions per year.

Conclusion

People waiting for treatment consume higher levels of healthcare than comparable individuals not on a waiting list. These findings are relevant for clinicians and managers in better understanding patient need and reducing harm. Results also highlight the possible ‘false economy’ in failing to promptly resolve long elective waits.

Highlights

Long waits for elective care can result in additional healthcare needs to manage symptoms up to the point of definitive treatment. While previous studies indicate some association, these mainly consider only a single elective specialty and are limited in the range of healthcare settings covered. The large number of long-wait pathways produced as a consequence of COVID-19 disruption allows for a more holistic analysis, covering the full range of elective treatment specialties and wider healthcare impacts across primary, secondary, mental health, and community care, as well as emergency service calls and prescriptions. Analysis of 44,616 elective care pathways reveals evidence of increases in wider healthcare consumption additional to that expected for similar patients not awaiting elective treatment. This suggests a ‘false economy’ in failing to promptly resolve elective pathways, which should be reflected by healthcare providers in long-term resource allocation decisions.",,doi:https://doi.org/10.1101/2023.07.25.23293143; html:https://europepmc.org/article/PPR/PPR698319; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR698319&type=FILE&fileName=EMS182115-pdf.pdf&mimeType=application/pdf PPR271404,https://doi.org/10.1101/2021.01.20.21250158,REACT-1 round 8 interim report: SARS-CoV-2 prevalence during the initial stages of the third national lockdown in England,"Riley S, Wang H, Eales O, Walters CE, Ainslie KEC, Atchison C, Fronterre C, Diggle PJ, Ashby D, Donnelly CA, Cooke G, Barclay W, Ward H, Darzi A, Elliott P.",,No Journal Info,2021,2021-01-22,Y,,,,"

Background

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

Methods

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

Results

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

Conclusion

During the initial 10 days of the third COVID-19 lockdown in England in January 2021, prevalence of SARS-CoV-2 was very high with no evidence of decline. Until prevalence in the community is reduced substantially, health services will remain under extreme pressure and the cumulative number of lives lost during this pandemic will continue to increase rapidly.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2021/01/22/2021.01.20.21250158.full.pdf; doi:https://doi.org/10.1101/2021.01.20.21250158; html:https://europepmc.org/article/PPR/PPR271404; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR271404&type=FILE&fileName=EMS113524-pdf.pdf&mimeType=application/pdf +PPR698319,https://doi.org/10.1101/2023.07.25.23293143,The Cost of Keeping Patients Waiting: Retrospective Treatment-Control Study of Additional Healthcare Utilisation for UK Patients Awaiting Elective Treatment Following COVID-19,"James C, Denholm R, Wood R.",,No Journal Info,2023,2023-07-27,Y,,,,"

Objective

The COVID-19 pandemic has led to increased waiting times for elective treatments in many countries. This study seeks to address a deficit in the literature concerning the effect of long waits on the wider consumption of healthcare resources.

Methods

We carried out a retrospective treatment-control study in a healthcare system in South West England from 15 June 2021 to 15 December 2021. We compared weekly contacts with health services of patients waiting over 18 weeks for treatment (‘Treatments’) and people not on a waiting list (‘Controls’). Controls were matched to Treatments based on age, sex, deprivation and multimorbidity. Treatments were stratified by the clinical specialty of the awaited treatment, with healthcare usage assessed over various healthcare settings. T-tests assessed whether there was an increase in healthcare utilisation and bootstrap resampling was used to estimate the magnitude of any differences.

Results

A total of 44,616 patients were waiting over 18 weeks (the constitutional target in England) for treatment during the study period. Evidence suggests increases (p < 0.05) in healthcare utilisation for all specialties. Patients in the Cardiothoracic Surgery specialty had the largest increase, requiring 17.9 [4.3, 33.8] additional contacts with secondary care and 17.3 [-1.1, 34.1] additional prescriptions per year.

Conclusion

People waiting for treatment consume higher levels of healthcare than comparable individuals not on a waiting list. These findings are relevant for clinicians and managers in better understanding patient need and reducing harm. Results also highlight the possible ‘false economy’ in failing to promptly resolve long elective waits.

Highlights

Long waits for elective care can result in additional healthcare needs to manage symptoms up to the point of definitive treatment. While previous studies indicate some association, these mainly consider only a single elective specialty and are limited in the range of healthcare settings covered. The large number of long-wait pathways produced as a consequence of COVID-19 disruption allows for a more holistic analysis, covering the full range of elective treatment specialties and wider healthcare impacts across primary, secondary, mental health, and community care, as well as emergency service calls and prescriptions. Analysis of 44,616 elective care pathways reveals evidence of increases in wider healthcare consumption additional to that expected for similar patients not awaiting elective treatment. This suggests a ‘false economy’ in failing to promptly resolve elective pathways, which should be reflected by healthcare providers in long-term resource allocation decisions.",,doi:https://doi.org/10.1101/2023.07.25.23293143; html:https://europepmc.org/article/PPR/PPR698319; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR698319&type=FILE&fileName=EMS182115-pdf.pdf&mimeType=application/pdf PPR423873,https://doi.org/10.1101/2021.11.22.21266584,"Behaviour, booster vaccines and waning immunity: modelling the medium-term dynamics of SARS-CoV-2 transmission in England in the Omicron era","Barnard RC, Davies NG, Jit M, Edmunds WJ, Centre for Mathematical Modelling of Infectious Diseases COVID-19 working group.",,No Journal Info,2021,2021-11-24,Y,,,,"England has experienced a heavy burden of COVID-19, with multiple waves of SARS-CoV-2 transmission since early 2020 and high infection levels following the emergence and spread of Omicron variants since late 2021. In response to rising Omicron cases, booster vaccinations were accelerated and offered to all adults in England. Using a model fitted to more than 2 years of epidemiological data, we project potential dynamics of SARS-CoV-2 infections, hospital admissions and deaths in England to December 2022. We consider key uncertainties including future behavioural change and waning immunity, and assess the effectiveness of booster vaccinations in mitigating SARS-CoV-2 disease burden between October 2021 and December 2022. If no new variants emerge, SARS-CoV-2 transmission is expected to decline, with low levels remaining in the coming months. The extent to which projected SARS-CoV-2 transmission resurges later in 2022 depends largely on assumptions around waning immunity and to some extent, behaviour and seasonality.",,doi:https://doi.org/10.1101/2021.11.22.21266584; html:https://europepmc.org/article/PPR/PPR423873; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR423873&type=FILE&fileName=EMS140157-pdf.pdf&mimeType=application/pdf PPR312488,https://doi.org/10.1101/2021.04.13.21255342,Protocol for the COG-UK hospital onset COVID-19 infection (HOCI) multicentre interventional clinical study: evaluating the efficacy of rapid genome sequencing of SARS-CoV-2 in limiting the spread of COVID-19 in United Kingdom NHS hospitals,"Blackstone J, Stirrup O, Mapp F, Panca M, Copas A, Flowers P, Hockey L, Price J, Partridge D, Peters C, de Silva T, Nebbia G, Snell LB, McComish R, Breuer J, the COVID-19 Genomics UK (COG-UK) Consortium.",,No Journal Info,2021,2021-04-15,N,,,,"

Introduction

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

Methods and analysis

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

Ethics and dissemination

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

Study Registration number

ISRCTN50212645

Strengths and limitations of this study

The COG-UK HOCI study harnesses the infrastructure of the UK’s existing national COVID-19 genome sequencing platform to evaluate the specific benefit of sequencing to hospital infection control. The evaluation is thought to be the first interventional study globally to assess effectiveness of genomic sequencing for infection control in an unbiased patient selection in secondary care settings. A range of institutional settings will participate, from specialist NHS-embedded or academic centres experienced in using pathogen genomics to district general hospitals. The findings are likely to have wider applicability in future decisions to utilise genome sequencing for infection control of other pathogens (such as influenza, respiratory syncytial virus, norovirus, clostridium difficile and antimicrobial resistant pathogens) in secondary care settings. The study has been awarded UK NIHR Urgent Public Health status, ensuring prioritised access to NIHR Clinical Research Network (CRN) research staff to recruit patients. The study does not have a randomised controlled design due to the logistics of managing this against diverse standard practice.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/4/e052514.full.pdf; doi:https://doi.org/10.1101/2021.04.13.21255342; html:https://europepmc.org/article/PPR/PPR312488; doi:https://doi.org/10.1101/2021.04.13.21255342 PPR463822,https://doi.org/10.21203/rs.3.rs-1140332/v1,The contribution of hospital-acquired infections to the COVID-19 epidemic in England in the first half of 2020,"Knight G, Pham TM, Stimson J, Funk S, Jafari Y, Pople D, Evans S, Yin M, Brown CS, Bhattacharya A, Hope R, Semple MG, Read JM, Cooper BS, Robotham JV.",,No Journal Info,2022,2022-03-03,Y,,,,"

Background:

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

Methods:

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

Results:

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

Conclusions:

Transmission of SARS-CoV-2 to hospitalised patients likely caused approximately a fifth of identified cases of hospitalised COVID-19 in the “first wave” in England, but less than 1% of all infections in England. Using time to symptom onset from admission for inpatients as a detection method likely misses a substantial proportion (>60%) of hospital-acquired infections.",,doi:https://doi.org/10.21203/rs.3.rs-1140332/v1; html:https://europepmc.org/article/PPR/PPR463822; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR463822&type=FILE&fileName=EMS147320-pdf.pdf&mimeType=application/pdf @@ -148,15 +148,15 @@ PPR411044,https://doi.org/10.1101/2021.10.14.21264965,REACT-1 study round 14: Hi PPR456152,https://doi.org/10.21203/rs.3.rs-1343889/v1,Assessment of 115 symptoms for Long COVID (post-COVID-19 condition) and their risk factors in non-hospitalised individuals: a retrospective matched cohort study in UK primary care,"Subramanian A, Nirantharakumar K, Hughes S, Myles P, Williams T, Gokhale K, Taverner T, Chandan J, Brown K, Simms-Williams N, Shah A, Singh M, Kidy F, Okoth K, Hotham R, Bashir N, Cockburn N, Lee S, Turner G, Gkoutos G, Aiyegbusi OL, McMullan C, Denniston A, Sapey E, Lord J, Wraith D, Leggett E, Iles C, Marshall T, Price M, Marwaha S, Davies E, Jackson L, Camaradou J, Calvert M, Haroon S.",,No Journal Info,2022,2022-02-15,Y,,,,"Severe Acute Respiratory Syndrome Coronavirus-2 (SARS CoV-2) infection is frequently associated with a wide range of persistent symptoms, now referred to as post-COVID-19 condition, or Long COVID. The objectives of this study were to assess which symptoms are associated with confirmed SARS CoV-2 beyond 12 weeks post-infection in non-hospitalised individuals, and the risk factors associated with developing persistent symptoms. We undertook a retrospective matched cohort study between 31st January 2020 and 15th April 2021 using data from a large database of UK-based primary care electronic health records, Clinical Practice Research Datalink (CPRD) Aurum. We selected 486,149 adult patients with a confirmed diagnosis of SARS CoV-2 infection that had not been hospitalised within 28 days of the diagnosis (infected cohort). We propensity score matched them to 1,944,580 patients without a coded record of either confirmed or suspected COVID-19 (uninfected cohort). Outcomes were the presence of 115 separate symptoms at ≥12 weeks post-infection, and Long COVID, defined as having at least one of the symptoms included in the World Health Organisation case definition. Separate Cox proportional hazards models were used to estimate adjusted hazard ratios (aHR) for individual symptoms and Long Covid. 62 symptoms were significantly associated with prior exposure to SARS CoV-2 after 12 weeks. The largest adjusted hazard ratios (aHR) were for anosmia (aHR 6.49, 95% CI 5.02 to 8.39), hair loss (3.99, 3.63 to 4.39), sneezing (2.77, 1.40 to 5.50), difficulties with ejaculation (2.63, 1.61 to 4.28), reduced libido (2.36, 1.61 to 3.47), shortness of breath at rest (2.20, 1.57 to 3.08), fatigue (1.92, 1.81 to 2.03), pleuritic chest pain (1.86, 1.41 to 2.46), hoarse voice (1.78, 1.44 to 2.20), and fever (1.75, 1.54 to 1.98). Among the infected cohort, risk factors for Long COVID included younger age (aHR 0.75, 95% CI 0.70 to 0.81, for those aged ≥70 years compared to those aged 18 to 30 years), female sex (1.52, 1.48 to 1.56), belonging to an ethnic minority group (1.14 [1.07 to 1.22] for mixed race, 1.21 [1.10 to 1.34] for black ethnic groups, and 1.06 [1.03 to 1.10] for other ethnic minority groups, compared to white ethnic groups), socioeconomic deprivation (1.11 [1.07 to 1.16] for the most compared to the least socioeconomically deprived quintile), smoking (1.12, 1.08 to 1.15), obesity (1.10, 1.07 to 1.14), and a wide range of comorbidities such as COPD. SARS CoV-2 in non-hospitalised individuals is associated with a plethora of symptoms being reported at ≥12 weeks post-infection, with a higher risk associated with younger age, female sex, ethnic minority groups, socioeconomic deprivation, smoking, obesity, and several comorbidities.",,pdf:https://www.nature.com/articles/s41591-022-01909-w.pdf; doi:https://doi.org/10.21203/rs.3.rs-1343889/v1; html:https://europepmc.org/article/PPR/PPR456152; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR456152&type=FILE&fileName=EMS147152-pdf.pdf&mimeType=application/pdf PPR393002,https://doi.org/10.1101/2021.09.02.21262979,"REACT-1 round 13 final report: exponential growth, high prevalence of SARS-CoV-2 and vaccine effectiveness associated with Delta variant in England during May to July 2021","Elliott P, Haw D, Wang H, Eales O, Walters CE, Ainslie KEC, Atchison C, Fronterre C, Diggle PJ, Page AJ, Trotter AJ, Prosolek SJ, Ashby D, Donnelly CA, Barclay W, Taylor G, Cooke G, Ward H, Darzi A, Riley S, The COVID-19 Genomics UK (COG-UK) Consortium.",,No Journal Info,2021,2021-09-10,Y,,,,"

Background

The prevalence of SARS-CoV-2 infection continues to drive rates of illness and hospitalisations despite high levels of vaccination, with the proportion of cases caused by the Delta lineage increasing in many populations. As vaccination programs roll out globally and social distancing is relaxed, future SARS-CoV-2 trends are uncertain.

Methods

We analysed prevalence trends and their drivers using reverse transcription-polymerase chain reaction (RT-PCR) swab-positivity data from round 12 (between 20 May and 7 June 2021) and round 13 (between 24 June and 12 July 2021) of the REal-time Assessment of Community Transmission-1 (REACT-1) study, with swabs sent to non-overlapping random samples of the population ages 5 years and over in England.

Results

We observed sustained exponential growth with an average doubling time in round 13 of 25 days (lower Credible Interval of 15 days) and an increase in average prevalence from 0.15% (0.12%, 0.18%) in round 12 to 0.63% (0.57%, 0.18%) in round 13. The rapid growth across and within rounds appears to have been driven by complete replacement of Alpha variant by Delta, and by the high prevalence in younger less-vaccinated age groups, with a nine-fold increase between rounds 12 and 13 among those aged 13 to 17 years. Prevalence among those who reported being unvaccinated was three-fold higher than those who reported being fully vaccinated. However, in round 13, 44% of infections occurred in fully vaccinated individuals, reflecting imperfect vaccine effectiveness against infection despite high overall levels of vaccination. Using self-reported vaccination status, we estimated adjusted vaccine effectiveness against infection in round 13 of 49% (22%, 67%) among participants aged 18 to 64 years, which rose to 58% (33%, 73%) when considering only strong positives (Cycle threshold [Ct] values < 27); also, we estimated adjusted vaccine effectiveness against symptomatic infection of 59% (23%, 78%), with any one of three common COVID-19 symptoms reported in the month prior to swabbing. Sex (round 13 only), ethnicity, household size and local levels of deprivation jointly contributed to the risk of higher prevalence of swab-positivity.

Discussion

From end May to beginning July 2021 in England, where there has been a highly successful vaccination campaign with high vaccine uptake, infections were increasing exponentially driven by the Delta variant and high infection prevalence among younger, unvaccinated individuals despite double vaccination continuing to effectively reduce transmission. Although slower growth or declining prevalence may be observed during the summer in the northern hemisphere, increased mixing during the autumn in the presence of the Delta variant may lead to renewed growth, even at high levels of vaccination.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2021/09/10/2021.09.02.21262979.full.pdf; doi:https://doi.org/10.1101/2021.09.02.21262979; html:https://europepmc.org/article/PPR/PPR393002; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR393002&type=FILE&fileName=EMS134814-pdf.pdf&mimeType=application/pdf PPR312539,https://doi.org/10.1101/2021.04.08.21255100,REACT-1 round 10 report: Level prevalence of SARS-CoV-2 swab-positivity in England during third national lockdown in March 2021,"Riley S, Eales O, Haw D, Walters CE, Wang H, Ainslie KEC, Atchison C, Fronterre C, Diggle PJ, Ashby D, Donnelly CA, Cooke G, Barclay W, Ward H, Darzi A, Elliott P.",,No Journal Info,2021,2021-04-15,Y,,,,"

Background

In England, hospitalisations and deaths due to SARS-CoV-2 have been falling consistently since January 2021 during the third national lockdown of the COVID-19 pandemic. The first significant relaxation of that lockdown occurred on 8 March when schools reopened.

Methods

The REal-time Assessment of Community Transmission-1 (REACT-1) study augments routine surveillance data for England by measuring swab-positivity for SARS-CoV-2 in the community. The current round, round 10, collected swabs from 11 to 30 March 2021 and is compared here to round 9, in which swabs were collected from 4 to 23 February 2021.

Results

During round 10, we estimated an R number of 1.00 (95% confidence interval 0.81, 1.21). Between rounds 9 and 10 we estimated national prevalence has dropped by ∼60% from 0.49% (0.44%, 0.55%) in February to 0.20% (0.17%, 0.23%) in March. There were substantial falls in weighted regional prevalence: in South East from 0.36% (0.29%, 0.44%) in round 9 to 0.07% (0.04%, 0.12%) in round 10; London from 0.60% (0.48%, 0.76%) to 0.16% (0.10%, 0.26%); East of England from 0.47% (0.36%, 0.60%) to 0.15% (0.10%, 0.24%); East Midlands from 0.59% (0.45%, 0.77%) to 0.19% (0.13%, 0.28%); and North West from 0.69% (0.54%, 0.88%) to 0.31% (0.21%, 0.45%). Areas of apparent higher prevalence remain in parts of the North West, and Yorkshire and The Humber. The highest prevalence in March was found among school-aged children 5 to 12 years at 0.41% (0.27%, 0.62%), compared with the lowest in those aged 65 to 74 and 75 and over at 0.09% (0.05%, 0.16%). The close approximation between prevalence of infections and deaths (suitably lagged) is diverging, suggesting that infections may have resulted in fewer hospitalisations and deaths since the start of widespread vaccination.

Conclusion

We report a sharp decline in prevalence of infections between February and March 2021. We did not observe an increase in the prevalence of SARS-CoV-2 following the reopening of schools in England, although the decline of prevalence appears to have stopped. Future rounds of REACT-1 will be able to measure the rate of growth or decline from this current plateau and hence help assess the effectiveness of the vaccination roll-out on transmission of the virus as well as the potential size of any third wave during the ensuing months.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2021/04/15/2021.04.08.21255100.full.pdf; doi:https://doi.org/10.1101/2021.04.08.21255100; html:https://europepmc.org/article/PPR/PPR312539; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR312539&type=FILE&fileName=EMS122836-pdf.pdf&mimeType=application/pdf -PPR573001,https://doi.org/10.1101/2022.11.16.22282338,Proteomic analysis of circulating immune cells identifies novel cellular phenotypes associated with COVID-19 severity,"Potts M, Fletcher-Etherington A, Nightingale K, Mescia F, Bergamaschi L, Calero-Nieto FJ, Antrobus R, Williamson J, Kingston N, Göttgens B, Bradley JR, Lehner PJ, Matheson NJ, Smith KG, Wills MR, Lyons PA, Weekes MP, Cambridge Institute of Therapeutic Immunology and Infectious Disease-National Institute of Health Research (CITIID-NIHR) COVID BioResource Collaboration.",,No Journal Info,2022,2022-11-18,Y,,,,"

Summary

Certain serum proteins, including CRP and D-dimer, have prognostic value in patients with SARS-CoV-2 infection. Nonetheless, these factors are non-specific, and provide limited mechanistic insight into the peripheral blood mononuclear cell (PBMC) populations which drive the pathogenesis of severe COVID-19. To identify novel cellular phenotypes associated with disease progression, we here describe a comprehensive, unbiased analysis of the total and plasma membrane proteomes of PBMCs from a cohort of 40 unvaccinated individuals with SARS-CoV-2 infection, spanning the whole spectrum of disease severity. Combined with RNA-seq and flow cytometry data from the same donors, we define a comprehensive multi-omic profile for each severity level, revealing cumulative immune cell dysregulation in progressive disease. In particular, the cell surface proteins CEACAMs1, 6 and 8, CD177, CD63 and CD89 are strongly associated with severe COVID-19, corresponding to the emergence of atypical CD3 + CD4 + CD177 + and CD16 + CEACAM1/6/8 + mononuclear cells. Utilisation of these markers may facilitate real-time patient assessment by flow cytometry, and identify immune cell populations that could be targeted to ameliorate immunopathology.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2022/11/18/2022.11.16.22282338.full.pdf; doi:https://doi.org/10.1101/2022.11.16.22282338; html:https://europepmc.org/article/PPR/PPR573001; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR573001&type=FILE&fileName=EMS157354-pdf.pdf&mimeType=application/pdf PPR241902,https://doi.org/10.1101/2020.11.19.20234120,Actionable druggable genome-wide Mendelian randomization identifies repurposing opportunities for COVID-19,"Gaziano L, Giambartolomei C, Pereira AC, Gaulton A, Posner DC, Swanson SA, Ho Y, Iyengar SK, Kosik NM, Vujkovic M, Gagnon DR, Bento AP, Beltrao P, Barrio-Hernandez I, Rönnblom L, Hagberg N, Lundtoft C, Langenberg C, Pietzner M, Valentine D, Allara E, Surendran P, Burgess S, Zhao JH, Peters JE, Prins BP, Danesh J, Devineni P, Shi Y, Lynch KE, DuVall SL, Garcon H, Thomann LO, Zhou JJ, Gorman BR, Huffman JE, O’Donnell CJ, Tsao PS, Beckham JC, Pyarajan S, Muralidhar S, Huang GD, Ramoni R, Hung AM, Chang K, Sun YV, Joseph J, Leach AR, Edwards TL, Cho K, Gaziano JM, Butterworth AS, Casas JP.",,No Journal Info,2020,2020-11-23,Y,,,,"Drug repurposing provides a rapid approach to meet the urgent need for therapeutics to address COVID-19. To identify therapeutic targets relevant to COVID-19, we conducted Mendelian randomization (MR) analyses, deriving genetic instruments based on transcriptomic and proteomic data for 1,263 actionable proteins that are targeted by approved drugs or in clinical phase of drug development. Using summary statistics from the Host Genetics Initiative and the Million Veteran Program, we studied 7,554 patients hospitalized with COVID-19 and >1 million controls. We found significant Mendelian randomization results for three proteins (ACE2: P= 1.6×10 −6 , IFNAR2: P= 9.8×10 −11 , and IL-10RB: P= 1.9×10 −14 ) using cis -eQTL genetic instruments that also had strong evidence for colocalization with COVID-19 hospitalization. To disentangle the shared eQTL signal for IL10RB and IFNAR2 , we conducted phenome-wide association scans and pathway enrichment analysis, which suggested that IFNAR2 is more likely to play a role in COVID-19 hospitalization. Our findings prioritize trials of drugs targeting IFNAR2 and ACE2 for early management of COVID-19.",,pdf:https://www.nature.com/articles/s41591-021-01310-z.pdf; doi:https://doi.org/10.1101/2020.11.19.20234120; html:https://europepmc.org/article/PPR/PPR241902; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR241902&type=FILE&fileName=EMS105387-pdf.pdf&mimeType=application/pdf +PPR573001,https://doi.org/10.1101/2022.11.16.22282338,Proteomic analysis of circulating immune cells identifies novel cellular phenotypes associated with COVID-19 severity,"Potts M, Fletcher-Etherington A, Nightingale K, Mescia F, Bergamaschi L, Calero-Nieto FJ, Antrobus R, Williamson J, Kingston N, Göttgens B, Bradley JR, Lehner PJ, Matheson NJ, Smith KG, Wills MR, Lyons PA, Weekes MP, Cambridge Institute of Therapeutic Immunology and Infectious Disease-National Institute of Health Research (CITIID-NIHR) COVID BioResource Collaboration.",,No Journal Info,2022,2022-11-18,Y,,,,"

Summary

Certain serum proteins, including CRP and D-dimer, have prognostic value in patients with SARS-CoV-2 infection. Nonetheless, these factors are non-specific, and provide limited mechanistic insight into the peripheral blood mononuclear cell (PBMC) populations which drive the pathogenesis of severe COVID-19. To identify novel cellular phenotypes associated with disease progression, we here describe a comprehensive, unbiased analysis of the total and plasma membrane proteomes of PBMCs from a cohort of 40 unvaccinated individuals with SARS-CoV-2 infection, spanning the whole spectrum of disease severity. Combined with RNA-seq and flow cytometry data from the same donors, we define a comprehensive multi-omic profile for each severity level, revealing cumulative immune cell dysregulation in progressive disease. In particular, the cell surface proteins CEACAMs1, 6 and 8, CD177, CD63 and CD89 are strongly associated with severe COVID-19, corresponding to the emergence of atypical CD3 + CD4 + CD177 + and CD16 + CEACAM1/6/8 + mononuclear cells. Utilisation of these markers may facilitate real-time patient assessment by flow cytometry, and identify immune cell populations that could be targeted to ameliorate immunopathology.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2022/11/18/2022.11.16.22282338.full.pdf; doi:https://doi.org/10.1101/2022.11.16.22282338; html:https://europepmc.org/article/PPR/PPR573001; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR573001&type=FILE&fileName=EMS157354-pdf.pdf&mimeType=application/pdf PPR579535,https://doi.org/10.1101/2022.12.02.22283049,Comparative effectiveness of sotrovimab and molnupiravir for preventing severe COVID-19 outcomes in non-hospitalised patients on kidney replacement therapy: observational cohort study using the OpenSAFELY-UKRR linked platform and SRR database,"The OpenSAFELY Collaborative, Zheng B, Campbell J, Carr EJ, Tazare J, Nab L, Mahalingasivam V, Mehrkar A, Santhakumaran S, Steenkamp R, Loud F, Lyon S, Scanlon M, Hulme WJ, Green AC, Curtis HJ, Fisher L, Parker E, Goldacre B, Douglas I, Evans S, MacKenna B, Bell S, Tomlinson LA, Nitsch D, The LH&W NCS (or CONVALESCENCE) Collaborative.",,No Journal Info,2022,2022-12-04,Y,,,,"

Background

Patients on kidney replacement therapy (KRT; dialysis and kidney transplantation) are at the highest risk of severe outcomes from COVID-19. Due to limited inclusion of patients on KRT in clinical trials, information is limited on the effectiveness of sotrovimab (a neutralising monoclonal antibody). We sought to address this by comparing its effectiveness against molnupiravir (an antiviral) in preventing severe COVID-19 outcomes in non-hospitalised adults with symptomatic COVID-19.

Methods

With the approval of NHS England we used routine clinical data from 24 million patients in England linked to the UK Renal Registry (UKRR) to identify patients on KRT, and data on antiviral treatments, COVID-19 test results, hospitalisation events and death from the OpenSAFELY-TPP data resource. Cox proportional hazards models (stratified for region) were used to estimate hazard ratios of sotrovimab vs. molnupiravir with regards to COVID-19 related hospitalisation or deaths in the subsequent 28 days (as the primary outcome). Further analyses were conducted using propensity score weighting (adjusted for region) and to investigate robustness of results with regards to different time periods, missing data, and adjustment variables. We also conducted a complementary analysis using data from patients in the Scottish Renal Registry (SRR) treated with sotrovimab or molnupiravir, following similar analytical approaches.

Results

Among the 2367 renal patients treated with sotrovimab (n=1852) or molnupiravir (n=515) between December 16, 2021 and August 1, 2022 in England, 38 cases (1.6%) of COVID-19 related hospitalisations/deaths were observed during the 28 days of follow-up after treatment initiation, with 21 (1.1%) in the sotrovimab group and 17 (3.3%) in the molnupiravir group. In multiple-adjusted analysis sotrovimab was associated with substantially lower risk of 28-day COVID-19 related hospitalisation/death than treatment with molnupiravir (hazard ratio, HR=0.35, 95% CI: 0.17 to 0.71; P=0.004), with results remaining robust in sensitivity analyses. In the SRR cohort, there were 19 cases (1.9%) of COVID-19 related hospitalisations/deaths during the 28 days of follow-up after treatment initiation of sotrovimab (n=723) or molnupiravir (n=270). In multiple-adjusted analysis, sotrovimab showed a trend toward lower risk of 28-day COVID-19 related hospitalisation/death than treatment with molnupiravir (HR=0.39, 95% CI: 0.13 to 1.21; P=0.106). In both datasets, sotrovimab had no evidence of association with other hospitalisation/death compared with molnupiravir (HRs ranging from 0.73-1.29; P>0.05).

Conclusions

In routine care of non-hospitalised patients with COVID-19 on kidney replacement therapy, those who received sotrovimab had substantially lower risk of severe COVID-19 outcomes than those receiving molnupiravir.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2022/12/05/2022.12.02.22283049.full.pdf; doi:https://doi.org/10.1101/2022.12.02.22283049; html:https://europepmc.org/article/PPR/PPR579535; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR579535&type=FILE&fileName=EMS158097-pdf.pdf&mimeType=application/pdf PPR225505,https://doi.org/10.1101/2020.10.12.20211342,Network Graph Representation of COVID-19 Scientific Publications to Aid Knowledge Discovery,"Cernile G, Heritage T, Sebire NJ, Gordon B, Schwering T, Kazemlou S, Borecki Y.",,No Journal Info,2020,2020-10-14,N,,,,"

Introduction

Numerous scientific journal articles have been rapidly published related to COVID-19 making navigation and understanding of relationships difficult.

Methods

A graph network was constructed from the publicly available CORD-19 database of COVID-19-related publications using an engine leveraging medical knowledgebases to identify discrete medical concepts and an open source tool (Gephi) used to visualise the network.

Results

The network shows connections between disease, medication and procedures identified from title and abstracts of 195,958 COVID-19 related publications (CORD-19 Dataset). Connections between terms with few publications, those unconnected to the main network and those irrelevant were not displayed. Nodes were coloured by knowledgebase and node size related to the number of publications containing the term. The dataset and visualisations made publicly accessible via a webtool.

Conclusion

Knowledge management approaches (text mining and graph networks) can effectively allow rapid navigation and exploration of entity interrelationships to improve understanding of diseases such as COVID-19.",,pdf:https://discovery.ucl.ac.uk/10119352/1/e100254.full.pdf; doi:https://doi.org/10.1101/2020.10.12.20211342; html:https://europepmc.org/article/PPR/PPR225505; doi:https://doi.org/10.1101/2020.10.12.20211342 PPR425049,https://doi.org/10.1101/2021.11.22.21266512,Association of COVID-19 with arterial and venous vascular diseases: a population-wide cohort study of 48 million adults in England and Wales,"Knight R, Walker V, Ip S, Cooper JA, Bolton T, Keene S, Denholm R, Akbari A, Abbasizanjani H, Torabi F, Omigie E, Hollings S, North T, Toms R, Di Angelantonio E, Denaxas S, Thygesen JH, Tomlinson C, Bray B, Smith CJ, Barber M, Smith GD, Chaturvedi N, Sudlow C, Whiteley WN, Wood A, Sterne JAC, for the CVD-COVID-UK/COVID-IMPACT consortium and the Longitudinal Health and Wellbeing COVID-19 National Core Study.",,No Journal Info,2021,2021-11-24,Y,,,,"

Importance

The long-term effects of COVID-19 on the incidence of vascular diseases are unclear.

Objective

To quantify the association between time since diagnosis of COVID-19 and vascular disease, overall and by age, sex, ethnicity, and pre-existing disease.

Design

Cohort study based on population-wide linked electronic health records, with follow up from January 1 st to December 7 th 2020.

Setting and participants

Adults registered with an NHS general practice in England or Wales and alive on January 1 st 2020.

Exposures

Time since diagnosis of COVID-19 (categorised as 0-6 days, 1-2 weeks, 3-4, 5-8, 9-12, 13-26 and 27-49 weeks since diagnosis), with and without hospitalisation within 28 days of diagnosis.

Main outcomes and measures

Primary outcomes were arterial thromboses (mainly acute myocardial infarction and ischaemic stroke) and venous thromboembolic events (VTE, mainly pulmonary embolism and lower limb deep vein thrombosis). We also studied other vascular events (transient ischaemic attack, haemorrhagic stroke, heart failure and angina). Hazard ratios were adjusted for demographic characteristics, previous disease diagnoses, comorbidities and medications.

Results

Among 48 million adults, 130,930 were and 1,315,471 were not hospitalised within 28 days of COVID-19. In England, there were 259,742 first arterial thromboses and 60,066 first VTE during 41.6 million person-years follow-up. Adjusted hazard ratios (aHRs) for first arterial thrombosis compared with no COVID-19 declined rapidly from 21.7 (95% CI 21.0-22.4) to 3.87 (3.58-4.19) in weeks 1 and 2 after COVID-19, 2.80 (2.61-3.01) during weeks 3-4 then to 1.34 (1.21-1.48) during weeks 27-49. aHRs for first VTE declined from 33.2 (31.3-35.2) and 8.52 (7.59-9.58) in weeks 1 and 2 to 7.95 (7.28-8.68) and 4.26 (3.86-4.69) during weeks 3-4 and 5-8, then 2.20 (1.99-2.44) and 1.80 (1.50-2.17) during weeks 13-26 and 27-49 respectively. aHRs were higher, for longer after diagnosis, after hospitalised than non-hospitalised COVID-19. aHRs were also higher among people of Black and Asian than White ethnicity and among people without than with a previous event. Across the whole population estimated increases in risk of arterial thromboses and VTEs were 2.5% and 0.6% respectively 49 weeks after COVID-19, corresponding to 7,197 and 3,517 additional events respectively after 1.4 million COVID-19 diagnoses.

Conclusions and Relevance

High rates of vascular disease early after COVID-19 diagnosis decline more rapidly for arterial thromboses than VTEs but rates remain elevated up to 49 weeks after COVID_19. These results support continued policies to avoid COVID-19 infection with effective COVID-19 vaccines and use of secondary preventive agents in high-risk patients.

Key points

Question

Is COVID-19 associated with higher long-term incidence of vascular diseases?

Findings

In this cohort study of 48 million adults in England and Wales, COVID-19 was associated with higher incidence, that declined with time since diagnosis, of both arterial thromboses [week 1: adjusted HR [aHR] 21.7 (95% CI 21.0-22.4) weeks 27-49: aHR 1.34 (1.21-1.48)] and venous thromboembolism [week 1: aHR 33.2 (31.3-35.2), weeks 27–49 1.80 (1.50-2.17)]. aHRs were higher, for longer, after hospitalised than non-hospitalised COVID-19. The estimated excess number of arterial thromboses and venous thromboembolisms was 10,500.

Meaning

Avoidance of COVID-19 infection through vaccination, and use of secondary preventive agents after infection in high-risk patients, may reduce post-COVID-19 acute vascular diseases.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2021/11/24/2021.11.22.21266512.full.pdf; doi:https://doi.org/10.1101/2021.11.22.21266512; html:https://europepmc.org/article/PPR/PPR425049; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR425049&type=FILE&fileName=EMS140221-pdf.pdf&mimeType=application/pdf PPR454901,https://doi.org/10.1101/2022.02.14.22270930,Determinants of antibody responses to two doses of ChAdOx1 nCoV-19 or BNT162b2 and a subsequent booster dose of BNT162b2 or mRNA-1273: population-based cohort study (COVIDENCE UK),"Jolliffe DA, Faustini SE, Holt H, Perdek N, Maltby S, Talaei M, Greenig M, Vivaldi G, Tydeman F, Symons J, Davies GA, Lyons RA, Griffiths CJ, Kee F, Sheikh A, Shaheen SO, Richter AG, Martineau AR.",,No Journal Info,2022,2022-02-15,Y,,,,"

Summary

Background

Antibody responses to SARS-CoV-2 vaccination vary for reasons that remain poorly understood.

Methods

We tested for presence of combined IgG, IgA and IgM (IgGAM) anti-spike antibodies before and after administration of two doses of ChAdOx1 nCoV-19 (ChAdOx1, Oxford-AstraZeneca) or BNT162b2 (Pfizer-BioNTech) in UK adults participating in a population-based longitudinal study who received their first dose of vaccine from December 15, 2020 to July 10, 2021. Information on sixty-six potential sociodemographic, behavioural, clinical, pharmacological and nutritional determinants of serological response to vaccination was captured using serial online questionnaires. We used logistic regression to estimate multivariable-adjusted odds ratios (aORs) for associations between independent variables and risk of seronegativity following two vaccine doses. Participants who were seronegative after receiving two vaccine doses were offered an additional antibody test following subsequent administration of a ‘booster’ dose of BNT162b2 or mRNA-1273 (Moderna) from September 23 to December 12, 2021.

Findings

Serology results following two vaccine doses were available for 9,101 participants, of whom 5,770 (63.4%) received ChAdOx1 and 3,331 (36.6%) received BNT162b2. Anti-spike IgGAM was undetectable in 378 (4.2%) participants at a median of 8.6 weeks (IQR 6.4-10.7 weeks) after their second dose of vaccine. Seronegativity following two doses of SARS-CoV-2 vaccination was associated with administration of ChAdOx1 vs BNT162b2 (aOR 7.03, 95% CI 4.39-11.24), shorter interval between first and second vaccine doses (aOR 2.37, 1.06-5.26, for <6 weeks vs >10 weeks; aOR 1.59, 1.18-2.13, for 6-10 weeks vs >10 weeks), poorer self-assessed general health (aOR 3.33, 1.49-7.46, for poor vs excellent), immunodeficiencies (aOR 6.75, 2.63-17.35) and prescription of systemic immunosuppressants (aOR 3.76, 2.44-5.78). By contrast, pre-vaccination SARS-CoV-2 seropositivity (aOR 0.16, 0.04-0.70, for symptomatic seropositives vs seronegatives) and supplemental vitamin D intake (aOR 0.73, 0.53-0.99) were associated with reduced risk of post-vaccination seronegativity. 247/378 (65.3%) of participants who were seronegative after two doses of ChAdOx1 vs BNT162b2 provided a third sample at a median of 7.8 weeks (IQR 5.8-10.4) after receiving a booster dose of BNT162b2 or mRNA-1273: eight (3.2%) of them remained seronegative after three vaccine doses, all of whom either had a primary immunodeficiency or were taking systemic immunosuppressant drugs.

Interpretation

We identify multiple determinants of antibody responses to two doses of ChAdOx1 or BNT162b2, many of which are potentially modifiable. Booster doses of BNT162b2 or mRNA-1273 were highly effective in achieving seroconversion in those who failed to mount antibody responses following two doses of ChAdOx1 or BNT162b2.

Study registration

https://clinicaltrials.gov/ct2/show/NCT04330599

Funding

Barts Charity, Fischer Family Trust, The Exilarch’s Foundation, DSM Nutritional Products, Health Data Research UK

Research in context

Evidence before this study

We searched PubMed, medRxiv, and Google Scholar for papers published from January 1, 2020, to February 1, 2022, using the search terms (antibody OR humoral OR serologic* OR immunogenic*) AND (SARS-CoV-2 vaccine OR ChAdOx1 or BNT162b2 coronavirus), with no language restrictions. Population-based studies investigating multiple potential determinants of vaccine immunogenicity in people with known pre-vaccination SARS-CoV-2 serostatus are lacking.

Added value of this study

This large population-based study, conducted in a population with known pre-vaccination SARS-CoV-2 serostatus, examines a comprehensive range of potential sociodemographic, behavioural, clinical, pharmacological and nutritional determinants of antibody responses to administration of two major SARS-CoV-2 vaccines (i.e., ChAdOx1 or BNT162b2), many of which have not previously been investigated. It is also the first population-based study to characterise antibody responses to booster doses of SARS-CoV-2 vaccines in adults who were seronegative after their primary course of vaccination.

Implications of all the available evidence

Increased risk of seronegativity following two doses of SARS-CoV-2 vaccines was associated with administration of ChAdOx1 vs BNT162b2, shorter interval between first and second vaccine doses, poorer self-assessed general health, immunocompromise and SARS-CoV-2 seronegativity pre-vaccination. Regular intake of vitamin D supplements was associated with reduced risk of post-vaccination seronegativity. Randomised controlled trials are now needed to test for causality. Booster doses of BNT162b2 or mRNA-1273 were highly effective in achieving seroconversion in the majority of people who failed to mount antibody responses following a primary course of vaccination, the few exceptions being a subset of those with primary immunodeficiency or systemic immunosuppressant drugs.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2022/02/15/2022.02.14.22270930.full.pdf; doi:https://doi.org/10.1101/2022.02.14.22270930; html:https://europepmc.org/article/PPR/PPR454901; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR454901&type=FILE&fileName=EMS148745-pdf.pdf&mimeType=application/pdf PPR160431,https://doi.org/10.1101/2020.05.05.20092296,Ethnicity and risk of death in patients hospitalised for COVID-19 infection in the UK: an observational cohort study in an urban catchment area,"Sapey E, Gallier S, Mainey C, Nightingale P, McNulty D, Crothers H, Evison F, Reeves K, Pagano D, Denniston A, Nirantharakumar K, Diggle P, Ball S.",,No Journal Info,2020,2020-05-09,N,,,,"

Background

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

Methods

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

Results

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

Conclusions

Those of South Asian ethnicity appear at risk of worse COVID-19 outcomes, further studies need to establish the underlying mechanistic pathways.","The objective of this study was to determine if specific ethnic groups are at higher risk of dying from covid-19 infection. They found that those of South Asian ethnicity may be at risk of worse COVID-19 outcomes. However, further studies are required to understand this better.",pdf:https://bmjopenrespres.bmj.com/content/bmjresp/7/1/e000644.full.pdf; doi:https://doi.org/10.1101/2020.05.05.20092296; html:https://europepmc.org/article/PPR/PPR160431; doi:https://doi.org/10.1101/2020.05.05.20092296 -PPR546386,https://doi.org/10.1101/2022.09.16.22279985,Conventional and Bayesian workflows for clinical prediction modelling of severe Covid-19 outcomes based on clinical biomarker test results: LabMarCS: Laboratory Markers of COVID-19 Severity - Bristol Cohort,"Sullivan B, Barker E, Williams P, MacGregor L, Bhamber R, Thomas M, Gurney S, Hyams C, Whiteway A, Cooper JA, McWilliams C, Turner K, Dowsey AW, Albur M.",,No Journal Info,2022,2022-09-17,N,,,,"We describe several regression models to predict severe outcomes in COVID-19 and challenges present in complex observational medical data. We demonstrate best practices for data curation, cross-validated statistical modelling, and variable selection emphasizing recent Bayesian methods. The study follows a retrospective observational cohort design using multicentre records across National Health Service (NHS) trusts in southwest England, UK. Participants included hospitalised adult patients positive for SARS-CoV 2 during March to October 2020, totalling 843 patients (mean age 71, 45% female, 32% died or needed ICU stay), split into training (n=590) and validation groups (n=253). Models were fit to predict severe outcomes (ICU admission or death within 28-days of admission to hospital for COVID-19, or a positive PCR result if already admitted) using demographic data and initial results from 30 biomarker tests collected within 3 days of admission or testing positive if already admitted. Cross-validation results showed standard logistic regression had an internal validation median AUC of 0.74 (95% Interval [0.62,0.83]), and external validation AUC of 0.68 [0.61, 0.71]; a Bayesian logistic regression (with horseshoe prior) internal AUC of 0.79 [0.71, 0.87], and external AUC of 0.70 [0.68, 0.71]. Variable selection performed using Bayesian predictive projection determined a four variable model using Age, Urea, Prothrombin time and Neutrophil-Lymphocyte ratio, with a median internal AUC of 0.79 [0.78, 0.80], and external AUC of 0.67 [0.65, 0.69]. We illustrate best-practices protocol for conventional and Bayesian prediction modelling on complex clinical data and reiterate the predictive value of previously identified biomarkers for COVID-19 severity assessment.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2023/01/27/2022.09.16.22279985.full.pdf; doi:https://doi.org/10.1101/2022.09.16.22279985; html:https://europepmc.org/article/PPR/PPR546386; doi:https://doi.org/10.1101/2022.09.16.22279985 PPR290302,https://doi.org/10.1101/2021.02.26.21252512,REACT-2 Round 5: increasing prevalence of SARS-CoV-2 antibodies demonstrate impact of the second wave and of vaccine roll-out in England,"Ward H, Cooke G, Whitaker M, Redd R, Eales O, Brown JC, Collet K, Cooper E, Daunt A, Jones K, Moshe M, Willicombe M, Day S, Atchison C, Darzi A, Donnelly CA, Riley S, Ashby D, Barclay WS, Elliott P.",,No Journal Info,2021,2021-03-01,Y,,,,"

Background

England has experienced high rates of SARS-CoV-2 infection during the COVID-19 pandemic, affecting in particular minority ethnic groups and more deprived communities. A vaccination programme began in England in December 2020, with priority given to administering the first dose to the largest number of older individuals, healthcare and care home workers.

Methods

A cross-sectional community survey in England undertaken between 26 January and 8 February 2021 as the fifth round of the REal-time Assessment of Community Transmission-2 (REACT-2) programme. Participants completed questionnaires, including demographic details and clinical and COVID-19 vaccination histories, and self-administered a lateral flow immunoassay (LFIA) test to detect IgG against SARS-CoV-2 spike protein. There were sufficient numbers of participants to analyse antibody positivity after 21 days from vaccination with the PfizerBioNTech but not the AstraZeneca/Oxford vaccine which was introduced slightly later.

Results

The survey comprised 172,099 people, with valid IgG antibody results from 155,172. The overall prevalence of antibodies (weighted to be representative of the population of England and adjusted for test sensitivity and specificity) in England was 13.9% (95% CI 13.7, 14.1) overall, 37.9% (37.2, 38.7) in vaccinated and 9.8% (9.6, 10.0) in unvaccinated people. The prevalence of antibodies (weighted) in unvaccinated people was highest in London at 16.9% (16.3, 17.5), and higher in people of Black (22.4%, 20.8, 24.1) and Asian (20.0%, 19.0, 21.0) ethnicity compared to white (8.5%, 8.3, 8.7) people. The uptake of vaccination by age was highest in those aged 80 years or older (93.5%). Vaccine confidence was high with 92.0% (91.9, 92.1) of people saying that they had accepted or intended to accept the offer. Vaccine confidence varied by age and ethnicity, with lower confidence in young people and those of Black ethnicity. Particular concerns were identified around pregnancy, fertility and allergies. In 971 individuals who received two doses of the Pfizer-BioNTech vaccine, the proportion testing positive was high across all age groups. Following a single dose of Pfizer-BioNTech vaccine after 21 days or more, 84.1% (82.2, 85.9) of people under 60 years tested positive (unadjusted) with a decreasing trend with increasing age, but high responses to a single dose in those with confirmed or suspected prior COVID at 90.1% (87.2, 92.4) across all age groups.

Conclusions

There is uneven distribution of SARS-CoV-2 antibodies in the population with a higher burden in key workers and some minority ethnic groups, similar to the pattern in the first wave. Confidence in the vaccine programme is high overall although it was lower in some of the higher prevalence groups which suggests the need for improved communication about specific perceived risks. Two doses of Pfizer-BioNTech vaccine, or a single dose following previous infection, confers high levels of antibody positivity across all ages. Further work is needed to understand the relationship between antibody positivity, clinical outcomes such as hospitalisation, and transmission.",,pdf:http://spiral.imperial.ac.uk/bitstream/10044/1/86241/2/REACT%202%20round%205%20preprint.pdf; doi:https://doi.org/10.1101/2021.02.26.21252512; html:https://europepmc.org/article/PPR/PPR290302; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR290302&type=FILE&fileName=EMS117860-pdf.pdf&mimeType=application/pdf +PPR546386,https://doi.org/10.1101/2022.09.16.22279985,Conventional and Bayesian workflows for clinical prediction modelling of severe Covid-19 outcomes based on clinical biomarker test results: LabMarCS: Laboratory Markers of COVID-19 Severity - Bristol Cohort,"Sullivan B, Barker E, Williams P, MacGregor L, Bhamber R, Thomas M, Gurney S, Hyams C, Whiteway A, Cooper JA, McWilliams C, Turner K, Dowsey AW, Albur M.",,No Journal Info,2022,2022-09-17,N,,,,"We describe several regression models to predict severe outcomes in COVID-19 and challenges present in complex observational medical data. We demonstrate best practices for data curation, cross-validated statistical modelling, and variable selection emphasizing recent Bayesian methods. The study follows a retrospective observational cohort design using multicentre records across National Health Service (NHS) trusts in southwest England, UK. Participants included hospitalised adult patients positive for SARS-CoV 2 during March to October 2020, totalling 843 patients (mean age 71, 45% female, 32% died or needed ICU stay), split into training (n=590) and validation groups (n=253). Models were fit to predict severe outcomes (ICU admission or death within 28-days of admission to hospital for COVID-19, or a positive PCR result if already admitted) using demographic data and initial results from 30 biomarker tests collected within 3 days of admission or testing positive if already admitted. Cross-validation results showed standard logistic regression had an internal validation median AUC of 0.74 (95% Interval [0.62,0.83]), and external validation AUC of 0.68 [0.61, 0.71]; a Bayesian logistic regression (with horseshoe prior) internal AUC of 0.79 [0.71, 0.87], and external AUC of 0.70 [0.68, 0.71]. Variable selection performed using Bayesian predictive projection determined a four variable model using Age, Urea, Prothrombin time and Neutrophil-Lymphocyte ratio, with a median internal AUC of 0.79 [0.78, 0.80], and external AUC of 0.67 [0.65, 0.69]. We illustrate best-practices protocol for conventional and Bayesian prediction modelling on complex clinical data and reiterate the predictive value of previously identified biomarkers for COVID-19 severity assessment.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2023/01/27/2022.09.16.22279985.full.pdf; doi:https://doi.org/10.1101/2022.09.16.22279985; html:https://europepmc.org/article/PPR/PPR546386; doi:https://doi.org/10.1101/2022.09.16.22279985 PPR602637,https://doi.org/10.2139/ssrn.4031570,Determinants of Antibody Responses to Two Doses of ChAdOx1 nCoV-19 or Bnt162b2 and a Subsequent Booster Dose of BNT162b2 or mRNA-1273: Population-Based Cohort Study (COVIDENCE UK),"Jolliffe D, Faustini S, Holt H, Perdek N, Maltby S, Talaei M, Greenig M, Vivaldi G, Tydeman F, Symons J, Davies GA, Lyons RA, Griffiths CJ, Kee F, Sheikh A, Shaheen SO, Richter AG, Martineau AR.",,No Journal Info,2022,2022-03-03,Y,,,,"Background: Antibody responses to SARS-CoV-2 vaccination vary for reasons that remain poorly understood.

Methods: We tested for presence of combined IgG, IgA and IgM (IgGAM) anti-spike antibodies before and after administration of two doses of ChAdOx1 nCoV-19 (ChAdOx1, Oxford-AstraZeneca) or BNT162b2 (Pfizer-BioNTech) in UK adults participating in a population-based longitudinal study who received their first dose of vaccine from December 15, 2020 to July 10, 2021. Information on sixty-six potential sociodemographic, behavioural, clinical, pharmacological and nutritional determinants of serological response to vaccination was captured using serial online questionnaires. We used logistic regression to estimate multivariable-adjusted odds ratios (aORs) for associations between independent variables and risk of seronegativity following two vaccine doses. Participants who were seronegative after receiving two vaccine doses were offered an additional antibody test following subsequent administration of a ‘booster’ dose of BNT162b2 or mRNA-1273 (Moderna) from September 23 to December 12, 2021.

Findings: Serology results following two vaccine doses were available for 9,101 participants, of whom 5,770 (63.4%) received ChAdOx1 and 3,331 (36.6%) received BNT162b2. Anti-spike IgGAM was undetectable in 378 (4.2%) participants at a median of 8.6 weeks (IQR 6.4-10.7 weeks) after their second dose of vaccine. Seronegativity following two doses of SARS-CoV-2 vaccination was associated with administration of ChAdOx1 vs BNT162b2 (aOR 7.03, 95% CI 4.39-11.24), shorter interval between first and second vaccine doses (aOR 2.37, 1.06-5.26, for <6 weeks vs >10 weeks; aOR 1.59, 1.18-2.13, for 6-10 weeks vs >10 weeks), poorer self-assessed general health (aOR 3.33, 1.49-7.46, for poor vs excellent), immunodeficiencies (aOR 6.75, 2.63-17.35) and prescription of systemic immunosuppressants (aOR 3.76, 2.44-5.78). By contrast, pre-vaccination SARS-CoV-2 seropositivity (aOR 0.16, 0.04-0.70, for symptomatic seropositives vs seronegatives) and supplemental vitamin D intake (aOR 0.73, 0.53-0.99) were associated with reduced risk of post-vaccination seronegativity. 247/378 (65.3%) of participants who were seronegative after two doses of ChAdOx1 vs BNT162b2 provided a third sample at a median of 7.8 weeks (IQR 5.8-10.4) after receiving a booster dose of BNT162b2 or mRNA-1273: eight (3.2%) of them remained seronegative after three vaccine doses, all of whom either had a primary immunodeficiency or were taking systemic immunosuppressant drugs.

Interpretation: We identify multiple determinants of antibody responses to two doses of ChAdOx1 or BNT162b2, many of which are potentially modifiable. Booster doses of BNT162b2 or mRNA-1273 were highly effective in achieving seroconversion in those who failed to mount antibody responses following two doses of ChAdOx1 or BNT162b2.

Trial Registration Details: Registered with ClinicalTrials.gov (NCT04330599).

Funding Information: This study was supported by a grant from Barts Charity to ARM and CJG (MGU0466) and by donations to Queen Mary University of London from the Fischer Family Trust, the Exilarch’s Foundation and DSM Nutritional Products Ltd. DAJ is supported by a Barts Charity Lectureship (MGU0459). MT is supported by a grant from the Rosetrees Trust and The Bloom Foundation (M771). The work was carried out with the support 20 of BREATHE - The Health Data Research Hub for Respiratory Health (MC_PC_19004) in partnership with SAIL Databank. BREATHE is funded through the UK Research and Innovation Industrial Strategy Challenge Fund and delivered through Health Data Research UK.

Declaration of Interests: JS declares receipt of payments from Reach plc for news stories written about recruitment to, and findings of, the COVIDENCE UK study. AS is a member of the Scottish Government Chief Medical Officer’s COVID-19 Advisory Group and its Standing Committee on Pandemics. He is also a member of the UK Government’s NERVTAG’s Risk Stratification Subgroup. ARM declares receipt of funding in the last 36 months to support vitamin D research from the following companies who manufacture or sell vitamin D supplements: Pharma Nord Ltd, DSM Nutritional Products Ltd, Thornton & Ross Ltd and Hyphens Pharma Ltd. ARM also declares support for attending meetings from the following companies who manufacture or sell vitamin D supplements: Pharma Nord Ltd and Abiogen Pharma Ltd. ARM also declares participation on the Data and Safety Monitoring Board for the Chair, DSMB, VITALITY trial (Vitamin D for Adolescents with HIV to reduce musculoskeletal morbidity and immunopathology). ARM also declares unpaid work as a Programme Committee member for the Vitamin D Workshop. ARM also declares receipt of vitamin D capsules for clinical trial use from Pharma Nord Ltd, Synergy Biologics Ltd and Cytoplan Ltd. All other authors have nothing to declare.

Ethics Approval Statement: Approved by Leicester South Research Ethics Committee (ref 20/EM/0117).
",,doi:https://doi.org/10.1101/2022.02.14.22270930; doi:https://doi.org/10.2139/ssrn.4031570; html:https://europepmc.org/article/PPR/PPR602637; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR602637&type=FILE&fileName=EMS165240-pdf.pdf&mimeType=application/pdf PPR551688,https://doi.org/10.21203/rs.3.rs-2109276/v1,"Harmonising electronic health records for reproducible research: challenges, solutions and recommendations from a UK-wide COVID-19 research collaboration","Abbasizanjani H, Torabi F, Bedston S, Bolton T, Davies G, Denaxas S, Griffiths R, Herbert L, Hollings S, Keene S, Khunti K, Lowthian E, Lyons J, Mizani MA, Nolan J, Sudlow C, Walker V, Whiteley W, Wood A, Akbari A.",,No Journal Info,2022,2022-09-28,Y,,,,"

Background:

The CVD-COVID-UK consortium was formed to understand the relationship between COVID-19 and cardiovascular diseases through analyses of harmonised electronic health records (EHRs) across the four UK nations. Beyond COVID-19, data harmonisation and common approaches enables analysis within and across independent Trusted Research Environments. Here we describe the reproducible harmonisation method developed using large-scale EHRs in Wales to accommodate the fast and efficient implementation of cross-nation analysis in England and Wales as part of the CVD-COVID-UK programme. We characterise current challenges and share lessons learnt. Methods Serving the scope and scalability of multiple study protocols, we used linked, anonymised individual-level EHR, demographic and administrative data held within the SAIL Databank for the population of Wales. The harmonisation method was implemented as a four-layer reproducible process, starting from raw data in the first layer. Then each of the layers two to four is framed by, but not limited to, the characterised challenges and lessons learnt. We achieved curated data as part of our second layer, followed by extracting phenotyped data in the third layer. We captured any project-specific requirements in the fourth layer. Results Using the implemented four-layer harmonisation method, we retrieved approximately 100 health-related variables for the 3.2 million individuals in Wales, which are harmonised with corresponding variables for > 56 million individuals in England. We processed 13 data sources into the first layer of our harmonisation method: five of these are updated daily or weekly, and the rest at various frequencies providing sufficient data flow updates for frequent capturing of up-to-date demographic, administrative and clinical information. Conclusions We implemented an efficient, transparent, scalable, and reproducible harmonisation method that enables multi-nation collaborative research. With a current focus on COVID-19 and its relationship with cardiovascular outcomes, the harmonised data has supported a wide range of research activities across the UK.",,pdf:https://bmcmedinformdecismak.biomedcentral.com/counter/pdf/10.1186/s12911-022-02093-0; doi:https://doi.org/10.21203/rs.3.rs-2109276/v1; html:https://europepmc.org/article/PPR/PPR551688; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR551688&type=FILE&fileName=EMS155094-pdf.pdf&mimeType=application/pdf PPR605135,https://doi.org/10.2139/ssrn.4066712,Using National Electronic Health Records for Pandemic Preparedness: Validation of a Parsimonious Model for Predicting Excess Deaths Among Those With COVID-19,"Mizani MA, Dashtban MH, Pasea L, Lai AG, Thygesen JH, Tomlinson C, Handy A, Mamza JB, Morris T, Khalid S, Zaccardi F, Macleod MJ, Torabi F, Canoy D, Akbari A, Berry C, Bolton T, Nolan J, Khunti K, Denaxas S, Hemingway H, Sudlow C, Banerjee A, CVD-COVID-UK Consortium.",,No Journal Info,2022,2022-03-25,N,,,,"Background: Throughout the pandemic, research, public health, and policy emphasised prediction and surveillance of excess deaths, which have mostly occurred in older individuals with underlying conditions, highlighting importance of baseline mortality risk, infection rate (IR) and pandemic-related relative risk (RR). We now use national, pre- and post-pandemic electronic health records (EHR) to develop and validate a model incorporating these factors for prediction of excess deaths.

Methods: In development (Clinical Practice Research Datalink) and validation (NHS Digital Trusted Research Environment) cohorts in primary and secondary care EHR in England, we included 3·8 million and 35·1 million individuals aged ≥30 years, respectively. For model development, we predicted excess deaths using baseline one-year all-cause mortality risk and assumed RR=3 and IR=10%. For model validation, we observed number of excess deaths from March 2020 to March 2021. We used baseline mortality risk, IR and RR (assumed and observed) to predict excess deaths related to COVID-19.

Findings: Among individuals with at least one high-risk condition, baseline (pre-pandemic) 1-year mortality risk at one year was 4·46% (95% CI 4·41–4·51) and 3.55% (3.54-3.57) in development and validation cohorts, respectively. In our original published model, we predicted 73,498 COVID-19 deaths over 1 year for the population of England. From 1st March 2020 to 1st March 2021, there were 127,020 observed excess deaths. Observed RR was 4·34 (4·31-4·38, 95% CI) and IR was 6·27% (6·26-6·28, 95%CI). In the validation cohort, predicted excess deaths over one year were 100,338 compared with the observed 127,020 deaths with a ratio of predicted to observed excess deaths of 0.79. We found that vaccination had a negligible effect on overall RR or IR between 1st December 2020 and 1st March 2021, compared to the likely effect of under-reported COVID-19 cases from the pre-vaccination period.

Interpretation: We show that a simple, parsimonious model incorporating baseline mortality risk, one-year infection rate and relative risk of the pandemic can be used to predict excess deaths. Our analyses show that EHR could inform pandemic planning and surveillance, despite limited use in emergency preparedness to-date. Although infection dynamics are important in prediction of morbidity and mortality, future models should take greater account of underlying conditions and their associated risks.

Funding Information: The British Heart Foundation Data Science Centre (grant No SP/19/3/34678, awarded to Health Data Research (HDR) UK) funded co-development (with NHS Digital) of the trusted research environment, provision of linked datasets, data access, user software licences, computational usage, and data management and wrangling support, with additional contributions from the HDR UK data and connectivity component of the UK Government Chief Scientific Adviser’s National Core Studies programme to coordinate national Covid-19 priority research. Consortium partner organisations funded the time of contributing data analysts, biostatisticians, epidemiologists, and clinicians. AB, MAM, MHD and LP were supported by research funding from AstraZeneca. AB has received funding from the National Institute for Health Research (NIHR), British Medical Association, and UK Research and Innovation. AB, SD and HH are part of the BigData@Heart Consortium, funded by the Innovative Medicines Initiative-2 Joint Undertaking under grant agreement No 116074. K.K. is supported by the National Institute for Health Research (NIHR) Applied Research Collaboration East Midlands (ARC EM) and NIHR Lifestyle BRC.

Declaration of Interests: JBM and TM are employees of AstraZeneca. KK is chair of the ethnicity subgroup of the Independent Scientific Advisory Group for Emergencies (SAGE) and director of the University of Leicester Centre for Black Minority Ethnic Health. KK and AB are trustees of the South Asian Health Foundation (SAHF). CS is Director of the BHF Data Science Centre. All other authors report no competing interests.

Ethics Approval Statement: Approval for the study in CPRD was granted by the Independent Scientific Advisory Committee (20_074R) of the Medicines and Healthcare products Regulatory Agency in the UK in accordance with the Declaration of Helsinki. The North East-Newcastle and North Tyneside 2 research ethics committee provided ethical approval for the CVD- COVID-UK research programme (REC No 20/NE/0161).
",,doi:https://doi.org/10.2139/ssrn.4066712; html:https://europepmc.org/article/PPR/PPR605135; doi:https://doi.org/10.2139/ssrn.4066712 @@ -174,8 +174,8 @@ PPR241057,https://doi.org/10.1101/2020.11.18.20233932,REACT-1 round 6 updated re PPR373640,https://doi.org/10.1101/2021.07.21.21260926,"Increasing SARS-CoV-2 antibody prevalence in England at the start of the second wave: REACT-2 Round 4 cross-sectional study in 160,000 adults","Ward H, Atchison C, Whitaker M, Donnelly CA, Riley S, Ashby D, Darzi A, Barclay WS, Cooke G, Elliott P, for the REACT study team.",,No Journal Info,2021,2021-07-22,Y,,,,"

Background

REACT-2 Study 5 is a population survey of the prevalence of SARS-CoV-2 antibodies in the community in England.

Methods

We contacted a random sample of the population by sending a letter to named individuals aged 18 or over from the NHS GP registrations list. We then sent respondents a lateral flow immunoassay (LFIA) kit for SARS-CoV-2 antibody self-testing and asked them to perform the test at home and complete a questionnaire, including reporting of their test result. Overall, 161,537 adults completed questionnaires and self-administered LFIA tests for IgG against SARS-CoV-2 between 27 October and 10 November 2020.

Results

The overall adjusted and weighted prevalence was 5.6% (95% CI 5.4-5.7). This was an increase from 4.4% (4.3-4.5) in round 3 (September), a relative increase of 26.9% (24.0-29.9).The largest increase by age was in the 18 to 24 year old age group, which increased (adjusted and weighted) from 6.7% (6.3-7.2) to 9.9% (9.3-10.4), and in students, (adjusted, unweighted) from 5.9% (4.8-7.1) to 12.1% (10.8-13.5). Prevalence increased most in Yorkshire and The Humber, from 3.4% (3.0-3.8) to 6.3% (5.9-6.8) and the North West from 4.5% (4.2-4.9) to 7.7% (7.2-8.1). In contrast, the prevalence in London was stable, at 9.5% (9.0-9.9) and 9.5% (9.1-10.0) in rounds 3 and 4 respectively. We found the highest prevalence in people of Bangladeshi 15.1% (10.9-20.5), Pakistani 13.9% (11.2-17.2) and African 13.5% (10.7-16.8) ethnicity, and lowest in those of white British ethnicity at 4.2% (4.0-4.3).

Interpretation

The second wave of infection in England is apparent in increasing antibody prevalence, particularly in younger people, students, and in the Northern Regions. By late October a large proportion of the population remained susceptible to SARS-CoV-2 infection in England based on naturally acquired immunity from the first and early second wave.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2021/07/22/2021.07.21.21260926.full.pdf; doi:https://doi.org/10.1101/2021.07.21.21260926; html:https://europepmc.org/article/PPR/PPR373640; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR373640&type=FILE&fileName=EMS132216-pdf.pdf&mimeType=application/pdf PPR365249,https://doi.org/10.1101/2021.06.28.21259452,"Persistent symptoms following SARS-CoV-2 infection in a random community sample of 508,707 people","Whitaker M, Elliott J, Chadeau-Hyam M, Riley S, Darzi A, Cooke G, Ward H, Elliott P.",,No Journal Info,2021,2021-07-03,Y,,,,"

Summary

Background

Long COVID, describing the long-term sequelae after SARS-CoV-2 infection, remains a poorly defined syndrome. There is uncertainty about its predisposing factors and the extent of the resultant public health burden, with estimates of prevalence and duration varying widely.

Methods

Within rounds 3–5 of the REACT-2 study, 508,707 people in the community in England were asked about a prior history of COVID-19 and the presence and duration of 29 different symptoms. We used uni-and multivariable models to identify predictors of persistence of symptoms (12 weeks or more). We estimated the prevalence of symptom persistence at 12 weeks, and used unsupervised learning to cluster individuals by symptoms experienced.

Findings

Among the 508,707 participants, the weighted prevalence of self-reported COVID-19 was 19.2% (95% CI: 19.1,19.3). 37.7% of 76,155 symptomatic people post COVID-19 experienced at least one symptom, while 14.8% experienced three or more symptoms, lasting 12 weeks or more. This gives a weighted population prevalence of persistent symptoms of 5.75% (5.68, 5.81) for one and 2.22% (2.1, 2.26) for three or more symptoms. Almost a third of people (8,771/28,713 [30.5%]) with at least one symptom lasting 12 weeks or more reported having had severe COVID-19 symptoms (“significant effect on my daily life”) at the time of their illness, giving a weighted prevalence overall for this group of 1.72% (1.69,1.76). The prevalence of persistent symptoms was higher in women than men (OR: 1.51 [1.46,1.55]) and, conditional on reporting symptoms, risk of persistent symptoms increased linearly with age by 3.5 percentage points per decade of life. Obesity, smoking or vaping, hospitalisation, and deprivation were also associated with a higher probability of persistent symptoms, while Asian ethnicity was associated with a lower probability. Two stable clusters were identified based on symptoms that persisted for 12 weeks or more: in the largest cluster, tiredness predominated, while in the second there was a high prevalence of respiratory and related symptoms.

Interpretation

A substantial proportion of people with symptomatic COVID-19 go on to have persistent symptoms for 12 weeks or more, which is age-dependent. Clinicians need to be aware of the differing manifestations of Long COVID which may require tailored therapeutic approaches. Managing the long-term sequelae of SARS-CoV-2 infection in the population will remain a major challenge for health services in the next stage of the pandemic.

Funding

The study was funded by the Department of Health and Social Care in England.

Research in context

Evidence before this study

Recent systematic reviews have documented the wide range of symptoms and reported prevalence of persistent symptoms following COVID-19. A dynamic review of Long COVID studies (NIHR Evidence) in March 2021 summarised the literature on the prevalence of persistent symptoms after acute COVID19, and reported that most studies (14) were of hospitalised patients, with higher prevalence of persistent symptoms compared with two community-based studies. There was limited evidence from community studies beyond 12 weeks. Another systematic review reported a median of over 70% of people with symptoms lasting at least 60 days. A review of risk factors for Long COVID found consistent evidence for an increased risk amongst women and those with high body mass index (BMI) but inconsistent findings on the role of age and little evidence concerning risks among different socioeconomic or ethnic groups which are often not well captured in routine healthcare records. Long COVID is increasingly recognised as heterogenous, likely underpinned by differing biological mechanisms, but there is not yet consensus on defining subtypes of the condition.

Added value of this study

This community-based study of over half a million people was designed to be representative of the adult population of England. A random sample of adults ages 18 years and above registered with a GP were invited irrespective of previous access to services for COVID-19, providing an estimate of population prevalence that was representative of the whole population. The findings show substantial declines in symptom prevalence over the first 12 weeks following Covid-19, reported by nearly one fifth of respondents, of whom over a third remained symptomatic at 12 weeks and beyond, with little evidence for decline thereafter. Risk factors identified for persistent symptoms (12 weeks or more) suggestive of Long COVID confirm some previous findings - an increased risk in women, obese and overweight individuals and those hospitalised for COVID-19, with strong evidence for an increasing risk with age. Additional evidence was found for an increased risk in those with lower income, smoking or vaping and healthcare or care home workers. A lower risk was found in those of Asian ethnicity. Clustering identified two distinct groups of individuals wit h different symptom profiles at 12 weeks, highlighting the heterogeneity of clinical presentation. The smaller cluster had higher prevalence of respiratory and related symptoms, while for those in the larger cluster tiredness was the dominant symptom, with lower prevalence of organ-specific symptoms.

Implications of available evidence

There is a high prevalence of persistent symptoms beyond 12 weeks after acute COVID-19, with little evidence of decline thereafter. This highlights the needs for greater support for patients, both through specialised services and, for those from low-income settings, financial support. The understanding that there are distinct clusters of persistent symptoms, the most common of which is dominated by fatigue, is important for the recognition and clinical management of the condition outside of specialised services.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2021/07/03/2021.06.28.21259452.full.pdf; doi:https://doi.org/10.1101/2021.06.28.21259452; html:https://europepmc.org/article/PPR/PPR365249; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR365249&type=FILE&fileName=EMS129876-pdf.pdf&mimeType=application/pdf PPR486740,https://doi.org/10.1101/2022.04.26.22274332,"Community factors and excess mortality in the COVID-19 pandemic in England, Italy and Sweden","Parkes B, Stafoggia M, Fecht D, Davies B, Bonander C, de’ Donato F, Michelozzi P, Piel FB, Strömberg U, Blangiardo M.",,No Journal Info,2022,2022-04-27,Y,,,,"

Background

Analyses of COVID-19 suggest specific risk factors make communities more or less vulnerable to pandemic related deaths within countries. What is unclear is whether the characteristics affecting vulnerability of small communities within countries produce similar patterns of excess mortality across countries with different demographics and public health responses to the pandemic. Our aim is to quantify community-level variations in excess mortality within England, Italy and Sweden and identify how such spatial variability was driven by community-level characteristics.

Methods

We applied a two-stage Bayesian model to quantify inequalities in excess mortality in people aged 40 years and older at the community level in England, Italy and Sweden during the first year of the pandemic (March 2020–February 2021). We used community characteristics measuring deprivation, air pollution, living conditions, population density and movement of people as covariates to quantify their associations with excess mortality.

Results

We found just under half of communities in England (48.1%) and Italy (45.8%) had an excess mortality of over 300 per 100,000 males over the age of 40, while for Sweden that covered 23.1% of communities. We showed that deprivation is a strong predictor of excess mortality across the three countries, and communities with high levels of overcrowding were associated with higher excess mortality in England and Sweden.

Conclusion

These results highlight some international similarities in factors affecting mortality that will help policy makers target public health measures to increase resilience to the mortality impacts of this and future pandemics.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2022/05/09/2022.04.26.22274332.full.pdf; doi:https://doi.org/10.1101/2022.04.26.22274332; html:https://europepmc.org/article/PPR/PPR486740; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR486740&type=FILE&fileName=EMS144662-pdf.pdf&mimeType=application/pdf -PPR433539,https://doi.org/10.1101/2021.12.16.21267934,Predictors of SARS-CoV-2 infection in a multi-ethnic cohort of United Kingdom healthcare workers: a prospective nationwide cohort study (UK-REACH),"Martin CA, Pan D, Melbourne C, Teece L, Aujayeb A, Baggaley RF, Bryant L, Carr S, Gregary B, Gupta A, Guyatt AL, John C, McManus IC, Nazareth J, Nellums LB, Reza R, Simpson S, Tobin MD, Woolf K, Zingwe S, Khunti K, Abrams KR, Gray LJ, Pareek M.",,No Journal Info,2021,2021-12-17,Y,,,,"

Introduction

Healthcare workers (HCWs), particularly those from ethnic minority groups, have been shown to be at disproportionately higher risk of infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) compared to the general population. However, there is insufficient evidence on how demographic and occupational factors influence infection risk among ethnic minority HCWs.

Methods

We conducted a cross-sectional analysis using data from the United Kingdom Research study into Ethnicity And COVID-19 Outcomes in Healthcare workers (UK-REACH) cohort study. We used logistic regression to examine associations of demographic, household and occupational predictor variables with SARS-CoV-2 infection (defined by PCR, serology or suspected COVID-19) in a diverse group of HCWs.

Results

2,496 of the 10,772 HCWs (23.2%) who worked during the first UK national lockdown in March 2020 reported previous SARS-CoV-2 infection. In an adjusted model, demographic and household factors associated with increased odds of infection included younger age, living with other key workers and higher religiosity. Important occupational risk factors associated with increased odds of infection included attending to a higher number of COVID-19 positive patients (aOR 2.49, 95%CI 2.03–3.05 for ≥21 patients per week vs none), working in a nursing or midwifery role (1.35, 1.15– 1.58, compared to doctors), reporting a lack of access to personal protective equipment (1.27, 1.15 – 1.41) and working in an ambulance (1.95, 1.52–2.50) or hospital inpatient setting (1.54, 1.37 – 1.74). Those who worked in Intensive Care Units were less likely to have been infected (0.76, 0.63–0.90) than those who did not. Black HCWs were more likely to have been infected than their White colleagues, an effect which attenuated after adjustment for other known predictors.

Conclusions

We identified key sociodemographic and occupational risk factors associated with SARS-CoV-2 infection amongst UK HCWs, and have determined factors that might contribute to a disproportionate odds of infection in HCWs from Black ethnic groups. These findings demonstrate the importance of social and occupational factors in driving ethnic disparities in COVID-19 outcomes, and should inform policies, including targeted vaccination strategies and risk assessments aimed at protecting HCWs in future waves of the COVID-19 pandemic.

Trial registration

ISRCTN 11811602",,pdf:https://www.medrxiv.org/content/medrxiv/early/2021/12/17/2021.12.16.21267934.full.pdf; doi:https://doi.org/10.1101/2021.12.16.21267934; html:https://europepmc.org/article/PPR/PPR433539; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR433539&type=FILE&fileName=EMS141796-pdf.pdf&mimeType=application/pdf PPR408448,https://doi.org/10.1101/2021.10.13.21264937,Comparative effectiveness of ChAdOx1 versus BNT162b2 COVID-19 vaccines in Health and Social Care workers in England: a cohort study using OpenSAFELY,"Hulme WJ, Williamson EJ, Green A, Bhaskaran K, McDonald HI, Rentsch CT, Schultze A, Tazare J, Curtis HJ, Walker AJ, Tomlinson L, Palmer T, Horne E, MacKenna B, Morton CE, Mehrkar A, Fisher L, Bacon S, Evans D, Inglesby P, Hickman G, Davy S, Ward T, Croker R, Eggo RM, Wong AY, Mathur R, Wing K, Forbes H, Grint D, Douglas IJ, Evans SJ, Smeeth L, Bates C, Cockburn J, Parry J, Hester F, Harper S, Sterne JA, Hernán M, Goldacre B.",,No Journal Info,2021,2021-10-18,Y,,,,"

Objectives

To compare the effectiveness of the BNT162b2 mRNA (Pfizer-BioNTech) and the ChAdOx1 (Oxford-AstraZeneca) COVID-19 vaccines against infection and COVID-19 disease in health and social care workers.

Design

Cohort study, emulating a comparative effectiveness trial.

Setting

Linked primary care, hospital, and COVID-19 surveillance records available within the OpenSAFELY-TPP research platform.

Participants

317,341 health and social care workers vaccinated between 4 January and 28 February 2021, registered with a GP practice using the TPP SystmOne clinical information system in England, and not clinically extremely vulnerable.

Interventions

Vaccination with either BNT162b2 or ChAdOx1 administered as part of the national COVID-19 vaccine roll-out.

Main outcome measures

Recorded SARS-CoV-2 positive test, or COVID-19 related Accident and Emergency attendance or hospital admission occurring within 20 weeks of vaccination.

Results

The cumulative incidence of each outcome was similar for both vaccines during the first 20 weeks post-vaccination. The cumulative incidence of recorded SARS-CoV-2 infection 6 weeks after vaccination with BNT162b2 was 19.2 per 1000 people (95%CI 18.6 to 19.7) and with ChAdOx1 was 18.9 (95%CI 17.6 to 20.3), representing a difference of -0.24 per 1000 people (95%CI -1.71 to 1.22). The difference in the cumulative incidence per 1000 people of COVID-19 accident and emergency attendance at 6 weeks was 0.01 per 1000 people (95%CI -0.27 to 0.28). For COVID-19 hospital admission, this difference was 0.03 per 1000 people (95%CI -0.22 to 0.27).

Conclusions

In this cohort of healthcare workers where we would not anticipate vaccine type to be related to health status, we found no substantial differences in the incidence of SARS-CoV-2 infection or COVID-19 disease up to 20 weeks after vaccination. Incidence dropped sharply after 3-4 weeks and there were very few COVID-19 hospital attendance and admission events after this period. This is in line with expected onset of vaccine-induced immunity, and suggests strong protection against COVID-19 disease for both vaccines.",,pdf:https://research-information.bris.ac.uk/files/345986511/bmj_2021_068946.full.pdf; doi:https://doi.org/10.1101/2021.10.13.21264937; html:https://europepmc.org/article/PPR/PPR408448; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR408448&type=FILE&fileName=EMS137186-pdf.pdf&mimeType=application/pdf +PPR433539,https://doi.org/10.1101/2021.12.16.21267934,Predictors of SARS-CoV-2 infection in a multi-ethnic cohort of United Kingdom healthcare workers: a prospective nationwide cohort study (UK-REACH),"Martin CA, Pan D, Melbourne C, Teece L, Aujayeb A, Baggaley RF, Bryant L, Carr S, Gregary B, Gupta A, Guyatt AL, John C, McManus IC, Nazareth J, Nellums LB, Reza R, Simpson S, Tobin MD, Woolf K, Zingwe S, Khunti K, Abrams KR, Gray LJ, Pareek M.",,No Journal Info,2021,2021-12-17,Y,,,,"

Introduction

Healthcare workers (HCWs), particularly those from ethnic minority groups, have been shown to be at disproportionately higher risk of infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) compared to the general population. However, there is insufficient evidence on how demographic and occupational factors influence infection risk among ethnic minority HCWs.

Methods

We conducted a cross-sectional analysis using data from the United Kingdom Research study into Ethnicity And COVID-19 Outcomes in Healthcare workers (UK-REACH) cohort study. We used logistic regression to examine associations of demographic, household and occupational predictor variables with SARS-CoV-2 infection (defined by PCR, serology or suspected COVID-19) in a diverse group of HCWs.

Results

2,496 of the 10,772 HCWs (23.2%) who worked during the first UK national lockdown in March 2020 reported previous SARS-CoV-2 infection. In an adjusted model, demographic and household factors associated with increased odds of infection included younger age, living with other key workers and higher religiosity. Important occupational risk factors associated with increased odds of infection included attending to a higher number of COVID-19 positive patients (aOR 2.49, 95%CI 2.03–3.05 for ≥21 patients per week vs none), working in a nursing or midwifery role (1.35, 1.15– 1.58, compared to doctors), reporting a lack of access to personal protective equipment (1.27, 1.15 – 1.41) and working in an ambulance (1.95, 1.52–2.50) or hospital inpatient setting (1.54, 1.37 – 1.74). Those who worked in Intensive Care Units were less likely to have been infected (0.76, 0.63–0.90) than those who did not. Black HCWs were more likely to have been infected than their White colleagues, an effect which attenuated after adjustment for other known predictors.

Conclusions

We identified key sociodemographic and occupational risk factors associated with SARS-CoV-2 infection amongst UK HCWs, and have determined factors that might contribute to a disproportionate odds of infection in HCWs from Black ethnic groups. These findings demonstrate the importance of social and occupational factors in driving ethnic disparities in COVID-19 outcomes, and should inform policies, including targeted vaccination strategies and risk assessments aimed at protecting HCWs in future waves of the COVID-19 pandemic.

Trial registration

ISRCTN 11811602",,pdf:https://www.medrxiv.org/content/medrxiv/early/2021/12/17/2021.12.16.21267934.full.pdf; doi:https://doi.org/10.1101/2021.12.16.21267934; html:https://europepmc.org/article/PPR/PPR433539; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR433539&type=FILE&fileName=EMS141796-pdf.pdf&mimeType=application/pdf PPR359256,https://doi.org/10.1101/2021.06.17.21259103,REACT-1 round 12 report: resurgence of SARS-CoV-2 infections in England associated with increased frequency of the Delta variant,"Riley S, Wang H, Eales O, Haw D, Walters CE, Ainslie KEC, Atchison C, Fronterre C, Diggle PJ, Page AJ, Prosolek SJ, Trotter AJ, Le Viet T, Alikhan N, Jackson LM, Ludden C, Ashby D, Donnelly CA, Cooke G, Barclay W, Ward H, Darzi A, Elliott P, The COVID-19 Genomics UK (COG-UK) Consortium.",,No Journal Info,2021,2021-06-21,Y,,,,"

Background

England entered a third national lockdown from 6 January 2021 due to the COVID-19 pandemic. Despite a successful vaccine rollout during the first half of 2021, cases and hospitalisations have started to increase since the end of May as the SARS-CoV-2 Delta (B.1.617.2) variant increases in frequency. The final step of relaxation of COVID-19 restrictions in England has been delayed from 21 June to 19 July 2021.

Methods

The REal-time Assessment of Community Transmision-1 (REACT-1) study measures the prevalence of swab-positivity among random samples of the population of England. Round 12 of REACT-1 obtained self-administered swab collections from participants from 20 May 2021 to 7 June 2021; results are compared with those for round 11, in which swabs were collected from 15 April to 3 May 2021.

Results

Between rounds 11 and 12, national prevalence increased from 0.10% (0.08%, 0.13%) to 0.15% (0.12%, 0.18%). During round 12, we detected exponential growth with a doubling time of 11 (7.1, 23) days and an R number of 1.44 (1.20, 1.73). The highest prevalence was found in the North West at 0.26% (0.16%, 0.41%) compared to 0.05% (0.02%, 0.12%) in the South West. In the North West, the locations of positive samples suggested a cluster in Greater Manchester and the east Lancashire area. Prevalence in those aged 5-49 was 2.5 times higher at 0.20% (0.16%, 0.26%) compared with those aged 50 years and above at 0.08% (0.06%, 0.11%). At the beginning of February 2021, the link between infection rates and hospitalisations and deaths started to weaken, although in late April 2021, infection rates and hospital admissions started to reconverge. When split by age, the weakened link between infection rates and hospitalisations at ages 65 years and above was maintained, while the trends converged below the age of 65 years. The majority of the infections in the younger group occurred in the unvaccinated population or those without a stated vaccine history. We observed the rapid replacement of the Alpha (B.1.1.7) variant of SARS-CoV-2 with the Delta variant during the period covered by rounds 11 and 12 of the study.

Discussion

The extent to which exponential growth continues, or slows down as a consequence of the continued rapid roll-out of the vaccination programme, including to young adults, requires close monitoring. Data on community prevalence are vital to track the course of the epidemic and inform ongoing decisions about the timing of further lifting of restrictions in England.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2021/06/21/2021.06.17.21259103.full.pdf; doi:https://doi.org/10.1101/2021.06.17.21259103; html:https://europepmc.org/article/PPR/PPR359256; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR359256&type=FILE&fileName=EMS128173-pdf.pdf&mimeType=application/pdf PPR380903,https://doi.org/10.1101/2021.08.10.21261834,Immuno-proteomic profiling reveals abundant airway CD8 T cells and ongoing epithelial injury in prolonged post-COVID19 respiratory disease,"Vijayakumar B, Boustani K, Ogger PP, Papadaki A, Tonkin J, Orton CM, Ghai P, Suveizdyte K, Hewitt RJ, Snelgrove RJ, Molyneaux PL, Garner JL, Peters JE, Shah PL, Lloyd CM, Harker JA.",,No Journal Info,2021,2021-08-10,Y,,,,"

Summary

Some patients hospitalized with acute COVID19 suffer respiratory symptoms that persist for many months. To characterize the local and systemic immune responses associated with this form of ‘Long COVID’, we delineated the immune and proteomic landscape in the airway and peripheral blood of normal volunteers and patients from 3 to 6 months after hospital discharge. The bronchoalveolar lavage (but not peripheral blood) proteome was abnormal in patients with post-COVID19 lung disease with significantly elevated concentration of proteins associated with apoptosis, tissue repair and epithelial injury. This correlated with an increase in cytotoxic lymphocytes (especially tissue resident CD8 + T cells), lactate dehydrogenase and albumin (biomarkers of cell death and barrier integrity). Follow-up of a subset of these patients greater than 1-year post-COVID19 indicated these abnormalities resolved over time. Collectively, these data indicate that COVID-19 results in a prolonged change to the airway immune landscape in those with persistent lung disease, with evidence of cell death and tissue repair linked to ongoing activation of cytotoxic T cells.

Highlights

The post-COVID19 airway is characterized by increased cytotoxic lymphocytes. Distinct airway proteomes are associated with the airway immune cell landscape. The peripheral blood does not predict immune-proteome alterations in the airway post-COVID19. Persistent abnormalities in the airway immune-proteome post-COVID19 airways correlate with ongoing epithelial damage.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2021/08/11/2021.08.10.21261834.full.pdf; doi:https://doi.org/10.1101/2021.08.10.21261834; html:https://europepmc.org/article/PPR/PPR380903; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR380903&type=FILE&fileName=EMS132662-pdf.pdf&mimeType=application/pdf PPR449587,https://doi.org/10.1101/2022.02.01.22270235,Hospitalisation for COVID-19 predicts long lasting cerebrovascular impairment: A prospective observational cohort study,"Tsvetanov KA, Spindler LRB, Stamatakis EA, Newcombe VF, Lupson VC, Chatfield DA, Manktelow AE, Outtrim JG, Elmer A, Kingston N, Bradley JR, Bullmore ET, Rowe JB, Menon DK, The Cambridge NeuroCOVID Group, The NIHR COVID-19 BioResource, The Cambridge NIHR Clinical Research Facility, The CITIID-NIHR BioResource COVID-19 Collaboration.",,No Journal Info,2022,2022-02-02,Y,,,,"Human coronavirus disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has multiple neurological consequences, but its long-term effect on brain health is still uncertain. The cerebrovascular consequences of COVID-19 may also affect brain health. Here we assess cerebrovascular health in 45 hospitalised patients using the resting state fluctuation amplitudes (RSFA) from functional magnetic resonance imaging, in relation to disease severity and in contrast with 42 controls. Widespread changes in frontoparietal RSFA were related to the severity of the acute COVID-19 episode, as indexed by COVID-19 WHO Progression Scale, inflammatory and coagulatory biomarkers. This relationship was not explained by chronic cardiorespiratory dysfunction, age, or sex. Exploratory analysis suggests that the level of cerebrovascular dysfunction is associated with cognitive, mental, and physical health at follow-up. The principal findings were consistent across univariate and multivariate approaches. The results indicate chronic cerebrovascular impairment following severe acute COVID-19, with the potential for long-term consequences on cognitive function and mental wellbeing.",,pdf:https://www.repository.cam.ac.uk/bitstreams/dc24fc5e-7064-4af8-a659-777a57181201/download; doi:https://doi.org/10.1101/2022.02.01.22270235; html:https://europepmc.org/article/PPR/PPR449587; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR449587&type=FILE&fileName=EMS143509-pdf.pdf&mimeType=application/pdf @@ -185,8 +185,8 @@ PPR445654,https://doi.org/10.1101/2022.01.21.22269605,Outcomes of SARS-CoV-2 Omi PPR167068,https://doi.org/10.1101/2020.05.19.20106278,Benefit-risk analysis of health benefits of routine childhood immunisation against the excess risk of SARS-CoV-2 infections during the COVID-19 pandemic in Africa,"Abbas K, Procter SR, van Zandvoort K, Clark A, Funk S, Mengistu T, Hogan D, Dansereau E, Jit M, Flasche S, LSHTM CMMID CMMID COVID-19 Working Group.",,No Journal Info,2020,2020-05-26,Y,,,,"

Summary

Background

National immunisation programmes globally are at risk of suspension due to the severe health system constraints and physical distancing measures in place to mitigate the ongoing COVID-19 pandemic. Our aim is to compare the health benefits of sustaining routine childhood immunisation in Africa against the risk of acquiring SARS-CoV-2 infections through visiting routine vaccination service delivery points.

Methods

We used two scenarios to approximate the child deaths that may be caused by immunisation coverage reductions during COVID-19 outbreaks. First, we used previously reported country-specific child mortality impact estimates of childhood immunisation for diphtheria, tetanus, pertussis, hepatitis B, Haemophilus influenzae type b, pneumococcal, rotavirus, measles, meningitis A, rubella, and yellow fever (DTP3, HepB3, Hib3, PCV3, RotaC, MCV1, MCV2, MenA, RCV, YFV) to approximate the future deaths averted before completing five years of age by routine childhood vaccination during a 6-month COVID-19 risk period without catch-up campaigns. Second, we analysed an alternative scenario that approximates the health benefits of sustaining routine childhood immunisation to only the child deaths averted from measles outbreaks during the COVID-19 risk period. The excess number of infections due to additional SARS-CoV-2 exposure during immunisation visits assumes that contact reducing interventions flatten the outbreak curve during the COVID-19 risk period, that 60% of the population will have been infected by the end of that period, that children can be infected by either vaccinators or during transport and that upon child infection the whole household would be infected. Country specific household age structure estimates and age dependent infection fatality rates are then applied to calculate the number of deaths attributable to the vaccination clinic visits. We present benefit-risk ratios for routine childhood immunisation alongside 95% uncertainty range estimates from probabilistic sensitivity analysis.

Findings

For every one excess COVID-19 death attributable to SARS-CoV-2 infections acquired during routine vaccination clinic visits, there could be 84 (14-267) deaths in children prevented by sustaining routine childhood immunisation in Africa. The benefit-risk ratio for the vaccinated children, siblings, parents or adult care-givers, and older adults in the households of vaccinated children are 85,000 (4,900 - 546,000), 75,000 (4,400 - 483,000), 769 (148 - 2,700), and 96 (14 - 307) respectively. In the alternative scenario that approximates the health benefits to only the child deaths averted from measles outbreaks, the benefit-risk ratio to the households of vaccinated children is 3 (0 - 10) under these highly conservative assumptions and if the risk to only the vaccinated children is considered, the benefit-risk ratio is 3,000 (182 - 21,000).

Interpretation

Our analysis suggests that the health benefits of deaths prevented by sustaining routine childhood immunisation in Africa far outweighs the excess risk of COVID-19 deaths associated with vaccination clinic visits, especially for the vaccinated children. However, there are other factors that must be considered for strategic decision making to sustain routine childhood immunisation in African countries during the COVID-19 pandemic. These include logistical constraints of vaccine supply chain problems caused by the COVID-19 pandemic, reallocation of immunisation providers to other prioritised health services, healthcare staff shortages caused by SARS-CoV-2 infections among the staff, decreased demand for vaccination arising from community reluctance to visit vaccination clinics for fear of contracting SARS-CoV-2 infections, and infection risk to healthcare staff providing immunisation services as well as to their households and onward SARS-CoV-2 transmission into the wider community.

Funding

Gavi, the Vaccine Alliance and Bill & Melinda Gates Foundation (OPP1157270)

Research in context

Evidence before the study

National immunisation programmes globally are at risk of disruption due to the severe health system constraints caused by the ongoing COVID-19 pandemic and the physical distancing measures to mitigate the outbreak. The decrease in vaccination coverage increases the proportion of susceptible children at risk of increased morbidity and mortality from vaccine-preventable disease outbreaks. Outbreaks of vaccine preventable disease have been observed during previous interruptions to routine immunisation services during an ongoing infectious disease epidemic, such as during the 2013-2016 Ebola outbreak in West Africa, when most health resources were shifted towards the Ebola response which led to decreasing vaccination coverage and consequently outbreaks of measles and other vaccine-preventable diseases.

Added value of this study

We estimated the benefit-risk ratio by comparing the deaths prevented by sustaining routine childhood immunisation for diphtheria, tetanus, pertussis, hepatitis B, Haemophilus influenzae type b, pneumococcal, rotavirus, measles, meningitis A, rubella, and yellow fever vaccines with the excess COVID-19 deaths associated with vaccination clinic visits. The benefit of routine childhood immunization programmes in all the 54 countries of Africa is higher than the COVID-19 risk associated with these vaccination clinic visits.

Implications of all the available evidence

Routine childhood immunisation programmes should be safeguarded for continued service delivery and prioritised for the prevention of infectious diseases, as logistically possible, as part of delivering essential health services during the COVID-19 pandemic in Africa. The current immunisation service models will require adaptation, including physical distancing measures, personal protective equipment, and good hygiene practices for infection control at the vaccination clinics, and have to be complemented by new immunisation service models for sustaining routine childhood immunisation in the African countries during the COVID-19 risk period.",,pdf:http://www.thelancet.com/article/S2214109X20303089/pdf; doi:https://doi.org/10.1101/2020.05.19.20106278; html:https://europepmc.org/article/PPR/PPR167068; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR167068&type=FILE&fileName=EMS90726-pdf.pdf&mimeType=application/pdf PPR468085,https://doi.org/10.1101/2022.03.11.22272276,Risk factors for SARS-CoV-2 infection after primary vaccination with ChAdOx1 nCoV-19 or BNT1262b2 and after booster vaccination with BNT1262b2 or mRNA-1273: a population-based cohort study (COVIDENCE UK),"Vivaldi G, Jolliffe DA, Holt H, Tydeman F, Talaei M, Davies GA, Lyons RA, Griffiths CJ, Kee F, Sheikh A, Shaheen SO, Martineau AR.",,No Journal Info,2022,2022-03-13,Y,,,,"

Background

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

Methods

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

Findings

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

Conclusions

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

Research in context

Evidence before this study

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

Added value of this study

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

Implications of all the available evidence

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

Background

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

Methods

This is a prospective diagnostic accuracy study.

Setting

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

Participants

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

Interventions

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

Main outcome measures

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

Results

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

Conclusions

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

Objectives

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

Design

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

Setting:

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

Participants

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

Primary and secondary outcome measures

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

Results

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

Conclusions

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

Strengths and limitations

This was one of the largest studies of the impact of the pandemic on deprivation inequalities, covering 20 million people in two countries (England and Denmark). Followed-up was until the end of 2021, which is longer than most previous studies. We compared the impact in two countries that have free at the point of use healthcare, but different responses to the pandemic. The measures of deprivation were different in the two countries, with the measure in England (Index of Multiple Deprivation 2019) capturing more aspects of deprivation compared to the Danish measure (income) which may have resulted in misclassification. Our results are descriptive so do not provide insight into the causes of observed differences.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2024/05/09/2024.05.09.24307105.full.pdf; doi:https://doi.org/10.1101/2024.05.09.24307105; html:https://europepmc.org/article/PPR/PPR850975 PPR417361,https://doi.org/10.1101/2021.11.08.21265312,"Understanding COVID-19 trajectories from a nationwide linked electronic health record cohort of 56 million people: phenotypes, severity, waves & vaccination","Thygesen JH, Tomlinson C, Hollings S, Mizani M, Handy A, Akbari A, Banerjee A, Cooper J, Lai A, Li K, Mateen B, Sattar N, Sofat R, Torralbo A, Wu H, Wood A, Sterne JAC, Pagel C, Whiteley W, Sudlow C, Hemingway H, Denaxas S.",,No Journal Info,2021,2021-11-09,Y,,,,"

Background

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

Methods

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

Findings

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

Interpretation

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

Research in Context

Evidence before the study

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

Added value of this study

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

Implications of all the available evidence

The COVID-19 phenotypes and trajectory analysis framework outlined produce a reproducible, extensible and repurposable means to generate national-scale data to support critical policy decision making. By modelling patient trajectories as a series of interactions with healthcare systems, and linking these to demographic and outcome data, we provide a means to identify and prioritise care pathways associated with adverse outcomes and highlight healthcare system ‘touch points’ which may act as tangible targets for intervention.",,pdf:http://www.thelancet.com/article/S2589750022000917/pdf; doi:https://doi.org/10.1101/2021.11.08.21265312; html:https://europepmc.org/article/PPR/PPR417361; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR417361&type=FILE&fileName=EMS138265-pdf.pdf&mimeType=application/pdf +PPR850975,https://doi.org/10.1101/2024.05.09.24307105,Impacts of the COVID-19 pandemic on deprivation-level differences in cardiovascular hospitalisations: A comparison of England and Denmark using the OpenSAFELY platform and National Registry Data,"Costello RE, Henderson AD, Tazare J, Pedersen L, Sorensen HT, Vandenbroucke JP, Mansfield KE, Mahalingasivam V, Zheng B, Carreira H, Bidulka P, Piehlmaier D, Wong AY, Warren-Gash C, Hayes JF, Quint JK, Katikireddi SV, MacKenna B, Mehrkar A, Bacon S, Goldacre B, Tomlinson L, Langan SM, Mathur R, The LH&W NCS (or CONVALESCENCE) Collaborative and the OpenSAFELYcollaborative.",,No Journal Info,2024,2024-05-09,Y,,,,"

Objectives

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

Design

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

Setting:

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

Participants

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

Primary and secondary outcome measures

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

Results

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

Conclusions

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

Strengths and limitations

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

SUMMARY

Background

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

Methods

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

Findings

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

Interpretation

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

Funding

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

Background

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

Methods

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

Results

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

Conclusions

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

Background

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

Methods

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

Results

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

Conclusion

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

Key Question

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

Key Finding

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

Take-home Message

There was increasing emergency cardiovascular admissions as a result of the pandemic, with substantial and sustained reduction in elective admissions and procedures. This is likely to increase further the demands on cardiovascular services over the coming years.",,pdf:https://eprints.keele.ac.uk/id/eprint/12374/1/2022.10.13.22281031v1.full.pdf; doi:https://doi.org/10.1101/2022.10.13.22281031; html:https://europepmc.org/article/PPR/PPR558653; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR558653&type=FILE&fileName=EMS155821-pdf.pdf&mimeType=application/pdf @@ -202,13 +202,13 @@ PPR367549,https://doi.org/10.1101/2021.07.08.21260185,REACT-1 round 13 interim r PPR397279,https://doi.org/10.1101/2021.09.16.21263629,Access to personal protective equipment in healthcare workers during the COVID-19 pandemic in the United Kingdom: results from a nationwide cohort study (UK-REACH),"Martin CA, Pan D, Nazareth J, Aujayeb A, Bryant L, Carr S, Gray LJ, Gregary B, Gupta A, Guyatt AL, Gopal A, Hine T, John C, McManus IC, Melbourne C, Nellums LB, Reza R, Simpson S, Tobin MD, Woolf K, Zingwe S, Khunti K, Pareek M.",,No Journal Info,2021,2021-09-21,Y,,,,"

Objectives

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

Design

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

Setting

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

Participants

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

Main outcome measure

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

Results

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

Conclusions

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

Trial registration

ISRCTN 11811602

What is already known on this topic

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

What this study adds

Only a third of HCWs reported having access to appropriate PPE all of the time during the first UK national lockdown. Older HCWs, those working in Intensive Care Units and those who trusted their employing organisation to deal with concerns about unsafe clinical practice, were more likely to report access to adequate PPE. Those from Asian ethnic groups (compared to White ethnic groups) and those who saw a high number of COVID-19 were less likely to report access to adequate PPE. Our findings have important implications for the mental and physical health of HCWs working during the pandemic in the UK.",,pdf:https://bmchealthservres.biomedcentral.com/counter/pdf/10.1186/s12913-022-08202-z; doi:https://doi.org/10.1101/2021.09.16.21263629; html:https://europepmc.org/article/PPR/PPR397279; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR397279&type=FILE&fileName=EMS135495-pdf.pdf&mimeType=application/pdf PPR179126,https://doi.org/10.1101/2020.06.22.20137216,"Proteomic blood profiling in mild, severe and critical COVID-19 patients","Patel H, Ashton NJ, Dobson RJ, Andersson L, Yilmaz A, Blennow K, Gisslen M, Zetterberg H.",,No Journal Info,2020,2020-06-23,N,,,,"The recent SARS-CoV-2 pandemic manifests itself as a mild respiratory tract infection in the majority of individuals leading to COVID-19 disease. However, in some infected individuals, this can progress to severe pneumonia and acute respiratory distress syndrome (ARDS), leading to multi-organ failure and death. The purpose of this study is to explore the proteomic differences between mild, severe and critical COVID-19 positive patients. Blood protein profiling was performed on 59 COVID-19 mild (n=26), severe (n=9) or critical (n=24) cases and 28 controls using the OLINK inflammation, autoimmune, cardiovascular and neurology panels. Differential expression analysis was performed within and between disease groups to generate nine different analyses. From the 368 proteins measured per individual, more than 75% were observed to be significantly perturbed in COVID-19 cases. Six proteins (IL6, CKAP4, Gal-9, IL-1ra, LILRB4 and PD-L1) were identified to be associated with disease severity. The results have been made readily available through an interactive web-based application for instant data exploration and visualization, and can be accessed at https://phidatalab-shiny.rosalind.kcl.ac.uk/COVID19/ . Our results demonstrate that dynamic changes in blood proteins that associate with disease severity can potentially be used as early biomarkers to monitor disease severity in COVID-19 and serve as potential therapeutic targets.",,pdf:https://www.nature.com/articles/s41598-021-85877-0.pdf; doi:https://doi.org/10.1101/2020.06.22.20137216; html:https://europepmc.org/article/PPR/PPR179126; doi:https://doi.org/10.1101/2020.06.22.20137216 PPR301060,https://doi.org/10.1101/2021.03.20.21254010,Older biological age is associated with adverse COVID-19 outcomes: A cohort study in UK Biobank,"Wang Q, Codd V, Raisi-Estabragh Z, Musicha C, Bountziouka V, Kaptoge S, Allara E, Angelantonio ED, Butterworth AS, Wood AM, Thompson JR, Petersen SE, Harvey NC, Danesh JN, Samani NJ, Nelson CP.",,No Journal Info,2021,2021-03-22,Y,,,,"

Background

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

Methods

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

Findings

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

Interpretation

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

Funding

UK Medical Research Council, Biotechnology and Biological Sciences Research Council and British Heart Foundation.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2021/03/22/2021.03.20.21254010.full.pdf; doi:https://doi.org/10.1101/2021.03.20.21254010; html:https://europepmc.org/article/PPR/PPR301060; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR301060&type=FILE&fileName=EMS120573-pdf.pdf&mimeType=application/pdf -PPR725396,https://doi.org/10.1101/2023.09.14.23295499,Mechanisms for Integrating Real Data into Search Game Simulations: An Application to Winter Health Service Pressures and Preventative Policies,"Chapman M, G-Medhin A, Daneshi K, Bramwell T, Durbaba S, Curcin V, Parmar D, Boulding H, Becares L, Morgan C, Molokhia M, McBurney P, Harding S, Wolfe I, Ashworth M, Poston L.",,No Journal Info,2023,2023-09-15,Y,,,,"While modelling and simulation are powerful techniques for exploring complex phenomena, if they are not coupled with suitable real-world data any results obtained are likely to require extensive validation. We consider this problem in the context of search game modelling, and suggest that both demographic and behaviour data are used to configure certain model parameters. We show this integration in practice by using a combined dataset of over 150,000 individuals to configure a specific search game model that captures the environment, population, interventions and individual behaviours relating to winter health service pressures. The presence of this data enables us to more accurately explore the potential impact of service pressure interventions, which we do across 33,000 simulations using a computational version of the model. We find government advice to be the best-performing intervention in simulation, in respect of improved health, reduced health inequalities, and thus reduced pressure on health service utilisation.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2023/09/15/2023.09.14.23295499.full.pdf; doi:https://doi.org/10.1101/2023.09.14.23295499; html:https://europepmc.org/article/PPR/PPR725396; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR725396&type=FILE&fileName=EMS188071-pdf.pdf&mimeType=application/pdf PPR401642,https://doi.org/10.1101/2021.09.27.21264166,Prevalence and duration of detectable SARS-CoV-2 nucleocapsid antibody in staff and residents of long-term care facilities over the first year of the pandemic (VIVALDI study): prospective cohort study,"Krutikov M, Palmer T, Tut G, Fuller C, Azmi B, Giddings R, Shrotri M, Kaur N, Sylla P, Lancaster T, Irwin-Singer A, Hayward A, Moss P, Copas A, Shallcross L.",,No Journal Info,2021,2021-09-29,Y,,,,"

Background

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

Methods

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

Results

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

Interpretation

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

Funding

UK Government Department of Health and Social Care.

Research in context

Evidence before this study

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

Added value of this study

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

Implications of all available research

A substantial proportion of the LTCF population will have some level of natural immunity to infection as a result of past infection. Immunological studies have highlighted greater antibody responses to vaccination in seropositive individuals, so vaccine efficacy in this population may be affected by this large pool of individuals who have survived past infection. In addition, although the presence of nucleocapsid-specific antibodies is generally considered as the standard marker for prior infection, we find that antibody waning is such that up to 50% of people will lose detectable antibody responses within eight months. Individual prior natural infection history is critical to assess the impact of factors such as vaccine response or protection against re-infection. These findings may have implications for duration of immunity following natural infection and indicate that alternative assays for prior infection should be developed.",,pdf:http://www.thelancet.com/article/S2666756821002828/pdf; doi:https://doi.org/10.1101/2021.09.27.21264166; html:https://europepmc.org/article/PPR/PPR401642; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR401642&type=FILE&fileName=EMS136680-pdf.pdf&mimeType=application/pdf +PPR725396,https://doi.org/10.1101/2023.09.14.23295499,Mechanisms for Integrating Real Data into Search Game Simulations: An Application to Winter Health Service Pressures and Preventative Policies,"Chapman M, G-Medhin A, Daneshi K, Bramwell T, Durbaba S, Curcin V, Parmar D, Boulding H, Becares L, Morgan C, Molokhia M, McBurney P, Harding S, Wolfe I, Ashworth M, Poston L.",,No Journal Info,2023,2023-09-15,Y,,,,"While modelling and simulation are powerful techniques for exploring complex phenomena, if they are not coupled with suitable real-world data any results obtained are likely to require extensive validation. We consider this problem in the context of search game modelling, and suggest that both demographic and behaviour data are used to configure certain model parameters. We show this integration in practice by using a combined dataset of over 150,000 individuals to configure a specific search game model that captures the environment, population, interventions and individual behaviours relating to winter health service pressures. The presence of this data enables us to more accurately explore the potential impact of service pressure interventions, which we do across 33,000 simulations using a computational version of the model. We find government advice to be the best-performing intervention in simulation, in respect of improved health, reduced health inequalities, and thus reduced pressure on health service utilisation.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2023/09/15/2023.09.14.23295499.full.pdf; doi:https://doi.org/10.1101/2023.09.14.23295499; html:https://europepmc.org/article/PPR/PPR725396; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR725396&type=FILE&fileName=EMS188071-pdf.pdf&mimeType=application/pdf PPR277515,https://doi.org/10.1101/2021.02.01.21250839,Extremely high SARS-CoV-2 seroprevalence in a strictly-Orthodox Jewish community in the UK,"Gaskell KM, Johnson M, Gould V, Hunt A, Stone NR, Waites W, Kasstan B, Chantler T, Lal S, Roberts Ch, Goldblatt D, Eggo RM, Marks M.",,No Journal Info,2021,2021-02-03,Y,,,,"

Background

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

Methods

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

Findings

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

Interpretation

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

Funding

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

Research In Context

Evidence before the study

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

Added value of the study

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

Implications of the available evidence

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

Background

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

Methods

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

Results

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

Conclusion

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

Background

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

Aims

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

Methods

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

Results

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

Conclusions

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

Teaser text

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

Background

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

Methods

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

Results

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

Conclusions

Community prevalence of swab-positivity has declined markedly between January and February 2021 during lockdown in England, but remains high; the rate of decline has slowed in the most recent period, with a suggestion of pockets of growth. Continued adherence to social distancing and public health measures is required so that infection rates fall to much lower levels. This will help to ensure that the benefits of the vaccination roll-out programme in England are fully realised.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2021/03/06/2021.03.03.21252856.full.pdf; doi:https://doi.org/10.1101/2021.03.03.21252856; html:https://europepmc.org/article/PPR/PPR293368; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR293368&type=FILE&fileName=EMS118777-pdf.pdf&mimeType=application/pdf PPR186543,https://doi.org/10.1101/2020.07.10.20150656,Diagnostic value of skin manifestation of SARS-CoV-2 infection,"Bataille V, Visconti A, Rossi N, Murray B, Bournot A, Wolf J, Wolf J, Ourselin S, Steves C, Spector T, Falchi M.",,No Journal Info,2020,2020-07-11,Y,,,,"SARS-CoV-2 causes multiple immune-related reactions at various stages of the disease. The wide variety of skin presentations has delayed linking these to the virus. Previous studies had attempted to look at the prevalence and timing of SARS-COV-2 rashes but were based on mostly hospitalized severe cases and had little follow up. Using data collected on a subset of 336,847 eligible UK users of the COVID Symptom Study app, we observed that 8.8% of the swab positive cases (total: 2,021 subjects) reported either a body rash or an acral rash, compared to 5.4% of those with a negative swab test (total: 25,136). Together, these two skin presentations showed an odds ratio (OR) of 1.67 (95% confidence interval [CI]: 1.41-1.96) for being swab positive. Skin rashes were also predictive in the larger untested group of symptomatic app users (N=54,652), as 8.2% of those who had reported at least one classical COVID-19 symptom, i . e ., fever, persistent cough, and/or anosmia, also reported a rash. Data from an independent online survey of 11,546 respondents with a rash showed that in 17% of swab positive cases, the rash was the initial presentation. Furthermore, in 21%, the rash was the only clinical sign. Skin rashes cluster with other COVID-19 symptoms, are predictive of a positive swab test and occur in a significant number of cases, either alone or before other classical symptoms. Recognising rashes is important in identifying new and earlier COVID-19 cases.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2020/10/26/2020.07.10.20150656.full.pdf; doi:https://doi.org/10.1101/2020.07.10.20150656; html:https://europepmc.org/article/PPR/PPR186543; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR186543&type=FILE&fileName=EMS87210-pdf.pdf&mimeType=application/pdf +PPR814122,https://doi.org/10.1101/2024.03.03.24303615,Redeployment Experiences of Healthcare Workers in the UK during COVID-19: data from the nationwide UK-REACH study,"Lal ZZ, Martin CA, Gogoi M, Qureshi I, Bryant L, Papineni P, Lagrata S, Nellums LB, Al-Oraibi A, Chaloner J, Woolf K, Pareek M.",,No Journal Info,2024,2024-03-04,Y,,,,"

Background

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

Aims

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

Methods

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

Results

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

Conclusions

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

Teaser text

This study explores how ethnicity, migration status, and occupation were associated with healthcare workers’ (HCWs) redeployment experiences during COVID-19. After adjustment of covariates, we found that nursing roles and migration to the UK increase redeployment likelihood. Asian HCWs reported lesser training and Black HCWs reported more supervision, compared to White colleagues. Redeployed Black and Asian HCWs were more likely to report interaction with COVID-19 patients. Findings highlight disparities in HCWs’ redeployment experiences in an ethnically diverse sample.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2024/03/04/2024.03.03.24303615.full.pdf; doi:https://doi.org/10.1101/2024.03.03.24303615; html:https://europepmc.org/article/PPR/PPR814122; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR814122&type=FILE&fileName=EMS194583-pdf.pdf&mimeType=application/pdf PPR695721,https://doi.org/10.1101/2023.07.19.23292289,Can computer simulation support strategic service planning? Modelling a large integrated mental health system on recovery from COVID-19,"Pierotti L, Cooper J, James C, Cassels K, Gara E, Denholm R, Wood R.",,No Journal Info,2023,2023-07-23,N,,,,"

Background

COVID-19 has had a significant impact on people’s mental health and mental health services. During the first year of the pandemic, existing demand was not fully met while new demand was generated, resulting in large numbers of people requiring support. To support mental health services to recover without being overwhelmed, it was important to know where services will experience increased pressure, and what strategies could be implemented to mitigate this.

Methods

We implemented a computer simulation model of patient flow through an integrated mental health service in Southwest England covering General Practice (GP), community-based ‘talking therapies’ (IAPT), acute hospital care, and specialist care settings. The model was calibrated on data from 1 April 2019 to 1 April 2021. Model parameters included patient demand, service-level length of stay, and probabilities of transitioning to other care settings. We used the model to compare ‘do nothing’ (baseline) scenarios to ‘what if’ (mitigation) scenarios, including increasing capacity and reducing length of stay, for two future demand trajectories from 1 April 2021 onwards.

Results

The results from the simulation model suggest that, without mitigation, the impact of COVID-19 will be an increase in pressure on GP and specialist community based services by 50% and 50-100% respectively. Simulating the impact of possible mitigation strategies, results show that increasing capacity in lower-acuity services, such as GP, results in demand being shifted to other parts of the mental health system while decreasing length of stay in higher acuity services is insufficient to mitigate the impact of increased demand.

Conclusion

In capturing the interrelation of patient flow related dynamics between various mental health care settings, we demonstrate the value of computer simulation for assessing the impact of interventions on system flow.",,doi:https://doi.org/10.1101/2023.07.19.23292289; html:https://europepmc.org/article/PPR/PPR695721; doi:https://doi.org/10.1101/2023.07.19.23292289 PPR294760,https://doi.org/10.1101/2021.03.09.21252736,"Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial","The RECOVERY Collaborative Group, Horby PW, Estcourt L, Peto L, Emberson JR, Emberson JR, Staplin N, Spata E, Pessoa-Amorim G, Campbell M, Roddick A, Brunskill NE, George T, Zehnder D, Tiberi S, Aung NN, Uriel A, Widdrington J, Koshy G, Brown T, Scott S, Baillie JK, Buch MH, Chappell LC, Day JN, Faust SN, Jaki T, Jeffery K, Juszczak E, Lim WS, Montgomery A, Mumford A, Rowan K, Thwaites G, Mafham M, Roberts D, Haynes R, Landray MJ.",,No Journal Info,2021,2021-03-10,Y,,,,"

ABSTRACT

Background

Treatment of COVID-19 patients with plasma containing anti-SARS-CoV-2 antibodies may have a beneficial effect on clinical outcomes. We aimed to evaluate the safety and efficacy of convalescent plasma in patients admitted to hospital with COVID-19.

Methods

In this randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) several possible treatments are being compared with usual care in patients hospitalised with COVID-19 in the UK. Eligible and consenting patients were randomly allocated to receive either usual care plus high titre convalescent plasma or usual care alone. The primary outcome was 28-day mortality.

Findings

Between 28 May 2020 and 15 January 2021, 5795 patients were randomly allocated to receive convalescent plasma and 5763 to usual care alone. There was no significant difference in 28-day mortality between the two groups: 1398 (24%) of 5795 patients allocated convalescent plasma and 1408 (24%) of 5763 patients allocated usual care died within 28 days (rate ratio [RR] 1·00; 95% confidence interval [CI] 0·93 to 1·07; p=0·93). The 28-day mortality rate ratio was similar in all prespecified subgroups of patients, including in those patients without detectable SARS-CoV-2 antibodies at randomisation. Allocation to convalescent plasma had no significant effect on the proportion of patients discharged from hospital within 28 days (66% vs . 67%; rate ratio 0·98; 95% CI 0·94-1·03, p=0·50). Among those not on invasive mechanical ventilation at baseline, there was no significant difference in the proportion meeting the composite endpoint of progression to invasive mechanical ventilation or death (28% vs . 29%; rate ratio 0·99; 95% CI 0·93-1·05, p=0·79).

Interpretation

Among patients hospitalised with COVID-19, high-titre convalescent plasma did not improve survival or other prespecified clinical outcomes.

Funding

UK Research and Innovation (Medical Research Council) and National Institute of Health Research (Grant refs: MC_PC_19056; COV19-RECPLA).",,pdf:https://discovery.dundee.ac.uk/files/70667710/PIIS0140673621008977.pdf; doi:https://doi.org/10.1101/2021.03.09.21252736; html:https://europepmc.org/article/PPR/PPR294760; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR294760&type=FILE&fileName=EMS119130-pdf.pdf&mimeType=application/pdf PPR454366,https://doi.org/,Inferring Risks of Coronavirus Transmission from Community Household Data,"House T, Riley H, Pellis L, Pouwels KB, Bacon S, Eidukas A, Jahanshahi K, Eggo RM, Walker AS.",,No Journal Info,2021,2021-12-02,N,,,,"The response of many governments to the COVID-19 pandemic has involved measures to control within- and between-household transmission, providing motivation to improve understanding of the absolute and relative risks in these contexts. Here, we perform exploratory, residual-based, and transmission-dynamic household analysis of the Office for National Statistics (ONS) COVID-19 Infection Survey (CIS) data from 26 April 2020 to 15 July 2021 in England. This provides evidence for: (i) temporally varying rates of introduction of infection into households broadly following the trajectory of the overall epidemic and vaccination programme; (ii) Susceptible-Infectious Transmission Probabilities (SITPs) of within-household transmission in the 15-35% range; (iii) the emergence of the Alpha and Delta variants, with the former being around 50% more infectious than wildtype and 35% less infectious than Delta within households; (iv) significantly (in the range 25-300%) more risk of bringing infection into the household for workers in patient-facing roles pre-vaccine; (v) increased risk for secondary school-age children of bringing the infection into the household when schools are open; (vi) increased risk for primary school-age children of bringing the infection into the household when schools were open since the emergence of new variants.",,arxiv:https://arxiv.org/abs/2104.04605v3; html:https://europepmc.org/article/PPR/PPR454366 @@ -264,8 +264,8 @@ PPR393010,https://doi.org/10.1101/2021.09.03.21263023,Evaluation of antithrombot PPR700382,https://doi.org/10.1101/2023.07.31.23293419,The impact of COVID-19 on medication reviews in English primary care. An OpenSAFELY-TPP analysis of 20 million adult electronic health records,"The OpenSAFELY Collaborative, Wood C, Speed V, Fisher L, Curtis HJ, Schaffer AL, Walker AJ, Croker R, Brown AD, Cunningham C, Hulme WJ, Andrews CD, Butler-Cole BFC, Evans D, Inglesby P, Dillingham I, Bacon SC, Davy S, Ward T, Hickman G, Bridges L, O’Dwyer T, Maude S, Smith RM, Mehrkar A, Bates C, Cockburn J, Parry J, Hester F, Harper S, Goldacre B, MacKenna B.",,No Journal Info,2023,2023-07-31,Y,,,,"

Background

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

Aim

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

Design and setting

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

Method

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

Results

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

Conclusion

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

What is already known about this subject

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

What this study adds

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

Objectives

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

Design

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

Setting

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

Main outcome measures

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

Data sources

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

Results

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

Conclusions

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

Background

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

Methods

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

Findings

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

Interpretation

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

Funding

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

Research in Context

Evidence before this study

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

Added value of this study

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

Implications of all the available evidence

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

Background:

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

Methods:

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

Results:

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

Conclusion:

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

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

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

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

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

Declaration of Interests: None to declare.

Ethics Approval Statement: Ethical approval for this study was granted by the East of England – Cambridge Central Research Ethics Committee (IRAS ID: 220277).",,pdf:https://www.repository.cam.ac.uk/bitstreams/3ef04015-fa68-40ca-84d6-076095101624/download; doi:https://doi.org/10.2139/ssrn.3724855; html:https://europepmc.org/article/PPR/PPR247907; doi:https://doi.org/10.2139/ssrn.3724855 +PPR626309,https://doi.org/10.21203/rs.3.rs-2573712/v1,How much did the Covid-19 shielding policy cost in Wales? A Retrospective Cost analysis within the EVITE Immunity study,"Sewell B, Farr A, Akbari A, Carson-Stevens A, Edwards A, Evans BA, John A, Torabi F, Dale J, Jolles S, Kingston MR, Lyons J, Lyons RA, Porter A, Watkins A, Williams V, Snooks H.",,No Journal Info,2023,2023-03-06,Y,,,,"

Background:

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

Methods:

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

Results:

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

Conclusion:

This is the first evaluation of the cost of the measures put in place to support those identified to shield in Wales. However, no data on opportunity cost was available. The true cost of shielding including its budget impact and opportunity costs need to be investigated to decide whether shielding is a worthwhile policy for future health emergencies.",,pdf:https://www.researchsquare.com/article/rs-2573712/latest.pdf; doi:https://doi.org/10.21203/rs.3.rs-2573712/v1; html:https://europepmc.org/article/PPR/PPR626309; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR626309&type=FILE&fileName=EMS171864-pdf.pdf&mimeType=application/pdf PPR233548,https://doi.org/10.1101/2020.11.01.20222315,Association between living with children and outcomes from COVID-19: an OpenSAFELY cohort study of 12 million adults in England,"Forbes H, Morton CE, Bacon S, McDonald HI, Minassian C, Brown JP, Rentsch CT, Mathur R, Schultze A, DeVito NJ, MacKenna B, Hulme WJ, Croker R, Walker AJ, Williamson EJ, Bates C, Mehrkar A, Curtis HJ, Evans D, Wing K, Inglesby P, Drysdale H, Wong AY, Cockburn J, McManus R, Parry J, Hester F, Harper S, Douglas IJ, Smeeth L, Evans SJ, Bhaskaran K, Eggo RM, Goldacre B, Tomlinson LA.",,No Journal Info,2020,2020-11-02,Y,,,,"

Background

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

Methods

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

Findings

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

Interpretation

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

Funding

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

Research in context

Evidence before this study

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

Added value of this study

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

Implications of all the available evidence

Our results demonstrate no evidence of serious harms from COVID-19 to adults in close contact with children, compared to those living in households without children. This has implications for determining the benefit-harm balance of children attending school in the COVID-19 pandemic.",,pdf:https://www.bmj.com/content/bmj/372/bmj.n628.full.pdf; doi:https://doi.org/10.1101/2020.11.01.20222315; html:https://europepmc.org/article/PPR/PPR233548; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR233548&type=FILE&fileName=EMS103455-pdf.pdf&mimeType=application/pdf PPR463503,https://doi.org/10.1101/2022.03.02.22271623,"Baricitinib in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial and updated meta-analysis","RECOVERY Collaborative Group, Horby PW, Emberson JR, Mafham M, Campbell M, Peto L, Pessoa-Amorim G, Spata E, Staplin N, Lowe C, Chadwick DR, Brightling C, Stewart R, Collini P, Ashish A, Green CA, Prudon B, Felton T, Kerry A, Baillie JK, Buch MH, Day JN, Faust SN, Jaki T, Jeffery K, Juszczak E, Knight M, Lim WS, Montgomery A, Mumford A, Rowan K, Thwaites G, Haynes R, Landray MJ.",,No Journal Info,2022,2022-03-03,Y,,,,"

SUMMARY

Background

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

Methods

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

Findings

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

Interpretation

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

Funding

UK Research and Innovation (Medical Research Council) and National Institute of Health Research (Grant ref: MC_PC_19056).",,pdf:https://nottingham-repository.worktribe.com/preview/9409854/PIIS0140673622011096.pdf; doi:https://doi.org/10.1101/2022.03.02.22271623; html:https://europepmc.org/article/PPR/PPR463503; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR463503&type=FILE&fileName=EMS148878-pdf.pdf&mimeType=application/pdf PPR371921,https://doi.org/,Explainable Automated Coding of Clinical Notes using Hierarchical Label-wise Attention Networks and Label Embedding Initialisation,"Dong H, Suárez-Paniagua V, Whiteley W, Wu H.",,No Journal Info,2021,2021-07-16,Y,,,,"Diagnostic or procedural coding of clinical notes aims to derive a coded summary of disease-related information about patients. Such coding is usually done manually in hospitals but could potentially be automated to improve the efficiency and accuracy of medical coding. Recent studies on deep learning for automated medical coding achieved promising performances. However, the explainability of these models is usually poor, preventing them to be used confidently in supporting clinical practice. Another limitation is that these models mostly assume independence among labels, ignoring the complex correlation among medical codes which can potentially be exploited to improve the performance. We propose a Hierarchical Label-wise Attention Network (HLAN), which aimed to interpret the model by quantifying importance (as attention weights) of words and sentences related to each of the labels. Secondly, we propose to enhance the major deep learning models with a label embedding (LE) initialisation approach, which learns a dense, continuous vector representation and then injects the representation into the final layers and the label-wise attention layers in the models. We evaluated the methods using three settings on the MIMIC-III discharge summaries: full codes, top-50 codes, and the UK NHS COVID-19 shielding codes. Experiments were conducted to compare HLAN and LE initialisation to the state-of-the-art neural network based methods. HLAN achieved the best Micro-level AUC and $F_1$ on the top-50 code prediction and comparable results on the NHS COVID-19 shielding code prediction to other models. By highlighting the most salient words and sentences for each label, HLAN showed more meaningful and comprehensive model interpretation compared to its downgraded baselines and the CNN-based models. LE initialisation consistently boosted most deep learning models for automated medical coding.",,arxiv:https://arxiv.org/abs/2010.15728v4; html:https://europepmc.org/article/PPR/PPR371921; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR371921&type=FILE&fileName=EMS130963-pdf.pdf&mimeType=application/pdf @@ -369,13 +369,13 @@ PPR204757,https://doi.org/10.1101/2020.08.21.20167965,Implications of the school PPR530179,https://doi.org/10.1101/2022.08.08.22278493,Inequalities in colorectal cancer screening uptake in Wales: an examination of the impact of the temporary suspension of the screening programme during the COVID-19 pandemic,"Bright D, Hillier S, Song J, Huws DW, Greene G, Hodgson K, Akbari A, Griffiths R, Davies AR, Gjini A.",,No Journal Info,2022,2022-08-09,Y,,,,"

Background

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

Methods

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

Results

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

Conclusions

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

ABSTRACT

Background

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

Methods

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

Findings

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

Interpretation

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

RESEARCH IN CONTEXT

Evidence before this study

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

Added value of the study

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

Implications of all of the available evidence

Our study offers insights into future risk mitigation strategies and SARS-CoV-2 vaccination priorities for individuals with IMIDs, as it highlights that those with IMIDs and those taking rituximab may be at risk of severe COVID-19 outcomes. Critically, our study does not show a link between most targeted immune modifying medications compared to standard systemics and severe COVID-19 outcomes. However, the increased risk of adverse COVID-19 outcomes that we saw in people with IMIDs and those treated with rituximab merits further study.",,pdf:https://qmro.qmul.ac.uk/xmlui/bitstream/123456789/83106/2/Mathur%20Risk%20of%20severe%20COVID-19%20outcomes%20associated%20with%20immune-mediated%20inflammatory%20diseases%20and%20immune-modifying%20therapies%3a%20a%20nationwide%20cohort%20study%20in%20the%20OpenSAFELY%20platform%202022%20Published.pdf; doi:https://doi.org/10.1101/2021.09.03.21262888; html:https://europepmc.org/article/PPR/PPR393011; doi:https://doi.org/10.1101/2021.09.03.21262888 PPR602738,https://doi.org/10.2139/ssrn.4023214,Challenging the Cultures of Racism at Work in the UK's Healthcare Sector,"Ramamurthy A, Bhabhbro S, Bruce F, Gumber A, Fero K.",,No Journal Info,2022,2022-02-01,N,,,,"Background: In UK’s health care sector, racism is rampant. It impacts Black and Brown staff working in NHS at all levels. We aimed to explore and understand the stories and experiences of Black and Brown health care staff during the pandemic and previously in their working lives.

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

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

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

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

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

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

Author Summary

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

Background

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

Methods

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

Results

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

Conclusions

COVID-19 vaccine hesitancy was greater among racial and ethnic minorities, and Black participants living in the U.S. were less likely to receive a vaccine than White participants. Lower uptake among Black participants in the U.S. during the initial vaccine rollout is attributable to both hesitancy and disparities in access.",,pdf:https://www.nature.com/articles/s41467-022-28200-3.pdf; doi:https://doi.org/10.1101/2021.02.25.21252402; html:https://europepmc.org/article/PPR/PPR290155; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR290155&type=FILE&fileName=EMS117911-pdf.pdf&mimeType=application/pdf +PPR609122,https://doi.org/10.1101/2023.01.25.23285005,Call detail record aggregation methodology impacts infectious disease models informed by human mobility,"Gibbs H, Musah A, Seidu O, Ampofo W, Asiedu-Bekoe F, Gray J, Adewole WA, Cheshire J, Marks M, Eggo RM.",,No Journal Info,2023,2023-01-28,Y,,,,"This paper demonstrates how two different methods used to calculate population-level mobility from Call Detail Records (CDR) produce varying predictions of the spread of epidemics informed by these data. Our findings are based on one CDR dataset describing inter-district movement in Ghana in 2021, produced using two different aggregation methodologies. One methodology, “all pairs,” is designed to retain long distance network connections while the other, “sequential” methodology is designed to accurately reflect the volume of travel between locations. We show how the choice of methodology feeds through models of human mobility to the predictions of a metapopulation SEIR model of disease transmission. We also show that this impact varies depending on the location of pathogen introduction and transmissibility. For central locations or highly transmissible diseases, we do not observe significant differences between aggregation methodologies on the predicted spread of disease. For less transmissible diseases or those introduced into remote locations, we find that the choice of aggregation methodology influences the speed of spatial spread as well as the size of the peak number of infections in individual districts. Our findings can help researchers and users of epidemiological models to understand how methodological choices at the level of model inputs may influence the results of models of infectious disease transmission, as well as the circumstances in which these choices do not alter model predictions.

Author Summary

Predicting the sub-national spread of infectious disease requires accurate measurements of inter-regional travel networks. Often, this information is derived from the patterns of mobile device connections to the cellular network. This travel data is then used as an input to epidemiological models of infection transmission, defining the likelihood that disease is “exported” between regions. In this paper, we use one mobile device dataset collected in Ghana in 2021, aggregated according to two different methodologies which represent different aspects of inter-regional travel. We show how the choice of aggregation methodology leads to different predicted epidemics, and highlight the conditions under which models of infection transmission may be influenced by methodological choices in the aggregation of travel data used to parameterize these models. For example, we show how aggregation methodology changes predicted epidemics for less-transmissible infections and under certain models of human movement. We also highlight areas of relative stability, where aggregation choices do not alter predicted epidemics, such as cases where an infection is highly transmissible or is introduced into a central location.",,pdf:https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1011368&type=printable; doi:https://doi.org/10.1101/2023.01.25.23285005; html:https://europepmc.org/article/PPR/PPR609122; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR609122&type=FILE&fileName=EMS163650-pdf.pdf&mimeType=application/pdf PPR170310,https://doi.org/10.1101/2020.05.27.20083287,Estimating excess mortality in people with cancer and multimorbidity in the COVID-19 emergency,"Lai AG, Pasea L, Banerjee A, Denaxas S, Katsoulis M, Chang WH, Williams B, Pillay D, Noursadeghi M, Linch D, Hughes D, Forster MD, Turnbull C, Fitzpatrick NK, Boyd K, Foster GR, Cooper M, Jones M, Pritchard-Jones K, Sullivan R, Hall G, Davie C, Lawler M, Hemingway H.",,No Journal Info,2020,2020-06-01,Y,,,,"

Background:

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

Methods:

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

Results:

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

Conclusion:

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

Aim

To estimate the infection and case fatality ratio of COVID-19, using data from passengers of the Diamond Princess cruise ship while correcting for delays between confirmation-and-death, and age-structure of the population.",,pdf:https://www.eurosurveillance.org/deliver/fulltext/eurosurveillance/25/12/eurosurv-25-12-3.pdf?itemId=%2Fcontent%2F10.2807%2F1560-7917.ES.2020.25.12.2000256&mimeType=pdf&containerItemId=content/eurosurveillance; doi:https://doi.org/10.1101/2020.03.05.20031773; html:https://europepmc.org/article/PPR/PPR116550; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR116550&type=FILE&fileName=EMS89041-pdf.pdf&mimeType=application/pdf PPR304173,https://doi.org/10.1101/2021.03.27.21254452,Risk factors for developing COVID-19: a population-based longitudinal study (COVIDENCE UK),"Holt H, Talaei M, Greenig M, Zenner D, Symons J, Relton C, Young KS, Davies MR, Thompson KN, Ashman J, Rajpoot SS, Kayyale AA, Rifai SE, Lloyd PJ, Jolliffe DA, Finer S, Ilidriomiti S, Miners A, Hopkinson NS, Alam B, Pfeffer PE, McCoy D, Davies GA, Lyons RA, Griffiths CJ, Kee F, Sheikh A, Breen G, Shaheen SO, Martineau AR.",,No Journal Info,2021,2021-03-29,Y,,,,"

Summary

Background

Risk factors for severe COVID-19 include older age, male sex, obesity, Black or Asian ethnicity and underlying medical conditions. Whether these factors also influence susceptibility to developing COVID-19 is uncertain.

Methods

We undertook a prospective, population-based cohort study (COVIDENCE UK) from 1 st May 2020 to 5 th February 2021. Baseline information on potential risk factors was captured by an online questionnaire. Monthly follow-up questionnaires captured incident COVID-19. We used logistic regression models to estimate multivariable-adjusted odds ratios (aORs) for associations between potential risk factors and risk of COVID-19.

Findings

We recorded 446 incident cases of COVID-19 in 15,227 participants (2.9%). Increased risk of developing COVID-19 was independently associated with Asian/Asian British vs . White ethnicity (aOR 2.31, 95% CI 1.35-3.95), household overcrowding (aOR per additional 0.5 people/bedroom 1.26, 1.11-1.43), any vs . no visits to/from other households in previous week (aOR 1.33, 1.07-1.64), number of visits to indoor public places (aOR per extra visit per week 1.05, 1.01-1.09), frontline occupation excluding health/social care vs . no frontline occupation (aOR 1.49, 1.12-1.98), and raised body mass index (BMI) (aOR 1.51 [1.20-1.90] for BMI 25.0-30.0 kg/m 2 and 1.38 [1.05-1.82] for BMI >30.0 kg/m 2 vs . BMI <25.0 kg/m 2 ). Atopic disease was independently associated with decreased risk (aOR 0.76, 0.59-0.98). No independent associations were seen for age, sex, other medical conditions, diet, or micronutrient supplement use.

Interpretation

After rigorous adjustment for factors influencing exposure to SARS-CoV-2, Asian/Asian British ethnicity and raised BMI were associated with increased risk of developing COVID-19, while atopic disease was associated with decreased risk.

Funding

Barts Charity, Health Data Research UK",,pdf:http://pure-oai.bham.ac.uk/ws/files/148236929/holth2021risk.pdf; doi:https://doi.org/10.1101/2021.03.27.21254452; html:https://europepmc.org/article/PPR/PPR304173; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR304173&type=FILE&fileName=EMS121246-pdf.pdf&mimeType=application/pdf -PPR645696,https://doi.org/10.1101/2023.04.14.23287661,"Determining prescriptions in electronic healthcare record (EHR) data: methods for development of standardized, reproducible drug codelists","Graul EL, Stone PW, Massen GM, Hatam S, Adamson A, Denaxas S, Peters NS, Quint JK.",,No Journal Info,2023,2023-04-17,Y,,,,"

ABSTRACT

Objective

Epidemiological research using electronic healthcare records(EHR) informing everyday patient care uses combinations of codes (“codelists”) to define diseases and prescriptions (or phenotypes). Yet methodology for codelist generation varies, manifesting in misclassification bias, while there are drug-specific codelist considerations.

Materials and Methods

We developed methods to generate drug codelists, testing this using the Clinical Practice Research Datalink (CPRD) Aurum database, accounting for missing data in “attribute” search variables. We generated codelists for 1)cardiovascular disease and 2)inhaled Chronic Obstructive Pulmonary Disease (COPD) therapies, applying them to a sample cohort of 335,931 COPD patients. We compared searching on all search variables (A,”gold standard”) to B) chemical and C) ontological information only.

Results

In Search A we determined 165,150 patients prescribed cardiovascular drugs(49.2% of cohort), and 317,963 prescribed COPD inhalers (94.7% of cohort). Considering output per value set, Search C missed substantial prescriptions, including vasodilator anti-hypertensives (A and B:19,696 prescriptions; C:1,145) and SAMA inhalers (A and B:35,310; C:564).

Discussion

We recommend the full methods (A) for comprehensiveness. There are special considerations when generating adaptable and generalizable drug codelists, including fluctuating status, cohort-specific drug indications, underlying hierarchical ontology, and statistical analyses.

Conclusions

Methods:

must have end-to-end clinical input, and be standardizable, reproducible, and understandable to all researchers across data contexts.

LAY ABSTRACT

Health research using patient records informs everyday medicine, using groups of codes (“codelists”) to define diseases and drugs. Yet methods to create drug codelists are inconsistent, may not include physician expertise, nor be reported. We developed a reproducible method to create drug codelists, testing it using de-identified healthcare records. We generated codelists for 1) heart conditions and 2) inhalers to identify prescriptions in a sample group of 335,931 patients with chronic lung disease. We compared our full methods (Search A) to two restricted searches to show prescriptions can be missed if necessary considerations are not made. In search A, we determined 165,150 people (49.2% of sample group) prescribed drugs from the heart codelist. For lung inhalers, we determined 317,963 prescriptions (94.7% of group). Search C missed substantial prescriptions, for drugs lowering blood pressure by opening vessels (A and B:19,696 prescriptions; C: 1,145), and short-term inhalers opening airways (A and B: 35,310; C:564). We recommend full methods(A) for completeness. Drug codelist methods must be consistent, duplicable, and include physician input at all research stages, and have special considerations including status (eg, new, taken off market), disease, and drug categorical system. Quality methods should be freely accessible and usable across study contexts.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2023/04/17/2023.04.14.23287661.full.pdf; doi:https://doi.org/10.1101/2023.04.14.23287661; html:https://europepmc.org/article/PPR/PPR645696; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR645696&type=FILE&fileName=EMS174337-pdf.pdf&mimeType=application/pdf PPR204755,https://doi.org/10.1101/2020.08.21.20177808,Quarantine and testing strategies in contact tracing for SARS-CoV-2,"Quilty BJ, Clifford S, Flasche S, Kucharski AJ, Edmunds WJ, CMMID COVID-19 Working Group.",,No Journal Info,2020,2020-08-24,Y,,,,"

Summary

Previous work has indicated that contact tracing and isolation of index case and quarantine of potential secondary cases can, in concert with physical distancing measures, be an effective strategy for reducing transmission of SARS-CoV-2 (1). Currently, contacts traced manually through the NHS Test and Trace scheme in the UK are asked to self-isolate for 14 days from the day they were exposed to the index case, which represents the upper bound for the incubation period (2). However, following previous work on screening strategies for air travellers (3,4) it may be possible that this quarantine period could be reduced if combined with PCR testing. Adapting the simulation model for contact tracing, we find that quarantine periods of at least 10 days combined with a PCR test on day 9 may largely emulate the results from a 14-day quarantine period in terms of the averted transmission potential from secondary cases (72% (95%UI: 3%, 100%) vs 75% (4%, 100%), respectively). These results assume the delays from testing index cases’ and tracing their contacts are minimised (no longer than 4.5 days on average). If secondary cases are traced and quarantined 1 day earlier on average, shorter quarantine periods of 8 days with a test on day 7 (76% (7%, 100%)) approach parity with the 14 day quarantine period with a 1 day longer delay to the index cases’ test. However, the risk of false-negative PCR tests early in a traced case’s infectious period likely prevents the use of testing to reduce quarantine periods further than this, and testing immediately upon tracing, with release if negative, will avert just 17% of transmission potential on average. In conclusion, the use of PCR testing is an effective strategy for reducing quarantine periods for secondary cases, while still reducing transmission of SARS-CoV-2, especially if delays in the test and trace system can be reduced, and may improve quarantine compliance rates.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2020/10/23/2020.08.21.20177808.full.pdf; doi:https://doi.org/10.1101/2020.08.21.20177808; html:https://europepmc.org/article/PPR/PPR204755; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR204755&type=FILE&fileName=EMS95490-pdf.pdf&mimeType=application/pdf +PPR645696,https://doi.org/10.1101/2023.04.14.23287661,"Determining prescriptions in electronic healthcare record (EHR) data: methods for development of standardized, reproducible drug codelists","Graul EL, Stone PW, Massen GM, Hatam S, Adamson A, Denaxas S, Peters NS, Quint JK.",,No Journal Info,2023,2023-04-17,Y,,,,"

ABSTRACT

Objective

Epidemiological research using electronic healthcare records(EHR) informing everyday patient care uses combinations of codes (“codelists”) to define diseases and prescriptions (or phenotypes). Yet methodology for codelist generation varies, manifesting in misclassification bias, while there are drug-specific codelist considerations.

Materials and Methods

We developed methods to generate drug codelists, testing this using the Clinical Practice Research Datalink (CPRD) Aurum database, accounting for missing data in “attribute” search variables. We generated codelists for 1)cardiovascular disease and 2)inhaled Chronic Obstructive Pulmonary Disease (COPD) therapies, applying them to a sample cohort of 335,931 COPD patients. We compared searching on all search variables (A,”gold standard”) to B) chemical and C) ontological information only.

Results

In Search A we determined 165,150 patients prescribed cardiovascular drugs(49.2% of cohort), and 317,963 prescribed COPD inhalers (94.7% of cohort). Considering output per value set, Search C missed substantial prescriptions, including vasodilator anti-hypertensives (A and B:19,696 prescriptions; C:1,145) and SAMA inhalers (A and B:35,310; C:564).

Discussion

We recommend the full methods (A) for comprehensiveness. There are special considerations when generating adaptable and generalizable drug codelists, including fluctuating status, cohort-specific drug indications, underlying hierarchical ontology, and statistical analyses.

Conclusions

Methods:

must have end-to-end clinical input, and be standardizable, reproducible, and understandable to all researchers across data contexts.

LAY ABSTRACT

Health research using patient records informs everyday medicine, using groups of codes (“codelists”) to define diseases and drugs. Yet methods to create drug codelists are inconsistent, may not include physician expertise, nor be reported. We developed a reproducible method to create drug codelists, testing it using de-identified healthcare records. We generated codelists for 1) heart conditions and 2) inhalers to identify prescriptions in a sample group of 335,931 patients with chronic lung disease. We compared our full methods (Search A) to two restricted searches to show prescriptions can be missed if necessary considerations are not made. In search A, we determined 165,150 people (49.2% of sample group) prescribed drugs from the heart codelist. For lung inhalers, we determined 317,963 prescriptions (94.7% of group). Search C missed substantial prescriptions, for drugs lowering blood pressure by opening vessels (A and B:19,696 prescriptions; C: 1,145), and short-term inhalers opening airways (A and B: 35,310; C:564). We recommend full methods(A) for completeness. Drug codelist methods must be consistent, duplicable, and include physician input at all research stages, and have special considerations including status (eg, new, taken off market), disease, and drug categorical system. Quality methods should be freely accessible and usable across study contexts.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2023/04/17/2023.04.14.23287661.full.pdf; doi:https://doi.org/10.1101/2023.04.14.23287661; html:https://europepmc.org/article/PPR/PPR645696; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR645696&type=FILE&fileName=EMS174337-pdf.pdf&mimeType=application/pdf PPR349882,https://doi.org/10.1101/2021.05.28.21257973,CoMix: Changes in social contacts as measured by the contact survey during the COVID-19 pandemic in England between March 2020 and March 2021,"Gimma A, Munday JD, Wong KL, Coletti P, van Zandvoort K, Prem K, Klepac P, Rubin GJ, Funk S, Edmunds WJ, Jarvis CI, CMMID COVID-19 working group.",,No Journal Info,2021,2021-05-30,Y,,,,"

Background

During the COVID-19 pandemic, the UK government imposed public health policies in England to reduce social contacts in hopes of curbing virus transmission. We measured contact patterns weekly from March 2020 to March 2021 to estimate the impact of these policies, covering three national lockdowns interspersed by periods of lower restrictions.

Methods

Data were collected using online surveys of representative samples of the UK population by age and gender. We calculated the mean daily contacts reported using a (clustered) bootstrap and fitted a censored negative binomial model to estimate age-stratified contact matrices and estimate proportional changes to the basic reproduction number under controlled conditions using the change in contacts as a scaling factor.

Results

The survey recorded 101,350 observations from 19,914 participants who reported 466,710 contacts over 53 weeks. Contact patterns changed over time and by participants’ age, personal risk factors, and perception of risk. The mean of reported contacts among adults have reduced compared to previous surveys with adults aged 18 to 59 reporting a mean of 2.39 (95% CI 2.20 - 2.60) contacts to 4.93 (95% CI 4.65 - 5.19) contacts, and the mean contacts for school-age children was 3.07 (95% CI 2.89 - 3.27) to 15.11 (95% CI 13.87 - 16.41). The use of face coverings outside the home has remained high since the government mandated use in some settings in July 2020.

Conclusions

The CoMix survey provides a unique longitudinal data set for a full year since the first lockdown for use in statistical analyses and mathematical modelling of COVID-19 and other diseases. Recorded contacts reduced dramatically compared to pre-pandemic levels, with changes correlated to government interventions throughout the pandemic. Despite easing of restrictions in the summer of 2020, mean reported contacts only returned to about half of that observed pre-pandemic.",,pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1003907&type=printable; doi:https://doi.org/10.1101/2021.05.28.21257973; html:https://europepmc.org/article/PPR/PPR349882; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR349882&type=FILE&fileName=EMS126781-pdf.pdf&mimeType=application/pdf PPR291776,https://doi.org/10.1101/2021.03.02.21252444,An overview of the National COVID-19 Chest Imaging Database: data quality and cohort analysis,"Cushnan D, Bennett O, Berka R, Bertolli O, Chopra A, Dorgham S, Favaro A, Ganepola T, Halling-Brown M, Imreh G, Jacob J, Jefferson E, Lemarchand F, Schofield D, Wyatt JC, NCCID Collaborative.",,No Journal Info,2021,2021-03-03,Y,,,,"The National COVID-19 Chest Imaging Database (NCCID) is a centralised database containing chest X-rays, chest Computed Tomography (CT) scans and cardiac Magnetic Resonance Images (MRI) from patients across the UK, jointly established by NHSX, the British Society of Thoracic Imaging (BSTI), Royal Surrey NHS Foundation Trust (RSNFT) and Faculty. The objective of the initiative is to support a better understanding of the coronavirus SARS-CoV-2 disease (COVID-19) and development of machine learning (ML) technologies that will improve care for patients hospitalised with a severe COVID-19 infection. The NCCID is now accumulating data from 20 NHS Trusts and Health Boards across England and Wales, with a total contribution of approximately 25,000 imaging studies in the training set (at time of writing) and is actively being used as a research tool by several organisations. This paper introduces the training dataset, including a snapshot analysis performed by NHSX covering: the completeness of clinical data, the availability of image data for the various use-cases (diagnosis, prognosis and longitudinal risk) and potential model confounders within the imaging data. The aim is to inform both existing and potential data users of the NCCID’s suitability for developing diagnostic/prognostic models. In addition, a cohort analysis was performed to measure the representativeness of the NCCID to the wider COVID-19 affected population. Three major aspects were included: geographic, demographic and temporal coverage, revealing good alignment in some categories, e.g., sex and identifying areas for improvements to data collection methods, particularly with respect to geographic coverage. All analyses and discussions are focused on the implications for building ML tools that will generalise well to the clinical use cases.",,pdf:https://discovery.dundee.ac.uk/files/69908473/giab076.pdf; doi:https://doi.org/10.1101/2021.03.02.21252444; html:https://europepmc.org/article/PPR/PPR291776; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR291776&type=FILE&fileName=EMS118552-pdf.pdf&mimeType=application/pdf PPR172602,https://doi.org/10.1101/2020.06.06.20122689,The impact of COVID-19 control measures on social contacts and transmission in Kenyan informal settlements,"Quaife M, van Zandvoort K, Gimma A, Shah K, McCreesh N, Prem K, Barasa E, Mwanga D, Kangwana B, Pinchoff J, Edmunds WJ, Jarvis CI, Austrian K, CMMID COVID-19 Working Group.",,No Journal Info,2020,2020-06-07,Y,,,,"

Background

Many low- and middle-income countries have implemented control measures against coronavirus disease 2019 (COVID-19). However, it is not clear to what extent these measures explain the low numbers of recorded COVID-19 cases and deaths in Africa. One of the main aims of control measures is to reduce respiratory pathogen transmission through direct contact with others. In this study we collect contact data from residents of informal settlements around Nairobi, Kenya to assess if control measures have changed contact patterns, and estimate the impact of changes on the basic reproduction number ( R 0 ).

Methods

We conducted a social contact survey with 213 residents of five informal settlements around Nairobi in early May 2020, four weeks after the Kenyan government introduced enhanced physical distancing measures and a curfew between 7pm and 5am. Respondents were asked to report all direct physical and non-physical contacts made the previous day, alongside a questionnaire asking about the social and economic impact of COVID-19 and control measures. We examined contact patterns by demographic factors, including socioeconomic status. We described the impact of COVID-19 and control measures on income and food security. We compared contact patterns during control measures to patterns from non-pandemic periods to estimate the change in R 0 .

Findings

We estimate that control measures reduced physical and non-physical contacts, reducing the R 0 from around 2.6 to between 0.5 and 0.7, depending on the pre-COVID-19 comparison matrix used. Masks were worn by at least one person in 92% of contacts. Respondents in the poorest socioeconomic quintile reported 1.5 times more contacts than those in the richest. 86% of respondents reported a total or partial loss of income due to COVID-19, and 74% reported eating less or skipping meals due to having too little money for food.

Interpretation

COVID-19 control measures have had a large impact on direct contacts and therefore transmission, but have also caused considerable economic and food insecurity. Reductions in R 0 are consistent with the linear epidemic growth in Kenya and other sub-Saharan African countries that implemented similar, early control measures. However, negative and inequitable impacts on economic and food security may mean control measures are not sustainable in the longer term.

Research in context

Evidence before this study

We conducted a PubMed search on 6 June 2020 with no language restrictions for studies published since inception, using the search terms (“social mix*” OR “social cont*” OR “contact pattern*) AND (“covid*”). The search yielded 53 articles, two of which reported changes in social contacts after COVID-19 control measures. The first study reported changes in contact patterns in Wuhan and Shanghai, and the second changes in contact patterns in the UK. We found no studies examining changes in contact patterns due to control measures in sub-Saharan Africa, and no studies disaggregating contacts by socioeconomic status.

Added value of this study

This is the first study to estimate the reproduction number of COVID-19 under control measures in sub-Saharan Africa using primary contact data. This study also moves beyond existing work to i) measure contacts in densely populated informal settlements, ii) explore how social contacts vary across socioeconomic status, and iii) assess the impact of control measures on economic and food security in these areas.

Implications of all the evidence

COVID-19 control measures have substantially reduced social contacts and disease transmission. People of lower socioeconomic status face greater transmission risk as they report more contacts. Control measures have led to considerable economic and food insecurity, and may not be sustainable in the long term without efforts to reduce the burden of control measures on households.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-020-01779-4; doi:https://doi.org/10.1101/2020.06.06.20122689; html:https://europepmc.org/article/PPR/PPR172602; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR172602&type=FILE&fileName=EMS91656-pdf.pdf&mimeType=application/pdf @@ -387,8 +387,8 @@ PPR291740,https://doi.org/10.1101/2021.03.03.21252737,"Ethnicity and COVID-19 ou PPR558613,https://doi.org/10.1101/2022.10.17.22281058,Eleven key measures for monitoring general practice clinical activity during COVID-19 using federated analytics on 48 million adults’ primary care records through OpenSAFELY,"Fisher L, Curtis HJ, Croker R, Wiedemann M, Speed V, Wood C, Brown A, Hopcroft LE, Higgins R, Massey J, Inglesby P, Morton CE, Walker AJ, Morley J, Mehrkar A, Bacon S, Hickman G, Macdonald O, Lewis T, Wood M, Myers M, Samuel M, Conibere R, Baqir W, Sood H, Drury C, Collison K, Bates C, Evans D, Dillingham I, Ward T, Davy S, Smith RM, Hulme W, Green A, Parry J, Hester F, Harper S, Cockburn J, O’Hanlon S, Eavis A, Jarvis R, Avramov D, Griffiths P, Fowles A, Parkes N, MacKenna B, Goldacre B.",,No Journal Info,2022,2022-10-17,Y,,,,"

Background

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

Objectives

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

Methods

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

Results

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

Conclusions

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

Objectives

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

Design and setting

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

Methods

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

Results

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

Conclusions

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

Summary boxes

What is already known on this topic

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

What this study adds

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

Background

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

Objective

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

Methods

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

Results

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

Conclusions

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

Background

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

Methods

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

Findings

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

Interpretation

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

Funding

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

Objectives

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

Design

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

Setting

260 hospitals across England, Scotland, and Wales.

Participants

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

Main outcome measures

In-hospital mortality.

Results

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

Conclusions

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

Study registration

ISRCTN66726260",,pdf:https://www.bmj.com/content/bmj/370/bmj.m3339.full.pdf; doi:https://doi.org/10.1101/2020.07.30.20165464; html:https://europepmc.org/article/PPR/PPR195140; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR195140&type=FILE&fileName=EMS95810-pdf.pdf&mimeType=application/pdf +PPR639769,https://doi.org/10.1101/2023.04.01.23287538,Trends in weight gain recorded in English primary care before and during the Coronavirus-19 pandemic: an observational cohort study using the OpenSAFELY platform,"Samuel M, Park RY, Eastwood SV, Eto F, Morton CE, Stow D, Bacon S, Mehrkar A, Morley J, Dillingham I, Inglesby P, Hulme WJ, Khunti K, Mathur R, Valabhji J, MacKenna B, Finer S, The OpenSAFELY Collaborative.",,No Journal Info,2023,2023-04-03,Y,,,,"

Background

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

Methods

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

Findings

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

Interpretation

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

Funding

NIHR",,pdf:https://www.medrxiv.org/content/medrxiv/early/2023/04/03/2023.04.01.23287538.full.pdf; doi:https://doi.org/10.1101/2023.04.01.23287538; html:https://europepmc.org/article/PPR/PPR639769; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR639769&type=FILE&fileName=EMS173550-pdf.pdf&mimeType=application/pdf PPR406625,https://doi.org/10.1101/2021.10.10.21264821,Modelling the effect of COVID-19 mass vaccination on acute admissions in a major English healthcare system,"Booton R, Powell A, Turner K, Wood R.",,No Journal Info,2021,2021-10-13,Y,,,,"

Background

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

Methods

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

Results

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

Conclusion

Modelling provided support to senior managers in setting the number of acute and intensive care beds to make available for COVID-19 patients, as well as highlighting the importance of public health in promoting high vaccine uptake among the population. Forecast accuracy has since been supported by actual data collected following the analysis, with observed peak bed occupancy falling comfortably within the inter-quartile range of modelled projections.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2021/10/13/2021.10.10.21264821.full.pdf; doi:https://doi.org/10.1101/2021.10.10.21264821; html:https://europepmc.org/article/PPR/PPR406625; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR406625&type=FILE&fileName=EMS136883-pdf.pdf&mimeType=application/pdf PPR157839,https://doi.org/10.1101/2020.04.27.20081711,Response strategies for COVID-19 epidemics in African settings: a mathematical modelling study,"Zandvoort Kv, Jarvis CI, Pearson CAB, Davies NG, Russell TW, Kucharski AJ, Jit M, Flasche S, Eggo RM, Checchi F, CMMID COVID-19 working group.",,No Journal Info,2020,2020-05-03,Y,,,,"

Background

The health impact of COVID-19 may differ in African settings as compared to countries in Europe or China due to demographic, epidemiological, environmental and socio-economic factors. We evaluated strategies to reduce SARS-CoV-2 burden in African countries, so as to support decisions that balance minimising mortality, protecting health services and safeguarding livelihoods.

Methods

We used a Susceptible-Exposed-Infectious-Recovered mathematical model, stratified by age, to predict the evolution of COVID-19 epidemics in three countries representing a range of age distributions in Africa (from oldest to youngest average age: Mauritius, Nigeria and Niger), under various effectiveness assumptions for combinations of different non-pharmaceutical interventions: self-isolation of symptomatic people, physical distancing, and ‘shielding’ (physical isolation) of the high-risk population. We adapted model parameters to better represent uncertainty about what might be expected in African populations, in particular by shifting the distribution of severity risk towards younger ages and increasing the case-fatality ratio.

Results

We predicted median clinical attack rates over the first 12 months of 17% (Niger) to 39% (Mauritius), peaking at 2–4 months, if epidemics were unmitigated. Self-isolation while symptomatic had a maximum impact of about 30% on reducing severe cases, while the impact of physical distancing varied widely depending on percent contact reduction and R 0 . The effect of shielding high-risk people, e.g. by rehousing them in physical isolation, was sensitive mainly to residual contact with low-risk people, and to a lesser extent to contact among shielded individuals. Response strategies incorporating self-isolation of symptomatic individuals, moderate physical distancing and high uptake of shielding reduced predicted peak bed demand by 46% to 54% and mortality by 60% to 75%. Lockdowns delayed epidemics by about 3 months. Estimates were sensitive to differences in age-specific social mixing patterns, as published in the literature.

Discussion

In African settings, as elsewhere, current evidence suggests large COVID-19 epidemics are expected. However, African countries have fewer means to suppress transmission and manage cases. We found that self-isolation of symptomatic persons and general physical distancing are unlikely to avert very large epidemics, unless distancing takes the form of stringent lockdown measures. However, both interventions help to mitigate the epidemic. Shielding of high-risk individuals can reduce health service demand and, even more markedly, mortality if it features high uptake and low contact of shielded and unshielded people, with no increase in contact among shielded people. Strategies combining self-isolation, moderate physical distancing and shielding will probably achieve substantial reductions in mortality in African countries. Temporary lockdowns, where socioeconomically acceptable, can help gain crucial time for planning and expanding health service capacity.","Zandvoort et al. used mathematical modelling and simulation methods to predict the impact of various control scenarios on outcome of COVID-19 epidemics in three African countries. They’ve shown that mixed strategies, including moderate physical distancing and shielding are more likely to achieve substantial reductions in mortality in African countries. ",pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-020-01789-2; doi:https://doi.org/10.1101/2020.04.27.20081711; html:https://europepmc.org/article/PPR/PPR157839; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR157839&type=FILE&fileName=EMS91299-pdf.pdf&mimeType=application/pdf PPR273714,https://doi.org/10.1101/2021.01.25.21250356,Trends and clinical characteristics of COVID-19 vaccine recipients: a federated analysis of 57.9 million patients’ primary care records in situ using OpenSAFELY,"The OpenSAFELY Collaborative, Curtis HJ, Inglesby P, Morton CE, MacKenna B, MacKenna B, Walker AJ, Morley J, Mehrkar A, Bacon S, Hickman G, Bates C, Croker R, Evans D, Ward T, Cockburn J, Davy S, Bhaskaran K, Schultze A, Rentsch CT, Williamson E, Hulme W, Green A, Rowan A, Fisher L, McDonald HI, Tomlinson L, Mathur R, Drysdale H, Eggo RM, Wing K, Wong AY, Forbes H, Parry J, Hester F, Harper S, O’Hanlon S, Eavis A, Jarvis R, Avramov D, Griffiths P, Fowles A, Parkes N, Douglas IJ, Evans SJ, Smeeth L, Goldacre B.",,No Journal Info,2021,2021-01-26,Y,,,,"

Background

On December 8th 2020, NHS England administered the first COVID-19 vaccination as part of an ambitious vaccination programme during a global health emergency.

Aims

To describe trends and variation in vaccine coverage by key clinical and demographic groups; to create a framework for near-real-time monitoring of vaccine coverage in key subgroups.

Methods

Working on behalf of NHS England we analysed 57.9 million patient records in situ and in near-real-time within the infrastructure of the Electronic Health Record (EHR) software vendors EMIS and TPP using OpenSAFELY. We describe vaccine coverage and time trends across a range of demographic and fine-grained clinical subgroups in eight Joint Committee on Vaccination and Immunisation (JCVI) priority cohorts.

Results

20,852,692 patients (36%) received a COVID-19 vaccine between December 8th 2020 and March 17th 2021. Of patients aged ≥80 not in a care home (JCVI group 2) 94.7% received a vaccine, but with substantial variation by ethnicity (White 96.2% vaccinated, Black 68.3%) and deprivation (least deprived 96.6%, most deprived 90.7%). Overall, patients with pre-existing medical conditions were equally or more likely to be vaccinated with two exceptions: severe mental illness (89.5% vaccinated) and learning disability (91.4%). 275,205 vaccine recipients were identified as care home residents (priority group 1; 91.2% coverage). 1,257,914 (6.0%) recipients have had a second dose. Detailed characteristics of recipients in all cohorts are reported.

Conclusions

The NHS in England has rapidly delivered mass vaccination. We were able to deploy a data monitoring framework using publicly auditable methods and a secure, in-situ processing model, using linked but pseudonymised patient-level NHS data on 57.9 million patients with very short delays from vaccine administration to completed analysis. Targeted activity may be needed to address lower vaccination coverage observed among certain key groups: ethnic minorities, those living in deprived areas, and people with severe mental illness or learning disabilities.",,pdf:https://researchonline.lshtm.ac.uk/id/eprint/4663784/1/BJGP.2021.0376.full.pdf; doi:https://doi.org/10.1101/2021.01.25.21250356; html:https://europepmc.org/article/PPR/PPR273714; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR273714&type=FILE&fileName=EMS114826-pdf.pdf&mimeType=application/pdf @@ -431,8 +431,8 @@ PPR812457,https://doi.org/10.1101/2024.02.28.24303461,"APOL1 variants G1, G2 and PPR187554,https://doi.org/10.1101/2020.07.14.20152629,COVID-19 infection and attributable mortality in UK care homes: Cohort study using active surveillance and electronic records (March-June 2020),"Dutey-Magni PF, Williams H, Jhass A, Rait G, Lorencatto F, Hemingway H, Hemingway H, Hayward A, Shallcross L.",,No Journal Info,2020,2020-07-15,Y,,,,"

Background

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

Methods

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

Results

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

Conclusions

Findingss:

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

Objectives

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

Methods

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

Results

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

Conclusions

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

Background

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

Objective

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

Methods

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

Results

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

Conclusions

We successfully delivered an open source software framework to describe trends and variation in clinical activity across an unprecedented scale of primary care data. The COVD-19 pandemic led to a substantial change in healthcare activity. Most laboratory tests showed substantial reduction, largely recovering to near-normal levels by September 2020, with some important tests less affected. Records of respiratory infections decreased with the exception of codes related to COVID-19, whilst activity of other respiratory disease codes was mixed. We are expanding the NHS Service Restoration Observatory in collaboration with clinicians, commissioners and researchers and welcome feedback.",,pdf:https://bjgp.org/content/bjgp/72/714/e63.full.pdf; doi:https://doi.org/10.1101/2021.01.06.21249352; html:https://europepmc.org/article/PPR/PPR263081; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR263081&type=FILE&fileName=EMS110198-pdf.pdf&mimeType=application/pdf -PPR755427,https://doi.org/10.21203/rs.3.rs-3568389/v1,Stigma relating to tuberculosis infection prevention and control implementation in rural health facilities in South Africa – a theoretical analysis with opportunities for mitigation,"Westhuizen H, Ehrlich R, Somdyala N, Greenhalgh T, Tonkin-Crine S, Butler CC.",,No Journal Info,2023,2023-11-08,Y,,,,"

Background:

Tuberculosis (TB) is a stigmatised disease due to its associations with poverty, HIV, transmission risk and mortality. The use of visible TB infection prevention and control (IPC) measures, such as masks or isolation, can contribute to stigma. Methods To explore stigma in this condition, we conducted in-depth individual interviews with 18 health workers and 15 patients in the rural Eastern Cape of South Africa using a semi-structured interview guide and narrative approach. We used reflexive thematic analysis and applied Link and Phelan’s theoretical model of stigma. Results Participants shared poignant narratives of TB stigma, often entailing TB IPC, with some feeling ‘less than human’. We found TB IPC measures sometimes exacerbated stigma, for example through introducing physical isolation that became prolonged, or through a mask marking the person out as being ill with TB. In this context, stigma emerged from the narrow definition of what mask-wearing symbolises, in contrast with broader uses of masks as a preventative measure. In this way, the health facility itself was shown to play an important role in generating and perpetuating IPC related stigma. We applied ‘ubuntu’ as African humanist conceptual framework to develop recommendations of how TB IPC implementation could be destigmatised. Conclusion Health facilities may unwittingly perpetuate stigma, but they also have the potential to reduce it. Ubuntu emphases shared humanity and collective wellbeing and could engage with some of the deep-rooted contributors to TB stigma. An ubuntu-informed approach could underpin a local policy change to universal masking, thereby destigmatising an important IPC practice.",,pdf:https://www.researchsquare.com/article/rs-3568389/latest.pdf; doi:https://doi.org/10.21203/rs.3.rs-3568389/v1; html:https://europepmc.org/article/PPR/PPR755427; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR755427&type=FILE&fileName=EMS191184-pdf.pdf&mimeType=application/pdf PPR230572,https://doi.org/10.1101/2020.10.26.20219550,Detecting behavioural changes in human movement to inform the spatial scale of interventions against COVID-19,"Gibbs H, Nightingale E, Liu Y, Cheshire J, Danon L, Smeeth L, Pearson CA, Grundy C, Kucharski AJ, Eggo RM, LSHTM CMMID COVID-19 working group.",,No Journal Info,2020,2020-10-27,Y,,,,"

Background

In 2020, the UK enacted an intensive, nationwide lockdown on March 23 to mitigate transmission of COVID-19. As restrictions began to ease, resurgences in transmission were targeted by geographically-limited interventions of various stringencies. Understanding the spatial scale of networks of human interaction, and how these networks change over time, is critical to inform interventions targeted at the most at-risk areas without unnecessarily restricting areas at low risk of resurgence.

Methods

We use detailed human mobility data aggregated from Facebook users to determine how the spatially-explicit network of movements changed before and during the lockdown period, in response to the easing of restrictions, and to the introduction of locally-targeted interventions. We also apply community detection techniques to the weighted, directed network of movements to identify geographically-explicit movement communities and measure the evolution of these community structures through time.

Findings

We found that the mobility network became more sparse and the number of mobility communities decreased under the national lockdown, a change that disproportionately affected long distance journeys central to the mobility network. We also found that the community structure of areas in which locally-targeted interventions were implemented following epidemic resurgence did not show reorganization of community structure but did show small decreases in indicators of travel outside of local areas.

Interpretation

We propose that communities detected using Facebook or other mobility data be used to assess the impact of spatially-targeted restrictions and may inform policymakers about the spatial extent of human movement patterns in the UK. These data are available in near real-time, allowing quantification of changes in the distribution of the population across the UK, as well as changes in travel patterns to inform our understanding of the impact of geographically-targeted interventions.

Putting Research Into Context

Evidence before this study

Large-scale intensive interventions in response to the COVID-19 pandemic have been implemented globally, significantly affecting human movement patterns. Mobility data show spatially-explicit network structure, but it is not clear how that structure changed in response to national or locally-targeted interventions.

Added value of this study

We used daily mobility data aggregated from Facebook users to quantify changes in the travel network in the UK during the national lockdown, and in response to local interventions. We identified changes in human behaviour in response to interventions and identified the community structure inherent in these networks. This approach to understanding changes in the travel network can help quantify the extent of strongly connected communities of interaction and their relationship to the extent of spatially-explicit interventions.

Implications of all the available evidence

We show that spatial mobility data available in near real-time can give information on connectivity that can be used to understand the impact of geographically-targeted interventions and in the future, to inform spatially-targeted intervention strategies.

Data Sharing

Data used in this study are available from the Facebook Data for Good Partner Program by application. Code and supplementary information for this paper are available online ( https://github.com/hamishgibbs/facebook_mobility_uk ), alongside publication.",,pdf:https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1009162&type=printable; doi:https://doi.org/10.1101/2020.10.26.20219550; html:https://europepmc.org/article/PPR/PPR230572; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR230572&type=FILE&fileName=EMS101630-pdf.pdf&mimeType=application/pdf +PPR755427,https://doi.org/10.21203/rs.3.rs-3568389/v1,Stigma relating to tuberculosis infection prevention and control implementation in rural health facilities in South Africa – a theoretical analysis with opportunities for mitigation,"Westhuizen H, Ehrlich R, Somdyala N, Greenhalgh T, Tonkin-Crine S, Butler CC.",,No Journal Info,2023,2023-11-08,Y,,,,"

Background:

Tuberculosis (TB) is a stigmatised disease due to its associations with poverty, HIV, transmission risk and mortality. The use of visible TB infection prevention and control (IPC) measures, such as masks or isolation, can contribute to stigma. Methods To explore stigma in this condition, we conducted in-depth individual interviews with 18 health workers and 15 patients in the rural Eastern Cape of South Africa using a semi-structured interview guide and narrative approach. We used reflexive thematic analysis and applied Link and Phelan’s theoretical model of stigma. Results Participants shared poignant narratives of TB stigma, often entailing TB IPC, with some feeling ‘less than human’. We found TB IPC measures sometimes exacerbated stigma, for example through introducing physical isolation that became prolonged, or through a mask marking the person out as being ill with TB. In this context, stigma emerged from the narrow definition of what mask-wearing symbolises, in contrast with broader uses of masks as a preventative measure. In this way, the health facility itself was shown to play an important role in generating and perpetuating IPC related stigma. We applied ‘ubuntu’ as African humanist conceptual framework to develop recommendations of how TB IPC implementation could be destigmatised. Conclusion Health facilities may unwittingly perpetuate stigma, but they also have the potential to reduce it. Ubuntu emphases shared humanity and collective wellbeing and could engage with some of the deep-rooted contributors to TB stigma. An ubuntu-informed approach could underpin a local policy change to universal masking, thereby destigmatising an important IPC practice.",,pdf:https://www.researchsquare.com/article/rs-3568389/latest.pdf; doi:https://doi.org/10.21203/rs.3.rs-3568389/v1; html:https://europepmc.org/article/PPR/PPR755427; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR755427&type=FILE&fileName=EMS191184-pdf.pdf&mimeType=application/pdf PPR846535,https://doi.org/10.1101/2024.04.30.24306314,Data Resource Profile: Whole Blood DNA Methylation Resource in Generation Scotland (MeGS),"Walker RM, McCartney DL, Carr K, Barber M, Shen X, Campbell A, Bernabeu E, Aitken E, Fawkes A, Wrobel N, Murphy L, Whalley HC, Howard DM, Adams MJ, Rawlik K, Navarro P, Tenesa A, Sudlow CL, Porteous DJ, Marioni R, McIntosh AM, Evans KL.",,No Journal Info,2024,2024-05-02,Y,,,,"We have generated whole-blood DNA methylation profiles from 18,869 Generation Scotland Scottish Family Health Study (GS) participants, resulting in, at the time of writing, the largest single-cohort DNA methylation resource for basic biological and medical research: Methylation in Generation Scotland (MeGS). GS is a community- and family-based cohort, which recruited over 24,000 participants from Scotland between 2006 and 2011. Comprehensive phenotype information, including detailed data on cognitive function, personality traits, and mental health, is available for all participants. The majority (83%) have genome-wide SNP genotype data (Illumina HumanOmniExpressExome-8 array v1.0 and v1.2), and over 97% of GS participants have given consent for health record linkage and re-contact. At baseline, blood-based DNA methylation was characterised at ∼850,000 sites across four batches using the Illumina EPICv1 array. MeGS participants were aged between 17 and 99 years at the time of enrolment to GS. Blood-based DNA methylation EPICv1 array profiles collected at a follow-up appointment that took place 4.3-12.2 years (mean=7.1 years) after baseline are also available for 796 MeGS participants. Access to MeGS for researchers in the UK and international collaborators is via application to the GS Access Committee ( access@generationscotland.org ).",,pdf:https://www.medrxiv.org/content/medrxiv/early/2024/05/02/2024.04.30.24306314.full.pdf; doi:https://doi.org/10.1101/2024.04.30.24306314; html:https://europepmc.org/article/PPR/PPR846535 PPR224937,https://doi.org/10.1101/2020.10.08.20209072,Estimating the impact of disruptions due to COVID-19 on HIV transmission and control among men who have sex with men in China,"Booton RD, Fu G, MacGregor L, Li J, Ong JJ, Tucker JD, Turner KM, Tang W, Vickerman P, Mitchell KM.",,No Journal Info,2020,2020-10-13,Y,,,,"

Introduction

The COVID-19 pandemic is impacting HIV care globally, with gaps in HIV treatment expected to increase HIV transmission and HIV-related mortality. We estimated how COVID-19-related disruptions could impact HIV transmission and mortality among men who have sex with men (MSM) in four cities in China.

Methods

Regional data from China indicated that the number of MSM undergoing facility-based HIV testing reduced by 59% during the COVID-19 pandemic, alongside reductions in ART initiation (34%), numbers of sexual partners (62%) and consistency of condom use (25%). A deterministic mathematical model of HIV transmission and treatment among MSM in China was used to estimate the impact of these disruptions on the number of new HIV infections and HIV-related deaths. Disruption scenarios were assessed for their individual and combined impact over 1 and 5 years for a 3-, 4- or 6-month disruption period.

Results

Our China model predicted that new HIV infections and HIV-related deaths would be increased most by disruptions to viral suppression, with 25% reductions for a 3-month period increasing HIV infections by 5-14% over 1 year and deaths by 7-12%. Observed reductions in condom use increased HIV infections by 5-14% but had minimal impact (<1%) on deaths. Smaller impacts on infections and deaths (<3%) were seen for disruptions to facility testing and ART initiation, but reduced partner numbers resulted in 11-23% fewer infections and 0.4-1.0% fewer deaths. Longer disruption periods of 4 and 6 months amplified the impact of combined disruption scenarios. When all realistic disruptions were modelled simultaneously, an overall decrease in new HIV infections was always predicted over one year (3-17%), but not over 5 years (1% increase-4% decrease), while deaths mostly increased over one year (1-2%) and 5 years (1.2 increase – 0.3 decrease).

Conclusions

The overall impact of COVID-19 on new HIV infections and HIV-related deaths is dependent on the nature, scale and length of the various disruptions. Resources should be directed to ensuring levels of viral suppression and condom use are maintained to mitigate any adverse effects of COVID-19 related disruption on HIV transmission and control among MSM in China.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7574267; doi:https://doi.org/10.1101/2020.10.08.20209072; html:https://europepmc.org/article/PPR/PPR224937; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR224937&type=FILE&fileName=EMS98388-pdf.pdf&mimeType=application/pdf PPR308156,https://doi.org/10.1101/2021.04.02.21254818,Covid-19 does not look like what you are looking for: Clustering symptoms by nation and multi-morbidities reveal substantial differences to the classical symptom triad,"Kadirvelu B, Burcea G, Quint JK, Costelloe CE, Faisal AA.",,No Journal Info,2021,2021-04-07,Y,,,,"

ABSTRACT

COVID-19 is by convention characterised by a triad of symptoms: cough, fever and loss of taste/smell. The aim of this study was to examine clustering of COVID-19 symptoms based on underlying chronic disease and geographical location. Using a large global symptom survey of 78,299 responders in 190 different countries, we examined symptom profiles in relation to geolocation (grouped by country) and underlying chronic disease (single, co- or multi-morbidities) associated with a positive COVID-19 test result using statistical and machine learning methods to group populations by underlying disease, countries, and symptoms. Taking the responses of 7980 responders with a COVID-19 positive test in the top 5 contributing countries, we find that the most frequently reported symptoms differ across the globe: For example, fatigue 4108(51.5%), headache 3640(45.6%) and loss of smell and taste 3563(44.6%) are the most reported symptoms globally. However, symptom patterns differ by continent; India reported a significantly lower proportion of headache (22.8% vs 45.6%, p<0.05) and itchy eyes (7.0% vs. 15.3%, p<0.05) than other countries, as does Pakistan (33.6% vs 45.6%, p<0.05 and 8.6% vs 15.3%, p<0.05). Mexico and Brazil report significantly less of these symptoms. As with geographic location, we find people differed in their reported symptoms, if they suffered from specific underlying diseases. For example, COVID-19 positive responders with asthma or other lung disease were more likely to report shortness of breath as a symptom, compared with COVID-19 positive responders who had no underlying disease (25.3% vs. 13.7%, p<0.05, and 24.2 vs.13.7%, p<0.05). Responders with no underlying chronic diseases were more likely to report loss of smell and tastes as a symptom (46%), compared with the responders with type 1 diabetes (21.3%), Type 2 diabetes (33.5%) lung disease (29.3%), or hypertension (37.8%). Global symptom ranking differs markedly from the well-known and commonly described symptoms for COVID-19, which are based on a few localised studies. None of the five countries studied in depth recorded cough or temperature as the most common symptoms. The most common symptoms reported were fatigue and loss of smell and taste. Amongst responders from Brazil cough was the second most frequently reported symptom, after fatigue. Moreover, we find that across countries and based on underlying chronic diseases, there are significant differences in symptom profiles at presentation, that cannot be fully explained by the different chronic disease profiles of these countries, and may be caused by differences in climate, environment and ethnicities. These factors uncovered by our global comorbidity survey of COVID-19 positive tested people may contribute to the apparent large asymptotic COVID-19 spread and put patients with underlying disease systematically more at risk.

Executive Summary

Evidence before this work

An early meta-analysis of epidemiological variation in COVID-19 inside and outside China studied patient characteristics including, gender, age, fatality rate, and symptoms of fever, cough, shortness of breath and diarrhoea in COVID-19 patients. They found that important symptom differences existed in patients in China compared to other countries and recommended that clinical symptoms of COVID-19 should not be generalized to fever, shortness of breath and cough only, but other symptoms such as diarrhoea are also shown to be prevalent in patients with COVID-19.

Added value of this work

W e find that across countries and based on underlying chronic diseases, there are significant differences in symptom profiles at presentation, that cannot be fully explained by the different chronic disease profiles of these countries, and may be caused by differences in climate, environment and ethnicities.

Implications of the evidence

These factors, uncovered by our global comorbidity survey of COVID-19 positive tested people may contribute to the apparent large asymptotic COVID-19 spread and put patients with underlying disease systematically more at risk.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2021/04/07/2021.04.02.21254818.full.pdf; doi:https://doi.org/10.1101/2021.04.02.21254818; html:https://europepmc.org/article/PPR/PPR308156; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR308156&type=FILE&fileName=EMS121846-pdf.pdf&mimeType=application/pdf @@ -483,8 +483,8 @@ PPR159091,https://doi.org/10.1101/2020.05.02.20078642,Impact of ethnicity on out PPR433263,https://doi.org/10.21203/rs.3.rs-1113627/v1,"Estimating the Local Burden of Disease During the First Wave of the COVID-19 Epidemic in England, Using Different Data Sources from Changing Surveillance Practices","Nightingale ES, Abbott S, Russell TW, Lowe R, Medley GF, Brady OJ.",,No Journal Info,2021,2021-12-16,Y,,,,"

Background:

The COVID-19 epidemic has differentially impacted communities across England, with regional variation in rates of confirmed cases, hospitalisations and deaths. Measurement of this burden changed substantially over the first months, as surveillance was expanded to accommodate the escalating epidemic. Laboratory confirmation was initially restricted to clinical need (“pillar 1”) before expanding to community-wide symptomatics (“pillar 2”). This study aimed to ascertain whether inconsistent measurement of case data resulting from varying testing coverage could be reconciled by drawing inference from COVID-19-related deaths. MethodsWe fit a Bayesian spatio-temporal model to weekly COVID-19-related deaths per local authority (LTLA) throughout the first wave (1 January - 30 June 2020), adjusting for the local epidemic timing and the age, deprivation and ethnic composition of its population. We combined predictions from this model with case data under community-wide, symptomatic testing and infection prevalence estimates from the ONS infection survey, to infer the likely trajectory of infections implied by the deaths in each LTLA.ResultsA model including temporally- and spatially-correlated random effects was found to best accommodate the observed variation in COVID-19-related deaths, after accounting for local population characteristics. Predicted case counts under community-wide symptomatic testing suggest a total of 275,000-420,000 cases over the first wave - a median of over 100,000 additional to the total confirmed in practice under varying testing coverage. This translates to a peak incidence of around 200,000 total infections per week across England. The extent to which estimated total infections are reflected in confirmed case counts was found to vary substantially across LTLAs, ranging from 7% in Leicester to 96% in Gloucester with a median of 23%. ConclusionsLimitations in testing capacity biased the observed trajectory of COVID-19 infections throughout the first wave. Basing inference on COVID-19-related mortality and higher-coverage testing later in the time period, we could explore the extent of this bias more explicitly. Evidence points towards substantial under-representation of initial growth and peak magnitude of infections nationally, to which different parts of the country contribute unequally.",,pdf:https://bmcpublichealth.biomedcentral.com/track/pdf/10.1186/s12889-022-13069-0; doi:https://doi.org/10.21203/rs.3.rs-1113627/v1; html:https://europepmc.org/article/PPR/PPR433263; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR433263&type=FILE&fileName=EMS141407-pdf.pdf&mimeType=application/pdf PPR532220,https://doi.org/10.1101/2022.08.15.22278736,Incidence and management of inflammatory arthritis in England before and during the COVID-19 pandemic: a population-level cohort study using OpenSAFELY,"Russell MD, Galloway JB, Andrews CD, MacKenna B, Goldacre B, Mehrkar A, Curtis HJ, Butler-Cole B, O’Dwyer T, Qureshi S, Ledingham JM, Mahto A, Rutherford AI, Adas MA, Alveyn E, Norton S, Cope AP, Bechman K, OpenSAFELY Collaborative.",,No Journal Info,2022,2022-08-16,N,,,,"

Objective

To use the OpenSAFELY platform to replicate key metrics from a national clinical audit, and assess the impact of COVID-19 on disease incidence and care delivery for inflammatory arthritis (IA) in England.

Design

Population-based cohort study, with the approval of NHS England.

Setting

Primary care and linked hospital outpatient data for more than 17 million people registered with general practices in England that use TPP electronic health record software.

Participants

Adults (18-110 years) with new diagnoses of IA (rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, undifferentiated IA) between 1 April 2019 and 31 March 2022.

Main outcome measures

The following outcomes were explored before and after April 2020: 1) incidence of IA diagnoses; 2) time from primary care referral to first rheumatology assessment; 3) time to first prescription of a disease-modifying anti-rheumatic drug (DMARD) in primary care.

Results

From a reference population of 17,683,500 adults, there were 31,280 incident IA diagnoses between April 2019 and March 2022. The incidence of IA decreased by 20.3% in the year commencing April 2020, relative to the preceding year (5.1 vs. 6.4 diagnoses per 10,000 adults, respectively). For those who presented with IA, the time to first rheumatology assessment was shorter during the pandemic (median 18 days; interquartile range 8 to 35 days) than before (21 days; 9 to 41 days). Overall, the proportion of patients prescribed DMARDs in primary care was comparable during the pandemic to before; however, the choice of medication changed, with fewer people prescribed methotrexate or leflunomide during the pandemic, and more people prescribed sulfasalazine or hydroxychloroquine.

Conclusions

The incidence of IA diagnoses in England decreased markedly during the early COVID-19 pandemic. However, for people who sought medical attention, the impact of the pandemic on service delivery was less marked than might have been anticipated. This study demonstrates that it is feasible to use routinely captured, near real-time data in the secure OpenSAFELY platform to benchmark care quality for long-term conditions on a national scale, without the need for manual data collection.",,pdf:https://researchonline.lshtm.ac.uk/id/eprint/4669009/1/Russell_etal_2022_Incidence-and-management-of-inflammatory.pdf; doi:https://doi.org/10.1101/2022.08.15.22278736; html:https://europepmc.org/article/PPR/PPR532220; doi:https://doi.org/10.1101/2022.08.15.22278736 PPR546510,https://doi.org/10.1101/2022.09.15.22279981,Hospital-wide Natural Language Processing summarising the health data of 1 million patients,"Bean D, Kraljevic Z, Shek A, Teo J, Dobson R.",,No Journal Info,2022,2022-09-15,Y,,,,"Electronic health records (EHRs) represent a major repository of real world clinical trajectories, interventions and outcomes. While modern enterprise EHR’s try to capture data in structured standardised formats, a significant bulk of the available information captured in the EHR is still recorded only in unstructured text format and can only be transformed into structured codes by manual processes. Recently, Natural Language Processing (NLP) algorithms have reached a level of performance suitable for large scale and accurate information extraction from clinical text. Here we describe the application of open-source named-entity-recognition and linkage (NER+L) methods (CogStack, MedCAT) to the entire text content of a large UK hospital trust (King’s College Hospital, London). The resulting dataset contains 157M SNOMED concepts generated from 9.5M documents for 1.07M patients over a period of 9 years. We present a summary of prevalence and disease onset as well as a patient embedding that captures major comorbidity patterns at scale. NLP has the potential to transform the health data lifecycle, through large-scale automation of a traditionally manual task.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2022/09/16/2022.09.15.22279981.full.pdf; doi:https://doi.org/10.1101/2022.09.15.22279981; html:https://europepmc.org/article/PPR/PPR546510; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR546510&type=FILE&fileName=EMS154557-pdf.pdf&mimeType=application/pdf -PPR760672,https://doi.org/10.1101/2023.11.17.23298637,"HFEgenotypes, haemochromatosis diagnosis and clinical outcomes to age 80: a prospective cohort study in UK Biobank","Lucas MR, Atkins JL, Pilling LC, Shearman J, Melzer D.",,No Journal Info,2023,2023-11-17,Y,,,,"

Objectives

HFE haemochromatosis genetic variants have an uncertain clinical penetrance, especially to older ages and in undiagnosed groups. We estimated p.C282Y and p.H63D variant cumulative incidence of multiple clinical outcomes in a large community cohort.

Design

Prospective cohort study.

Setting

22 assessment centres across England, Scotland, and Wales in the UK Biobank (2006-2010).

Participants

451,270 participants genetically similar to the 1000-Genomes European reference population, with a mean 13.3-year follow-up through hospital inpatient, cancer registries and death certificate data.

Main outcome measures

Cox proportional hazard ratios of incident clinical outcomes and mortality in those with HFE p.C282Y-p.H63D mutations compared to those with no variants, stratified by sex and adjusted for age, assessment centre and genetic stratification. Cumulative incidences were estimated from age 40 to 80 years.

Results

12.1% of p.C282Y+/+ males had baseline (mean age 57) haemochromatosis diagnoses, with age 80 cumulative incidence of 56.4%. 33.1% died vs. 25.4% without HFE variants (Hazard Ratio [HR] 1.29, 95% CI: 1.12-1.48, p=4.7*10 -4 ); 27.9% vs 17.1% had joint replacements, 20.3% vs 8.3% had liver disease, and there was excess delirium, dementia, and Parkinson’s disease, but not depression. Associations, including excess mortality, were similar in the group undiagnosed with haemochromatosis. 3.4% of p.C282Y+/+ females had baseline haemochromatosis diagnoses, with cumulative age 80 incidence of 40.5%. There was excess incident liver disease (8.9% vs 6.8%; HR 1.62, 95% CI: 1.27-2.05, p=7.8*10 -5 ), joint replacements and delirium, with similar results in the undiagnosed. p.C282Y/p.H63D and p.H63D+/+ men or women had no statistically significant excess fatigue or depression at baseline and no excess incident outcomes.

Conclusions

Male and female p.C282Y homozygotes experienced greater excess morbidity than previously documented, including those undiagnosed with haemochromatosis in the community. As haemochromatosis diagnosis rates were low at baseline despite treatment being considered effective, trials of screening to identify people with p.C282Y homozygosity early appear justified.

Strengths and limitations of this study

We analyzed largescale data on community volunteers from the UK Biobank, one of the world’s largest HFE genotyped cohorts. We have analyzed incident disease outcomes during an extended follow-up period of mean 13.3 years. We have provided the first clinical outcome data to age 80 years in those with haemochromatosis genotypes, including those undiagnosed with haemochromatosis at baseline, expanding the life-course evidence on HFE penetrance. UK Biobank participants were somewhat healthier than the general population, but HFE allele frequencies were similar to previous UK studies. Incident outcomes were from hospital inpatient and cancer registry follow-up, so did not rely on potentially biased patient self-reporting, but community diagnosed conditions may be underestimated.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2023/11/17/2023.11.17.23298637.full.pdf; doi:https://doi.org/10.1101/2023.11.17.23298637; html:https://europepmc.org/article/PPR/PPR760672; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR760672&type=FILE&fileName=EMS191324-pdf.pdf&mimeType=application/pdf PPR273987,https://doi.org/10.2139/ssrn.3751318,Development and External Validation of Prognostic Models for COVID-19 to Support Risk Stratification in Secondary Care,"Adderley NJ, Taverner T, Price M, Sainsbury C, Greenwood D, Chandan JS, Takwoingi Y, Haniffa R, Welch C, Parekh D, Gallier S, Gokhale KM, Denniston A, Sapey E, Nirantharakumar K.",,No Journal Info,2021,2021-01-25,N,,,,"Background: Existing UK prognostic models for patients admitted to hospital with COVID-19 are limited by reliance on comorbidities, which are under-recorded in secondary care, and lack of imaging data among the candidate predictors. Our aims were to develop and externally validate novel prognostic models for adverse outcomes (death, intensive therapy unit (ITU) admission) in UK secondary care; and externally validate the existing 4C score.

Methods: Patients with COVID-19 admitted to University Hospitals Birmingham (UHB) January-August 2020 were included. Candidate predictors included demographic variables, symptoms, physiological measures, imaging, laboratory tests. Final models used logistic regression with stepwise selection. External validation was performed in the CovidCollab dataset.

Findings: 1040 patients with COVID-19 were included in the derivation cohort; 288 (28%) died and 183 (18%) were admitted to ITU within 28 days of admission. Area under the receiver operating curve (AUROC) for mortality was 0.791 (95%CI 0.761-0.822) in UHB and 0.767 (95%CI 0.754-0.780) in CovidCollab; AUROC for ITU admission was 0.906 (95%CI 0.883-0.929) in UHB and 0.811 (95%CI 0.795-0.828) in CovidCollab. Models showed good calibration. Addition of comorbidities to candidate predictors did not improve model performance. AUROC for the 4C score in the UHB dataset was 0.754 (95%CI 0.721-0.786).

Interpretation: The novel prognostic models showed good discrimination and calibration in derivation and external validation datasets, and outperformed the existing 4C score. The models can be integrated into electronic medical records systems to calculate each individual patient’s probability of death or ITU admission at the time of hospital admission. Implementation of the models and clinical utility should be evaluated.

Funding: Medical Research Council UK Research and Innovation.

Declaration of Interests: NJA, ES, KN, MP, AD, CS, TT and YT report a grant from UKRI MRC during the conduct of the study. ES reports grants from National Institute for Health Research (NIHR), Wellcome Trust, MRC, Health Data Research UK (HDR-UK), British Lung Foundation, and Alpha 1 Foundation outside the submitted work. KN reports grants from MRC and HDR-UK outside the submitted work. DP reports grants from NIHR, MRC, and Chernakovsky Foundation outside the submitted work. All other authors have nothing to declare.

Ethics Approval Statement: Ethical approval was provided by the East Midlands – Derby REC (reference: 20/EM/0158) for the PIONEER Research Database.",,pdf:http://pure-oai.bham.ac.uk/ws/files/159150135/AdderleyN2022Develop.pdf; doi:https://doi.org/10.2139/ssrn.3751318; html:https://europepmc.org/article/PPR/PPR273987; doi:https://doi.org/10.2139/ssrn.3751318 +PPR760672,https://doi.org/10.1101/2023.11.17.23298637,"HFEgenotypes, haemochromatosis diagnosis and clinical outcomes to age 80: a prospective cohort study in UK Biobank","Lucas MR, Atkins JL, Pilling LC, Shearman J, Melzer D.",,No Journal Info,2023,2023-11-17,Y,,,,"

Objectives

HFE haemochromatosis genetic variants have an uncertain clinical penetrance, especially to older ages and in undiagnosed groups. We estimated p.C282Y and p.H63D variant cumulative incidence of multiple clinical outcomes in a large community cohort.

Design

Prospective cohort study.

Setting

22 assessment centres across England, Scotland, and Wales in the UK Biobank (2006-2010).

Participants

451,270 participants genetically similar to the 1000-Genomes European reference population, with a mean 13.3-year follow-up through hospital inpatient, cancer registries and death certificate data.

Main outcome measures

Cox proportional hazard ratios of incident clinical outcomes and mortality in those with HFE p.C282Y-p.H63D mutations compared to those with no variants, stratified by sex and adjusted for age, assessment centre and genetic stratification. Cumulative incidences were estimated from age 40 to 80 years.

Results

12.1% of p.C282Y+/+ males had baseline (mean age 57) haemochromatosis diagnoses, with age 80 cumulative incidence of 56.4%. 33.1% died vs. 25.4% without HFE variants (Hazard Ratio [HR] 1.29, 95% CI: 1.12-1.48, p=4.7*10 -4 ); 27.9% vs 17.1% had joint replacements, 20.3% vs 8.3% had liver disease, and there was excess delirium, dementia, and Parkinson’s disease, but not depression. Associations, including excess mortality, were similar in the group undiagnosed with haemochromatosis. 3.4% of p.C282Y+/+ females had baseline haemochromatosis diagnoses, with cumulative age 80 incidence of 40.5%. There was excess incident liver disease (8.9% vs 6.8%; HR 1.62, 95% CI: 1.27-2.05, p=7.8*10 -5 ), joint replacements and delirium, with similar results in the undiagnosed. p.C282Y/p.H63D and p.H63D+/+ men or women had no statistically significant excess fatigue or depression at baseline and no excess incident outcomes.

Conclusions

Male and female p.C282Y homozygotes experienced greater excess morbidity than previously documented, including those undiagnosed with haemochromatosis in the community. As haemochromatosis diagnosis rates were low at baseline despite treatment being considered effective, trials of screening to identify people with p.C282Y homozygosity early appear justified.

Strengths and limitations of this study

We analyzed largescale data on community volunteers from the UK Biobank, one of the world’s largest HFE genotyped cohorts. We have analyzed incident disease outcomes during an extended follow-up period of mean 13.3 years. We have provided the first clinical outcome data to age 80 years in those with haemochromatosis genotypes, including those undiagnosed with haemochromatosis at baseline, expanding the life-course evidence on HFE penetrance. UK Biobank participants were somewhat healthier than the general population, but HFE allele frequencies were similar to previous UK studies. Incident outcomes were from hospital inpatient and cancer registry follow-up, so did not rely on potentially biased patient self-reporting, but community diagnosed conditions may be underestimated.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2023/11/17/2023.11.17.23298637.full.pdf; doi:https://doi.org/10.1101/2023.11.17.23298637; html:https://europepmc.org/article/PPR/PPR760672; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR760672&type=FILE&fileName=EMS191324-pdf.pdf&mimeType=application/pdf PPR360902,https://doi.org/10.2139/ssrn.3854027,Reconstructing the Symptomatic-Case Epidemic from COVID-19-Related Deaths in England: A Spatiotemporal Modelling Study,"Nightingale E, Abbott S, Russell TW, group CCw, Medley GF, Brady O.",,No Journal Info,2021,2021-05-26,Y,,,,"Background: The COVID-19 epidemic has differentially impacted communities across England, with regional variation in rates of confirmed cases, hospitalisations and deaths. Measurement of this burden changed substantially over the first months, as surveillance was expanded to accommodate the escalating epidemic. Laboratory confirmation was initially restricted to clinical need (“pillar 1”) before expanding to community-wide symptomatics (“pillar 2”). This study aimed to ascertain whether biases in case data resulting from varying testing coverage could be addressed by drawing inference from COVID-19-related deaths.

Methods: We fit a Bayesian spatio-temporal model to weekly COVID-19-related deaths per local authority (LTLA) throughout the first wave (1 January - 30 June 2020), with respect to the local epidemic timing and the age, deprivation and ethnic composition of its population. We drew predictions averaging these sources of case-fatality variation, and back-translated according to a population case fatality ratio estimated under community-wide testing.

Results: A model including temporally- and spatially-correlated random effects best accommodated the observed variation in mortality, after accounting for local population characteristics. Final predictions suggest a total of 276,219-420,491 cases over the first wave - an increase of 19-81% from the reported.

Conclusions: Limitations in testing capacity biased the observed trajectory of COVID-19 cases throughout the first wave. Basing inference on COVID-19-related mortality and higher-coverage testing later in the time period, we could explore the extent of this bias more explicitly. Evidence points towards substantial under-representation of initial growth and peak magnitude of symptomatic infections nationally, to which different parts of the country contribute unequally.

Funding Information:

The following funding sources are acknowledged as providing funding for the named authors:

This research was partly funded by the Bill & Melinda Gates Foundation (NTD Modelling Consortium OPP1184344: GFM; OPP1183986: ESN). Royal Society (Dorothy Hodgkin Fellowship: RL). Wellcome Trust (206250/Z/17/Z: TWR; 206471/Z/17/Z: OJB; 210758/Z/18/Z: SA).

The following funding sources are acknowledged as providing funding for the working group
authors:

This research was partly funded by the Bill & Melinda Gates Foundation (INV-001754: MQ; INV-003174: JYL, KP, MJ, YL; INV-016832: SRP; NTD Modelling Consortium OPP1184344: CABP; OPP1139859: BJQ; OPP1191821: KO'R). BMGF (INV-016832; OPP1157270: KA). CADDE MR/S0195/1 & FAPESP 18/14389-0 (PM). EDCTP2 (RIA2020EF-2983-CSIGN: HPG). Elrha R2HC/UK FCDO/Wellcome Trust/This research was partly funded by the National Institute for Health Research (NIHR) using UK aid from the UK Government to support global health research. The views expressed in this publication are those of the author(s) and not necessarily those of the NIHR or the UK Department of Health and Social Care (KvZ). ERC Starting Grant (#757699: MQ). ERC (SG 757688: CJVA, KEA). This project has received funding from the European Union's Horizon 2020 research and innovation programme - project EpiPose (101003688: AG, KP, MJ, RCB, WJE, YL). FCDO/Wellcome Trust (Epidemic Preparedness Coronavirus research programme 221303/Z/20/Z: CABP, KvZ). This research was partly funded by the Global Challenges Research Fund (GCRF) project 'RECAP' managed through RCUK and ESRC (ES/P010873/1: CIJ, TJ). HDR UK (MR/S003975/1: RME). HPRU (NIHR200908: NIB). Innovation Fund (01VSF18015: FK). MRC (MR/N013638/1: EF, NRW; MR/V027956/1: WW). Nakajima Foundation (AE). NIHR (16/136/46: BJQ; 16/137/109: BJQ, FYS, MJ, YL; 1R01AI141534-01A1: DH; Health Protection Research Unit for Modelling Methodology HPRU-2012-10096: TJ; NIHR200908: AJK, RME; NIHR200929: CVM, FGS, MJ, NGD; PR-OD-1017-20002: AR, WJE). Singapore Ministry of Health (RP). UK DHSC/UK Aid/NIHR (PR-OD-1017-20001: HPG). UK MRC (MC_PC_19065 - Covid 19: Understanding the dynamics and drivers of the COVID-19 epidemic using real-time outbreak analytics: NGD, RME, SC, TJ, WJE, YL; MR/P014658/1: GMK). Authors of this research receive funding from UK Public Health Rapid Support Team funded by the United Kingdom Department of Health and Social Care (TJ). UKRI Research England (NGD). UKRI (MR/V028456/1: YJ). Wellcome Trust (206250/Z/17/Z: AJK; 208812/Z/17/Z: SC, SFlasche; 210758/Z/18/Z: JDM, JH, SFunk, SRM; 221303/Z/20/Z: MK; UNS110424: FK). No funding (AMF, DCT, YWDC).

Declaration of Interests: The authors declare no competing interests.

Ethics Approval Statement: Approval for the use of anonymised linelist data was granted by Public Health England and the Department for Health and Social Care. Consent of individuals was not required as no patient identifiable information was used.",,doi:https://doi.org/10.2139/ssrn.3854027; html:https://europepmc.org/article/PPR/PPR360902; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR360902&type=FILE&fileName=EMS128447-pdf.pdf&mimeType=application/pdf PPR302376,https://doi.org/10.1101/2021.03.16.21253371,Axes of Prognosis: Identifying Subtypes of COVID-19 Outcomes,"Whitfield E, Coffey C, Zhang H, Shi T, Wu X, Li Q, Wu H.",,No Journal Info,2021,2021-03-24,Y,,,,"COVID-19 is a disease with vast impact, yet much remains unclear about patient outcomes. Most approaches to risk prediction of COVID-19 focus on binary or tertiary severity outcomes, despite the heterogeneity of the disease. In this work, we identify heterogeneous subtypes of COVID-19 outcomes by considering ‘axes’ of prognosis. We propose two innovative clustering approaches − ‘Layered Axes’ and ‘Prognosis Space’ – to apply on patients’ outcome data. We then show how these clusters can help predict a patient’s deterioration pathway on their hospital admission, using random forest classification. We illustrate this methodology on a cohort from Wuhan in early 2020. We discover interesting subgroups of poor prognosis, particularly within respiratory patients, and predict respiratory subgroup membership with high accuracy. This work could assist clinicians in identifying appropriate treatments at patients’ hospital admission. Moreover, our method could be used to explore subtypes of ‘long COVID’ and other diseases with heterogeneous outcomes.",,pdf:https://www.medrxiv.org/content/medrxiv/early/2021/03/24/2021.03.16.21253371.full.pdf; doi:https://doi.org/10.1101/2021.03.16.21253371; html:https://europepmc.org/article/PPR/PPR302376; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR302376&type=FILE&fileName=EMS120764-pdf.pdf&mimeType=application/pdf PPR341783,https://doi.org/10.2139/ssrn.3820510,Post-Acute COVID-19 Sequelae in Cases Managed in the Community or Hospital in the UK: A Population Based Study,"Whittaker HR, Gulea C, Koteci A, Kallis C, Morgan AD, Iwundu C, Weeks M, Gupta R, Quint J.",,No Journal Info,2021,2021-04-06,N,,,,"Background: It is unknown whether post-COVID-19 sequelae differ depending on infection severity.

Methods: This population-based study using Clinical Practice Research Database Aurum included COVID-19 cases between 1st August - 17th October 2020 . Patients were classified as hospitalised (hospitalisation within two weeks of diagnosis) or non-hospitalised and followed up to three months. Event rates were calculated for new symptoms, diseases, prescriptions, healthcare utilisation and compared across groups with Cox regression. Outcomes were compared at 6 and 12 months prior to index date, equating to the first UK wave and a pre-pandemic period. Non-hospitalised group outcomes were stratified by age and sex.

Findings: Of 46,687 patients, 45,272 were managed in the community; 1,415 hospitalised. Hospitalised patients had higher risk of 13/26 symptoms and 11/20 diseases post-COVID-19 diagnosis than the community group. The largest differences were noted for rates per 100 000 person-weeks [95%CI] of breathlessness: 536 [432 - 663] v. 85 [77-93]; joint pain: 295 [221-392] v. 168 [158-179]; diabetes: 303 [225 - 416] v. 36 [32 - 42], hypertension: 244 [178-344] v. 47 [41-53]. Although low, rates of chest tightness, tinnitus and lung fibrosis were higher in the community group . The hospitalised group received more prescriptions and utilised more healthcare. 3·5% of the community group had a post-acute burden; anxiety, breathlessness, chest pain and fatigue were most frequently reported, alongside bronchodilator prescriptions. In those non-hospitalised, age and sex differences existed in rates of symptoms, diseases and prescriptions. Healthcare utilisation in the community group increased 28·5% post-COVID-19 relative to pre-pandemic.

Interpretation: Post-COVID-19 sequelae differ between hospitalised and non-hospitalised individuals, with age and sex-specific differences in symptoms, diseases and prescriptions post-COVID-19 in the community. Most people who have COVID-19 managed in the community have no ongoing issues. Post-COVID-19 follow-up and management strategies need to be tailored to specific needs.

Funding: This work is supported by BREATHE - The Health Data Research Hub for Respiratory Health [MC_PC_19004].

Declaration of Interest: HRW, CG, AK, CK, AM, CI, MW have nothing to declare. RG is a current employee of Gilead Sciences, outside the submitted work. JKQ reports grants from AUK-BLF, The Health Foundation, grants and personal fees from AZ, BI, GSK, Bayer, grants from Chiesi, outside the submitted work.

Ethical Approval: This work is based on data from the Clinical Practice Research Datalink (CPRD) obtained under license from the United Kingdom (UK) Medicines and Healthcare products Regulatory Agency (MHRA). The data is provided by patients and collected by the National Health Service (NHS) as part of their care and support.",,doi:https://doi.org/10.1101/2021.04.09.21255199; doi:https://doi.org/10.2139/ssrn.3820510; html:https://europepmc.org/article/PPR/PPR341783; pdf:https://europepmc.org/api/fulltextRepo?pprId=PPR341783&type=FILE&fileName=EMS124847-pdf.pdf&mimeType=application/pdf; doi:https://doi.org/10.2139/ssrn.3820510 diff --git a/data/covid/papers.csv b/data/covid/papers.csv index 05131f8c..4fe6a0aa 100644 --- a/data/covid/papers.csv +++ b/data/covid/papers.csv @@ -24,9 +24,9 @@ id,doi,title,authorString,authorAffiliations,journalTitle,pubYear,date,isOpenAcc 37118449,https://doi.org/10.1038/s43587-022-00224-w,Robust SARS-CoV-2-specific and heterologous immune responses in vaccine-naïve residents of long-term care facilities who survive natural infection.,"Tut G, Lancaster T, Butler MS, Sylla P, Spalkova E, Bone D, Kaur N, Bentley C, Amin U, Jadir AT, Hulme S, Ayodel M, Dowell AC, Pearce H, Zuo J, Margielewska-Davies S, Verma K, Nicol S, Begum J, Jinks E, Tut E, Bruton R, Krutikov M, Shrotri M, Giddings R, Azmi B, Fuller C, Irwin-Singer A, Hayward A, Copas A, Shallcross L, Moss P.",,Nature aging,2022,2022-05-30,Y,,,,"We studied humoral and cellular immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 152 long-term care facility staff and 124 residents over a prospective 4-month period shortly after the first wave of infection in England. We show that residents of long-term care facilities developed high and stable levels of antibodies against spike protein and receptor-binding domain. Nucleocapsid-specific responses were also elevated but waned over time. Antibodies showed stable and equivalent levels of functional inhibition against spike-angiotensin-converting enzyme 2 binding in all age groups with comparable activity against viral variants of concern. SARS-CoV-2 seropositive donors showed high levels of antibodies to other beta-coronaviruses but serostatus did not impact humoral immunity to influenza or other respiratory syncytial viruses. SARS-CoV-2-specific cellular responses were similar across all ages but virus-specific populations showed elevated levels of activation in older donors. Thus, survivors of SARS-CoV-2 infection show a robust and stable immunity against the virus that does not negatively impact responses to other seasonal viruses.",,pdf:https://www.nature.com/articles/s43587-022-00224-w.pdf; doi:https://doi.org/10.1038/s43587-022-00224-w; html:https://europepmc.org/articles/PMC10154219; pdf:https://europepmc.org/articles/PMC10154219?pdf=render 37056776,https://doi.org/10.3389/fimmu.2023.1146702,"SARS-CoV-2 antibody responses associate with sex, age and disease severity in previously uninfected people admitted to hospital with COVID-19: An ISARIC4C prospective study.","Parker E, Thomas J, Roper KJ, Ijaz S, Edwards T, Marchesin F, Katsanovskaja K, Lett L, Jones C, Hardwick HE, Davis C, Vink E, McDonald SE, Moore SC, Dicks S, Jegatheesan K, Cook NJ, Hope J, Cherepanov P, McClure MO, Baillie JK, Openshaw PJM, Turtle L, Ho A, Semple MG, Paxton WA, Tedder RS, Pollakis G, ISARIC4C Investigators.",,Frontiers in immunology,2023,2023-03-15,Y,Serology; Virus; Disease; immunology; Neutralisation; Covid-19; Sars-cov-2,,,"The SARS-CoV-2 pandemic enables the analysis of immune responses induced against a novel coronavirus infecting immunologically naïve individuals. This provides an opportunity for analysis of immune responses and associations with age, sex and disease severity. Here we measured an array of solid-phase binding antibody and viral neutralising Ab (nAb) responses in participants (n=337) of the ISARIC4C cohort and characterised their correlation with peak disease severity during acute infection and early convalescence. Overall, the responses in a Double Antigen Binding Assay (DABA) for antibody to the receptor binding domain (anti-RBD) correlated well with IgM as well as IgG responses against viral spike, S1 and nucleocapsid protein (NP) antigens. DABA reactivity also correlated with nAb. As we and others reported previously, there is greater risk of severe disease and death in older men, whilst the sex ratio was found to be equal within each severity grouping in younger people. In older males with severe disease (mean age 68 years), peak antibody levels were found to be delayed by one to two weeks compared with women, and nAb responses were delayed further. Additionally, we demonstrated that solid-phase binding antibody responses reached higher levels in males as measured via DABA and IgM binding against Spike, NP and S1 antigens. In contrast, this was not observed for nAb responses. When measuring SARS-CoV-2 RNA transcripts (as a surrogate for viral shedding) in nasal swabs at recruitment, we saw no significant differences by sex or disease severity status. However, we have shown higher antibody levels associated with low nasal viral RNA indicating a role of antibody responses in controlling viral replication and shedding in the upper airway. In this study, we have shown discernible differences in the humoral immune responses between males and females and these differences associate with age as well as with resultant disease severity.",,pdf:https://www.frontiersin.org/articles/10.3389/fimmu.2023.1146702/pdf; doi:https://doi.org/10.3389/fimmu.2023.1146702; html:https://europepmc.org/articles/PMC10087108; pdf:https://europepmc.org/articles/PMC10087108?pdf=render 37228015,https://doi.org/10.1371/journal.pbio.3002118,Dynamics of SARS-CoV-2 infection hospitalisation and infection fatality ratios over 23 months in England.,"Eales O, Haw D, Wang H, Atchison C, Ashby D, Cooke GS, Barclay W, Ward H, Darzi A, Donnelly CA, Chadeau-Hyam M, Elliott P, Riley S.",,PLoS biology,2023,2023-05-25,Y,,,,"The relationship between prevalence of infection and severe outcomes such as hospitalisation and death changed over the course of the COVID-19 pandemic. Reliable estimates of the infection fatality ratio (IFR) and infection hospitalisation ratio (IHR) along with the time-delay between infection and hospitalisation/death can inform forecasts of the numbers/timing of severe outcomes and allow healthcare services to better prepare for periods of increased demand. The REal-time Assessment of Community Transmission-1 (REACT-1) study estimated swab positivity for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection in England approximately monthly from May 2020 to March 2022. Here, we analyse the changing relationship between prevalence of swab positivity and the IFR and IHR over this period in England, using publicly available data for the daily number of deaths and hospitalisations, REACT-1 swab positivity data, time-delay models, and Bayesian P-spline models. We analyse data for all age groups together, as well as in 2 subgroups: those aged 65 and over and those aged 64 and under. Additionally, we analysed the relationship between swab positivity and daily case numbers to estimate the case ascertainment rate of England's mass testing programme. During 2020, we estimated the IFR to be 0.67% and the IHR to be 2.6%. By late 2021/early 2022, the IFR and IHR had both decreased to 0.097% and 0.76%, respectively. The average case ascertainment rate over the entire duration of the study was estimated to be 36.1%, but there was some significant variation in continuous estimates of the case ascertainment rate. Continuous estimates of the IFR and IHR of the virus were observed to increase during the periods of Alpha and Delta's emergence. During periods of vaccination rollout, and the emergence of the Omicron variant, the IFR and IHR decreased. During 2020, we estimated a time-lag of 19 days between hospitalisation and swab positivity, and 26 days between deaths and swab positivity. By late 2021/early 2022, these time-lags had decreased to 7 days for hospitalisations and 18 days for deaths. Even though many populations have high levels of immunity to SARS-CoV-2 from vaccination and natural infection, waning of immunity and variant emergence will continue to be an upwards pressure on the IHR and IFR. As investments in community surveillance of SARS-CoV-2 infection are scaled back, alternative methods are required to accurately track the ever-changing relationship between infection, hospitalisation, and death and hence provide vital information for healthcare provision and utilisation.",,pdf:https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3002118&type=printable; doi:https://doi.org/10.1371/journal.pbio.3002118; html:https://europepmc.org/articles/PMC10212114; pdf:https://europepmc.org/articles/PMC10212114?pdf=render +37124948,https://doi.org/10.1016/j.lanepe.2023.100638,Severity of Omicron BA.5 variant and protective effect of vaccination: national cohort and matched analyses in Scotland.,"Robertson C, Kerr S, Sheikh A.",,The Lancet regional health. Europe,2023,2023-04-14,Y,,,,,,doi:https://doi.org/10.1016/j.lanepe.2023.100638; doi:https://doi.org/10.1016/j.lanepe.2023.100638; html:https://europepmc.org/articles/PMC10139952; pdf:https://europepmc.org/articles/PMC10139952?pdf=render 38381822,https://doi.org/10.1126/sciadv.adi9379,"Spontaneous, persistent, T cell-dependent IFN-γ release in patients who progress to Long Covid.","Krishna BA, Lim EY, Metaxaki M, Jackson S, Mactavous L, NIHR BioResource, Lyons PA, Doffinger R, Bradley JR, Smith KGC, Sinclair J, Matheson NJ, Lehner PJ, Sithole N, Wills MR.",,Science advances,2024,2024-02-21,Y,,,,"After acute infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a proportion of patients experience persistent symptoms beyond 12 weeks, termed Long Covid. Understanding the mechanisms that cause this debilitating disease and identifying biomarkers for diagnostic, therapeutic, and monitoring purposes are urgently required. We detected persistently high levels of interferon-γ (IFN-γ) from peripheral blood mononuclear cells of patients with Long Covid using highly sensitive FluoroSpot assays. This IFN-γ release was seen in the absence of ex vivo peptide stimulation and remains persistently elevated in patients with Long Covid, unlike the resolution seen in patients recovering from acute SARS-CoV-2 infection. The IFN-γ release was CD8+ T cell-mediated and dependent on antigen presentation by CD14+ cells. Longitudinal follow-up of our study cohort showed that symptom improvement and resolution correlated with a decrease in IFN-γ production to baseline levels. Our study highlights a potential mechanism underlying Long Covid, enabling the search for biomarkers and therapeutics in patients with Long Covid.",,pdf:https://www.science.org/doi/pdf/10.1126/sciadv.adi9379?download=true; doi:https://doi.org/10.1126/sciadv.adi9379; html:https://europepmc.org/articles/PMC10881041; pdf:https://europepmc.org/articles/PMC10881041?pdf=render 38036541,https://doi.org/10.1038/s41467-023-43661-w,"True prevalence of long-COVID in a nationwide, population cohort study.","Hastie CE, Lowe DJ, McAuley A, Mills NL, Winter AJ, Black C, Scott JT, O'Donnell CA, Blane DN, Browne S, Ibbotson TR, Pell JP.",,Nature communications,2023,2023-11-30,Y,,,,"Long-COVID prevalence estimates vary widely and should take account of symptoms that would have occurred anyway. Here we determine the prevalence of symptoms attributable to SARS-CoV-2 infection, taking account of background rates and confounding, in a nationwide population cohort study of 198,096 Scottish adults. 98,666 (49.8%) had symptomatic laboratory-confirmed SARS-CoV-2 infections and 99,430 (50.2%) were age-, sex-, and socioeconomically-matched and never-infected. While 41,775 (64.5%) reported at least one symptom 6 months following SARS-CoV-2 infection, this was also true of 34,600 (50.8%) of those never-infected. The crude prevalence of one or more symptom attributable to SARS-CoV-2 infection was 13.8% (13.2%,14.3%), 12.8% (11.9%,13.6%), and 16.3% (14.4%,18.2%) at 6, 12, and 18 months respectively. Following adjustment for potential confounders, these figures were 6.6% (6.3%, 6.9%), 6.5% (6.0%, 6.9%) and 10.4% (9.1%, 11.6%) respectively. Long-COVID is characterised by a wide range of symptoms that, apart from altered taste and smell, are non-specific. Care should be taken in attributing symptoms to previous SARS-CoV-2 infection.",,pdf:https://www.nature.com/articles/s41467-023-43661-w.pdf; doi:https://doi.org/10.1038/s41467-023-43661-w; html:https://europepmc.org/articles/PMC10689486; pdf:https://europepmc.org/articles/PMC10689486?pdf=render -37124948,https://doi.org/10.1016/j.lanepe.2023.100638,Severity of Omicron BA.5 variant and protective effect of vaccination: national cohort and matched analyses in Scotland.,"Robertson C, Kerr S, Sheikh A.",,The Lancet regional health. Europe,2023,2023-04-14,Y,,,,,,doi:https://doi.org/10.1016/j.lanepe.2023.100638; doi:https://doi.org/10.1016/j.lanepe.2023.100638; html:https://europepmc.org/articles/PMC10139952; pdf:https://europepmc.org/articles/PMC10139952?pdf=render 38416429,https://doi.org/10.1056/nejmoa2311330,Cognition and Memory after Covid-19 in a Large Community Sample.,"Hampshire A, Azor A, Atchison C, Trender W, Hellyer PJ, Giunchiglia V, Husain M, Cooke GS, Cooper E, Lound A, Donnelly CA, Chadeau-Hyam M, Ward H, Elliott P.",,The New England journal of medicine,2024,2024-02-01,Y,,,,"

Background

Cognitive symptoms after coronavirus disease 2019 (Covid-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are well-recognized. Whether objectively measurable cognitive deficits exist and how long they persist are unclear.

Methods

We invited 800,000 adults in a study in England to complete an online assessment of cognitive function. We estimated a global cognitive score across eight tasks. We hypothesized that participants with persistent symptoms (lasting ≥12 weeks) after infection onset would have objectively measurable global cognitive deficits and that impairments in executive functioning and memory would be observed in such participants, especially in those who reported recent poor memory or difficulty thinking or concentrating (""brain fog"").

Results

Of the 141,583 participants who started the online cognitive assessment, 112,964 completed it. In a multiple regression analysis, participants who had recovered from Covid-19 in whom symptoms had resolved in less than 4 weeks or at least 12 weeks had similar small deficits in global cognition as compared with those in the no-Covid-19 group, who had not been infected with SARS-CoV-2 or had unconfirmed infection (-0.23 SD [95% confidence interval {CI}, -0.33 to -0.13] and -0.24 SD [95% CI, -0.36 to -0.12], respectively); larger deficits as compared with the no-Covid-19 group were seen in participants with unresolved persistent symptoms (-0.42 SD; 95% CI, -0.53 to -0.31). Larger deficits were seen in participants who had SARS-CoV-2 infection during periods in which the original virus or the B.1.1.7 variant was predominant than in those infected with later variants (e.g., -0.17 SD for the B.1.1.7 variant vs. the B.1.1.529 variant; 95% CI, -0.20 to -0.13) and in participants who had been hospitalized than in those who had not been hospitalized (e.g., intensive care unit admission, -0.35 SD; 95% CI, -0.49 to -0.20). Results of the analyses were similar to those of propensity-score-matching analyses. In a comparison of the group that had unresolved persistent symptoms with the no-Covid-19 group, memory, reasoning, and executive function tasks were associated with the largest deficits (-0.33 to -0.20 SD); these tasks correlated weakly with recent symptoms, including poor memory and brain fog. No adverse events were reported.

Conclusions

Participants with resolved persistent symptoms after Covid-19 had objectively measured cognitive function similar to that in participants with shorter-duration symptoms, although short-duration Covid-19 was still associated with small cognitive deficits after recovery. Longer-term persistence of cognitive deficits and any clinical implications remain uncertain. (Funded by the National Institute for Health and Care Research and others.).",,pdf:https://www.nejm.org/doi/pdf/10.1056/NEJMoa2311330?articleTools=true; doi:https://doi.org/10.1056/NEJMoa2311330; html:https://europepmc.org/articles/PMC7615803; pdf:https://europepmc.org/articles/PMC7615803?pdf=render 35724769,https://doi.org/10.1016/j.kint.2022.05.015,A retrospective cohort study predicting and validating impact of the COVID-19 pandemic in individuals with chronic kidney disease.,"Dashtban A, Mizani MA, Denaxas S, Nitsch D, Quint J, Corbett R, Mamza JB, Morris T, Mamas M, Lawlor DA, Khunti K, CVD-COVID-UK Consortium, Sudlow C, Hemingway H, Banerjee A.",,Kidney international,2022,2022-06-17,Y,Mortality; Chronic Kidney Disease; Sars-cov-2,,,"Chronic kidney disease (CKD) is associated with increased risk of baseline mortality and severe COVID-19, but analyses across CKD stages, and comorbidities are lacking. In prevalent and incident CKD, we investigated comorbidities, baseline risk, COVID-19 incidence, and predicted versus observed one-year excess death. In a national dataset (NHS Digital Trusted Research Environment [NHSD TRE]) for England encompassing 56 million individuals), we conducted a retrospective cohort study (March 2020 to March 2021) for prevalence of comorbidities by incident and prevalent CKD, SARS-CoV-2 infection and mortality. Baseline mortality risk, incidence and outcome of infection by comorbidities, controlling for age, sex and vaccination were assessed. Observed versus predicted one-year mortality at varying population infection rates and pandemic-related relative risks using our published model in pre-pandemic CKD cohorts (NHSD TRE and Clinical Practice Research Datalink [CPRD]) were compared. Among individuals with CKD (prevalent:1,934,585, incident:144,969), comorbidities were common (73.5% and 71.2% with one or more condition[s] in respective data sets, and 13.2% and 11.2% with three or more conditions, in prevalent and incident CKD), and associated with SARS-CoV-2 infection, particularly dialysis/transplantation (odds ratio 2.08, 95% confidence interval 2.04-2.13) and heart failure (1.73, 1.71-1.76), but not cancer (1.01, 1.01-1.04). One-year all-cause mortality varied by age, sex, multi-morbidity and CKD stage. Compared with 34,265 observed excess deaths, in the NHSD-TRE and CPRD databases respectively, we predicted 28,746 and 24,546 deaths (infection rates 10% and relative risks 3.0), and 23,754 and 20,283 deaths (observed infection rates 6.7% and relative risks 3.7). Thus, in this largest, national-level study, individuals with CKD have a high burden of comorbidities and multi-morbidity, and high risk of pre-pandemic and pandemic mortality. Hence, treatment of comorbidities, non-pharmaceutical measures, and vaccination are priorities for people with CKD and management of long-term conditions is important during and beyond the pandemic.",,doi:https://doi.org/10.1016/j.kint.2022.05.015; doi:https://doi.org/10.1016/j.kint.2022.05.015; html:https://europepmc.org/articles/PMC9212366; pdf:https://europepmc.org/articles/PMC9212366?pdf=render 37949372,https://doi.org/10.1016/j.jhin.2023.10.021,COVID-19-related mortality and hospital admissions in the VIVALDI study cohort: October 2020 to March 2023.,"Stirrup O, Krutikov M, Azmi B, Monakhov I, Hayward A, Copas A, Shallcross L.",,The Journal of hospital infection,2024,2023-11-08,Y,Care Homes; Covid-19; Sars-cov-2; Infection Fatality Ratio; Infection Hospitalization Ratio,,,"

Background

Long-term-care facilities (LTCFs) were heavily affected by COVID-19 early in the pandemic, but the impact of the virus has reduced over time with vaccination campaigns and build-up of immunity from prior infection.

Objectives

To evaluate the mortality and hospital admissions associated with SARS-CoV-2 in LTCFs in England over the course of the VIVALDI study, from October 2020 to March 2023.

Methods

We included residents aged ≥65 years from participating LTCFs who had available follow-up time within the analysis period. We calculated incidence rates (IRs) of COVID-19-linked mortality and hospital admissions per calendar quarter, along with infection fatality ratios (IFRs, within 28 days) and infection hospitalization ratios (IHRs, within 14 days) following positive SARS-CoV-2 test.

Results

A total of 26,286 residents were included, with at least one positive test for SARS-CoV-2 in 8513 (32.4%). The IR of COVID-19-related mortality peaked in the first quarter (Q1) of 2021 at 0.47 per 1000 person-days (1 kpd) (around a third of all deaths), in comparison with 0.10 per 1 kpd for Q1 2023 which had a similar IR of SARS-CoV-2 infections. There was a fall in observed IFR for SARS-CoV-2 infections from 24.9% to 6.7% between these periods, with a fall in IHR from 12.1% to 8.8%. The population had high overall IRs for mortality for each quarter evaluated, corresponding to annual mortality probability of 28.8-41.3%.

Conclusions

Standardized real-time monitoring of hospitalization and mortality following infection in LTCFs could inform policy on the need for non-pharmaceutical interventions to prevent transmission.",,pdf:http://www.journalofhospitalinfection.com/article/S0195670123003572/pdf; doi:https://doi.org/10.1016/j.jhin.2023.10.021; html:https://europepmc.org/articles/PMC10927615; pdf:https://europepmc.org/articles/PMC10927615?pdf=render @@ -174,8 +174,8 @@ PMC10929454,https://doi.org/,Optimising data curation pipelines for population-l 34132940,https://doi.org/10.1007/s10654-021-00765-1,Ethnic differences in COVID-19 mortality during the first two waves of the Coronavirus Pandemic: a nationwide cohort study of 29 million adults in England.,"Nafilyan V, Islam N, Mathur R, Ayoubkhani D, Banerjee A, Glickman M, Humberstone B, Diamond I, Khunti K.",,European journal of epidemiology,2021,2021-06-16,Y,Mortality; Ethnicity; Covid-19,,,"Ethnic minorities have experienced disproportionate COVID-19 mortality rates in the UK and many other countries. We compared the differences in the risk of COVID-19 related death between ethnic groups in the first and second waves the of COVID-19 pandemic in England. We also investigated whether the factors explaining differences in COVID-19 death between ethnic groups changed between the two waves. Using data from the Office for National Statistics Public Health Data Asset, a linked dataset combining the 2011 Census with primary care and hospital records and death registrations, we conducted an observational cohort study to examine differences in the risk of death involving COVID-19 between ethnic groups in the first wave (from 24th January 2020 until 31st August 2020) and the first part of the second wave (from 1st September to 28th December 2020). We estimated age-standardised mortality rates (ASMR) in the two waves stratified by ethnic groups and sex. We also estimated hazard ratios (HRs) for ethnic-minority groups compared with the White British population, adjusted for geographical factors, socio-demographic characteristics, and pre-pandemic health conditions. The study population included over 28.9 million individuals aged 30-100 years living in private households. In the first wave, all ethnic minority groups had a higher risk of COVID-19 related death compared to the White British population. In the second wave, the risk of COVID-19 death remained elevated for people from Pakistani (ASMR: 339.9 [95% CI: 303.7-376.2] and 166.8 [141.7-191.9] deaths per 100,000 population in men and women) and Bangladeshi (318.7 [247.4-390.1] and 127.1 [91.1-171.3] in men and women) background but not for people from Black ethnic groups. Adjustment for geographical factors explained a large proportion of the differences in COVID-19 mortality in the first wave but not in the second wave. Despite an attenuation of the elevated risk of COVID-19 mortality after adjusting for sociodemographic characteristics and health status, the risk was substantially higher in people from Bangladeshi and Pakistani background in both the first and the second waves. Between the first and second waves of the pandemic, the reduction in the difference in COVID-19 mortality between people from Black ethnic background and people from the White British group shows that ethnic inequalities in COVID-19 mortality can be addressed. The continued higher rate of mortality in people from Bangladeshi and Pakistani background is alarming and requires focused public health campaign and policy changes.",,pdf:https://link.springer.com/content/pdf/10.1007/s10654-021-00765-1.pdf; doi:https://doi.org/10.1007/s10654-021-00765-1; html:https://europepmc.org/articles/PMC8206182; pdf:https://europepmc.org/articles/PMC8206182?pdf=render 33728401,https://doi.org/10.1038/s42254-020-0178-4,Modelling COVID-19.,"Vespignani A, Tian H, Dye C, Lloyd-Smith JO, Eggo RM, Shrestha M, Scarpino SV, Gutierrez B, Kraemer MUG, Wu J, Leung K, Leung GM.",,Nature reviews. Physics,2020,2020-05-06,Y,Applied Mathematics; Complex Networks,,,"As the COVID-19 pandemic continues, mathematical epidemiologists share their views on what models reveal about how the disease has spread, the current state of play and what work still needs to be done.",Vespignani et al. used mathematical models to model the epidemic of covid-19 and to predict future scenarios for possible interventions and inform policy and practice.,pdf:https://www.nature.com/articles/s42254-020-0178-4.pdf; doi:https://doi.org/10.1038/s42254-020-0178-4; html:https://europepmc.org/articles/PMC7201389; pdf:https://europepmc.org/articles/PMC7201389?pdf=render 36350810,https://doi.org/10.1371/journal.pone.0276781,"Primary hypertension, anti-hypertensive medications and the risk of severe COVID-19 in UK Biobank.","Pavey H, Kulkarni S, Wood A, Ben-Shlomo Y, Sever P, McEniery C, Wilkinson I.",,PloS one,2022,2022-11-09,Y,,,,"Hypertension appears to be one of the commonest comorbidities in COVID-19 patients, although whether hypertensive individuals have a higher risk of severe COVID-19 compared with non-hypertensives is unclear. It is also unclear whether the absolute level of systolic blood pressure, or the type of anti-hypertensive medication is related to this risk. Analyses were conducted using data from the UK Biobank and linked health records. Logistic regression models were fitted to assess the impact of hypertension, systolic blood pressure (SBP) and medications on the risk of severe COVID-19. 16,134 individuals tested positive for severe acute respiratory syndrome-coronavirus, 22% (n = 3,584) developed severe COVID-19 and 40% (n = 6,517) were hypertensive. Hypertension was associated with 22% higher odds of severe COVID-19 (Odds ratio (OR) 1.22; 95% confidence interval (CI) 1.12, 1.33), compared with normotension after adjusting for confounding variables. In those taking anti-hypertensive medications, elevated SBP showed a dose-response relationship with severe COVID-19 (150-159mmHg versus 120-129mmHg (OR 1.91; 95% CI 1.44, 2.53), >180+mmHg versus 120-129mmHg (OR 1.93; 95% CI 1.06, 3.51)). SBP <120mmHg was associated with greater odds of severe COVID-19 (OR 1.40; 95% CI 1.11, 1.78). Angiotensin-converting enzyme inhibitors or angiotensin-II receptor blockers were not associated with altered risk of severe COVID-19. Hypertension is an important risk factor for COVID-19. A better understanding of the underlying mechanisms is warranted in case of more severe strains or other viruses in the future.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0276781&type=printable; doi:https://doi.org/10.1371/journal.pone.0276781; html:https://europepmc.org/articles/PMC9645600; pdf:https://europepmc.org/articles/PMC9645600?pdf=render -38448987,https://doi.org/10.1186/s13033-024-00623-z,Can computer simulation support strategic service planning? Modelling a large integrated mental health system on recovery from COVID-19.,"Pierotti L, Cooper J, James C, Cassels K, Gara E, Denholm R, Wood R.",,International journal of mental health systems,2024,2024-03-07,Y,Computer simulation; Coronavirus; Mental Health Services; Computer Modelling; Service Design; Covid-19,,,"

Background

COVID-19 has had a significant impact on people's mental health and mental health services. During the first year of the pandemic, existing demand was not fully met while new demand was generated, resulting in large numbers of people requiring support. To support mental health services to recover without being overwhelmed, it was important to know where services will experience increased pressure, and what strategies could be implemented to mitigate this.

Methods

We implemented a computer simulation model of patient flow through an integrated mental health service in Southwest England covering General Practice (GP), community-based 'talking therapies' (IAPT), acute hospital care, and specialist care settings. The model was calibrated on data from 1 April 2019 to 1 April 2021. Model parameters included patient demand, service-level length of stay, and probabilities of transitioning to other care settings. We used the model to compare 'do nothing' (baseline) scenarios to 'what if' (mitigation) scenarios, including increasing capacity and reducing length of stay, for two future demand trajectories from 1 April 2021 onwards.

Results

The results from the simulation model suggest that, without mitigation, the impact of COVID-19 will be an increase in pressure on GP and specialist community based services by 50% and 50-100% respectively. Simulating the impact of possible mitigation strategies, results show that increasing capacity in lower-acuity services, such as GP, causes a shift in demand to other parts of the mental health system while decreasing length of stay in higher acuity services is insufficient to mitigate the impact of increased demand.

Conclusion

In capturing the interrelation of patient flow related dynamics between various mental health care settings, we demonstrate the value of computer simulation for assessing the impact of interventions on system flow.",,pdf:https://ijmhs.biomedcentral.com/counter/pdf/10.1186/s13033-024-00623-z; doi:https://doi.org/10.1186/s13033-024-00623-z; html:https://europepmc.org/articles/PMC10918932; pdf:https://europepmc.org/articles/PMC10918932?pdf=render 36058413,https://doi.org/10.1016/j.jinf.2022.08.030,A prospective study of risk factors associated with seroprevalence of SARS-CoV-2 antibodies in healthcare workers at a large UK teaching hospital.,"Cooper DJ, Lear S, Watson L, Shaw A, Ferris M, Doffinger R, Bousfield R, Sharrocks K, Weekes MP, Warne B, Sparkes D, Jones NK, Rivett L, Routledge M, Chaudhry A, Dempsey K, Matson M, Lakha A, Gathercole G, O'Connor O, Wilson E, Shahzad O, Toms K, Thompson R, Halsall I, Halsall D, Houghton S, Papadia S, Kingston N, Stirrups KE, Graves B, Townsend P, Walker N, Stark H, CITIID-NIHR BioResource COVID-19 Collaboration, De Angelis D, Seaman S, Dougan G, Bradley JR, Török ME, Goodfellow I, Baker S.",,The Journal of infection,2022,2022-09-02,Y,Healthcare Workers; Sero-epidemiology; Risk Factor Analysis; Covid-19; Sars-cov-2,,,"

Objectives

To describe the risk factors for SARS-CoV-2 infection in UK healthcare workers (HCWs).

Methods

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

Results

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

Conclusions

Risk of SARS-CoV-2 infection amongst HCWs is highly heterogeneous and influenced by COVID-19 working location, role, age and ethnicity. Increased risk amongst BAME staff cannot be accounted for solely by occupational factors.",,pdf:https://www.repository.cam.ac.uk/bitstream/1810/341240/2/1-s2.0-S016344532200514X-main.pdf; doi:https://doi.org/10.1016/j.jinf.2022.08.030; html:https://europepmc.org/articles/PMC9436870; pdf:https://europepmc.org/articles/PMC9436870?pdf=render +38448987,https://doi.org/10.1186/s13033-024-00623-z,Can computer simulation support strategic service planning? Modelling a large integrated mental health system on recovery from COVID-19.,"Pierotti L, Cooper J, James C, Cassels K, Gara E, Denholm R, Wood R.",,International journal of mental health systems,2024,2024-03-07,Y,Computer simulation; Coronavirus; Mental Health Services; Computer Modelling; Service Design; Covid-19,,,"

Background

COVID-19 has had a significant impact on people's mental health and mental health services. During the first year of the pandemic, existing demand was not fully met while new demand was generated, resulting in large numbers of people requiring support. To support mental health services to recover without being overwhelmed, it was important to know where services will experience increased pressure, and what strategies could be implemented to mitigate this.

Methods

We implemented a computer simulation model of patient flow through an integrated mental health service in Southwest England covering General Practice (GP), community-based 'talking therapies' (IAPT), acute hospital care, and specialist care settings. The model was calibrated on data from 1 April 2019 to 1 April 2021. Model parameters included patient demand, service-level length of stay, and probabilities of transitioning to other care settings. We used the model to compare 'do nothing' (baseline) scenarios to 'what if' (mitigation) scenarios, including increasing capacity and reducing length of stay, for two future demand trajectories from 1 April 2021 onwards.

Results

The results from the simulation model suggest that, without mitigation, the impact of COVID-19 will be an increase in pressure on GP and specialist community based services by 50% and 50-100% respectively. Simulating the impact of possible mitigation strategies, results show that increasing capacity in lower-acuity services, such as GP, causes a shift in demand to other parts of the mental health system while decreasing length of stay in higher acuity services is insufficient to mitigate the impact of increased demand.

Conclusion

In capturing the interrelation of patient flow related dynamics between various mental health care settings, we demonstrate the value of computer simulation for assessing the impact of interventions on system flow.",,pdf:https://ijmhs.biomedcentral.com/counter/pdf/10.1186/s13033-024-00623-z; doi:https://doi.org/10.1186/s13033-024-00623-z; html:https://europepmc.org/articles/PMC10918932; pdf:https://europepmc.org/articles/PMC10918932?pdf=render 35793922,https://doi.org/10.1136/bmjopen-2021-059385,Deriving and validating a risk prediction model for long COVID-19: protocol for an observational cohort study using linked Scottish data.,"Daines L, Mulholland RH, Vasileiou E, Hammersley V, Weatherill D, Katikireddi SV, Kerr S, Moore E, Pesenti E, Quint JK, Shah SA, Shi T, Simpson CR, Robertson C, Sheikh A.",,BMJ open,2022,2022-07-06,Y,Public Health; Protocols & Guidelines; Covid-19,,,"

Introduction

COVID-19 is commonly experienced as an acute illness, yet some people continue to have symptoms that persist for weeks, or months (commonly referred to as 'long-COVID'). It remains unclear which patients are at highest risk of developing long-COVID. In this protocol, we describe plans to develop a prediction model to identify individuals at risk of developing long-COVID.

Methods and analysis

We will use the national Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II) platform, a population-level linked dataset of routine electronic healthcare data from 5.4 million individuals in Scotland. We will identify potential indicators for long-COVID by identifying patterns in primary care data linked to information from out-of-hours general practitioner encounters, accident and emergency visits, hospital admissions, outpatient visits, medication prescribing/dispensing and mortality. We will investigate the potential indicators of long-COVID by performing a matched analysis between those with a positive reverse transcriptase PCR (RT-PCR) test for SARS-CoV-2 infection and two control groups: (1) individuals with at least one negative RT-PCR test and never tested positive; (2) the general population (everyone who did not test positive) of Scotland. Cluster analysis will then be used to determine the final definition of the outcome measure for long-COVID. We will then derive, internally and externally validate a prediction model to identify the epidemiological risk factors associated with long-COVID.

Ethics and dissemination

The EAVE II study has obtained approvals from the Research Ethics Committee (reference: 12/SS/0201), and the Public Benefit and Privacy Panel for Health and Social Care (reference: 1920-0279). Study findings will be published in peer-reviewed journals and presented at conferences. Understanding the predictors for long-COVID and identifying the patient groups at greatest risk of persisting symptoms will inform future treatments and preventative strategies for long-COVID.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/7/e059385.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-059385; html:https://europepmc.org/articles/PMC9260199; pdf:https://europepmc.org/articles/PMC9260199?pdf=render 35813279,https://doi.org/10.1016/s2666-7568(22)00147-7,"Duration of vaccine effectiveness against SARS-CoV-2 infection, hospitalisation, and death in residents and staff of long-term care facilities in England (VIVALDI): a prospective cohort study.","Shrotri M, Krutikov M, Nacer-Laidi H, Azmi B, Palmer T, Giddings R, Fuller C, Irwin-Singer A, Baynton V, Tut G, Moss P, Hayward A, Copas A, Shallcross L.",,The lancet. Healthy longevity,2022,2022-07-04,Y,,,,"

Background

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

Methods

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

Findings

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

Interpretation

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

Funding

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

Background

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

Methods

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

Findings

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

Interpretation

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

Funding

Department of Health and Social Care, England.",,pdf:http://www.thelancet.com/article/S2589537022001493/pdf; doi:https://doi.org/10.1016/j.eclinm.2022.101419; html:https://europepmc.org/articles/PMC9076030; pdf:https://europepmc.org/articles/PMC9076030?pdf=render @@ -191,14 +191,14 @@ PMC10929454,https://doi.org/,Optimising data curation pipelines for population-l 33243817,https://doi.org/10.1136/bmjopen-2020-042813,COVID-19 in Pregnancy in Scotland (COPS): protocol for an observational study using linked Scottish national data.,"Stock SJ, McAllister D, Vasileiou E, Simpson CR, Stagg HR, Agrawal U, McCowan C, Hopkins L, Donaghy J, Ritchie L, Robertson C, Sheikh A, Wood R.",,BMJ open,2020,2020-11-26,Y,Obstetrics; epidemiology; Neonatology; Perinatology; Covid-19,,,"

Introduction

The effects of SARS-CoV-2 in pregnancy are not fully delineated. We will describe the incidence of COVID-19 in pregnancy at population level in Scotland, in a prospective cohort study using linked data. We will determine associations between COVID-19 and adverse pregnancy, neonatal and maternal outcomes and the proportion of confirmed cases of SARS-CoV-2 infection in neonates associated with maternal COVID-19.

Methods and analysis

Prospective cohort study using national linked data sets. We will include all women in Scotland, UK, who were pregnant on or became pregnant after, 1 March 2020 (the date of the first confirmed case of SARS-CoV-2 infection in Scotland) and all births in Scotland from 1 March 2020 onwards. Individual-level data will be extracted from data sets containing details of all livebirths, stillbirth, terminations of pregnancy and miscarriages and ectopic pregnancies treated in hospital or attending general practice. Records will be linked within the Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II) platform, which includes primary care records, virology and serology results and details of COVID-19 Community Hubs and Assessment Centre contacts and deaths. We will perform analyses using definitions for confirmed, probable and possible COVID-19 and report serology results (where available). Outcomes will include congenital anomaly, miscarriage, stillbirth, termination of pregnancy, preterm birth, neonatal infection, severe maternal disease and maternal deaths. We will perform descriptive analyses and appropriate modelling, adjusting for demographic and pregnancy characteristics and the presence of comorbidities. The cohort will provide a platform for future studies of the effectiveness and safety of therapeutic interventions and immunisations for COVID-19 and their effects on childhood and developmental outcomes.

Ethics and dissemination

COVID-19 in Pregnancy in Scotland is a substudy of EAVE II(, which has approval from the National Research Ethics Service Committee. Findings will be reported to Scottish Government, Public Health Scotland and published in peer-reviewed journals.",,pdf:https://bmjopen.bmj.com/content/bmjopen/10/11/e042813.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-042813; html:https://europepmc.org/articles/PMC7691999; pdf:https://europepmc.org/articles/PMC7691999?pdf=render 32975552,https://doi.org/10.1001/jamapediatrics.2020.4573,Susceptibility to SARS-CoV-2 Infection Among Children and Adolescents Compared With Adults: A Systematic Review and Meta-analysis.,"Viner RM, Mytton OT, Bonell C, Melendez-Torres GJ, Ward J, Hudson L, Waddington C, Thomas J, Russell S, van der Klis F, Koirala A, Ladhani S, Panovska-Griffiths J, Davies NG, Booy R, Eggo RM.",,JAMA pediatrics,2021,2021-02-01,N,,,,"

Importance

The degree to which children and adolescents are infected by and transmit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unclear. The role of children and adolescents in transmission of SARS-CoV-2 is dependent on susceptibility, symptoms, viral load, social contact patterns, and behavior.

Objective

To systematically review the susceptibility to and transmission of SARS-CoV-2 among children and adolescents compared with adults.

Data sources

PubMed and medRxiv were searched from database inception to July 28, 2020, and a total of 13 926 studies were identified, with additional studies identified through hand searching of cited references and professional contacts.

Study selection

Studies that provided data on the prevalence of SARS-CoV-2 in children and adolescents (younger than 20 years) compared with adults (20 years and older) derived from contact tracing or population screening were included. Single-household studies were excluded.

Data extraction and synthesis

PRISMA guidelines for abstracting data were followed, which was performed independently by 2 reviewers. Quality was assessed using a critical appraisal checklist for prevalence studies. Random-effects meta-analysis was undertaken.

Main outcomes and measures

Secondary infection rate (contact-tracing studies) or prevalence or seroprevalence (population screening studies) among children and adolescents compared with adults.

Results

A total of 32 studies comprising 41 640 children and adolescents and 268 945 adults met inclusion criteria, including 18 contact-tracing studies and 14 population screening studies. The pooled odds ratio of being an infected contact in children compared with adults was 0.56 (95% CI, 0.37-0.85), with substantial heterogeneity (I2 = 94.6%). Three school-based contact-tracing studies found minimal transmission from child or teacher index cases. Findings from population screening studies were heterogenous and were not suitable for meta-analysis. Most studies were consistent with lower seroprevalence in children compared with adults, although seroprevalence in adolescents appeared similar to adults.

Conclusions and relevance

In this meta-analysis, there is preliminary evidence that children and adolescents have lower susceptibility to SARS-CoV-2, with an odds ratio of 0.56 for being an infected contact compared with adults. There is weak evidence that children and adolescents play a lesser role than adults in transmission of SARS-CoV-2 at a population level. This study provides no information on the infectivity of children.",,html:https://europepmc.org/articles/pmc7519436; doi:https://doi.org/10.1001/jamapediatrics.2020.4573; html:https://europepmc.org/articles/PMC7519436; doi:https://doi.org/10.1001/jamapediatrics.2020.4573 36098502,https://doi.org/10.7554/elife.78427,"Effectiveness of rapid SARS-CoV-2 genome sequencing in supporting infection control for hospital-onset COVID-19 infection: Multicentre, prospective study.","Stirrup O, Blackstone J, Mapp F, MacNeil A, Panca M, Holmes A, Machin N, Shin GY, Mahungu T, Saeed K, Saluja T, Taha Y, Mahida N, Pope C, Chawla A, Cutino-Moguel MT, Tamuri A, Williams R, Darby A, Robertson DL, Flaviani F, Nastouli E, Robson S, Smith D, Loose M, Laing K, Monahan I, Kele B, Haldenby S, George R, Bashton M, Witney AA, Byott M, Coll F, Chapman M, Peacock SJ, COG-UK HOCI Investigators, COVID-19 Genomics UK (COG-UK) consortium, Hughes J, Nebbia G, Partridge DG, Parker M, Price JR, Peters C, Roy S, Snell LB, de Silva TI, Thomson E, Flowers P, Copas A, Breuer J.",,eLife,2022,2022-09-13,Y,Human; Microbiology; Infectious disease; Molecular epidemiology; Infection control; epidemiology; Global Health; Hospital-acquired Infection; Infection Prevention; Viral Genomics; Healthcare-associated Infection; Covid-19,,,"

Background

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

Methods

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

Results

A total of 2170 HOCI cases were recorded from October 2020 to April 2021, corresponding to a period of extreme strain on the health service, with sequence reports returned for 650/1320 (49.2%) during intervention phases. We did not detect a statistically significant change in weekly incidence of HAIs in longer-turnaround (incidence rate ratio 1.60, 95% CI 0.85-3.01; p=0.14) or rapid (0.85, 0.48-1.50; p=0.54) intervention phases compared to baseline phase. However, IPC practice was changed in 7.8 and 7.4% of all HOCI cases in rapid and longer-turnaround phases, respectively, and 17.2 and 11.6% of cases where the report was returned. In a 'per-protocol' sensitivity analysis, there was an impact on IPC actions in 20.7% of HOCI cases when the SRT report was returned within 5 days. Capacity to respond effectively to insights from sequencing was breached in most sites by the volume of cases and limited resources.

Conclusions

While we did not demonstrate a direct impact of sequencing on the incidence of nosocomial transmission, our results suggest that sequencing can inform IPC response to HOCIs, particularly when returned within 5 days.

Funding

COG-UK is supported by funding from the Medical Research Council (MRC) part of UK Research & Innovation (UKRI), the National Institute of Health Research (NIHR) (grant code: MC_PC_19027), and Genome Research Limited, operating as the Wellcome Sanger Institute.

Clinical trial number

NCT04405934.",,doi:https://doi.org/10.7554/elife.78427; doi:https://doi.org/10.7554/eLife.78427; html:https://europepmc.org/articles/PMC9596156; pdf:https://europepmc.org/articles/PMC9596156?pdf=render -38049846,https://doi.org/10.1186/s13012-023-01321-z,Implementing Germ Defence digital behaviour change intervention via all primary care practices in England to reduce respiratory infections during the COVID-19 pandemic: an efficient cluster randomised controlled trial using the OpenSAFELY platform.,"Ainsworth B, Horwood J, Walter SR, Miller S, Chalder M, De Vocht F, Denison-Day J, Elwenspoek MMC, Curtis HJ, Bates C, Mehrkar A, Bacon S, Goldacre B, OpenSAFELY Collaborative, Craggs P, Amlôt R, Francis N, Little P, Macleod J, Moore M, Morton K, Rice C, Sterne J, Stuart B, Towler L, Willcox ML, Yardley L.",,Implementation science : IS,2023,2023-12-04,Y,Infection control; Respiratory Tract Infections; Primary Care; Rct; Behaviour Change; Ehealth; Covid-19; Efficient Trial Design; Digital Medicine,,,"

Background

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

Methods

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

Results

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

Conclusions

While the RCT did not demonstrate a difference in health outcomes, we demonstrated that rapid large-scale implementation of a digital behavioural intervention is possible and can be evaluated with a novel efficient prospective RCT methodology analysing routinely collected patient data entirely within a trusted research environment.

Trial registration

This trial was registered in the ISRCTN registry (14602359) on 12 August 2020.",,pdf:https://implementationscience.biomedcentral.com/counter/pdf/10.1186/s13012-023-01321-z; doi:https://doi.org/10.1186/s13012-023-01321-z; html:https://europepmc.org/articles/PMC10694966; pdf:https://europepmc.org/articles/PMC10694966?pdf=render PMC9023380,https://doi.org/,Assessing the spread risk of COVID-19 associated with multi-mode transportation networks in China,"Xu X, Liu X, Wang L, Wu Y, Lu X, Wang X, Pei S.",,Fundamental Research,2022,2022-04-22,Y,Complex Network; Spatial Spread; Human Mobility; Transportation Networks; Covid-19,,,"The spatial spread of COVID-19 during early 2020 in China was primarily driven by outbound travelers leaving the epicenter, Wuhan, Hubei province. Existing studies focus on the influence of aggregated out-bound population flows originating from Wuhan; however, the impacts of different modes of transportation and the network structure of transportation systems on the early spread of COVID-19 in China are not well understood. Here, we assess the roles of the road, railway, and air transportation networks in driving the spatial spread of COVID-19 in China. We find that the short-range spread within Hubei province was dominated by ground traffic, notably, the railway transportation. In contrast, long-range spread to cities in other provinces was mediated by multiple factors, including a higher risk of case importation associated with air transportation and a larger outbreak size in hub cities located at the center of transportation networks. We further show that, although the dissemination of SARS-CoV-2 across countries and continents is determined by the worldwide air transportation network, the early geographic dispersal of COVID-19 within China is better predicted by the railway traffic. Given the recent emergence of multiple more transmissible variants of SARS-CoV-2, our findings can support a better assessment of the spread risk of those variants and improve future pandemic preparedness and responses. Graphical abstract Image, graphical abstract.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9023380/?tool=EBI; pdf:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9023380/pdf/?tool=EBI; html:https://europepmc.org/articles/PMC9023380; pdf:https://europepmc.org/articles/PMC9023380?pdf=render -37528841,https://doi.org/10.1016/j.eclinm.2023.102064,Repeated antibiotic exposure and risk of hospitalisation and death following COVID-19 infection (OpenSAFELY): a matched case-control study.,"Yang YT, Wong D, Ashcroft DM, Massey J, MacKenna B, Fisher L, Mehrkar A, Bacon SC, OpenSAFELY collaborative, Hand K, Zhong X, Fahmi A, Goldacre B, van Staa T, Palin V.",,EClinicalMedicine,2023,2023-07-05,Y,Antibiotics; Primary Care; Severe Outcome; Covid-19,,,"

Background

Identifying potential risk factors related to severe COVID-19 outcomes is important. Repeated intermittent antibiotic use is known be associated with adverse outcomes. This study aims to examine whether prior frequent antibiotic exposure is associated with severe COVID-19 outcomes.

Methods

With the approval of NHS England, we used the OpenSAFELY platform, which integrated primary and secondary care, COVID-19 test, and death registration data. This matched case-control study included 0.67 million patients (aged 18-110 years) from an eligible 2.47 million patients with incident COVID-19 by matching with replacement. Inclusion criteria included registration within one general practice for at least 3 years and infection with incident COVID-19. Cases were identified according to different severity of COVID-19 outcomes. Cases and eligible controls were 1:6 matched on age, sex, region of GP practice, and index year and month of COVID-19 infection. Five quintile groups, based on the number of previous 3-year antibiotic prescriptions, were created to indicate the frequency of prior antibiotic exposure. Conditional logistic regression used to compare the differences between case and control groups, adjusting for ethnicity, body mass index, comorbidities, vaccination history, deprivation, and care home status. Sensitivity analyses were done to explore potential confounding and the effects of missing data.

Findings

Based on our inclusion criteria, between February 1, 2020 and December 31, 2021, 98,420 patients were admitted to hospitals and 22,660 died. 55 unique antibiotics were prescribed. A dose-response relationship between number of antibiotic prescriptions and risk of severe COVID-19 outcome was observed. Patients in the highest quintile with history of prior antibiotic exposure had 1.80 times greater odds of hospitalisation compared to patients without antibiotic exposure (adjusted odds ratio [OR] 1.80, 95% Confidence Interval [CI] 1.75-1.84). Similarly, the adjusted OR for hospitalised patients with death outcomes was 1.34 (95% CI 1.28-1.41). Larger number of prior antibiotic type was also associated with more severe COVID-19 related hospital admission. The adjusted OR of quintile 5 exposure (the most frequent) with more than 3 antibiotic types was around 2 times larger than quintile 1 (only 1 type; OR 1.80, 95% CI 1.75-1.84 vs. OR 1.03, 95% CI 1.01-1.05).

Interpretation

Our observational study has provided evidence that antibiotic exposure frequency and diversity may be associated with COVID-19 severity, potentially suggesting adverse effects of repeated intermittent antibiotic use. Future work could work to elucidate causal links and potential mechanisms. Antibiotic stewardship should put more emphasis on long-term antibiotic exposure and its adverse outcome to increase the awareness of appropriate antibiotics use.

Funding

Health Data Research UK and National Institute for Health Research.",,doi:https://doi.org/10.1016/j.eclinm.2023.102064; html:https://europepmc.org/articles/PMC10388579; pdf:https://europepmc.org/articles/PMC10388579?pdf=render 34018481,https://doi.org/10.2807/1560-7917.es.2021.26.20.2100428,The potential for vaccination-induced herd immunity against the SARS-CoV-2 B.1.1.7 variant.,"Hodgson D, Flasche S, Jit M, Kucharski AJ, CMMID COVID-19 Working Group, Centre for Mathematical Modelling of Infectious Disease (CMMID) COVID-19 Working Group.",,Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin,2021,2021-05-01,Y,Vaccination; Herd immunity; Seroprevalence; Sars-cov-2,,,"We assess the feasibility of reaching the herd immunity threshold against SARS-CoV-2 through vaccination, considering vaccine effectiveness (VE), transmissibility of the virus and the level of pre-existing immunity in populations, as well as their age structure. If highly transmissible variants of concern become dominant in areas with low levels of naturally-acquired immunity and/or in populations with large proportions of < 15 year-olds, control of infection without non-pharmaceutical interventions may only be possible with a VE ≥ 80%, and coverage extended to children.",,pdf:https://www.eurosurveillance.org/deliver/fulltext/eurosurveillance/26/20/eurosurv-26-20-1.pdf?itemId=%2Fcontent%2F10.2807%2F1560-7917.ES.2021.26.20.2100428&mimeType=pdf&containerItemId=content/eurosurveillance; doi:https://doi.org/10.2807/1560-7917.ES.2021.26.20.2100428; html:https://europepmc.org/articles/PMC8138959; pdf:https://europepmc.org/articles/PMC8138959?pdf=render +37528841,https://doi.org/10.1016/j.eclinm.2023.102064,Repeated antibiotic exposure and risk of hospitalisation and death following COVID-19 infection (OpenSAFELY): a matched case-control study.,"Yang YT, Wong D, Ashcroft DM, Massey J, MacKenna B, Fisher L, Mehrkar A, Bacon SC, OpenSAFELY collaborative, Hand K, Zhong X, Fahmi A, Goldacre B, van Staa T, Palin V.",,EClinicalMedicine,2023,2023-07-05,Y,Antibiotics; Primary Care; Severe Outcome; Covid-19,,,"

Background

Identifying potential risk factors related to severe COVID-19 outcomes is important. Repeated intermittent antibiotic use is known be associated with adverse outcomes. This study aims to examine whether prior frequent antibiotic exposure is associated with severe COVID-19 outcomes.

Methods

With the approval of NHS England, we used the OpenSAFELY platform, which integrated primary and secondary care, COVID-19 test, and death registration data. This matched case-control study included 0.67 million patients (aged 18-110 years) from an eligible 2.47 million patients with incident COVID-19 by matching with replacement. Inclusion criteria included registration within one general practice for at least 3 years and infection with incident COVID-19. Cases were identified according to different severity of COVID-19 outcomes. Cases and eligible controls were 1:6 matched on age, sex, region of GP practice, and index year and month of COVID-19 infection. Five quintile groups, based on the number of previous 3-year antibiotic prescriptions, were created to indicate the frequency of prior antibiotic exposure. Conditional logistic regression used to compare the differences between case and control groups, adjusting for ethnicity, body mass index, comorbidities, vaccination history, deprivation, and care home status. Sensitivity analyses were done to explore potential confounding and the effects of missing data.

Findings

Based on our inclusion criteria, between February 1, 2020 and December 31, 2021, 98,420 patients were admitted to hospitals and 22,660 died. 55 unique antibiotics were prescribed. A dose-response relationship between number of antibiotic prescriptions and risk of severe COVID-19 outcome was observed. Patients in the highest quintile with history of prior antibiotic exposure had 1.80 times greater odds of hospitalisation compared to patients without antibiotic exposure (adjusted odds ratio [OR] 1.80, 95% Confidence Interval [CI] 1.75-1.84). Similarly, the adjusted OR for hospitalised patients with death outcomes was 1.34 (95% CI 1.28-1.41). Larger number of prior antibiotic type was also associated with more severe COVID-19 related hospital admission. The adjusted OR of quintile 5 exposure (the most frequent) with more than 3 antibiotic types was around 2 times larger than quintile 1 (only 1 type; OR 1.80, 95% CI 1.75-1.84 vs. OR 1.03, 95% CI 1.01-1.05).

Interpretation

Our observational study has provided evidence that antibiotic exposure frequency and diversity may be associated with COVID-19 severity, potentially suggesting adverse effects of repeated intermittent antibiotic use. Future work could work to elucidate causal links and potential mechanisms. Antibiotic stewardship should put more emphasis on long-term antibiotic exposure and its adverse outcome to increase the awareness of appropriate antibiotics use.

Funding

Health Data Research UK and National Institute for Health Research.",,doi:https://doi.org/10.1016/j.eclinm.2023.102064; html:https://europepmc.org/articles/PMC10388579; pdf:https://europepmc.org/articles/PMC10388579?pdf=render +38049846,https://doi.org/10.1186/s13012-023-01321-z,Implementing Germ Defence digital behaviour change intervention via all primary care practices in England to reduce respiratory infections during the COVID-19 pandemic: an efficient cluster randomised controlled trial using the OpenSAFELY platform.,"Ainsworth B, Horwood J, Walter SR, Miller S, Chalder M, De Vocht F, Denison-Day J, Elwenspoek MMC, Curtis HJ, Bates C, Mehrkar A, Bacon S, Goldacre B, OpenSAFELY Collaborative, Craggs P, Amlôt R, Francis N, Little P, Macleod J, Moore M, Morton K, Rice C, Sterne J, Stuart B, Towler L, Willcox ML, Yardley L.",,Implementation science : IS,2023,2023-12-04,Y,Infection control; Respiratory Tract Infections; Primary Care; Rct; Behaviour Change; Ehealth; Covid-19; Efficient Trial Design; Digital Medicine,,,"

Background

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

Methods

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

Results

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

Conclusions

While the RCT did not demonstrate a difference in health outcomes, we demonstrated that rapid large-scale implementation of a digital behavioural intervention is possible and can be evaluated with a novel efficient prospective RCT methodology analysing routinely collected patient data entirely within a trusted research environment.

Trial registration

This trial was registered in the ISRCTN registry (14602359) on 12 August 2020.",,pdf:https://implementationscience.biomedcentral.com/counter/pdf/10.1186/s13012-023-01321-z; doi:https://doi.org/10.1186/s13012-023-01321-z; html:https://europepmc.org/articles/PMC10694966; pdf:https://europepmc.org/articles/PMC10694966?pdf=render 36522333,https://doi.org/10.1038/s41467-022-35454-4,Multi-omics identify falling LRRC15 as a COVID-19 severity marker and persistent pro-thrombotic signals in convalescence.,"Gisby JS, Buang NB, Papadaki A, Clarke CL, Malik TH, Medjeral-Thomas N, Pinheiro D, Mortimer PM, Lewis S, Sandhu E, McAdoo SP, Prendecki MF, Willicombe M, Pickering MC, Botto M, Thomas DC, Peters JE.",,Nature communications,2022,2022-12-15,Y,,,,"Patients with end-stage kidney disease (ESKD) are at high risk of severe COVID-19. Here, we perform longitudinal blood sampling of ESKD haemodialysis patients with COVID-19, collecting samples pre-infection, serially during infection, and after clinical recovery. Using plasma proteomics, and RNA-sequencing and flow cytometry of immune cells, we identify transcriptomic and proteomic signatures of COVID-19 severity, and find distinct temporal molecular profiles in patients with severe disease. Supervised learning reveals that the plasma proteome is a superior indicator of clinical severity than the PBMC transcriptome. We show that a decreasing trajectory of plasma LRRC15, a proposed co-receptor for SARS-CoV-2, is associated with a more severe clinical course. We observe that two months after the acute infection, patients still display dysregulated gene expression related to vascular, platelet and coagulation pathways, including PF4 (platelet factor 4), which may explain the prolonged thrombotic risk following COVID-19.",,pdf:https://www.nature.com/articles/s41467-022-35454-4.pdf; doi:https://doi.org/10.1038/s41467-022-35454-4; html:https://europepmc.org/articles/PMC9753891; pdf:https://europepmc.org/articles/PMC9753891?pdf=render 37562853,https://doi.org/10.1136/bmjment-2023-300842,Living alone and mental health: parallel analyses in UK longitudinal population surveys and electronic health records prior to and during the COVID-19 pandemic.,"McElroy E, Herrett E, Patel K, Piehlmaier DM, Gessa GD, Huggins C, Green MJ, Kwong ASF, Thompson EJ, Zhu J, Mansfield KE, Silverwood RJ, Mansfield R, Maddock J, Mathur R, Costello RE, Matthews A, Tazare J, Henderson A, Wing K, Bridges L, Bacon S, Mehrkar A, OpenSAFELY Collaborative, Shaw RJ, Wels J, Katikireddi SV, Chaturvedi N, Tomlinson LA, Patalay P, Longitudinal Health and Wellbeing Collaborative.",,BMJ mental health,2023,2023-08-01,Y,Psychiatry; Anxiety Disorders; Covid-19,,,"

Background

People who live alone experience greater levels of mental illness; however, it is unclear whether the COVID-19 pandemic had a disproportionately negative impact on this demographic.

Objective

To describe the mental health gap between those who live alone and with others in the UK prior to and during the COVID-19 pandemic.

Methods

Self-reported psychological distress and life satisfaction in 10 prospective longitudinal population surveys (LPSs) assessed in the nearest pre-pandemic sweep and three periods during the pandemic. Recorded diagnosis of common and severe mental illnesses between March 2018 and January 2022 in electronic healthcare records (EHRs) within the OpenSAFELY-TPP.

Findings

In 37 544 LPS participants, pooled models showed greater psychological distress (standardised mean difference (SMD): 0.09 (95% CI: 0.04; 0.14); relative risk: 1.25 (95% CI: 1.12; 1.39)) and lower life satisfaction (SMD: -0.22 (95% CI: -0.30; -0.15)) for those living alone pre-pandemic. This gap did not change during the pandemic. In the EHR analysis of c.16 million records, mental health conditions were more common in those who lived alone (eg, depression 26 (95% CI: 18 to 33) and severe mental illness 58 (95% CI: 54 to 62) more cases more per 100 000). For common mental health disorders, the gap in recorded cases in EHRs narrowed during the pandemic.

Conclusions

People living alone have poorer mental health and lower life satisfaction. During the pandemic, this gap in self-reported distress remained; however, there was a narrowing of the gap in service use.

Clinical implications

Greater mental health need and potentially greater barriers to mental healthcare access for those who live alone need to be considered in healthcare planning.",,pdf:https://mentalhealth.bmj.com/content/ebmental/26/1/e300842.full.pdf; doi:https://doi.org/10.1136/bmjment-2023-300842; html:https://europepmc.org/articles/PMC10577768; pdf:https://europepmc.org/articles/PMC10577768?pdf=render -38803829,https://doi.org/10.1136/bmjmed-2023-000791,Incidence and treatment of group A streptococcal infections during covid-19 pandemic and 2022 outbreak: retrospective cohort study in England using OpenSAFELY-TPP.,"Cunningham C, Fisher L, Wood C, Speed V, Brown AD, Curtis H, Higgins R, Croker R, Butler-Cole BF, Evans D, Inglesby P, Dillingham I, Bacon SC, Beech E, Hand K, Davy S, Ward T, Hickman G, Bridges L, O'Dwyer T, Maude S, Smith RM, Mehrkar A, Hart LC, Bates C, Cockburn J, Parry J, Hester F, Harper S, Goldacre B, MacKenna B.",,BMJ medicine,2024,2024-05-24,Y,Primary Health Care; Infectious Disease Medicine; Covid-19,,,"

Objective

To investigate the effect of the covid-19 pandemic on the number of patients with group A streptococcal infections and related antibiotic prescriptions.

Design

Retrospective cohort study in England using OpenSAFELY-TPP.

Setting

Primary care practices in England that used TPP SystmOne software, 1 January 2018 to 31 March 2023, with the approval of NHS England.

Participants

Patients registered at a TPP practice at the start of each month of the study period. Patients with missing data for sex or age were excluded, resulting in a population of 23 816 470 in January 2018, increasing to 25 541 940 by March 2023.

Main outcome measures

Monthly counts and crude rates of patients with group A streptococcal infections (sore throat or tonsillitis, scarlet fever, and invasive group A streptococcal infections), and recommended firstline, alternative, and reserved antibiotic prescriptions linked with a group A streptococcal infection before (pre-April 2020), during, and after (post-April 2021) covid-19 restrictions. Maximum and minimum count and rate for each infectious season (time from September to August), as well as the rate ratio of the 2022-23 season compared with the last comparably high season (2017-18).

Results

The number of patients with group A streptococcal infections, and antibiotic prescriptions linked to an indication of group A streptococcal infection, peaked in December 2022, higher than the peak in 2017-18. The rate ratios for monthly sore throat or tonsillitis (possible group A streptococcal throat infection), scarlet fever, and invasive group A streptococcal infection in 2022-23 relative to 2017-18 were 1.39 (95% confidence interval (CI) 1.38 to 1.40), 2.68 (2.59 to 2.77), and 4.37 (2.94 to 6.48), respectively. The rate ratio for prescriptions of first line, alternative, and reserved antibiotics to patients with group A streptococcal infections in 2022-23 relative to 2017-18 were 1.37 (95% CI 1.35 to 1.38), 2.30 (2.26 to 2.34), and 2.42 (2.24 to 2.61), respectively. For individual antibiotic prescriptions in 2022-23, azithromycin showed the greatest relative increase versus 2017-18, with a rate ratio of 7.37 (6.22 to 8.74). This finding followed a marked decrease in the recording of patients with group A streptococcal infections and associated prescriptions during the period of covid-19 restrictions where the maximum count and rates were lower than any minimum rates before the covid-19 pandemic.

Conclusions

Recording of rates of scarlet fever, sore throat or tonsillitis, and invasive group A streptococcal infections, and associated antibiotic prescribing, peaked in December 2022. Primary care data can supplement existing infectious disease surveillance through linkages with relevant prescribing data and detailed analysis of clinical and demographic subgroups.",,doi:https://doi.org/10.1136/bmjmed-2023-000791; html:https://europepmc.org/articles/PMC11129040; pdf:https://europepmc.org/articles/PMC11129040?pdf=render 35902613,https://doi.org/10.1038/s41467-022-32096-4,Dynamics of competing SARS-CoV-2 variants during the Omicron epidemic in England.,"Eales O, de Oliveira Martins L, Page AJ, Wang H, Bodinier B, Tang D, Haw D, Jonnerby J, Atchison C, Ashby D, Barclay W, Taylor G, Cooke G, Ward H, Darzi A, Riley S, Elliott P, Donnelly CA, Chadeau-Hyam M.",,Nature communications,2022,2022-07-28,Y,,,,"The SARS-CoV-2 pandemic has been characterised by the regular emergence of genomic variants. With natural and vaccine-induced population immunity at high levels, evolutionary pressure favours variants better able to evade SARS-CoV-2 neutralising antibodies. The Omicron variant (first detected in November 2021) exhibited a high degree of immune evasion, leading to increased infection rates worldwide. However, estimates of the magnitude of this Omicron wave have often relied on routine testing data, which are prone to several biases. Using data from the REal-time Assessment of Community Transmission-1 (REACT-1) study, a series of cross-sectional surveys assessing prevalence of SARS-CoV-2 infection in England, we estimated the dynamics of England's Omicron wave (from 9 September 2021 to 1 March 2022). We estimate an initial peak in national Omicron prevalence of 6.89% (5.34%, 10.61%) during January 2022, followed by a resurgence in SARS-CoV-2 infections as the more transmissible Omicron sub-lineage, BA.2 replaced BA.1 and BA.1.1. Assuming the emergence of further distinct variants, intermittent epidemics of similar magnitudes may become the 'new normal'.",,pdf:https://www.nature.com/articles/s41467-022-32096-4.pdf; doi:https://doi.org/10.1038/s41467-022-32096-4; html:https://europepmc.org/articles/PMC9330949; pdf:https://europepmc.org/articles/PMC9330949?pdf=render +38803829,https://doi.org/10.1136/bmjmed-2023-000791,Incidence and treatment of group A streptococcal infections during covid-19 pandemic and 2022 outbreak: retrospective cohort study in England using OpenSAFELY-TPP.,"Cunningham C, Fisher L, Wood C, Speed V, Brown AD, Curtis H, Higgins R, Croker R, Butler-Cole BF, Evans D, Inglesby P, Dillingham I, Bacon SC, Beech E, Hand K, Davy S, Ward T, Hickman G, Bridges L, O'Dwyer T, Maude S, Smith RM, Mehrkar A, Hart LC, Bates C, Cockburn J, Parry J, Hester F, Harper S, Goldacre B, MacKenna B.",,BMJ medicine,2024,2024-05-24,Y,Primary Health Care; Infectious Disease Medicine; Covid-19,,,"

Objective

To investigate the effect of the covid-19 pandemic on the number of patients with group A streptococcal infections and related antibiotic prescriptions.

Design

Retrospective cohort study in England using OpenSAFELY-TPP.

Setting

Primary care practices in England that used TPP SystmOne software, 1 January 2018 to 31 March 2023, with the approval of NHS England.

Participants

Patients registered at a TPP practice at the start of each month of the study period. Patients with missing data for sex or age were excluded, resulting in a population of 23 816 470 in January 2018, increasing to 25 541 940 by March 2023.

Main outcome measures

Monthly counts and crude rates of patients with group A streptococcal infections (sore throat or tonsillitis, scarlet fever, and invasive group A streptococcal infections), and recommended firstline, alternative, and reserved antibiotic prescriptions linked with a group A streptococcal infection before (pre-April 2020), during, and after (post-April 2021) covid-19 restrictions. Maximum and minimum count and rate for each infectious season (time from September to August), as well as the rate ratio of the 2022-23 season compared with the last comparably high season (2017-18).

Results

The number of patients with group A streptococcal infections, and antibiotic prescriptions linked to an indication of group A streptococcal infection, peaked in December 2022, higher than the peak in 2017-18. The rate ratios for monthly sore throat or tonsillitis (possible group A streptococcal throat infection), scarlet fever, and invasive group A streptococcal infection in 2022-23 relative to 2017-18 were 1.39 (95% confidence interval (CI) 1.38 to 1.40), 2.68 (2.59 to 2.77), and 4.37 (2.94 to 6.48), respectively. The rate ratio for prescriptions of first line, alternative, and reserved antibiotics to patients with group A streptococcal infections in 2022-23 relative to 2017-18 were 1.37 (95% CI 1.35 to 1.38), 2.30 (2.26 to 2.34), and 2.42 (2.24 to 2.61), respectively. For individual antibiotic prescriptions in 2022-23, azithromycin showed the greatest relative increase versus 2017-18, with a rate ratio of 7.37 (6.22 to 8.74). This finding followed a marked decrease in the recording of patients with group A streptococcal infections and associated prescriptions during the period of covid-19 restrictions where the maximum count and rates were lower than any minimum rates before the covid-19 pandemic.

Conclusions

Recording of rates of scarlet fever, sore throat or tonsillitis, and invasive group A streptococcal infections, and associated antibiotic prescribing, peaked in December 2022. Primary care data can supplement existing infectious disease surveillance through linkages with relevant prescribing data and detailed analysis of clinical and demographic subgroups.",,doi:https://doi.org/10.1136/bmjmed-2023-000791; html:https://europepmc.org/articles/PMC11129040; pdf:https://europepmc.org/articles/PMC11129040?pdf=render 37182748,https://doi.org/10.1016/j.jinf.2023.05.010,The impact of COVID-19 on antibiotic prescribing in primary care in England: Evaluation and risk prediction of appropriateness of type and repeat prescribing.,"Zhong X, Pate A, Yang YT, Fahmi A, Ashcroft DM, Goldacre B, MacKenna B, Mehrkar A, Bacon SCJ, Massey J, Fisher L, Inglesby P, OpenSAFELY collaborative, Hand K, van Staa T, Palin V.",,The Journal of infection,2023,2023-05-12,Y,Infection; Antibiotics; Primary Care; Antibiotic Stewardship; Covid-19 Pandemic,,,"

Background

This study aimed to predict risks of potentially inappropriate antibiotic type and repeat prescribing and assess changes during COVID-19.

Methods

With the approval of NHS England, we used OpenSAFELY platform to access the TPP SystmOne electronic health record (EHR) system and selected patients prescribed antibiotics from 2019 to 2021. Multinomial logistic regression models predicted patient's probability of receiving inappropriate antibiotic type or repeat antibiotic course for each common infection.

Results

The population included 9.1 million patients with 29.2 million antibiotic prescriptions. 29.1% of prescriptions were identified as repeat prescribing. Those with same day incident infection coded in the EHR had considerably lower rates of repeat prescribing (18.0%) and 8.6% had potentially inappropriate type. No major changes in the rates of repeat antibiotic prescribing during COVID-19 were found. In the 10 risk prediction models, good levels of calibration and moderate levels of discrimination were found.

Conclusions

Our study found no evidence of changes in level of inappropriate or repeat antibiotic prescribing after the start of COVID-19. Repeat antibiotic prescribing was frequent and varied according to regional and patient characteristics. There is a need for treatment guidelines to be developed around antibiotic failure and clinicians provided with individualised patient information.",,pdf:http://www.journalofinfection.com/article/S0163445323002888/pdf; doi:https://doi.org/10.1016/j.jinf.2023.05.010; html:https://europepmc.org/articles/PMC10176893; pdf:https://europepmc.org/articles/PMC10176893?pdf=render 35879616,https://doi.org/10.1038/s41591-022-01909-w,Symptoms and risk factors for long COVID in non-hospitalized adults.,"Subramanian A, Nirantharakumar K, Hughes S, Myles P, Williams T, Gokhale KM, Taverner T, Chandan JS, Brown K, Simms-Williams N, Shah AD, Singh M, Kidy F, Okoth K, Hotham R, Bashir N, Cockburn N, Lee SI, Turner GM, Gkoutos GV, Aiyegbusi OL, McMullan C, Denniston AK, Sapey E, Lord JM, Wraith DC, Leggett E, Iles C, Marshall T, Price MJ, Marwaha S, Davies EH, Jackson LJ, Matthews KL, Camaradou J, Calvert M, Haroon S.",,Nature medicine,2022,2022-07-25,Y,,,,"Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is associated with a range of persistent symptoms impacting everyday functioning, known as post-COVID-19 condition or long COVID. We undertook a retrospective matched cohort study using a UK-based primary care database, Clinical Practice Research Datalink Aurum, to determine symptoms that are associated with confirmed SARS-CoV-2 infection beyond 12 weeks in non-hospitalized adults and the risk factors associated with developing persistent symptoms. We selected 486,149 adults with confirmed SARS-CoV-2 infection and 1,944,580 propensity score-matched adults with no recorded evidence of SARS-CoV-2 infection. Outcomes included 115 individual symptoms, as well as long COVID, defined as a composite outcome of 33 symptoms by the World Health Organization clinical case definition. Cox proportional hazards models were used to estimate adjusted hazard ratios (aHRs) for the outcomes. A total of 62 symptoms were significantly associated with SARS-CoV-2 infection after 12 weeks. The largest aHRs were for anosmia (aHR 6.49, 95% CI 5.02-8.39), hair loss (3.99, 3.63-4.39), sneezing (2.77, 1.40-5.50), ejaculation difficulty (2.63, 1.61-4.28) and reduced libido (2.36, 1.61-3.47). Among the cohort of patients infected with SARS-CoV-2, risk factors for long COVID included female sex, belonging to an ethnic minority, socioeconomic deprivation, smoking, obesity and a wide range of comorbidities. The risk of developing long COVID was also found to be increased along a gradient of decreasing age. SARS-CoV-2 infection is associated with a plethora of symptoms that are associated with a range of sociodemographic and clinical risk factors.",,pdf:https://www.nature.com/articles/s41591-022-01909-w.pdf; doi:https://doi.org/10.1038/s41591-022-01909-w; html:https://europepmc.org/articles/PMC9388369; pdf:https://europepmc.org/articles/PMC9388369?pdf=render 34104901,https://doi.org/10.1016/s2666-7568(21)00093-3,Incidence of SARS-CoV-2 infection according to baseline antibody status in staff and residents of 100 long-term care facilities (VIVALDI): a prospective cohort study.,"Krutikov M, Palmer T, Tut G, Fuller C, Shrotri M, Williams H, Davies D, Irwin-Singer A, Robson J, Hayward A, Moss P, Copas A, Shallcross L.",,The lancet. Healthy longevity,2021,2021-06-03,Y,,,,"

Background

SARS-CoV-2 infection represents a major challenge for long-term care facilities (LTCFs) and many residents and staff are seropositive following persistent outbreaks. We aimed to investigate the association between the SARS-CoV-2 antibody status at baseline and subsequent infection in this population.

Methods

We did a prospective cohort study of SARS-CoV-2 infection in staff (aged <65 years) and residents (aged >65 years) at 100 LTCFs in England between Oct 1, 2020, and Feb 1, 2021. Blood samples were collected between June and November, 2020, at baseline, and 2 and 4 months thereafter and tested for IgG antibodies to SARS-CoV-2 nucleocapsid and spike proteins. PCR testing for SARS-CoV-2 was done weekly in staff and monthly in residents. Cox regression was used to estimate hazard ratios (HRs) of a PCR-positive test by baseline antibody status, adjusted for age and sex, and stratified by LTCF.

Findings

682 residents from 86 LCTFs and 1429 staff members from 97 LTCFs met study inclusion criteria. At baseline, IgG antibodies to nucleocapsid were detected in 226 (33%) of 682 residents and 408 (29%) of 1429 staff members. 93 (20%) of 456 residents who were antibody-negative at baseline had a PCR-positive test (infection rate 0·054 per month at risk) compared with four (2%) of 226 residents who were antibody-positive at baseline (0·007 per month at risk). 111 (11%) of 1021 staff members who were antibody-negative at baseline had PCR-positive tests (0·042 per month at risk) compared with ten (2%) of 408 staff members who were antibody-positive staff at baseline (0·009 per month at risk). The risk of PCR-positive infection was higher for residents who were antibody-negative at baseline than residents who were antibody-positive at baseline (adjusted HR [aHR] 0·15, 95% CI 0·05-0·44, p=0·0006), and the risk of a PCR-positive infection was also higher for staff who were antibody-negative at baseline compared with staff who were antibody-positive at baseline (aHR 0·39, 0·19-0·82; p=0·012). 12 of 14 reinfected participants had available data on symptoms, and 11 of these participants were symptomatic. Antibody titres to spike and nucleocapsid proteins were comparable in PCR-positive and PCR-negative cases.

Interpretation

The presence of IgG antibodies to nucleocapsid protein was associated with substantially reduced risk of reinfection in staff and residents for up to 10 months after primary infection.

Funding

UK Government Department of Health and Social Care.",,pdf:http://www.thelancet.com/article/S2666756821000933/pdf; doi:https://doi.org/10.1016/S2666-7568(21)00093-3; html:https://europepmc.org/articles/PMC8175048; pdf:https://europepmc.org/articles/PMC8175048?pdf=render @@ -208,8 +208,8 @@ PMC9023380,https://doi.org/,Assessing the spread risk of COVID-19 associated wit 35790970,https://doi.org/10.1186/s12913-022-08202-z,Access to personal protective equipment in healthcare workers during the COVID-19 pandemic in the United Kingdom: results from a nationwide cohort study (UK-REACH).,"Martin CA, Pan D, Nazareth J, Aujayeb A, Bryant L, Carr S, Gray LJ, Gregary B, Gupta A, Guyatt AL, Gopal A, Hine T, John C, McManus IC, Melbourne C, Nellums LB, Reza R, Simpson S, Tobin MD, Woolf K, Zingwe S, Khunti K, Pareek M, UK-REACH Study Collaborative Group.",,BMC health services research,2022,2022-07-05,Y,Personal Protective Equipment; Ethnicity; Healthcare Worker; Ppe; Covid-19,,,"

Background

Healthcare workers (HCWs) are at high risk of SARS-CoV-2 infection. Effective use of personal protective equipment (PPE) reduces this risk. We sought to determine the prevalence and predictors of self-reported access to appropriate PPE (aPPE) for HCWs in the UK during the COVID-19 pandemic.

Methods

We conducted cross sectional analyses using data from a nationwide questionnaire-based cohort study administered between December 2020-February 2021. The outcome was a binary measure of self-reported aPPE (access all of the time vs access most of the time or less frequently) at two timepoints: the first national lockdown in the UK in March 2020 (primary analysis) and at the time of questionnaire response (secondary analysis).

Results

Ten thousand five hundred eight HCWs were included in the primary analysis, and 12,252 in the secondary analysis. 35.2% of HCWs reported aPPE at all times in the primary analysis; 83.9% reported aPPE at all times in the secondary analysis. In the primary analysis, after adjustment (for age, sex, ethnicity, migration status, occupation, aerosol generating procedure exposure, work sector and region, working hours, night shift frequency and trust in employing organisation), older HCWs and those working in Intensive Care Units were more likely to report aPPE at all times. Asian HCWs (aOR:0.77, 95%CI 0.67-0.89 [vs White]), those in allied health professional and dental roles (vs those in medical roles), and those who saw a higher number of COVID-19 patients compared to those who saw none (≥ 21 patients/week 0.74, 0.61-0.90) were less likely to report aPPE at all times. Those who trusted their employing organisation to deal with concerns about unsafe clinical practice, compared to those who did not, were twice as likely to report aPPE at all times. Significant predictors were largely unchanged in the secondary analysis.

Conclusions

Only a third of HCWs in the UK reported aPPE at all times during the first lockdown and that aPPE had improved later in the pandemic. We also identified key determinants of aPPE during the first UK lockdown, which have mostly persisted since lockdown was eased. These findings have important implications for the safe delivery of healthcare during the pandemic.",,pdf:https://bmchealthservres.biomedcentral.com/counter/pdf/10.1186/s12913-022-08202-z; doi:https://doi.org/10.1186/s12913-022-08202-z; html:https://europepmc.org/articles/PMC9255515; pdf:https://europepmc.org/articles/PMC9255515?pdf=render 35511729,https://doi.org/10.1093/ageing/afac084,"COVID-19 risk factors amongst 14,786 care home residents: an observational longitudinal analysis including daily community positive test rates of COVID-19, hospital stays and vaccination status in Wales (UK) between 1 September 2020 and 1 May 2021.","Hollinghurst J, Hollinghurst R, North L, Mizen A, Akbari A, Long S, Lyons RA, Fry R.",,Age and ageing,2022,2022-05-01,Y,Vaccination; Hospital infection; Older People; Care Homes; Covid-19; Pcr Tests,,,"

Background

COVID-19 vaccinations have been prioritised for high risk individuals.

Aim

Determine individual-level risk factors for care home residents testing positive for SARS-CoV-2.

Study design

Longitudinal observational cohort study using individual-level linked data from the Secure Anonymised Information Linkage (SAIL) databank.

Setting

Fourteen thousand seven hundred and eighty-six older care home residents (aged 65+) living in Wales between 1 September 2020 and 1 May 2021. Our dataset consisted of 2,613,341 individual-level daily observations within 697 care homes.

Methods

We estimated odds ratios (ORs [95% confidence interval]) using multilevel logistic regression models. Our outcome of interest was a positive SARS-CoV-2 PCR test. We included time-dependent covariates for the estimated community positive test rate of COVID-19, hospital inpatient status, vaccination status and frailty. Additional covariates were included for age, sex and specialist care home services.

Results

The multivariable regression model indicated an increase in age (OR 1.01 [1.00,1.01] per year), community positive test rate (OR 1.13 [1.12,1.13] per percent increase), hospital inpatients (OR 7.40 [6.54,8.36]), and residents in care homes with non-specialist dementia care (OR 1.42 [1.01,1.99]) had an increased odds of a positive test. Having a positive test prior to the observation period (OR 0.58 [0.49,0.68]) and either one or two doses of a vaccine (0.21 [0.17,0.25] and 0.05 [0.02,0.09], respectively) were associated with a decreased odds.

Conclusions

Care providers need to remain vigilant despite the vaccination rollout, and extra precautions should be taken when caring for the most vulnerable. Minimising potential COVID-19 infection for care home residents when admitted to hospital should be prioritised.",,pdf:https://academic.oup.com/ageing/article-pdf/51/5/afac084/43520659/afac084.pdf; doi:https://doi.org/10.1093/ageing/afac084; html:https://europepmc.org/articles/PMC9070807; pdf:https://europepmc.org/articles/PMC9070807?pdf=render 38330197,https://doi.org/10.7189/jogh.14.03006,Caveats in reporting of national vaccine uptake.,"Millington T, Morrison K, Jeffrey K, Sullivan C, Kurdi A, Fagbamigbe AF, Swallow B, Shi T, Shah SA, Kerr S, Simpson CR, Ritchie LD, Robertson C, Sheikh A, Rudan I.",,Journal of global health,2024,2024-02-09,Y,,,,,,doi:https://doi.org/10.7189/jogh.14.03006; html:https://europepmc.org/articles/PMC10852533; pdf:https://europepmc.org/articles/PMC10852533?pdf=render -37434746,https://doi.org/10.1016/j.eclinm.2023.102077,"Ethnic differences in the indirect effects of the COVID-19 pandemic on clinical monitoring and hospitalisations for non-COVID conditions in England: a population-based, observational cohort study using the OpenSAFELY platform.","Costello RE, Tazare J, Piehlmaier D, Herrett E, Parker EPK, Zheng B, Mansfield KE, Henderson AD, Carreira H, Bidulka P, Wong AYS, Warren-Gash C, Hayes JF, Quint JK, MacKenna B, Mehrkar A, Eggo RM, Katikireddi SV, Tomlinson L, Langan SM, Mathur R, LH&W NCS (or CONVALESCENCE) Collaborative, OpenSAFELY collaborative.",,EClinicalMedicine,2023,2023-06-29,Y,Pandemic; Healthcare Utilisation; Ethnic Differences,,,"

Background

The COVID-19 pandemic disrupted healthcare and may have impacted ethnic inequalities in healthcare. We aimed to describe the impact of pandemic-related disruption on ethnic differences in clinical monitoring and hospital admissions for non-COVID conditions in England.

Methods

In this population-based, observational cohort study we used primary care electronic health record data with linkage to hospital episode statistics data and mortality data within OpenSAFELY, a data analytics platform created, with approval of NHS England, to address urgent COVID-19 research questions. We included adults aged 18 years and over registered with a TPP practice between March 1, 2018, and April 30, 2022. We excluded those with missing age, sex, geographic region, or Index of Multiple Deprivation. We grouped ethnicity (exposure), into five categories: White, Asian, Black, Other, and Mixed. We used interrupted time-series regression to estimate ethnic differences in clinical monitoring frequency (blood pressure and Hba1c measurements, chronic obstructive pulmonary disease and asthma annual reviews) before and after March 23, 2020. We used multivariable Cox regression to quantify ethnic differences in hospitalisations related to diabetes, cardiovascular disease, respiratory disease, and mental health before and after March 23, 2020.

Findings

Of 33,510,937 registered with a GP as of 1st January 2020, 19,064,019 were adults, alive and registered for at least 3 months, 3,010,751 met the exclusion criteria and 1,122,912 were missing ethnicity. This resulted in 14,930,356 adults with known ethnicity (92% of sample): 86.6% were White, 7.3% Asian, 2.6% Black, 1.4% Mixed ethnicity, and 2.2% Other ethnicities. Clinical monitoring did not return to pre-pandemic levels for any ethnic group. Ethnic differences were apparent pre-pandemic, except for diabetes monitoring, and remained unchanged, except for blood pressure monitoring in those with mental health conditions where differences narrowed during the pandemic. For those of Black ethnicity, there were seven additional admissions for diabetic ketoacidosis per month during the pandemic, and relative ethnic differences narrowed during the pandemic compared to the White ethnic group (Pre-pandemic hazard ratio (HR): 0.50, 95% confidence interval (CI) 0.41, 0.60, Pandemic HR: 0.75, 95% CI: 0.65, 0.87). There was increased admissions for heart failure during the pandemic for all ethnic groups, though highest in those of White ethnicity (heart failure risk difference: 5.4). Relatively, ethnic differences narrowed for heart failure admission in those of Asian (Pre-pandemic HR 1.56, 95% CI 1.49, 1.64, Pandemic HR 1.24, 95% CI 1.19, 1.29) and Black ethnicity (Pre-pandemic HR 1.41, 95% CI: 1.30, 1.53, Pandemic HR: 1.16, 95% CI 1.09, 1.25) compared with White ethnicity. For other outcomes the pandemic had minimal impact on ethnic differences.

Interpretation

Our study suggests that ethnic differences in clinical monitoring and hospitalisations remained largely unchanged during the pandemic for most conditions. Key exceptions were hospitalisations for diabetic ketoacidosis and heart failure, which warrant further investigation to understand the causes.

Funding

LSHTM COVID-19 Response Grant (DONAT15912).",,pdf:http://www.thelancet.com/article/S2589537023002547/pdf; doi:https://doi.org/10.1016/j.eclinm.2023.102077; html:https://europepmc.org/articles/PMC10331810; pdf:https://europepmc.org/articles/PMC10331810?pdf=render 34446426,https://doi.org/10.1136/bmj.n1931,Risk of thrombocytopenia and thromboembolism after covid-19 vaccination and SARS-CoV-2 positive testing: self-controlled case series study.,"Hippisley-Cox J, Patone M, Mei XW, Saatci D, Dixon S, Khunti K, Zaccardi F, Watkinson P, Shankar-Hari M, Doidge J, Harrison DA, Griffin SJ, Sheikh A, Coupland CAC.",,BMJ (Clinical research ed.),2021,2021-08-26,Y,,,,"

Objective

To assess the association between covid-19 vaccines and risk of thrombocytopenia and thromboembolic events in England among adults.

Design

Self-controlled case series study using national data on covid-19 vaccination and hospital admissions.

Setting

Patient level data were obtained for approximately 30 million people vaccinated in England between 1 December 2020 and 24 April 2021. Electronic health records were linked with death data from the Office for National Statistics, SARS-CoV-2 positive test data, and hospital admission data from the United Kingdom's health service (NHS).

Participants

29 121 633 people were vaccinated with first doses (19 608 008 with Oxford-AstraZeneca (ChAdOx1 nCoV-19) and 9 513 625 with Pfizer-BioNTech (BNT162b2 mRNA)) and 1 758 095 people had a positive SARS-CoV-2 test. People aged ≥16 years who had first doses of the ChAdOx1 nCoV-19 or BNT162b2 mRNA vaccines and any outcome of interest were included in the study.

Main outcome measures

The primary outcomes were hospital admission or death associated with thrombocytopenia, venous thromboembolism, and arterial thromboembolism within 28 days of three exposures: first dose of the ChAdOx1 nCoV-19 vaccine; first dose of the BNT162b2 mRNA vaccine; and a SARS-CoV-2 positive test. Secondary outcomes were subsets of the primary outcomes: cerebral venous sinus thrombosis (CVST), ischaemic stroke, myocardial infarction, and other rare arterial thrombotic events.

Results

The study found increased risk of thrombocytopenia after ChAdOx1 nCoV-19 vaccination (incidence rate ratio 1.33, 95% confidence interval 1.19 to 1.47 at 8-14 days) and after a positive SARS-CoV-2 test (5.27, 4.34 to 6.40 at 8-14 days); increased risk of venous thromboembolism after ChAdOx1 nCoV-19 vaccination (1.10, 1.02 to 1.18 at 8-14 days) and after SARS-CoV-2 infection (13.86, 12.76 to 15.05 at 8-14 days); and increased risk of arterial thromboembolism after BNT162b2 mRNA vaccination (1.06, 1.01 to 1.10 at 15-21 days) and after SARS-CoV-2 infection (2.02, 1.82 to 2.24 at 15-21 days). Secondary analyses found increased risk of CVST after ChAdOx1 nCoV-19 vaccination (4.01, 2.08 to 7.71 at 8-14 days), after BNT162b2 mRNA vaccination (3.58, 1.39 to 9.27 at 15-21 days), and after a positive SARS-CoV-2 test; increased risk of ischaemic stroke after BNT162b2 mRNA vaccination (1.12, 1.04 to 1.20 at 15-21 days) and after a positive SARS-CoV-2 test; and increased risk of other rare arterial thrombotic events after ChAdOx1 nCoV-19 vaccination (1.21, 1.02 to 1.43 at 8-14 days) and after a positive SARS-CoV-2 test.

Conclusion

Increased risks of haematological and vascular events that led to hospital admission or death were observed for short time intervals after first doses of the ChAdOx1 nCoV-19 and BNT162b2 mRNA vaccines. The risks of most of these events were substantially higher and more prolonged after SARS-CoV-2 infection than after vaccination in the same population.",,pdf:https://www.bmj.com/content/bmj/374/bmj.n1931.full.pdf; doi:https://doi.org/10.1136/bmj.n1931; html:https://europepmc.org/articles/PMC8388189; pdf:https://europepmc.org/articles/PMC8388189?pdf=render +37434746,https://doi.org/10.1016/j.eclinm.2023.102077,"Ethnic differences in the indirect effects of the COVID-19 pandemic on clinical monitoring and hospitalisations for non-COVID conditions in England: a population-based, observational cohort study using the OpenSAFELY platform.","Costello RE, Tazare J, Piehlmaier D, Herrett E, Parker EPK, Zheng B, Mansfield KE, Henderson AD, Carreira H, Bidulka P, Wong AYS, Warren-Gash C, Hayes JF, Quint JK, MacKenna B, Mehrkar A, Eggo RM, Katikireddi SV, Tomlinson L, Langan SM, Mathur R, LH&W NCS (or CONVALESCENCE) Collaborative, OpenSAFELY collaborative.",,EClinicalMedicine,2023,2023-06-29,Y,Pandemic; Healthcare Utilisation; Ethnic Differences,,,"

Background

The COVID-19 pandemic disrupted healthcare and may have impacted ethnic inequalities in healthcare. We aimed to describe the impact of pandemic-related disruption on ethnic differences in clinical monitoring and hospital admissions for non-COVID conditions in England.

Methods

In this population-based, observational cohort study we used primary care electronic health record data with linkage to hospital episode statistics data and mortality data within OpenSAFELY, a data analytics platform created, with approval of NHS England, to address urgent COVID-19 research questions. We included adults aged 18 years and over registered with a TPP practice between March 1, 2018, and April 30, 2022. We excluded those with missing age, sex, geographic region, or Index of Multiple Deprivation. We grouped ethnicity (exposure), into five categories: White, Asian, Black, Other, and Mixed. We used interrupted time-series regression to estimate ethnic differences in clinical monitoring frequency (blood pressure and Hba1c measurements, chronic obstructive pulmonary disease and asthma annual reviews) before and after March 23, 2020. We used multivariable Cox regression to quantify ethnic differences in hospitalisations related to diabetes, cardiovascular disease, respiratory disease, and mental health before and after March 23, 2020.

Findings

Of 33,510,937 registered with a GP as of 1st January 2020, 19,064,019 were adults, alive and registered for at least 3 months, 3,010,751 met the exclusion criteria and 1,122,912 were missing ethnicity. This resulted in 14,930,356 adults with known ethnicity (92% of sample): 86.6% were White, 7.3% Asian, 2.6% Black, 1.4% Mixed ethnicity, and 2.2% Other ethnicities. Clinical monitoring did not return to pre-pandemic levels for any ethnic group. Ethnic differences were apparent pre-pandemic, except for diabetes monitoring, and remained unchanged, except for blood pressure monitoring in those with mental health conditions where differences narrowed during the pandemic. For those of Black ethnicity, there were seven additional admissions for diabetic ketoacidosis per month during the pandemic, and relative ethnic differences narrowed during the pandemic compared to the White ethnic group (Pre-pandemic hazard ratio (HR): 0.50, 95% confidence interval (CI) 0.41, 0.60, Pandemic HR: 0.75, 95% CI: 0.65, 0.87). There was increased admissions for heart failure during the pandemic for all ethnic groups, though highest in those of White ethnicity (heart failure risk difference: 5.4). Relatively, ethnic differences narrowed for heart failure admission in those of Asian (Pre-pandemic HR 1.56, 95% CI 1.49, 1.64, Pandemic HR 1.24, 95% CI 1.19, 1.29) and Black ethnicity (Pre-pandemic HR 1.41, 95% CI: 1.30, 1.53, Pandemic HR: 1.16, 95% CI 1.09, 1.25) compared with White ethnicity. For other outcomes the pandemic had minimal impact on ethnic differences.

Interpretation

Our study suggests that ethnic differences in clinical monitoring and hospitalisations remained largely unchanged during the pandemic for most conditions. Key exceptions were hospitalisations for diabetic ketoacidosis and heart failure, which warrant further investigation to understand the causes.

Funding

LSHTM COVID-19 Response Grant (DONAT15912).",,pdf:http://www.thelancet.com/article/S2589537023002547/pdf; doi:https://doi.org/10.1016/j.eclinm.2023.102077; html:https://europepmc.org/articles/PMC10331810; pdf:https://europepmc.org/articles/PMC10331810?pdf=render 38151278,https://doi.org/10.1136/bmjopen-2023-075958,External validation of the QCovid 2 and 3 risk prediction algorithms for risk of COVID-19 hospitalisation and mortality in adults: a national cohort study in Scotland.,"Kerr S, Millington T, Rudan I, McCowan C, Tibble H, Jeffrey K, Fagbamigbe AF, Simpson CR, Robertson C, Hippisley-Cox J, Sheikh A.",,BMJ open,2023,2023-12-27,Y,epidemiology; Health Informatics; Respiratory Medicine (See Thoracic Medicine),,,"

Objective

The QCovid 2 and 3 algorithms are risk prediction tools developed during the second wave of the COVID-19 pandemic that can be used to predict the risk of COVID-19 hospitalisation and mortality, taking vaccination status into account. In this study, we assess their performance in Scotland.

Methods

We used the Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 national data platform consisting of individual-level data for the population of Scotland (5.4 million residents). Primary care data were linked to reverse-transcription PCR virology testing, hospitalisation and mortality data. We assessed the discrimination and calibration of the QCovid 2 and 3 algorithms in predicting COVID-19 hospitalisations and deaths between 8 December 2020 and 15 June 2021.

Results

Our validation dataset comprised 465 058 individuals, aged 19-100. We found the following performance metrics (95% CIs) for QCovid 2 and 3: Harrell's C 0.84 (0.82 to 0.86) for hospitalisation, and 0.92 (0.90 to 0.94) for death, observed-expected ratio of 0.24 for hospitalisation and 0.26 for death (ie, both the number of hospitalisations and the number of deaths were overestimated), and a Brier score of 0.0009 (0.00084 to 0.00096) for hospitalisation and 0.00036 (0.00032 to 0.0004) for death.

Conclusions

We found good discrimination of the QCovid 2 and 3 algorithms in Scotland, although performance was worse in higher age groups. Both the number of hospitalisations and the number of deaths were overestimated.",,pdf:https://bmjopen.bmj.com/content/bmjopen/13/12/e075958.full.pdf; doi:https://doi.org/10.1136/bmjopen-2023-075958; html:https://europepmc.org/articles/PMC10753764; pdf:https://europepmc.org/articles/PMC10753764?pdf=render 33222494,https://doi.org/10.1177/2048872620974605,Cardiac complications in patients hospitalised with COVID-19.,"Linschoten M, Peters S, van Smeden M, Jewbali LS, Schaap J, Siebelink HM, Smits PC, Tieleman RG, van der Harst P, van Gilst WH, Asselbergs FW, CAPACITY-COVID collaborative consortium.",,European heart journal. Acute cardiovascular care,2020,2020-11-21,Y,Pulmonary embolism; Cohorts; Cardiac Complications; Patient Registry; Covid-19/coronavirus,,,"

Aims

To determine the frequency and pattern of cardiac complications in patients hospitalised with coronavirus disease (COVID-19).

Methods and results

CAPACITY-COVID is an international patient registry established to determine the role of cardiovascular disease in the COVID-19 pandemic. In this registry, data generated during routine clinical practice are collected in a standardised manner for patients with a (highly suspected) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection requiring hospitalisation. For the current analysis, consecutive patients with laboratory confirmed COVID-19 registered between 28 March and 3 July 2020 were included. Patients were followed for the occurrence of cardiac complications and pulmonary embolism from admission to discharge. In total, 3011 patients were included, of which 1890 (62.8%) were men. The median age was 67 years (interquartile range 56-76); 937 (31.0%) patients had a history of cardiac disease, with pre-existent coronary artery disease being most common (n=463, 15.4%). During hospitalisation, 595 (19.8%) patients died, including 16 patients (2.7%) with cardiac causes. Cardiac complications were diagnosed in 349 (11.6%) patients, with atrial fibrillation (n=142, 4.7%) being most common. The incidence of other cardiac complications was 1.8% for heart failure (n=55), 0.5% for acute coronary syndrome (n=15), 0.5% for ventricular arrhythmia (n=14), 0.1% for bacterial endocarditis (n=4) and myocarditis (n=3), respectively, and 0.03% for pericarditis (n=1). Pulmonary embolism was diagnosed in 198 (6.6%) patients.

Conclusion

This large study among 3011 hospitalised patients with COVID-19 shows that the incidence of cardiac complications during hospital admission is low, despite a frequent history of cardiovascular disease. Long-term cardiac outcomes and the role of pre-existing cardiovascular disease in COVID-19 outcome warrants further investigation.",,pdf:https://academic.oup.com/ehjacc/article-pdf/9/8/817/49790126/ehjacc0817.pdf; doi:https://doi.org/10.1177/2048872620974605; html:https://europepmc.org/articles/PMC7734244; pdf:https://europepmc.org/articles/PMC7734244?pdf=render 35051442,https://doi.org/10.1016/j.jviromet.2022.114471,Reduced amplification efficiency of the RNA-dependent-RNA-polymerase target enables tracking of the Delta SARS-CoV-2 variant using routine diagnostic tests.,"Valley-Omar Z, Marais G, Iranzadeh A, Naidoo M, Korsman S, Maponga T, Hussey H, Davies MA, Boulle A, Doolabh D, Laubscher M, Wojno J, Deetlefs JD, Maritz J, Scott L, Msomi N, Naicker C, Tegally H, de Oliveira T, Bhiman J, Williamson C, Preiser W, Hardie D, Hsiao NY.",,Journal of virological methods,2022,2022-01-18,Y,Surveillance; Diagnostic test; South Africa; Covid-19; Sars-cov-2; Delta Variant,,,"Routine SARS-CoV-2 surveillance in the Western Cape region of South Africa (January-August 2021) found a reduced RT-PCR amplification efficiency of the RdRp-gene target of the Seegene, Allplex 2019-nCoV diagnostic assay from June 2021 when detecting the Delta variant. We investigated whether the reduced amplification efficiency denoted by an increased RT-PCR cycle threshold value (RΔE) can be used as an indirect measure of SARS-CoV-2 Delta variant prevalence. We found a significant increase in the median RΔE for patient samples tested from June 2021, which coincided with the emergence of the SARS-CoV-2 Delta variant within our sample set. Whole genome sequencing on a subset of patient samples identified a highly conserved G15451A, non-synonymous mutation exclusively within the RdRp gene of Delta variants, which may cause reduced RT-PCR amplification efficiency. While whole genome sequencing plays an important in identifying novel SARS-CoV-2 variants, monitoring RΔE value can serve as a useful surrogate for rapid tracking of Delta variant prevalence.",,doi:https://doi.org/10.1016/j.jviromet.2022.114471; doi:https://doi.org/10.1016/j.jviromet.2022.114471; html:https://europepmc.org/articles/PMC8763409; pdf:https://europepmc.org/articles/PMC8763409?pdf=render @@ -219,8 +219,8 @@ PMC9023380,https://doi.org/,Assessing the spread risk of COVID-19 associated wit 38846423,https://doi.org/10.1016/j.lanepe.2024.100938,Modifiable risk factors for asthma exacerbations during the COVID-19 pandemic: a population-based repeated cross-sectional study using the Research and Surveillance Centre primary care database.,"Mukherjee M, Okusi C, Jamie G, Byford R, Ferreira F, Agarwal U, Weatherill D, Fletcher M, Quint JK, Romel Bhuia M, de Lusignan S, Sheikh SA.",,The Lancet regional health. Europe,2024,2024-05-24,N,Cluster analysis; Prevalence; Asthma; risk factors; Exacerbations; Covid-19,,,"

Background

There were substantial reductions in asthma exacerbations during the COVID-19 pandemic for reasons that remain poorly understood. We investigated changes in modifiable risk factors which might help explain the reductions in asthma exacerbations.

Methods

Multilevel generalised linear mixed models were fitted to examine changes in modifiable risk factors for asthma exacerbations during 2020-2022, compared to pre-pandemic year (2019), using observational, routine data from general practices in the Oxford-Royal College of General Practitioners Research and Surveillance Centre. Asthma exacerbations were defined as any of GP recorded: asthma exacerbations, prescriptions of prednisolone, accident and emergency department attendance or hospitalisation for asthma. Modifiable risk factors of interest were ownership of asthma self-management plan, asthma annual review, inhaled-corticosteroid (ICS) prescriptions, influenza vaccinations and respiratory-tract-infections (RTI).

Findings

Compared with 2019 (n = 550,995), in 2020 (n = 565,956) and 2022 (n = 562,167) (p < 0.05): asthma exacerbations declined from 67.1% to 51.9% and 61.1%, the proportion of people who had: asthma exacerbations reduced from 20.4% to 15.1% and 18.5%, asthma self-management plans increased from 28.6% to 37.7% and 55.9%; ICS prescriptions increased from 69.9% to 72.0% and 71.1%; influenza vaccinations increased from 14.2% to 25.4% and 55.3%; current smoking declined from 15.0% to 14.5% and 14.7%; lower-RTI declined from 10.5% to 5.3% and 8.1%; upper-RTI reduced from 10.7% to 5.8% and 7.6%. There was cluster effect of GP practices on asthma exacerbations (p = 0.001). People with asthma were more likely (p < 0.05) to have exacerbations if they had LRTI (seven times(x)), had URTI and ILI (both twice), were current smokers (1.4x), PPV vaccinated (1.3x), seasonal flu vaccinated (1.01x), took ICS (1.3x), had asthma reviews (1.09x). People with asthma were less likely to have exacerbations if they had self-management plan (7%), and were partially (4%) than fully COVID-19 vaccinated.

Interpretation

We have identified changes in modifiable risk factors for asthma exacerbation that need to be maintained in the post-pandemic era.

Funding

Asthma UK Centre for Applied Research and Health Data Research UK.",,doi:https://doi.org/10.1016/j.lanepe.2024.100938 35922409,https://doi.org/10.1038/s41467-022-32121-6,Dynamics of a national Omicron SARS-CoV-2 epidemic during January 2022 in England.,"Elliott P, Eales O, Bodinier B, Tang D, Wang H, Jonnerby J, Haw D, Elliott J, Whitaker M, Walters CE, Atchison C, Diggle PJ, Page AJ, Trotter AJ, Ashby D, Barclay W, Taylor G, Ward H, Darzi A, Cooke GS, Chadeau-Hyam M, Donnelly CA.",,Nature communications,2022,2022-08-03,Y,,,,"Rapid transmission of the SARS-CoV-2 Omicron variant has led to record-breaking case incidence rates around the world. Since May 2020, the REal-time Assessment of Community Transmission-1 (REACT-1) study tracked the spread of SARS-CoV-2 infection in England through RT-PCR of self-administered throat and nose swabs from randomly-selected participants aged 5 years and over. In January 2022, we found an overall weighted prevalence of 4.41% (n = 102,174), three-fold higher than in November to December 2021; we sequenced 2,374 (99.2%) Omicron infections (19 BA.2), and only 19 (0.79%) Delta, with a growth rate advantage for BA.2 compared to BA.1 or BA.1.1. Prevalence was decreasing overall (reproduction number R = 0.95, 95% credible interval [CrI], 0.93, 0.97), but increasing in children aged 5 to 17 years (R = 1.13, 95% CrI, 1.09, 1.18). In England during January 2022, we observed unprecedented levels of SARS-CoV-2 infection, especially among children, driven by almost complete replacement of Delta by Omicron.",,pdf:https://www.nature.com/articles/s41467-022-32121-6.pdf; doi:https://doi.org/10.1038/s41467-022-32121-6; html:https://europepmc.org/articles/PMC9349208; pdf:https://europepmc.org/articles/PMC9349208?pdf=render 34942103,https://doi.org/10.1016/s0140-6736(21)02754-9,"Two-dose ChAdOx1 nCoV-19 vaccine protection against COVID-19 hospital admissions and deaths over time: a retrospective, population-based cohort study in Scotland and Brazil.","Katikireddi SV, Cerqueira-Silva T, Vasileiou E, Robertson C, Amele S, Pan J, Taylor B, Boaventura V, Werneck GL, Flores-Ortiz R, Agrawal U, Docherty AB, McCowan C, McMenamin J, Moore E, Ritchie LD, Rudan I, Shah SA, Shi T, Simpson CR, Barreto ML, Oliveira VA, Barral-Netto M, Sheikh A.",,"Lancet (London, England)",2022,2021-12-20,Y,,,,"

Background

Reports suggest that COVID-19 vaccine effectiveness is decreasing, but whether this reflects waning or new SARS-CoV-2 variants-especially delta (B.1.617.2)-is unclear. We investigated the association between time since two doses of ChAdOx1 nCoV-19 vaccine and risk of severe COVID-19 outcomes in Scotland (where delta was dominant), with comparative analyses in Brazil (where delta was uncommon).

Methods

In this retrospective, population-based cohort study in Brazil and Scotland, we linked national databases from the EAVE II study in Scotland; and the COVID-19 Vaccination Campaign, Acute Respiratory Infection Suspected Cases, and Severe Acute Respiratory Infection/Illness datasets in Brazil) for vaccination, laboratory testing, clinical, and mortality data. We defined cohorts of adults (aged ≥18 years) who received two doses of ChAdOx1 nCoV-19 and compared rates of severe COVID-19 outcomes (ie, COVID-19 hospital admission or death) across fortnightly periods, relative to 2-3 weeks after the second dose. Entry to the Scotland cohort started from May 19, 2021, and entry to the Brazil cohort started from Jan 18, 2021. Follow-up in both cohorts was until Oct 25, 2021. Poisson regression was used to estimate rate ratios (RRs) and vaccine effectiveness, with 95% CIs.

Findings

1 972 454 adults received two doses of ChAdOx1 nCoV-19 in Scotland and 42 558 839 in Brazil, with longer follow-up in Scotland because two-dose vaccination began earlier in Scotland than in Brazil. In Scotland, RRs for severe COVID-19 increased to 2·01 (95% CI 1·54-2·62) at 10-11 weeks, 3·01 (2·26-3·99) at 14-15 weeks, and 5·43 (4·00-7·38) at 18-19 weeks after the second dose. The pattern of results was similar in Brazil, with RRs of 2·29 (2·01-2·61) at 10-11 weeks, 3·10 (2·63-3·64) at 14-15 weeks, and 4·71 (3·83-5·78) at 18-19 weeks after the second dose. In Scotland, vaccine effectiveness decreased from 83·7% (95% CI 79·7-87·0) at 2-3 weeks, to 75·9% (72·9-78·6) at 14-15 weeks, and 63·7% (59·6-67·4) at 18-19 weeks after the second dose. In Brazil, vaccine effectiveness decreased from 86·4% (85·4-87·3) at 2-3 weeks, to 59·7% (54·6-64·2) at 14-15 weeks, and 42·2% (32·4-50·6) at 18-19 weeks.

Interpretation

We found waning vaccine protection of ChAdOx1 nCoV-19 against COVID-19 hospital admissions and deaths in both Scotland and Brazil, this becoming evident within three months of the second vaccine dose. Consideration needs to be given to providing booster vaccine doses for people who have received ChAdOx1 nCoV-19.

Funding

UK Research and Innovation (Medical Research Council), Scottish Government, Research and Innovation Industrial Strategy Challenge Fund, Health Data Research UK, Fiocruz, Fazer o Bem Faz Bem Programme; Conselho Nacional de Desenvolvimento Científico e Tecnológico, Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro.

Translation

For the Portuguese translation of the abstract see Supplementary Materials section.",,pdf:http://www.thelancet.com/article/S0140673621027549/pdf; doi:https://doi.org/10.1016/S0140-6736(21)02754-9; html:https://europepmc.org/articles/PMC8687670 -38693557,https://doi.org/10.1186/s12913-024-10931-2,The cost of keeping patients waiting: retrospective treatment-control study of additional healthcare utilisation for UK patients awaiting elective treatment.,"James C, Denholm R, Wood R.",,BMC health services research,2024,2024-04-30,Y,Utilisation; Waiting Times; Waitlist; Elective Recovery; Failure-demand,,,"

Objective

Long waiting times for elective hospital treatments are common in many countries. This study seeks to address a deficit in the literature concerning the effect of long waits on the wider consumption of healthcare resources.

Methods

We carried out a retrospective treatment-control study in a healthcare system in South West England from 15 June 2021 to 15 December 2021. We compared weekly contacts with health services of patients waiting over 18 weeks for treatment ('Treatments') and people not on a waiting list ('Controls'). Controls were matched to Treatments based on age, sex, deprivation and multimorbidity. Treatments were stratified by the clinical specialty of the awaited hospital treatment, with healthcare usage assessed over various healthcare settings. Wilcoxon signed-rank tests assessed whether there was an increase in healthcare utilisation and bootstrap resampling was used to estimate the magnitude of any differences.

Results

A total of 44,616 patients were waiting over 18 weeks (the constitutional target in England) for treatment during the study period. There was an increase (p < 0.0004) in healthcare utilisation for all specialties. Patients in the Cardiothoracic Surgery specialty had the largest increase, with 17.9 [interquartile-range: 4.3, 33.8] additional contacts with secondary care and 17.3 [-1.1, 34.1] additional prescriptions per year.

Conclusion

People waiting for treatment consume higher levels of healthcare than comparable individuals not on a waiting list. These findings are relevant for clinicians and managers in better understanding patient need and reducing harm. Results also highlight the possible 'false economy' in failing to promptly resolve long elective waits.",,doi:https://doi.org/10.1186/s12913-024-10931-2; html:https://europepmc.org/articles/PMC11061904; pdf:https://europepmc.org/articles/PMC11061904?pdf=render 35104687,https://doi.org/10.1016/j.retram.2022.103333,A common TMPRSS2 variant has a protective effect against severe COVID-19.,"David A, Parkinson N, Peacock TP, Pairo-Castineira E, Khanna T, Cobat A, Tenesa A, Sancho-Shimizu V, GenOMICC Consortium, ISARIC4C Investigators, Casanova JL, Abel L, Barclay WS, Baillie JK, Sternberg MJ.",,Current research in translational medicine,2022,2022-01-10,Y,Tmprss2; Covid-19; Sars-cov-2; Targeting The Host To Prevent Covid19 Severity,,,"

Background

The human protein transmembrane protease serine type 2 (TMPRSS2) plays a key role in SARS-CoV-2 infection, as it is required to activate the virus' spike protein, facilitating entry into target cells. We hypothesized that naturally-occurring TMPRSS2 human genetic variants affecting the structure and function of the TMPRSS2 protein may modulate the severity of SARS-CoV-2 infection.

Methods

We focused on the only common TMPRSS2 non-synonymous variant predicted to be damaging (rs12329760 C>T, p.V160M), which has a minor allele frequency ranging from 0.14 in Ashkenazi Jewish to 0.38 in East Asians. We analysed the association between the rs12329760 and COVID-19 severity in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units recruited as part of the GenOMICC (Genetics Of Mortality In Critical Care) study. Logistic regression analyses were adjusted for sex, age and deprivation index. For in vitro studies, HEK293 cells were co-transfected with ACE2 and either TMPRSS2 wild type or mutant (TMPRSS2V160M). A SARS-CoV-2 pseudovirus entry assay was used to investigate the ability of TMPRSS2V160M to promote viral entry.

Results

We show that the T allele of rs12329760 is associated with a reduced likelihood of developing severe COVID-19 (OR 0.87, 95%CI:0.79-0.97, p = 0.01). This association was stronger in homozygous individuals when compared to the general population (OR 0.65, 95%CI:0.50-0.84, p = 1.3 × 10-3). We demonstrate in vitro that this variant, which causes the amino acid substitution valine to methionine, affects the catalytic activity of TMPRSS2 and is less able to support SARS-CoV-2 spike-mediated entry into cells.

Conclusion

TMPRSS2 rs12329760 is a common variant associated with a significantly decreased risk of severe COVID-19. Further studies are needed to assess the expression of TMPRSS2 across different age groups. Moreover, our results identify TMPRSS2 as a promising drug target, with a potential role for camostat mesilate, a drug approved for the treatment of chronic pancreatitis and postoperative reflux esophagitis, in the treatment of COVID-19. Clinical trials are needed to confirm this.",,doi:https://doi.org/10.1016/j.retram.2022.103333; doi:https://doi.org/10.1016/j.retram.2022.103333; html:https://europepmc.org/articles/PMC8743599; pdf:https://europepmc.org/articles/PMC8743599?pdf=render +38693557,https://doi.org/10.1186/s12913-024-10931-2,The cost of keeping patients waiting: retrospective treatment-control study of additional healthcare utilisation for UK patients awaiting elective treatment.,"James C, Denholm R, Wood R.",,BMC health services research,2024,2024-04-30,Y,Utilisation; Waiting Times; Waitlist; Elective Recovery; Failure-demand,,,"

Objective

Long waiting times for elective hospital treatments are common in many countries. This study seeks to address a deficit in the literature concerning the effect of long waits on the wider consumption of healthcare resources.

Methods

We carried out a retrospective treatment-control study in a healthcare system in South West England from 15 June 2021 to 15 December 2021. We compared weekly contacts with health services of patients waiting over 18 weeks for treatment ('Treatments') and people not on a waiting list ('Controls'). Controls were matched to Treatments based on age, sex, deprivation and multimorbidity. Treatments were stratified by the clinical specialty of the awaited hospital treatment, with healthcare usage assessed over various healthcare settings. Wilcoxon signed-rank tests assessed whether there was an increase in healthcare utilisation and bootstrap resampling was used to estimate the magnitude of any differences.

Results

A total of 44,616 patients were waiting over 18 weeks (the constitutional target in England) for treatment during the study period. There was an increase (p < 0.0004) in healthcare utilisation for all specialties. Patients in the Cardiothoracic Surgery specialty had the largest increase, with 17.9 [interquartile-range: 4.3, 33.8] additional contacts with secondary care and 17.3 [-1.1, 34.1] additional prescriptions per year.

Conclusion

People waiting for treatment consume higher levels of healthcare than comparable individuals not on a waiting list. These findings are relevant for clinicians and managers in better understanding patient need and reducing harm. Results also highlight the possible 'false economy' in failing to promptly resolve long elective waits.",,doi:https://doi.org/10.1186/s12913-024-10931-2; html:https://europepmc.org/articles/PMC11061904; pdf:https://europepmc.org/articles/PMC11061904?pdf=render 35192611,https://doi.org/10.1371/journal.pmed.1003916,Uptake of infant and preschool immunisations in Scotland and England during the COVID-19 pandemic: An observational study of routinely collected data.,"McQuaid F, Mulholland R, Sangpang Rai Y, Agrawal U, Bedford H, Cameron JC, Gibbons C, Roy P, Sheikh A, Shi T, Simpson CR, Tait J, Tessier E, Turner S, Villacampa Ortega J, White J, Wood R.",,PLoS medicine,2022,2022-02-22,Y,,,,"

Background

In 2020, the SARS-CoV-2 (COVID-19) pandemic and lockdown control measures threatened to disrupt routine childhood immunisation programmes with early reports suggesting uptake would fall. In response, public health bodies in Scotland and England collected national data for childhood immunisations on a weekly or monthly basis to allow for rapid analysis of trends. The aim of this study was to use these data to assess the impact of different phases of the pandemic on infant and preschool immunisation uptake rates.

Methods and findings

We conducted an observational study using routinely collected data for the year prior to the pandemic (2019) and immediately before (22 January to March 2020), during (23 March to 26 July), and after (27 July to 4 October) the first UK ""lockdown"". Data were obtained for Scotland from the Public Health Scotland ""COVID19 wider impacts on the health care system"" dashboard and for England from ImmForm. Five vaccinations delivered at different ages were evaluated; 3 doses of ""6-in-1"" diphtheria, tetanus, pertussis, polio, Haemophilus influenzae type b, and hepatitis B vaccine (DTaP/IPV/Hib/HepB) and 2 doses of measles, mumps, and rubella (MMR) vaccine. This represented 439,754 invitations to be vaccinated in Scotland and 4.1 million for England. Uptake during the 2020 periods was compared to the previous year (2019) using binary logistic regression analysis. For Scotland, uptake within 4 weeks of a child becoming eligible by age was analysed along with geographical region and indices of deprivation. For Scotland and England, we assessed whether immunisations were up-to-date at approximately 6 months (all doses 6-in-1) and 16 to 18 months (first MMR) of age. We found that uptake within 4 weeks of eligibility in Scotland for all the 5 vaccines was higher during lockdown than in 2019. Differences ranged from 1.3% for first dose 6-in-1 vaccine (95.3 versus 94%, odds ratio [OR] compared to 2019 1.28, 95% confidence intervals [CIs] 1.18 to 1.39) to 14.3% for second MMR dose (66.1 versus 51.8%, OR compared to 2019 1.8, 95% CI 1.74 to 1.87). Significant increases in uptake were seen across all deprivation levels. In England, fewer children due to receive their immunisations during the lockdown period were up to date at 6 months (6-in-1) or 18 months (first dose MMR). The fall in percentage uptake ranged from 0.5% for first 6-in-1 (95.8 versus 96.3%, OR compared to 2019 0.89, 95% CI 0.86- to 0.91) to 2.1% for third 6-in-1 (86.6 versus 88.7%, OR compared to 2019 0.82, 95% CI 0.81 to 0.83). The use of routinely collected data used in this study was a limiting factor as detailed information on potential confounding factors were not available and we were unable to eliminate the possibility of seasonal trends in immunisation uptake.

Conclusions

In this study, we observed that the national lockdown in Scotland was associated with an increase in timely childhood immunisation uptake; however, in England, uptake fell slightly. Reasons for the improved uptake in Scotland may include active measures taken to promote immunisation at local and national levels during this period and should be explored further. Promoting immunisation uptake and addressing potential vaccine hesitancy is particularly important given the ongoing pandemic and COVID-19 vaccination campaigns.",,pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1003916&type=printable; doi:https://doi.org/10.1371/journal.pmed.1003916; html:https://europepmc.org/articles/PMC8863286; pdf:https://europepmc.org/articles/PMC8863286?pdf=render 35296643,https://doi.org/10.1038/s41467-022-28517-z,"Antibody decay, T cell immunity and breakthrough infections following two SARS-CoV-2 vaccine doses in inflammatory bowel disease patients treated with infliximab and vedolizumab.","Lin S, Kennedy NA, Saifuddin A, Sandoval DM, Reynolds CJ, Seoane RC, Kottoor SH, Pieper FP, Lin KM, Butler DK, Chanchlani N, Nice R, Chee D, Bewshea C, Janjua M, McDonald TJ, Sebastian S, Alexander JL, Constable L, Lee JC, Murray CD, Hart AL, Irving PM, Jones GR, Kok KB, Lamb CA, Lees CW, Altmann DM, Boyton RJ, Goodhand JR, Powell N, Ahmad T, CLARITY IBD study.",,Nature communications,2022,2022-03-16,Y,,,,"Anti tumour necrosis factor (anti-TNF) drugs increase the risk of serious respiratory infection and impair protective immunity following pneumococcal and influenza vaccination. Here we report SARS-CoV-2 vaccine-induced immune responses and breakthrough infections in patients with inflammatory bowel disease, who are treated either with the anti-TNF antibody, infliximab, or with vedolizumab targeting a gut-specific anti-integrin that does not impair systemic immunity. Geometric mean [SD] anti-S RBD antibody concentrations are lower and half-lives shorter in patients treated with infliximab than vedolizumab, following two doses of BNT162b2 (566.7 U/mL [6.2] vs 4555.3 U/mL [5.4], p <0.0001; 26.8 days [95% CI 26.2 - 27.5] vs 47.6 days [45.5 - 49.8], p <0.0001); similar results are also observed with ChAdOx1 nCoV-19 vaccination (184.7 U/mL [5.0] vs 784.0 U/mL [3.5], p <0.0001; 35.9 days [34.9 - 36.8] vs 58.0 days [55.0 - 61.3], p value < 0.0001). One fifth of patients fail to mount a T cell response in both treatment groups. Breakthrough SARS-CoV-2 infections are more frequent (5.8% (201/3441) vs 3.9% (66/1682), p = 0.0039) in patients treated with infliximab than vedolizumab, and the risk of breakthrough SARS-CoV-2 infection is predicted by peak anti-S RBD antibody concentration after two vaccine doses. Irrespective of the treatments, higher, more sustained antibody levels are observed in patients with a history of SARS-CoV-2 infection prior to vaccination. Our results thus suggest that adapted vaccination schedules may be required to induce immunity in at-risk, anti-TNF-treated patients.",,pdf:https://www.nature.com/articles/s41467-022-28517-z.pdf; doi:https://doi.org/10.1038/s41467-022-28517-z; html:https://europepmc.org/articles/PMC8927425; pdf:https://europepmc.org/articles/PMC8927425?pdf=render 36227072,https://doi.org/10.1093/jamia/ocac203,Transforming and evaluating the UK Biobank to the OMOP Common Data Model for COVID-19 research and beyond.,"Papez V, Moinat M, Voss EA, Bazakou S, Van Winzum A, Peviani A, Payralbe S, Kallfelz M, Asselbergs FW, Prieto-Alhambra D, Dobson RJB, Denaxas S.",,Journal of the American Medical Informatics Association : JAMIA,2022,2022-12-01,Y,Phenotyping; Electronic Health Records; Omop; Common Data Model; Medical Ontologies,,,"

Objective

The coronavirus disease 2019 (COVID-19) pandemic has demonstrated the value of real-world data for public health research. International federated analyses are crucial for informing policy makers. Common data models (CDMs) are critical for enabling these studies to be performed efficiently. Our objective was to convert the UK Biobank, a study of 500 000 participants with rich genetic and phenotypic data to the Observational Medical Outcomes Partnership (OMOP) CDM.

Materials and methods

We converted UK Biobank data to OMOP CDM v. 5.3. We transformedparticipant research data on diseases collected at recruitment and electronic health records (EHRs) from primary care, hospitalizations, cancer registrations, and mortality from providers in England, Scotland, and Wales. We performed syntactic and semantic validations and compared comorbidities and risk factors between source and transformed data.

Results

We identified 502 505 participants (3086 with COVID-19) and transformed 690 fields (1 373 239 555 rows) to the OMOP CDM using 8 different controlled clinical terminologies and bespoke mappings. Specifically, we transformed self-reported noncancer illnesses 946 053 (83.91% of all source entries), cancers 37 802 (70.81%), medications 1 218 935 (88.25%), and prescriptions 864 788 (86.96%). In EHR, we transformed 13 028 182 (99.95%) hospital diagnoses, 6 465 399 (89.2%) procedures, 337 896 333 primary care diagnoses (CTV3, SNOMED-CT), 139 966 587 (98.74%) prescriptions (dm+d) and 77 127 (99.95%) deaths (ICD-10). We observed good concordance across demographic, risk factor, and comorbidity factors between source and transformed data.

Discussion and conclusion

Our study demonstrated that the OMOP CDM can be successfully leveraged to harmonize complex large-scale biobanked studies combining rich multimodal phenotypic data. Our study uncovered several challenges when transforming data from questionnaires to the OMOP CDM which require further research. The transformed UK Biobank resource is a valuable tool that can enable federated research, like COVID-19 studies.",,pdf:https://academic.oup.com/jamia/article-pdf/30/1/103/47829607/ocac203.pdf; doi:https://doi.org/10.1093/jamia/ocac203; html:https://europepmc.org/articles/PMC9619789; pdf:https://europepmc.org/articles/PMC9619789?pdf=render @@ -242,8 +242,8 @@ PMC9023380,https://doi.org/,Assessing the spread risk of COVID-19 associated wit 33123364,https://doi.org/10.1093/ckj/sfaa192,Temporal changes in complement activation in haemodialysis patients with COVID-19 as a predictor of disease progression.,"Prendecki M, Clarke C, Medjeral-Thomas N, McAdoo SP, Sandhu E, Peters JE, Thomas DC, Willicombe M, Botto M, Pickering MC.",,Clinical kidney journal,2020,2020-10-02,Y,Complement; Haemodialysis; Covid-19,,,"

Background

Complement activation may play a pathogenic role in patients with severe coronavirus disease 2019 (COVID-19) by contributing to tissue inflammation and microvascular thrombosis.

Methods

Serial samples were collected from patients receiving maintenance haemodialysis (HD). Thirty-nine patients had confirmed COVID-19 and 10 patients had no evidence of COVID-19. Plasma C5a and C3a levels were measured using enzyme-linked immunosorbent assay.

Results

We identified elevated levels of plasma C3a and C5a in HD patients with severe COVID-19 compared with controls. Serial sampling identified that C5a levels were elevated prior to clinical deterioration in patients who developed severe disease. C3a more closely mirrored both clinical and biochemical disease severity.

Conclusions

Our findings suggest that activation of complement plays a role in the pathogenesis of COVID-19, leading to endothelial injury and lung damage. C5a may be an earlier biomarker of disease severity than conventional parameters such as C-reactive protein and this warrants further investigation in dedicated biomarker studies. Our data support the testing of complement inhibition as a therapeutic strategy for patients with severe COVID-19.",,pdf:https://academic.oup.com/ckj/article-pdf/13/5/889/33980535/sfaa192.pdf; doi:https://doi.org/10.1093/ckj/sfaa192; html:https://europepmc.org/articles/PMC7577776; pdf:https://europepmc.org/articles/PMC7577776?pdf=render 37034358,https://doi.org/10.1016/j.eclinm.2023.101932,Contextualising adverse events of special interest to characterise the baseline incidence rates in 24 million patients with COVID-19 across 26 databases: a multinational retrospective cohort study.,"Voss EA, Shoaibi A, Yin Hui Lai L, Blacketer C, Alshammari T, Makadia R, Haynes K, Sena AG, Rao G, van Sandijk S, Fraboulet C, Boyer L, Le Carrour T, Horban S, Morales DR, Martínez Roldán J, Ramírez-Anguita JM, Mayer MA, de Wilde M, John LH, Duarte-Salles T, Roel E, Pistillo A, Kolde R, Maljković F, Denaxas S, Papez V, Kahn MG, Natarajan K, Reich C, Secora A, Minty EP, Shah NH, Posada JD, Garcia Morales MT, Bosca D, Cadenas Juanino H, Diaz Holgado A, Pedrera Jiménez M, Serrano Balazote P, García Barrio N, Şen S, Üresin AY, Erdogan B, Belmans L, Byttebier G, Malbrain MLNG, Dedman DJ, Cuccu Z, Vashisht R, Butte AJ, Patel A, Dahm L, Han C, Bu F, Arshad F, Ostropolets A, Nyberg F, Hripcsak G, Suchard MA, Prieto-Alhambra D, Rijnbeek PR, Schuemie MJ, Ryan PB.",,EClinicalMedicine,2023,2023-04-04,Y,Observational Research; Omop Cdm; Covid-19; Adverse Events Of Special Interest,,,"

Background

Adverse events of special interest (AESIs) were pre-specified to be monitored for the COVID-19 vaccines. Some AESIs are not only associated with the vaccines, but with COVID-19. Our aim was to characterise the incidence rates of AESIs following SARS-CoV-2 infection in patients and compare these to historical rates in the general population.

Methods

A multi-national cohort study with data from primary care, electronic health records, and insurance claims mapped to a common data model. This study's evidence was collected between Jan 1, 2017 and the conclusion of each database (which ranged from Jul 2020 to May 2022). The 16 pre-specified prevalent AESIs were: acute myocardial infarction, anaphylaxis, appendicitis, Bell's palsy, deep vein thrombosis, disseminated intravascular coagulation, encephalomyelitis, Guillain- Barré syndrome, haemorrhagic stroke, non-haemorrhagic stroke, immune thrombocytopenia, myocarditis/pericarditis, narcolepsy, pulmonary embolism, transverse myelitis, and thrombosis with thrombocytopenia. Age-sex standardised incidence rate ratios (SIR) were estimated to compare post-COVID-19 to pre-pandemic rates in each of the databases.

Findings

Substantial heterogeneity by age was seen for AESI rates, with some clearly increasing with age but others following the opposite trend. Similarly, differences were also observed across databases for same health outcome and age-sex strata. All studied AESIs appeared consistently more common in the post-COVID-19 compared to the historical cohorts, with related meta-analytic SIRs ranging from 1.32 (1.05 to 1.66) for narcolepsy to 11.70 (10.10 to 13.70) for pulmonary embolism.

Interpretation

Our findings suggest all AESIs are more common after COVID-19 than in the general population. Thromboembolic events were particularly common, and over 10-fold more so. More research is needed to contextualise post-COVID-19 complications in the longer term.

Funding

None.",,doi:https://doi.org/10.1016/j.eclinm.2023.101932; doi:https://doi.org/10.1016/j.eclinm.2023.101932; html:https://europepmc.org/articles/PMC10072853; pdf:https://europepmc.org/articles/PMC10072853?pdf=render 35531432,https://doi.org/10.1016/s2666-7568(22)00093-9,"Outcomes of SARS-CoV-2 omicron infection in residents of long-term care facilities in England (VIVALDI): a prospective, cohort study.","Krutikov M, Stirrup O, Nacer-Laidi H, Azmi B, Fuller C, Tut G, Palmer T, Shrotri M, Irwin-Singer A, Baynton V, Hayward A, Moss P, Copas A, Shallcross L, COVID-19 Genomics UK consortium.",,The lancet. Healthy longevity,2022,2022-05-04,Y,,,,"

Background

The SARS-CoV-2 omicron variant (B.1.1.529) is highly transmissible, but disease severity appears to be reduced compared with previous variants such as alpha and delta. We investigated the risk of severe outcomes following infection in residents of long-term care facilities.

Methods

We did a prospective cohort study in residents of long-term care facilities in England who were tested regularly for SARS-CoV-2 between Sept 1, 2021, and Feb 1, 2022, and who were participants of the VIVALDI study. Residents were eligible for inclusion if they had a positive PCR or lateral flow device test during the study period, which could be linked to a National Health Service (NHS) number, enabling linkage to hospital admissions and mortality datasets. PCR or lateral flow device test results were linked to national hospital admission and mortality records using the NHS-number-based pseudo-identifier. We compared the risk of hospital admission (within 14 days following a positive SARS-CoV-2 test) or death (within 28 days) in residents who had tested positive for SARS-CoV-2 in the period shortly before omicron emerged (delta-dominant) and in the omicron-dominant period, adjusting for age, sex, primary vaccine course, past infection, and booster vaccination. Variants were confirmed by sequencing or spike-gene status in a subset of samples.

Results

795 233 tests were done in 333 long-term care facilities, of which 159 084 (20·0%) could not be linked to a pseudo-identifier and 138 012 (17·4%) were done in residents. Eight residents had two episodes of infection (>28 days apart) and in these cases the second episode was excluded from the analysis. 2264 residents in 259 long-term care facilities (median age 84·5 years, IQR 77·9-90·0) were diagnosed with SARS-CoV-2, of whom 253 (11·2%) had a previous infection and 1468 (64·8%) had received a booster vaccination. About a third of participants were male. Risk of hospital admissions was markedly lower in the 1864 residents infected in the omicron-period (4·51%, 95% CI 3·65-5·55) than in the 400 residents infected in the pre-omicron period (10·50%, 7·87-13·94), as was risk of death (5·48% [4·52-6·64] vs 10·75% [8·09-14·22]). Adjusted hazard ratios (aHR) also indicated a reduction in hospital admissions (0·64, 95% CI 0·41-1·00; p=0·051) and mortality (aHR 0·68, 0·44-1·04; p=0·076) in the omicron versus the pre-omicron period. Findings were similar in residents with a confirmed variant.

Interpretation

Observed reduced severity of the omicron variant compared with previous variants suggests that the wave of omicron infections is unlikely to lead to a major surge in severe disease in long-term care facility populations with high levels of vaccine coverage or natural immunity. Continued surveillance in this vulnerable population is important to protect residents from infection and monitor the public health effect of emerging variants.

Funding

UK Department of Health and Social Care.",,pdf:http://www.thelancet.com/article/S2666756822000939/pdf; doi:https://doi.org/10.1016/S2666-7568(22)00093-9; html:https://europepmc.org/articles/PMC9067940; pdf:https://europepmc.org/articles/PMC9067940?pdf=render -37674175,https://doi.org/10.1186/s12884-023-05958-y,Using the COM-B framework to elucidate facilitators and barriers to COVID-19 vaccine uptake in pregnant women: a qualitative study.,"Patterson L, Berry E, Parsons C, Clarke B, Little A, Beggs J, Chuter A, Jackson T, Hsia Y, McGrath H, Millman C, Murphy S, Bradley DT, Milligan S.",,BMC pregnancy and childbirth,2023,2023-09-06,Y,Pregnancy; Qualitative; Barriers; Facilitators; Com-b; Covid-19 Vaccination,,,"Since April 2021, COVID-19 vaccines have been recommended for pregnant women. Despite this, COVID-19 vaccine uptake in this group is low compared to the non-pregnant population of childbearing age. Our aim was to understand barriers and facilitators to COVID-19 vaccine uptake among pregnant women in Northern Ireland using the COM-B framework, and so to make recommendations for public health interventions. The COM-B proposes that human behaviour is influenced by the extent to which a person has the capability, opportunity, and motivation to enact that behaviour. Understanding the factors underpinning behaviour through this lens helps discern what needs to change to change behaviour, therefore supporting the development of targeted interventions.This study consisted of eight semi-structured interviews with new/expectant mothers who did not receive a COVID-19 vaccine dose while pregnant since April 2021, and a focus group with five participants who received at least one COVID-19 vaccine dose while pregnant. Interview and focus group data were analysed using semi-deductive reflexive thematic analysis framed by a subtle realist approach. The COM-B was used to categorise codes and subthemes were developed within each COM-B construct.Within Psychological Capability, subthemes captured the need for consistent and reliable COVID-19 vaccine information and access to balanced and jargon-free, risk-benefit information that is tailored to the pregnant individual. The behaviour/opinions of family, friends, and local healthcare providers had a powerful influence on COVID-19 vaccine decisions (Social Opportunity). Integrating the COVID-19 vaccine as part of routine antenatal pathways was believed to support access and sense of familiarity (Physical Opportunity). Participants valued health autonomy, however experienced internal conflict driven by concerns about long-term side effects for their baby (Reflective Motivation). Feelings of fear, lack of empathy from healthcare providers, and anticipated guilt commonly underpinned indecision as to whether to get the vaccine (Automatic Motivation).Our study highlighted that the choice to accept a vaccine during pregnancy generates internal conflict and worry. Several participants cited their concern was primarily around the safety for their baby. Healthcare professionals (HCPs) play a significant part when it comes to decision making about COVID-19 vaccines among pregnant women. HCPs and pregnant women should be involved in the development of interventions to improve the delivery and communication of information.",,pdf:https://bmcpregnancychildbirth.biomedcentral.com/counter/pdf/10.1186/s12884-023-05958-y; doi:https://doi.org/10.1186/s12884-023-05958-y; html:https://europepmc.org/articles/PMC10481472; pdf:https://europepmc.org/articles/PMC10481472?pdf=render 33739254,https://doi.org/10.2807/1560-7917.es.2021.26.11.2100256,"Case fatality risk of the SARS-CoV-2 variant of concern B.1.1.7 in England, 16 November to 5 February.","Grint DJ, Wing K, Williamson E, McDonald HI, Bhaskaran K, Evans D, Evans SJ, Walker AJ, Hickman G, Nightingale E, Schultze A, Rentsch CT, Bates C, Cockburn J, Curtis HJ, Morton CE, Bacon S, Davy S, Wong AY, Mehrkar A, Tomlinson L, Douglas IJ, Mathur R, Blomquist P, MacKenna B, Ingelsby P, Croker R, Parry J, Hester F, Harper S, DeVito NJ, Hulme W, Tazare J, Goldacre B, Smeeth L, Eggo RM.",,Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin,2021,2021-03-01,Y,Mortality; Coronavirus; Cfr; Case Fatality Risk; Covid-19; Sars-cov-2; Variant Of Concern,,,The SARS-CoV-2 B.1.1.7 variant of concern (VOC) is increasing in prevalence across Europe. Accurate estimation of disease severity associated with this VOC is critical for pandemic planning. We found increased risk of death for VOC compared with non-VOC cases in England (hazard ratio: 1.67; 95% confidence interval: 1.34-2.09; p < 0.0001). Absolute risk of death by 28 days increased with age and comorbidities. This VOC has potential to spread faster with higher mortality than the pandemic to date.,,pdf:https://www.eurosurveillance.org/deliver/fulltext/eurosurveillance/26/11/eurosurv-26-11-2.pdf?itemId=%2Fcontent%2F10.2807%2F1560-7917.ES.2021.26.11.2100256&mimeType=pdf&containerItemId=content/eurosurveillance; doi:https://doi.org/10.2807/1560-7917.ES.2021.26.11.2100256; html:https://europepmc.org/articles/PMC7976383; pdf:https://europepmc.org/articles/PMC7976383?pdf=render +37674175,https://doi.org/10.1186/s12884-023-05958-y,Using the COM-B framework to elucidate facilitators and barriers to COVID-19 vaccine uptake in pregnant women: a qualitative study.,"Patterson L, Berry E, Parsons C, Clarke B, Little A, Beggs J, Chuter A, Jackson T, Hsia Y, McGrath H, Millman C, Murphy S, Bradley DT, Milligan S.",,BMC pregnancy and childbirth,2023,2023-09-06,Y,Pregnancy; Qualitative; Barriers; Facilitators; Com-b; Covid-19 Vaccination,,,"Since April 2021, COVID-19 vaccines have been recommended for pregnant women. Despite this, COVID-19 vaccine uptake in this group is low compared to the non-pregnant population of childbearing age. Our aim was to understand barriers and facilitators to COVID-19 vaccine uptake among pregnant women in Northern Ireland using the COM-B framework, and so to make recommendations for public health interventions. The COM-B proposes that human behaviour is influenced by the extent to which a person has the capability, opportunity, and motivation to enact that behaviour. Understanding the factors underpinning behaviour through this lens helps discern what needs to change to change behaviour, therefore supporting the development of targeted interventions.This study consisted of eight semi-structured interviews with new/expectant mothers who did not receive a COVID-19 vaccine dose while pregnant since April 2021, and a focus group with five participants who received at least one COVID-19 vaccine dose while pregnant. Interview and focus group data were analysed using semi-deductive reflexive thematic analysis framed by a subtle realist approach. The COM-B was used to categorise codes and subthemes were developed within each COM-B construct.Within Psychological Capability, subthemes captured the need for consistent and reliable COVID-19 vaccine information and access to balanced and jargon-free, risk-benefit information that is tailored to the pregnant individual. The behaviour/opinions of family, friends, and local healthcare providers had a powerful influence on COVID-19 vaccine decisions (Social Opportunity). Integrating the COVID-19 vaccine as part of routine antenatal pathways was believed to support access and sense of familiarity (Physical Opportunity). Participants valued health autonomy, however experienced internal conflict driven by concerns about long-term side effects for their baby (Reflective Motivation). Feelings of fear, lack of empathy from healthcare providers, and anticipated guilt commonly underpinned indecision as to whether to get the vaccine (Automatic Motivation).Our study highlighted that the choice to accept a vaccine during pregnancy generates internal conflict and worry. Several participants cited their concern was primarily around the safety for their baby. Healthcare professionals (HCPs) play a significant part when it comes to decision making about COVID-19 vaccines among pregnant women. HCPs and pregnant women should be involved in the development of interventions to improve the delivery and communication of information.",,pdf:https://bmcpregnancychildbirth.biomedcentral.com/counter/pdf/10.1186/s12884-023-05958-y; doi:https://doi.org/10.1186/s12884-023-05958-y; html:https://europepmc.org/articles/PMC10481472; pdf:https://europepmc.org/articles/PMC10481472?pdf=render 35538704,https://doi.org/10.1177/1357633x221093434,"The development, validation and application of remote blood sample collection in telehealth programmes.","Koulman A, Rennie KL, Parkington D, Tyrrell CS, Catt M, Gkrania-Klotsas E, Wareham NJ.",,Journal of telemedicine and telecare,2024,2022-05-10,Y,Pathology; Self-care; Telehealth; Blood Sampling; Home Telecare,,,"

Introduction

The ability to collect blood samples remotely without the involvement of healthcare professionals is a key element of future telehealth applications. We developed and validated the application of the Drawbridge OneDraw device for use at home for blood sample collection. The device was then applied in a large population-based remote monitoring study to assess changes in SARS-CoV-2 IgG antibody levels.

Methods

We tested: (1) feasibility of participants using the device at home without a healthcare professional on the upper arm and thigh sites (2) stability of the dried blood sample collected remotely (3) participant acceptability of the device compared with finger-prick and venous blood samples and the validity of SARS-CoV-2 virus antibody measurement versus venous blood sample (4) application to the Fenland COVID-19 study in which 4023 participants at 3 timepoints across 6 months.

Results

Participant acceptability was high, with a significantly lower median perceived pain score and 76% of participants preferring the OneDraw device over the other blood collection methods. There was high level of agreement in SARS-CoV-2 virus antibody results with venous blood samples in 120 participants (Cohen's kappa 0.68 (95% CI 0.56, 0.83). In the Fenland COVID-19 study, 92% of participants returned a sample at baseline (3702/4023), 89% at 3 months (3492/3918) and 93% at 6 months (3453/3731), with almost all samples received successfully processed (99.9%).

Discussion

The OneDraw device enables a standardised blood sample collection at home by participants themselves. Due to its ease-of-use and acceptability the OneDraw device is particularly useful in telehealth approaches where multiple samples need to be collected.",,pdf:https://journals.sagepub.com/doi/pdf/10.1177/1357633X221093434; doi:https://doi.org/10.1177/1357633X221093434; html:https://europepmc.org/articles/PMC11027437; pdf:https://europepmc.org/articles/PMC11027437?pdf=render 36680646,https://doi.org/10.1007/s10654-022-00962-6,Characterising patterns of COVID-19 and long COVID symptoms: evidence from nine UK longitudinal studies.,"Bowyer RCE, Huggins C, Toms R, Shaw RJ, Hou B, Thompson EJ, Kwong ASF, Williams DM, Kibble M, Ploubidis GB, Timpson NJ, Sterne JAC, Chaturvedi N, Steves CJ, Tilling K, Silverwood RJ, CONVALESCENCE Study.",,European journal of epidemiology,2023,2023-01-21,Y,Clustering; Longitudinal Studies; Symptom Patterns; Covid-19; Long Covid,,,"Multiple studies across global populations have established the primary symptoms characterising Coronavirus Disease 2019 (COVID-19) and long COVID. However, as symptoms may also occur in the absence of COVID-19, a lack of appropriate controls has often meant that specificity of symptoms to acute COVID-19 or long COVID, and the extent and length of time for which they are elevated after COVID-19, could not be examined. We analysed individual symptom prevalences and characterised patterns of COVID-19 and long COVID symptoms across nine UK longitudinal studies, totalling over 42,000 participants. Conducting latent class analyses separately in three groups ('no COVID-19', 'COVID-19 in last 12 weeks', 'COVID-19 > 12 weeks ago'), the data did not support the presence of more than two distinct symptom patterns, representing high and low symptom burden, in each group. Comparing the high symptom burden classes between the 'COVID-19 in last 12 weeks' and 'no COVID-19' groups we identified symptoms characteristic of acute COVID-19, including loss of taste and smell, fatigue, cough, shortness of breath and muscle pains or aches. Comparing the high symptom burden classes between the 'COVID-19 > 12 weeks ago' and 'no COVID-19' groups we identified symptoms characteristic of long COVID, including fatigue, shortness of breath, muscle pain or aches, difficulty concentrating and chest tightness. The identified symptom patterns among individuals with COVID-19 > 12 weeks ago were strongly associated with self-reported length of time unable to function as normal due to COVID-19 symptoms, suggesting that the symptom pattern identified corresponds to long COVID. Building the evidence base regarding typical long COVID symptoms will improve diagnosis of this condition and the ability to elicit underlying biological mechanisms, leading to better patient access to treatment and services.",,pdf:https://link.springer.com/content/pdf/10.1007/s10654-022-00962-6.pdf; doi:https://doi.org/10.1007/s10654-022-00962-6; html:https://europepmc.org/articles/PMC9860244; pdf:https://europepmc.org/articles/PMC9860244?pdf=render 34345715,https://doi.org/10.23889/ijpds.v5i4.1656,Establishing the impact of COVID-19 on the health outcomes of domiciliary care workers in Wales using routine data: a protocol for the OSCAR study.,"Lugg-Widger F, Cannings-John R, Akbari A, Brookes-Howell L, Hood K, John A, Jones H, Prout H, Schoenbuchner S, Thomas D, Robling M.",,International journal of population data science,2020,2020-01-01,Y,Mortality; Administrative Data; Natural Experiment; Domiciliary Care Worker; Covid-19,,,"

Introduction

Domiciliary care workers (DCWs) continued providing social care to adults in their own homes throughout the COVID-19 pandemic. Evidence of the impact of COVID-19 on health outcomes of DCWs is currently mixed, probably reflecting methodological limitations of existing studies. The risk of COVID-19 to workers providing care in people's homes remains unknown.

Objectives

To quantify the impact of COVID-19 upon health outcomes of DCWs in Wales, to explore causes of variation, and to extrapolate to the rest of the UK DCW population.

Methods

Mixed methods design comprising cohort study of DCWs and exploratory qualitative interviews. Data for all registered DCWs in Wales is available via the SAIL Databank using a secured, privacy-protecting encrypted anonymisation process. Occupational registration data for DCWs working during the pandemic will be combined with EHR outcome data within the SAIL Databank including clinical codes that identify suspected and confirmed COVID-19 cases. We will report rates of suspected and confirmed COVID-19 infections and key health outcomes including mortality and explore variation (by factors such as age, sex, ethnicity, deprivation quintile, rurality, employer, comorbidities) using regression modelling, adjusting for clustering of outcome within Health Board, region and employer. A maximum variation sample of Welsh DCWs will be approached for qualitative interview using a strategy to include participants that vary across factors such as sex, age, ethnicity and employer. The interviews will inform the quantitative analysis modelling. We will generalise the quantitative findings to other UK nations.

Discussion

Using anonymised linked occupational and EHR data and qualitative interviews, the OSCAR study will quantify the risk of COVID-19 on DCWs' health and explore sources of variation. This will provide a secure base for informing public health policy and occupational guidance.",,pdf:https://ijpds.org/article/download/1656/3219; doi:https://doi.org/10.23889/ijpds.v5i4.1656; html:https://europepmc.org/articles/PMC8280712; pdf:https://europepmc.org/articles/PMC8280712?pdf=render @@ -260,9 +260,9 @@ PMC9023380,https://doi.org/,Assessing the spread risk of COVID-19 associated wit 34596018,https://doi.org/10.2807/1560-7917.es.2021.26.39.2001440,"Strategies to reduce the risk of SARS-CoV-2 importation from international travellers: modelling estimations for the United Kingdom, July 2020.","Clifford S, Quilty BJ, Russell TW, Liu Y, Chan YD, Pearson CAB, Eggo RM, Endo A, CMMID COVID-19 Working Group, Flasche S, Edmunds WJ, Centre for Mathematical Modelling of Infectious Diseases (CMMID) COVID-19 Working Group.",,Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin,2021,2021-09-01,Y,Quarantine; Pcr Testing; Travel Screening; Covid-19; Sars-cov-2,,,"BackgroundTo mitigate SARS-CoV-2 transmission risks from international air travellers, many countries implemented a combination of up to 14 days of self-quarantine upon arrival plus PCR testing in the early stages of the COVID-19 pandemic in 2020.AimTo assess the effectiveness of quarantine and testing of international travellers to reduce risk of onward SARS-CoV-2 transmission into a destination country in the pre-COVID-19 vaccination era.MethodsWe used a simulation model of air travellers arriving in the United Kingdom from the European Union or the United States, incorporating timing of infection stages while varying quarantine duration and timing and number of PCR tests.ResultsQuarantine upon arrival with a PCR test on day 7 plus a 1-day delay for results can reduce the number of infectious arriving travellers released into the community by a median 94% (95% uncertainty interval (UI): 89-98) compared with a no quarantine/no test scenario. This reduction is similar to that achieved by a 14-day quarantine period (median > 99%; 95% UI: 98-100). Even shorter quarantine periods can prevent a substantial amount of transmission; all strategies in which travellers spend at least 5 days (mean incubation period) in quarantine and have at least one negative test before release are highly effective (median reduction 89%; 95% UI: 83-95)).ConclusionThe effect of different screening strategies impacts asymptomatic and symptomatic individuals differently. The choice of an optimal quarantine and testing strategy for unvaccinated air travellers may vary based on the number of possible imported infections relative to domestic incidence.",,pdf:https://www.eurosurveillance.org/deliver/fulltext/eurosurveillance/26/39/eurosurv-26-39-5.pdf?itemId=%2Fcontent%2F10.2807%2F1560-7917.ES.2021.26.39.2001440&mimeType=pdf&containerItemId=content/eurosurveillance; doi:https://doi.org/10.2807/1560-7917.ES.2021.26.39.2001440; html:https://europepmc.org/articles/PMC8485583; pdf:https://europepmc.org/articles/PMC8485583?pdf=render 37994361,https://doi.org/10.12688/gatesopenres.13654.1,"Higher mortality associated with the SARS-CoV-2 Delta variant in the Western Cape, South Africa, using RdRp target delay as a proxy: a cross-sectional study.","Hussey H, Davies MA, Heekes A, Williamson C, Valley-Omar Z, Hardie D, Korsman S, Doolabh D, Preiser W, Maponga T, Iranzadeh A, Engelbrecht S, Wasserman S, Schrueder N, Boloko L, Symons G, Raubenheimer P, Viljoen A, Parker A, Cohen C, Jasat W, Lessells R, Wilkinson RJ, Boulle A, Hsiao M.",,Gates open research,2022,2022-08-31,Y,DELTA; South Africa; Clinical Severity; Sars-cov-2; B.1.617.2; Rdrp Target Delay,,,"Background: The SARS-CoV-2 Delta variant (B.1.617.2) has been associated with more severe disease, particularly when compared to the Alpha variant. Most of this data, however, is from high income countries and less is understood about the variant's disease severity in other settings, particularly in an African context, and when compared to the Beta variant. Methods: A novel proxy marker, RNA-dependent RNA polymerase (RdRp) target delay in the Seegene Allplex TM 2019-nCoV (polymerase chain reaction) PCR assay, was used to identify suspected Delta variant infection in routine laboratory data. All cases diagnosed on this assay in the public sector in the Western Cape, South Africa, from 1 April to 31 July 2021, were included in the dataset provided by the Western Cape Provincial Health Data Centre (PHDC). The PHDC collates information on all COVID-19 related laboratory tests, hospital admissions and deaths for the province. Odds ratios for the association between the proxy marker and death were calculated, adjusted for prior diagnosed infection and vaccination status. Results: A total of 11,355 cases with 700 deaths were included in this study. RdRp target delay (suspected Delta variant) was associated with higher mortality (adjusted odds ratio [aOR] 1.45; 95% confidence interval [CI]: 1.13-1.86), compared to presumptive Beta infection. Prior diagnosed infection during the previous COVID-19 wave, which was driven by the Beta variant, was protective (aOR 0.32; 95%CI: 0.11-0.92) as was vaccination (aOR [95%CI] 0.15 [0.03-0.62] for complete vaccination [≥28 days post a single dose of Ad26.COV2.S or ≥14 days post second BNT162b2 dose]). Conclusion: RdRp target delay, a proxy for infection with the Delta variant, is associated with an increased risk of mortality amongst those who were tested for COVID-19 in our setting.",,doi:https://doi.org/10.12688/gatesopenres.13654.1; html:https://europepmc.org/articles/PMC10663174; pdf:https://europepmc.org/articles/PMC10663174?pdf=render 32735547,https://doi.org/10.2196/20169,Can Robots Improve Testing Capacity for SARS-CoV-2?,"Cresswell K, Ramalingam S, Sheikh A.",,Journal of medical Internet research,2020,2020-08-12,Y,Virus; Infectious disease; Testing; Robotics; Pandemic; Covid-19; Sars-cov-2,,,"There is currently increasing interest internationally in deploying robotic applications for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing, as these can help to reduce the risk of transmission of the virus to health care staff and patients. We provide an overview of key recent developments in this area. We argue that, although there is some potential for deploying robots to help with SARS-CoV-2 testing, the potential of patient-facing applications is likely to be limited. This is due to the high costs associated with patient-facing functionality, and risks of potentially adverse impacts on health care staff work practices and patient interactions. In contrast, back-end laboratory-based robots dealing with sample extraction and amplification, that effectively integrate with established processes, software, and interfaces to process samples, are much more likely to result in safety and efficiency gains. Consideration should therefore be given to deploying these at scale.",,pdf:https://www.jmir.org/2020/8/e20169/PDF; doi:https://doi.org/10.2196/20169; html:https://europepmc.org/articles/PMC7450371 -36849590,https://doi.org/10.1038/s41562-023-01522-y,Changes in preterm birth and stillbirth during COVID-19 lockdowns in 26 countries.,"Calvert C, Brockway MM, Zoega H, Miller JE, Been JV, Amegah AK, Racine-Poon A, Oskoui SE, Abok II, Aghaeepour N, Akwaowo CD, Alshaikh BN, Ayede AI, Bacchini F, Barekatain B, Barnes R, Bebak K, Berard A, Bhutta ZA, Brook JR, Bryan LR, Cajachagua-Torres KN, Campbell-Yeo M, Chu DT, Connor KL, Cornette L, Cortés S, Daly M, Debauche C, Dedeke IOF, Einarsdóttir K, Engjom H, Estrada-Gutierrez G, Fantasia I, Fiorentino NM, Franklin M, Fraser A, Gachuno OW, Gallo LA, Gissler M, Håberg SE, Habibelahi A, Häggström J, Hookham L, Hui L, Huicho L, Hunter KJ, Huq S, Kc A, Kadambari S, Kelishadi R, Khalili N, Kippen J, Le Doare K, Llorca J, Magee LA, Magnus MC, Man KKC, Mburugu PM, Mediratta RP, Morris AD, Muhajarine N, Mulholland RH, Bonnard LN, Nakibuuka V, Nassar N, Nyadanu SD, Oakley L, Oladokun A, Olayemi OO, Olutekunbi OA, Oluwafemi RO, Ogunkunle TO, Orton C, Örtqvist AK, Ouma J, Oyapero O, Palmer KR, Pedersen LH, Pereira G, Pereyra I, Philip RK, Pruski D, Przybylski M, Quezada-Pinedo HG, Regan AK, Rhoda NR, Rihs TA, Riley T, Rocha TAH, Rolnik DL, Saner C, Schneuer FJ, Souter VL, Stephansson O, Sun S, Swift EM, Szabó M, Temmerman M, Tooke L, Urquia ML, von Dadelszen P, Wellenius GA, Whitehead C, Wong ICK, Wood R, Wróblewska-Seniuk K, Yeboah-Antwi K, Yilgwan CS, Zawiejska A, Sheikh A, Rodriguez N, Burgner D, Stock SJ, Azad MB.",,Nature human behaviour,2023,2023-02-27,Y,,,,"Preterm birth (PTB) is the leading cause of infant mortality worldwide. Changes in PTB rates, ranging from -90% to +30%, were reported in many countries following early COVID-19 pandemic response measures ('lockdowns'). It is unclear whether this variation reflects real differences in lockdown impacts, or perhaps differences in stillbirth rates and/or study designs. Here we present interrupted time series and meta-analyses using harmonized data from 52 million births in 26 countries, 18 of which had representative population-based data, with overall PTB rates ranging from 6% to 12% and stillbirth ranging from 2.5 to 10.5 per 1,000 births. We show small reductions in PTB in the first (odds ratio 0.96, 95% confidence interval 0.95-0.98, P value <0.0001), second (0.96, 0.92-0.99, 0.03) and third (0.97, 0.94-1.00, 0.09) months of lockdown, but not in the fourth month of lockdown (0.99, 0.96-1.01, 0.34), although there were some between-country differences after the first month. For high-income countries in this study, we did not observe an association between lockdown and stillbirths in the second (1.00, 0.88-1.14, 0.98), third (0.99, 0.88-1.12, 0.89) and fourth (1.01, 0.87-1.18, 0.86) months of lockdown, although we have imprecise estimates due to stillbirths being a relatively rare event. We did, however, find evidence of increased risk of stillbirth in the first month of lockdown in high-income countries (1.14, 1.02-1.29, 0.02) and, in Brazil, we found evidence for an association between lockdown and stillbirth in the second (1.09, 1.03-1.15, 0.002), third (1.10, 1.03-1.17, 0.003) and fourth (1.12, 1.05-1.19, <0.001) months of lockdown. With an estimated 14.8 million PTB annually worldwide, the modest reductions observed during early pandemic lockdowns translate into large numbers of PTB averted globally and warrant further research into causal pathways.",,pdf:https://www.nature.com/articles/s41562-023-01522-y.pdf; doi:https://doi.org/10.1038/s41562-023-01522-y; html:https://europepmc.org/articles/PMC10129868; pdf:https://europepmc.org/articles/PMC10129868?pdf=render 35133177,https://doi.org/10.1126/science.abn8347,Rapid increase in Omicron infections in England during December 2021: REACT-1 study.,"Elliott P, Bodinier B, Eales O, Wang H, Haw D, Elliott J, Whitaker M, Jonnerby J, Tang D, Walters CE, Atchison C, Diggle PJ, Page AJ, Trotter AJ, Ashby D, Barclay W, Taylor G, Ward H, Darzi A, Cooke GS, Chadeau-Hyam M, Donnelly CA.",,"Science (New York, N.Y.)",2022,2022-02-08,Y,,,,"The unprecedented rise in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections during December 2021 was concurrent with rapid spread of the Omicron variant in England and globally. We analyzed the prevalence of SARS-CoV-2 and its dynamics in England from the end of November to mid-December 2021 among almost 100,000 participants in the REACT-1 study. Prevalence was high with rapid growth nationally and particularly in London during December 2021, with an increasing proportion of infections due to Omicron. We observed large decreases in swab positivity among mostly vaccinated older children (12 to 17 years) relative to unvaccinated younger children (5 to 11 years), and in adults who received a third (booster) vaccine dose versus two doses. Our results reinforce the importance of vaccination and booster campaigns, although additional measures have been needed to control the rapid growth of the Omicron variant.",,pdf:http://spiral.imperial.ac.uk/bitstream/10044/1/94586/2/science.abn8347.pdf; doi:https://doi.org/10.1126/science.abn8347; html:https://europepmc.org/articles/PMC8939772; pdf:https://europepmc.org/articles/PMC8939772?pdf=render 35440446,https://doi.org/10.1136/bmjopen-2021-052514,Protocol for the COG-UK hospital-onset COVID-19 infection (HOCI) multicentre interventional clinical study: evaluating the efficacy of rapid genome sequencing of SARS-CoV-2 in limiting the spread of COVID-19 in UK NHS hospitals.,"Blackstone J, Stirrup O, Mapp F, Panca M, Copas A, Flowers P, Hockey L, Price J, Partridge D, Peters C, de Silva T, Nebbia G, Snell LB, McComish R, COVID-19 Genomics UK (COG-UK) Consortium, Breuer J.",,BMJ open,2022,2022-04-19,Y,Molecular biology; Infection control; epidemiology; Covid-19,,,"

Objectives

Nosocomial transmission of SARS-CoV-2 has been a significant cause of mortality in National Health Service (NHS) hospitals during the COVID-19 pandemic. The COG-UK Consortium Hospital-Onset COVID-19 Infections (COG-UK HOCI) study aims to evaluate whether the use of rapid whole-genome sequencing of SARS-CoV-2, supported by a novel probabilistic reporting methodology, can inform infection prevention and control (IPC) practice within NHS hospital settings.

Design

Multicentre, prospective, interventional, superiority study.

Setting

14 participating NHS hospitals over winter-spring 2020/2021 in the UK.

Participants

Eligible patients must be admitted to hospital with first-confirmed SARS-CoV-2 PCR-positive test result >48 hour from time of admission, where COVID-19 diagnosis not suspected on admission. The projected sample size is 2380 patients.

Intervention

The intervention is the return of a sequence report, within 48 hours in one phase (rapid local lab processing) and within 5-10 days in a second phase (mimicking central lab), comparing the viral genome from an eligible study participant with others within and outside the hospital site.

Primary and secondary outcome measures

The primary outcomes are incidence of Public Health England (PHE)/IPC-defined SARS-CoV-2 hospital-acquired infection during the baseline and two interventional phases, and proportion of hospital-onset cases with genomic evidence of transmission linkage following implementation of the intervention where such linkage was not suspected by initial IPC investigation. Secondary outcomes include incidence of hospital outbreaks, with and without sequencing data; actual and desirable changes to IPC actions; periods of healthcare worker (HCW) absence. Health economic analysis will be conducted to determine cost benefit of the intervention. A process evaluation using qualitative interviews with HCWs will be conducted alongside the study.

Trial registration number

ISRCTN50212645. Pre-results stage. This manuscript is based on protocol V.6.0. 2 September 2021.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/4/e052514.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-052514; html:https://europepmc.org/articles/PMC9019828; pdf:https://europepmc.org/articles/PMC9019828?pdf=render +36849590,https://doi.org/10.1038/s41562-023-01522-y,Changes in preterm birth and stillbirth during COVID-19 lockdowns in 26 countries.,"Calvert C, Brockway MM, Zoega H, Miller JE, Been JV, Amegah AK, Racine-Poon A, Oskoui SE, Abok II, Aghaeepour N, Akwaowo CD, Alshaikh BN, Ayede AI, Bacchini F, Barekatain B, Barnes R, Bebak K, Berard A, Bhutta ZA, Brook JR, Bryan LR, Cajachagua-Torres KN, Campbell-Yeo M, Chu DT, Connor KL, Cornette L, Cortés S, Daly M, Debauche C, Dedeke IOF, Einarsdóttir K, Engjom H, Estrada-Gutierrez G, Fantasia I, Fiorentino NM, Franklin M, Fraser A, Gachuno OW, Gallo LA, Gissler M, Håberg SE, Habibelahi A, Häggström J, Hookham L, Hui L, Huicho L, Hunter KJ, Huq S, Kc A, Kadambari S, Kelishadi R, Khalili N, Kippen J, Le Doare K, Llorca J, Magee LA, Magnus MC, Man KKC, Mburugu PM, Mediratta RP, Morris AD, Muhajarine N, Mulholland RH, Bonnard LN, Nakibuuka V, Nassar N, Nyadanu SD, Oakley L, Oladokun A, Olayemi OO, Olutekunbi OA, Oluwafemi RO, Ogunkunle TO, Orton C, Örtqvist AK, Ouma J, Oyapero O, Palmer KR, Pedersen LH, Pereira G, Pereyra I, Philip RK, Pruski D, Przybylski M, Quezada-Pinedo HG, Regan AK, Rhoda NR, Rihs TA, Riley T, Rocha TAH, Rolnik DL, Saner C, Schneuer FJ, Souter VL, Stephansson O, Sun S, Swift EM, Szabó M, Temmerman M, Tooke L, Urquia ML, von Dadelszen P, Wellenius GA, Whitehead C, Wong ICK, Wood R, Wróblewska-Seniuk K, Yeboah-Antwi K, Yilgwan CS, Zawiejska A, Sheikh A, Rodriguez N, Burgner D, Stock SJ, Azad MB.",,Nature human behaviour,2023,2023-02-27,Y,,,,"Preterm birth (PTB) is the leading cause of infant mortality worldwide. Changes in PTB rates, ranging from -90% to +30%, were reported in many countries following early COVID-19 pandemic response measures ('lockdowns'). It is unclear whether this variation reflects real differences in lockdown impacts, or perhaps differences in stillbirth rates and/or study designs. Here we present interrupted time series and meta-analyses using harmonized data from 52 million births in 26 countries, 18 of which had representative population-based data, with overall PTB rates ranging from 6% to 12% and stillbirth ranging from 2.5 to 10.5 per 1,000 births. We show small reductions in PTB in the first (odds ratio 0.96, 95% confidence interval 0.95-0.98, P value <0.0001), second (0.96, 0.92-0.99, 0.03) and third (0.97, 0.94-1.00, 0.09) months of lockdown, but not in the fourth month of lockdown (0.99, 0.96-1.01, 0.34), although there were some between-country differences after the first month. For high-income countries in this study, we did not observe an association between lockdown and stillbirths in the second (1.00, 0.88-1.14, 0.98), third (0.99, 0.88-1.12, 0.89) and fourth (1.01, 0.87-1.18, 0.86) months of lockdown, although we have imprecise estimates due to stillbirths being a relatively rare event. We did, however, find evidence of increased risk of stillbirth in the first month of lockdown in high-income countries (1.14, 1.02-1.29, 0.02) and, in Brazil, we found evidence for an association between lockdown and stillbirth in the second (1.09, 1.03-1.15, 0.002), third (1.10, 1.03-1.17, 0.003) and fourth (1.12, 1.05-1.19, <0.001) months of lockdown. With an estimated 14.8 million PTB annually worldwide, the modest reductions observed during early pandemic lockdowns translate into large numbers of PTB averted globally and warrant further research into causal pathways.",,pdf:https://www.nature.com/articles/s41562-023-01522-y.pdf; doi:https://doi.org/10.1038/s41562-023-01522-y; html:https://europepmc.org/articles/PMC10129868; pdf:https://europepmc.org/articles/PMC10129868?pdf=render 36423925,https://doi.org/10.1136/thorax-2022-219591,Rebound in asthma exacerbations following relaxation of COVID-19 restrictions: a longitudinal population-based study (COVIDENCE UK).,"Tydeman F, Pfeffer PE, Vivaldi G, Holt H, Talaei M, Jolliffe D, Davies G, Lyons RA, Griffiths C, Kee F, Sheikh A, Shaheen SO, Martineau AR.",,Thorax,2023,2022-11-23,Y,Asthma; Covid-19,,,"

Background

The imposition of restrictions on social mixing early in the COVID-19 pandemic was followed by a reduction in asthma exacerbations in multiple settings internationally. Temporal trends in social mixing, incident acute respiratory infections (ARI) and asthma exacerbations following relaxation of COVID-19 restrictions have not yet been described.

Methods

We conducted a population-based longitudinal study in 2312 UK adults with asthma between November 2020 and April 2022. Details of face covering use, social mixing, incident ARI and severe asthma exacerbations were collected via monthly online questionnaires. Temporal changes in these parameters were visualised using Poisson generalised additive models. Multilevel logistic regression was used to test for associations between incident ARI and risk of asthma exacerbations, adjusting for potential confounders.

Results

Relaxation of COVID-19 restrictions from April 2021 coincided with reduced face covering use (p<0.001), increased frequency of indoor visits to public places and other households (p<0.001) and rising incidence of COVID-19 (p<0.001), non-COVID-19 ARI (p<0.001) and severe asthma exacerbations (p=0.007). Incident non-COVID-19 ARI associated independently with increased risk of asthma exacerbation (adjusted OR 5.75, 95% CI 4.75 to 6.97) as did incident COVID-19, both prior to emergence of the omicron variant of SARS-CoV-2 (5.89, 3.45 to 10.04) and subsequently (5.69, 3.89 to 8.31).

Conclusions

Relaxation of COVID-19 restrictions coincided with decreased face covering use, increased social mixing and a rebound in ARI and asthma exacerbations. Associations between incident ARI and risk of severe asthma exacerbation were similar for non-COVID-19 ARI and COVID-19, both before and after emergence of the SARS-CoV-2 omicron variant.

Study registration number

NCT04330599.",,pdf:https://thorax.bmj.com/content/thoraxjnl/early/2022/12/29/thorax-2022-219591.full.pdf; doi:https://doi.org/10.1136/thorax-2022-219591; html:https://europepmc.org/articles/PMC10359556; pdf:https://europepmc.org/articles/PMC10359556?pdf=render 34056579,https://doi.org/10.3389/frai.2021.652669,"The Promise of AI in Detection, Diagnosis, and Epidemiology for Combating COVID-19: Beyond the Hype.","Abdulkareem M, Petersen SE.",,Frontiers in artificial intelligence,2021,2021-05-14,Y,Artificial intelligence; Detection; Diagnosis; Medical imaging; epidemiology; Contact tracing; Social Control; Covid-19,,,"COVID-19 has created enormous suffering, affecting lives, and causing deaths. The ease with which this type of coronavirus can spread has exposed weaknesses of many healthcare systems around the world. Since its emergence, many governments, research communities, commercial enterprises, and other institutions and stakeholders around the world have been fighting in various ways to curb the spread of the disease. Science and technology have helped in the implementation of policies of many governments that are directed toward mitigating the impacts of the pandemic and in diagnosing and providing care for the disease. Recent technological tools, artificial intelligence (AI) tools in particular, have also been explored to track the spread of the coronavirus, identify patients with high mortality risk and diagnose patients for the disease. In this paper, areas where AI techniques are being used in the detection, diagnosis and epidemiological predictions, forecasting and social control for combating COVID-19 are discussed, highlighting areas of successful applications and underscoring issues that need to be addressed to achieve significant progress in battling COVID-19 and future pandemics. Several AI systems have been developed for diagnosing COVID-19 using medical imaging modalities such as chest CT and X-ray images. These AI systems mainly differ in their choices of the algorithms for image segmentation, classification and disease diagnosis. Other AI-based systems have focused on predicting mortality rate, long-term patient hospitalization and patient outcomes for COVID-19. AI has huge potential in the battle against the COVID-19 pandemic but successful practical deployments of these AI-based tools have so far been limited due to challenges such as limited data accessibility, the need for external evaluation of AI models, the lack of awareness of AI experts of the regulatory landscape governing the deployment of AI tools in healthcare, the need for clinicians and other experts to work with AI experts in a multidisciplinary context and the need to address public concerns over data collection, privacy, and protection. Having a dedicated team with expertise in medical data collection, privacy, access and sharing, using federated learning whereby AI scientists hand over training algorithms to the healthcare institutions to train models locally, and taking full advantage of biomedical data stored in biobanks can alleviate some of problems posed by these challenges. Addressing these challenges will ultimately accelerate the translation of AI research into practical and useful solutions for combating pandemics.",,pdf:https://www.frontiersin.org/articles/10.3389/frai.2021.652669/pdf; doi:https://doi.org/10.3389/frai.2021.652669; html:https://europepmc.org/articles/PMC8160471; pdf:https://europepmc.org/articles/PMC8160471?pdf=render 36503414,https://doi.org/10.1186/s12879-022-07856-8,"COVID-19 vaccination in pregnancy: views and vaccination uptake rates in pregnancy, a mixed methods analysis from SAIL and the Born-In-Wales Birth Cohort.","Mhereeg M, Jones H, Kennedy J, Seaborne M, Parker M, Kennedy N, Beeson S, Akbari A, Zuccolo L, Davies A, Brophy S.",,BMC infectious diseases,2022,2022-12-12,Y,Pregnancy; Vaccine Uptake; Vaccine Hesitancy; Sail; Covid-19 Vaccination,,,"

Background

Vaccine hesitancy amongst pregnant women has been found to be a concern during past epidemics. This study aimed to (1) estimate COVID-19 vaccination rates among pregnant women in Wales and their association with age, ethnicity, and area of deprivation, using electronic health record (EHR) data linkage, and (2) explore pregnant women's views on receiving the COVID-19 vaccine during pregnancy using data from a survey recruiting via social media (Facebook, Twitter), through midwives, and posters in hospitals (Born-In-Wales Cohort).

Methods

This was a mixed-methods study utilising routinely collected linked data from the Secure Anonymised Information Linkage (SAIL) Databank (Objective 1) and the Born-In-Wales Birth Cohort participants (Objective 2). Pregnant women were identified from 13th April 2021 to 31st December 2021. Survival analysis was utilised to examine and compare the length of time to vaccination uptake in pregnancy, and variation in uptake by; age, ethnic group, and deprivation area was examined using hazard ratios (HR) from Cox regression. Survey respondents were women who had a baby during the COVID-19 pandemic or were pregnant between 1st November 2021 and 24th March 2022 and participating in Born-In-Wales. Codebook thematic analysis was used to generate themes from an open-ended question on the survey.

Results

Population-level data linkage (objective 1): Within the population cohort, 8203 (32.7%) received at least one dose of the COVID-19 vaccine during pregnancy, 8572 (34.1%) remained unvaccinated throughout the follow-up period, and 8336 (33.2%) received the vaccine postpartum. Younger women (< 30 years) were less likely to have the vaccine, and those living in areas of high deprivation were also less likely to have the vaccine (HR = 0.88, 95% CI 0.82 to 0.95). Asian and Other ethnic groups were 1.12 and 1.18 times more likely to have the vaccine in pregnancy compared with White women (HR = 1.12, 95% CI 1.00 to 1.25) and (HR = 1.18, 95% CI 1.03 to 1.37) respectively. Survey responses (objective 2): 207 (69%) of participants stated that they would be happy to have the vaccine during pregnancy. The remaining 94 (31%) indicated they would not have the vaccine during pregnancy. Reasons for having the vaccine included protecting self and baby, perceived risk level, and receipt of sufficient evidence and advice. Reasons for vaccine refusal included lack of research about long-term outcomes for the baby, anxiety about vaccines, inconsistent advice/information, and preference to wait until after the pregnancy.

Conclusion

Potentially only 1 in 3 pregnant women would have the COVID-19 vaccine during pregnancy, even though 2 in 3 reported they would have the vaccination, thus it is critical to develop tailored strategies to increase its acceptance rate and decrease vaccine hesitancy. A targeted approach to vaccinations may be required for groups such as younger people and those living in higher deprivation areas.",,pdf:https://bmcinfectdis.biomedcentral.com/counter/pdf/10.1186/s12879-022-07856-8; doi:https://doi.org/10.1186/s12879-022-07856-8; html:https://europepmc.org/articles/PMC9742024; pdf:https://europepmc.org/articles/PMC9742024?pdf=render @@ -274,8 +274,8 @@ PMC9023380,https://doi.org/,Assessing the spread risk of COVID-19 associated wit 35673545,https://doi.org/10.12688/wellcomeopenres.17231.2,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody lateral flow assay for antibody prevalence studies following vaccination: a diagnostic accuracy study.,"Cann A, Clarke C, Brown J, Thomson T, Prendecki M, Moshe M, Badhan A, Simmons B, Klaber B, Elliott P, Darzi A, Riley S, Ashby D, Martin P, Gleeson S, Willicombe M, Kelleher P, Ward H, Barclay WS, Cooke GS.",,Wellcome open research,2021,2021-01-01,Y,Antibodies; Seroprevalence; Lateral Flow; Neutralisation; Lfia; Covid-19; Sars-cov-2,,,"Background: Lateral flow immunoassays (LFIAs) are able to achieve affordable, large scale antibody testing and provide rapid results without the support of central laboratories. As part of the development of the REACT programme extensive evaluation of LFIA performance was undertaken with individuals following natural infection. Here we assess the performance of the selected LFIA to detect antibody responses in individuals who have received at least one dose of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. Methods: This was a prospective diagnostic accuracy study. Sampling was carried out at renal outpatient clinic and healthcare worker testing sites at Imperial College London NHS Trust. Two cohorts of patients were recruited; the first was a cohort of 108 renal transplant patients attending clinic following two doses of SARS-CoV-2 vaccine, the second cohort comprised 40 healthcare workers attending for first SARS-CoV-2 vaccination and subsequent follow up. During the participants visit, finger-prick blood samples were analysed on LFIA device, while paired venous sampling was sent for serological assessment of antibodies to the spike protein (anti-S) antibodies. Anti-S IgG was detected using the Abbott Architect SARS-CoV-2 IgG Quant II CMIA. A total of 186 paired samples were collected. The accuracy of Fortress LFIA in detecting IgG antibodies to SARS-CoV-2 compared to anti-spike protein detection on Abbott Assay Results: The LFIA had an estimated sensitivity of 92.0% (114/124; 95% confidence interval [CI] 85.7% to 96.1%) and specificity of 93.6% (58/62; 95% CI 84.3% to 98.2%) using the Abbott assay as reference standard (using the threshold for positivity of 7.10 BAU/ml) Conclusions: Fortress LFIA performs well in the detection of antibody responses for intended purpose of population level surveillance but does not meet criteria for individual testing.",,doi:https://doi.org/10.12688/wellcomeopenres.17231.2; html:https://europepmc.org/articles/PMC9152464; pdf:https://europepmc.org/articles/PMC9152464?pdf=render 36773891,https://doi.org/10.1016/j.jinf.2023.02.012,"Real-world effectiveness of molnupiravir, nirmatrelvir-ritonavir, and sotrovimab on preventing hospital admission among higher-risk patients with COVID-19 in Wales: A retrospective cohort study.","Evans A, Qi C, Adebayo JO, Underwood J, Coulson J, Bailey R, Lyons R, Edwards A, Cooper A, John G, Akbari A.",,The Journal of infection,2023,2023-02-10,Y,Health protection; Public Health; Covid-19,,,"

Objective

To compare the effectiveness of molnupiravir, nirmatrelvir-ritonavir, and sotrovimab with no treatment in preventing hospital admission or death in higher-risk patients infected with SARS-CoV-2 in the community.

Design

Retrospective cohort study of non-hospitalized adult patients with COVID-19 using the Secure Anonymised Information Linkage (SAIL) Databank.

Setting

A real-world cohort study was conducted within the SAIL Databank (a secure trusted research environment containing anonymised, individual, population-scale electronic health record (EHR) data) for the population of Wales, UK.

Participants

Adult patients with COVID-19 in the community, at higher risk of hospitalization and death, testing positive for SARS-CoV-2 between 16th December 2021 and 22nd April 2022.

Interventions

Molnupiravir, nirmatrelvir-ritonavir, and sotrovimab given in the community by local health boards and the National Antiviral Service in Wales.

Main outcome measures

All-cause admission to hospital or death within 28 days of a positive test for SARS-CoV-2.

Statistical analysis

Cox proportional hazard model with treatment status (treated/untreated) as a time-dependent covariate and adjusted for age, sex, number of comorbidities, Welsh Index of Multiple Deprivation, and vaccination status. Secondary subgroup analyses were by treatment type, number of comorbidities, and before and on or after 20th February 2022, when omicron BA.1 and omicron BA.2 were the dominant subvariants in Wales.

Results

Between 16th December 2021 and 22nd April 2022, 7013 higher-risk patients were eligible for inclusion in the study. Of these, 2040 received treatment with molnupiravir (359, 17.6%), nirmatrelvir-ritonavir (602, 29.5%), or sotrovimab (1079, 52.9%). Patients in the treatment group were younger (mean age 53 vs 57 years), had fewer comorbidities, and a higher proportion had received four or more doses of the COVID-19 vaccine (36.3% vs 17.6%). Within 28 days of a positive test, 628 (9.0%) patients were admitted to hospital or died (84 treated and 544 untreated). The primary analysis indicated a lower risk of hospitalization or death at any point within 28 days in treated participants compared to those not receiving treatment. The adjusted hazard rate was 35% (95% CI: 18-49%) lower in treated than untreated participants. There was no indication of the superiority of one treatment over another and no evidence of a reduction in risk of hospitalization or death within 28 days for patients with no or only one comorbidity. In patients treated with sotrovimab, the event rates before and on or after 20th February 2022 were similar (5.0% vs 4.9%) with no significant difference in the hazard ratios for sotrovimab between the time periods.

Conclusions

In higher-risk adult patients in the community with COVID-19, those who received treatment with molnupiravir, nirmatrelvir-ritonavir, or sotrovimab were at lower risk of hospitalization or death than those not receiving treatment.",,pdf:http://www.journalofinfection.com/article/S0163445323000828/pdf; doi:https://doi.org/10.1016/j.jinf.2023.02.012; html:https://europepmc.org/articles/PMC9911979; pdf:https://europepmc.org/articles/PMC9911979?pdf=render 38166330,https://doi.org/10.1148/ryai.220266,The Scottish Medical Imaging Archive: 57.3 Million Radiology Studies Linked to Their Medical Records.,"Baxter R, Nind T, Sutherland J, McAllister G, Hardy D, Hume A, MacLeod R, Caldwell J, Krueger S, Tramma L, Teviotdale R, Gillen K, Scobbie D, Baillie I, Brooks A, Prodan B, Kerr W, Sloan-Murphy D, Herrera JFR, van Beek EJR, Reel PS, Reel S, Mansouri-Benssassi E, Mudie R, Steele D, Doney A, Trucco E, Morris C, Wallace R, Morris A, Parsons M, Jefferson E.",,Radiology. Artificial intelligence,2024,2024-01-01,Y,MRI; CT; ultrasound; angiography; Conventional Radiography; mammography; Imaging Sequences,,,"Keywords: MRI, Imaging Sequences, Ultrasound, Mammography, CT, Angiography, Conventional Radiography Published under a CC BY 4.0 license. See also the commentary by Whitman and Vining in this issue.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10831519; doi:https://doi.org/10.1148/ryai.220266; html:https://europepmc.org/articles/PMC10831519; pdf:https://europepmc.org/articles/PMC10831519?pdf=render -36882868,https://doi.org/10.1186/s12916-023-02784-z,"Assessing the impacts of COVID-19 vaccination programme's timing and speed on health benefits, cost-effectiveness, and relative affordability in 27 African countries.","Liu Y, Procter SR, Pearson CAB, Montero AM, Torres-Rueda S, Asfaw E, Uzochukwu B, Drake T, Bergren E, Eggo RM, Ruiz F, Ndembi N, Nonvignon J, Jit M, Vassall A.",,BMC medicine,2023,2023-03-08,Y,Mathematical models; Vaccination; Economic evaluation; decision-making; Affordability; Programme Evaluation; Public Health Interventions; Covid-19 | Sars-cov-2,,,"

Background

The COVID-19 vaccine supply shortage in 2021 constrained roll-out efforts in Africa while populations experienced waves of epidemics. As supply improves, a key question is whether vaccination remains an impactful and cost-effective strategy given changes in the timing of implementation.

Methods

We assessed the impact of vaccination programme timing using an epidemiological and economic model. We fitted an age-specific dynamic transmission model to reported COVID-19 deaths in 27 African countries to approximate existing immunity resulting from infection before substantial vaccine roll-out. We then projected health outcomes (from symptomatic cases to overall disability-adjusted life years (DALYs) averted) for different programme start dates (01 January to 01 December 2021, n = 12) and roll-out rates (slow, medium, fast; 275, 826, and 2066 doses/million population-day, respectively) for viral vector and mRNA vaccines by the end of 2022. Roll-out rates used were derived from observed uptake trajectories in this region. Vaccination programmes were assumed to prioritise those above 60 years before other adults. We collected data on vaccine delivery costs, calculated incremental cost-effectiveness ratios (ICERs) compared to no vaccine use, and compared these ICERs to GDP per capita. We additionally calculated a relative affordability measure of vaccination programmes to assess potential nonmarginal budget impacts.

Results

Vaccination programmes with early start dates yielded the most health benefits and lowest ICERs compared to those with late starts. While producing the most health benefits, fast vaccine roll-out did not always result in the lowest ICERs. The highest marginal effectiveness within vaccination programmes was found among older adults. High country income groups, high proportions of populations over 60 years or non-susceptible at the start of vaccination programmes are associated with low ICERs relative to GDP per capita. Most vaccination programmes with small ICERs relative to GDP per capita were also relatively affordable.

Conclusion

Although ICERs increased significantly as vaccination programmes were delayed, programmes starting late in 2021 may still generate low ICERs and manageable affordability measures. Looking forward, lower vaccine purchasing costs and vaccines with improved efficacies can help increase the economic value of COVID-19 vaccination programmes.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-023-02784-z; doi:https://doi.org/10.1186/s12916-023-02784-z; html:https://europepmc.org/articles/PMC9991879; pdf:https://europepmc.org/articles/PMC9991879?pdf=render 32564639,https://doi.org/10.1177/0300060520931298,Mortality statistics in England and Wales: the SARS-CoV-2 paradox.,"Harrison G, Newport D, Robbins T, Arvanitis TN, Stein A.",,The Journal of international medical research,2020,2020-06-01,Y,Respiratory disease; United Kingdom; Mortality Rate; Paradox; Covid-19; Sars-cov-2,,,"

Objective

To analyse mortality statistics in the United Kingdom during the initial phases of the severe acute respiratory coronavirus 2 (SARS-CoV-2) pandemic and to understand the impact of the pandemic on national mortality.

Methods

Retrospective review of weekly national mortality statistics in the United Kingdom over the past 5 years, including subgroup analysis of respiratory mortality rates.

Results

During the early phases of the SARS-CoV-2 pandemic in the first months of 2020, there were consistently fewer deaths per week compared with the preceding 5 years. This pattern was not observed at any other time within the past 5 years. We have termed this phenomenon the ""SARS-CoV-2 paradox."" We postulate potential explanations for this seeming paradox and explore the implications of these data.

Conclusions

Paradoxically, but potentially importantly, lower rather than higher weekly mortality rates were observed during the early stages of the SARS-CoV-2 pandemic. This paradox may have implications for current and future healthcare utilisation. A rebound increase in non-SARS-CoV-2 mortality later this year might coincide with the peak of SARS-CoV-2 admissions and mortality.",,doi:https://doi.org/10.1177/0300060520931298; doi:https://doi.org/10.1177/0300060520931298; html:https://europepmc.org/articles/PMC7307394; pdf:https://europepmc.org/articles/PMC7307394?pdf=render +36882868,https://doi.org/10.1186/s12916-023-02784-z,"Assessing the impacts of COVID-19 vaccination programme's timing and speed on health benefits, cost-effectiveness, and relative affordability in 27 African countries.","Liu Y, Procter SR, Pearson CAB, Montero AM, Torres-Rueda S, Asfaw E, Uzochukwu B, Drake T, Bergren E, Eggo RM, Ruiz F, Ndembi N, Nonvignon J, Jit M, Vassall A.",,BMC medicine,2023,2023-03-08,Y,Mathematical models; Vaccination; Economic evaluation; decision-making; Affordability; Programme Evaluation; Public Health Interventions; Covid-19 | Sars-cov-2,,,"

Background

The COVID-19 vaccine supply shortage in 2021 constrained roll-out efforts in Africa while populations experienced waves of epidemics. As supply improves, a key question is whether vaccination remains an impactful and cost-effective strategy given changes in the timing of implementation.

Methods

We assessed the impact of vaccination programme timing using an epidemiological and economic model. We fitted an age-specific dynamic transmission model to reported COVID-19 deaths in 27 African countries to approximate existing immunity resulting from infection before substantial vaccine roll-out. We then projected health outcomes (from symptomatic cases to overall disability-adjusted life years (DALYs) averted) for different programme start dates (01 January to 01 December 2021, n = 12) and roll-out rates (slow, medium, fast; 275, 826, and 2066 doses/million population-day, respectively) for viral vector and mRNA vaccines by the end of 2022. Roll-out rates used were derived from observed uptake trajectories in this region. Vaccination programmes were assumed to prioritise those above 60 years before other adults. We collected data on vaccine delivery costs, calculated incremental cost-effectiveness ratios (ICERs) compared to no vaccine use, and compared these ICERs to GDP per capita. We additionally calculated a relative affordability measure of vaccination programmes to assess potential nonmarginal budget impacts.

Results

Vaccination programmes with early start dates yielded the most health benefits and lowest ICERs compared to those with late starts. While producing the most health benefits, fast vaccine roll-out did not always result in the lowest ICERs. The highest marginal effectiveness within vaccination programmes was found among older adults. High country income groups, high proportions of populations over 60 years or non-susceptible at the start of vaccination programmes are associated with low ICERs relative to GDP per capita. Most vaccination programmes with small ICERs relative to GDP per capita were also relatively affordable.

Conclusion

Although ICERs increased significantly as vaccination programmes were delayed, programmes starting late in 2021 may still generate low ICERs and manageable affordability measures. Looking forward, lower vaccine purchasing costs and vaccines with improved efficacies can help increase the economic value of COVID-19 vaccination programmes.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-023-02784-z; doi:https://doi.org/10.1186/s12916-023-02784-z; html:https://europepmc.org/articles/PMC9991879; pdf:https://europepmc.org/articles/PMC9991879?pdf=render 34599903,https://doi.org/10.1016/s2213-2600(21)00380-5,COVID-19 hospital admissions and deaths after BNT162b2 and ChAdOx1 nCoV-19 vaccinations in 2·57 million people in Scotland (EAVE II): a prospective cohort study.,"Agrawal U, Katikireddi SV, McCowan C, Mulholland RH, Azcoaga-Lorenzo A, Amele S, Fagbamigbe AF, Vasileiou E, Grange Z, Shi T, Kerr S, Moore E, Murray JLK, Shah SA, Ritchie L, O'Reilly D, Stock SJ, Beggs J, Chuter A, Torabi F, Akbari A, Bedston S, McMenamin J, Wood R, Tang RSM, de Lusignan S, Hobbs FDR, Woolhouse M, Simpson CR, Robertson C, Sheikh A.",,The Lancet. Respiratory medicine,2021,2021-09-29,Y,,,,"

Background

The UK COVID-19 vaccination programme has prioritised vaccination of those at the highest risk of COVID-19 mortality and hospitalisation. The programme was rolled out in Scotland during winter 2020-21, when SARS-CoV-2 infection rates were at their highest since the pandemic started, despite social distancing measures being in place. We aimed to estimate the frequency of COVID-19 hospitalisation or death in people who received at least one vaccine dose and characterise these individuals.

Methods

We conducted a prospective cohort study using the Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II) national surveillance platform, which contained linked vaccination, primary care, RT-PCR testing, hospitalisation, and mortality records for 5·4 million people (around 99% of the population) in Scotland. Individuals were followed up from receiving their first dose of the BNT162b2 (Pfizer-BioNTech) or ChAdOx1 nCoV-19 (Oxford-AstraZeneca) COVID-19 vaccines until admission to hospital for COVID-19, death, or the end of the study period on April 18, 2021. We used a time-dependent Poisson regression model to estimate rate ratios (RRs) for demographic and clinical factors associated with COVID-19 hospitalisation or death 14 days or more after the first vaccine dose, stratified by vaccine type.

Findings

Between Dec 8, 2020, and April 18, 2021, 2 572 008 individuals received their first dose of vaccine-841 090 (32·7%) received BNT162b2 and 1 730 918 (67·3%) received ChAdOx1. 1196 (<0·1%) individuals were admitted to hospital or died due to COVID-19 illness (883 hospitalised, of whom 228 died, and 313 who died due to COVID-19 without hospitalisation) 14 days or more after their first vaccine dose. These severe COVID-19 outcomes were associated with older age (≥80 years vs 18-64 years adjusted RR 4·75, 95% CI 3·85-5·87), comorbidities (five or more risk groups vs less than five risk groups 4·24, 3·34-5·39), hospitalisation in the previous 4 weeks (3·00, 2·47-3·65), high-risk occupations (ten or more previous COVID-19 tests vs less than ten previous COVID-19 tests 2·14, 1·62-2·81), care home residence (1·63, 1·32-2·02), socioeconomic deprivation (most deprived quintile vs least deprived quintile 1·57, 1·30-1·90), being male (1·27, 1·13-1·43), and being an ex-smoker (ex-smoker vs non-smoker 1·18, 1·01-1·38). A history of COVID-19 before vaccination was protective (0·40, 0·29-0·54).

Interpretation

COVID-19 hospitalisations and deaths were uncommon 14 days or more after the first vaccine dose in this national analysis in the context of a high background incidence of SARS-CoV-2 infection and with extensive social distancing measures in place. Sociodemographic and clinical features known to increase the risk of severe disease in unvaccinated populations were also associated with severe outcomes in people receiving their first dose of vaccine and could help inform case management and future vaccine policy formulation.

Funding

UK Research and Innovation (Medical Research Council), Research and Innovation Industrial Strategy Challenge Fund, Scottish Government, and Health Data Research UK.",,pdf:http://www.thelancet.com/article/S2213260021003805/pdf; doi:https://doi.org/10.1016/S2213-2600(21)00380-5; html:https://europepmc.org/articles/PMC8480963 32614817,https://doi.org/10.1371/journal.pcbi.1008031,Estimation of country-level basic reproductive ratios for novel Coronavirus (SARS-CoV-2/COVID-19) using synthetic contact matrices.,"Hilton J, Keeling MJ.",,PLoS computational biology,2020,2020-07-02,Y,,,,"The 2019-2020 pandemic of atypical pneumonia (COVID-19) caused by the virus SARS-CoV-2 has spread globally and has the potential to infect large numbers of people in every country. Estimating the country-specific basic reproductive ratio is a vital first step in public-health planning. The basic reproductive ratio (R0) is determined by both the nature of pathogen and the network of human contacts through which the disease can spread, which is itself dependent on population age structure and household composition. Here we introduce a transmission model combining age-stratified contact frequencies with age-dependent susceptibility, probability of clinical symptoms, and transmission from asymptomatic (or mild) cases, which we use to estimate the country-specific basic reproductive ratio of COVID-19 for 152 countries. Using early outbreak data from China and a synthetic contact matrix, we estimate an age-stratified transmission structure which can then be extrapolated to 151 other countries for which synthetic contact matrices also exist. This defines a set of country-specific transmission structures from which we can calculate the basic reproductive ratio for each country. Our predicted R0 is critically sensitive to the intensity of transmission from asymptomatic cases; with low asymptomatic transmission the highest values are predicted across Eastern Europe and Japan and the lowest across Africa, Central America and South-Western Asia. This pattern is largely driven by the ratio of children to older adults in each country and the observed propensity of clinical cases in the elderly. If asymptomatic cases have comparable transmission to detected cases, the pattern is reversed. Our results demonstrate the importance of age-specific heterogeneities going beyond contact structure to the spread of COVID-19. These heterogeneities give COVID-19 the capacity to spread particularly quickly in countries with older populations, and that intensive control measures are likely to be necessary to impede its progress in these countries.",,pdf:https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1008031&type=printable; doi:https://doi.org/10.1371/journal.pcbi.1008031; html:https://europepmc.org/articles/PMC7363110; pdf:https://europepmc.org/articles/PMC7363110?pdf=render 32485082,https://doi.org/10.1002/ejhf.1924,Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers are not associated with severe COVID-19 infection in a multi-site UK acute hospital trust.,"Bean DM, Kraljevic Z, Searle T, Bendayan R, Kevin O, Pickles A, Folarin A, Roguski L, Noor K, Shek A, Zakeri R, Shah AM, Teo JTH, Dobson RJB.",,European journal of heart failure,2020,2020-06-01,Y,Hypertension; Angiotensin-converting enzyme inhibitors; Disease Outcome; Covid-19,,,"

Aims

The SARS-CoV-2 virus binds to the angiotensin-converting enzyme 2 (ACE2) receptor for cell entry. It has been suggested that angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB), which are commonly used in patients with hypertension or diabetes and may raise tissue ACE2 levels, could increase the risk of severe COVID-19 infection.

Methods and results

We evaluated this hypothesis in a consecutive cohort of 1200 acute inpatients with COVID-19 at two hospitals with a multi-ethnic catchment population in London (UK). The mean age was 68 ± 17 years (57% male) and 74% of patients had at least one comorbidity. Overall, 415 patients (34.6%) reached the primary endpoint of death or transfer to a critical care unit for organ support within 21 days of symptom onset. A total of 399 patients (33.3%) were taking ACEi or ARB. Patients on ACEi/ARB were significantly older and had more comorbidities. The odds ratio for the primary endpoint in patients on ACEi and ARB, after adjustment for age, sex and co-morbidities, was 0.63 (95% confidence interval 0.47-0.84, P < 0.01).

Conclusions

There was no evidence for increased severity of COVID-19 in hospitalised patients on chronic treatment with ACEi or ARB. A trend towards a beneficial effect of ACEi/ARB requires further evaluation in larger meta-analyses and randomised clinical trials.","This study aimed to determine whether or not two specific types of medication (ACE inhibitors and angiotensin-2 blockers - ACEi/ARB) used for hypertension or diabetes are associated with increased risk of severe COVID-19 infection in a sample of 1,200 inpatients (one third of whom were taking the medications under investigation) in two London hospitals. The researchers used data from electonic medical notes and electronic health records. The patients who were taking the medication were, on average, older and had more underlying health conditions than patients who were not. After accounting for these differences in patient health the researchers found that the risk of severe COVID infection was not higher for patients taking ACEi/ARB. This finding is important for patients because it suggests that they should continue to take ACEi/ARB that have been presecribed to them.",pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ejhf.1924; doi:https://doi.org/10.1002/ejhf.1924; html:https://europepmc.org/articles/PMC7301045; pdf:https://europepmc.org/articles/PMC7301045?pdf=render @@ -320,8 +320,8 @@ PMC9023380,https://doi.org/,Assessing the spread risk of COVID-19 associated wit 34598993,https://doi.org/10.1136/bmjopen-2021-054410,"Changes in neonatal admissions, care processes and outcomes in England and Wales during the COVID-19 pandemic: a whole population cohort study.","Greenbury SF, Longford N, Ougham K, Angelini ED, Battersby C, Uthaya S, Modi N.",,BMJ open,2021,2021-10-01,Y,Public Health; Neonatology; Neonatal Intensive & Critical Care,,,"

Objectives

The COVID-19 pandemic instigated multiple societal and healthcare interventions with potential to affect perinatal practice. We evaluated population-level changes in preterm and full-term admissions to neonatal units, care processes and outcomes.

Design

Observational cohort study using the UK National Neonatal Research Database.

Setting

England and Wales.

Participants

Admissions to National Health Service neonatal units from 2012 to 2020.

Main outcome measures

Admissions by gestational age, ethnicity and Index of Multiple Deprivation, and key care processes and outcomes.

Methods

We calculated differences in numbers and rates between April and June 2020 (spring), the first 3 months of national lockdown (COVID-19 period), and December 2019-February 2020 (winter), prior to introduction of mitigation measures, and compared them with the corresponding differences in the previous 7 years. We considered the COVID-19 period highly unusual if the spring-winter difference was smaller or larger than all previous corresponding differences, and calculated the level of confidence in this conclusion.

Results

Marked fluctuations occurred in all measures over the 8 years with several highly unusual changes during the COVID-19 period. Total admissions fell, having risen over all previous years (COVID-19 difference: -1492; previous 7-year difference range: +100, +1617; p<0.001); full-term black admissions rose (+66; -64, +35; p<0.001) whereas Asian (-137; -14, +101; p<0.001) and white (-319; -235, +643: p<0.001) admissions fell. Transfers to higher and lower designation neonatal units increased (+129; -4, +88; p<0.001) and decreased (-47; -25, +12; p<0.001), respectively. Total preterm admissions decreased (-350; -26, +479; p<0.001). The fall in extremely preterm admissions was most marked in the two lowest socioeconomic quintiles.

Conclusions

Our findings indicate substantial changes occurred in care pathways and clinical thresholds, with disproportionate effects on black ethnic groups, during the immediate COVID-19 period, and raise the intriguing possibility that non-healthcare interventions may reduce extremely preterm births.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/10/e054410.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-054410; html:https://europepmc.org/articles/PMC8488283; pdf:https://europepmc.org/articles/PMC8488283?pdf=render 32880390,https://doi.org/10.1210/clinem/dgaa627,"Systemic Corticosteroids and Mortality in Severe and Critical COVID-19 Patients in Wuhan, China.","Wu J, Huang J, Zhu G, Liu Y, Xiao H, Zhou Q, Si X, Yi H, Wang C, Yang D, Chen S, Liu X, Liu Z, Wang Q, Lv Q, Huang Y, Yu Y, Guan X, Li Y, Nirantharakumar K, Cheng K, Peng S, Xiao H.",,The Journal of clinical endocrinology and metabolism,2020,2020-12-01,Y,Mortality; Systemic Corticosteroids; Covid-19; Severe And Critical,,,"

Background

Systemic corticosteroids are now recommended in many treatment guidelines, although supporting evidence is limited to 1 randomized controlled clinical trial (RECOVERY).

Objective

To identify whether corticosteroids were beneficial to COVID-19 patients.

Methods

A total of 1514 severe and 249 critical hospitalized COVID-19 patients from 2 medical centers in Wuhan, China. Multivariable Cox models, Cox model with time-varying exposure and propensity score analysis (inverse-probability-of-treatment-weighting [IPTW] and propensity score matching [PSM]) were used to estimate the association of corticosteroid use with risk of in-hospital mortality in severe and critical cases.

Results

Corticosteroids were administered in 531 (35.1%) severe and 159 (63.9%) critical patients. Compared to the non-corticosteroid group, systemic corticosteroid use was not associated with beneficial effect in reducing in-hospital mortality in either severe cases (HR = 1.77; 95% CI, 1.08-2.89; P = 0.023), or critical cases (HR = 2.07; 95% CI, 1.08-3.98; P = 0.028). Findings were similar in time-varying Cox analysis. For patients with severe COVID-19 at admission, corticosteroid use was not associated with improved or harmful outcome in either PSM or IPTW analysis. For critical COVID-19 patients at admission, results were consistent with multivariable Cox model analysis.

Conclusion

Corticosteroid use was not associated with beneficial effect in reducing in-hospital mortality for severe or critical cases in Wuhan. Absence of the beneficial effect in our study in contrast to that observed in the RECOVERY clinical trial may be due to biases in observational data, in particular prescription by indication bias, differences in clinical characteristics of patients, choice of corticosteroid used, timing of initiation of treatment, and duration of treatment.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7499588; doi:https://doi.org/10.1210/clinem/dgaa627; html:https://europepmc.org/articles/PMC7499588; pdf:https://europepmc.org/articles/PMC7499588?pdf=render 35440465,https://doi.org/10.3399/bjgp.2021.0689,Association between oral anticoagulants and COVID-19-related outcomes: a population-based cohort study.,"Wong AY, Tomlinson L, Brown JP, Elson W, Walker AJ, Schultze A, Morton CE, Evans D, Inglesby P, MacKenna B, Bhaskaran K, Rentsch CT, Powell E, Williamson E, Croker R, Bacon S, Hulme W, Bates C, Curtis HJ, Mehrkar A, Cockburn J, McDonald HI, Mathur R, Wing K, Forbes H, Eggo RM, Evans SJ, Smeeth L, Goldacre B, Douglas IJ, (The OpenSAFELY Collaborative).",,The British journal of general practice : the journal of the Royal College of General Practitioners,2022,2022-06-30,Y,Warfarin; Factor Xa Inhibitors; Dabigatran; Covid-19,,,"

Background

Early evidence has shown that anticoagulant reduces the risk of thrombotic events in those infected with COVID-19. However, evidence of the role of routinely prescribed oral anticoagulants (OACs) in COVID-19 outcomes is limited.

Aim

To investigate the association between OACs and COVID-19 outcomes in those with atrial fibrillation and a CHA2DS2-VASc score of 2.

Design and setting

On behalf of NHS England, a population-based cohort study was conducted.

Method

The study used primary care data and pseudonymously-linked SARS-CoV-2 antigen testing data, hospital admissions, and death records from England. Cox regression was used to estimate hazard ratios (HRs) for COVID-19 outcomes comparing people with current OAC use versus non-use, accounting for age, sex, comorbidities, other medications, deprivation, and general practice.

Results

Of 71 103 people with atrial fibrillation and a CHA2DS2-VASc score of 2, there were 52 832 current OAC users and 18 271 non-users. No difference in risk of being tested for SARS-CoV-2 was associated with current use (adjusted HR [aHR] 0.99, 95% confidence interval [CI] = 0.95 to 1.04) versus non-use. A lower risk of testing positive for SARS-CoV-2 (aHR 0.77, 95% CI = 0.63 to 0.95) and a marginally lower risk of COVID-19-related death (aHR, 0.74, 95% CI = 0.53 to 1.04) were associated with current use versus non-use.

Conclusion

Among those at low baseline stroke risk, people receiving OACs had a lower risk of testing positive for SARS-CoV-2 and severe COVID-19 outcomes than non-users; this might be explained by a causal effect of OACs in preventing severe COVID-19 outcomes or unmeasured confounding, including more cautious behaviours leading to reduced infection risk.",,pdf:https://bjgp.org/content/bjgp/early/2022/04/19/BJGP.2021.0689.full.pdf; doi:https://doi.org/10.3399/BJGP.2021.0689; html:https://europepmc.org/articles/PMC9037187; pdf:https://europepmc.org/articles/PMC9037187?pdf=render -38192590,https://doi.org/10.1016/j.eclinm.2023.102321,Clinical and health inequality risk factors for non-COVID-related sepsis during the global COVID-19 pandemic: a national case-control and cohort study.,"Zhong X, Ashiru-Oredope D, Pate A, Martin GP, Sharma A, Dark P, Felton T, Lake C, MacKenna B, Mehrkar A, Bacon SCJ, Massey J, Inglesby P, Goldacre B, OpenSAFELY Collaborative, Hand K, Bladon S, Cunningham N, Gilham E, Brown CS, Mirfenderesky M, Palin V, van Staa TP.",,EClinicalMedicine,2023,2023-11-23,Y,Sepsis; Morbidity; Primary Care; Deprivation; Health Inequality; Covid-19 Pandemic,,,"

Background

Sepsis, characterised by significant morbidity and mortality, is intricately linked to socioeconomic disparities and pre-admission clinical histories. This study aspires to elucidate the association between non-COVID-19 related sepsis and health inequality risk factors amidst the pandemic in England, with a secondary focus on their association with 30-day sepsis mortality.

Methods

With the approval of NHS England, we harnessed the OpenSAFELY platform to execute a cohort study and a 1:6 matched case-control study. A sepsis diagnosis was identified from the incident hospital admissions record using ICD-10 codes. This encompassed 248,767 cases with non-COVID-19 sepsis from a cohort of 22.0 million individuals spanning January 1, 2019, to June 31, 2022. Socioeconomic deprivation was gauged using the Index of Multiple Deprivation score, reflecting indicators like income, employment, and education. Hospitalisation-related sepsis diagnoses were categorised as community-acquired or hospital-acquired. Cases were matched to controls who had no recorded diagnosis of sepsis, based on age (stepwise), sex, and calendar month. The eligibility criteria for controls were established primarily on the absence of a recorded sepsis diagnosis. Associations between potential predictors and odds of developing non-COVID-19 sepsis underwent assessment through conditional logistic regression models, with multivariable regression determining odds ratios (ORs) for 30-day mortality.

Findings

The study included 224,361 (10.2%) cases with non-COVID-19 sepsis and 1,346,166 matched controls. The most socioeconomic deprived quintile was associated with higher odds of developing non-COVID-19 sepsis than the least deprived quintile (crude OR 1.80 [95% CI 1.77-1.83]). Other risk factors (after adjusting comorbidities) such as learning disability (adjusted OR 3.53 [3.35-3.73]), chronic liver disease (adjusted OR 3.08 [2.97-3.19]), chronic kidney disease (stage 4: adjusted OR 2.62 [2.55-2.70], stage 5: adjusted OR 6.23 [5.81-6.69]), cancer, neurological disease, immunosuppressive conditions were also associated with developing non-COVID-19 sepsis. The incidence rate of non-COVID-19 sepsis decreased during the COVID-19 pandemic and rebounded to pre-pandemic levels (April 2021) after national lockdowns had been lifted. The 30-day mortality risk in cases with non-COVID-19 sepsis was higher for the most deprived quintile across all periods.

Interpretation

Socioeconomic deprivation, comorbidity and learning disabilities were associated with an increased odds of developing non-COVID-19 related sepsis and 30-day mortality in England. This study highlights the need to improve the prevention of sepsis, including more precise targeting of antimicrobials to higher-risk patients.

Funding

The UK Health Security Agency, Health Data Research UK, and National Institute for Health Research.",,doi:https://doi.org/10.1016/j.eclinm.2023.102321; html:https://europepmc.org/articles/PMC10772239; pdf:https://europepmc.org/articles/PMC10772239?pdf=render 34183342,https://doi.org/10.1136/bmjopen-2020-046392,"United Kingdom Research study into Ethnicity And COVID-19 outcomes in Healthcare workers (UK-REACH): a retrospective cohort study using linked routinely collected data, study protocol.","Teece L, Gray LJ, Melbourne C, Orton C, Ford DV, Martin CA, McAllister D, Khunti K, Tobin M, John C, Abrams KR, Pareek M, UK-REACH Study Collaborative Group.",,BMJ open,2021,2021-06-28,Y,epidemiology; Public Health; Adult Intensive & Critical Care; Covid-19,,,"

Introduction

COVID-19 has spread rapidly worldwide, causing significant morbidity and mortality. People from ethnic minorities, particularly those working in healthcare settings, have been disproportionately affected. Current evidence of the association between ethnicity and COVID-19 outcomes in people working in healthcare settings is insufficient to inform plans to address health inequalities.

Methods and analysis

This study combines anonymised human resource databases with professional registration and National Health Service data sets to assess associations between ethnicity and COVID-19 diagnosis, hospitalisation and death in healthcare workers in the UK. Adverse COVID-19 outcomes will be assessed between 1 February 2020 (date following first confirmed COVID-19 case in UK) and study end date (31 January 2021), allowing 1-year of follow-up. Planned analyses include multivariable Poisson, logistic and flexible parametric time-to-event regression within each country, adjusting for core predictors, followed by meta-analysis of country-specific results to produce combined effect estimates for the UK. Mediation analysis methods will be explored to examine the direct, indirect and mediated interactive effects between ethnicity, occupational group and COVID-19 outcomes.

Ethics and dissemination

Ethical approval for the UK-REACH programme has been obtained via the expedited HRA COVID-19 processes (REC ref: 20/HRA/4718, IRAS ID: 288316). Research information will be anonymised via the Secure Anonymised Information Linkage Databank before release to researchers. Study results will be submitted for publication in an open access peer-reviewed journal and made available on our dedicated website (https://uk-reach.org/).

Trial registration number

ISRCTN11811602.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/6/e046392.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-046392; html:https://europepmc.org/articles/PMC8245289; pdf:https://europepmc.org/articles/PMC8245289?pdf=render +38192590,https://doi.org/10.1016/j.eclinm.2023.102321,Clinical and health inequality risk factors for non-COVID-related sepsis during the global COVID-19 pandemic: a national case-control and cohort study.,"Zhong X, Ashiru-Oredope D, Pate A, Martin GP, Sharma A, Dark P, Felton T, Lake C, MacKenna B, Mehrkar A, Bacon SCJ, Massey J, Inglesby P, Goldacre B, OpenSAFELY Collaborative, Hand K, Bladon S, Cunningham N, Gilham E, Brown CS, Mirfenderesky M, Palin V, van Staa TP.",,EClinicalMedicine,2023,2023-11-23,Y,Sepsis; Morbidity; Primary Care; Deprivation; Health Inequality; Covid-19 Pandemic,,,"

Background

Sepsis, characterised by significant morbidity and mortality, is intricately linked to socioeconomic disparities and pre-admission clinical histories. This study aspires to elucidate the association between non-COVID-19 related sepsis and health inequality risk factors amidst the pandemic in England, with a secondary focus on their association with 30-day sepsis mortality.

Methods

With the approval of NHS England, we harnessed the OpenSAFELY platform to execute a cohort study and a 1:6 matched case-control study. A sepsis diagnosis was identified from the incident hospital admissions record using ICD-10 codes. This encompassed 248,767 cases with non-COVID-19 sepsis from a cohort of 22.0 million individuals spanning January 1, 2019, to June 31, 2022. Socioeconomic deprivation was gauged using the Index of Multiple Deprivation score, reflecting indicators like income, employment, and education. Hospitalisation-related sepsis diagnoses were categorised as community-acquired or hospital-acquired. Cases were matched to controls who had no recorded diagnosis of sepsis, based on age (stepwise), sex, and calendar month. The eligibility criteria for controls were established primarily on the absence of a recorded sepsis diagnosis. Associations between potential predictors and odds of developing non-COVID-19 sepsis underwent assessment through conditional logistic regression models, with multivariable regression determining odds ratios (ORs) for 30-day mortality.

Findings

The study included 224,361 (10.2%) cases with non-COVID-19 sepsis and 1,346,166 matched controls. The most socioeconomic deprived quintile was associated with higher odds of developing non-COVID-19 sepsis than the least deprived quintile (crude OR 1.80 [95% CI 1.77-1.83]). Other risk factors (after adjusting comorbidities) such as learning disability (adjusted OR 3.53 [3.35-3.73]), chronic liver disease (adjusted OR 3.08 [2.97-3.19]), chronic kidney disease (stage 4: adjusted OR 2.62 [2.55-2.70], stage 5: adjusted OR 6.23 [5.81-6.69]), cancer, neurological disease, immunosuppressive conditions were also associated with developing non-COVID-19 sepsis. The incidence rate of non-COVID-19 sepsis decreased during the COVID-19 pandemic and rebounded to pre-pandemic levels (April 2021) after national lockdowns had been lifted. The 30-day mortality risk in cases with non-COVID-19 sepsis was higher for the most deprived quintile across all periods.

Interpretation

Socioeconomic deprivation, comorbidity and learning disabilities were associated with an increased odds of developing non-COVID-19 related sepsis and 30-day mortality in England. This study highlights the need to improve the prevention of sepsis, including more precise targeting of antimicrobials to higher-risk patients.

Funding

The UK Health Security Agency, Health Data Research UK, and National Institute for Health Research.",,doi:https://doi.org/10.1016/j.eclinm.2023.102321; html:https://europepmc.org/articles/PMC10772239; pdf:https://europepmc.org/articles/PMC10772239?pdf=render 34145260,https://doi.org/10.1038/s41467-021-23935-x,Community factors and excess mortality in first wave of the COVID-19 pandemic in England.,"Davies B, Parkes BL, Bennett J, Fecht D, Blangiardo M, Ezzati M, Elliott P.",,Nature communications,2021,2021-06-18,Y,,,,"Risk factors for increased risk of death from COVID-19 have been identified, but less is known on characteristics that make communities resilient or vulnerable to the mortality impacts of the pandemic. We applied a two-stage Bayesian spatial model to quantify inequalities in excess mortality in people aged 40 years and older at the community level during the first wave of the pandemic in England, March-May 2020 compared with 2015-2019. Here we show that communities with an increased risk of excess mortality had a high density of care homes, and/or high proportion of residents on income support, living in overcrowded homes and/or with a non-white ethnicity. We found no association between population density or air pollution and excess mortality. Effective and timely public health and healthcare measures that target the communities at greatest risk are urgently needed to avoid further widening of inequalities in mortality patterns as the pandemic progresses.",,pdf:https://www.nature.com/articles/s41467-021-23935-x.pdf; doi:https://doi.org/10.1038/s41467-021-23935-x; html:https://europepmc.org/articles/PMC8213785; pdf:https://europepmc.org/articles/PMC8213785?pdf=render 33031764,https://doi.org/10.1016/s0140-6736(20)32013-4,"Lopinavir-ritonavir in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial.",RECOVERY Collaborative Group.,,"Lancet (London, England)",2020,2020-10-05,Y,,,,"

Background

Lopinavir-ritonavir has been proposed as a treatment for COVID-19 on the basis of in vitro activity, preclinical studies, and observational studies. Here, we report the results of a randomised trial to assess whether lopinavir-ritonavir improves outcomes in patients admitted to hospital with COVID-19.

Methods

In this randomised, controlled, open-label, platform trial, a range of possible treatments was compared with usual care in patients admitted to hospital with COVID-19. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients were randomly allocated to either usual standard of care alone or usual standard of care plus lopinavir-ritonavir (400 mg and 100 mg, respectively) by mouth for 10 days or until discharge (or one of the other RECOVERY treatment groups: hydroxychloroquine, dexamethasone, or azithromycin) using web-based simple (unstratified) randomisation with allocation concealment. Randomisation to usual care was twice that of any of the active treatment groups (eg, 2:1 in favour of usual care if the patient was eligible for only one active group, 2:1:1 if the patient was eligible for two active groups). The primary outcome was 28-day all-cause mortality. Analyses were done on an intention-to-treat basis in all randomly assigned participants. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.

Findings

Between March 19, 2020, and June 29, 2020, 1616 patients were randomly allocated to receive lopinavir-ritonavir and 3424 patients to receive usual care. Overall, 374 (23%) patients allocated to lopinavir-ritonavir and 767 (22%) patients allocated to usual care died within 28 days (rate ratio 1·03, 95% CI 0·91-1·17; p=0·60). Results were consistent across all prespecified subgroups of patients. We observed no significant difference in time until discharge alive from hospital (median 11 days [IQR 5 to >28] in both groups) or the proportion of patients discharged from hospital alive within 28 days (rate ratio 0·98, 95% CI 0·91-1·05; p=0·53). Among patients not on invasive mechanical ventilation at baseline, there was no significant difference in the proportion who met the composite endpoint of invasive mechanical ventilation or death (risk ratio 1·09, 95% CI 0·99-1·20; p=0·092).

Interpretation

In patients admitted to hospital with COVID-19, lopinavir-ritonavir was not associated with reductions in 28-day mortality, duration of hospital stay, or risk of progressing to invasive mechanical ventilation or death. These findings do not support the use of lopinavir-ritonavir for treatment of patients admitted to hospital with COVID-19.

Funding

Medical Research Council and National Institute for Health Research.",,pdf:http://www.thelancet.com/article/S0140673620320134/pdf; doi:https://doi.org/10.1016/S0140-6736(20)32013-4; html:https://europepmc.org/articles/PMC7535623 36083213,https://doi.org/10.1093/jamia/ocac158,Translating and evaluating historic phenotyping algorithms using SNOMED CT.,"Elkheder M, Gonzalez-Izquierdo A, Qummer Ul Arfeen M, Kuan V, Lumbers RT, Denaxas S, Shah AD.",,Journal of the American Medical Informatics Association : JAMIA,2023,2023-01-01,Y,Terminology; Phenotype; Ontology; Electronic Health Records; Snomed Ct,,,"

Objective

Patient phenotype definitions based on terminologies are required for the computational use of electronic health records. Within UK primary care research databases, such definitions have typically been represented as flat lists of Read terms, but Systematized Nomenclature of Medicine-Clinical Terms (SNOMED CT) (a widely employed international reference terminology) enables the use of relationships between concepts, which could facilitate the phenotyping process. We implemented SNOMED CT-based phenotyping approaches and investigated their performance in the CPRD Aurum primary care database.

Materials and methods

We developed SNOMED CT phenotype definitions for 3 exemplar diseases: diabetes mellitus, asthma, and heart failure, using 3 methods: ""primary"" (primary concept and its descendants), ""extended"" (primary concept, descendants, and additional relations), and ""value set"" (based on text searches of term descriptions). We also derived SNOMED CT codelists in a semiautomated manner for 276 disease phenotypes used in a study of health across the lifecourse. Cohorts selected using each codelist were compared to ""gold standard"" manually curated Read codelists in a sample of 500 000 patients from CPRD Aurum.

Results

SNOMED CT codelists selected a similar set of patients to Read, with F1 scores exceeding 0.93, and age and sex distributions were similar. The ""value set"" and ""extended"" codelists had slightly greater recall but lower precision than ""primary"" codelists. We were able to represent 257 of the 276 phenotypes by a single concept hierarchy, and for 135 phenotypes, the F1 score was greater than 0.9.

Conclusions

SNOMED CT provides an efficient way to define disease phenotypes, resulting in similar patient populations to manually curated codelists.",,pdf:https://discovery.ucl.ac.uk/id/eprint/10155637/1/ocac158.pdf; doi:https://doi.org/10.1093/jamia/ocac158; html:https://europepmc.org/articles/PMC9846670; pdf:https://europepmc.org/articles/PMC9846670?pdf=render @@ -371,19 +371,19 @@ PMC9023380,https://doi.org/,Assessing the spread risk of COVID-19 associated wit 33611594,https://doi.org/10.1093/eurjpc/zwaa155,Excess deaths in people with cardiovascular diseases during the COVID-19 pandemic.,"Banerjee A, Chen S, Pasea L, Lai AG, Katsoulis M, Denaxas S, Nafilyan V, Williams B, Wong WK, Bakhai A, Khunti K, Pillay D, Noursadeghi M, Wu H, Pareek N, Bromage D, McDonagh TA, Byrne J, Teo JTH, Shah AM, Humberstone B, Tang LV, Shah ASV, Rubboli A, Guo Y, Hu Y, Sudlow CLM, Lip GYH, Hemingway H.",,European journal of preventive cardiology,2021,2021-12-01,Y,Cardiovascular disease; Public Health; Health Policy; Global Health; Coronavirus-2019,,,"

Aims

Cardiovascular diseases (CVDs) increase mortality risk from coronavirus infection (COVID-19). There are also concerns that the pandemic has affected supply and demand of acute cardiovascular care. We estimated excess mortality in specific CVDs, both 'direct', through infection, and 'indirect', through changes in healthcare.

Methods and results

We used (i) national mortality data for England and Wales to investigate trends in non-COVID-19 and CVD excess deaths; (ii) routine data from hospitals in England (n = 2), Italy (n = 1), and China (n = 5) to assess indirect pandemic effects on referral, diagnosis, and treatment services for CVD; and (iii) population-based electronic health records from 3 862 012 individuals in England to investigate pre- and post-COVID-19 mortality for people with incident and prevalent CVD. We incorporated pre-COVID-19 risk (by age, sex, and comorbidities), estimated population COVID-19 prevalence, and estimated relative risk (RR) of mortality in those with CVD and COVID-19 compared with CVD and non-infected (RR: 1.2, 1.5, 2.0, and 3.0).Mortality data suggest indirect effects on CVD will be delayed rather than contemporaneous (peak RR 1.14). CVD service activity decreased by 60-100% compared with pre-pandemic levels in eight hospitals across China, Italy, and England. In China, activity remained below pre-COVID-19 levels for 2-3 months even after easing lockdown and is still reduced in Italy and England. For total CVD (incident and prevalent), at 10% COVID-19 prevalence, we estimated direct impact of 31 205 and 62 410 excess deaths in England (RR 1.5 and 2.0, respectively), and indirect effect of 49 932 to 99 865 deaths.

Conclusion

Supply and demand for CVD services have dramatically reduced across countries with potential for substantial, but avoidable, excess mortality during and after the pandemic.",,pdf:https://academic.oup.com/eurjpc/article-pdf/28/14/1599/41827245/zwaa155.pdf; doi:https://doi.org/10.1093/eurjpc/zwaa155; html:https://europepmc.org/articles/PMC7928969; pdf:https://europepmc.org/articles/PMC7928969?pdf=render 34645794,https://doi.org/10.1038/s41467-021-25914-8,A cross-sectional analysis of meteorological factors and SARS-CoV-2 transmission in 409 cities across 26 countries.,"Sera F, Armstrong B, Abbott S, Meakin S, O'Reilly K, von Borries R, Schneider R, Royé D, Hashizume M, Pascal M, Tobias A, Vicedo-Cabrera AM, MCC Collaborative Research Network, CMMID COVID-19 Working Group, Gasparrini A, Lowe R.",,Nature communications,2021,2021-10-13,Y,,,,"There is conflicting evidence on the influence of weather on COVID-19 transmission. Our aim is to estimate weather-dependent signatures in the early phase of the pandemic, while controlling for socio-economic factors and non-pharmaceutical interventions. We identify a modest non-linear association between mean temperature and the effective reproduction number (Re) in 409 cities in 26 countries, with a decrease of 0.087 (95% CI: 0.025; 0.148) for a 10 °C increase. Early interventions have a greater effect on Re with a decrease of 0.285 (95% CI 0.223; 0.347) for a 5th - 95th percentile increase in the government response index. The variation in the effective reproduction number explained by government interventions is 6 times greater than for mean temperature. We find little evidence of meteorological conditions having influenced the early stages of local epidemics and conclude that population behaviour and government interventions are more important drivers of transmission.",,pdf:https://www.nature.com/articles/s41467-021-25914-8.pdf; doi:https://doi.org/10.1038/s41467-021-25914-8; html:https://europepmc.org/articles/PMC8514574; pdf:https://europepmc.org/articles/PMC8514574?pdf=render 35611160,https://doi.org/10.1016/j.eclinm.2022.101462,Impact of first UK COVID-19 lockdown on hospital admissions: Interrupted time series study of 32 million people.,"Shah SA, Brophy S, Kennedy J, Fisher L, Walker A, Mackenna B, Curtis H, Inglesby P, Davy S, Bacon S, Goldacre B, Agrawal U, Moore E, Simpson CR, Macleod J, Cooksey R, Sheikh A, Katikireddi SV.",,EClinicalMedicine,2022,2022-05-20,Y,Pandemic; Healthcare Inequalities; Healthcare Disruption; Interrupted Time Series Analysis; Covid-19; Sars-cov-2,,,"

Background

Uncontrolled infection and lockdown measures introduced in response have resulted in an unprecedented challenge for health systems internationally. Whether such unprecedented impact was due to lockdown itself and recedes when such measures are lifted is unclear. We assessed the short- and medium-term impacts of the first lockdown measures on hospital care for tracer non-COVID-19 conditions in England, Scotland and Wales across diseases, sexes, and socioeconomic and ethnic groups.

Methods

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

Findings

Our combined dataset included 32 million people who contributed over 74 million person-years. Admission rates for all three conditions fell by 34.2% (Confidence Interval (CI): -43.0, -25.3) in England, 20.9% (CI: -27.8, -14.1) in Scotland, and 24.7% (CI: -36.7, -12.7) in Wales, with falls across every stratum considered. In all three nations, cancer-related admissions fell the most while respiratory-related admissions fell the least (e.g., rates fell by 40.5% (CI: -47.4, -33.6), 21.9% (CI: -35.4, -8.4), and 19.0% (CI: -30.6, -7.4) in England for cancer, cardiovascular-related, and respiratory-related admissions respectively). Unscheduled admissions rates fell more in the most than the least deprived quintile across all three nations. Some ethnic minority groups experienced greater falls in admissions (e.g., in England, unscheduled admissions fell by 9.5% (CI: -20.2, 1.2) for Whites, but 44.3% (CI: -71.0, -17.6), 34.6% (CI: -63.8, -5.3), and 25.6% (CI: -45.0, -6.3) for Mixed, Other and Black ethnic groups respectively). Despite easing of restrictions, the overall admission rates remained lower in England, Scotland, and Wales by 20.8%, 21.6%, and 22.0%, respectively when compared to the same period (August-September) during the pre-pandemic years. This corresponds to a reduction of 26.2, 23.8 and 30.2 admissions per 100,000 people in England, Scotland, and Wales respectively.

Interpretation

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

Funding

This work was funded by the Medical Research Council as part of the Lifelong Health and Wellbeing study as part of National Core Studies (MC_PC_20030). SVK acknowledges funding from the Medical Research Council (MC_UU_00022/2), and the Scottish Government Chief Scientist Office (SPHSU17). EAVE II is funded by the Medical Research Council (MR/R008345/1) with the support of BREATHE - The Health Data Research Hub for Respiratory Health (MC_PC_19004), which is funded through the UK Research and Innovation Industrial Strategy Challenge Fund and delivered through Health Data Research UK. BG has received research funding from the NHS National Institute for Health Research (NIHR), the Wellcome Trust, Health Data Research UK, Asthma UK, the British Lung Foundation, and the Longitudinal Health and Wellbeing strand of the National Core Studies programme.",,pdf:http://www.thelancet.com/article/S2589537022001924/pdf; doi:https://doi.org/10.1016/j.eclinm.2022.101462; html:https://europepmc.org/articles/PMC9121886; pdf:https://europepmc.org/articles/PMC9121886?pdf=render -38512523,https://doi.org/10.1007/s00415-024-12284-6,Prevalence and temporal relationship of clinical co-morbidities in idiopathic dystonia: a UK linkage-based study.,"Bailey GA, Rawlings A, Torabi F, Pickrell WO, Peall KJ.",,Journal of neurology,2024,2024-03-21,Y,epidemiology; Dystonia; Co-morbidity; Linked Clinical Data,,,"While motor and psychiatric phenotypes in idiopathic dystonia are increasingly well understood, a few studies have examined the rate, type, and temporal pattern of other clinical co-morbidities in dystonia. Here, we determine the rates of clinical diagnoses across 13 broad systems-based diagnostic groups, comparing an overall idiopathic dystonia cohort, and sub-cohorts of cervical dystonia, blepharospasm, and dystonic tremor, to a matched-control cohort. Using the SAIL databank, we undertook a longitudinal population-based cohort study (January 1st 1994-December 31st 2017) using anonymised electronic healthcare records for individuals living in Wales (UK), identifying those diagnosed with dystonia through use of a previously validated algorithm. Clinical co-morbid diagnoses were identified from primary health care records, with a 10% prevalence threshold required for onward analysis. Using this approach, 54,166 dystonia cases were identified together with 216,574 matched controls. Within this cohort, ten of the main ICD-10 diagnostic codes exceeded the 10% prevalence threshold over the 20-year period (infection, neurological, respiratory, gastrointestinal, genitourinary, dermatological, musculoskeletal, circulatory, neoplastic, and endocrinological). In the overall dystonia cohort, musculoskeletal (aOR: 1.89, aHR: 1.74), respiratory (aOR: 1.84; aHR: 1.65), and gastrointestinal (aOR: 1.72; aHR: 1.6) disorders had the strongest associations both pre- and post-dystonia diagnosis. However, variation in the rate of association of individual clinical co-morbidities was observed across the cervical, blepharospasm, and tremor dystonia groups. This study suggests an increased rate of specific co-morbid clinical disorders both pre- and post-dystonia diagnosis which should be considered during clinical assessment of those with dystonia to enable optimum symptomatic management.",,pdf:https://link.springer.com/content/pdf/10.1007/s00415-024-12284-6.pdf; doi:https://doi.org/10.1007/s00415-024-12284-6; html:https://europepmc.org/articles/PMC11136734; pdf:https://europepmc.org/articles/PMC11136734?pdf=render 35698725,https://doi.org/10.1016/s2665-9913(22)00098-4,Risk of severe COVID-19 outcomes associated with immune-mediated inflammatory diseases and immune-modifying therapies: a nationwide cohort study in the OpenSAFELY platform.,"MacKenna B, Kennedy NA, Mehrkar A, Rowan A, Galloway J, Matthewman J, Mansfield KE, Bechman K, Yates M, Brown J, Schultze A, Norton S, Walker AJ, Morton CE, Harrison D, Bhaskaran K, Rentsch CT, Williamson E, Croker R, Bacon S, Hickman G, Ward T, Davy S, Green A, Fisher L, Hulme W, Bates C, Curtis HJ, Tazare J, Eggo RM, Evans D, Inglesby P, Cockburn J, McDonald HI, Tomlinson LA, Mathur R, Wong AYS, Forbes H, Parry J, Hester F, Harper S, Douglas IJ, Smeeth L, Lees CW, Evans SJW, Goldacre B, Smith CH, Langan SM.",,The Lancet. Rheumatology,2022,2022-06-09,Y,,,,"

Background

The risk of severe COVID-19 outcomes in people with immune-mediated inflammatory diseases and on immune-modifying drugs might not be fully mediated by comorbidities and might vary by factors such as ethnicity. We aimed to assess the risk of severe COVID-19 in adults with immune-mediated inflammatory diseases and in those on immune-modifying therapies.

Methods

We did a cohort study, using OpenSAFELY (an analytics platform for electronic health records) and TPP (a software provider for general practitioners), analysing routinely collected primary care data linked to hospital admission, death, and previously unavailable hospital prescription data. We included people aged 18 years or older on March 1, 2020, who were registered with TPP practices with at least 12 months of primary care records before March, 2020. We used Cox regression (adjusting for confounders and mediators) to estimate hazard ratios (HRs) comparing the risk of COVID-19-related death, critical care admission or death, and hospital admission (from March 1 to Sept 30, 2020) in people with immune-mediated inflammatory diseases compared with the general population, and in people with immune-mediated inflammatory diseases on targeted immune-modifying drugs (eg, biologics) compared with those on standard systemic treatment (eg, methotrexate).

Findings

We identified 17 672 065 adults; 1 163 438 adults (640 164 [55·0%] women and 523 274 [45·0%] men, and 827 457 [71·1%] of White ethnicity) had immune-mediated inflammatory diseases, and 16 508 627 people (8 215 020 [49·8%] women and 8 293 607 [50·2%] men, and 10 614 096 [64·3%] of White ethnicity) were included as the general population. Of 1 163 438 adults with immune-mediated inflammatory diseases, 19 119 (1·6%) received targeted immune-modifying therapy and 181 694 (15·6%) received standard systemic therapy. Compared with the general population, adults with immune-mediated inflammatory diseases had an increased risk of COVID-19-related death after adjusting for confounders (age, sex, deprivation, and smoking status; HR 1·23, 95% CI 1·20-1·27) and further adjusting for mediators (body-mass index [BMI], cardiovascular disease, diabetes, and current glucocorticoid use; 1·15, 1·11-1·18). Adults with immune-mediated inflammatory diseases also had an increased risk of COVID-19-related critical care admission or death (confounder-adjusted HR 1·24, 95% CI 1·21-1·28; mediator-adjusted 1·16, 1·12-1·19) and hospital admission (confounder-adjusted 1·32, 1·29-1·35; mediator-adjusted 1·20, 1·17-1·23). In post-hoc analyses, the risk of severe COVID-19 outcomes in people with immune-mediated inflammatory diseases was higher in non-White ethnic groups than in White ethnic groups (as it was in the general population). We saw no evidence of increased COVID-19-related death in adults on targeted, compared with those on standard systemic, therapy after adjusting for confounders (age, sex, deprivation, BMI, immune-mediated inflammatory diseases [bowel, joint, and skin], cardiovascular disease, cancer [excluding non-melanoma skin cancer], stroke, and diabetes (HR 1·03, 95% CI 0·80-1·33), and after additionally adjusting for current glucocorticoid use (1·01, 0·78-1·30). There was no evidence of increased COVID-19-related death in adults prescribed tumour necrosis factor inhibitors, interleukin (IL)-12/IL‑23 inhibitors, IL-17 inhibitors, IL-6 inhibitors, or Janus kinase inhibitors compared with those on standard systemic therapy. Rituximab was associated with increased COVID-19-related death (HR 1·68, 95% CI 1·11-2·56), with some attenuation after excluding people with haematological malignancies or organ transplants (1·54, 0·95-2·49).

Interpretation

COVID-19 deaths and hospital admissions were higher in people with immune-mediated inflammatory diseases. We saw no increased risk of adverse COVID-19 outcomes in those on most targeted immune-modifying drugs for immune-mediated inflammatory diseases compared with those on standard systemic therapy.

Funding

UK Medical Research Council, NIHR Biomedical Research Centre at King's College London and Guy's and St Thomas' NHS Foundation Trust, and Wellcome Trust.",,pdf:http://www.thelancet.com/article/S2665991322000984/pdf; doi:https://doi.org/10.1016/S2665-9913(22)00098-4; html:https://europepmc.org/articles/PMC9179144; pdf:https://europepmc.org/articles/PMC9179144?pdf=render +38512523,https://doi.org/10.1007/s00415-024-12284-6,Prevalence and temporal relationship of clinical co-morbidities in idiopathic dystonia: a UK linkage-based study.,"Bailey GA, Rawlings A, Torabi F, Pickrell WO, Peall KJ.",,Journal of neurology,2024,2024-03-21,Y,epidemiology; Dystonia; Co-morbidity; Linked Clinical Data,,,"While motor and psychiatric phenotypes in idiopathic dystonia are increasingly well understood, a few studies have examined the rate, type, and temporal pattern of other clinical co-morbidities in dystonia. Here, we determine the rates of clinical diagnoses across 13 broad systems-based diagnostic groups, comparing an overall idiopathic dystonia cohort, and sub-cohorts of cervical dystonia, blepharospasm, and dystonic tremor, to a matched-control cohort. Using the SAIL databank, we undertook a longitudinal population-based cohort study (January 1st 1994-December 31st 2017) using anonymised electronic healthcare records for individuals living in Wales (UK), identifying those diagnosed with dystonia through use of a previously validated algorithm. Clinical co-morbid diagnoses were identified from primary health care records, with a 10% prevalence threshold required for onward analysis. Using this approach, 54,166 dystonia cases were identified together with 216,574 matched controls. Within this cohort, ten of the main ICD-10 diagnostic codes exceeded the 10% prevalence threshold over the 20-year period (infection, neurological, respiratory, gastrointestinal, genitourinary, dermatological, musculoskeletal, circulatory, neoplastic, and endocrinological). In the overall dystonia cohort, musculoskeletal (aOR: 1.89, aHR: 1.74), respiratory (aOR: 1.84; aHR: 1.65), and gastrointestinal (aOR: 1.72; aHR: 1.6) disorders had the strongest associations both pre- and post-dystonia diagnosis. However, variation in the rate of association of individual clinical co-morbidities was observed across the cervical, blepharospasm, and tremor dystonia groups. This study suggests an increased rate of specific co-morbid clinical disorders both pre- and post-dystonia diagnosis which should be considered during clinical assessment of those with dystonia to enable optimum symptomatic management.",,pdf:https://link.springer.com/content/pdf/10.1007/s00415-024-12284-6.pdf; doi:https://doi.org/10.1007/s00415-024-12284-6; html:https://europepmc.org/articles/PMC11136734; pdf:https://europepmc.org/articles/PMC11136734?pdf=render 34935001,https://doi.org/10.1016/s2666-7568(21)00282-8,Prevalence and duration of detectable SARS-CoV-2 nucleocapsid antibodies in staff and residents of long-term care facilities over the first year of the pandemic (VIVALDI study): prospective cohort study in England.,"Krutikov M, Palmer T, Tut G, Fuller C, Azmi B, Giddings R, Shrotri M, Kaur N, Sylla P, Lancaster T, Irwin-Singer A, Hayward A, Moss P, Copas A, Shallcross L.",,The lancet. Healthy longevity,2022,2021-12-16,Y,,,,"

Background

Long-term care facilities (LTCFs) have reported high SARS-CoV-2 infection rates and related mortality, but the proportion of infected people among those who have survived, and duration of the antibody response to natural infection, is unknown. We determined the prevalence and stability of nucleocapsid antibodies (the standard assay for detection of previous infection) in staff and residents in LTCFs in England.

Methods

This was a prospective cohort study of residents 65 years or older and of staff 65 years or younger in 201 LTCFs in England between March 1, 2020, and May 7, 2021. Participants were linked to a unique pseudo-identifier based on their UK National Health Service identification number. Serial blood samples were tested for IgG antibodies against SARS-CoV-2 nucleocapsid protein using the Abbott ARCHITECT i-system (Abbott, Maidenhead, UK) immunoassay. Primary endpoints were prevalence and cumulative incidence of antibody positivity, which were weighted to the LTCF population. Incidence rate of loss of antibodies (seroreversion) was estimated from Kaplan-Meier curves.

Findings

9488 samples were included, 8636 (91·0%) of which could be individually linked to 1434 residents and 3288 staff members. The cumulative incidence of nucleocapsid seropositivity was 34·6% (29·6-40·0) in residents and 26·1% (23·0-29·5) in staff over 11 months. 239 (38·6%) residents and 503 women (81·3%) were included in the antibody-waning analysis, and median follow-up was 149 days (IQR 107-169). The incidence rate of seroreversion was 2·1 per 1000 person-days at risk, and median time to reversion was 242·5 days.

Interpretation

At least a quarter of staff and a third of surviving residents were infected with SAR-CoV-2 during the first two waves of the pandemic in England. Nucleocapsid-specific antibodies often become undetectable within the first year following infection, which is likely to lead to marked underestimation of the true proportion of people with previous infection. Given that natural infection might act to boost vaccine responses, better assays to identify natural infection should be developed.

Funding

UK Government Department of Health and Social Care.",,pdf:http://www.thelancet.com/article/S2666756821002828/pdf; doi:https://doi.org/10.1016/S2666-7568(21)00282-8; html:https://europepmc.org/articles/PMC8676418 35459950,https://doi.org/10.1093/intqhc/mzac031,Modelling the effect of COVID-19 mass vaccination on acute hospital admissions.,"Booton RD, Powell AL, Turner KME, Wood RM.",,International journal for quality in health care : journal of the International Society for Quality in Health Care,2022,2022-05-01,N,Vaccination; Coronavirus; Mathematical Modelling; Bed Management; Hospital Capacity; Covid-19,,,"

Background

Managing high levels of acute COVID-19 bed occupancy can affect the quality of care provided to both affected patients and those requiring other hospital services. Mass vaccination has offered a route to reduce societal restrictions while protecting hospitals from being overwhelmed. Yet, early in the mass vaccination effort, the possible impact on future bed pressures remained subject to considerable uncertainty.

Objective

The aim of this study was to model the effect of vaccination on projections of acute and intensive care bed demand within a 1 million resident healthcare system located in South West England.

Methods

An age-structured epidemiological model of the susceptible-exposed-infectious-recovered type was fitted to local data up to the time of the study, in early March 2021. Model parameters and vaccination scenarios were calibrated through a system-wide multidisciplinary working group, comprising public health intelligence specialists, healthcare planners, epidemiologists and academics. Scenarios assumed incremental relaxations to societal restrictions according to the envisaged UK Government timeline, with all restrictions to be removed by 21 June 2021.

Results

Achieving 95% vaccine uptake in adults by 31 July 2021 would not avert the third wave in autumn 2021 but would produce a median peak bed requirement ∼6% (IQR: 1-24%) of that experienced during the second wave (January 2021). A 2-month delay in vaccine rollout would lead to significantly higher peak bed occupancy, at 66% (11-146%) of that of the second wave. If only 75% uptake was achieved (the amount typically associated with vaccination campaigns), then the second wave peak for acute and intensive care beds would be exceeded by 4% and 19%, respectively, an amount which would seriously pressure hospital capacity.

Conclusion

Modelling influenced decision-making among senior managers in setting COVID-19 bed capacity levels, as well as highlighting the importance of public health in promoting high vaccine uptake among the population. Forecast accuracy has since been supported by actual data collected following the analysis, with observed peak bed occupancy falling comfortably within the inter-quartile range of modelled projections.",,pdf:https://academic.oup.com/intqhc/article-pdf/34/2/mzac031/43704475/mzac031.pdf; doi:https://doi.org/10.1093/intqhc/mzac031 36374585,https://doi.org/10.1177/01410768221131897,Using national electronic health records for pandemic preparedness: validation of a parsimonious model for predicting excess deaths among those with COVID-19-a data-driven retrospective cohort study.,"Mizani MA, Dashtban A, Pasea L, Lai AG, Thygesen J, Tomlinson C, Handy A, Mamza JB, Morris T, Khalid S, Zaccardi F, Macleod MJ, Torabi F, Canoy D, Akbari A, Berry C, Bolton T, Nolan J, Khunti K, Denaxas S, Hemingway H, Sudlow C, Banerjee A, CVD-COVID-UK Consortium.",,Journal of the Royal Society of Medicine,2023,2022-11-14,N,Infectious diseases; Clinical; epidemiology; Public Health; Health Informatics,,,"

Objectives

To use national, pre- and post-pandemic electronic health records (EHR) to develop and validate a scenario-based model incorporating baseline mortality risk, infection rate (IR) and relative risk (RR) of death for prediction of excess deaths.

Design

An EHR-based, retrospective cohort study.

Setting

Linked EHR in Clinical Practice Research Datalink (CPRD); and linked EHR and COVID-19 data in England provided in NHS Digital Trusted Research Environment (TRE).

Participants

In the development (CPRD) and validation (TRE) cohorts, we included 3.8 million and 35.1 million individuals aged ≥30 years, respectively.

Main outcome measures

One-year all-cause excess deaths related to COVID-19 from March 2020 to March 2021.

Results

From 1 March 2020 to 1 March 2021, there were 127,020 observed excess deaths. Observed RR was 4.34% (95% CI, 4.31-4.38) and IR was 6.27% (95% CI, 6.26-6.28). In the validation cohort, predicted one-year excess deaths were 100,338 compared with the observed 127,020 deaths with a ratio of predicted to observed excess deaths of 0.79.

Conclusions

We show that a simple, parsimonious model incorporating baseline mortality risk, one-year IR and RR of the pandemic can be used for scenario-based prediction of excess deaths in the early stages of a pandemic. Our analyses show that EHR could inform pandemic planning and surveillance, despite limited use in emergency preparedness to date. Although infection dynamics are important in the prediction of mortality, future models should take greater account of underlying conditions.",,pdf:https://journals.sagepub.com/doi/pdf/10.1177/01410768221131897; doi:https://doi.org/10.1177/01410768221131897; html:https://europepmc.org/articles/PMC9909113; pdf:https://europepmc.org/articles/PMC9909113?pdf=render; doi:https://doi.org/10.1177/01410768221131897 33617936,https://doi.org/10.1016/j.jhin.2021.02.012,Global and national estimates of the number of healthcare workers at high risk of SARS-CoV-2 infection.,"McCarthy CV, Sandmann FG, CMMID COVID-19 Working Group, Jit M.",,The Journal of hospital infection,2021,2021-02-20,Y,,,,,,pdf:https://researchonline.lshtm.ac.uk/id/eprint/4660358/1/Global%20and%20national%20estimates%20of%20the%20number%20of%20healthcare%20workers%20at%20high%20risk%20of%20SARS-CoV-2%20infection.pdf; doi:https://doi.org/10.1016/j.jhin.2021.02.012; html:https://europepmc.org/articles/PMC7896121; pdf:https://europepmc.org/articles/PMC7896121?pdf=render -37303488,https://doi.org/10.1136/bmjmed-2022-000392,"Changes in medication safety indicators in England throughout the covid-19 pandemic using OpenSAFELY: population based, retrospective cohort study of 57 million patients using federated analytics.","Fisher L, Hopcroft LE, Rodgers S, Barrett J, Oliver K, Avery AJ, Evans D, Curtis H, Croker R, Macdonald O, Morley J, Mehrkar A, Bacon S, Davy S, Dillingham I, Evans D, Hickman G, Inglesby P, Morton CE, Smith B, Ward T, Hulme W, Green A, Massey J, Walker AJ, Bates C, Cockburn J, Parry J, Hester F, Harper S, O'Hanlon S, Eavis A, Jarvis R, Avramov D, Griffiths P, Fowles A, Parkes N, Goldacre B, MacKenna B.",,BMJ medicine,2023,2023-05-11,Y,Primary Health Care; Medical Informatics; Covid-19,,,"

Objective

To implement complex, PINCER (pharmacist led information technology intervention) prescribing indicators, on a national scale with general practice data to describe the impact of the covid-19 pandemic on safe prescribing.

Design

Population based, retrospective cohort study using federated analytics.

Setting

Electronic general practice health record data from 56.8 million NHS patients by use of the OpenSAFELY platform, with the approval of the National Health Service (NHS) England.

Participants

NHS patients (aged 18-120 years) who were alive and registered at a general practice that used TPP or EMIS computer systems and were recorded as at risk of at least one potentially hazardous PINCER indicator.

Main outcome measure

Between 1 September 2019 and 1 September 2021, monthly trends and between practice variation for compliance with 13 PINCER indicators, as calculated on the first of every month, were reported. Prescriptions that do not adhere to these indicators are potentially hazardous and can cause gastrointestinal bleeds; are cautioned against in specific conditions (specifically heart failure, asthma, and chronic renal failure); or require blood test monitoring. The percentage for each indicator is formed of a numerator of patients deemed to be at risk of a potentially hazardous prescribing event and the denominator is of patients for which assessment of the indicator is clinically meaningful. Higher indicator percentages represent potentially poorer performance on medication safety.

Results

The PINCER indicators were successfully implemented across general practice data for 56.8 million patient records from 6367 practices in OpenSAFELY. Hazardous prescribing remained largely unchanged during the covid-19 pandemic, with no evidence of increases in indicators of harm as captured by the PINCER indicators. The percentage of patients at risk of potentially hazardous prescribing, as defined by each PINCER indicator, at mean quarter 1 (Q1) 2020 (representing before the pandemic) ranged from 1.11% (age ≥65 years and non-steroidal anti-inflammatory drugs) to 36.20% (amiodarone and no thyroid function test), while Q1 2021 (representing after the pandemic) percentages ranged from 0.75% (age ≥65 years and non-steroidal anti-inflammatory drugs) to 39.23% (amiodarone and no thyroid function test). Transient delays occurred in blood test monitoring for some medications, particularly angiotensin-converting enzyme inhibitors (where blood monitoring worsened from a mean of 5.16% in Q1 2020 to 12.14% in Q1 2021, and began to recover in June 2021). All indicators substantially recovered by September 2021. We identified 1 813 058 patients (3.1%) at risk of at least one potentially hazardous prescribing event.

Conclusion

NHS data from general practices can be analysed at national scale to generate insights into service delivery. Potentially hazardous prescribing was largely unaffected by the covid-19 pandemic in primary care health records in England.",,pdf:https://bmjmedicine.bmj.com/content/bmjmed/2/1/e000392.full.pdf; doi:https://doi.org/10.1136/bmjmed-2022-000392; html:https://europepmc.org/articles/PMC10254692; pdf:https://europepmc.org/articles/PMC10254692?pdf=render 35189575,https://doi.org/10.1016/j.ebiom.2022.103878,The impact of hypoxia on B cells in COVID-19.,"Kotagiri P, Mescia F, Hanson AL, Turner L, Bergamaschi L, Peñalver A, Richoz N, Moore SD, Ortmann BM, Dunmore BJ, Morgan MD, Tuong ZK, Cambridge Institute of Therapeutic Immunology and Infectious Disease-National Institute of Health Research (CITIID-NIHR) COVID BioResource Collaboration, Göttgens B, Toshner M, Hess C, Maxwell PH, Clatworthy MR, Nathan JA, Bradley JR, Lyons PA, Burrows N, Smith KGC.",,EBioMedicine,2022,2022-02-19,Y,Hypoxia; B cells; Lymphopenia; Covid-19,,,"

Background

Prominent early features of COVID-19 include severe, often clinically silent, hypoxia and a pronounced reduction in B cells, the latter important in defence against SARS-CoV-2. This presentation resembles the phenotype of mice with VHL-deficient B cells, in which Hypoxia-Inducible Factors are constitutively active, suggesting hypoxia might drive B cell abnormalities in COVID-19.

Methods

Detailed B cell phenotyping was undertaken by flow-cytometry on longitudinal samples from patients with COVID-19 across a range of severities (NIHR Cambridge BioResource). The impact of hypoxia on the transcriptome was assessed by single-cell and whole blood RNA sequencing analysis. The direct effect of hypoxia on B cells was determined through immunisation studies in genetically modified and hypoxia-exposed mice.

Findings

We demonstrate the breadth of early and persistent defects in B cell subsets in moderate/severe COVID-19, including reduced marginal zone-like, memory and transitional B cells, changes also observed in B cell VHL-deficient mice. These findings were associated with hypoxia-related transcriptional changes in COVID-19 patient B cells, and similar B cell abnormalities were seen in mice kept in hypoxic conditions.

Interpretation

Hypoxia may contribute to the pronounced and persistent B cell pathology observed in acute COVID-19 pneumonia. Assessment of the impact of early oxygen therapy on these immune defects should be considered, as their correction could contribute to improved outcomes.

Funding

Evelyn Trust, Addenbrooke's Charitable Trust, UKRI/NIHR, Wellcome Trust.",,pdf:http://www.thelancet.com/article/S2352396422000627/pdf; doi:https://doi.org/10.1016/j.ebiom.2022.103878; html:https://europepmc.org/articles/PMC8856886; pdf:https://europepmc.org/articles/PMC8856886?pdf=render 34972825,https://doi.org/10.1038/s41564-021-01029-0,Improving local prevalence estimates of SARS-CoV-2 infections using a causal debiasing framework.,"Nicholson G, Lehmann B, Padellini T, Pouwels KB, Jersakova R, Lomax J, King RE, Mallon AM, Diggle PJ, Richardson S, Blangiardo M, Holmes C.",,Nature microbiology,2022,2021-12-31,Y,,,,"Global and national surveillance of SARS-CoV-2 epidemiology is mostly based on targeted schemes focused on testing individuals with symptoms. These tested groups are often unrepresentative of the wider population and exhibit test positivity rates that are biased upwards compared with the true population prevalence. Such data are routinely used to infer infection prevalence and the effective reproduction number, Rt, which affects public health policy. Here, we describe a causal framework that provides debiased fine-scale spatiotemporal estimates by combining targeted test counts with data from a randomized surveillance study in the United Kingdom called REACT. Our probabilistic model includes a bias parameter that captures the increased probability of an infected individual being tested, relative to a non-infected individual, and transforms observed test counts to debiased estimates of the true underlying local prevalence and Rt. We validated our approach on held-out REACT data over a 7-month period. Furthermore, our local estimates of Rt are indicative of 1-week- and 2-week-ahead changes in SARS-CoV-2-positive case numbers. We also observed increases in estimated local prevalence and Rt that reflect the spread of the Alpha and Delta variants. Our results illustrate how randomized surveys can augment targeted testing to improve statistical accuracy in monitoring the spread of emerging and ongoing infectious disease.",,pdf:https://www.nature.com/articles/s41564-021-01029-0.pdf; doi:https://doi.org/10.1038/s41564-021-01029-0; html:https://europepmc.org/articles/PMC8727294; pdf:https://europepmc.org/articles/PMC8727294?pdf=render +37303488,https://doi.org/10.1136/bmjmed-2022-000392,"Changes in medication safety indicators in England throughout the covid-19 pandemic using OpenSAFELY: population based, retrospective cohort study of 57 million patients using federated analytics.","Fisher L, Hopcroft LE, Rodgers S, Barrett J, Oliver K, Avery AJ, Evans D, Curtis H, Croker R, Macdonald O, Morley J, Mehrkar A, Bacon S, Davy S, Dillingham I, Evans D, Hickman G, Inglesby P, Morton CE, Smith B, Ward T, Hulme W, Green A, Massey J, Walker AJ, Bates C, Cockburn J, Parry J, Hester F, Harper S, O'Hanlon S, Eavis A, Jarvis R, Avramov D, Griffiths P, Fowles A, Parkes N, Goldacre B, MacKenna B.",,BMJ medicine,2023,2023-05-11,Y,Primary Health Care; Medical Informatics; Covid-19,,,"

Objective

To implement complex, PINCER (pharmacist led information technology intervention) prescribing indicators, on a national scale with general practice data to describe the impact of the covid-19 pandemic on safe prescribing.

Design

Population based, retrospective cohort study using federated analytics.

Setting

Electronic general practice health record data from 56.8 million NHS patients by use of the OpenSAFELY platform, with the approval of the National Health Service (NHS) England.

Participants

NHS patients (aged 18-120 years) who were alive and registered at a general practice that used TPP or EMIS computer systems and were recorded as at risk of at least one potentially hazardous PINCER indicator.

Main outcome measure

Between 1 September 2019 and 1 September 2021, monthly trends and between practice variation for compliance with 13 PINCER indicators, as calculated on the first of every month, were reported. Prescriptions that do not adhere to these indicators are potentially hazardous and can cause gastrointestinal bleeds; are cautioned against in specific conditions (specifically heart failure, asthma, and chronic renal failure); or require blood test monitoring. The percentage for each indicator is formed of a numerator of patients deemed to be at risk of a potentially hazardous prescribing event and the denominator is of patients for which assessment of the indicator is clinically meaningful. Higher indicator percentages represent potentially poorer performance on medication safety.

Results

The PINCER indicators were successfully implemented across general practice data for 56.8 million patient records from 6367 practices in OpenSAFELY. Hazardous prescribing remained largely unchanged during the covid-19 pandemic, with no evidence of increases in indicators of harm as captured by the PINCER indicators. The percentage of patients at risk of potentially hazardous prescribing, as defined by each PINCER indicator, at mean quarter 1 (Q1) 2020 (representing before the pandemic) ranged from 1.11% (age ≥65 years and non-steroidal anti-inflammatory drugs) to 36.20% (amiodarone and no thyroid function test), while Q1 2021 (representing after the pandemic) percentages ranged from 0.75% (age ≥65 years and non-steroidal anti-inflammatory drugs) to 39.23% (amiodarone and no thyroid function test). Transient delays occurred in blood test monitoring for some medications, particularly angiotensin-converting enzyme inhibitors (where blood monitoring worsened from a mean of 5.16% in Q1 2020 to 12.14% in Q1 2021, and began to recover in June 2021). All indicators substantially recovered by September 2021. We identified 1 813 058 patients (3.1%) at risk of at least one potentially hazardous prescribing event.

Conclusion

NHS data from general practices can be analysed at national scale to generate insights into service delivery. Potentially hazardous prescribing was largely unaffected by the covid-19 pandemic in primary care health records in England.",,pdf:https://bmjmedicine.bmj.com/content/bmjmed/2/1/e000392.full.pdf; doi:https://doi.org/10.1136/bmjmed-2022-000392; html:https://europepmc.org/articles/PMC10254692; pdf:https://europepmc.org/articles/PMC10254692?pdf=render 34308406,https://doi.org/10.1016/j.lanepe.2021.100180,Ethnic differences in SARS-CoV-2 vaccine hesitancy in United Kingdom healthcare workers: Results from the UK-REACH prospective nationwide cohort study.,"Woolf K, McManus IC, Martin CA, Nellums LB, Guyatt AL, Melbourne C, Bryant L, Gogoi M, Wobi F, Al-Oraibi A, Hassan O, Gupta A, John C, Tobin MD, Carr S, Simpson S, Gregary B, Aujayeb A, Zingwe S, Reza R, Gray LJ, Khunti K, Pareek M, UK-REACH Study Collaborative Group.",,The Lancet regional health. Europe,2021,2021-07-19,Y,,,,"

Background

In most countries, healthcare workers (HCWs) represent a priority group for vaccination against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) due to their elevated risk of COVID-19 and potential contribution to nosocomial SARS-CoV-2 transmission. Concerns have been raised that HCWs from ethnic minority groups are more likely to be vaccine hesitant (defined by the World Health Organisation as refusing or delaying a vaccination) than those of White ethnicity, but there are limited data on SARS-CoV-2 vaccine hesitancy and its predictors in UK HCWs.

Methods

Nationwide prospective cohort study and qualitative study in a multi-ethnic cohort of clinical and non-clinical UK HCWs. We analysed ethnic differences in SARS-CoV-2 vaccine hesitancy adjusting for demographics, vaccine trust, and perceived risk of COVID-19. We explored reasons for hesitancy in qualitative data using a framework analysis.

Findings

11,584 HCWs were included in the cohort analysis. 23% (2704) reported vaccine hesitancy. Compared to White British HCWs (21.3% hesitant), HCWs from Black Caribbean (54.2%), Mixed White and Black Caribbean (38.1%), Black African (34.4%), Chinese (33.1%), Pakistani (30.4%), and White Other (28.7%) ethnic groups were significantly more likely to be hesitant. In adjusted analysis, Black Caribbean (aOR 3.37, 95% CI 2.11 - 5.37), Black African (aOR 2.05, 95% CI 1.49 - 2.82), White Other ethnic groups (aOR 1.48, 95% CI 1.19 - 1.84) were significantly more likely to be hesitant. Other independent predictors of hesitancy were younger age, female sex, higher score on a COVID-19 conspiracy beliefs scale, lower trust in employer, lack of influenza vaccine uptake in the previous season, previous COVID-19, and pregnancy. Qualitative data from 99 participants identified the following contributors to hesitancy: lack of trust in government and employers, safety concerns due to the speed of vaccine development, lack of ethnic diversity in vaccine studies, and confusing and conflicting information. Participants felt uptake in ethnic minority communities might be improved through inclusive communication, involving HCWs in the vaccine rollout, and promoting vaccination through trusted networks.

Interpretation

Despite increased risk of COVID-19, HCWs from some ethnic minority groups are more likely to be vaccine hesitant than their White British colleagues. Strategies to build trust and dispel myths surrounding the COVID-19 vaccine in these communities are urgently required. Emphasis should be placed on the safety and benefit of SARS-CoV-2 vaccination in pregnancy and in those with previous COVID-19. Public health communications should be inclusive, non-stigmatising and utilise trusted networks.

Funding

UKRI-MRC and NIHR.",,doi:https://doi.org/10.1016/j.lanepe.2021.100180; doi:https://doi.org/10.1016/j.lanepe.2021.100180; html:https://europepmc.org/articles/PMC8287519; pdf:https://europepmc.org/articles/PMC8287519?pdf=render 32951042,https://doi.org/10.1093/ageing/afaa207,"The impact of COVID-19 on adjusted mortality risk in care homes for older adults in Wales, UK: a retrospective population-based cohort study for mortality in 2016-2020.","Hollinghurst J, Lyons J, Fry R, Akbari A, Gravenor M, Watkins A, Verity F, Lyons RA.",,Age and ageing,2021,2021-01-01,Y,Mortality; Frailty; Older People; Care Homes; Covid-19,,,"

Background

mortality in care homes has had a prominent focus during the COVID-19 outbreak. Care homes are particularly vulnerable to the spread of infectious diseases, which may lead to increased mortality risk. Multiple and interconnected challenges face the care home sector in the prevention and management of outbreaks of COVID-19, including adequate supply of personal protective equipment, staff shortages and insufficient or lack of timely COVID-19 testing.

Aim

to analyse the mortality of older care home residents in Wales during COVID-19 lockdown and compare this across the population of Wales and the previous 4 years.

Study design and setting

we used anonymised electronic health records and administrative data from the secure anonymised information linkage databank to create a cross-sectional cohort study. We anonymously linked data for Welsh residents to mortality data up to the 14th June 2020.

Methods

we calculated survival curves and adjusted Cox proportional hazards models to estimate hazard ratios (HRs) for the risk of mortality. We adjusted HRs for age, gender, social economic status and prior health conditions.

Results

survival curves show an increased proportion of deaths between 23rd March and 14th June 2020 in care homes for older people, with an adjusted HR of 1.72 (1.55, 1.90) compared with 2016. Compared with the general population in 2016-2019, adjusted care home mortality HRs for older adults rose from 2.15 (2.11, 2.20) in 2016-2019 to 2.94 (2.81, 3.08) in 2020.

Conclusions

the survival curves and increased HRs show a significantly increased risk of death in the 2020 study periods.",,pdf:https://academic.oup.com/ageing/article-pdf/50/1/25/42362959/afaa207.pdf; doi:https://doi.org/10.1093/ageing/afaa207; html:https://europepmc.org/articles/PMC7546151; pdf:https://europepmc.org/articles/PMC7546151?pdf=render -38296965,https://doi.org/10.1038/s41467-023-43644-x,"Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial.","RECOVERY Collaborative Group, Horby PW, Peto L, Staplin N, Campbell M, Pessoa-Amorim G, Mafham M, Emberson JR, Stewart R, Prudon B, Uriel A, Green CA, Dhasmana DJ, Malein F, Majumdar J, Collini P, Shurmer J, Yates B, Baillie JK, Buch MH, Day J, Faust SN, Jaki T, Jeffery K, Juszczak E, Knight M, Lim WS, Montgomery A, Mumford A, Rowan K, Thwaites G, Haynes R, Landray MJ.",,Nature communications,2024,2024-01-31,Y,,,,"Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome.",,pdf:https://www.nature.com/articles/s41467-023-43644-x.pdf; doi:https://doi.org/10.1038/s41467-023-43644-x; html:https://europepmc.org/articles/PMC10831058; pdf:https://europepmc.org/articles/PMC10831058?pdf=render 35413949,https://doi.org/10.1038/s41467-022-29521-z,"Persistent COVID-19 symptoms in a community study of 606,434 people in England.","Whitaker M, Elliott J, Chadeau-Hyam M, Riley S, Darzi A, Cooke G, Ward H, Elliott P.",,Nature communications,2022,2022-04-12,Y,,,,"Long COVID remains a broadly defined syndrome, with estimates of prevalence and duration varying widely. We use data from rounds 3-5 of the REACT-2 study (n = 508,707; September 2020 - February 2021), a representative community survey of adults in England, and replication data from round 6 (n = 97,717; May 2021) to estimate the prevalence and identify predictors of persistent symptoms lasting 12 weeks or more; and unsupervised learning to cluster individuals by reported symptoms. At 12 weeks in rounds 3-5, 37.7% experienced at least one symptom, falling to 21.6% in round 6. Female sex, increasing age, obesity, smoking, vaping, hospitalisation with COVID-19, deprivation, and being a healthcare worker are associated with higher probability of persistent symptoms in rounds 3-5, and Asian ethnicity with lower probability. Clustering analysis identifies a subset of participants with predominantly respiratory symptoms. Managing the long-term sequelae of COVID-19 will remain a major challenge for affected individuals and their families and for health services.",,pdf:https://www.nature.com/articles/s41467-022-29521-z.pdf; doi:https://doi.org/10.1038/s41467-022-29521-z; html:https://europepmc.org/articles/PMC9005552; pdf:https://europepmc.org/articles/PMC9005552?pdf=render +38296965,https://doi.org/10.1038/s41467-023-43644-x,"Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial.","RECOVERY Collaborative Group, Horby PW, Peto L, Staplin N, Campbell M, Pessoa-Amorim G, Mafham M, Emberson JR, Stewart R, Prudon B, Uriel A, Green CA, Dhasmana DJ, Malein F, Majumdar J, Collini P, Shurmer J, Yates B, Baillie JK, Buch MH, Day J, Faust SN, Jaki T, Jeffery K, Juszczak E, Knight M, Lim WS, Montgomery A, Mumford A, Rowan K, Thwaites G, Haynes R, Landray MJ.",,Nature communications,2024,2024-01-31,Y,,,,"Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome.",,pdf:https://www.nature.com/articles/s41467-023-43644-x.pdf; doi:https://doi.org/10.1038/s41467-023-43644-x; html:https://europepmc.org/articles/PMC10831058; pdf:https://europepmc.org/articles/PMC10831058?pdf=render 33328453,https://doi.org/10.1038/s41467-020-19996-z,Genetic architecture of host proteins involved in SARS-CoV-2 infection.,"Pietzner M, Wheeler E, Carrasco-Zanini J, Raffler J, Kerrison ND, Oerton E, Auyeung VPW, Luan J, Finan C, Casas JP, Ostroff R, Williams SA, Kastenmüller G, Ralser M, Gamazon ER, Wareham NJ, Hingorani AD, Langenberg C.",,Nature communications,2020,2020-12-16,Y,,,,"Understanding the genetic architecture of host proteins interacting with SARS-CoV-2 or mediating the maladaptive host response to COVID-19 can help to identify new or repurpose existing drugs targeting those proteins. We present a genetic discovery study of 179 such host proteins among 10,708 individuals using an aptamer-based technique. We identify 220 host DNA sequence variants acting in cis (MAF 0.01-49.9%) and explaining 0.3-70.9% of the variance of 97 of these proteins, including 45 with no previously known protein quantitative trait loci (pQTL) and 38 encoding current drug targets. Systematic characterization of pQTLs across the phenome identified protein-drug-disease links and evidence that putative viral interaction partners such as MARK3 affect immune response. Our results accelerate the evaluation and prioritization of new drug development programmes and repurposing of trials to prevent, treat or reduce adverse outcomes. Rapid sharing and detailed interrogation of results is facilitated through an interactive webserver ( https://omicscience.org/apps/covidpgwas/ ).",,pdf:https://www.nature.com/articles/s41467-020-19996-z.pdf; doi:https://doi.org/10.1038/s41467-020-19996-z; html:https://europepmc.org/articles/PMC7744536; pdf:https://europepmc.org/articles/PMC7744536?pdf=render 34210356,https://doi.org/10.1186/s13059-021-02395-y,CLIMB-COVID: continuous integration supporting decentralised sequencing for SARS-CoV-2 genomic surveillance.,"Nicholls SM, Poplawski R, Bull MJ, Underwood A, Chapman M, Abu-Dahab K, Taylor B, Colquhoun RM, Rowe WPM, Jackson B, Hill V, O'Toole Á, Rey S, Southgate J, Amato R, Livett R, Gonçalves S, Harrison EM, Peacock SJ, Aanensen DM, Rambaut A, Connor TR, Loman NJ, COVID-19 Genomics UK (COG-UK) Consortium.",,Genome biology,2021,2021-07-01,Y,,,,"In response to the ongoing SARS-CoV-2 pandemic in the UK, the COVID-19 Genomics UK (COG-UK) consortium was formed to rapidly sequence SARS-CoV-2 genomes as part of a national-scale genomic surveillance strategy. The network consists of universities, academic institutes, regional sequencing centres and the four UK Public Health Agencies. We describe the development and deployment of CLIMB-COVID, an encompassing digital infrastructure to address the challenge of collecting and integrating both genomic sequencing data and sample-associated metadata produced across the COG-UK network.",,pdf:https://genomebiology.biomedcentral.com/counter/pdf/10.1186/s13059-021-02395-y; doi:https://doi.org/10.1186/s13059-021-02395-y; html:https://europepmc.org/articles/PMC8247108; pdf:https://europepmc.org/articles/PMC8247108?pdf=render 36447940,https://doi.org/10.1016/s2665-9913(22)00305-8,Incidence and management of inflammatory arthritis in England before and during the COVID-19 pandemic: a population-level cohort study using OpenSAFELY.,"Russell MD, Galloway JB, Andrews CD, MacKenna B, Goldacre B, Mehrkar A, Curtis HJ, Butler-Cole B, O'Dwyer T, Qureshi S, Ledingham JM, Mahto A, Rutherford AI, Adas MA, Alveyn E, Norton S, Cope AP, Bechman K, OpenSAFELY Collaborative.",,The Lancet. Rheumatology,2022,2022-11-03,Y,,,,"

Background

The impact of the COVID-19 pandemic on the incidence and management of inflammatory arthritis is not understood. Routinely captured data in secure platforms, such as OpenSAFELY, offer unique opportunities to understand how care for patients with inflammatory arthritis was impacted upon by the pandemic. Our objective was to use OpenSAFELY to assess the effects of the pandemic on diagnostic incidence and care delivery for inflammatory arthritis in England and to replicate key metrics from the National Early Inflammatory Arthritis Audit.

Methods

In this population-level cohort study, we used primary care and hospital data for 17·7 million adults registered with general practices using TPP health record software, to explore the following outcomes between April 1, 2019, and March 31, 2022: (1) incidence of inflammatory arthritis diagnoses (rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, and undifferentiated inflammatory arthritis) recorded in primary care; (2) time to first rheumatology assessment; (3) time to first prescription of a disease-modifying antirheumatic drug (DMARD) in primary care; and (4) choice of first DMARD.

Findings

Among 17 683 500 adults, there were 31 280 incident inflammatory arthritis diagnoses recorded between April 1, 2019, and March 31, 2022. The mean age of diagnosed patients was 55·4 years (SD 16·6), 18 615 (59·5%) were female, 12 665 (40·5%) were male, and 22 925 (88·3%) of 25 960 with available ethnicity data were White. New inflammatory arthritis diagnoses decreased by 20·3% in the year commencing April, 2020, relative to the preceding year (5·1 vs 6·4 diagnoses per 10 000 adults). The median time to first rheumatology assessment was shorter during the pandemic (18 days; IQR 8-35) than before (21 days; 9-41). The proportion of patients prescribed DMARDs in primary care was similar before and during the pandemic; however, during the pandemic, fewer people were prescribed methotrexate or leflunomide, and more were prescribed sulfasalazine or hydroxychloroquine.

Interpretation

Inflammatory arthritis diagnoses decreased markedly during the early phase of the pandemic. The impact on rheumatology assessment times and DMARD prescribing in primary care was less marked than might have been anticipated. This study demonstrates the feasibility of using routinely captured, near real-time data in the secure OpenSAFELY platform to benchmark care quality on a national scale, without the need for manual data collection.

Funding

None.",,pdf:https://researchonline.lshtm.ac.uk/id/eprint/4669009/1/Russell_etal_2022_Incidence-and-management-of-inflammatory.pdf; doi:https://doi.org/10.1016/S2665-9913(22)00305-8; html:https://europepmc.org/articles/PMC9691150; pdf:https://europepmc.org/articles/PMC9691150?pdf=render @@ -414,16 +414,16 @@ PMC9023380,https://doi.org/,Assessing the spread risk of COVID-19 associated wit 37253531,https://doi.org/10.1136/bmjgh-2022-009997,Effectiveness of a multicomponent intervention to face the COVID-19 pandemic in Rio de Janeiro's favelas: difference-in-differences analysis.,"Batista-da-Silva AA, Moraes CB, Bozza HR, Bastos LDSL, Ranzani OT, Hamacher S, Bozza FA, Comitê Gestor Conexão Saúde.",,BMJ global health,2023,2023-05-01,Y,"Control strategies; Public Health; Intervention Study; Infections, Diseases, Disorders, Injuries; Covid-19",,,"

Introduction

Few community-based interventions addressing the transmission control and clinical management of COVID-19 cases have been reported, especially in poor urban communities from low-income and middle-income countries. Here, we analyse the impact of a multicomponent intervention that combines community engagement, mobile surveillance, massive testing and telehealth on COVID-19 cases detection and mortality rates in a large vulnerable community (Complexo da Maré) in Rio de Janeiro, Brazil.

Methods

We performed a difference-in-differences (DID) analysis to estimate the impact of the multicomponent intervention in Maré, before (March-August 2020) and after the intervention (September 2020 to April 2021), compared with equivalent local vulnerable communities. We applied a negative binomial regression model to estimate the intervention effect in weekly cases and mortality rates in Maré.

Results

Before the intervention, Maré presented lower rates of reported COVID-19 cases compared with the control group (1373 vs 1579 cases/100 000 population), comparable mortality rates (309 vs 287 deaths/100 000 population) and higher case fatality rates (13.7% vs 12.2%). After the intervention, Maré displayed a 154% (95% CI 138.6% to 170.4%) relative increase in reported case rates. Relative changes in reported death rates were -60% (95% CI -69.0% to -47.9%) in Maré and -28% (95% CI -42.0% to -9.8%) in the control group. The case fatality rate was reduced by 77% (95% CI -93.1% to -21.1%) in Maré and 52% (95% CI -81.8% to -29.4%) in the control group. The DID showed a reduction of 46% (95% CI 17% to 65%) of weekly reported deaths and an increased 23% (95% CI 5% to 44%) of reported cases in Maré after intervention onset.

Conclusion

An integrated intervention combining communication, surveillance and telehealth, with a strong community engagement component, could reduce COVID-19 mortality and increase case detection in a large vulnerable community in Rio de Janeiro. These findings show that investment in community-based interventions may reduce mortality and improve pandemic control in poor communities from low-income and middle-income countries.",,doi:https://doi.org/10.1136/bmjgh-2022-009997; doi:https://doi.org/10.1136/bmjgh-2022-009997; html:https://europepmc.org/articles/PMC10230340; pdf:https://europepmc.org/articles/PMC10230340?pdf=render 37198478,https://doi.org/10.1038/s41586-023-06034-3,GWAS and meta-analysis identifies 49 genetic variants underlying critical COVID-19.,"Pairo-Castineira E, Rawlik K, Bretherick AD, Qi T, Wu Y, Nassiri I, McConkey GA, Zechner M, Klaric L, Griffiths F, Oosthuyzen W, Kousathanas A, Richmond A, Millar J, Russell CD, Malinauskas T, Thwaites R, Morrice K, Keating S, Maslove D, Nichol A, Semple MG, Knight J, Shankar-Hari M, Summers C, Hinds C, Horby P, Ling L, McAuley D, Montgomery H, Openshaw PJM, Begg C, Walsh T, Tenesa A, Flores C, Riancho JA, Rojas-Martinez A, Lapunzina P, GenOMICC Investigators, SCOURGE Consortium, ISARICC Investigators, 23andMe COVID-19 Team, Yang J, Ponting CP, Wilson JF, Vitart V, Abedalthagafi M, Luchessi AD, Parra EJ, Cruz R, Carracedo A, Fawkes A, Murphy L, Rowan K, Pereira AC, Law A, Fairfax B, Hendry SC, Baillie JK.",,Nature,2023,2023-05-17,Y,,,,"Critical illness in COVID-19 is an extreme and clinically homogeneous disease phenotype that we have previously shown1 to be highly efficient for discovery of genetic associations2. Despite the advanced stage of illness at presentation, we have shown that host genetics in patients who are critically ill with COVID-19 can identify immunomodulatory therapies with strong beneficial effects in this group3. Here we analyse 24,202 cases of COVID-19 with critical illness comprising a combination of microarray genotype and whole-genome sequencing data from cases of critical illness in the international GenOMICC (11,440 cases) study, combined with other studies recruiting hospitalized patients with a strong focus on severe and critical disease: ISARIC4C (676 cases) and the SCOURGE consortium (5,934 cases). To put these results in the context of existing work, we conduct a meta-analysis of the new GenOMICC genome-wide association study (GWAS) results with previously published data. We find 49 genome-wide significant associations, of which 16 have not been reported previously. To investigate the therapeutic implications of these findings, we infer the structural consequences of protein-coding variants, and combine our GWAS results with gene expression data using a monocyte transcriptome-wide association study (TWAS) model, as well as gene and protein expression using Mendelian randomization. We identify potentially druggable targets in multiple systems, including inflammatory signalling (JAK1), monocyte-macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).",,pdf:https://www.nature.com/articles/s41586-023-06034-3.pdf; doi:https://doi.org/10.1038/s41586-023-06034-3; html:https://europepmc.org/articles/PMC10208981; pdf:https://europepmc.org/articles/PMC10208981?pdf=render 35434685,https://doi.org/10.1016/j.lanepe.2022.100381,Dosing interval strategies for two-dose COVID-19 vaccination in 13 middle-income countries of Europe: Health impact modelling and benefit-risk analysis.,"Liu Y, Pearson CAB, Sandmann FG, Barnard RC, Kim JH, CMMID COVID-19 Working Group, Flasche S, Jit M, Abbas K.",,The Lancet regional health. Europe,2022,2022-04-11,Y,"Quantitative Methods; Mathematical Modelling; Public Health Intervention; Vaccine Policy; Ve, Vaccine Efficacy; Covid-19; Sars-cov-2; Voc, Variant Of Concern; Mic, Middle Income Country; Aefi, Adverse Events Following Immunisation",,,"

Background

In settings where the COVID-19 vaccine supply is constrained, extending the intervals between the first and second doses of the COVID-19 vaccine may allow more people receive their first doses earlier. Our aim is to estimate the health impact of COVID-19 vaccination alongside benefit-risk assessment of different dosing intervals in 13 middle-income countries (MICs) of Europe.

Methods

We fitted a dynamic transmission model to country-level daily reported COVID-19 mortality in 13 MICs in Europe (Albania, Armenia, Azerbaijan, Belarus, Bosnia and Herzegovina, Bulgaria, Georgia, Republic of Moldova, Russian Federation, Serbia, North Macedonia, Turkey, and Ukraine). A vaccine product with characteristics similar to those of the Oxford/AstraZeneca COVID-19 (AZD1222) vaccine was used in the base case scenario and was complemented by sensitivity analyses around efficacies similar to other COVID-19 vaccines. Both fixed dosing intervals at 4, 8, 12, 16, and 20 weeks and dose-specific intervals that prioritise specific doses for certain age groups were tested. Optimal intervals minimise COVID-19 mortality between March 2021 and December 2022. We incorporated the emergence of variants of concern (VOCs) into the model and conducted a benefit-risk assessment to quantify the tradeoff between health benefits versus adverse events following immunisation.

Findings

In all countries modelled, optimal strategies are those that prioritise the first doses among older adults (60+ years) or adults (20+ years), which lead to dosing intervals longer than six months. In comparison, a four-week fixed dosing interval may incur 10.1% [range: 4.3% - 19.0%; n = 13 (countries)] more deaths. The rapid waning of the immunity induced by the first dose (i.e. with means ranging 60-120 days as opposed to 360 days in the base case) resulted in shorter optimal dosing intervals of 8-20 weeks. Benefit-risk ratios were the highest for fixed dosing intervals of 8-12 weeks.

Interpretation

We infer that longer dosing intervals of over six months could reduce COVID-19 mortality in MICs of Europe. Certain parameters, such as rapid waning of first-dose induced immunity and increased immune escape through the emergence of VOCs, could significantly shorten the optimal dosing intervals.

Funding

World Health Organization.",,doi:https://doi.org/10.1016/j.lanepe.2022.100381; doi:https://doi.org/10.1016/j.lanepe.2022.100381; html:https://europepmc.org/articles/PMC8996067; pdf:https://europepmc.org/articles/PMC8996067?pdf=render -37745706,https://doi.org/10.3389/fendo.2023.1266557,"Editorial: Integrative multi-modal, multi-omics analytics for the better understanding of metabolic diseases.","Acharjee A, Agarwal P, Gkoutos GV.",,Frontiers in endocrinology,2023,2023-09-08,Y,Biomarker; Therapeutic; Diagnostic; Metabolic Disease; Omics,,,,,doi:https://doi.org/10.3389/fendo.2023.1266557; html:https://europepmc.org/articles/PMC10516571; pdf:https://europepmc.org/articles/PMC10516571?pdf=render 36476601,https://doi.org/10.1186/s12911-022-02055-6,Neural-signature methods for structured EHR prediction.,"Vauvelle A, Creed P, Denaxas S.",,BMC medical informatics and decision making,2022,2022-12-07,Y,Machine Learning; Electronic Healthcare Records; Signature Methods,,,"Models that can effectively represent structured Electronic Healthcare Records (EHR) are central to an increasing range of applications in healthcare. Due to the sequential nature of health data, Recurrent Neural Networks have emerged as the dominant component within state-of-the-art architectures. The signature transform represents an alternative modelling paradigm for sequential data. This transform provides a non-learnt approach to creating a fixed vector representation of temporal features and has shown strong performances across an increasing number of domains, including medical data. However, the signature method has not yet been applied to structured EHR data. To this end, we follow recent work that enables the signature to be used as a differentiable layer within a neural architecture enabling application in high dimensional domains where calculation would have previously been intractable. Using a heart failure prediction task as an exemplar, we provide an empirical evaluation of different variations of the signature method and compare against state-of-the-art baselines. This first application of neural-signature methods in real-world healthcare data shows a competitive performance when compared to strong baselines and thus warrants further investigation within the health domain.",,pdf:https://bmcmedinformdecismak.biomedcentral.com/counter/pdf/10.1186/s12911-022-02055-6; doi:https://doi.org/10.1186/s12911-022-02055-6; html:https://europepmc.org/articles/PMC9730578; pdf:https://europepmc.org/articles/PMC9730578?pdf=render +37745706,https://doi.org/10.3389/fendo.2023.1266557,"Editorial: Integrative multi-modal, multi-omics analytics for the better understanding of metabolic diseases.","Acharjee A, Agarwal P, Gkoutos GV.",,Frontiers in endocrinology,2023,2023-09-08,Y,Biomarker; Therapeutic; Diagnostic; Metabolic Disease; Omics,,,,,doi:https://doi.org/10.3389/fendo.2023.1266557; html:https://europepmc.org/articles/PMC10516571; pdf:https://europepmc.org/articles/PMC10516571?pdf=render 32835195,https://doi.org/10.1016/s2589-7500(20)30134-5,The effects of physical distancing on population mobility during the COVID-19 pandemic in the UK.,"Drake TM, Docherty AB, Weiser TG, Yule S, Sheikh A, Harrison EM.",,The Lancet. Digital health,2020,2020-06-12,Y,,,,,,doi:https://doi.org/10.1016/s2589-7500(20)30134-5; doi:https://doi.org/10.1016/S2589-7500(20)30134-5; html:https://europepmc.org/articles/PMC7292602; pdf:https://europepmc.org/articles/PMC7292602?pdf=render 35231023,https://doi.org/10.1371/journal.pmed.1003907,Changes in social contacts in England during the COVID-19 pandemic between March 2020 and March 2021 as measured by the CoMix survey: A repeated cross-sectional study.,"Gimma A, Munday JD, Wong KLM, Coletti P, van Zandvoort K, Prem K, CMMID COVID-19 working group, Klepac P, Rubin GJ, Funk S, Edmunds WJ, Jarvis CI.",,PLoS medicine,2022,2022-03-01,Y,,,,"

Background

During the Coronavirus Disease 2019 (COVID-19) pandemic, the United Kingdom government imposed public health policies in England to reduce social contacts in hopes of curbing virus transmission. We conducted a repeated cross-sectional study to measure contact patterns weekly from March 2020 to March 2021 to estimate the impact of these policies, covering 3 national lockdowns interspersed by periods of less restrictive policies.

Methods and findings

The repeated cross-sectional survey data were collected using online surveys of representative samples of the UK population by age and gender. Survey participants were recruited by the online market research company Ipsos MORI through internet-based banner and social media ads and email campaigns. The participant data used for this analysis are restricted to those who reported living in England. We calculated the mean daily contacts reported using a (clustered) bootstrap and fitted a censored negative binomial model to estimate age-stratified contact matrices and estimate proportional changes to the basic reproduction number under controlled conditions using the change in contacts as a scaling factor. To put the findings in perspective, we discuss contact rates recorded throughout the year in terms of previously recorded rates from the POLYMOD study social contact study. The survey recorded 101,350 observations from 19,914 participants who reported 466,710 contacts over 53 weeks. We observed changes in social contact patterns in England over time and by participants' age, personal risk factors, and perception of risk. The mean reported contacts for adults 18 to 59 years old ranged between 2.39 (95% confidence interval [CI] 2.20 to 2.60) contacts and 4.93 (95% CI 4.65 to 5.19) contacts during the study period. The mean contacts for school-age children (5 to 17 years old) ranged from 3.07 (95% CI 2.89 to 3.27) to 15.11 (95% CI 13.87 to 16.41). This demonstrates a sustained decrease in social contacts compared to a mean of 11.08 (95% CI 10.54 to 11.57) contacts per participant in all age groups combined as measured by the POLYMOD social contact study in 2005 to 2006. Contacts measured during periods of lockdowns were lower than in periods of eased social restrictions. The use of face coverings outside the home has remained high since the government mandated use in some settings in July 2020. The main limitations of this analysis are the potential for selection bias, as participants are recruited through internet-based campaigns, and recall bias, in which participants may under- or overreport the number of contacts they have made.

Conclusions

In this study, we observed that recorded contacts reduced dramatically compared to prepandemic levels (as measured in the POLYMOD study), with changes in reported contacts correlated with government interventions throughout the pandemic. Despite easing of restrictions in the summer of 2020, the mean number of reported contacts only returned to about half of that observed prepandemic at its highest recorded level. The CoMix survey provides a unique repeated cross-sectional data set for a full year in England, from the first day of the first lockdown, for use in statistical analyses and mathematical modelling of COVID-19 and other diseases.",,pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1003907&type=printable; doi:https://doi.org/10.1371/journal.pmed.1003907; html:https://europepmc.org/articles/PMC8887739; pdf:https://europepmc.org/articles/PMC8887739?pdf=render 33419870,https://doi.org/10.1136/bmjhci-2020-100254,Network graph representation of COVID-19 scientific publications to aid knowledge discovery.,"Cernile G, Heritage T, Sebire NJ, Gordon B, Schwering T, Kazemlou S, Borecki Y.",,BMJ health & care informatics,2021,2021-01-01,Y,Health care; Medical Informatics; Information Science; Bmj Health Informatics,,,"

Introduction

Numerous scientific journal articles related to COVID-19 have been rapidly published, making navigation and understanding of relationships difficult.

Methods

A graph network was constructed from the publicly available COVID-19 Open Research Dataset (CORD-19) of COVID-19-related publications using an engine leveraging medical knowledge bases to identify discrete medical concepts and an open-source tool (Gephi) to visualise the network.

Results

The network shows connections between diseases, medications and procedures identified from the title and abstract of 195 958 COVID-19-related publications (CORD-19 Dataset). Connections between terms with few publications, those unconnected to the main network and those irrelevant were not displayed. Nodes were coloured by knowledge base and the size of the node related to the number of publications containing the term. The data set and visualisations were made publicly accessible via a webtool.

Conclusion

Knowledge management approaches (text mining and graph networks) can effectively allow rapid navigation and exploration of entity inter-relationships to improve understanding of diseases such as COVID-19.",,pdf:https://informatics.bmj.com/content/bmjhci/28/1/e100254.full.pdf; doi:https://doi.org/10.1136/bmjhci-2020-100254; html:https://europepmc.org/articles/PMC7798427; pdf:https://europepmc.org/articles/PMC7798427?pdf=render 38238056,https://doi.org/10.1136/bmjopen-2023-076711,"Cohort profile: Born in Wales-a birth cohort with maternity, parental and child data linkage for life course research in Wales, UK.","Jones H, Seaborne MJ, Kennedy NL, James M, Dredge S, Bandyopadhyay A, Battaglia A, Davies S, Brophy S.",,BMJ open,2024,2024-01-18,Y,epidemiology; Public Health; Community Child Health; Surveys And Questionnaires,,,"

Purpose

Using Wales's national dataset for maternity and births as a core dataset, we have linked related datasets to create a more complete and comprehensive entire country birth cohort. Data of anonymised identified persons are linked on the individual level to data from health, social care and education data within the Secure Anonymised Information Linkage (SAIL) Databank. Each individual is assigned an encrypted Anonymised Linking Field; this field is used to link anonymised individuals across datasets. We present the descriptive data available in the core dataset, and the future expansion plans for the database beyond its initial development stage.

Participants

Descriptive information from 2011 to 2023 has been gathered from the National Community Child Health Database (NCCHD) in SAIL. This comprehensive dataset comprises over 400 000 child electronic records. Additionally, survey responses about health and well-being from a cross-section of the population including 2500 parents and 30 000 primary school children have been collected for enriched personal responses and linkage to the data spine.

Findings to date

The electronic cohort comprises all children born in Wales since 2011, with follow-up conducted until they finish primary school at age 11. The child cohort is 51%: 49% female: male, and 7.8% are from ethnic minority backgrounds. When considering age distribution, 26.8% of children are under the age of 5, while 63.2% fall within the age range of 5-11.

Future plans

Born in Wales will expand by 30 000 new births annually in Wales (in NCCHD), while including follow-up data of children and parents already in the database. Supplementary datasets complement the existing linkage, including primary care, hospital data, educational attainment and social care. Future research includes exploring the long-term implications of COVID-19 on child health and development, and examining the impact of parental work environment on child health and development.",,pdf:https://bmjopen.bmj.com/content/bmjopen/14/1/e076711.full.pdf; doi:https://doi.org/10.1136/bmjopen-2023-076711; html:https://europepmc.org/articles/PMC10806724; pdf:https://europepmc.org/articles/PMC10806724?pdf=render 33758017,https://doi.org/10.1126/science.abf9648,The impact of population-wide rapid antigen testing on SARS-CoV-2 prevalence in Slovakia.,"Pavelka M, Van-Zandvoort K, Abbott S, Sherratt K, Majdan M, CMMID COVID-19 working group, Inštitút Zdravotných Analýz, Jarčuška P, Krajčí M, Flasche S, Funk S.",,"Science (New York, N.Y.)",2021,2021-03-23,Y,,,,"Slovakia conducted multiple rounds of population-wide rapid antigen testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in late 2020, combined with a period of additional contact restrictions. Observed prevalence decreased by 58% (95% confidence interval: 57 to 58%) within 1 week in the 45 counties that were subject to two rounds of mass testing, an estimate that remained robust when adjusting for multiple potential confounders. Adjusting for epidemic growth of 4.4% (1.1 to 6.9%) per day preceding the mass testing campaign, the estimated decrease in prevalence compared with a scenario of unmitigated growth was 70% (67 to 73%). Modeling indicated that this decrease could not be explained solely by infection control measures but required the addition of the isolation and quarantine of household members of those testing positive.",,pdf:https://www.science.org/cms/asset/e974db95-138d-4a9f-aa91-2f8f6c705f36/pap.pdf; doi:https://doi.org/10.1126/science.abf9648; html:https://europepmc.org/articles/PMC8139426; pdf:https://europepmc.org/articles/PMC8139426?pdf=render 38434747,https://doi.org/10.12688/wellcomeopenres.19858.1,"Interpreting pathology test result values with comparators (<, >) in Electronic Health Records research: an OpenSAFELY short data report.","Curtis HJ, Fisher L, Evans D, OpenSAFELY Collaborative, Bacon S, Mehrkar A, Goldacre B, MacKenna B.",,Wellcome open research,2023,2023-11-22,Y,Pathology; Kidney function tests; Electronic Health Records,,,"

Background

Numeric results of pathology tests are sometimes returned as a range rather than a precise value, e.g. ""<10"". In health data research, test result values above or below clinical threshold values are often used to categorise patients into groups; however comparators (<, > etc) are typically stored separately to the numeric values and often ignored, but may influence interpretation.

Methods

With the approval of NHS England we used routine clinical data from 24 million patients in OpenSAFELY to identify pathology tests with comparators commonly attached to result values. For each test we report: the proportion returned with comparators present, split by comparator type and geographic region; the specific numeric result values returned with comparators, and the associated reference limits.

Results

We identified 11 common test codes where at least one in four results had comparators. Three codes related to glomerular filtration rate (GFR) tests/calculations, with 31-45% of results returned with ""≥"" comparators. At least 90% of tests with numeric values 60 and 90 represented ranges (≥60 and ≥90 respectively) rather than exact values. The other tests - four blood tests (Nucleated red blood cell count, Plasma C reactive protein, Tissue transglutaminase immunoglobulin A, and Rheumatoid factor), two urine tests (albumin/microalbumin) and two faecal tests (calprotectin and quantitative faecal immunochemical test) - were returned with ""≤"" comparators (29-86%).

Conclusions

Comparators appear commonly in certain pathology tests in electronic health records. For most common affected tests, we expect there to be minimal implications for researchers for most use-cases. However, care should be taken around whether results falling exactly on clinical threshold values should be considered ""normal"" or ""abnormal"". Results from GFR tests/calculations cannot reliably distinguish between mild kidney disease (60-<90) versus healthy kidney function (90+). More broadly, health data researchers using numeric test result values should consider the impact of comparators.",,doi:https://doi.org/10.12688/wellcomeopenres.19858.1; html:https://europepmc.org/articles/PMC10904973; pdf:https://europepmc.org/articles/PMC10904973?pdf=render -36426419,https://doi.org/10.1111/hsc.14109,"""I don't mean to be rude, but could you put a mask on while I'm here?"" A qualitative study of risks experienced by domiciliary care workers in Wales during the COVID-19 pandemic.","Prout H, Lugg-Widger FV, Brookes-Howell L, Cannings-John R, Akbari A, John A, Thomas DR, Robling M.",,Health & social care in the community,2022,2022-11-24,Y,Qualitative; risk; Social Care; Covid-19; Domiciliary Care Workers,,,"Domiciliary care workers (DCWs) continued to provide care to adults in their own homes throughout the COVID-19 pandemic. The evidence of the impact of COVID-19 on health outcomes of DCWs is currently mixed. The OSCAR study will quantify the impact of COVID-19 upon health outcomes of DCWs in Wales, explore causes of variation and extrapolate to the rest of the UK DCW population. An embedded qualitative study aimed to explore DCW experiences during the pandemic, including factors that may have varied risk of exposure to COVID-19 and adverse health and wellbeing outcomes. Registered DCWs working throughout Wales were invited to participate in a semi-structured telephone interview. 24 DCWs were interviewed between February and July 2021. Themes were identified through inductive analysis using thematic coding. Several themes emerged relating to risk of exposure to COVID-19. First, general changes to the role of the DCW during the pandemic were identified. Second, practical challenges for DCWs in the workplace were reported, including staff shortages, clients and families not following safety procedures, initial shortages of personal protective equipment (PPE), DCW criticism of standard use PPE, client difficulty with PPE and management of rapid antigen testing. Third, lack of government/employer preparation for a pandemic was described, including the reorganisation of staff clients and services, inadequate or confusing information for many DCWs, COVID-19 training and the need for improved practical instruction and limited official standard risk assessments for DCWs. Pressure to attend work and perceptions of COVID-19 risk and vaccination was also reported. In summary, this paper describes the risk factors associated with working during the pandemic. We have mapped recommendations for each problem using these qualitative findings including tailored training and better support for isolated team members and identified the required changes at several socio-ecological levels.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/hsc.14109; doi:https://doi.org/10.1111/hsc.14109; html:https://europepmc.org/articles/PMC10100139; pdf:https://europepmc.org/articles/PMC10100139?pdf=render 33667930,https://doi.org/10.1016/j.ijmedinf.2021.104400,Real-time spatial health surveillance: Mapping the UK COVID-19 epidemic.,"Fry R, Hollinghurst J, Stagg HR, Thompson DA, Fronterre C, Orton C, Lyons RA, Ford DV, Sheikh A, Diggle PJ.",,International journal of medical informatics,2021,2021-01-28,Y,,,,"Introduction The COVID-19 pandemic has highlighted the need for robust data linkage systems and methods for identifying outbreaks of disease in near real-time. Objectives The primary objective of this study was to develop a real-time geospatial surveillance system to monitor the spread of COVID-19 across the UK. Methods Using self-reported app data and the Secure Anonymised Information Linkage (SAIL) Databank, we demonstrate the use of sophisticated spatial modelling for near-real-time prediction of COVID-19 prevalence at small-area resolution to inform strategic government policy areas. Results We demonstrate that using a combination of crowd-sourced app data and sophisticated geo-statistical techniques it is possible to predict hot spots of COVID-19 at fine geographic scales, nationally. We are also able to produce estimates of their precision, which is an important pre-requisite to an effective control strategy to guard against over-reaction to potentially spurious features of 'best guess' predictions. Conclusion In the UK, important emerging risk-factors such as social deprivation or ethnicity vary over small distances, hence risk needs to be modelled at fine spatial resolution to avoid aggregation bias. We demonstrate that existing geospatial statistical methods originally developed for global health applications are well-suited to this task and can be used in an anonymised databank environment, thus preserving the privacy of the individuals who contribute their data.",,doi:https://doi.org/10.1016/j.ijmedinf.2021.104400; doi:https://doi.org/10.1016/j.ijmedinf.2021.104400; html:https://europepmc.org/articles/PMC7843148 +36426419,https://doi.org/10.1111/hsc.14109,"""I don't mean to be rude, but could you put a mask on while I'm here?"" A qualitative study of risks experienced by domiciliary care workers in Wales during the COVID-19 pandemic.","Prout H, Lugg-Widger FV, Brookes-Howell L, Cannings-John R, Akbari A, John A, Thomas DR, Robling M.",,Health & social care in the community,2022,2022-11-24,Y,Qualitative; risk; Social Care; Covid-19; Domiciliary Care Workers,,,"Domiciliary care workers (DCWs) continued to provide care to adults in their own homes throughout the COVID-19 pandemic. The evidence of the impact of COVID-19 on health outcomes of DCWs is currently mixed. The OSCAR study will quantify the impact of COVID-19 upon health outcomes of DCWs in Wales, explore causes of variation and extrapolate to the rest of the UK DCW population. An embedded qualitative study aimed to explore DCW experiences during the pandemic, including factors that may have varied risk of exposure to COVID-19 and adverse health and wellbeing outcomes. Registered DCWs working throughout Wales were invited to participate in a semi-structured telephone interview. 24 DCWs were interviewed between February and July 2021. Themes were identified through inductive analysis using thematic coding. Several themes emerged relating to risk of exposure to COVID-19. First, general changes to the role of the DCW during the pandemic were identified. Second, practical challenges for DCWs in the workplace were reported, including staff shortages, clients and families not following safety procedures, initial shortages of personal protective equipment (PPE), DCW criticism of standard use PPE, client difficulty with PPE and management of rapid antigen testing. Third, lack of government/employer preparation for a pandemic was described, including the reorganisation of staff clients and services, inadequate or confusing information for many DCWs, COVID-19 training and the need for improved practical instruction and limited official standard risk assessments for DCWs. Pressure to attend work and perceptions of COVID-19 risk and vaccination was also reported. In summary, this paper describes the risk factors associated with working during the pandemic. We have mapped recommendations for each problem using these qualitative findings including tailored training and better support for isolated team members and identified the required changes at several socio-ecological levels.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/hsc.14109; doi:https://doi.org/10.1111/hsc.14109; html:https://europepmc.org/articles/PMC10100139; pdf:https://europepmc.org/articles/PMC10100139?pdf=render 36820079,https://doi.org/10.1183/23120541.00274-2022,Characteristics and risk factors for post-COVID-19 breathlessness after hospitalisation for COVID-19.,"Daines L, Zheng B, Elneima O, Harrison E, Lone NI, Hurst JR, Brown JS, Sapey E, Chalmers JD, Quint JK, Pfeffer P, Siddiqui S, Walker S, Poinasamy K, McAuley H, Sereno M, Shikotra A, Singapuri A, Docherty AB, Marks M, Toshner M, Howard LS, Horsley A, Jenkins G, Porter JC, Ho LP, Raman B, Wain LV, Brightling CE, Evans RA, Heaney LG, De Soyza A, Sheikh A.",,ERJ open research,2023,2023-01-01,Y,,,,"

Background

Persistence of respiratory symptoms, particularly breathlessness, after acute coronavirus disease 2019 (COVID-19) infection has emerged as a significant clinical problem. We aimed to characterise and identify risk factors for patients with persistent breathlessness following COVID-19 hospitalisation.

Methods

PHOSP-COVID is a multicentre prospective cohort study of UK adults hospitalised for COVID-19. Clinical data were collected during hospitalisation and at a follow-up visit. Breathlessness was measured by a numeric rating scale of 0-10. We defined post-COVID-19 breathlessness as an increase in score of ≥1 compared to the pre-COVID-19 level. Multivariable logistic regression was used to identify risk factors and to develop a prediction model for post-COVID-19 breathlessness.

Results

We included 1226 participants (37% female, median age 59 years, 22% mechanically ventilated). At a median 5 months after discharge, 50% reported post-COVID-19 breathlessness. Risk factors for post-COVID-19 breathlessness were socioeconomic deprivation (adjusted OR 1.67, 95% CI 1.14-2.44), pre-existing depression/anxiety (adjusted OR 1.58, 95% CI 1.06-2.35), female sex (adjusted OR 1.56, 95% CI 1.21-2.00) and admission duration (adjusted OR 1.01, 95% CI 1.00-1.02). Black ethnicity (adjusted OR 0.56, 95% CI 0.35-0.89) and older age groups (adjusted OR 0.31, 95% CI 0.14-0.66) were less likely to report post-COVID-19 breathlessness. Post-COVID-19 breathlessness was associated with worse performance on the shuttle walk test and forced vital capacity, but not with obstructive airflow limitation. The prediction model had fair discrimination (concordance statistic 0.66, 95% CI 0.63-0.69) and good calibration (calibration slope 1.00, 95% CI 0.80-1.21).

Conclusions

Post-COVID-19 breathlessness was commonly reported in this national cohort of patients hospitalised for COVID-19 and is likely to be a multifactorial problem with physical and emotional components.",,pdf:https://openres.ersjournals.com/content/erjor/early/2023/01/26/23120541.00274-2022.full.pdf; doi:https://doi.org/10.1183/23120541.00274-2022; html:https://europepmc.org/articles/PMC9790090; pdf:https://europepmc.org/articles/PMC9790090?pdf=render 34461893,https://doi.org/10.1186/s12916-021-02096-0,The association between mechanical ventilator compatible bed occupancy and mortality risk in intensive care patients with COVID-19: a national retrospective cohort study.,"Wilde H, Mellan T, Hawryluk I, Dennis JM, Denaxas S, Pagel C, Duncan A, Bhatt S, Flaxman S, Mateen BA, Vollmer SJ.",,BMC medicine,2021,2021-08-30,Y,Critical Care; Hospital Mortality; Quality Of Healthcare; Public Health Surveillance; Coronavirus Infection,,,"

Background

The literature paints a complex picture of the association between mortality risk and ICU strain. In this study, we sought to determine if there is an association between mortality risk in intensive care units (ICU) and occupancy of beds compatible with mechanical ventilation, as a proxy for strain.

Methods

A national retrospective observational cohort study of 89 English hospital trusts (i.e. groups of hospitals functioning as single operational units). Seven thousand one hundred thirty-three adults admitted to an ICU in England between 2 April and 1 December, 2020 (inclusive), with presumed or confirmed COVID-19, for whom data was submitted to the national surveillance programme and met study inclusion criteria. A Bayesian hierarchical approach was used to model the association between hospital trust level (mechanical ventilation compatible), bed occupancy, and in-hospital all-cause mortality. Results were adjusted for unit characteristics (pre-pandemic size), individual patient-level demographic characteristics (age, sex, ethnicity, deprivation index, time-to-ICU admission), and recorded chronic comorbidities (obesity, diabetes, respiratory disease, liver disease, heart disease, hypertension, immunosuppression, neurological disease, renal disease).

Results

One hundred thirty-five thousand six hundred patient days were observed, with a mortality rate of 19.4 per 1000 patient days. Adjusting for patient-level factors, mortality was higher for admissions during periods of high occupancy (> 85% occupancy versus the baseline of 45 to 85%) [OR 1.23 (95% posterior credible interval (PCI): 1.08 to 1.39)]. In contrast, mortality was decreased for admissions during periods of low occupancy (< 45% relative to the baseline) [OR 0.83 (95% PCI 0.75 to 0.94)].

Conclusion

Increasing occupancy of beds compatible with mechanical ventilation, a proxy for operational strain, is associated with a higher mortality risk for individuals admitted to ICU. Further research is required to establish if this is a causal relationship or whether it reflects strain on other operational factors such as staff. If causal, the result highlights the importance of strategies to keep ICU occupancy low to mitigate the impact of this type of resource saturation.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-021-02096-0; doi:https://doi.org/10.1186/s12916-021-02096-0; html:https://europepmc.org/articles/PMC8404408; pdf:https://europepmc.org/articles/PMC8404408?pdf=render 37067557,https://doi.org/10.1007/s00134-023-07039-2,Variants of concern and clinical outcomes in critically ill COVID-19 patients.,DP-EFFECT-BRAZIL investigators.,,Intensive care medicine,2023,2023-04-17,Y,,,,,,pdf:https://link.springer.com/content/pdf/10.1007/s00134-023-07039-2.pdf; doi:https://doi.org/10.1007/s00134-023-07039-2; html:https://europepmc.org/articles/PMC10108805; pdf:https://europepmc.org/articles/PMC10108805?pdf=render @@ -457,15 +457,15 @@ PMC9023380,https://doi.org/,Assessing the spread risk of COVID-19 associated wit 36526323,https://doi.org/10.1136/bmjopen-2022-068252,"Identification of risk factors associated with prolonged hospital stay following primary knee replacement surgery: a retrospective, longitudinal observational study.","Wilson R, Margelyte R, Redaniel MT, Eyles E, Jones T, Penfold C, Blom A, Elliott A, Harper A, Keen T, Pitt M, Judge A.",,BMJ open,2022,2022-12-16,Y,Knee; Rheumatology; Statistics & Research Methods; Orthopaedic & Trauma Surgery; Adult Orthopaedics,,,"

Objectives

To identify risk factors associated with prolonged length of hospital stay and staying in hospital longer than medically necessary following primary knee replacement surgery.

Design

Retrospective, longitudinal observational study.

Setting

Elective knee replacement surgeries between 2016 and 2019 were identified using routinely collected data from an NHS Trust in England.

Participants

There were 2295 knee replacement patients with complete data included in analysis. The mean age was 68 (SD 11) and 60% were female.

Outcome measures

We assessed a binary length of stay outcome (>7 days), a continuous length of stay outcome (≤30 days) and a binary measure of whether patients remained in hospital when they were medically fit for discharge.

Results

The mean length of stay was 5.0 days (SD 3.9), 15.4% of patients were in hospital for >7 days and 7.1% remained in hospital when they were medically fit for discharge. Longer length of stay was associated with older age (b=0.08, 95% CI 0.07 to 0.09), female sex (b=0.36, 95% CI 0.06 to 0.67), high deprivation (b=0.98, 95% CI 0.47 to 1.48) and more comorbidities (b=2.48, 95% CI 0.15 to 4.81). Remaining in hospital beyond being medically fit for discharge was associated with older age (OR=1.07, 95% CI 1.05 to 1.09), female sex (OR=1.71, 95% CI 1.19 to 2.47) and high deprivation (OR=2.27, 95% CI 1.27 to 4.06).

Conclusions

The regression models could be used to identify which patients are likely to occupy hospital beds for longer. This could be helpful in scheduling operations to aid hospital efficiency by planning these patients' operations for when the hospital is less busy.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/12/e068252.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-068252; html:https://europepmc.org/articles/PMC9764602; pdf:https://europepmc.org/articles/PMC9764602?pdf=render 37544968,https://doi.org/10.1007/s11357-023-00890-7,"Does physical activity moderate the association between shorter leukocyte telomere length and incident coronary heart disease? Data from 54,180 UK Biobank participants.","Xiang M, Pilling LC, Melzer D, Kirk B, Duque G, Liu R, Kuchel GA, Wood AR, Metcalf B, Diniz BS, Hillsdon M, Kuo CL.",,GeroScience,2024,2023-08-07,Y,Interaction; epidemiology; Population-based Study; Prospective Cohort Study; Accelerometer; Moderation; Accelerometry; Time To Event Survival Data,,,"Telomere shortening is a biological aging hallmark. The effect of short telomere length may be targeted by increased physical activity to reduce the risk of multiple aging-related diseases, including coronary heart disease (CHD). The objective was to assess the moderation effect of accelerometer-based physical activity (aPA) on the association between shorter leukocyte telomere length (LTL) relatively in the population sample and incident CHD. Data were from the UK Biobank participants with well-calibrated accelerometer data for at least 6.5 days (n = 54,180). Relative mean LTL at baseline (5-6 years prior to aPA assessment) was measured in T/S ratio, using a multiplex quantitative polymerase chain reaction (qPCR) technology, by comparing the amount of the telomere amplification product (T) to that of a single-copy gene (S). aPA measures included total number of events (at least 10-s continued physical activity > 32 milligravities [mg]), total volume, mean duration, mean intensity, and peak intensity of all events. LTL, aPA measures, and their interactions were associated with incident CHD (mean follow-up 6.8 years) using Cox proportional hazards models adjusting for covariates. Longer LTL (relative to the sample distribution) was associated with reduced incidence of CHD (adjusted hazard ratio [aHR] = 0.94 per standard deviation [SD] increase in LTL, [95% CI, 0.90 to 0.99], P = .010). Incidence of CHD was reduced by higher total volume of aPA (aHR = 0.82 per SD increase in LTL, [95% CI, 0.71 to 0.95], P = .010) but increased by higher total number of events (aHR = 1.11 per SD increase in LTL, [95% CI, 1.02 to 1.21], P = .020) after controlling for other aPA measures and covariates. However, none of the interactions between LTL and aPA measures was statistically significant (P = .171).",,pdf:https://link.springer.com/content/pdf/10.1007/s11357-023-00890-7.pdf; doi:https://doi.org/10.1007/s11357-023-00890-7; html:https://europepmc.org/articles/PMC10828302; pdf:https://europepmc.org/articles/PMC10828302?pdf=render 33725121,https://doi.org/10.1093/rheumatology/keab250,COVID-19 in patients with autoimmune diseases: characteristics and outcomes in a multinational network of cohorts across three countries.,"Tan EH, Sena AG, Prats-Uribe A, You SC, Ahmed WU, Kostka K, Reich C, Duvall SL, Lynch KE, Matheny ME, Duarte-Salles T, Bertolin SF, Hripcsak G, Natarajan K, Falconer T, Spotnitz M, Ostropolets A, Blacketer C, Alshammari TM, Alghoul H, Alser O, Lane JCE, Dawoud DM, Shah K, Yang Y, Zhang L, Areia C, Golozar A, Recalde M, Casajust P, Jonnagaddala J, Subbian V, Vizcaya D, Lai LYH, Nyberg F, Morales DR, Posada JD, Shah NH, Gong M, Vivekanantham A, Abend A, Minty EP, Suchard M, Rijnbeek P, Ryan PB, Prieto-Alhambra D.",,"Rheumatology (Oxford, England)",2021,2021-10-01,Y,Mortality; Hospitalization; Open Science; Autoimmune Condition; Observational Health Data Sciences And Informatics (Ohdsi); Observational Medical Outcomes Partnership (Omop); Covid-19,,,"

Objective

Patients with autoimmune diseases were advised to shield to avoid coronavirus disease 2019 (COVID-19), but information on their prognosis is lacking. We characterized 30-day outcomes and mortality after hospitalization with COVID-19 among patients with prevalent autoimmune diseases, and compared outcomes after hospital admissions among similar patients with seasonal influenza.

Methods

A multinational network cohort study was conducted using electronic health records data from Columbia University Irving Medical Center [USA, Optum (USA), Department of Veterans Affairs (USA), Information System for Research in Primary Care-Hospitalization Linked Data (Spain) and claims data from IQVIA Open Claims (USA) and Health Insurance and Review Assessment (South Korea). All patients with prevalent autoimmune diseases, diagnosed and/or hospitalized between January and June 2020 with COVID-19, and similar patients hospitalized with influenza in 2017-18 were included. Outcomes were death and complications within 30 days of hospitalization.

Results

We studied 133 589 patients diagnosed and 48 418 hospitalized with COVID-19 with prevalent autoimmune diseases. Most patients were female, aged ≥50 years with previous comorbidities. The prevalence of hypertension (45.5-93.2%), chronic kidney disease (14.0-52.7%) and heart disease (29.0-83.8%) was higher in hospitalized vs diagnosed patients with COVID-19. Compared with 70 660 hospitalized with influenza, those admitted with COVID-19 had more respiratory complications including pneumonia and acute respiratory distress syndrome, and higher 30-day mortality (2.2-4.3% vs 6.32-24.6%).

Conclusion

Compared with influenza, COVID-19 is a more severe disease, leading to more complications and higher mortality.",,pdf:https://academic.oup.com/rheumatology/article-pdf/60/SI/SI37/40544680/keab250.pdf; doi:https://doi.org/10.1093/rheumatology/keab250; html:https://europepmc.org/articles/PMC7989171; pdf:https://europepmc.org/articles/PMC7989171?pdf=render -37080124,https://doi.org/10.1016/j.seizure.2023.04.006,COVID-19 vaccination uptake in people with epilepsy in wales.,"Strafford H, Lacey AS, Hollinghurst J, Akbari A, Watkins A, Paterson J, Jennings D, Lyons RA, Powell HR, Kerr MP, Chin RW, Pickrell WO.",,Seizure,2023,2023-04-06,Y,"Epilepsy; Vaccination; Data Linkage; Electronic Health Records; Pandemic, Covid-19",,,"

Purpose

People with epilepsy (PWE) are at increased risk of severe COVID-19. Assessing COVID-19 vaccine uptake is therefore important. We compared COVID-19 vaccination uptake for PWE in Wales with a matched control cohort.

Methods

We performed a retrospective, population, cohort study using linked, anonymised, Welsh electronic health records within the Secure Anonymised Information Linkage (SAIL) Databank (Welsh population=3.1 million).We identified PWE in Wales between 1st March 2020 and 31st December 2021 and created a control cohort using exact 5:1 matching (sex, age and socioeconomic status). We recorded 1st, 2nd and booster COVID-19 vaccinations.

Results

There were 25,404 adults with epilepsy (127,020 controls). 23,454 (92.3%) had a first vaccination, 22,826 (89.9%) a second, and 17,797 (70.1%) a booster. Comparative figures for controls were: 112,334 (87.8%), 109,057 (85.2%) and 79,980 (62.4%).PWE had higher vaccination rates in all age, sex and socioeconomic subgroups apart from booster uptake in older subgroups. Vaccination rates were higher in older subgroups, women and less deprived areas for both cohorts. People with intellectual disability and epilepsy had higher vaccination rates when compared with controls with intellectual disability.

Conclusions

COVID-19 vaccination uptake for PWE in Wales was higher than that for a matched control group.",,pdf:http://www.seizure-journal.com/article/S1059131123001000/pdf; doi:https://doi.org/10.1016/j.seizure.2023.04.006; html:https://europepmc.org/articles/PMC10076248; pdf:https://europepmc.org/articles/PMC10076248?pdf=render 35079022,https://doi.org/10.1038/s41467-022-28157-3,Regional excess mortality during the 2020 COVID-19 pandemic in five European countries.,"Konstantinoudis G, Cameletti M, Gómez-Rubio V, Gómez IL, Pirani M, Baio G, Larrauri A, Riou J, Egger M, Vineis P, Blangiardo M.",,Nature communications,2022,2022-01-25,Y,,,,"The impact of the COVID-19 pandemic on excess mortality from all causes in 2020 varied across and within European countries. Using data for 2015-2019, we applied Bayesian spatio-temporal models to quantify the expected weekly deaths at the regional level had the pandemic not occurred in England, Greece, Italy, Spain, and Switzerland. With around 30%, Madrid, Castile-La Mancha, Castile-Leon (Spain) and Lombardia (Italy) were the regions with the highest excess mortality. In England, Greece and Switzerland, the regions most affected were Outer London and the West Midlands (England), Eastern, Western and Central Macedonia (Greece), and Ticino (Switzerland), with 15-20% excess mortality in 2020. Our study highlights the importance of the large transportation hubs for establishing community transmission in the first stages of the pandemic. Here, we show that acting promptly to limit transmission around these hubs is essential to prevent spread to other regions and countries.",,pdf:https://www.nature.com/articles/s41467-022-28157-3.pdf; doi:https://doi.org/10.1038/s41467-022-28157-3; html:https://europepmc.org/articles/PMC8789777; pdf:https://europepmc.org/articles/PMC8789777?pdf=render +37080124,https://doi.org/10.1016/j.seizure.2023.04.006,COVID-19 vaccination uptake in people with epilepsy in wales.,"Strafford H, Lacey AS, Hollinghurst J, Akbari A, Watkins A, Paterson J, Jennings D, Lyons RA, Powell HR, Kerr MP, Chin RW, Pickrell WO.",,Seizure,2023,2023-04-06,Y,"Epilepsy; Vaccination; Data Linkage; Electronic Health Records; Pandemic, Covid-19",,,"

Purpose

People with epilepsy (PWE) are at increased risk of severe COVID-19. Assessing COVID-19 vaccine uptake is therefore important. We compared COVID-19 vaccination uptake for PWE in Wales with a matched control cohort.

Methods

We performed a retrospective, population, cohort study using linked, anonymised, Welsh electronic health records within the Secure Anonymised Information Linkage (SAIL) Databank (Welsh population=3.1 million).We identified PWE in Wales between 1st March 2020 and 31st December 2021 and created a control cohort using exact 5:1 matching (sex, age and socioeconomic status). We recorded 1st, 2nd and booster COVID-19 vaccinations.

Results

There were 25,404 adults with epilepsy (127,020 controls). 23,454 (92.3%) had a first vaccination, 22,826 (89.9%) a second, and 17,797 (70.1%) a booster. Comparative figures for controls were: 112,334 (87.8%), 109,057 (85.2%) and 79,980 (62.4%).PWE had higher vaccination rates in all age, sex and socioeconomic subgroups apart from booster uptake in older subgroups. Vaccination rates were higher in older subgroups, women and less deprived areas for both cohorts. People with intellectual disability and epilepsy had higher vaccination rates when compared with controls with intellectual disability.

Conclusions

COVID-19 vaccination uptake for PWE in Wales was higher than that for a matched control group.",,pdf:http://www.seizure-journal.com/article/S1059131123001000/pdf; doi:https://doi.org/10.1016/j.seizure.2023.04.006; html:https://europepmc.org/articles/PMC10076248; pdf:https://europepmc.org/articles/PMC10076248?pdf=render 36812516,https://doi.org/10.1371/journal.pdig.0000007,A proteomic survival predictor for COVID-19 patients in intensive care.,"Demichev V, Tober-Lau P, Nazarenko T, Lemke O, Kaur Aulakh S, Whitwell HJ, Röhl A, Freiwald A, Mittermaier M, Szyrwiel L, Ludwig D, Correia-Melo C, Lippert LJ, Helbig ET, Stubbemann P, Olk N, Thibeault C, Grüning NM, Blyuss O, Vernardis S, White M, Messner CB, Joannidis M, Sonnweber T, Klein SJ, Pizzini A, Wohlfarter Y, Sahanic S, Hilbe R, Schaefer B, Wagner S, Machleidt F, Garcia C, Ruwwe-Glösenkamp C, Lingscheid T, Bosquillon de Jarcy L, Stegemann MS, Pfeiffer M, Jürgens L, Denker S, Zickler D, Spies C, Edel A, Müller NB, Enghard P, Zelezniak A, Bellmann-Weiler R, Weiss G, Campbell A, Hayward C, Porteous DJ, Marioni RE, Uhrig A, Zoller H, Löffler-Ragg J, Keller MA, Tancevski I, Timms JF, Zaikin A, Hippenstiel S, Ramharter M, Müller-Redetzky H, Witzenrath M, Suttorp N, Lilley K, Mülleder M, Sander LE, PA-COVID-19 Study group, Kurth F, Ralser M.",,PLOS digital health,2022,2022-01-18,Y,,,,"Global healthcare systems are challenged by the COVID-19 pandemic. There is a need to optimize allocation of treatment and resources in intensive care, as clinically established risk assessments such as SOFA and APACHE II scores show only limited performance for predicting the survival of severely ill COVID-19 patients. Additional tools are also needed to monitor treatment, including experimental therapies in clinical trials. Comprehensively capturing human physiology, we speculated that proteomics in combination with new data-driven analysis strategies could produce a new generation of prognostic discriminators. We studied two independent cohorts of patients with severe COVID-19 who required intensive care and invasive mechanical ventilation. SOFA score, Charlson comorbidity index, and APACHE II score showed limited performance in predicting the COVID-19 outcome. Instead, the quantification of 321 plasma protein groups at 349 timepoints in 50 critically ill patients receiving invasive mechanical ventilation revealed 14 proteins that showed trajectories different between survivors and non-survivors. A predictor trained on proteomic measurements obtained at the first time point at maximum treatment level (i.e. WHO grade 7), which was weeks before the outcome, achieved accurate classification of survivors (AUROC 0.81). We tested the established predictor on an independent validation cohort (AUROC 1.0). The majority of proteins with high relevance in the prediction model belong to the coagulation system and complement cascade. Our study demonstrates that plasma proteomics can give rise to prognostic predictors substantially outperforming current prognostic markers in intensive care.",,pdf:https://journals.plos.org/digitalhealth/article/file?id=10.1371/journal.pdig.0000007&type=printable; doi:https://doi.org/10.1371/journal.pdig.0000007; html:https://europepmc.org/articles/PMC9931303; pdf:https://europepmc.org/articles/PMC9931303?pdf=render 33782427,https://doi.org/10.1038/s41598-021-86266-3,Analysis of temporal trends in potential COVID-19 cases reported through NHS Pathways England.,"Leclerc QJ, Nightingale ES, Abbott S, CMMID COVID-19 Working Group, Jombart T.",,Scientific reports,2021,2021-03-29,Y,,,,"The National Health Service (NHS) Pathways triage system collates data on enquiries to 111 and 999 services in England. Since the 18th of March 2020, these data have been made publically available for potential COVID-19 symptoms self-reported by members of the public. Trends in such reports over time are likely to reflect behaviour of the ongoing epidemic within the wider community, potentially capturing valuable information across a broader severity profile of cases than hospital admission data. We present a fully reproducible analysis of temporal trends in NHS Pathways reports until 14th May 2020, nationally and regionally, and demonstrate that rates of growth/decline and effective reproduction number estimated from these data may be useful in monitoring transmission. This is a particularly pressing issue as lockdown restrictions begin to be lifted and evidence of disease resurgence must be constantly reassessed. We further assess the correlation between NHS Pathways reports and a publicly available NHS dataset of COVID-19-associated deaths in England, finding that enquiries to 111/999 were strongly associated with daily deaths reported 16 days later. Our results highlight the potential of NHS Pathways as the basis of an early warning system. However, this dataset relies on self-reported symptoms, which are at risk of being severely biased. Further detailed work is therefore necessary to investigate potential behavioural issues which might otherwise explain our conclusions.",,pdf:https://www.nature.com/articles/s41598-021-86266-3.pdf; doi:https://doi.org/10.1038/s41598-021-86266-3; html:https://europepmc.org/articles/PMC8007605; pdf:https://europepmc.org/articles/PMC8007605?pdf=render 33711543,https://doi.org/10.1016/j.jbi.2021.103728,Explainable automated coding of clinical notes using hierarchical label-wise attention networks and label embedding initialisation.,"Dong H, Suárez-Paniagua V, Whiteley W, Wu H.",,Journal of biomedical informatics,2021,2021-03-09,N,Natural Language Processing; Multi-label Classification; Deep Learning; Attention Mechanisms; Automated Medical Coding; Explainability; Label Correlation,,,"

Background

Diagnostic or procedural coding of clinical notes aims to derive a coded summary of disease-related information about patients. Such coding is usually done manually in hospitals but could potentially be automated to improve the efficiency and accuracy of medical coding. Recent studies on deep learning for automated medical coding achieved promising performances. However, the explainability of these models is usually poor, preventing them to be used confidently in supporting clinical practice. Another limitation is that these models mostly assume independence among labels, ignoring the complex correlations among medical codes which can potentially be exploited to improve the performance.

Methods

To address the issues of model explainability and label correlations, we propose a Hierarchical Label-wise Attention Network (HLAN), which aimed to interpret the model by quantifying importance (as attention weights) of words and sentences related to each of the labels. Secondly, we propose to enhance the major deep learning models with a label embedding (LE) initialisation approach, which learns a dense, continuous vector representation and then injects the representation into the final layers and the label-wise attention layers in the models. We evaluated the methods using three settings on the MIMIC-III discharge summaries: full codes, top-50 codes, and the UK NHS (National Health Service) COVID-19 (Coronavirus disease 2019) shielding codes. Experiments were conducted to compare the HLAN model and label embedding initialisation to the state-of-the-art neural network based methods, including variants of Convolutional Neural Networks (CNNs) and Recurrent Neural Networks (RNNs).

Results

HLAN achieved the best Micro-level AUC and F1 on the top-50 code prediction, 91.9% and 64.1%, respectively; and comparable results on the NHS COVID-19 shielding code prediction to other models: around 97% Micro-level AUC. More importantly, in the analysis of model explanations, by highlighting the most salient words and sentences for each label, HLAN showed more meaningful and comprehensive model interpretation compared to the CNN-based models and its downgraded baselines, HAN and HA-GRU. Label embedding (LE) initialisation significantly boosted the previous state-of-the-art model, CNN with attention mechanisms, on the full code prediction to 52.5% Micro-level F1. The analysis of the layers initialised with label embeddings further explains the effect of this initialisation approach. The source code of the implementation and the results are openly available at https://github.com/acadTags/Explainable-Automated-Medical-Coding.

Conclusion

We draw the conclusion from the evaluation results and analyses. First, with hierarchical label-wise attention mechanisms, HLAN can provide better or comparable results for automated coding to the state-of-the-art, CNN-based models. Second, HLAN can provide more comprehensive explanations for each label by highlighting key words and sentences in the discharge summaries, compared to the n-grams in the CNN-based models and the downgraded baselines, HAN and HA-GRU. Third, the performance of deep learning based multi-label classification for automated coding can be consistently boosted by initialising label embeddings that captures the correlations among labels. We further discuss the advantages and drawbacks of the overall method regarding its potential to be deployed to a hospital and suggest areas for future studies.",,doi:https://doi.org/10.1016/j.jbi.2021.103728; doi:https://doi.org/10.1016/j.jbi.2021.103728 34606520,https://doi.org/10.1371/journal.pmed.1003815,"COVID-19 vaccination in Sindh Province, Pakistan: A modelling study of health impact and cost-effectiveness.","Pearson CAB, Bozzani F, Procter SR, Davies NG, Huda M, Jensen HT, Keogh-Brown M, Khalid M, Sweeney S, Torres-Rueda S, CHiL COVID-19 Working Group, CMMID COVID-19 Working Group, Eggo RM, Vassall A, Jit M.",,PLoS medicine,2021,2021-10-04,Y,,,,"

Background

Multiple Coronavirus Disease 2019 (COVID-19) vaccines appear to be safe and efficacious, but only high-income countries have the resources to procure sufficient vaccine doses for most of their eligible populations. The World Health Organization has published guidelines for vaccine prioritisation, but most vaccine impact projections have focused on high-income countries, and few incorporate economic considerations. To address this evidence gap, we projected the health and economic impact of different vaccination scenarios in Sindh Province, Pakistan (population: 48 million).

Methods and findings

We fitted a compartmental transmission model to COVID-19 cases and deaths in Sindh from 30 April to 15 September 2020. We then projected cases, deaths, and hospitalisation outcomes over 10 years under different vaccine scenarios. Finally, we combined these projections with a detailed economic model to estimate incremental costs (from healthcare and partial societal perspectives), disability-adjusted life years (DALYs), and incremental cost-effectiveness ratio (ICER) for each scenario. We project that 1 year of vaccine distribution, at delivery rates consistent with COVAX projections, using an infection-blocking vaccine at $3/dose with 70% efficacy and 2.5-year duration of protection is likely to avert around 0.9 (95% credible interval (CrI): 0.9, 1.0) million cases, 10.1 (95% CrI: 10.1, 10.3) thousand deaths, and 70.1 (95% CrI: 69.9, 70.6) thousand DALYs, with an ICER of $27.9 per DALY averted from the health system perspective. Under a broad range of alternative scenarios, we find that initially prioritising the older (65+) population generally prevents more deaths. However, unprioritised distribution has almost the same cost-effectiveness when considering all outcomes, and both prioritised and unprioritised programmes can be cost-effective for low per-dose costs. High vaccine prices ($10/dose), however, may not be cost-effective, depending on the specifics of vaccine performance, distribution programme, and future pandemic trends. The principal drivers of the health outcomes are the fitted values for the overall transmission scaling parameter and disease natural history parameters from other studies, particularly age-specific probabilities of infection and symptomatic disease, as well as social contact rates. Other parameters are investigated in sensitivity analyses. This study is limited by model approximations, available data, and future uncertainty. Because the model is a single-population compartmental model, detailed impacts of nonpharmaceutical interventions (NPIs) such as household isolation cannot be practically represented or evaluated in combination with vaccine programmes. Similarly, the model cannot consider prioritising groups like healthcare or other essential workers. The model is only fitted to the reported case and death data, which are incomplete and not disaggregated by, e.g., age. Finally, because the future impact and implementation cost of NPIs are uncertain, how these would interact with vaccination remains an open question.

Conclusions

COVID-19 vaccination can have a considerable health impact and is likely to be cost-effective if more optimistic vaccine scenarios apply. Preventing severe disease is an important contributor to this impact. However, the advantage of prioritising older, high-risk populations is smaller in generally younger populations. This reduction is especially true in populations with more past transmission, and if the vaccine is likely to further impede transmission rather than just disease. Those conditions are typical of many low- and middle-income countries.",,pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1003815&type=printable; doi:https://doi.org/10.1371/journal.pmed.1003815; html:https://europepmc.org/articles/PMC8523052; pdf:https://europepmc.org/articles/PMC8523052?pdf=render 33203640,https://doi.org/10.1136/bmjopen-2020-043828,"Estimated impact of the COVID-19 pandemic on cancer services and excess 1-year mortality in people with cancer and multimorbidity: near real-time data on cancer care, cancer deaths and a population-based cohort study.","Lai AG, Pasea L, Banerjee A, Hall G, Denaxas S, Chang WH, Katsoulis M, Williams B, Pillay D, Noursadeghi M, Linch D, Hughes D, Forster MD, Turnbull C, Fitzpatrick NK, Boyd K, Foster GR, Enver T, Nafilyan V, Humberstone B, Neal RD, Cooper M, Jones M, Pritchard-Jones K, Sullivan R, Davie C, Lawler M, Hemingway H.",,BMJ open,2020,2020-11-17,Y,Oncology; Health Informatics; Covid-19,,,"

Objectives

To estimate the impact of the COVID-19 pandemic on cancer care services and overall (direct and indirect) excess deaths in people with cancer.

Methods

We employed near real-time weekly data on cancer care to determine the adverse effect of the pandemic on cancer services. We also used these data, together with national death registrations until June 2020 to model deaths, in excess of background (pre-COVID-19) mortality, in people with cancer. Background mortality risks for 24 cancers with and without COVID-19-relevant comorbidities were obtained from population-based primary care cohort (Clinical Practice Research Datalink) on 3 862 012 adults in England.

Results

Declines in urgent referrals (median=-70.4%) and chemotherapy attendances (median=-41.5%) to a nadir (lowest point) in the pandemic were observed. By 31 May, these declines have only partially recovered; urgent referrals (median=-44.5%) and chemotherapy attendances (median=-31.2%). There were short-term excess death registrations for cancer (without COVID-19), with peak relative risk (RR) of 1.17 at week ending on 3 April. The peak RR for all-cause deaths was 2.1 from week ending on 17 April. Based on these findings and recent literature, we modelled 40% and 80% of cancer patients being affected by the pandemic in the long-term. At 40% affected, we estimated 1-year total (direct and indirect) excess deaths in people with cancer as between 7165 and 17 910, using RRs of 1.2 and 1.5, respectively, where 78% of excess deaths occured in patients with ≥1 comorbidity.

Conclusions

Dramatic reductions were detected in the demand for, and supply of, cancer services which have not fully recovered with lockdown easing. These may contribute, over a 1-year time horizon, to substantial excess mortality among people with cancer and multimorbidity. It is urgent to understand how the recovery of general practitioner, oncology and other hospital services might best mitigate these long-term excess mortality risks.",,pdf:https://bmjopen.bmj.com/content/bmjopen/10/11/e043828.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-043828; html:https://europepmc.org/articles/PMC7674020; pdf:https://europepmc.org/articles/PMC7674020?pdf=render -36446465,https://doi.org/10.1136/bmjopen-2022-065142,"Prevalence, pathophysiology, prediction and health-related quality of life of long COVID: study protocol of the longitudinal multiple cohort CORona Follow Up (CORFU) study.","Ghossein-Doha C, Wintjens MSJN, Janssen EBNJ, Klein D, Heemskerk SCM, Asselbergs FW, Birnie E, Bonsel GJ, van Bussel BCT, Cals JWL, Ten Cate H, Haagsma J, Hemmen B, van der Horst ICC, Kietselaer BLJH, Klok FA, de Kruif MD, Linschoten M, van Santen S, Vernooy K, Willems LH, Westerborg R, Warle M, van Kuijk SMJ.",,BMJ open,2022,2022-11-29,Y,epidemiology; Public Health; Protocols & Guidelines; Covid-19,,,"

Introduction

The variety, time patterns and long-term prognosis of persistent COVID-19 symptoms (long COVID-19) in patients who suffered from mild to severe acute COVID-19 are incompletely understood. Cohort studies will be combined to describe the prevalence of long COVID-19 symptoms, and to explore the pathophysiological mechanisms and impact on health-related quality of life. A prediction model for long COVID-19 will be developed and internally validated to guide care in future patients.

Methods and analysis

Data from seven COVID-19 cohorts will be aggregated in the longitudinal multiple cohort CORona Follow Up (CORFU) study. CORFU includes Dutch patients who suffered from COVID-19 at home, were hospitalised without or with intensive care unit treatment, needed inpatient or outpatient rehabilitation and controls who did not suffer from COVID-19. Individual cohort study designs were aligned and follow-up has been synchronised. Cohort participants will be followed up for a maximum of 24 months after acute infection. Next to the clinical characteristics measured in individual cohorts, the CORFU questionnaire on long COVID-19 outcomes and determinants will be administered digitally at 3, 6, 12, 18 and 24 months after the infection. The primary outcome is the prevalence of long COVID-19 symptoms up to 2 years after acute infection. Secondary outcomes are health-related quality of life (eg, EQ-5D), physical functioning, and the prevalence of thromboembolic complications, respiratory complications, cardiovascular diseases and endothelial dysfunction. A prediction model and a patient platform prototype will be developed.

Ethics and dissemination

Approval was obtained from the medical research ethics committee of Maastricht University Medical Center+ and Maastricht University (METC 2021-2990) and local committees of the participating cohorts. The project is supported by ZonMW and EuroQol Research Foundation. Results will be published in open access peer-reviewed scientific journals and presented at (inter)national conferences.

Trial registration number

NCT05240742.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/11/e065142.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-065142; html:https://europepmc.org/articles/PMC9709810; pdf:https://europepmc.org/articles/PMC9709810?pdf=render 32576605,https://doi.org/10.1136/jech-2020-214051,Efficacy of contact tracing for the containment of the 2019 novel coronavirus (COVID-19).,"Keeling MJ, Hollingsworth TD, Read JM.",,Journal of epidemiology and community health,2020,2020-06-23,Y,epidemiology; Communicable Diseases; Public Health Policy; Disease Modeling,,,"

Objective

Contact tracing is a central public health response to infectious disease outbreaks, especially in the early stages of an outbreak when specific treatments are limited. Importation of novel coronavirus (COVID-19) from China and elsewhere into the UK highlights the need to understand the impact of contact tracing as a control measure.

Design

Detailed survey information on social encounters from over 5800 respondents is coupled to predictive models of contact tracing and control. This is used to investigate the likely efficacy of contact tracing and the distribution of secondary cases that may go untraced.

Results

Taking recent estimates for COVID-19 transmission we predict that under effective contact tracing less than 1 in 6 cases will generate any subsequent untraced infections, although this comes at a high logistical burden with an average of 36 individuals traced per case. Changes to the definition of a close contact can reduce this burden, but with increased risk of untraced cases; we find that tracing using a contact definition requiring more than 4 hours of contact is unlikely to control spread.

Conclusions

The current contact tracing strategy within the UK is likely to identify a sufficient proportion of infected individuals such that subsequent spread could be prevented, although the ultimate success will depend on the rapid detection of cases and isolation of contacts. Given the burden of tracing a large number of contacts to find new cases, there is the potential the system could be overwhelmed if imports of infection occur at a rapid rate.",,pdf:https://jech.bmj.com/content/jech/74/10/861.full.pdf; doi:https://doi.org/10.1136/jech-2020-214051; html:https://europepmc.org/articles/PMC7307459; pdf:https://europepmc.org/articles/PMC7307459?pdf=render +36446465,https://doi.org/10.1136/bmjopen-2022-065142,"Prevalence, pathophysiology, prediction and health-related quality of life of long COVID: study protocol of the longitudinal multiple cohort CORona Follow Up (CORFU) study.","Ghossein-Doha C, Wintjens MSJN, Janssen EBNJ, Klein D, Heemskerk SCM, Asselbergs FW, Birnie E, Bonsel GJ, van Bussel BCT, Cals JWL, Ten Cate H, Haagsma J, Hemmen B, van der Horst ICC, Kietselaer BLJH, Klok FA, de Kruif MD, Linschoten M, van Santen S, Vernooy K, Willems LH, Westerborg R, Warle M, van Kuijk SMJ.",,BMJ open,2022,2022-11-29,Y,epidemiology; Public Health; Protocols & Guidelines; Covid-19,,,"

Introduction

The variety, time patterns and long-term prognosis of persistent COVID-19 symptoms (long COVID-19) in patients who suffered from mild to severe acute COVID-19 are incompletely understood. Cohort studies will be combined to describe the prevalence of long COVID-19 symptoms, and to explore the pathophysiological mechanisms and impact on health-related quality of life. A prediction model for long COVID-19 will be developed and internally validated to guide care in future patients.

Methods and analysis

Data from seven COVID-19 cohorts will be aggregated in the longitudinal multiple cohort CORona Follow Up (CORFU) study. CORFU includes Dutch patients who suffered from COVID-19 at home, were hospitalised without or with intensive care unit treatment, needed inpatient or outpatient rehabilitation and controls who did not suffer from COVID-19. Individual cohort study designs were aligned and follow-up has been synchronised. Cohort participants will be followed up for a maximum of 24 months after acute infection. Next to the clinical characteristics measured in individual cohorts, the CORFU questionnaire on long COVID-19 outcomes and determinants will be administered digitally at 3, 6, 12, 18 and 24 months after the infection. The primary outcome is the prevalence of long COVID-19 symptoms up to 2 years after acute infection. Secondary outcomes are health-related quality of life (eg, EQ-5D), physical functioning, and the prevalence of thromboembolic complications, respiratory complications, cardiovascular diseases and endothelial dysfunction. A prediction model and a patient platform prototype will be developed.

Ethics and dissemination

Approval was obtained from the medical research ethics committee of Maastricht University Medical Center+ and Maastricht University (METC 2021-2990) and local committees of the participating cohorts. The project is supported by ZonMW and EuroQol Research Foundation. Results will be published in open access peer-reviewed scientific journals and presented at (inter)national conferences.

Trial registration number

NCT05240742.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/11/e065142.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-065142; html:https://europepmc.org/articles/PMC9709810; pdf:https://europepmc.org/articles/PMC9709810?pdf=render 32426117,https://doi.org/10.7189/jogh.10.010348,Novel approaches to estimate compliance with lockdown measures in the COVID-19 pandemic.,"Sheikh A, Sheikh Z, Sheikh A.",,Journal of global health,2020,2020-06-01,Y,,,,,This is a summary of new methods for estimating phyiscal distancing and compliance with lockdown. I haven't scored the content because it isn't primary research.,doi:https://doi.org/10.7189/jogh.10.010348; doi:https://doi.org/10.7189/jogh.10.010348; html:https://europepmc.org/articles/PMC7211415; pdf:https://europepmc.org/articles/PMC7211415?pdf=render 36716318,https://doi.org/10.1371/journal.pmed.1004174,Therapeutic potential of IL6R blockade for the treatment of sepsis and sepsis-related death: A Mendelian randomisation study.,"Hamilton FW, Thomas M, Arnold D, Palmer T, Moran E, Mentzer AJ, Maskell N, Baillie K, Summers C, Hingorani A, MacGowan A, Khandaker GM, Mitchell R, Davey Smith G, Ghazal P, Timpson NJ.",,PLoS medicine,2023,2023-01-30,Y,,,,"

Background

Sepsis is characterised by dysregulated, life-threatening immune responses, which are thought to be driven by cytokines such as interleukin 6 (IL-6). Genetic variants in IL6R known to down-regulate IL-6 signalling are associated with improved Coronavirus Disease 2019 (COVID-19) outcomes, a finding later confirmed in randomised trials of IL-6 receptor antagonists (IL6RAs). We hypothesised that blockade of IL6R could also improve outcomes in sepsis.

Methods and findings

We performed a Mendelian randomisation (MR) analysis using single nucleotide polymorphisms (SNPs) in and near IL6R to evaluate the likely causal effects of IL6R blockade on sepsis (primary outcome), sepsis severity, other infections, and COVID-19 (secondary outcomes). We weighted SNPs by their effect on CRP and combined results across them in inverse variance weighted meta-analysis, proxying the effect of IL6RA. Our outcomes were measured in UK Biobank, FinnGen, the COVID-19 Host Genetics Initiative (HGI), and the GenOSept and GainS consortium. We performed several sensitivity analyses to test assumptions of our methods, including utilising variants around CRP and gp130 in a similar analysis. In the UK Biobank cohort (N = 486,484, including 11,643 with sepsis), IL6R blockade was associated with a decreased risk of our primary outcome, sepsis (odds ratio (OR) = 0.80; 95% confidence interval (CI) 0.66 to 0.96, per unit of natural log-transformed CRP decrease). The size of this effect increased with severity, with larger effects on 28-day sepsis mortality (OR = 0.74; 95% CI 0.47 to 1.15); critical care admission with sepsis (OR = 0.48, 95% CI 0.30 to 0.78) and critical care death with sepsis (OR = 0.37, 95% CI 0.14 to 0.98). Similar associations were seen with severe respiratory infection: OR for pneumonia in critical care 0.69 (95% CI 0.49 to 0.97) and for sepsis survival in critical care (OR = 0.22; 95% CI 0.04 to 1.31) in the GainS and GenOSept consortium, although this result had a large degree of imprecision. We also confirm the previously reported protective effect of IL6R blockade on severe COVID-19 (OR = 0.69, 95% CI 0.57 to 0.84) in the COVID-19 HGI, which was of similar magnitude to that seen in sepsis. Sensitivity analyses did not alter our primary results. These results are subject to the limitations and assumptions of MR, which in this case reflects interpretation of these SNP effects as causally acting through blockade of IL6R, and reflect lifetime exposure to IL6R blockade, rather than the effect of therapeutic IL6R blockade.

Conclusions

IL6R blockade is causally associated with reduced incidence of sepsis. Similar but imprecisely estimated results supported a causal effect also on sepsis related mortality and critical care admission with sepsis. These effects are comparable in size to the effect seen in severe COVID-19, where IL-6 receptor antagonists were shown to improve survival. These data suggest that a randomised trial of IL-6 receptor antagonists in sepsis should be considered.",,pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1004174&type=printable; doi:https://doi.org/10.1371/journal.pmed.1004174; html:https://europepmc.org/articles/PMC9925069; pdf:https://europepmc.org/articles/PMC9925069?pdf=render 35671273,https://doi.org/10.1371/journal.pone.0268837,Optimising the balance of acute and intermediate care capacity for the complex discharge pathway: Computer modelling study during COVID-19 recovery in England.,"Onen-Dumlu Z, Harper AL, Forte PG, Powell AL, Pitt M, Vasilakis C, Wood RM.",,PloS one,2022,2022-06-07,Y,,,,"

Objectives

While there has been significant research on the pressures facing acute hospitals during the COVID-19 pandemic, there has been less interest in downstream community services which have also been challenged in meeting demand. This study aimed to estimate the theoretical cost-optimal capacity requirement for 'step down' intermediate care services within a major healthcare system in England, at a time when considerable uncertainty remained regarding vaccination uptake and the easing of societal restrictions.

Methods

Demand for intermediate care was projected using an epidemiological model (for COVID-19 demand) and regressing upon public mobility (for non-COVID-19 demand). These were inputted to a computer simulation model of patient flow from acute discharge readiness to bedded and home-based Discharge to Assess (D2A) intermediate care services. Cost-optimal capacity was defined as that which yielded the lowest total cost of intermediate care provision and corresponding acute discharge delays.

Results

Increased intermediate care capacity is likely to bring about lower system-level costs, with the additional D2A investment more than offset by substantial reductions in costly acute discharge delays (leading also to improved patient outcome and experience). Results suggest that completely eliminating acute 'bed blocking' is unlikely economical (requiring large amounts of downstream capacity), and that health systems should instead target an appropriate tolerance based upon the specific characteristics of the pathway.

Conclusions

Computer modelling can be a valuable asset for determining optimal capacity allocation along the complex care pathway. With results supporting a Business Case for increased downstream capacity, this study demonstrates how modelling can be applied in practice and provides a blueprint for use alongside the freely-available model code.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0268837&type=printable; doi:https://doi.org/10.1371/journal.pone.0268837; html:https://europepmc.org/articles/PMC9173611; pdf:https://europepmc.org/articles/PMC9173611?pdf=render @@ -473,15 +473,15 @@ PMC9023380,https://doi.org/,Assessing the spread risk of COVID-19 associated wit 33177070,https://doi.org/10.1136/bmj.m4262,"Accuracy of UK Rapid Test Consortium (UK-RTC) ""AbC-19 Rapid Test"" for detection of previous SARS-CoV-2 infection in key workers: test accuracy study.","Mulchandani R, Jones HE, Taylor-Phillips S, Shute J, Perry K, Jamarani S, Brooks T, Charlett A, Hickman M, Oliver I, Kaptoge S, Danesh J, Di Angelantonio E, Ades AE, Wyllie DH, EDSAB-HOME and COMPARE Investigators.",,BMJ (Clinical research ed.),2020,2020-11-11,Y,,,,"

Objective

To assess the accuracy of the AbC-19 Rapid Test lateral flow immunoassay for the detection of previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Design

Test accuracy study.

Setting

Laboratory based evaluation.

Participants

2847 key workers (healthcare staff, fire and rescue officers, and police officers) in England in June 2020 (268 with a previous polymerase chain reaction (PCR) positive result (median 63 days previously), 2579 with unknown previous infection status); and 1995 pre-pandemic blood donors.

Main outcome measures

AbC-19 sensitivity and specificity, estimated using known negative (pre-pandemic) and known positive (PCR confirmed) samples as reference standards and secondly using the Roche Elecsys anti-nucleoprotein assay, a highly sensitive laboratory immunoassay, as a reference standard in samples from key workers.

Results

Test result bands were often weak, with positive/negative discordance by three trained laboratory staff for 3.9% of devices. Using consensus readings, for known positive and negative samples sensitivity was 92.5% (95% confidence interval 88.8% to 95.1%) and specificity was 97.9% (97.2% to 98.4%). Using an immunoassay reference standard, sensitivity was 94.2% (90.7% to 96.5%) among PCR confirmed cases but 84.7% (80.6% to 88.1%) among other people with antibodies. This is consistent with AbC-19 being more sensitive when antibody concentrations are higher, as people with PCR confirmation tended to have more severe disease whereas only 62% (218/354) of seropositive participants had had symptoms. If 1 million key workers were tested with AbC-19 and 10% had actually been previously infected, 84 700 true positive and 18 900 false positive results would be projected. The probability that a positive result was correct would be 81.7% (76.8% to 85.8%).

Conclusions

AbC-19 sensitivity was lower among unselected populations than among PCR confirmed cases of SARS-CoV-2, highlighting the scope for overestimation of assay performance in studies involving only PCR confirmed cases, owing to ""spectrum bias."" Assuming that 10% of the tested population have had SARS-CoV-2 infection, around one in five key workers testing positive with AbC-19 would be false positives.

Study registration

ISRCTN 56609224.",,pdf:https://www.bmj.com/content/bmj/371/bmj.m4262.full.pdf; doi:https://doi.org/10.1136/bmj.m4262; html:https://europepmc.org/articles/PMC7656121; pdf:https://europepmc.org/articles/PMC7656121?pdf=render 35879886,https://doi.org/10.1017/s0033291722002501,"Depression, anxiety and PTSD symptoms before and during the COVID-19 pandemic in the UK.","Young KS, Purves KL, Hübel C, Davies MR, Thompson KN, Bristow S, Krebs G, Danese A, Hirsch C, Parsons CE, Vassos E, Adey BN, Bright S, Hegemann L, Lee YT, Kalsi G, Monssen D, Mundy J, Peel AJ, Rayner C, Rogers HC, Ter Kuile A, Ward C, York K, Lin Y, Palmos AB, Schmidt U, Veale D, Nicholson TR, Pollak TA, Stevelink SAM, Moukhtarian T, Martineau AR, Holt H, Maughan B, Al-Chalabi A, Chaudhuri KR, Richardson MP, Bradley JR, Chinnery PF, Kingston N, Papadia S, Stirrups KE, Linger R, Hotopf M, Eley TC, Breen G.",,Psychological medicine,2023,2022-07-26,Y,Depression; Anxiety; Ptsd; Covid-19,,,"

Background

The impact of the coronavirus disease 2019 (COVID-19) pandemic on mental health is still being unravelled. It is important to identify which individuals are at greatest risk of worsening symptoms. This study aimed to examine changes in depression, anxiety and post-traumatic stress disorder (PTSD) symptoms using prospective and retrospective symptom change assessments, and to find and examine the effect of key risk factors.

Method

Online questionnaires were administered to 34 465 individuals (aged 16 years or above) in April/May 2020 in the UK, recruited from existing cohorts or via social media. Around one-third (n = 12 718) of included participants had prior diagnoses of depression or anxiety and had completed pre-pandemic mental health assessments (between September 2018 and February 2020), allowing prospective investigation of symptom change.

Results

Prospective symptom analyses showed small decreases in depression (PHQ-9: -0.43 points) and anxiety [generalised anxiety disorder scale - 7 items (GAD)-7: -0.33 points] and increases in PTSD (PCL-6: 0.22 points). Conversely, retrospective symptom analyses demonstrated significant large increases (PHQ-9: 2.40; GAD-7 = 1.97), with 55% reported worsening mental health since the beginning of the pandemic on a global change rating. Across both prospective and retrospective measures of symptom change, worsening depression, anxiety and PTSD symptoms were associated with prior mental health diagnoses, female gender, young age and unemployed/student status.

Conclusions

We highlight the effect of prior mental health diagnoses on worsening mental health during the pandemic and confirm previously reported sociodemographic risk factors. Discrepancies between prospective and retrospective measures of changes in mental health may be related to recall bias-related underestimation of prior symptom severity.",,pdf:https://www.cambridge.org/core/services/aop-cambridge-core/content/view/8C3760ED596F1ED8B80F729AC5E47B9B/S0033291722002501a.pdf/div-class-title-depression-anxiety-and-ptsd-symptoms-before-and-during-the-covid-19-pandemic-in-the-uk-div.pdf; doi:https://doi.org/10.1017/S0033291722002501; html:https://europepmc.org/articles/PMC10482709; pdf:https://europepmc.org/articles/PMC10482709?pdf=render 34870256,https://doi.org/10.1016/j.lanepe.2021.100267,Optimising health and economic impacts of COVID-19 vaccine prioritisation strategies in the WHO European Region: a mathematical modelling study.,"Liu Y, Sandmann FG, Barnard RC, Pearson CAB, Pastore R, Pebody R, Flasche S, Jit M.",,The Lancet regional health. Europe,2022,2021-11-30,Y,Europe; Health Economics; Mathematical Modelling; Policy Evaluation; Vaccine Policy; Multicountry Analysis; Covid-19,,,"

Background

Countries in the World Health Organization (WHO) European Region differ in terms of the COVID-19 vaccine supply conditions. We evaluated the health and economic impact of different age-based vaccine prioritisation strategies across this demographically and socio-economically diverse region.

Methods

We fitted age-specific compartmental models to the reported daily COVID-19 mortality in 2020 to inform the immunity level before vaccine roll-out. Models capture country-specific differences in population structures, contact patterns, epidemic history, life expectancy, and GDP per capita.We examined four strategies that prioritise: all adults (V+), younger (20-59 year-olds) followed by older adults (60+) (V20), older followed by younger adults (V60), and the oldest adults (75+) (V75) followed by incrementally younger age groups. We explored four roll-out scenarios (R1-4) - the slowest scenario (R1) reached 30% coverage by December 2022 and the fastest (R4) 80% by December 2021. Five decision-making metrics were summarised over 2021-22: mortality, morbidity, and losses in comorbidity-adjusted life expectancy, comorbidity- and quality-adjusted life years, and human capital. Six vaccine profiles were tested - the highest performing vaccine has 95% efficacy against both infection and disease, and the lowest 50% against diseases and 0% against infection.

Findings

Of the 20 decision-making metrics and roll-out scenario combinations, the same optimal strategy applied to all countries in only one combination; V60 was more or similarly desirable than V75 in 19 combinations. Of the 38 countries with fitted models, 11-37 countries had variable optimal strategies by decision-making metrics or roll-out scenarios. There are greater benefits in prioritising older adults when roll-out is slow and when vaccine profiles are less favourable.

Interpretation

The optimal age-based vaccine prioritisation strategies were sensitive to country characteristics, decision-making metrics, and roll-out speeds. A prioritisation strategy involving more age-based stages (V75) does not necessarily lead to better health and economic outcomes than targeting broad age groups (V60). Countries expecting a slow vaccine roll-out may particularly benefit from prioritising older adults.

Funding

World Health Organization, Bill and Melinda Gates Foundation, the Medical Research Council (United Kingdom), the National Institute of Health Research (United Kingdom), the European Commission, the Foreign, Commonwealth and Development Office (United Kingdom), Wellcome Trust.",,doi:https://doi.org/10.1016/j.lanepe.2021.100267; doi:https://doi.org/10.1016/j.lanepe.2021.100267; html:https://europepmc.org/articles/PMC8629724; pdf:https://europepmc.org/articles/PMC8629724?pdf=render -33939952,https://doi.org/10.1016/s0140-6736(21)00949-1,COVID-19 and disparities affecting ethnic minorities.,"Morales DR, Ali SN.",,"Lancet (London, England)",2021,2021-04-30,Y,,,,,,pdf:http://www.thelancet.com/article/S0140673621009491/pdf; doi:https://doi.org/10.1016/S0140-6736(21)00949-1; html:https://europepmc.org/articles/PMC9755653; pdf:https://europepmc.org/articles/PMC9755653?pdf=render 32878619,https://doi.org/10.1186/s12916-020-01726-3,COVID-19 length of hospital stay: a systematic review and data synthesis.,"Rees EM, Nightingale ES, Jafari Y, Waterlow NR, Clifford S, B Pearson CA, Group CW, Jombart T, Procter SR, Knight GM.",,BMC medicine,2020,2020-09-03,Y,Length Of Stay; Hospitalisation; Icu Capacity; Covid-19; Sars-cov-2; Bed Demand,,,"

Background

The COVID-19 pandemic has placed an unprecedented strain on health systems, with rapidly increasing demand for healthcare in hospitals and intensive care units (ICUs) worldwide. As the pandemic escalates, determining the resulting needs for healthcare resources (beds, staff, equipment) has become a key priority for many countries. Projecting future demand requires estimates of how long patients with COVID-19 need different levels of hospital care.

Methods

We performed a systematic review of early evidence on length of stay (LoS) of patients with COVID-19 in hospital and in ICU. We subsequently developed a method to generate LoS distributions which combines summary statistics reported in multiple studies, accounting for differences in sample sizes. Applying this approach, we provide distributions for total hospital and ICU LoS from studies in China and elsewhere, for use by the community.

Results

We identified 52 studies, the majority from China (46/52). Median hospital LoS ranged from 4 to 53 days within China, and 4 to 21 days outside of China, across 45 studies. ICU LoS was reported by eight studies-four each within and outside China-with median values ranging from 6 to 12 and 4 to 19 days, respectively. Our summary distributions have a median hospital LoS of 14 (IQR 10-19) days for China, compared with 5 (IQR 3-9) days outside of China. For ICU, the summary distributions are more similar (median (IQR) of 8 (5-13) days for China and 7 (4-11) days outside of China). There was a visible difference by discharge status, with patients who were discharged alive having longer LoS than those who died during their admission, but no trend associated with study date.

Conclusion

Patients with COVID-19 in China appeared to remain in hospital for longer than elsewhere. This may be explained by differences in criteria for admission and discharge between countries, and different timing within the pandemic. In the absence of local data, the combined summary LoS distributions provided here can be used to model bed demands for contingency planning and then updated, with the novel method presented here, as more studies with aggregated statistics emerge outside China.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-020-01726-3; doi:https://doi.org/10.1186/s12916-020-01726-3; html:https://europepmc.org/articles/PMC7467845; pdf:https://europepmc.org/articles/PMC7467845?pdf=render +33939952,https://doi.org/10.1016/s0140-6736(21)00949-1,COVID-19 and disparities affecting ethnic minorities.,"Morales DR, Ali SN.",,"Lancet (London, England)",2021,2021-04-30,Y,,,,,,pdf:http://www.thelancet.com/article/S0140673621009491/pdf; doi:https://doi.org/10.1016/S0140-6736(21)00949-1; html:https://europepmc.org/articles/PMC9755653; pdf:https://europepmc.org/articles/PMC9755653?pdf=render 36240828,https://doi.org/10.1016/s2214-109x(22)00358-8,Prediction of upcoming global infection burden of influenza seasons after relaxation of public health and social measures during the COVID-19 pandemic: a modelling study.,"Ali ST, Lau YC, Shan S, Ryu S, Du Z, Wang L, Xu XK, Chen D, Xiong J, Tae J, Tsang TK, Wu P, Lau EHY, Cowling BJ.",,The Lancet. Global health,2022,2022-11-01,Y,,,,"

Background

The transmission dynamics of influenza were affected by public health and social measures (PHSMs) implemented globally since early 2020 to mitigate the COVID-19 pandemic. We aimed to assess the effect of COVID-19 PHSMs on the transmissibility of influenza viruses and to predict upcoming influenza epidemics.

Methods

For this modelling study, we used surveillance data on influenza virus activity for 11 different locations and countries in 2017-22. We implemented a data-driven mechanistic predictive modelling framework to predict future influenza seasons on the basis of pre-COVID-19 dynamics and the effect of PHSMs during the COVID-19 pandemic. We simulated the potential excess burden of upcoming influenza epidemics in terms of fold rise in peak magnitude and epidemic size compared with pre-COVID-19 levels. We also examined how a proactive influenza vaccination programme could mitigate this effect.

Findings

We estimated that COVID-19 PHSMs reduced influenza transmissibility by a maximum of 17·3% (95% CI 13·3-21·4) to 40·6% (35·2-45·9) and attack rate by 5·1% (1·5-7·2) to 24·8% (20·8-27·5) in the 2019-20 influenza season. We estimated a 10-60% increase in the population susceptibility for influenza, which might lead to a maximum of 1-5-fold rise in peak magnitude and 1-4-fold rise in epidemic size for the upcoming 2022-23 influenza season across locations, with a significantly higher fold rise in Singapore and Taiwan. The infection burden could be mitigated by additional proactive one-off influenza vaccination programmes.

Interpretation

Our results suggest the potential for substantial increases in infection burden in upcoming influenza seasons across the globe. Strengthening influenza vaccination programmes is the best preventive measure to reduce the effect of influenza virus infections in the community.

Funding

Health and Medical Research Fund, Hong Kong.",,pdf:https://www.repository.cam.ac.uk/bitstreams/bb5465bd-c08f-4c3d-ab0e-87fee39fc92b/download; doi:https://doi.org/10.1016/S2214-109X(22)00358-8; html:https://europepmc.org/articles/PMC9573849 35962974,https://doi.org/10.1093/ije/dyac158,Association between household composition and severe COVID-19 outcomes in older people by ethnicity: an observational cohort study using the OpenSAFELY platform.,"Wing K, Grint DJ, Mathur R, Gibbs HP, Hickman G, Nightingale E, Schultze A, Forbes H, Nafilyan V, Bhaskaran K, Williamson E, House T, Pellis L, Herrett E, Gautam N, Curtis HJ, Rentsch CT, Wong AYS, MacKenna B, Mehrkar A, Bacon S, Douglas IJ, Evans SJW, Tomlinson L, Goldacre B, Eggo RM.",,International journal of epidemiology,2022,2022-12-01,Y,Household; Older People; Ethnicity; Deprivation; Comorbidities; Multigenerational; Population-level; Covid-19; Opensafely,,,"

Background

Ethnic differences in the risk of severe COVID-19 may be linked to household composition. We quantified the association between household composition and risk of severe COVID-19 by ethnicity for older individuals.

Methods

With the approval of NHS England, we analysed ethnic differences in the association between household composition and severe COVID-19 in people aged 67 or over in England. We defined households by number of age-based generations living together, and used multivariable Cox regression stratified by location and wave of the pandemic and accounted for age, sex, comorbidities, smoking, obesity, housing density and deprivation. We included 2 692 223 people over 67 years in Wave 1 (1 February 2020-31 August 2020) and 2 731 427 in Wave 2 (1 September 2020-31 January 2021).

Results

Multigenerational living was associated with increased risk of severe COVID-19 for White and South Asian older people in both waves [e.g. Wave 2, 67+ living with three other generations vs 67+-year-olds only: White hazard ratio (HR) 1.61 95% CI 1.38-1.87, South Asian HR 1.76 95% CI 1.48-2.10], with a trend for increased risks of severe COVID-19 with increasing generations in Wave 2. There was also an increased risk of severe COVID-19 in Wave 1 associated with living alone for White (HR 1.35 95% CI 1.30-1.41), South Asian (HR 1.47 95% CI 1.18-1.84) and Other (HR 1.72 95% CI 0.99-2.97) ethnicities, an effect that persisted for White older people in Wave 2.

Conclusions

Both multigenerational living and living alone were associated with severe COVID-19 in older adults. Older South Asian people are over-represented within multigenerational households in England, especially in the most deprived settings, whereas a substantial proportion of White older people live alone. The number of generations in a household, number of occupants, ethnicity and deprivation status are important considerations in the continued roll-out of COVID-19 vaccination and targeting of interventions for future pandemics.",,pdf:https://academic.oup.com/ije/article-pdf/51/6/1745/47882630/dyac158.pdf; doi:https://doi.org/10.1093/ije/dyac158; html:https://europepmc.org/articles/PMC9384728; pdf:https://europepmc.org/articles/PMC9384728?pdf=render -37751444,https://doi.org/10.1371/journal.pone.0290583,Long Covid symptoms and diagnosis in primary care: A cohort study using structured and unstructured data in The Health Improvement Network primary care database.,"Shah AD, Subramanian A, Lewis J, Dhalla S, Ford E, Haroon S, Kuan V, Nirantharakumar K.",,PloS one,2023,2023-09-26,Y,,,,"

Background

Long Covid is a widely recognised consequence of COVID-19 infection, but little is known about the burden of symptoms that patients present with in primary care, as these are typically recorded only in free text clinical notes.

Aims

To compare symptoms in patients with and without a history of COVID-19, and investigate symptoms associated with a Long Covid diagnosis.

Methods

We used primary care electronic health record data until the end of December 2020 from The Health Improvement Network (THIN), a Cegedim database. We included adults registered with participating practices in England, Scotland or Wales. We extracted information about 89 symptoms and 'Long Covid' diagnoses from free text using natural language processing. We calculated hazard ratios (adjusted for age, sex, baseline medical conditions and prior symptoms) for each symptom from 12 weeks after the COVID-19 diagnosis.

Results

We compared 11,015 patients with confirmed COVID-19 and 18,098 unexposed controls. Only 20% of symptom records were coded, with 80% in free text. A wide range of symptoms were associated with COVID-19 at least 12 weeks post-infection, with strongest associations for fatigue (adjusted hazard ratio (aHR) 3.46, 95% confidence interval (CI) 2.87, 4.17), shortness of breath (aHR 2.89, 95% CI 2.48, 3.36), palpitations (aHR 2.59, 95% CI 1.86, 3.60), and phlegm (aHR 2.43, 95% CI 1.65, 3.59). However, a limited subset of symptoms were recorded within 7 days prior to a Long Covid diagnosis in more than 20% of cases: shortness of breath, chest pain, pain, fatigue, cough, and anxiety / depression.

Conclusions

Numerous symptoms are reported to primary care at least 12 weeks after COVID-19 infection, but only a subset are commonly associated with a GP diagnosis of Long Covid.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0290583&type=printable; doi:https://doi.org/10.1371/journal.pone.0290583; html:https://europepmc.org/articles/PMC10521988; pdf:https://europepmc.org/articles/PMC10521988?pdf=render 33743846,https://doi.org/10.1016/s1473-3099(21)00079-7,The potential health and economic value of SARS-CoV-2 vaccination alongside physical distancing in the UK: a transmission model-based future scenario analysis and economic evaluation.,"Sandmann FG, Davies NG, Vassall A, Edmunds WJ, Jit M, Centre for the Mathematical Modelling of Infectious Diseases COVID-19 working group.",,The Lancet. Infectious diseases,2021,2021-03-18,Y,,,,"

Background

In response to the COVID-19 pandemic, the UK first adopted physical distancing measures in March, 2020. Vaccines against SARS-CoV-2 became available in December, 2020. We explored the health and economic value of introducing SARS-CoV-2 immunisation alongside physical distancing in the UK to gain insights about possible future scenarios in a post-vaccination era.

Methods

We used an age-structured dynamic transmission and economic model to explore different scenarios of UK mass immunisation programmes over 10 years. We compared vaccinating 75% of individuals aged 15 years or older (and annually revaccinating 50% of individuals aged 15-64 years and 75% of individuals aged 65 years or older) to no vaccination. We assumed either 50% vaccine efficacy against disease and 45-week protection (worst-case scenario) or 95% vaccine efficacy against infection and 3-year protection (best-case scenario). Natural immunity was assumed to wane within 45 weeks. We also explored the additional impact of physical distancing on vaccination by assuming either an initial lockdown followed by voluntary physical distancing, or an initial lockdown followed by increased physical distancing mandated above a certain threshold of incident daily infections. We considered benefits in terms of quality-adjusted life-years (QALYs) and costs, both to the health-care payer and the national economy. We discounted future costs and QALYs at 3·5% annually and assumed a monetary value per QALY of £20 000 and a conservative long-run cost per vaccine dose of £15. We explored and varied these parameters in sensitivity analyses. We expressed the health and economic benefits of each scenario with the net monetary value: QALYs × (monetary value per QALY) - costs.

Findings

Without the initial lockdown, vaccination, and increased physical distancing, we estimated 148·0 million (95% uncertainty interval 48·5-198·8) COVID-19 cases and 3·1 million (0·84-4·5) deaths would occur in the UK over 10 years. In the best-case scenario, vaccination minimises community transmission without future periods of increased physical distancing, whereas SARS-CoV-2 becomes endemic with biannual epidemics in the worst-case scenario. Ongoing transmission is also expected in intermediate scenarios with vaccine efficacy similar to published clinical trial data. From a health-care perspective, introducing vaccination leads to incremental net monetary values ranging from £12·0 billion to £334·7 billion in the best-case scenario and from -£1·1 billion to £56·9 billion in the worst-case scenario. Incremental net monetary values of increased physical distancing might be negative from a societal perspective if national economy losses are persistent and large.

Interpretation

Our model findings highlight the substantial health and economic value of introducing SARS-CoV-2 vaccination. Smaller outbreaks could continue even with vaccines, but population-wide implementation of increased physical distancing might no longer be justifiable. Our study provides early insights about possible future post-vaccination scenarios from an economic and epidemiological perspective.

Funding

National Institute for Health Research, European Commission, Bill & Melinda Gates Foundation.",,pdf:http://www.thelancet.com/article/S1473309921000797/pdf; doi:https://doi.org/10.1016/S1473-3099(21)00079-7; html:https://europepmc.org/articles/PMC7972313 -38419826,https://doi.org/10.23889/ijpds.v8i4.2164,Common governance model: a way to avoid data segregation between existing trusted research environment.,"Torabi F, Orton C, Squires E, Heys S, Hier R, Lyons RA, Thompson S.",,International journal of population data science,2023,2023-11-08,Y,Data Protection; Data Governance; Trusted Research Environments,,,"

Background

Trusted Research Environments provide a legitimate basis for data access along with a set of technologies to support implementation of the ""five-safes"" framework for privacy protection. Lack of standard approaches in achieving compliance with the ""five-safes"" framework results in a diversity of approaches across different TREs. Data access and analysis across multiple TREs has a range of benefits including improved precision of analysis due to larger sample sizes and broader availability of out-of-sample records, particularly in the study of rare conditions. Knowledge of governance approaches used across UK-TREs is limited.

Objective

To document key governance features in major UK-TRE contributing to UK wide analysis and to identify elements that would directly facilitate multi TRE collaborations and federated analysis in future.

Method

We summarised three main characteristics across 15 major UK-based TREs: 1) data access environment; 2) data access requests and disclosure control procedures; and 3) governance models. We undertook case studies of collaborative analyses conducted in more than one TRE. We identified an array of TREs operating on an equivalent level of governance. We further identify commonly governed TREs with architectural considerations for achieving an equivalent level of information security management system standards to facilitate multi TRE functionality and federated analytics.

Results

All 15 UK-TREs allow pooling and analysis of aggregated research outputs only when they have passed human-operated disclosure control checks. Data access requests procedures are unique to each TRE. We also observed a variability in disclosure control procedures across various TREs with no or minimal researcher guidance on best practices for file out request procedures. In 2023, six TREs (40.0%) held ISO 20071 accreditation, while 9 TREs (56.2%) participated in four-nation analyses.

Conclusion

Secure analysis of individual-level data from multiple TREs is possible through existing technical solutions but requires development of a well-established governance framework meeting all stakeholder requirements and addressing public and patient concerns. Formation of a standard model could act as the catalyst for evolution of current TREs governance models to a multi TRE ecosystem within the UK and beyond.",,doi:https://doi.org/10.23889/ijpds.v8i4.2164; html:https://europepmc.org/articles/PMC10900179; pdf:https://europepmc.org/articles/PMC10900179?pdf=render +37751444,https://doi.org/10.1371/journal.pone.0290583,Long Covid symptoms and diagnosis in primary care: A cohort study using structured and unstructured data in The Health Improvement Network primary care database.,"Shah AD, Subramanian A, Lewis J, Dhalla S, Ford E, Haroon S, Kuan V, Nirantharakumar K.",,PloS one,2023,2023-09-26,Y,,,,"

Background

Long Covid is a widely recognised consequence of COVID-19 infection, but little is known about the burden of symptoms that patients present with in primary care, as these are typically recorded only in free text clinical notes.

Aims

To compare symptoms in patients with and without a history of COVID-19, and investigate symptoms associated with a Long Covid diagnosis.

Methods

We used primary care electronic health record data until the end of December 2020 from The Health Improvement Network (THIN), a Cegedim database. We included adults registered with participating practices in England, Scotland or Wales. We extracted information about 89 symptoms and 'Long Covid' diagnoses from free text using natural language processing. We calculated hazard ratios (adjusted for age, sex, baseline medical conditions and prior symptoms) for each symptom from 12 weeks after the COVID-19 diagnosis.

Results

We compared 11,015 patients with confirmed COVID-19 and 18,098 unexposed controls. Only 20% of symptom records were coded, with 80% in free text. A wide range of symptoms were associated with COVID-19 at least 12 weeks post-infection, with strongest associations for fatigue (adjusted hazard ratio (aHR) 3.46, 95% confidence interval (CI) 2.87, 4.17), shortness of breath (aHR 2.89, 95% CI 2.48, 3.36), palpitations (aHR 2.59, 95% CI 1.86, 3.60), and phlegm (aHR 2.43, 95% CI 1.65, 3.59). However, a limited subset of symptoms were recorded within 7 days prior to a Long Covid diagnosis in more than 20% of cases: shortness of breath, chest pain, pain, fatigue, cough, and anxiety / depression.

Conclusions

Numerous symptoms are reported to primary care at least 12 weeks after COVID-19 infection, but only a subset are commonly associated with a GP diagnosis of Long Covid.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0290583&type=printable; doi:https://doi.org/10.1371/journal.pone.0290583; html:https://europepmc.org/articles/PMC10521988; pdf:https://europepmc.org/articles/PMC10521988?pdf=render 33782396,https://doi.org/10.1038/s41467-021-22213-0,Implications of the school-household network structure on SARS-CoV-2 transmission under school reopening strategies in England.,"Munday JD, Sherratt K, Meakin S, Endo A, Pearson CAB, Hellewell J, Abbott S, Bosse NI, CMMID COVID-19 Working Group, Atkins KE, Wallinga J, Edmunds WJ, van Hoek AJ, Funk S.",,Nature communications,2021,2021-03-29,Y,,,,"In early 2020 many countries closed schools to mitigate the spread of SARS-CoV-2. Since then, governments have sought to relax the closures, engendering a need to understand associated risks. Using address records, we construct a network of schools in England connected through pupils who share households. We evaluate the risk of transmission between schools under different reopening scenarios. We show that whilst reopening select year-groups causes low risk of large-scale transmission, reopening secondary schools could result in outbreaks affecting up to 2.5 million households if unmitigated, highlighting the importance of careful monitoring and within-school infection control to avoid further school closures or other restrictions.",,pdf:https://www.nature.com/articles/s41467-021-22213-0.pdf; doi:https://doi.org/10.1038/s41467-021-22213-0; html:https://europepmc.org/articles/PMC8007691; pdf:https://europepmc.org/articles/PMC8007691?pdf=render 34161326,https://doi.org/10.1371/journal.pcbi.1009121,Contrasting factors associated with COVID-19-related ICU admission and death outcomes in hospitalised patients by means of Shapley values.,"Cavallaro M, Moiz H, Keeling MJ, McCarthy ND.",,PLoS computational biology,2021,2021-06-23,Y,,,,"Identification of those at greatest risk of death due to the substantial threat of COVID-19 can benefit from novel approaches to epidemiology that leverage large datasets and complex machine-learning models, provide data-driven intelligence, and guide decisions such as intensive-care unit admission (ICUA). The objective of this study is two-fold, one substantive and one methodological: substantively to evaluate the association of demographic and health records with two related, yet different, outcomes of severe COVID-19 (viz., death and ICUA); methodologically to compare interpretations based on logistic regression and on gradient-boosted decision tree (GBDT) predictions interpreted by means of the Shapley impacts of covariates. Very different association of some factors, e.g., obesity and chronic respiratory diseases, with death and ICUA may guide review of practice. Shapley explanation of GBDTs identified varying effects of some factors among patients, thus emphasising the importance of individual patient assessment. The results of this study are also relevant for the evaluation of complex automated clinical decision systems, which should optimise prediction scores whilst remaining interpretable to clinicians and mitigating potential biases.",,pdf:https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1009121&type=printable; doi:https://doi.org/10.1371/journal.pcbi.1009121; html:https://europepmc.org/articles/PMC8259985; pdf:https://europepmc.org/articles/PMC8259985?pdf=render +38419826,https://doi.org/10.23889/ijpds.v8i4.2164,Common governance model: a way to avoid data segregation between existing trusted research environment.,"Torabi F, Orton C, Squires E, Heys S, Hier R, Lyons RA, Thompson S.",,International journal of population data science,2023,2023-11-08,Y,Data Protection; Data Governance; Trusted Research Environments,,,"

Background

Trusted Research Environments provide a legitimate basis for data access along with a set of technologies to support implementation of the ""five-safes"" framework for privacy protection. Lack of standard approaches in achieving compliance with the ""five-safes"" framework results in a diversity of approaches across different TREs. Data access and analysis across multiple TREs has a range of benefits including improved precision of analysis due to larger sample sizes and broader availability of out-of-sample records, particularly in the study of rare conditions. Knowledge of governance approaches used across UK-TREs is limited.

Objective

To document key governance features in major UK-TRE contributing to UK wide analysis and to identify elements that would directly facilitate multi TRE collaborations and federated analysis in future.

Method

We summarised three main characteristics across 15 major UK-based TREs: 1) data access environment; 2) data access requests and disclosure control procedures; and 3) governance models. We undertook case studies of collaborative analyses conducted in more than one TRE. We identified an array of TREs operating on an equivalent level of governance. We further identify commonly governed TREs with architectural considerations for achieving an equivalent level of information security management system standards to facilitate multi TRE functionality and federated analytics.

Results

All 15 UK-TREs allow pooling and analysis of aggregated research outputs only when they have passed human-operated disclosure control checks. Data access requests procedures are unique to each TRE. We also observed a variability in disclosure control procedures across various TREs with no or minimal researcher guidance on best practices for file out request procedures. In 2023, six TREs (40.0%) held ISO 20071 accreditation, while 9 TREs (56.2%) participated in four-nation analyses.

Conclusion

Secure analysis of individual-level data from multiple TREs is possible through existing technical solutions but requires development of a well-established governance framework meeting all stakeholder requirements and addressing public and patient concerns. Formation of a standard model could act as the catalyst for evolution of current TREs governance models to a multi TRE ecosystem within the UK and beyond.",,doi:https://doi.org/10.23889/ijpds.v8i4.2164; html:https://europepmc.org/articles/PMC10900179; pdf:https://europepmc.org/articles/PMC10900179?pdf=render 34518162,https://doi.org/10.1136/bjophthalmol-2021-319383,Predicting the immediate impact of national lockdown on neovascular age-related macular degeneration and associated visual morbidity: an INSIGHT Health Data Research Hub for Eye Health report.,"Mollan SP, Fu DJ, Chuo CY, Gannon JG, Lee WH, Hopkins JJ, Hughes C, Denniston AK, Keane PA, Cantrell R.",,The British journal of ophthalmology,2023,2021-09-13,Y,Clinical Trial; Neovascularisation; Covid-19,,,"

Objective

Predicting the impact of neovascular age-related macular degeneration (nAMD) service disruption on visual outcomes following national lockdown in the UK to contain SARS-CoV-2.

Methods and analysis

This retrospective cohort study includes deidentified data from 2229 UK patients from the INSIGHT Health Data Research digital hub. We forecasted the number of treatment-naïve nAMD patients requiring anti-vascular endothelial growth factor (anti-VEGF) initiation during UK lockdown (16 March 2020 through 31 July 2020) at Moorfields Eye Hospital (MEH) and University Hospitals Birmingham (UHB). Best-measured visual acuity (VA) changes without anti-VEGF therapy were predicted using post hoc analysis of Minimally Classic/Occult Trial of the Anti-VEGF Antibody Ranibizumab in the Treatment of Neovascular AMD trial sham-control arm data (n=238).

Results

At our centres, 376 patients were predicted to require anti-VEGF initiation during lockdown (MEH: 325; UHB: 51). Without treatment, mean VA was projected to decline after 12 months. The proportion of eyes in the MEH cohort predicted to maintain the key positive visual outcome of ≥70 ETDRS letters (Snellen equivalent 6/12) fell from 25.5% at baseline to 5.8% at 12 months (UHB: 9.8%-7.8%). Similarly, eyes with VA <25 ETDRS letters (6/96) were predicted to increase from 4.3% to 14.2% at MEH (UHB: 5.9%-7.8%) after 12 months without treatment.

Conclusions

Here, we demonstrate how combining data from a recently founded national digital health data repository with historical industry-funded clinical trial data can enhance predictive modelling in nAMD. The demonstrated detrimental effects of prolonged treatment delay should incentivise healthcare providers to support nAMD patients accessing care in safe environments.

Trial registration number

NCT00056836.",,pdf:https://discovery.ucl.ac.uk/10164981/1/267.full.pdf; doi:https://doi.org/10.1136/bjophthalmol-2021-319383; html:https://europepmc.org/articles/PMC9887382; pdf:https://europepmc.org/articles/PMC9887382?pdf=render 35967893,https://doi.org/10.1080/20008066.2022.2105577,Factors influencing the mental health of an ethnically diverse healthcare workforce during COVID-19: a qualitative study in the United Kingdom.,"Qureshi I, Gogoi M, Al-Oraibi A, Wobi F, Chaloner J, Gray L, Guyatt AL, Hassan O, Nellums LB, Pareek M, UK-REACH Collaborative Group.",,European journal of psychotraumatology,2022,2022-08-09,Y,Stress; Trauma; Anxiety; Mental health; Workforce; Healthcare; Ethnic Minority; Covid-19,,,"Background: Healthcare workers (HCWs) have been reported to be experiencing a deterioration in their mental health due to COVID-19. In addition, ethnic minority populations in the United Kingdom are disproportionately affected by COVID-19. It is imperative that HCWs are appropriately supported and protected from mental harm during the pandemic. Our research aims to add to the evidence base by providing greater insight into the lived experience of HCWs from diverse ethnic backgrounds during the pandemic that had an impact on their mental health. Methods: We undertook a qualitative work package as part of the United Kingdom Research study into Ethnicity And COVID-19 outcomes among Healthcare workers (UK-REACH). As part of the qualitative research, we carried out 16 focus groups with a total of 61 HCWs between December 2020 and July 2021. The aim of the study was to explore topics such as their experiences, fears and concerns, while working during the pandemic. The purposive sample included ancillary healthcare workers, doctors, nurses, midwives and allied health professionals from diverse ethnic backgrounds to ensure inclusion of underrepresented and disproportionately impacted individuals. We conducted discussions using Microsoft Teams. Recordings were transcribed and thematically analysed. Results: Several factors were identified which impacted on the mental health of HCWs during this period including anxiety (due to inconsistent protocols and policy); fear (of infection); trauma (due to increased exposure to severe illness and death); guilt (of potentially infecting loved ones); and stress (due to longer working hours and increased workload). Conclusion: COVID-19 has affected the mental health of HCWs. We identified a number of factors which may be contributing to a deterioration in mental health for participants from diverse ethnic backgrounds. Healthcare organisations should consider developing strategies to counter the negative impact of these factors, including recommendations made by HCWs themselves.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9364733; doi:https://doi.org/10.1080/20008066.2022.2105577; html:https://europepmc.org/articles/PMC9364733; pdf:https://europepmc.org/articles/PMC9364733?pdf=render 33087179,https://doi.org/10.1186/s12916-020-01790-9,Reconstructing the early global dynamics of under-ascertained COVID-19 cases and infections.,"Russell TW, Golding N, Hellewell J, Abbott S, Wright L, Pearson CAB, van Zandvoort K, Jarvis CI, Gibbs H, Liu Y, Eggo RM, Edmunds WJ, Kucharski AJ, CMMID COVID-19 working group.",,BMC medicine,2020,2020-10-22,Y,Surveillance; Situational Awareness; Under-reporting; Case Ascertainment; Outbreak Analysis; Covid-19; Sars-cov-2,,,"

Background

Asymptomatic or subclinical SARS-CoV-2 infections are often unreported, which means that confirmed case counts may not accurately reflect underlying epidemic dynamics. Understanding the level of ascertainment (the ratio of confirmed symptomatic cases to the true number of symptomatic individuals) and undetected epidemic progression is crucial to informing COVID-19 response planning, including the introduction and relaxation of control measures. Estimating case ascertainment over time allows for accurate estimates of specific outcomes such as seroprevalence, which is essential for planning control measures.

Methods

Using reported data on COVID-19 cases and fatalities globally, we estimated the proportion of symptomatic cases (i.e. any person with any of fever ≥ 37.5 °C, cough, shortness of breath, sudden onset of anosmia, ageusia or dysgeusia illness) that were reported in 210 countries and territories, given those countries had experienced more than ten deaths. We used published estimates of the baseline case fatality ratio (CFR), which was adjusted for delays and under-ascertainment, then calculated the ratio of this baseline CFR to an estimated local delay-adjusted CFR to estimate the level of under-ascertainment in a particular location. We then fit a Bayesian Gaussian process model to estimate the temporal pattern of under-ascertainment.

Results

Based on reported cases and deaths, we estimated that, during March 2020, the median percentage of symptomatic cases detected across the 84 countries which experienced more than ten deaths ranged from 2.4% (Bangladesh) to 100% (Chile). Across the ten countries with the highest number of total confirmed cases as of 6 July 2020, we estimated that the peak number of symptomatic cases ranged from 1.4 times (Chile) to 18 times (France) larger than reported. Comparing our model with national and regional seroprevalence data where available, we find that our estimates are consistent with observed values. Finally, we estimated seroprevalence for each country. As of 7 June, our seroprevalence estimates range from 0% (many countries) to 13% (95% CrI 5.6-24%) (Belgium).

Conclusions

We found substantial under-ascertainment of symptomatic cases, particularly at the peak of the first wave of the SARS-CoV-2 pandemic, in many countries. Reported case counts will therefore likely underestimate the rate of outbreak growth initially and underestimate the decline in the later stages of an epidemic. Although there was considerable under-reporting in many locations, our estimates were consistent with emerging serological data, suggesting that the proportion of each country's population infected with SARS-CoV-2 worldwide is generally low.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-020-01790-9; doi:https://doi.org/10.1186/s12916-020-01790-9; html:https://europepmc.org/articles/PMC7577796; pdf:https://europepmc.org/articles/PMC7577796?pdf=render @@ -501,14 +501,14 @@ PMC9023380,https://doi.org/,Assessing the spread risk of COVID-19 associated wit 35013731,https://doi.org/10.1016/j.lanepe.2021.100299,Persistent hesitancy for SARS-CoV-2 vaccines among healthcare workers in the United Kingdom: analysis of longitudinal data from the UK-REACH cohort study.,"Martin CA, Woolf K, Bryant L, Carr S, Gray LJ, Gupta A, Guyatt AL, John C, Melbourne C, McManus IC, Nazareth J, Nellums LB, Tobin MD, Pan D, Khunti K, Pareek M, UK-REACH Study Collaborative Group.",,The Lancet regional health. Europe,2022,2022-01-04,Y,,,,,,doi:https://doi.org/10.1016/j.lanepe.2021.100299; doi:https://doi.org/10.1016/j.lanepe.2021.100299; html:https://europepmc.org/articles/PMC8730737; pdf:https://europepmc.org/articles/PMC8730737?pdf=render 37248229,https://doi.org/10.1038/s41467-023-38756-3,Evidence-driven spatiotemporal COVID-19 hospitalization prediction with Ising dynamics.,"Gao J, Heintz J, Mack C, Glass L, Cross A, Sun J.",,Nature communications,2023,2023-05-29,Y,,,,"In this work, we aim to accurately predict the number of hospitalizations during the COVID-19 pandemic by developing a spatiotemporal prediction model. We propose HOIST, an Ising dynamics-based deep learning model for spatiotemporal COVID-19 hospitalization prediction. By drawing the analogy between locations and lattice sites in statistical mechanics, we use the Ising dynamics to guide the model to extract and utilize spatial relationships across locations and model the complex influence of granular information from real-world clinical evidence. By leveraging rich linked databases, including insurance claims, census information, and hospital resource usage data across the U.S., we evaluate the HOIST model on the large-scale spatiotemporal COVID-19 hospitalization prediction task for 2299 counties in the U.S. In the 4-week hospitalization prediction task, HOIST achieves 368.7 mean absolute error, 0.6 [Formula: see text] and 0.89 concordance correlation coefficient score on average. Our detailed number needed to treat (NNT) and cost analysis suggest that future COVID-19 vaccination efforts may be most impactful in rural areas. This model may serve as a resource for future county and state-level vaccination efforts.",,doi:https://doi.org/10.1038/s41467-023-38756-3; doi:https://doi.org/10.1038/s41467-023-38756-3; html:https://europepmc.org/articles/PMC10226446; pdf:https://europepmc.org/articles/PMC10226446?pdf=render 34139154,https://doi.org/10.1016/j.cels.2021.05.005,A time-resolved proteomic and prognostic map of COVID-19.,"Demichev V, Tober-Lau P, Lemke O, Nazarenko T, Thibeault C, Whitwell H, Röhl A, Freiwald A, Szyrwiel L, Ludwig D, Correia-Melo C, Aulakh SK, Helbig ET, Stubbemann P, Lippert LJ, Grüning NM, Blyuss O, Vernardis S, White M, Messner CB, Joannidis M, Sonnweber T, Klein SJ, Pizzini A, Wohlfarter Y, Sahanic S, Hilbe R, Schaefer B, Wagner S, Mittermaier M, Machleidt F, Garcia C, Ruwwe-Glösenkamp C, Lingscheid T, Bosquillon de Jarcy L, Stegemann MS, Pfeiffer M, Jürgens L, Denker S, Zickler D, Enghard P, Zelezniak A, Campbell A, Hayward C, Porteous DJ, Marioni RE, Uhrig A, Müller-Redetzky H, Zoller H, Löffler-Ragg J, Keller MA, Tancevski I, Timms JF, Zaikin A, Hippenstiel S, Ramharter M, Witzenrath M, Suttorp N, Lilley K, Mülleder M, Sander LE, PA-COVID-19 Study group, Ralser M, Kurth F.",,Cell systems,2021,2021-06-14,Y,Proteomics; Biomarkers; Physiological parameters; Machine Learning; Disease Prognosis; Clinical Disease Progression; Covid-19; Longitudinal Profiling; Patient Trajectories,,,"COVID-19 is highly variable in its clinical presentation, ranging from asymptomatic infection to severe organ damage and death. We characterized the time-dependent progression of the disease in 139 COVID-19 inpatients by measuring 86 accredited diagnostic parameters, such as blood cell counts and enzyme activities, as well as untargeted plasma proteomes at 687 sampling points. We report an initial spike in a systemic inflammatory response, which is gradually alleviated and followed by a protein signature indicative of tissue repair, metabolic reconstitution, and immunomodulation. We identify prognostic marker signatures for devising risk-adapted treatment strategies and use machine learning to classify therapeutic needs. We show that the machine learning models based on the proteome are transferable to an independent cohort. Our study presents a map linking routinely used clinical diagnostic parameters to plasma proteomes and their dynamics in an infectious disease.",,pdf:http://www.cell.com/article/S2405471221001605/pdf; doi:https://doi.org/10.1016/j.cels.2021.05.005; html:https://europepmc.org/articles/PMC8201874 -35706489,https://doi.org/10.1016/j.eclinm.2022.101428,Impact of ethnicity on the accuracy of measurements of oxygen saturations: A retrospective observational cohort study.,"Bangash MN, Hodson J, Evison F, Patel JM, Johnston AM, Gallier S, Sapey E, Parekh D.",,EClinicalMedicine,2022,2022-05-06,Y,Inequalities; Ethnicity; Oxygen Saturations,,,"

Background

Pulse oximeters are routinely used in community and hospital settings worldwide as a rapid, non-invasive, and readily available bedside tool to approximate blood oxygenation. Potential racial biases in peripheral oxygen saturation (SpO2) measurements may influence the accuracy of pulse oximetry readings and impact clinical decision making. We aimed to assess whether the accuracy of oxygen saturation measured by SpO2, relative to arterial blood gas (SaO2), varies by ethnicity.

Methods

In this large retrospective observational cohort study covering four NHS Hospitals serving a large urban population in Birmingham, United Kingdom, consecutive pairs of SpO2 and SaO2 measurements taken on the same patient within an interval of less than 20 min were identified from electronic patient records. Where multiple pairs of measurements were recorded in a spell, only the first was included in the analysis. The differences between SpO2 and SaO2 measurements were compared across groups of self-identified ethnicity. These differences were subsequently adjusted for age, sex, bilirubin, systolic blood pressure, carboxyhaemaglobin saturations and the time interval between SpO2 and SaO2 measurements.

Findings

Paired O2 saturation measurements from 16,818 inpatient spells between 1st January 2017 and 18th February 2021 were analysed. The cohort self-identified as being of White (81.2%), Asian (11.7%), Black (4.0%), or Other (3.2%) ethnicities. Across the cohort, SpO2 was statistically significantly higher than SaO2 (p < 0.0001), with medians of 98% (interquartile range [IQR]: 95-100%) vs. 97% (IQR: 96-99%), and a median difference of 0.5% points (pps; 95% confidence interval [CI]: 0.5-0.6). However, the size of this difference varied considerably with the magnitude of SaO2, with SpO2 overestimating by a median by 3.8pp (IQR: 0.4, 8.8) for SaO2 values <90% but underestimating by a median of 0.4pp (IQR: -2.0, 1.4) for an SaO2 of 95%. The differences between SpO2 and SaO2 were also found to vary by ethnicity, with this difference being 0.8pp (95% CI: 0.6-1.0, p < 0.0001) greater in those of Black vs. White ethnicity. These differences resulted in 8.7% vs. 6.1% of Black vs. White patients who were classified as normoxic on SpO2 actually being hypoxic on the gold standard SaO2 (odds ratio: 1.47, 95% CI: 1.09-1.98, p = 0.012).

Interpretation

Pulse oximetry may overestimate O2 saturation, and this is possibly more pronounced in patients of Black ethnicity. Prospective studies are urgently warranted to assess the impact of ethnicity on the accuracy of pulse oximetry, to ensure care is optimised for all.

Funding

PIONEER, the Health Data Research UK (HDR-UK) Health Data Research Hub in acute care.",,pdf:http://www.thelancet.com/article/S2589537022001584/pdf; doi:https://doi.org/10.1016/j.eclinm.2022.101428; html:https://europepmc.org/articles/PMC9096912; pdf:https://europepmc.org/articles/PMC9096912?pdf=render 33821553,https://doi.org/10.1002/jia2.25697,The impact of disruptions due to COVID-19 on HIV transmission and control among men who have sex with men in China.,"Booton RD, Fu G, MacGregor L, Li J, Ong JJ, Tucker JD, Turner KM, Tang W, Vickerman P, Mitchell KM.",,Journal of the International AIDS Society,2021,2021-04-01,Y,Modelling; Hiv Transmission; Men Who Have Sex With Men; People’s Republic Of China; Key And Vulnerable Populations; Covid-19 Pandemic,,,"

Introduction

The COVID-19 pandemic is impacting HIV care globally, with gaps in HIV treatment expected to increase HIV transmission and HIV-related mortality. We estimated how COVID-19-related disruptions could impact HIV transmission and mortality among men who have sex with men (MSM) in four cities in China, over a one- and five-year time horizon.

Methods

Regional data from China indicated that the number of MSM undergoing facility-based HIV testing reduced by 59% during the COVID-19 pandemic, alongside reductions in ART initiation (34%), numbers of all sexual partners (62%) and consistency of condom use (25%), but initial data indicated no change in viral suppression. A mathematical model of HIV transmission/treatment among MSM was used to estimate the impact of disruptions on HIV infections/HIV-related deaths. Disruption scenarios were assessed for their individual and combined impact over one and five years for 3/4/6-month disruption periods, starting from 1 January 2020.

Results

Our model predicted new HIV infections and HIV-related deaths would be increased most by disruptions to viral suppression, with 25% reductions (25% virally suppressed MSM stop taking ART) for a three-month period increasing HIV infections by 5% to 14% over one year and deaths by 7% to 12%. Observed reductions in condom use increased HIV infections by 5% to 14% but had minimal impact (<1%) on deaths. Smaller impacts on infections and deaths (<3%) were seen for disruptions to facility HIV testing and ART initiation, but reduced partner numbers resulted in 11% to 23% fewer infections and 0.4% to 1.0% fewer deaths. Longer disruption periods (4/6 months) amplified the impact of disruption scenarios. When realistic disruptions were modelled simultaneously, an overall decrease in new HIV infections occurred over one year (3% to 17%), but not for five years (1% increase to 4% decrease), whereas deaths mostly increased over one year (1% to 2%) and five years (1.2 increase to 0.3 decrease).

Conclusions

The overall impact of COVID-19 on new HIV infections and HIV-related deaths is dependent on the nature, scale and length of the various disruptions. Resources should be directed to ensuring levels of viral suppression and condom use are maintained to mitigate any adverse effects of COVID-19-related disruption on HIV transmission and control among MSM in China.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/jia2.25697; doi:https://doi.org/10.1002/jia2.25697; html:https://europepmc.org/articles/PMC8022092; pdf:https://europepmc.org/articles/PMC8022092?pdf=render +35706489,https://doi.org/10.1016/j.eclinm.2022.101428,Impact of ethnicity on the accuracy of measurements of oxygen saturations: A retrospective observational cohort study.,"Bangash MN, Hodson J, Evison F, Patel JM, Johnston AM, Gallier S, Sapey E, Parekh D.",,EClinicalMedicine,2022,2022-05-06,Y,Inequalities; Ethnicity; Oxygen Saturations,,,"

Background

Pulse oximeters are routinely used in community and hospital settings worldwide as a rapid, non-invasive, and readily available bedside tool to approximate blood oxygenation. Potential racial biases in peripheral oxygen saturation (SpO2) measurements may influence the accuracy of pulse oximetry readings and impact clinical decision making. We aimed to assess whether the accuracy of oxygen saturation measured by SpO2, relative to arterial blood gas (SaO2), varies by ethnicity.

Methods

In this large retrospective observational cohort study covering four NHS Hospitals serving a large urban population in Birmingham, United Kingdom, consecutive pairs of SpO2 and SaO2 measurements taken on the same patient within an interval of less than 20 min were identified from electronic patient records. Where multiple pairs of measurements were recorded in a spell, only the first was included in the analysis. The differences between SpO2 and SaO2 measurements were compared across groups of self-identified ethnicity. These differences were subsequently adjusted for age, sex, bilirubin, systolic blood pressure, carboxyhaemaglobin saturations and the time interval between SpO2 and SaO2 measurements.

Findings

Paired O2 saturation measurements from 16,818 inpatient spells between 1st January 2017 and 18th February 2021 were analysed. The cohort self-identified as being of White (81.2%), Asian (11.7%), Black (4.0%), or Other (3.2%) ethnicities. Across the cohort, SpO2 was statistically significantly higher than SaO2 (p < 0.0001), with medians of 98% (interquartile range [IQR]: 95-100%) vs. 97% (IQR: 96-99%), and a median difference of 0.5% points (pps; 95% confidence interval [CI]: 0.5-0.6). However, the size of this difference varied considerably with the magnitude of SaO2, with SpO2 overestimating by a median by 3.8pp (IQR: 0.4, 8.8) for SaO2 values <90% but underestimating by a median of 0.4pp (IQR: -2.0, 1.4) for an SaO2 of 95%. The differences between SpO2 and SaO2 were also found to vary by ethnicity, with this difference being 0.8pp (95% CI: 0.6-1.0, p < 0.0001) greater in those of Black vs. White ethnicity. These differences resulted in 8.7% vs. 6.1% of Black vs. White patients who were classified as normoxic on SpO2 actually being hypoxic on the gold standard SaO2 (odds ratio: 1.47, 95% CI: 1.09-1.98, p = 0.012).

Interpretation

Pulse oximetry may overestimate O2 saturation, and this is possibly more pronounced in patients of Black ethnicity. Prospective studies are urgently warranted to assess the impact of ethnicity on the accuracy of pulse oximetry, to ensure care is optimised for all.

Funding

PIONEER, the Health Data Research UK (HDR-UK) Health Data Research Hub in acute care.",,pdf:http://www.thelancet.com/article/S2589537022001584/pdf; doi:https://doi.org/10.1016/j.eclinm.2022.101428; html:https://europepmc.org/articles/PMC9096912; pdf:https://europepmc.org/articles/PMC9096912?pdf=render 34535484,https://doi.org/10.1136/bmjopen-2021-050647,The United Kingdom Research study into Ethnicity And COVID-19 outcomes in Healthcare workers (UK-REACH): protocol for a prospective longitudinal cohort study of healthcare and ancillary workers in UK healthcare settings.,"Woolf K, Melbourne C, Bryant L, Guyatt AL, McManus IC, Gupta A, Free RC, Nellums L, Carr S, John C, Martin CA, Wain LV, Gray LJ, Garwood C, Modhwadia V, Abrams KR, Tobin MD, Khunti K, Pareek M, UK-REACH Study Collaborative Group+.",,BMJ open,2021,2021-09-17,Y,Mental health; Public Health; Covid-19,,,"

Introduction

The COVID-19 pandemic has resulted in significant morbidity and mortality and devastated economies globally. Among groups at increased risk are healthcare workers (HCWs) and ethnic minority groups. Emerging evidence suggests that HCWs from ethnic minority groups are at increased risk of adverse COVID-19-related outcomes. To date, there has been no large-scale analysis of these risks in UK HCWs or ancillary workers in healthcare settings, stratified by ethnicity or occupation, and adjusted for confounders. This paper reports the protocol for a prospective longitudinal questionnaire study of UK HCWs, as part of the UK-REACH programme (The United Kingdom Research study into Ethnicity And COVID-19 outcomes in Healthcare workers).

Methods and analysis

A baseline questionnaire will be administered to a national cohort of UK HCWs and ancillary workers in healthcare settings, and those registered with UK healthcare regulators, with follow-up questionnaires administered at 4 and 8 months. With consent, questionnaire data will be linked to health records with 25-year follow-up. Univariate associations between ethnicity and clinical COVID-19 outcomes, physical and mental health, and key confounders/explanatory variables will be tested. Multivariable analyses will test for associations between ethnicity and key outcomes adjusted for the confounder/explanatory variables. We will model changes over time by ethnic group, facilitating understanding of absolute and relative risks in different ethnic groups, and generalisability of findings.

Ethics and dissemination

The study is approved by Health Research Authority (reference 20/HRA/4718), and carries minimal risk. We aim to manage the small risk of participant distress about questions on sensitive topics by clearly participant information that the questionnaire covers sensitive topics and there is no obligation to answer these or any other questions, and by providing support organisation links. Results will be disseminated with reports to Government and papers submitted to pre-print servers and peer reviewed journals.

Trial registration number

ISRCTN11811602; Pre-results.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/9/e050647.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-050647; html:https://europepmc.org/articles/PMC8450967; pdf:https://europepmc.org/articles/PMC8450967?pdf=render 34672950,https://doi.org/10.1016/s2213-2600(21)00435-5,"Colchicine in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial.",RECOVERY Collaborative Group.,,The Lancet. Respiratory medicine,2021,2021-10-18,Y,,,,"

Background

Colchicine has been proposed as a treatment for COVID-19 based on its anti-inflammatory actions. We aimed to evaluate the efficacy and safety of colchicine in patients admitted to hospital with COVID-19.

Methods

In this streamlined, randomised, controlled, open-label trial, underway at 177 hospitals in the UK, two hospitals in Indonesia, and two hospitals in Nepal, several possible treatments were compared with usual care in patients hospitalised with COVID-19. Patients were eligible for inclusion in the study if they were admitted to hospital with clinically suspected or laboratory confirmed SARS-CoV-2 infection and had no medical history that might, in the opinion of the attending clinician, put the patient at significant risk if they were to participate in the trial. Eligible and consenting adults were randomly assigned (1:1) to receive either usual standard of care alone (usual care group) or usual standard of care plus colchicine (colchicine group) using web-based simple (unstratified) randomisation with allocation concealment. Participants received colchicine 1 mg after randomisation followed by 500 μg 12 h later and then 500 μg twice a day by mouth or nasogastric tube for 10 days in total or until discharge. Dose frequency was halved for patients receiving a moderate CYP3A4 inhibitor (eg, diltiazem), patients with an estimated glomerular filtration rate of less than 30 mL/min per 1·73m2, and those with an estimated bodyweight of less than 70 kg. The primary outcome was 28-day mortality, secondary endpoints included time to discharge, the proportion of patients discharged from hospital within 28 days, and, in patients not on invasive mechanical ventilation at randomisation, a composite endpoint of invasive mechanical ventilation or death. All analyses were by intention-to-treat. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.

Findings

Between Nov 27, 2020, and March 4, 2021, 11 340 (58%) of 19 423 patients enrolled into the RECOVERY trial were eligible to receive colchicine; 5610 (49%) patients were randomly assigned to the colchicine group and 5730 (51%) to the usual care group. Overall, 1173 (21%) patients in the colchicine group and 1190 (21%) patients in the usual care group died within 28 days (rate ratio 1·01 [95% CI 0·93 to 1·10]; p=0·77). Consistent results were seen in all prespecified subgroups of patients. Median time to discharge alive (10 days [IQR 5 to >28]) was the same in both groups, and there was no significant difference in the proportion of patients discharged from hospital alive within 28 days (3901 [70%] patients in the colchicine group and 4032 [70%] usual care group; rate ratio 0·98 [95% CI 0·94 to 1·03]; p=0·44). In those not on invasive mechanical ventilation at baseline, there was no significant difference in the proportion meeting the composite endpoint of invasive mechanical ventilation or death (1344 [25%] in the colchicine group vs 1343 [25%] patients in the usual care group; risk ratio 1·02 [95% CI 0·96 to 1·09]; p=0·47).

Interpretation

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

Funding

UK Research and Innovation (Medical Research Council), National Institute of Health Research, and Wellcome Trust.",,pdf:http://www.thelancet.com/article/S2213260021004355/pdf; doi:https://doi.org/10.1016/S2213-2600(21)00435-5; html:https://europepmc.org/articles/PMC8523117 34847950,https://doi.org/10.1186/s12916-021-02190-3,Models of COVID-19 vaccine prioritisation: a systematic literature search and narrative review.,"Saadi N, Chi YL, Ghosh S, Eggo RM, McCarthy CV, Quaife M, Dawa J, Jit M, Vassall A.",,BMC medicine,2021,2021-12-01,Y,"Covid-19, Vaccination, Mathematical Modelling",,,"

Background

How best to prioritise COVID-19 vaccination within and between countries has been a public health and an ethical challenge for decision-makers globally. We reviewed epidemiological and economic modelling evidence on population priority groups to minimise COVID-19 mortality, transmission, and morbidity outcomes.

Methods

We searched the National Institute of Health iSearch COVID-19 Portfolio (a database of peer-reviewed and pre-print articles), Econlit, the Centre for Economic Policy Research, and the National Bureau of Economic Research for mathematical modelling studies evaluating the impact of prioritising COVID-19 vaccination to population target groups. The first search was conducted on March 3, 2021, and an updated search on the LMIC literature was conducted from March 3, 2021, to September 24, 2021. We narratively synthesised the main study conclusions on prioritisation and the conditions under which the conclusions changed.

Results

The initial search identified 1820 studies and 36 studies met the inclusion criteria. The updated search on LMIC literature identified 7 more studies. 43 studies in total were narratively synthesised. 74% of studies described outcomes in high-income countries (single and multi-country). We found that for countries seeking to minimise deaths, prioritising vaccination of senior adults was the optimal strategy and for countries seeking to minimise cases the young were prioritised. There were several exceptions to the main conclusion, notably that reductions in deaths could be increased if groups at high risk of both transmission and death could be further identified. Findings were also sensitive to the level of vaccine coverage.

Conclusion

The evidence supports WHO SAGE recommendations on COVID-19 vaccine prioritisation. There is, however, an evidence gap on optimal prioritisation for low- and middle-income countries, studies that included an economic evaluation, and studies that explore prioritisation strategies if the aim is to reduce overall health burden including morbidity.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-021-02190-3; doi:https://doi.org/10.1186/s12916-021-02190-3; html:https://europepmc.org/articles/PMC8632563; pdf:https://europepmc.org/articles/PMC8632563?pdf=render PMC10686417,https://doi.org/,The impact of restricted provision of publicly funded elective hip and knee joints replacement during the COVID-19 pandemic in England,"Penfold C, Blom A, Redaniel M, Jones T, Eyles E, Keen T, Elliott A, Judge A.",,PloS one,2023,2023-01-01,Y,,,,,,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10686417/?tool=EBI; pdf:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10686417/pdf/?tool=EBI; html:https://europepmc.org/articles/PMC10686417; pdf:https://europepmc.org/articles/PMC10686417?pdf=render -38626948,https://doi.org/10.1136/bmj-2023-078378,TRIPOD+AI statement: updated guidance for reporting clinical prediction models that use regression or machine learning methods.,"Collins GS, Moons KGM, Dhiman P, Riley RD, Beam AL, Van Calster B, Ghassemi M, Liu X, Reitsma JB, van Smeden M, Boulesteix AL, Camaradou JC, Celi LA, Denaxas S, Denniston AK, Glocker B, Golub RM, Harvey H, Heinze G, Hoffman MM, Kengne AP, Lam E, Lee N, Loder EW, Maier-Hein L, Mateen BA, McCradden MD, Oakden-Rayner L, Ordish J, Parnell R, Rose S, Singh K, Wynants L, Logullo P.",,BMJ (Clinical research ed.),2024,2024-04-16,Y,,,,,,pdf:https://www.bmj.com/content/bmj/385/bmj-2023-078378.full.pdf; doi:https://doi.org/10.1136/bmj-2023-078378; html:https://europepmc.org/articles/PMC11019967 35197114,https://doi.org/10.1186/s41512-022-00120-2,Comparison of methods for predicting COVID-19-related death in the general population using the OpenSAFELY platform.,"OpenSAFELY Collaborative, Williamson EJ, Tazare J, Bhaskaran K, McDonald HI, Walker AJ, Tomlinson L, Wing K, Bacon S, Bates C, Curtis HJ, Forbes HJ, Minassian C, Morton CE, Nightingale E, Mehrkar A, Evans D, Nicholson BD, Leon DA, Inglesby P, MacKenna B, Davies NG, DeVito NJ, Drysdale H, Cockburn J, Hulme WJ, Morley J, Douglas I, Rentsch CT, Mathur R, Wong A, Schultze A, Croker R, Parry J, Hester F, Harper S, Grieve R, Harrison DA, Steyerberg EW, Eggo RM, Diaz-Ordaz K, Keogh R, Evans SJW, Smeeth L, Goldacre B.",,Diagnostic and prognostic research,2022,2022-02-24,Y,Mortality; Infectious disease; Risk stratification; Statistical methodology; Risk Prediction; Covid-19,,,"

Background

Obtaining accurate estimates of the risk of COVID-19-related death in the general population is challenging in the context of changing levels of circulating infection.

Methods

We propose a modelling approach to predict 28-day COVID-19-related death which explicitly accounts for COVID-19 infection prevalence using a series of sub-studies from new landmark times incorporating time-updating proxy measures of COVID-19 infection prevalence. This was compared with an approach ignoring infection prevalence. The target population was adults registered at a general practice in England in March 2020. The outcome was 28-day COVID-19-related death. Predictors included demographic characteristics and comorbidities. Three proxies of local infection prevalence were used: model-based estimates, rate of COVID-19-related attendances in emergency care, and rate of suspected COVID-19 cases in primary care. We used data within the TPP SystmOne electronic health record system linked to Office for National Statistics mortality data, using the OpenSAFELY platform, working on behalf of NHS England. Prediction models were developed in case-cohort samples with a 100-day follow-up. Validation was undertaken in 28-day cohorts from the target population. We considered predictive performance (discrimination and calibration) in geographical and temporal subsets of data not used in developing the risk prediction models. Simple models were contrasted to models including a full range of predictors.

Results

Prediction models were developed on 11,972,947 individuals, of whom 7999 experienced COVID-19-related death. All models discriminated well between individuals who did and did not experience the outcome, including simple models adjusting only for basic demographics and number of comorbidities: C-statistics 0.92-0.94. However, absolute risk estimates were substantially miscalibrated when infection prevalence was not explicitly modelled.

Conclusions

Our proposed models allow absolute risk estimation in the context of changing infection prevalence but predictive performance is sensitive to the proxy for infection prevalence. Simple models can provide excellent discrimination and may simplify implementation of risk prediction tools.",,pdf:https://diagnprognres.biomedcentral.com/track/pdf/10.1186/s41512-022-00120-2; doi:https://doi.org/10.1186/s41512-022-00120-2; html:https://europepmc.org/articles/PMC8865947; pdf:https://europepmc.org/articles/PMC8865947?pdf=render +38626948,https://doi.org/10.1136/bmj-2023-078378,TRIPOD+AI statement: updated guidance for reporting clinical prediction models that use regression or machine learning methods.,"Collins GS, Moons KGM, Dhiman P, Riley RD, Beam AL, Van Calster B, Ghassemi M, Liu X, Reitsma JB, van Smeden M, Boulesteix AL, Camaradou JC, Celi LA, Denaxas S, Denniston AK, Glocker B, Golub RM, Harvey H, Heinze G, Hoffman MM, Kengne AP, Lam E, Lee N, Loder EW, Maier-Hein L, Mateen BA, McCradden MD, Oakden-Rayner L, Ordish J, Parnell R, Rose S, Singh K, Wynants L, Logullo P.",,BMJ (Clinical research ed.),2024,2024-04-16,Y,,,,,,pdf:https://www.bmj.com/content/bmj/385/bmj-2023-078378.full.pdf; doi:https://doi.org/10.1136/bmj-2023-078378; html:https://europepmc.org/articles/PMC11019967 34849869,https://doi.org/10.1093/gigascience/giab076,An overview of the National COVID-19 Chest Imaging Database: data quality and cohort analysis.,"Cushnan D, Bennett O, Berka R, Bertolli O, Chopra A, Dorgham S, Favaro A, Ganepola T, Halling-Brown M, Imreh G, Jacob J, Jefferson E, Lemarchand F, Schofield D, Wyatt JC, NCCID Collaborative.",,GigaScience,2021,2021-11-01,Y,Medical imaging; Machine Learning; Thoracic Imaging; Covid-19; Sars-cov2,,,"

Background

The National COVID-19 Chest Imaging Database (NCCID) is a centralized database containing mainly chest X-rays and computed tomography scans from patients across the UK. The objective of the initiative is to support a better understanding of the coronavirus SARS-CoV-2 disease (COVID-19) and the development of machine learning technologies that will improve care for patients hospitalized with a severe COVID-19 infection. This article introduces the training dataset, including a snapshot analysis covering the completeness of clinical data, and availability of image data for the various use-cases (diagnosis, prognosis, longitudinal risk). An additional cohort analysis measures how well the NCCID represents the wider COVID-19-affected UK population in terms of geographic, demographic, and temporal coverage.

Findings

The NCCID offers high-quality DICOM images acquired across a variety of imaging machinery; multiple time points including historical images are available for a subset of patients. This volume and variety make the database well suited to development of diagnostic/prognostic models for COVID-associated respiratory conditions. Historical images and clinical data may aid long-term risk stratification, particularly as availability of comorbidity data increases through linkage to other resources. The cohort analysis revealed good alignment to general UK COVID-19 statistics for some categories, e.g., sex, whilst identifying areas for improvements to data collection methods, particularly geographic coverage.

Conclusion

The NCCID is a growing resource that provides researchers with a large, high-quality database that can be leveraged both to support the response to the COVID-19 pandemic and as a test bed for building clinically viable medical imaging models.",,pdf:https://academic.oup.com/gigascience/article-pdf/10/11/giab076/41395024/giab076.pdf; doi:https://doi.org/10.1093/gigascience/giab076; html:https://europepmc.org/articles/PMC8633457; pdf:https://europepmc.org/articles/PMC8633457?pdf=render 37432340,https://doi.org/10.1093/rheumatology/kead346,Trends for opioid prescribing and the impact of the COVID-19 pandemic in patients with rheumatic and musculoskeletal diseases between 2006 and 2021.,"Huang YT, Jenkins DA, Yimer BB, Benitez-Aurioles J, Peek N, Lunt M, Dixon WG, Jani M.",,"Rheumatology (Oxford, England)",2024,2024-04-01,Y,RA; SLE; Trend; PSA; Opioids; Oa; Axial Spondyloarthritis; Fm; Covid-19,,,"

Objective

To investigate opioid prescribing trends and assess the impact of the COVID-19 pandemic on opioid prescribing in rheumatic and musculoskeletal diseases (RMDs).

Methods

Adult patients with RA, PsA, axial spondyloarthritis (AxSpA), SLE, OA and FM with opioid prescriptions between 1 January 2006 and 31 August 2021 without cancer in UK primary care were included. Age- and gender-standardized yearly rates of new and prevalent opioid users were calculated between 2006 and 2021. For prevalent users, monthly measures of mean morphine milligram equivalents (MME)/day were calculated between 2006 and 2021. To assess the impact of the pandemic, we fitted regression models to the monthly number of prevalent opioid users between January 2015 and August 2021. The time coefficient reflects the trend pre-pandemic and the interaction term coefficient represents the change in the trend during the pandemic.

Results

The study included 1 313 519 RMD patients. New opioid users for RA, PsA and FM increased from 2.6, 1.0 and 3.4/10 000 persons in 2006 to 4.5, 1.8 and 8.7, respectively, in 2018 or 2019. This was followed by a fall to 2.4, 1.2 and 5.9, respectively, in 2021. Prevalent opioid users for all RMDs increased from 2006 but plateaued or dropped beyond 2018, with a 4.5-fold increase in FM between 2006 and 2021. In this period, MME/day increased for all RMDs, with the highest for FM (≥35). During COVID-19 lockdowns, RA, PsA and FM showed significant changes in the trend of prevalent opioid users. The trend for FM increased pre-pandemic and started decreasing during the pandemic.

Conclusion

The plateauing or decreasing trend of opioid users for RMDs after 2018 may reflect the efforts to tackle rising opioid prescribing in the UK. The pandemic led to fewer people on opioids for most RMDs, providing reassurance that there was no sudden increase in opioid prescribing during the pandemic.",,pdf:https://academic.oup.com/rheumatology/advance-article-pdf/doi/10.1093/rheumatology/kead346/50930066/kead346.pdf; doi:https://doi.org/10.1093/rheumatology/kead346; html:https://europepmc.org/articles/PMC10986805; pdf:https://europepmc.org/articles/PMC10986805?pdf=render 36982069,https://doi.org/10.3390/ijerph20065161,The Impact of COVID-19 Lockdown on Adults with Major Depressive Disorder from Catalonia: A Decentralized Longitudinal Study.,"Lavalle R, Condominas E, Haro JM, Giné-Vázquez I, Bailon R, Laporta E, Garcia E, Kontaxis S, Alacid GR, Lombardini F, Preti A, Peñarrubia-Maria MT, Coromina M, Arranz B, Vilella E, Rubio-Alacid E, Radar-Mdd Spain, Matcham F, Lamers F, Hotopf M, Penninx BWJH, Annas P, Narayan V, Simblett SK, Siddi S, The Radar-Cns Consortium.",,International journal of environmental research and public health,2023,2023-03-15,Y,Quarantine; Depression; Anxiety; Spain; Lockdown; Remote Measurement Technology; Sars-cov-2; Decentralized Study,,,"The present study analyzes the effects of each containment phase of the first COVID-19 wave on depression levels in a cohort of 121 adults with a history of major depressive disorder (MDD) from Catalonia recruited from 1 November 2019, to 16 October 2020. This analysis is part of the Remote Assessment of Disease and Relapse-MDD (RADAR-MDD) study. Depression was evaluated with the Patient Health Questionnaire-8 (PHQ-8), and anxiety was evaluated with the Generalized Anxiety Disorder-7 (GAD-7). Depression's levels were explored across the phases (pre-lockdown, lockdown, and four post-lockdown phases) according to the restrictions of Spanish/Catalan governments. Then, a mixed model was fitted to estimate how depression varied over the phases. A significant rise in depression severity was found during the lockdown and phase 0 (early post-lockdown), compared with the pre-lockdown. Those with low pre-lockdown depression experienced an increase in depression severity during the ""new normality"", while those with high pre-lockdown depression decreased compared with the pre-lockdown. These findings suggest that COVID-19 restrictions affected the depression level depending on their pre-lockdown depression severity. Individuals with low levels of depression are more reactive to external stimuli than those with more severe depression, so the lockdown may have worse detrimental effects on them.",,pdf:https://www.mdpi.com/1660-4601/20/6/5161/pdf?version=1678866764; doi:https://doi.org/10.3390/ijerph20065161; html:https://europepmc.org/articles/PMC10048808; pdf:https://europepmc.org/articles/PMC10048808?pdf=render @@ -519,8 +519,8 @@ PMC10686417,https://doi.org/,The impact of restricted provision of publicly fund 37193316,https://doi.org/10.1016/j.xops.2023.100293,"A Datasheet for the INSIGHT Birmingham, Solihull, and Black Country Diabetic Retinopathy Screening Dataset.","Kale AU, Mills A, Guggenheim E, Gee D, Bodza S, Anumakonda A, Doal R, Williams R, Gallier S, Lee WH, Galsworthy P, Benning M, Fanning H, Keane PA, Denniston AK, Mollan SP.",,Ophthalmology science,2023,2023-02-26,Y,Diabetes mellitus; Diabetic retinopathy; Imaging; Dataset; Biomedical Data,,,"

Purpose

Diabetic retinopathy (DR) is the most common microvascular complication associated with diabetes mellitus (DM), affecting approximately 40% of this patient population. Early detection of DR is vital to ensure monitoring of disease progression and prompt sight saving treatments as required. This article describes the data contained within the INSIGHT Birmingham, Solihull, and Black Country Diabetic Retinopathy Dataset.

Design

Dataset descriptor for routinely collected eye screening data.

Participants

All diabetic patients aged 12 years and older, attending annual digital retinal photography-based screening within the Birmingham, Solihull, and Black Country Eye Screening Programme.

Methods

The INSIGHT Health Data Research Hub for Eye Health is a National Health Service (NHS)-led ophthalmic bioresource that provides researchers with safe access to anonymized, routinely collected data from contributing NHS hospitals to advance research for patient benefit. This report describes the INSIGHT Birmingham, Solihull, and Black Country DR Screening Dataset, a dataset of anonymized images and linked screening data derived from the United Kingdom's largest regional DR screening program.

Main outcome measures

This dataset consists of routinely collected data from the eye screening program. The data primarily include retinal photographs with the associated DR grading data. Additional data such as corresponding demographic details, information regarding patients' diabetic status, and visual acuity data are also available. Further details regarding available data points are available in the supplementary information, in addition to the INSIGHT webpage included below.

Results

At the time point of this analysis (December 31, 2019), the dataset comprised 6 202 161 images from 246 180 patients, with a dataset inception date of January 1, 2007. The dataset includes 1 360 547 grading episodes between R0M0 and R3M1.

Conclusions

This dataset descriptor article summarizes the content of the dataset, how it has been curated, and what its potential uses are. Data are available through a structured application process for research studies that support discovery, clinical evidence analyses, and innovation in artificial intelligence technologies for patient benefit. Further information regarding the data repository and contact details can be found at https://www.insight.hdrhub.org/.

Financial disclosures

Proprietary or commercial disclosure may be found after the references.",,pdf:http://www.ophthalmologyscience.org/article/S2666914523000258/pdf; doi:https://doi.org/10.1016/j.xops.2023.100293; html:https://europepmc.org/articles/PMC10182318; pdf:https://europepmc.org/articles/PMC10182318?pdf=render 35247983,https://doi.org/10.1186/s12877-021-02673-1,"Age is the main determinant of COVID-19 related in-hospital mortality with minimal impact of pre-existing comorbidities, a retrospective cohort study.","Henkens MTHM, Raafs AG, Verdonschot JAJ, Linschoten M, van Smeden M, Wang P, van der Hooft BHM, Tieleman R, Janssen MLF, Ter Bekke RMA, Hazebroek MR, van der Horst ICC, Asselbergs FW, Magdelijns FJH, Heymans SRB, CAPACITY-COVID collaborative consortium.",,BMC geriatrics,2022,2022-03-05,Y,Mortality; Hospitalization; Netherlands; Mediation Analysis; Covid-19,,,"

Background

Age and comorbidities increase COVID-19 related in-hospital mortality risk, but the extent by which comorbidities mediate the impact of age remains unknown.

Methods

In this multicenter retrospective cohort study with data from 45 Dutch hospitals, 4806 proven COVID-19 patients hospitalized in Dutch hospitals (between February and July 2020) from the CAPACITY-COVID registry were included (age 69[58-77]years, 64% men). The primary outcome was defined as a combination of in-hospital mortality or discharge with palliative care. Logistic regression analysis was performed to analyze the associations between sex, age, and comorbidities with the primary outcome. The effect of comorbidities on the relation of age with the primary outcome was evaluated using mediation analysis.

Results

In-hospital COVID-19 related mortality occurred in 1108 (23%) patients, 836 (76%) were aged ≥70 years (70+). Both age 70+ and female sex were univariably associated with outcome (odds ratio [OR]4.68, 95%confidence interval [4.02-5.45], OR0.68[0.59-0.79], respectively;both p<  0.001). All comorbidities were univariably associated with outcome (p<0.001), and all but dyslipidemia remained significant after adjustment for age70+ and sex. The impact of comorbidities was attenuated after age-spline adjustment, only leaving female sex, diabetes mellitus (DM), chronic kidney disease (CKD), and chronic pulmonary obstructive disease (COPD) significantly associated (female OR0.65[0.55-0.75], DM OR1.47[1.26-1.72], CKD OR1.61[1.32-1.97], COPD OR1.30[1.07-1.59]). Pre-existing comorbidities in older patients negligibly (<6% in all comorbidities) mediated the association between higher age and outcome.

Conclusions

Age is the main determinant of COVID-19 related in-hospital mortality, with negligible mediation effect of pre-existing comorbidities.

Trial registration

CAPACITY-COVID ( NCT04325412 ).",,doi:https://doi.org/10.1186/s12877-021-02673-1; doi:https://doi.org/10.1186/s12877-021-02673-1; html:https://europepmc.org/articles/PMC8897728; pdf:https://europepmc.org/articles/PMC8897728?pdf=render 33493433,https://doi.org/10.1016/s1470-2045(20)30743-9,"The impact of the COVID-19 pandemic on radiotherapy services in England, UK: a population-based study.","Spencer K, Jones CM, Girdler R, Roe C, Sharpe M, Lawton S, Miller L, Lewis P, Evans M, Sebag-Montefiore D, Roques T, Smittenaar R, Morris E.",,The Lancet. Oncology,2021,2021-01-22,Y,,,,"

Background

The indirect impact of the COVID-19 pandemic on cancer outcomes is of increasing concern. However, the extent to which key treatment modalities have been affected is unclear. We aimed to assess the impact of the pandemic on radiotherapy activity in England.

Methods

In this population-based study, data relating to all radiotherapy delivered for cancer in the English NHS, between Feb 4, 2019, and June 28, 2020, were extracted from the National Radiotherapy Dataset. Changes in mean weekly radiotherapy courses, attendances (reflecting fractions), and fractionation patterns following the start of the UK lockdown were compared with corresponding months in 2019 overall, for specific diagnoses, and across age groups. The significance of changes in radiotherapy activity during lockdown was examined using interrupted time-series (ITS) analysis.

Findings

In 2020, mean weekly radiotherapy courses fell by 19·9% in April, 6·2% in May, and 11·6% in June compared with corresponding months in 2019. A relatively greater fall was observed for attendances (29·1% in April, 31·4% in May, and 31·5% in June). These changes were significant on ITS analysis (p<0·0001). A greater reduction in treatment courses between 2019 and 2020 was seen for patients aged 70 years or older compared with those aged younger than 70 years (34·4% vs 7·3% in April). By diagnosis, the largest reduction from 2019 to 2020 in treatment courses was for prostate cancer (77·0% in April) and non-melanoma skin cancer (72·4% in April). Conversely, radiotherapy courses in April, 2020, compared with April, 2019, increased by 41·2% in oesophageal cancer, 64·2% in bladder cancer, and 36·3% in rectal cancer. Increased use of ultra-hypofractionated (26 Gy in five fractions) breast radiotherapy as a percentage of all courses (0·2% in April, 2019, to 60·6% in April, 2020; ITS p<0·0001) contributed to the substantial reduction in attendances.

Interpretation

Radiotherapy activity fell significantly, but use of hypofractionated regimens rapidly increased in the English NHS during the first peak of the COVID-19 pandemic. An increase in treatments for some cancers suggests that radiotherapy compensated for reduced surgical activity. These data will assist health-care providers in understanding the indirect consequences of the pandemic and the role of radiotherapy services in minimising these consequences.

Funding

None.",,pdf:http://www.thelancet.com/article/S1470204520307439/pdf; doi:https://doi.org/10.1016/S1470-2045(20)30743-9; html:https://europepmc.org/articles/PMC7825861; pdf:https://europepmc.org/articles/PMC7825861?pdf=render -36769519,https://doi.org/10.3390/jcm12030872,Patterns of Healthcare Resource Utilisation of Critical Care Survivors between 2006 and 2017 in Wales: A Population-Based Study.,"Alsallakh M, Tan L, Pugh R, Akbari A, Bailey R, Griffiths R, Lyons RA, Szakmany T.",,Journal of clinical medicine,2023,2023-01-21,Y,Wales; Healthcare Resource Utilisation; Critical Care Survivorship,,,"In this retrospective cohort study, we used the Secure Anonymised Information Linkage (SAIL) Databank to characterise and identify predictors of the one-year post-discharge healthcare resource utilisation (HRU) of adults who were admitted to critical care units in Wales between 1 April 2006 and 31 December 2017. We modelled one-year post-critical-care HRU using negative binomial models and used linear models for the difference from one-year pre-critical-care HRU. We estimated the association between critical illness and post-hospitalisation HRU using multilevel negative binomial models among people hospitalised in 2015. We studied 55,151 patients. Post-critical-care HRU was 11-87% greater than pre-critical-care levels, whereas emergency department (ED) attendances decreased by 30%. Age ≥50 years was generally associated with greater post-critical-care HRU; those over 80 had three times longer hospital readmissions than those younger than 50 (incidence rate ratio (IRR): 2.96, 95% CI: 2.84, 3.09). However, ED attendances were higher in those younger than 50. High comorbidity was associated with 22-62% greater post-critical-care HRU than no or low comorbidity. The most socioeconomically deprived quintile was associated with 24% more ED attendances (IRR: 1.24 [1.16, 1.32]) and 13% longer hospital stays (IRR: 1.13 [1.09, 1.17]) than the least deprived quintile. Critical care survivors had greater 1-year post-discharge HRU than non-critical inpatients, including 68% longer hospital stays (IRR: 1.68 [1.63, 1.74]). Critical care survivors, particularly those with older ages, high comorbidity, and socioeconomic deprivation, used significantly more primary and secondary care resources after discharge compared with their baseline and non-critical inpatients. Interventions are needed to ensure that key subgroups are identified and adequately supported.",,pdf:https://www.mdpi.com/2077-0383/12/3/872/pdf?version=1674984751; doi:https://doi.org/10.3390/jcm12030872; html:https://europepmc.org/articles/PMC9917699; pdf:https://europepmc.org/articles/PMC9917699?pdf=render 32685698,https://doi.org/10.12688/wellcomeopenres.15842.3,Estimating the overdispersion in COVID-19 transmission using outbreak sizes outside China.,"Endo A, Centre for the Mathematical Modelling of Infectious Diseases COVID-19 Working Group, Abbott S, Kucharski AJ, Funk S.",,Wellcome open research,2020,2020-07-10,Y,Branching Process; Overdispersion; Novel Coronavirus; Superspreading; Covid-19; Sars-cov-2,,,"Background: A novel coronavirus disease (COVID-19) outbreak has now spread to a number of countries worldwide. While sustained transmission chains of human-to-human transmission suggest high basic reproduction number R 0, variation in the number of secondary transmissions (often characterised by so-called superspreading events) may be large as some countries have observed fewer local transmissions than others. Methods: We quantified individual-level variation in COVID-19 transmission by applying a mathematical model to observed outbreak sizes in affected countries. We extracted the number of imported and local cases in the affected countries from the World Health Organization situation report and applied a branching process model where the number of secondary transmissions was assumed to follow a negative-binomial distribution. Results: Our model suggested a high degree of individual-level variation in the transmission of COVID-19. Within the current consensus range of R 0 (2-3), the overdispersion parameter k of a negative-binomial distribution was estimated to be around 0.1 (median estimate 0.1; 95% CrI: 0.05-0.2 for R0 = 2.5), suggesting that 80% of secondary transmissions may have been caused by a small fraction of infectious individuals (~10%). A joint estimation yielded likely ranges for R 0 and k (95% CrIs: R 0 1.4-12; k 0.04-0.2); however, the upper bound of R 0 was not well informed by the model and data, which did not notably differ from that of the prior distribution. Conclusions: Our finding of a highly-overdispersed offspring distribution highlights a potential benefit to focusing intervention efforts on superspreading. As most infected individuals do not contribute to the expansion of an epidemic, the effective reproduction number could be drastically reduced by preventing relatively rare superspreading events.",,doi:https://doi.org/10.12688/wellcomeopenres.15842.3; html:https://europepmc.org/articles/PMC7338915; pdf:https://europepmc.org/articles/PMC7338915?pdf=render +36769519,https://doi.org/10.3390/jcm12030872,Patterns of Healthcare Resource Utilisation of Critical Care Survivors between 2006 and 2017 in Wales: A Population-Based Study.,"Alsallakh M, Tan L, Pugh R, Akbari A, Bailey R, Griffiths R, Lyons RA, Szakmany T.",,Journal of clinical medicine,2023,2023-01-21,Y,Wales; Healthcare Resource Utilisation; Critical Care Survivorship,,,"In this retrospective cohort study, we used the Secure Anonymised Information Linkage (SAIL) Databank to characterise and identify predictors of the one-year post-discharge healthcare resource utilisation (HRU) of adults who were admitted to critical care units in Wales between 1 April 2006 and 31 December 2017. We modelled one-year post-critical-care HRU using negative binomial models and used linear models for the difference from one-year pre-critical-care HRU. We estimated the association between critical illness and post-hospitalisation HRU using multilevel negative binomial models among people hospitalised in 2015. We studied 55,151 patients. Post-critical-care HRU was 11-87% greater than pre-critical-care levels, whereas emergency department (ED) attendances decreased by 30%. Age ≥50 years was generally associated with greater post-critical-care HRU; those over 80 had three times longer hospital readmissions than those younger than 50 (incidence rate ratio (IRR): 2.96, 95% CI: 2.84, 3.09). However, ED attendances were higher in those younger than 50. High comorbidity was associated with 22-62% greater post-critical-care HRU than no or low comorbidity. The most socioeconomically deprived quintile was associated with 24% more ED attendances (IRR: 1.24 [1.16, 1.32]) and 13% longer hospital stays (IRR: 1.13 [1.09, 1.17]) than the least deprived quintile. Critical care survivors had greater 1-year post-discharge HRU than non-critical inpatients, including 68% longer hospital stays (IRR: 1.68 [1.63, 1.74]). Critical care survivors, particularly those with older ages, high comorbidity, and socioeconomic deprivation, used significantly more primary and secondary care resources after discharge compared with their baseline and non-critical inpatients. Interventions are needed to ensure that key subgroups are identified and adequately supported.",,pdf:https://www.mdpi.com/2077-0383/12/3/872/pdf?version=1674984751; doi:https://doi.org/10.3390/jcm12030872; html:https://europepmc.org/articles/PMC9917699; pdf:https://europepmc.org/articles/PMC9917699?pdf=render 34183745,https://doi.org/10.1038/s41598-021-92874-w,Frailty assessed by administrative tools and mortality in patients with pneumonia admitted to the hospital and ICU in Wales.,"Szakmany T, Hollinghurst J, Pugh R, Akbari A, Griffiths R, Bailey R, Lyons RA.",,Scientific reports,2021,2021-06-28,Y,,,,"The ideal method of identifying frailty is uncertain, and data on long-term outcomes is relatively limited. We examined frailty indices derived from population-scale linked data on Intensive Care Unit (ICU) and hospitalised non-ICU patients with pneumonia to elucidate the influence of frailty on mortality. Longitudinal cohort study between 2010-2018 using population-scale anonymised data linkage of healthcare records for adults admitted to hospital with pneumonia in Wales. Primary outcome was in-patient mortality. Odds Ratios (ORs [95% confidence interval]) for age, hospital frailty risk score (HFRS), electronic frailty index (eFI), Charlson comorbidity index (CCI), and social deprivation index were estimated using multivariate logistic regression models. The area under the receiver operating characteristic curve (AUC) was estimated to determine the best fitting models. Of the 107,188 patients, mean (SD) age was 72.6 (16.6) years, 50% were men. The models adjusted for the two frailty indices and the comorbidity index had an increased odds of in-patient mortality for individuals with an ICU admission (ORs for ICU admission in the eFI model 2.67 [2.55, 2.79], HFRS model 2.30 [2.20, 2.41], CCI model 2.62 [2.51, 2.75]). Models indicated advancing age, increased frailty and comorbidity were also associated with an increased odds of in-patient mortality (eFI, baseline fit, ORs: mild 1.09 [1.04, 1.13], moderate 1.13 [1.08, 1.18], severe 1.17 [1.10, 1.23]. HFRS, baseline low, ORs: intermediate 2.65 [2.55, 2.75], high 3.31 [3.17, 3.45]). CCI, baseline < 1, ORs: '1-10' 1.15 [1.11, 1.20], > 10 2.50 [2.41, 2.60]). For predicting inpatient deaths, the CCI and HFRS based models were similar, however for longer term outcomes the CCI based model was superior. Frailty and comorbidity are significant risk factors for patients admitted to hospital with pneumonia. Frailty and comorbidity scores based on administrative data have only moderate ability to predict outcome.",,pdf:https://www.nature.com/articles/s41598-021-92874-w.pdf; doi:https://doi.org/10.1038/s41598-021-92874-w; html:https://europepmc.org/articles/PMC8239046; pdf:https://europepmc.org/articles/PMC8239046?pdf=render 36333839,https://doi.org/10.1002/gps.5834,The impact of the first UK COVID-19 lockdown on presentations with psychosis to mental health services for older adults: An electronic health records study in South London.,"Simkin L, Yung P, Greig F, Perera G, Tsamakis K, Rizos E, Stewart R, Velayudhan L, Mueller C.",,International journal of geriatric psychiatry,2022,2022-10-24,Y,Dementia; Hallucinations; Delusions; Psychosis; Older Adults; Lockdown; Covid-19; Non-white Ethnicity,,,"

Objectives

Social distancing restrictions in the COVID-19 pandemic may have had adverse effects on older adults' mental health. Whereby the impact on mood is well-described, less is known about psychotic symptoms. The aim of this study was to compare characteristics associated with psychotic symptoms during the first UK lockdown and a pre-pandemic comparison period.

Methods

In this retrospective observational study we analysed anonymised records from patients referred to mental health services for older adults in South London in the 16-week period of the UK lockdown starting in March 2020, and in the comparable pre-pandemic period in 2019. We used logistic regression models to compare the associations of different patient characteristics with increased odds of presenting with any psychotic symptom (defined as hallucinations and/or delusion), hallucinations, or delusions, during lockdown and the corresponding pre-pandemic period.

Results

1991 referrals were identified. There were fewer referrals during lockdown but a higher proportion of presentations with any psychotic symptom (48.7% vs. 42.8%, p = 0.018), particularly hallucinations (41.0% vs. 27.8%, p < 0.001). Patients of non-White ethnicity (adjusted odds ratio (OR): 1.83; 95% confidence interval (CI): 1.13-2.99) and patients with dementia (adjusted OR: 3.09; 95% CI: 1.91-4.99) were more likely to be referred with psychotic symptoms during lockdown. While a weaker association between dementia and psychotic symptoms was found in the pre-COVID period (adjusted OR: 1.55; 95% CI: 1.19-2.03), interaction terms indicated higher odds of patients of non-White ethnicity or dementia to present with psychosis during the lockdown period.

Conclusions

During lockdown, referrals to mental health services for adults decreased, but contained a higher proportion with psychotic symptoms. The stronger association with psychotic symptoms in non-White ethnic groups and patients with dementia during lockdown suggests that barriers in accessing care might have increased during the COVID-19 pandemic.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/gps.5834; doi:https://doi.org/10.1002/gps.5834; html:https://europepmc.org/articles/PMC9828419; pdf:https://europepmc.org/articles/PMC9828419?pdf=render 32702311,https://doi.org/10.1016/s1470-2045(20)30392-2,Effect of delays in the 2-week-wait cancer referral pathway during the COVID-19 pandemic on cancer survival in the UK: a modelling study.,"Sud A, Torr B, Jones ME, Broggio J, Scott S, Loveday C, Garrett A, Gronthoud F, Nicol DL, Jhanji S, Boyce SA, Williams M, Riboli E, Muller DC, Kipps E, Larkin J, Navani N, Swanton C, Lyratzopoulos G, McFerran E, Lawler M, Houlston R, Turnbull C.",,The Lancet. Oncology,2020,2020-07-20,Y,,,,"

Background

During the COVID-19 lockdown, referrals via the 2-week-wait urgent pathway for suspected cancer in England, UK, are reported to have decreased by up to 84%. We aimed to examine the impact of different scenarios of lockdown-accumulated backlog in cancer referrals on cancer survival, and the impact on survival per referred patient due to delayed referral versus risk of death from nosocomial infection with severe acute respiratory syndrome coronavirus 2.

Methods

In this modelling study, we used age-stratified and stage-stratified 10-year cancer survival estimates for patients in England, UK, for 20 common tumour types diagnosed in 2008-17 at age 30 years and older from Public Health England. We also used data for cancer diagnoses made via the 2-week-wait referral pathway in 2013-16 from the Cancer Waiting Times system from NHS Digital. We applied per-day hazard ratios (HRs) for cancer progression that we generated from observational studies of delay to treatment. We quantified the annual numbers of cancers at stage I-III diagnosed via the 2-week-wait pathway using 2-week-wait age-specific and stage-specific breakdowns. From these numbers, we estimated the aggregate number of lives and life-years lost in England for per-patient delays of 1-6 months in presentation, diagnosis, or cancer treatment, or a combination of these. We assessed three scenarios of a 3-month period of lockdown during which 25%, 50%, and 75% of the normal monthly volumes of symptomatic patients delayed their presentation until after lockdown. Using referral-to-diagnosis conversion rates and COVID-19 case-fatality rates, we also estimated the survival increment per patient referred.

Findings

Across England in 2013-16, an average of 6281 patients with stage I-III cancer were diagnosed via the 2-week-wait pathway per month, of whom 1691 (27%) would be predicted to die within 10 years from their disease. Delays in presentation via the 2-week-wait pathway over a 3-month lockdown period (with an average presentational delay of 2 months per patient) would result in 181 additional lives and 3316 life-years lost as a result of a backlog of referrals of 25%, 361 additional lives and 6632 life-years lost for a 50% backlog of referrals, and 542 additional lives and 9948 life-years lost for a 75% backlog in referrals. Compared with all diagnostics for the backlog being done in month 1 after lockdown, additional capacity across months 1-3 would result in 90 additional lives and 1662 live-years lost due to diagnostic delays for the 25% backlog scenario, 183 additional lives and 3362 life-years lost under the 50% backlog scenario, and 276 additional lives and 5075 life-years lost under the 75% backlog scenario. However, a delay in additional diagnostic capacity with provision spread across months 3-8 after lockdown would result in 401 additional lives and 7332 life-years lost due to diagnostic delays under the 25% backlog scenario, 811 additional lives and 14 873 life-years lost under the 50% backlog scenario, and 1231 additional lives and 22 635 life-years lost under the 75% backlog scenario. A 2-month delay in 2-week-wait investigatory referrals results in an estimated loss of between 0·0 and 0·7 life-years per referred patient, depending on age and tumour type.

Interpretation

Prompt provision of additional capacity to address the backlog of diagnostics will minimise deaths as a result of diagnostic delays that could add to those predicted due to expected presentational delays. Prioritisation of patient groups for whom delay would result in most life-years lost warrants consideration as an option for mitigating the aggregate burden of mortality in patients with cancer.

Funding

None.",,pdf:http://www.thelancet.com/article/S1470204520303922/pdf; doi:https://doi.org/10.1016/S1470-2045(20)30392-2; html:https://europepmc.org/articles/PMC7116538; pdf:https://europepmc.org/articles/PMC7116538?pdf=render @@ -576,8 +576,8 @@ PMC9644982,https://doi.org/,Assessing the impacts of COVID-19 on Care Homes in W 32355555,https://doi.org/10.7189/jogh.10.010104,COVID-19 must catalyse key global natural experiments.,"Been JV, Sheikh A.",,Journal of global health,2020,2020-06-01,Y,,,,,"""Been and Sheikh’s editorial about COVID-19, outlines the importance of two natural experiments: a- how different countries responded to the pandemic and its effects and b- impact of improvements in air quality on human and planetary health.""",doi:https://doi.org/10.7189/jogh.10.010104; doi:https://doi.org/10.7189/jogh.10.010104; html:https://europepmc.org/articles/PMC7179980; pdf:https://europepmc.org/articles/PMC7179980?pdf=render 32518842,https://doi.org/10.12688/wellcomeopenres.15786.1,Inferring the number of COVID-19 cases from recently reported deaths.,"Jombart T, van Zandvoort K, Russell TW, Jarvis CI, Gimma A, Abbott S, Clifford S, Funk S, Gibbs H, Liu Y, Pearson CAB, Bosse NI, Centre for the Mathematical Modelling of Infectious Diseases COVID-19 Working Group, Eggo RM, Kucharski AJ, Edmunds WJ.",,Wellcome open research,2020,2020-04-27,Y,Estimation; Statistics; epidemics; outbreak; Modelling; Covid-19; Sars-cov-2,,,"We estimate the number of COVID-19 cases from newly reported deaths in a population without previous reports. Our results suggest that by the time a single death occurs, hundreds to thousands of cases are likely to be present in that population. This suggests containment via contact tracing will be challenging at this point, and other response strategies should be considered. Our approach is implemented in a publicly available, user-friendly, online tool.",,doi:https://doi.org/10.12688/wellcomeopenres.15786.1; html:https://europepmc.org/articles/PMC7255910; pdf:https://europepmc.org/articles/PMC7255910?pdf=render 38346686,https://doi.org/10.1093/ageing/afae004,The impact of digital technology in care homes on unplanned secondary care usage and associated costs.,"Garner A, Lewis J, Dixon S, Preston N, Caiado CCS, Hanratty B, Jones M, Knight J, Mason SM.",,Age and ageing,2024,2024-02-01,Y,Older People; Emergency Medicine; Care Homes; Long-term Care; Telehealth; Routinely Collected Data,,,"

Background

A substantial number of Emergency Department (ED) attendances by care home residents are potentially avoidable. Health Call Digital Care Homes is an app-based technology that aims to streamline residents' care by recording their observations such as vital parameters electronically. Observations are triaged by remote clinical staff. This study assessed the effectiveness of the Health Call technology to reduce unplanned secondary care usage and associated costs.

Methods

A retrospective analysis of health outcomes and economic impact based on an intervention. The study involved 118 care homes across the North East of UK from 2018 to 2021. Routinely collected NHS secondary care data from County Durham and Darlington NHS Foundation Trust was linked with data from the Health Call app. Three outcomes were modelled monthly using Generalised Linear Mixed Models: counts of emergency attendances, emergency admissions and length of stay of emergency admissions. A similar approach was taken for costs. The impact of Health Call was tested on each outcome using the models.

Findings

Data from 8,702 residents were used in the analysis. Results show Health Call reduces the number of emergency attendances by 11% [6-15%], emergency admissions by 25% [20-39%] and length of stay by 11% [3-18%] (with an additional month-by-month decrease of 28% [24-34%]). The cost analysis found a cost reduction of £57 per resident in 2018, increasing to £113 in 2021.

Interpretation

The introduction of a digital technology, such as Health Call, could significantly reduce contacts with and costs resulting from unplanned secondary care usage by care home residents.",,pdf:https://academic.oup.com/ageing/article-pdf/53/2/afae004/56661196/afae004.pdf; doi:https://doi.org/10.1093/ageing/afae004; html:https://europepmc.org/articles/PMC10861323; pdf:https://europepmc.org/articles/PMC10861323?pdf=render -38296292,https://doi.org/10.1136/bmjopen-2023-078135,"Risk factor associations for severe COVID-19, influenza and pneumonia in people with diabetes to inform future pandemic preparations: UK population-based cohort study.","Hopkins R, Young KG, Thomas NJ, Godwin J, Raja D, Mateen BA, Challen RJ, Vollmer SJ, Shields BM, McGovern AP, Dennis JM.",,BMJ open,2024,2024-01-31,Y,risk factors; Electronic Health Records; Diabetes & Endocrinology; Covid-19,,,"

Objective

This study aimed to compare clinical and sociodemographic risk factors for severe COVID-19, influenza and pneumonia, in people with diabetes.

Design

Population-based cohort study.

Setting

UK primary care records (Clinical Practice Research Datalink) linked to mortality and hospital records.

Participants

Individuals with type 1 and type 2 diabetes (COVID-19 cohort: n=43 033 type 1 diabetes and n=584 854 type 2 diabetes, influenza and pneumonia cohort: n=42 488 type 1 diabetes and n=585 289 type 2 diabetes).

Primary and secondary outcome measures

COVID-19 hospitalisation from 1 February 2020 to 31 October 2020 (pre-COVID-19 vaccination roll-out), and influenza and pneumonia hospitalisation from 1 September 2016 to 31 May 2019 (pre-COVID-19 pandemic). Secondary outcomes were COVID-19 and pneumonia mortality. Associations between clinical and sociodemographic risk factors and each outcome were assessed using multivariable Cox proportional hazards models. In people with type 2 diabetes, we explored modifying effects of glycated haemoglobin (HbA1c) and body mass index (BMI) by age, sex and ethnicity.

Results

In type 2 diabetes, poor glycaemic control and severe obesity were consistently associated with increased risk of hospitalisation for COVID-19, influenza and pneumonia. The highest HbA1c and BMI-associated relative risks were observed in people aged under 70 years. Sociodemographic-associated risk differed markedly by respiratory infection, particularly for ethnicity. Compared with people of white ethnicity, black and south Asian groups had a greater risk of COVID-19 hospitalisation, but a lesser risk of pneumonia hospitalisation. Risk factor associations for type 1 diabetes and for type 2 diabetes mortality were broadly consistent with the primary analysis.

Conclusions

Clinical risk factors of high HbA1c and severe obesity are consistently associated with severe outcomes from COVID-19, influenza and pneumonia, especially in younger people. In contrast, associations with sociodemographic risk factors differed by type of respiratory infection. This emphasises that risk stratification should be specific to individual respiratory infections.",,doi:https://doi.org/10.1136/bmjopen-2023-078135; html:https://europepmc.org/articles/PMC10831438; pdf:https://europepmc.org/articles/PMC10831438?pdf=render 35991675,https://doi.org/10.1016/j.lana.2022.100335,Primary healthcare protects vulnerable populations from inequity in COVID-19 vaccination: An ecological analysis of nationwide data from Brazil.,"Bastos LSL, Aguilar S, Rache B, Maçaira P, Baião F, Cerbino-Neto J, Rocha R, Hamacher S, Ranzani OT, Bozza FA.",,Lancet regional health. Americas,2022,2022-08-17,Y,Vaccine; Socioeconomic Factors; Human Development; Primary Healthcare; Low-and-middle-income Countries; Covid19,,,"

Background

There is limited information on the inequity of access to vaccination in low-and-middle-income countries during the COVID-19 pandemic. Here, we described the progression of the Brazilian immunisation program for COVID-19, and the association of socioeconomic development with vaccination rates, considering the potential protective effect of primary health care coverage.

Methods

We performed an ecological analysis of COVID-19 immunisation data from the Brazilian National Immunization Program from January 17 to August 31, 2021. We analysed the dynamics of vaccine coverage in the adult population of 5,570 Brazilian municipalities. We estimated the association of human development index (HDI) levels (low, medium, and high) with age-sex standardised first dose coverage using a multivariable negative binomial regression model. We evaluated the interaction between the HDI and primary health care coverage. Finally, we compared the adjusted monthly progression of vaccination rates, hospital admission and in-hospital death rates among HDI levels.

Findings

From January 17 to August 31, 2021, 202,427,355 COVID-19 vaccine doses were administered in Brazil. By the end of the period, 64·2% of adults had first and 31·4% second doses, with more than 90% of those aged ≥60 years with primary scheme completed. Four distinct vaccine platforms were used in the country, ChAdOx1-S/nCoV-19, Sinovac-CoronaVac, BNT162b2, Ad26.COV2.S, composing 44·8%, 33·2%, 19·6%, and 2·4% of total doses, respectively. First dose coverage differed between municipalities with high, medium, and low HDI (Median [interquartile range] 72 [66, 79], 68 [61, 75] and 63 [55, 70] doses per 100 people, respectively). Municipalities with low (Rate Ratio [RR, 95% confidence interval]: 0·87 [0·85-0·88]) and medium (RR [95% CI]: 0·94 [0·93-0·95]) development were independently associated with lower vaccination rates compared to those with high HDI. Primary health care coverage modified the association of HDI and vaccination rate, improving vaccination rates in those municipalities of low HDI and high primary health care coverage. Low HDI municipalities presented a delayed decrease in adjusted in-hospital death rates by first dose coverage compared to high HDI locations.

Interpretation

In Brazil, socioeconomic disparities negatively impacted the first dose vaccination rate. However, the primary health care mitigated these disparities, suggesting that the primary health care coverage guarantees more equitable access to vaccines in vulnerable locations.

Funding

This work is part of the Grand Challenges ICODA pilot initiative, delivered by Health Data Research UK and funded by the Bill & Melinda Gates Foundation and the Minderoo Foundation. This study was supported by the National Council for Scientific and Technological Development (CNPq), the Coordination for the Improvement of Higher Education Personnel (CAPES) - Finance Code 001, Carlos Chagas Filho Foundation for Research Support of the State of Rio de Janeiro (FAPERJ) and the Pontifical Catholic University of Rio de Janeiro.",,doi:https://doi.org/10.1016/j.lana.2022.100335; doi:https://doi.org/10.1016/j.lana.2022.100335; html:https://europepmc.org/articles/PMC9381845; pdf:https://europepmc.org/articles/PMC9381845?pdf=render +38296292,https://doi.org/10.1136/bmjopen-2023-078135,"Risk factor associations for severe COVID-19, influenza and pneumonia in people with diabetes to inform future pandemic preparations: UK population-based cohort study.","Hopkins R, Young KG, Thomas NJ, Godwin J, Raja D, Mateen BA, Challen RJ, Vollmer SJ, Shields BM, McGovern AP, Dennis JM.",,BMJ open,2024,2024-01-31,Y,risk factors; Electronic Health Records; Diabetes & Endocrinology; Covid-19,,,"

Objective

This study aimed to compare clinical and sociodemographic risk factors for severe COVID-19, influenza and pneumonia, in people with diabetes.

Design

Population-based cohort study.

Setting

UK primary care records (Clinical Practice Research Datalink) linked to mortality and hospital records.

Participants

Individuals with type 1 and type 2 diabetes (COVID-19 cohort: n=43 033 type 1 diabetes and n=584 854 type 2 diabetes, influenza and pneumonia cohort: n=42 488 type 1 diabetes and n=585 289 type 2 diabetes).

Primary and secondary outcome measures

COVID-19 hospitalisation from 1 February 2020 to 31 October 2020 (pre-COVID-19 vaccination roll-out), and influenza and pneumonia hospitalisation from 1 September 2016 to 31 May 2019 (pre-COVID-19 pandemic). Secondary outcomes were COVID-19 and pneumonia mortality. Associations between clinical and sociodemographic risk factors and each outcome were assessed using multivariable Cox proportional hazards models. In people with type 2 diabetes, we explored modifying effects of glycated haemoglobin (HbA1c) and body mass index (BMI) by age, sex and ethnicity.

Results

In type 2 diabetes, poor glycaemic control and severe obesity were consistently associated with increased risk of hospitalisation for COVID-19, influenza and pneumonia. The highest HbA1c and BMI-associated relative risks were observed in people aged under 70 years. Sociodemographic-associated risk differed markedly by respiratory infection, particularly for ethnicity. Compared with people of white ethnicity, black and south Asian groups had a greater risk of COVID-19 hospitalisation, but a lesser risk of pneumonia hospitalisation. Risk factor associations for type 1 diabetes and for type 2 diabetes mortality were broadly consistent with the primary analysis.

Conclusions

Clinical risk factors of high HbA1c and severe obesity are consistently associated with severe outcomes from COVID-19, influenza and pneumonia, especially in younger people. In contrast, associations with sociodemographic risk factors differed by type of respiratory infection. This emphasises that risk stratification should be specific to individual respiratory infections.",,doi:https://doi.org/10.1136/bmjopen-2023-078135; html:https://europepmc.org/articles/PMC10831438; pdf:https://europepmc.org/articles/PMC10831438?pdf=render 35288697,https://doi.org/10.1038/s41591-022-01750-1,COVID-19 and resilience of healthcare systems in ten countries.,"Arsenault C, Gage A, Kim MK, Kapoor NR, Akweongo P, Amponsah F, Aryal A, Asai D, Awoonor-Williams JK, Ayele W, Bedregal P, Doubova SV, Dulal M, Gadeka DD, Gordon-Strachan G, Mariam DH, Hensman D, Joseph JP, Kaewkamjornchai P, Eshetu MK, Gelaw SK, Kubota S, Leerapan B, Margozzini P, Mebratie AD, Mehata S, Moshabela M, Mthethwa L, Nega A, Oh J, Park S, Passi-Solar Á, Pérez-Cuevas R, Phengsavanh A, Reddy T, Rittiphairoj T, Sapag JC, Thermidor R, Tlou B, Valenzuela Guiñez F, Bauhoff S, Kruk ME.",,Nature medicine,2022,2022-03-14,Y,,,,"Declines in health service use during the Coronavirus Disease 2019 (COVID-19) pandemic could have important effects on population health. In this study, we used an interrupted time series design to assess the immediate effect of the pandemic on 31 health services in two low-income (Ethiopia and Haiti), six middle-income (Ghana, Lao People's Democratic Republic, Mexico, Nepal, South Africa and Thailand) and high-income (Chile and South Korea) countries. Despite efforts to maintain health services, disruptions of varying magnitude and duration were found in every country, with no clear patterns by country income group or pandemic intensity. Disruptions in health services often preceded COVID-19 waves. Cancer screenings, TB screening and detection and HIV testing were most affected (26-96% declines). Total outpatient visits declined by 9-40% at national levels and remained lower than predicted by the end of 2020. Maternal health services were disrupted in approximately half of the countries, with declines ranging from 5% to 33%. Child vaccinations were disrupted for shorter periods, but we estimate that catch-up campaigns might not have reached all children missed. By contrast, provision of antiretrovirals for HIV was not affected. By the end of 2020, substantial disruptions remained in half of the countries. Preliminary data for 2021 indicate that disruptions likely persisted. Although a portion of the declines observed might result from decreased needs during lockdowns (from fewer infectious illnesses or injuries), a larger share likely reflects a shortfall of health system resilience. Countries must plan to compensate for missed healthcare during the current pandemic and invest in strategies for better health system resilience for future emergencies.",,pdf:https://www.nature.com/articles/s41591-022-01750-1.pdf; doi:https://doi.org/10.1038/s41591-022-01750-1; html:https://europepmc.org/articles/PMC9205770; pdf:https://europepmc.org/articles/PMC9205770?pdf=render 33716109,https://doi.org/10.1016/j.jinf.2021.03.002,Short durations of corticosteroids for hospitalised COVID-19 patients are associated with a high readmission rate.,"Chaudhry Z, Shawe-Taylor M, Rampling T, Cutfield T, Bidwell G, Chan XHS, Last A, Williams B, Logan S, Marks M, Esmail H.",,The Journal of infection,2021,2021-03-11,Y,Dexamethasone; Corticosteroids; Hospital; Readmissions; Covid-19,,,"

Objective

Our objective was to describe the characteristics of patients admitted, discharged and readmitted, due to COVID-19, to a central London acute-care hospital during the second peak, in particular in relation to corticosteroids use.

Methods

We reviewed patients admitted from the community to University College Hospital (UCH) with COVID-19 as their primary diagnosis between 1st-31st December 2020. Re-attendance and readmission data were collected for patients who re-presented within 10 days following discharge. Data were retrospectively collected.

Results

196 patients were admitted from the community with a diagnosis of COVID-19 and discharged alive in December 2020. Corticosteroids were prescribed in hospital for a median of 5 days (IQR 3-8). 20 patients (10.2%) were readmitted within 10 days. 11/20 received corticosteroids in the first admission of which 10 had received 1-3 days of corticosteroids. Readmission rate in those receiving 1-3 days of corticosteroids was 25%.

Conclusions

Most international guidelines have recommended providing up to 10 days of corticosteroids for severe COVID-19 but stopping on discharge. Our findings show shorter courses of corticosteroids during admission are associated with an increased risk of being readmitted and support continuing the course of corticosteroids after hospital discharge monitored in the virtual ward setting.",,pdf:http://www.journalofinfection.com/article/S0163445321001158/pdf; doi:https://doi.org/10.1016/j.jinf.2021.03.002; html:https://europepmc.org/articles/PMC7948670; pdf:https://europepmc.org/articles/PMC7948670?pdf=render 33588321,https://doi.org/10.1016/j.retram.2021.103276,Biological responses to COVID-19: Insights from physiological and blood biomarker profiles.,"Zakeri R, Pickles A, Carr E, Bean DM, O'Gallagher K, Kraljewic Z, Searle T, Shek A, Galloway JB, Teo JTH, Shah AM, Dobson RJB, Bendayan R.",,Current research in translational medicine,2021,2021-02-03,Y,Inflammation; Biomarkers; Classes; Sars-cov-2,,,"

Background

Understanding the spectrum and course of biological responses to coronavirus disease 2019 (COVID-19) may have important therapeutic implications. We sought to characterise biological responses among patients hospitalised with severe COVID-19 based on serial, routinely collected, physiological and blood biomarker values.

Methods and findings

We performed a retrospective cohort study of 1335 patients hospitalised with laboratory-confirmed COVID-19 (median age 70 years, 56 % male), between 1st March and 30th April 2020. Latent profile analysis was performed on serial physiological and blood biomarkers. Patient characteristics, comorbidities and rates of death and admission to intensive care, were compared between the latent classes. A five class solution provided the best fit. Class 1 ""Typical response"" exhibited a moderately elevated and rising C-reactive protein (CRP), stable lymphopaenia, and the lowest rates of 14-day adverse outcomes. Class 2 ""Rapid hyperinflammatory response"" comprised older patients, with higher admission white cell and neutrophil counts, which declined over time, accompanied by a very high and rising CRP and platelet count, and exibited the highest mortality risk. Class 3 ""Progressive inflammatory response"" was similar to the typical response except for a higher and rising CRP, though similar mortality rate. Class 4 ""Inflammatory response with kidney injury"" had prominent lymphopaenia, moderately elevated (and rising) CRP, and severe renal failure. Class 5 ""Hyperinflammatory response with kidney injury"" comprised older patients, with a very high and rising CRP, and severe renal failure that attenuated over time. Physiological measures did not substantially vary between classes at baseline or early admission.

Conclusions and relevance

Our identification of five distinct classes of biomarker profiles provides empirical evidence for heterogeneous biological responses to COVID-19. Early hyperinflammatory responses and kidney injury may signify unique pathophysiology that requires targeted therapy.",,doi:https://doi.org/10.1016/j.retram.2021.103276; doi:https://doi.org/10.1016/j.retram.2021.103276; html:https://europepmc.org/articles/PMC7857048; pdf:https://europepmc.org/articles/PMC7857048?pdf=render @@ -663,8 +663,8 @@ PMC8855010,https://doi.org/,POS-894 PREDICTING PANDEMIC-RELATED EXCESS-DEATH USI 33785494,https://doi.org/10.1136/bmjopen-2020-046365,Impact of the COVID-19 pandemic on remote mental healthcare and prescribing in psychiatry: an electronic health record study.,"Patel R, Irving J, Brinn A, Broadbent M, Shetty H, Pritchard M, Downs J, Stewart R, Harland R, McGuire P.",,BMJ open,2021,2021-03-30,Y,Psychiatry; Mental health; epidemiology; Telemedicine; Health Informatics,,,"

Objectives

The recent COVID-19 pandemic has disrupted mental healthcare delivery, with many services shifting from in-person to remote patient contact. We investigated the impact of the pandemic on the use of remote consultation and on the prescribing of psychiatric medications.

Design and setting

The Clinical Record Interactive Search tool was used to examine deidentified electronic health records of people receiving mental healthcare from the South London and Maudsley (SLaM) NHS Foundation Trust. Data from the period before and after the onset of the pandemic were analysed using linear regression, and visualised using locally estimated scatterplot smoothing.

Participants

All patients receiving care from SLaM between 7 January 2019 and 20 September 2020 (around 37 500 patients per week).

Outcome measures

(i) The number of clinical contacts (in-person, remote or non-attended) with mental healthcare professionals per week.(ii) Prescribing of antipsychotic and mood stabiliser medications per week.

Results

Following the onset of the pandemic, the frequency of in-person contacts was significantly reduced compared with that in the previous year (β coefficient: -5829.6 contacts, 95% CI -6919.5 to -4739.6, p<0.001), while the frequency of remote contacts significantly increased (β coefficient: 3338.5 contacts, 95% CI 3074.4 to 3602.7, p<0.001). Rates of remote consultation were lower in older adults than in working age adults, children and adolescents. Despite this change in the type of patient contact, antipsychotic and mood stabiliser prescribing remained at similar levels.

Conclusions

The COVID-19 pandemic has been associated with a marked increase in remote consultation, particularly among younger patients. However, there was no evidence that this has led to changes in psychiatric prescribing. Nevertheless, further work is needed to ensure that older patients are able to access mental healthcare remotely.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/3/e046365.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-046365; html:https://europepmc.org/articles/PMC8728386; pdf:https://europepmc.org/articles/PMC8728386?pdf=render 38388919,https://doi.org/10.1186/s12913-024-10716-7,"Spatio-temporal modelling of referrals to outpatient respiratory clinics in the integrated care system of the Morecambe Bay area, England.","Mountain R, Knight J, Heys K, Giorgi E, Gatheral T.",,BMC health services research,2024,2024-02-22,Y,Spatio-temporal; Integrated Care; Chronic Respiratory Disease; Routinely Collected Data; Outpatient Referrals,,,"

Background

Promoting integrated care is a key goal of the NHS Long Term Plan to improve population respiratory health, yet there is limited data-driven evidence of its effectiveness. The Morecambe Bay Respiratory Network is an integrated care initiative operating in the North-West of England since 2017. A key target area has been reducing referrals to outpatient respiratory clinics by upskilling primary care teams. This study aims to explore space-time patterns in referrals from general practice in the Morecambe Bay area to evaluate the impact of the initiative.

Methods

Data on referrals to outpatient clinics and chronic respiratory disease patient counts between 2012-2020 were obtained from the Morecambe Bay Community Data Warehouse, a large store of routinely collected healthcare data. For analysis, the data is aggregated by year and small area geography. The methodology comprises of two parts. The first explores the issues that can arise when using routinely collected primary care data for space-time analysis and applies spatio-temporal conditional autoregressive modelling to adjust for data complexities. The second part models the rate of outpatient referral via a Poisson generalised linear mixed model that adjusts for changes in demographic factors and number of respiratory disease patients.

Results

The first year of the Morecambe Bay Respiratory Network was not associated with a significant difference in referral rate. However, the second and third years saw significant reductions in areas that had received intervention, with full intervention associated with a 31.8% (95% CI 17.0-43.9) and 40.5% (95% CI 27.5-50.9) decrease in referral rate in 2018 and 2019, respectively.

Conclusions

Routinely collected data can be used to robustly evaluate key outcome measures of integrated care. The results demonstrate that effective integrated care has real potential to ease the burden on respiratory outpatient services by reducing the need for an onward referral. This is of great relevance given the current pressure on outpatient services globally, particularly long waiting lists following the COVID-19 pandemic and the need for more innovative models of care.",,doi:https://doi.org/10.1186/s12913-024-10716-7; html:https://europepmc.org/articles/PMC10882730; pdf:https://europepmc.org/articles/PMC10882730?pdf=render 36721180,https://doi.org/10.1186/s12961-022-00956-6,Tracking health system performance in times of crisis using routine health data: lessons learned from a multicountry consortium.,"Turcotte-Tremblay AM, Leerapan B, Akweongo P, Amponsah F, Aryal A, Asai D, Awoonor-Williams JK, Ayele W, Bauhoff S, Doubova SV, Gadeka DD, Dulal M, Gage A, Gordon-Strachan G, Haile-Mariam D, Joseph JP, Kaewkamjornchai P, Kapoor NR, Gelaw SK, Kim MK, Kruk ME, Kubota S, Margozzini P, Mehata S, Mthethwa L, Nega A, Oh J, Park SK, Passi-Solar A, Perez Cuevas RE, Reddy T, Rittiphairoj T, Sapag JC, Thermidor R, Tlou B, Arsenault C.",,Health research policy and systems,2023,2023-01-31,Y,Quality Of Care; Health Systems; Routine Health Information Systems; Covid-19,,,"COVID-19 has prompted the use of readily available administrative data to track health system performance in times of crisis and to monitor disruptions in essential healthcare services. In this commentary we describe our experience working with these data and lessons learned across countries. Since April 2020, the Quality Evidence for Health System Transformation (QuEST) network has used administrative data and routine health information systems (RHIS) to assess health system performance during COVID-19 in Chile, Ethiopia, Ghana, Haiti, Lao People's Democratic Republic, Mexico, Nepal, South Africa, Republic of Korea and Thailand. We compiled a large set of indicators related to common health conditions for the purpose of multicountry comparisons. The study compiled 73 indicators. A total of 43% of the indicators compiled pertained to reproductive, maternal, newborn and child health (RMNCH). Only 12% of the indicators were related to hypertension, diabetes or cancer care. We also found few indicators related to mental health services and outcomes within these data systems. Moreover, 72% of the indicators compiled were related to volume of services delivered, 18% to health outcomes and only 10% to the quality of processes of care. While several datasets were complete or near-complete censuses of all health facilities in the country, others excluded some facility types or population groups. In some countries, RHIS did not capture services delivered through non-visit or nonconventional care during COVID-19, such as telemedicine. We propose the following recommendations to improve the analysis of administrative and RHIS data to track health system performance in times of crisis: ensure the scope of health conditions covered is aligned with the burden of disease, increase the number of indicators related to quality of care and health outcomes; incorporate data on nonconventional care such as telehealth; continue improving data quality and expand reporting from private sector facilities; move towards collecting patient-level data through electronic health records to facilitate quality-of-care assessment and equity analyses; implement more resilient and standardized health information technologies; reduce delays and loosen restrictions for researchers to access the data; complement routine data with patient-reported data; and employ mixed methods to better understand the underlying causes of service disruptions.",,pdf:https://health-policy-systems.biomedcentral.com/counter/pdf/10.1186/s12961-022-00956-6; doi:https://doi.org/10.1186/s12961-022-00956-6; html:https://europepmc.org/articles/PMC9888332; pdf:https://europepmc.org/articles/PMC9888332?pdf=render -37060915,https://doi.org/10.1016/s0140-6736(23)00510-x,"Higher dose corticosteroids in patients admitted to hospital with COVID-19 who are hypoxic but not requiring ventilatory support (RECOVERY): a randomised, controlled, open-label, platform trial.","RECOVERY Collaborative Group. Electronic address: recoverytrial@ndph.ox.ac.uk, RECOVERY Collaborative Group.",,"Lancet (London, England)",2023,2023-04-13,Y,,,,"

Background

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

Methods

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

Findings

Between May 25, 2021, and May 13, 2022, 1272 patients with COVID-19 and hypoxia receiving no oxygen (eight [1%]) or simple oxygen only (1264 [99%]) were randomly allocated to receive usual care plus higher dose corticosteroids (659 patients) versus usual care alone (613 patients, of whom 87% received low-dose corticosteroids during the follow-up period). Of those randomly assigned, 745 (59%) were in Asia, 512 (40%) in the UK, and 15 (1%) in Africa. 248 (19%) had diabetes and 769 (60%) were male. Overall, 123 (19%) of 659 patients allocated to higher dose corticosteroids versus 75 (12%) of 613 patients allocated to usual care died within 28 days (rate ratio 1·59 [95% CI 1·20-2·10]; p=0·0012). There was also an excess of pneumonia reported to be due to non-COVID infection (64 cases [10%] vs 37 cases [6%]; absolute difference 3·7% [95% CI 0·7-6·6]) and an increase in hyperglycaemia requiring increased insulin dose (142 [22%] vs 87 [14%]; absolute difference 7·4% [95% CI 3·2-11·5]).

Interpretation

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

Funding

UK Research and Innovation (Medical Research Council), National Institute of Health and Care Research, and Wellcome Trust.",,doi:https://doi.org/10.1016/s0140-6736(23)00510-x; doi:https://doi.org/10.1016/S0140-6736(23)00510-X; html:https://europepmc.org/articles/PMC10156147; pdf:https://europepmc.org/articles/PMC10156147?pdf=render 34965929,https://doi.org/10.1136/bmj-2021-065834,GP consultation rates for sequelae after acute covid-19 in patients managed in the community or hospital in the UK: population based study.,"Whittaker HR, Gulea C, Koteci A, Kallis C, Morgan AD, Iwundu C, Weeks M, Gupta R, Quint JK.",,BMJ (Clinical research ed.),2021,2021-12-29,Y,,,,"

Objectives

To describe the rates for consulting a general practitioner (GP) for sequelae after acute covid-19 in patients admitted to hospital with covid-19 and those managed in the community, and to determine how the rates change over time for patients in the community and after vaccination for covid-19.

Design

Population based study.

Setting

1392 general practices in England contributing to the Clinical Practice Research Datalink Aurum database.

Participants

456 002 patients with a diagnosis of covid-19 between 1 August 2020 and 14 February 2021 (44.7% men; median age 61 years), admitted to hospital within two weeks of diagnosis or managed in the community, and followed-up for a maximum of 9.2 months. A negative control group included individuals without covid-19 (n=38 511) and patients with influenza before the pandemic (n=21 803).

Main outcome measures

Comparison of rates for consulting a GP for new symptoms, diseases, prescriptions, and healthcare use in individuals admitted to hospital and those managed in the community, separately, before and after covid-19 infection, using Cox regression and negative binomial regression for healthcare use. The analysis was repeated for the negative control and influenza cohorts. In individuals in the community, outcomes were also described over time after a diagnosis of covid-19, and compared before and after vaccination for individuals who were symptomatic after covid-19 infection, using negative binomial regression.

Results

Relative to the negative control and influenza cohorts, patients in the community (n=437 943) had significantly higher GP consultation rates for multiple sequelae, and the most common were loss of smell or taste, or both (adjusted hazard ratio 5.28, 95% confidence interval 3.89 to 7.17, P<0.001); venous thromboembolism (3.35, 2.87 to 3.91, P<0.001); lung fibrosis (2.41, 1.37 to 4.25, P=0.002), and muscle pain (1.89, 1.63 to 2.20, P<0.001); and also for healthcare use after a diagnosis of covid-19 compared with 12 months before infection. For absolute proportions, the most common outcomes ≥4 weeks after a covid-19 diagnosis in patients in the community were joint pain (2.5%), anxiety (1.2%), and prescriptions for non-steroidal anti-inflammatory drugs (1.2%). Patients admitted to hospital (n=18 059) also had significantly higher GP consultation rates for multiple sequelae, most commonly for venous thromboembolism (16.21, 11.28 to 23.31, P<0.001), nausea (4.64, 2.24 to 9.21, P<0.001), prescriptions for paracetamol (3.68, 2.86 to 4.74, P<0.001), renal failure (3.42, 2.67 to 4.38, P<0.001), and healthcare use after a covid-19 diagnosis compared with 12 months before infection. For absolute proportions, the most common outcomes ≥4 weeks after a covid-19 diagnosis in patients admitted to hospital were venous thromboembolism (3.5%), joint pain (2.7%), and breathlessness (2.8%). In patients in the community, anxiety and depression, abdominal pain, diarrhoea, general pain, nausea, chest tightness, and tinnitus persisted throughout follow-up. GP consultation rates were reduced for all symptoms, prescriptions, and healthcare use, except for neuropathic pain, cognitive impairment, strong opiates, and paracetamol use in patients in the community after the first vaccination dose for covid-19 relative to before vaccination. GP consultation rates were also reduced for ischaemic heart disease, asthma, and gastro-oesophageal disease.

Conclusions

GP consultation rates for sequelae after acute covid-19 infection differed between patients with covid-19 who were admitted to hospital and those managed in the community. For individuals in the community, rates of some sequelae decreased over time but those for others, such as anxiety and depression, persisted. Rates of some outcomes decreased after vaccination in this group.",,pdf:https://www.bmj.com/content/bmj/375/bmj-2021-065834.full.pdf; doi:https://doi.org/10.1136/bmj-2021-065834; html:https://europepmc.org/articles/PMC8715128; pdf:https://europepmc.org/articles/PMC8715128?pdf=render +37060915,https://doi.org/10.1016/s0140-6736(23)00510-x,"Higher dose corticosteroids in patients admitted to hospital with COVID-19 who are hypoxic but not requiring ventilatory support (RECOVERY): a randomised, controlled, open-label, platform trial.","RECOVERY Collaborative Group. Electronic address: recoverytrial@ndph.ox.ac.uk, RECOVERY Collaborative Group.",,"Lancet (London, England)",2023,2023-04-13,Y,,,,"

Background

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

Methods

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

Findings

Between May 25, 2021, and May 13, 2022, 1272 patients with COVID-19 and hypoxia receiving no oxygen (eight [1%]) or simple oxygen only (1264 [99%]) were randomly allocated to receive usual care plus higher dose corticosteroids (659 patients) versus usual care alone (613 patients, of whom 87% received low-dose corticosteroids during the follow-up period). Of those randomly assigned, 745 (59%) were in Asia, 512 (40%) in the UK, and 15 (1%) in Africa. 248 (19%) had diabetes and 769 (60%) were male. Overall, 123 (19%) of 659 patients allocated to higher dose corticosteroids versus 75 (12%) of 613 patients allocated to usual care died within 28 days (rate ratio 1·59 [95% CI 1·20-2·10]; p=0·0012). There was also an excess of pneumonia reported to be due to non-COVID infection (64 cases [10%] vs 37 cases [6%]; absolute difference 3·7% [95% CI 0·7-6·6]) and an increase in hyperglycaemia requiring increased insulin dose (142 [22%] vs 87 [14%]; absolute difference 7·4% [95% CI 3·2-11·5]).

Interpretation

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

Funding

UK Research and Innovation (Medical Research Council), National Institute of Health and Care Research, and Wellcome Trust.",,doi:https://doi.org/10.1016/s0140-6736(23)00510-x; doi:https://doi.org/10.1016/S0140-6736(23)00510-X; html:https://europepmc.org/articles/PMC10156147; pdf:https://europepmc.org/articles/PMC10156147?pdf=render 34716166,https://doi.org/10.1136/bmjopen-2021-053268,Electronic reminders and rewards to improve adherence to inhaled asthma treatment in adolescents: a non-randomised feasibility study in tertiary care.,"De Simoni A, Fleming L, Holliday L, Horne R, Priebe S, Bush A, Sheikh A, Griffiths C.",,BMJ open,2021,2021-10-29,Y,Asthma; Respiratory Medicine (See Thoracic Medicine); Paediatric Thoracic Medicine,,,"

Objective

To test the feasibility and acceptability of a short-term reminder and incentives intervention in adolescents with low adherence to asthma medications.

Methods

Mixed-methods feasibility study in a tertiary care clinic. Adolescents recruited to a 24-week programme with three 8-weekly visits, receiving electronic reminders to prompt inhaled corticosteroid (ICS) inhalation through a mobile app coupled with electronic monitoring devices (EMD). From the second visit, monetary incentives based on adherence of ICS inhalation: £1 per dose, maximum £2 /day, up to £112/study, collected as gift cards at the third visit. End of study interviews and questionnaires assessing perceptions of asthma and ICS, analysed using the Perceptions and Practicalities Framework.

Participants

Adolescents (11-18 years) with documented low ICS adherence (<80% by EMD), and poor asthma control at the first clinic visit.

Results

10 out of 12 adolescents approached were recruited (7 males, 3 females, 12-16 years). Eight participants provided adherence measures up to the fourth visits and received rewards. Mean study duration was 281 days, with 7/10 participants unable to attend their fourth visit due to COVID-19 lockdown. Only 3/10 participants managed to pair the app/EMD up to the fourth visit, which was associated with improved ICS adherence (from 0.51, SD 0.07 to 0.86, SD 0.05). Adherence did not change in adolescents unable to pair the app/EMD. The intervention was acceptable to participants and parents/guardians. Exit interviews showed that participants welcomed reminders and incentives, though expressed frustration with app/EMD technological difficulties. Participants stated the intervention helped through reminding ICS doses, promoting self-monitoring and increasing motivation to take inhalers.

Conclusions

An intervention using electronic reminders and incentives through an app coupled with an EMD was feasible and acceptable to adolescents with asthma. A pilot randomised controlled trial is warranted to better estimate the effect size on adherence, with improved technical support for the EMD.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/10/e053268.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-053268; html:https://europepmc.org/articles/PMC8559117; pdf:https://europepmc.org/articles/PMC8559117?pdf=render 35471746,https://doi.org/10.1186/s13613-022-01011-x,The resilient intensive care unit.,"Salluh JIF, Kurtz P, Bastos LSL, Quintairos A, Zampieri FG, Bozza FA.",,Annals of intensive care,2022,2022-04-26,Y,,,,"

Background

The COVID-19 pandemic tested the capacity of intensive care units (ICU) to respond to a crisis and demonstrated their fragility. Unsurprisingly, higher than usual mortality rates, lengths of stay (LOS), and ICU-acquired complications occurred during the pandemic. However, worse outcomes were not universal nor constant across ICUs and significant variation in outcomes was reported, demonstrating that some ICUs could adequately manage the surge of COVID-19.

Methods

In the present editorial, we discuss the concept of a resilient Intensive Care Unit, including which metrics can be used to address the capacity to respond, sustain results and incorporate new practices that lead to improvement.

Results

We believe that a resiliency analysis adds a component of preparedness to the usual ICU performance evaluation and outcomes metrics to be used during the crisis and in regular times.

Conclusions

The COVID-19 pandemic demonstrated the need for a resilient health system. Although this concept has been discussed for health systems, it was not tested in intensive care. Future studies should evaluate this concept to improve ICU organization for standard and pandemic times.",,pdf:https://annalsofintensivecare.springeropen.com/track/pdf/10.1186/s13613-022-01011-x; doi:https://doi.org/10.1186/s13613-022-01011-x; html:https://europepmc.org/articles/PMC9038989; pdf:https://europepmc.org/articles/PMC9038989?pdf=render 36084076,https://doi.org/10.1371/journal.pone.0273687,"""The vaccination is positive; I don't think it's the panacea"": A qualitative study on COVID-19 vaccine attitudes among ethnically diverse healthcare workers in the United Kingdom.","Gogoi M, Wobi F, Qureshi I, Al-Oraibi A, Hassan O, Chaloner J, Nellums LB, Pareek M, UK-REACH Collaborative Group.",,PloS one,2022,2022-09-09,Y,,,,"

Background

Globally, healthcare workers (HCWs) were prioritised for receiving vaccinations against the coronavirus disease-2019 (COVID-19). Previous research has shown disparities in COVID-19 vaccination uptake among HCWs based on ethnicity, job role, sex, age, and deprivation. However, vaccine attitudes underpinning these variations and factors influencing these attitudes are yet to be fully explored.

Methods

We conducted a qualitative study with 164 HCWs from different ethnicities, sexes, job roles, migration statuses, and regions in the United Kingdom (UK). Interviews and focus groups were conducted online or telephonically, and recorded with participants' permission. Recordings were transcribed and a two-pronged analytical approach was adopted: content analysis for categorising vaccine attitudes and thematic analysis for identifying factors influencing vaccine attitudes.

Findings

We identified four different COVID-19 vaccine attitudes among HCWs: Active Acceptance, Passive Acceptance, Passive Decline, and Active Decline. Content analysis of the transcripts showed that HCWs from ethnic minority communities and female HCWs were more likely to either decline (actively/passively) or passively accept vaccination-reflecting hesitancy. Factors influencing these attitudes included: trust; risk perception; social influences; access and equity; considerations about the future.

Interpretation

Our data show that attitudes towards COVID-19 vaccine are diverse, and elements of hesitancy may persist even after uptake. This has implications for the sustainability of the COVID-19 vaccine programme, particularly as new components (for example boosters) are being offered. We also found that vaccine attitudes differed by ethnicity, sex and job role, which calls for an intersectional and dynamic approach for improving vaccine uptake among HCWs. Trust, risk perception, social influences, access and equity and future considerations all influence vaccine attitudes and have a bearing on HCWs' decision about accepting or declining the COVID-19 vaccine. Based on our findings, we recommend building trust, addressing structural inequities and, designing inclusive and accessible information to address hesitancy.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0273687&type=printable; doi:https://doi.org/10.1371/journal.pone.0273687; html:https://europepmc.org/articles/PMC9462779; pdf:https://europepmc.org/articles/PMC9462779?pdf=render @@ -674,8 +674,8 @@ PMC8855010,https://doi.org/,POS-894 PREDICTING PANDEMIC-RELATED EXCESS-DEATH USI 36936594,https://doi.org/10.1136/bmjmed-2022-000247,Measuring multimorbidity in research: Delphi consensus study.,"Ho ISS, Azcoaga-Lorenzo A, Akbari A, Davies J, Khunti K, Kadam UT, Lyons RA, McCowan C, Mercer SW, Nirantharakumar K, Staniszewska S, Guthrie B.",,BMJ medicine,2022,2022-07-27,Y,Medicine; epidemiology; Primary Health Care; Public Health; Research Design,,,"

Objective

To develop international consensus on the definition and measurement of multimorbidity in research.

Design

Delphi consensus study.

Setting

International consensus; data collected in three online rounds from participants between 30 November 2020 and 18 May 2021.

Participants

Professionals interested in multimorbidity and people with long term conditions were recruited to professional and public panels.

Results

150 professional and 25 public participants completed the first survey round. Response rates for rounds 2/3 were 83%/92% for professionals and 88%/93% in the public panel, respectively. Across both panels, the consensus was that multimorbidity should be defined as two or more long term conditions. Complex multimorbidity was perceived to be a useful concept, but the panels were unable to agree on how to define it. Both panels agreed that conditions should be included in a multimorbidity measure if they were one or more of the following: currently active; permanent in their effects; requiring current treatment, care, or therapy; requiring surveillance; or relapsing-remitting conditions requiring ongoing care. Consensus was reached for 24 conditions to always include in multimorbidity measures, and 35 conditions to usually include unless a good reason not to existed. Simple counts were preferred for estimating prevalence and examining clustering or trajectories, and weighted measures were preferred for risk adjustment and outcome prediction.

Conclusions

Previous multimorbidity research is limited by inconsistent definitions and approaches to measuring multimorbidity. This Delphi study identifies professional and public panel consensus guidance to facilitate consistency of definition and measurement, and to improve study comparability and reproducibility.",,pdf:https://bmjmedicine.bmj.com/content/bmjmed/1/1/e000247.full.pdf; doi:https://doi.org/10.1136/bmjmed-2022-000247; html:https://europepmc.org/articles/PMC9978673; pdf:https://europepmc.org/articles/PMC9978673?pdf=render 32877352,https://doi.org/10.2196/19992,Using Smartphones and Wearable Devices to Monitor Behavioral Changes During COVID-19.,"Sun S, Folarin AA, Ranjan Y, Rashid Z, Conde P, Stewart C, Cummins N, Matcham F, Dalla Costa G, Simblett S, Leocani L, Lamers F, Sørensen PS, Buron M, Zabalza A, Guerrero Pérez AI, Penninx BW, Siddi S, Haro JM, Myin-Germeys I, Rintala A, Wykes T, Narayan VA, Comi G, Hotopf M, Dobson RJ, RADAR-CNS Consortium.",,Journal of medical Internet research,2020,2020-09-25,Y,Mobility; Smartphones; Mobile Health; Behavioral Monitoring; Wearable Devices; Phone Use; Covid-19,,,"

Background

In the absence of a vaccine or effective treatment for COVID-19, countries have adopted nonpharmaceutical interventions (NPIs) such as social distancing and full lockdown. An objective and quantitative means of passively monitoring the impact and response of these interventions at a local level is needed.

Objective

We aim to explore the utility of the recently developed open-source mobile health platform Remote Assessment of Disease and Relapse (RADAR)-base as a toolbox to rapidly test the effect and response to NPIs intended to limit the spread of COVID-19.

Methods

We analyzed data extracted from smartphone and wearable devices, and managed by the RADAR-base from 1062 participants recruited in Italy, Spain, Denmark, the United Kingdom, and the Netherlands. We derived nine features on a daily basis including time spent at home, maximum distance travelled from home, the maximum number of Bluetooth-enabled nearby devices (as a proxy for physical distancing), step count, average heart rate, sleep duration, bedtime, phone unlock duration, and social app use duration. We performed Kruskal-Wallis tests followed by post hoc Dunn tests to assess differences in these features among baseline, prelockdown, and during lockdown periods. We also studied behavioral differences by age, gender, BMI, and educational background.

Results

We were able to quantify expected changes in time spent at home, distance travelled, and the number of nearby Bluetooth-enabled devices between prelockdown and during lockdown periods (P<.001 for all five countries). We saw reduced sociality as measured through mobility features and increased virtual sociality through phone use. People were more active on their phones (P<.001 for Italy, Spain, and the United Kingdom), spending more time using social media apps (P<.001 for Italy, Spain, the United Kingdom, and the Netherlands), particularly around major news events. Furthermore, participants had a lower heart rate (P<.001 for Italy and Spain; P=.02 for Denmark), went to bed later (P<.001 for Italy, Spain, the United Kingdom, and the Netherlands), and slept more (P<.001 for Italy, Spain, and the United Kingdom). We also found that young people had longer homestay than older people during the lockdown and fewer daily steps. Although there was no significant difference between the high and low BMI groups in time spent at home, the low BMI group walked more.

Conclusions

RADAR-base, a freely deployable data collection platform leveraging data from wearables and mobile technologies, can be used to rapidly quantify and provide a holistic view of behavioral changes in response to public health interventions as a result of infectious outbreaks such as COVID-19. RADAR-base may be a viable approach to implementing an early warning system for passively assessing the local compliance to interventions in epidemics and pandemics, and could help countries ease out of lockdown.",,pdf:https://www.jmir.org/2020/9/e19992/PDF; doi:https://doi.org/10.2196/19992; html:https://europepmc.org/articles/PMC7527031 34107928,https://doi.org/10.1186/s12913-021-06509-x,Importance of patient bed pathways and length of stay differences in predicting COVID-19 hospital bed occupancy in England.,"Leclerc QJ, Fuller NM, Keogh RH, Diaz-Ordaz K, Sekula R, Semple MG, ISARIC4C Investigators, CMMID COVID-19 Working Group, Atkins KE, Procter SR, Knight GM.",,BMC health services research,2021,2021-06-09,Y,Length Of Stay; Hospitalisation; Bed Occupancy; Covid-19; Sars-cov-2; Bed Pathway,,,"

Background

Predicting bed occupancy for hospitalised patients with COVID-19 requires understanding of length of stay (LoS) in particular bed types. LoS can vary depending on the patient's ""bed pathway"" - the sequence of transfers of individual patients between bed types during a hospital stay. In this study, we characterise these pathways, and their impact on predicted hospital bed occupancy.

Methods

We obtained data from University College Hospital (UCH) and the ISARIC4C COVID-19 Clinical Information Network (CO-CIN) on hospitalised patients with COVID-19 who required care in general ward or critical care (CC) beds to determine possible bed pathways and LoS. We developed a discrete-time model to examine the implications of using either bed pathways or only average LoS by bed type to forecast bed occupancy. We compared model-predicted bed occupancy to publicly available bed occupancy data on COVID-19 in England between March and August 2020.

Results

In both the UCH and CO-CIN datasets, 82% of hospitalised patients with COVID-19 only received care in general ward beds. We identified four other bed pathways, present in both datasets: ""Ward, CC, Ward"", ""Ward, CC"", ""CC"" and ""CC, Ward"". Mean LoS varied by bed type, pathway, and dataset, between 1.78 and 13.53 days. For UCH, we found that using bed pathways improved the accuracy of bed occupancy predictions, while only using an average LoS for each bed type underestimated true bed occupancy. However, using the CO-CIN LoS dataset we were not able to replicate past data on bed occupancy in England, suggesting regional LoS heterogeneities.

Conclusions

We identified five bed pathways, with substantial variation in LoS by bed type, pathway, and geography. This might be caused by local differences in patient characteristics, clinical care strategies, or resource availability, and suggests that national LoS averages may not be appropriate for local forecasts of bed occupancy for COVID-19.

Trial registration

The ISARIC WHO CCP-UK study ISRCTN66726260 was retrospectively registered on 21/04/2020 and designated an Urgent Public Health Research Study by NIHR.",,pdf:https://bmchealthservres.biomedcentral.com/counter/pdf/10.1186/s12913-021-06509-x; doi:https://doi.org/10.1186/s12913-021-06509-x; html:https://europepmc.org/articles/PMC8188158; pdf:https://europepmc.org/articles/PMC8188158?pdf=render -36545688,https://doi.org/10.1192/bjb.2022.83,EDIFY (Eating Disorders: Delineating Illness and Recovery Trajectories to Inform Personalised Prevention and Early Intervention in Young People): project outline.,"Hemmings A, Sharpe H, Allen K, Bartel H, Campbell IC, Desrivières S, Dobson RJB, Folarin AA, French T, Kelly J, Micali N, Raman S, Treasure J, Abbas R, Heslop B, Street T, Schmidt U.",,BJPsych bulletin,2023,2023-12-01,Y,Eating Disorders; Risk And Resilience; Prevention And Early Intervention; Youth Engagement; Interdisciplinary Working,,,"EDIFY (Eating Disorders: Delineating Illness and Recovery Trajectories to Inform Personalised Prevention and Early Intervention in Young People) is an ambitious research project aiming to revolutionise how eating disorders are perceived, prevented and treated. Six integrated workstreams will address key questions, including: What are young people's experiences of eating disorders and recovery? What are the unique and shared risk factors in different groups? What helps or hinders recovery? How do the brain and behaviour change from early- to later-stage illness? How can we intervene earlier, quicker and in a more personalised way? This 4-year project, involving over 1000 participants, integrates arts, design and humanities with advanced neurobiological, psychosocial and bioinformatics approaches. Young people with lived experience of eating disorders are at the heart of EDIFY, serving as advisors and co-producers throughout. Ultimately, this work will expand public and professional perceptions of eating disorders, uplift under-represented voices and stimulate much-needed advances in policy and practice.",,pdf:https://www.cambridge.org/core/services/aop-cambridge-core/content/view/C1E5FCC67F1D627908A5495EED02577B/S2056469422000833a.pdf/div-class-title-edify-eating-disorders-delineating-illness-and-recovery-trajectories-to-inform-personalised-prevention-and-early-intervention-in-young-people-project-outline-div.pdf; doi:https://doi.org/10.1192/bjb.2022.83; html:https://europepmc.org/articles/PMC10694679; pdf:https://europepmc.org/articles/PMC10694679?pdf=render 33934335,https://doi.org/10.1111/anae.15466,Long-term trends in critical care admissions in Wales*.,"Pugh RJ, Bailey R, Szakmany T, Al Sallakh M, Hollinghurst J, Akbari A, Griffiths R, Battle C, Thorpe C, Subbe CP, Lyons RA.",,Anaesthesia,2021,2021-05-02,Y,Ageing; Frailty; Outcomes; Comorbidity; Critical Care Capacity,,,"As national populations age, demands on critical care services are expected to increase. In many healthcare settings, longitudinal trends indicate rising numbers and proportions of patients admitted to ICU who are older; elsewhere, including some parts of the UK, a decrease has raised concerns with regard to rationing according to age. Our aim was to investigate admission trends in Wales, where critical care capacity has not risen in the last decade. We used the Secure Anonymised Information Linkage Databank to identify and characterise critical care admissions in patients aged ≥ 18 years from 1 January 2008 to 31 December 2017. We categorised 85,629 ICU admissions as youngest (18-64 years), older (65-79 years) and oldest (≥ 80 years). The oldest group accounted for 15% of admissions, the older age group 39% and the youngest group 46%. Relative to the national population, the incidence of admission rates per 10,000 population in the oldest group decreased significantly over the study period from 91.5/10,000 in 2008 to 77.5/10,000 (a relative decrease of 15%), and among the older group from 89.2/10,000 in 2008 to 75.3/10,000 in 2017 (a relative decrease of 16%). We observed significant decreases in admissions with high comorbidity (modified Charlson comorbidity index); increases in the proportion of older patients admitted who were considered 'fit' rather than frail (electronic frailty index); and decreases in admissions with a medical diagnosis. In contrast to other healthcare settings, capacity constraints and surgical imperatives appear to have contributed to a relative exclusion of older patients presenting with acute medical illness.",,pdf:https://cronfa.swan.ac.uk/Record/cronfa56830/Download/56830__24941__ed34d96421c74ecca52d5a3aaf9afc85.pdf; doi:https://doi.org/10.1111/anae.15466; html:https://europepmc.org/articles/PMC10138728; pdf:https://europepmc.org/articles/PMC10138728?pdf=render +36545688,https://doi.org/10.1192/bjb.2022.83,EDIFY (Eating Disorders: Delineating Illness and Recovery Trajectories to Inform Personalised Prevention and Early Intervention in Young People): project outline.,"Hemmings A, Sharpe H, Allen K, Bartel H, Campbell IC, Desrivières S, Dobson RJB, Folarin AA, French T, Kelly J, Micali N, Raman S, Treasure J, Abbas R, Heslop B, Street T, Schmidt U.",,BJPsych bulletin,2023,2023-12-01,Y,Eating Disorders; Risk And Resilience; Prevention And Early Intervention; Youth Engagement; Interdisciplinary Working,,,"EDIFY (Eating Disorders: Delineating Illness and Recovery Trajectories to Inform Personalised Prevention and Early Intervention in Young People) is an ambitious research project aiming to revolutionise how eating disorders are perceived, prevented and treated. Six integrated workstreams will address key questions, including: What are young people's experiences of eating disorders and recovery? What are the unique and shared risk factors in different groups? What helps or hinders recovery? How do the brain and behaviour change from early- to later-stage illness? How can we intervene earlier, quicker and in a more personalised way? This 4-year project, involving over 1000 participants, integrates arts, design and humanities with advanced neurobiological, psychosocial and bioinformatics approaches. Young people with lived experience of eating disorders are at the heart of EDIFY, serving as advisors and co-producers throughout. Ultimately, this work will expand public and professional perceptions of eating disorders, uplift under-represented voices and stimulate much-needed advances in policy and practice.",,pdf:https://www.cambridge.org/core/services/aop-cambridge-core/content/view/C1E5FCC67F1D627908A5495EED02577B/S2056469422000833a.pdf/div-class-title-edify-eating-disorders-delineating-illness-and-recovery-trajectories-to-inform-personalised-prevention-and-early-intervention-in-young-people-project-outline-div.pdf; doi:https://doi.org/10.1192/bjb.2022.83; html:https://europepmc.org/articles/PMC10694679; pdf:https://europepmc.org/articles/PMC10694679?pdf=render 35038301,https://doi.org/10.2196/30523,Requirements for a Bespoke Intensive Care Unit Dashboard in Response to the COVID-19 Pandemic: Semistructured Interview Study.,"Davidson B, Ferrer Portillo KM, Wac M, McWilliams C, Bourdeaux C, Craddock I.",,JMIR human factors,2022,2022-04-13,Y,Development; Monitoring; Design; Disease monitoring; ICU; Interview; Intensive Care; Critical Care; Ehealth; Dashboard; Human-centered Design; Covid-19,,,"

Background

Intensive care units (ICUs) around the world are in high demand due to patients with COVID-19 requiring hospitalization. As researchers at the University of Bristol, we were approached to develop a bespoke data visualization dashboard to assist two local ICUs during the pandemic that will centralize disparate data sources in the ICU to help reduce the cognitive load on busy ICU staff in the ever-evolving pandemic.

Objective

The aim of this study was to conduct interviews with ICU staff in University Hospitals Bristol and Weston National Health Service Foundation Trust to elicit requirements for a bespoke dashboard to monitor the high volume of patients, particularly during the COVID-19 pandemic.

Methods

We conducted six semistructured interviews with clinical staff to obtain an overview of their requirements for the dashboard and to ensure its ultimate suitability for end users. Interview questions aimed to understand the job roles undertaken in the ICU, potential uses of the dashboard, specific issues associated with managing COVID-19 patients, key data of interest, and any concerns about the introduction of a dashboard into the ICU.

Results

From our interviews, we found the following design requirements: (1) a flexible dashboard, where the functionality can be updated quickly and effectively to respond to emerging information about the management of this new disease; (2) a mobile dashboard, which allows staff to move around on wards with a dashboard, thus potentially replacing paper forms to enable detailed and consistent data entry; (3) a customizable and intuitive dashboard, where individual users would be able to customize the appearance of the dashboard to suit their role; (4) real-time data and trend analysis via informative data visualizations that help busy ICU staff to understand a patient's clinical trajectory; and (5) the ability to manage tasks and staff, tracking both staff and patient movements, handovers, and task monitoring to ensure the highest quality of care.

Conclusions

The findings of this study confirm that digital solutions for ICU use would potentially reduce the cognitive load of ICU staff and reduce clinical errors at a time of notably high demand of intensive health care.",,pdf:https://humanfactors.jmir.org/2022/2/e30523/PDF; doi:https://doi.org/10.2196/30523; html:https://europepmc.org/articles/PMC9009380 38198154,https://doi.org/10.1093/bjs/znad347,Natural language processing to automate a web-based model of care and modernize skin cancer multidisciplinary team meetings.,"Ali SR, Dobbs TD, Tarafdar A, Strafford H, Fonferko-Shadrach B, Lacey AS, Pickrell WO, Hutchings HA, Whitaker IS.",,The British journal of surgery,2024,2024-01-01,Y,,,,"

Background

Cancer multidisciplinary team (MDT) meetings are under intense pressure to reform given the rapidly rising incidence of cancer and national mandates for protocolized streaming of cases. The aim of this study was to validate a natural language processing (NLP)-based web platform to automate evidence-based MDT decisions for skin cancer with basal cell carcinoma as a use case.

Methods

A novel and validated NLP information extraction model was used to extract perioperative tumour and surgical factors from histopathology reports. A web application with a bespoke application programming interface used data from this model to provide an automated clinical decision support system, mapped to national guidelines and generating a patient letter to communicate ongoing management. Performance was assessed against retrospectively derived recommendations by two independent and blinded expert clinicians.

Results

There were 893 patients (1045 lesions) used to internally validate the model. High accuracy was observed when compared against human predictions, with an overall value of 0.92. Across all classifiers the virtual skin MDT was highly specific (0.96), while sensitivity was lower (0.72).

Conclusion

This study demonstrates the feasibility of a fully automated, virtual, web-based service model to host the skin MDT with good system performance. This platform could be used to support clinical decision-making during MDTs as 'human in the loop' approach to aid protocolized streaming. Future prospective studies are needed to validate the model in tumour types where guidelines are more complex.",,pdf:https://academic.oup.com/bjs/article-pdf/111/1/znad347/55374438/znad347.pdf; doi:https://doi.org/10.1093/bjs/znad347; html:https://europepmc.org/articles/PMC10782209; pdf:https://europepmc.org/articles/PMC10782209?pdf=render 36472984,https://doi.org/10.1371/journal.pmed.1004124,Association between antidementia medication use and mortality in people diagnosed with dementia with Lewy bodies in the UK: A retrospective cohort study.,"Chen S, Price AC, Cardinal RN, Moylett S, Kershenbaum AD, Fitzgerald J, Mueller C, Stewart R, O'Brien JT.",,PLoS medicine,2022,2022-12-06,Y,,,,"

Background

Dementia with Lewy bodies (DLBs) is a common cause of dementia but has higher mortality than Alzheimer's disease (AD). The reasons for this are unclear, but antidementia drugs (including acetylcholinesterase inhibitors [AChEIs] and memantine) symptomatically benefit people with DLB and might improve outcomes. We investigated whether AChEIs and/or memantine were associated with reduced hospital admissions and mortality.

Methods and findings

We performed a retrospective cohort study of those diagnosed with DLB between 1 January 2005 and 31 December 2019, using data from electronic clinical records of secondary care mental health services in Cambridgeshire and Peterborough NHS Foundation Trust (CPFT), United Kingdom (catchment area population approximately 0.86 million), as well as linked records from national Hospital Episode Statistics (HES) data. Eligible patients were those who started AChEIs or memantine within 3 months of their diagnosis (cases) and those who never used AChEIs or memantine (controls). Outcomes included admission, length of stay, and mortality. Cox proportional hazard and linear regression models were used. Of 592 patients with DLB, 219 never took AChEIs or memantine, 100 took AChEIs only, and 273 took both AChEIs and memantine. The cohorts were followed up for an average of 896 days, 981 days, and 1,004 days, respectively. There were no significant differences in the cohorts' baseline characteristics, except for socioeconomic status that was lower in patients who never took AChEIs or memantine (χ2 = 23.34, P = 0.003). After controlling for confounding by sociodemographic factors (age, sex, marital status, ethnicity, socioeconomic status), antipsychotic use, antidepressant use, cognitive status, physical comorbidity, anticholinergic burden, and global health performance, compared with patients who never took AChEIs or memantine, patients taking AChEIs only or taking both had a significantly lower risk of death (adjusted hazard ratio (HR) = 0.67, 95% CI = 0.48 to 0.93, p = 0.02; adjusted HR = 0.64, 95% CI = 0.50 to 0.83, P = 0.001, respectively). Those taking AChEIs or both AChEIs and memantine had significantly shorter periods of unplanned hospital admission for physical disorders (adjusted coefficient -13.48, 95% CI = [-26.87, -0.09], P = 0.049; adjusted coefficient -14.21, 95% CI = [-24.58, -3.85], P = 0.007, respectively), but no difference in length of stay for planned admissions for physical disorders, or for admissions for mental health disorders. No significant additional associations of memantine on admission, length of stay, and mortality were found (all P > 0.05). The main limitation was that this was a naturalistic study and possible confounds cannot be fully controlled, and there may be selection bias resulting from nonrandom prescription behaviour in clinical practice. However, we mimicked the intention-to-treat design of clinical trials, and the majority of baseline characters were balanced between cohorts. In addition, our series of sensitivity analyses confirmed the consistency of our results.

Conclusion

In this study, we observed that use of AChEIs with or without memantine in DLB was associated with shorter duration of hospital admissions and decreased risk of mortality. Although our study was naturalistic, it supports further the use of AChEIs in DLB.",,pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1004124&type=printable; doi:https://doi.org/10.1371/journal.pmed.1004124; html:https://europepmc.org/articles/PMC9725132; pdf:https://europepmc.org/articles/PMC9725132?pdf=render @@ -686,8 +686,8 @@ PMC8855010,https://doi.org/,POS-894 PREDICTING PANDEMIC-RELATED EXCESS-DEATH USI 35726508,https://doi.org/10.1177/10398562221103117,Improving quantification of anticholinergic burden using the Anticholinergic Effect on Cognition Scale - a healthcare improvement study in a geriatric ward setting.,"Balasundaram B, Ang WST, Stewart R, Bishara D, Ooi CH, Li F, Akram F, Eu Kwek AB.",,Australasian psychiatry : bulletin of Royal Australian and New Zealand College of Psychiatrists,2022,2022-06-21,Y,Dementia; Delirium; Anticholinergic drugs; Anticholinergic Burden Scales; Anticholinergic Effect On Cognition Scale,,,"

Objective

Anticholinergic burden refers to the cumulative effects of taking multiple medications with anticholinergic effects. This study was carried out in a public hospital in Singapore, aimed to improve and achieve a 100% comprehensive identification and review of measured, anticholinergic burden in a geriatric psychiatry liaison service to geriatric wards. We evaluated changes in pre-to post-assessment anticholinergic burden scores and trainee feedback.

Method

Plan Do Study Act methodology was employed, and Anticholinergic Effect on Cognition scale (AEC) was implemented as the study intervention. A survey instrument evaluated trainee feedback.

Results

There was no measured anticholinergic burden in a baseline of 170 assessments. 75 liaison psychiatry assessments were conducted between June and November 2021 in two cycles. 94.7% of pre-assessments (at the time of assessment) and 71.1% of post-assessments (following assessment) had a record of AEC scores in clinical documentation in cycle one, improving in the second cycle to 100%, 94.6%, respectively. A high post-assessment AEC score of 3 and over reduced from 15.8% in cycle one to 5.4% in cycle two. The trainee feedback suggested an enriching educational experience.

Conclusions

Using the AEC scale, the findings support the feasibility of comprehensive identification and review of measured anticholinergic burden in older people with neurocognitive disorders.",,doi:https://doi.org/10.1177/10398562221103117; doi:https://doi.org/10.1177/10398562221103117; html:https://europepmc.org/articles/PMC9379386; pdf:https://europepmc.org/articles/PMC9379386?pdf=render 35337642,https://doi.org/10.1016/s2589-7500(22)00018-8,"Implementation of corticosteroids in treatment of COVID-19 in the ISARIC WHO Clinical Characterisation Protocol UK: prospective, cohort study.","Närhi F, Moonesinghe SR, Shenkin SD, Drake TM, Mulholland RH, Donegan C, Dunning J, Fairfield CJ, Girvan M, Hardwick HE, Ho A, Leeming G, Nguyen-Van-Tam JS, Pius R, Russell CD, Shaw CA, Spencer RG, Turtle L, Openshaw PJM, Baillie JK, Harrison EM, Semple MG, Docherty AB, ISARIC4C investigators.",,The Lancet. Digital health,2022,2022-04-01,Y,,,,"

Background

Dexamethasone was the first intervention proven to reduce mortality in patients with COVID-19 being treated in hospital. We aimed to evaluate the adoption of corticosteroids in the treatment of COVID-19 in the UK after the RECOVERY trial publication on June 16, 2020, and to identify discrepancies in care.

Methods

We did an audit of clinical implementation of corticosteroids in a prospective, observational, cohort study in 237 UK acute care hospitals between March 16, 2020, and April 14, 2021, restricted to patients aged 18 years or older with proven or high likelihood of COVID-19, who received supplementary oxygen. The primary outcome was administration of dexamethasone, prednisolone, hydrocortisone, or methylprednisolone. This study is registered with ISRCTN, ISRCTN66726260.

Findings

Between June 17, 2020, and April 14, 2021, 47 795 (75·2%) of 63 525 of patients on supplementary oxygen received corticosteroids, higher among patients requiring critical care than in those who received ward care (11 185 [86·6%] of 12 909 vs 36 415 [72·4%] of 50 278). Patients 50 years or older were significantly less likely to receive corticosteroids than those younger than 50 years (adjusted odds ratio 0·79 [95% CI 0·70-0·89], p=0·0001, for 70-79 years; 0·52 [0·46-0·58], p<0·0001, for >80 years), independent of patient demographics and illness severity. 84 (54·2%) of 155 pregnant women received corticosteroids. Rates of corticosteroid administration increased from 27·5% in the week before June 16, 2020, to 75-80% in January, 2021.

Interpretation

Implementation of corticosteroids into clinical practice in the UK for patients with COVID-19 has been successful, but not universal. Patients older than 70 years, independent of illness severity, chronic neurological disease, and dementia, were less likely to receive corticosteroids than those who were younger, as were pregnant women. This could reflect appropriate clinical decision making, but the possibility of inequitable access to life-saving care should be considered.

Funding

UK National Institute for Health Research and UK Medical Research Council.",,pdf:http://www.thelancet.com/article/S2589750022000188/pdf; doi:https://doi.org/10.1016/S2589-7500(22)00018-8; html:https://europepmc.org/articles/PMC8940185 34000257,https://doi.org/10.1016/s0140-6736(21)00897-7,"Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial.",RECOVERY Collaborative Group.,,"Lancet (London, England)",2021,2021-05-14,Y,,,,"

Background

Many patients with COVID-19 have been treated with plasma containing anti-SARS-CoV-2 antibodies. We aimed to evaluate the safety and efficacy of convalescent plasma therapy in patients admitted to hospital with COVID-19.

Methods

This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. The trial is underway at 177 NHS hospitals from across the UK. Eligible and consenting patients were randomly assigned (1:1) to receive either usual care alone (usual care group) or usual care plus high-titre convalescent plasma (convalescent plasma group). The primary outcome was 28-day mortality, analysed on an intention-to-treat basis. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.

Findings

Between May 28, 2020, and Jan 15, 2021, 11558 (71%) of 16287 patients enrolled in RECOVERY were eligible to receive convalescent plasma and were assigned to either the convalescent plasma group or the usual care group. There was no significant difference in 28-day mortality between the two groups: 1399 (24%) of 5795 patients in the convalescent plasma group and 1408 (24%) of 5763 patients in the usual care group died within 28 days (rate ratio 1·00, 95% CI 0·93-1·07; p=0·95). The 28-day mortality rate ratio was similar in all prespecified subgroups of patients, including in those patients without detectable SARS-CoV-2 antibodies at randomisation. Allocation to convalescent plasma had no significant effect on the proportion of patients discharged from hospital within 28 days (3832 [66%] patients in the convalescent plasma group vs 3822 [66%] patients in the usual care group; rate ratio 0·99, 95% CI 0·94-1·03; p=0·57). Among those not on invasive mechanical ventilation at randomisation, there was no significant difference in the proportion of patients meeting the composite endpoint of progression to invasive mechanical ventilation or death (1568 [29%] of 5493 patients in the convalescent plasma group vs 1568 [29%] of 5448 patients in the usual care group; rate ratio 0·99, 95% CI 0·93-1·05; p=0·79).

Interpretation

In patients hospitalised with COVID-19, high-titre convalescent plasma did not improve survival or other prespecified clinical outcomes.

Funding

UK Research and Innovation (Medical Research Council) and National Institute of Health Research.",,pdf:http://www.thelancet.com/article/S0140673621008977/pdf; doi:https://doi.org/10.1016/S0140-6736(21)00897-7; html:https://europepmc.org/articles/PMC8121538 -37474660,https://doi.org/10.1038/s41591-023-02445-x,Considerations for patient and public involvement and engagement in health research.,"Aiyegbusi OL, McMullan C, Hughes SE, Turner GM, Subramanian A, Hotham R, Davies EH, Frost C, Alder Y, Agyen L, Buckland L, Camaradou J, Chong A, Jeyes F, Kumar S, Matthews KL, Moore P, Ormerod J, Price G, Saint-Cricq M, Stanton D, Walker A, Haroon S, Denniston AK, Calvert MJ, TLC Study Group.",,Nature medicine,2023,2023-07-20,N,,,,"Patient and public involvement and engagement (PPIE) can provide valuable insights into the experiences of those living with and affected by a disease or health condition. Inclusive collaboration between patients, the public and researchers can lead to productive relationships, ensuring that health research addresses patient needs. Guidelines are available to support effective PPIE; however, evaluation of the impact of PPIE strategies in health research is limited. In this Review, we evaluate the impact of PPIE in the 'Therapies for Long COVID in non-hospitalised individuals' (TLC) Study, using a combination of group discussions and interviews with patient partners and researchers. We identify areas of good practice and reflect on areas for improvement. Using these insights and the results of a survey, we synthesize two checklists of considerations for PPIE, and we propose that research teams use these checklists to optimize the impact of PPIE for both patients and researchers in future studies.",,doi:https://doi.org/10.1038/s41591-023-02445-x 34319235,https://doi.org/10.2196/28873,Remote Assessment of Lung Disease and Impact on Physical and Mental Health (RALPMH): Protocol for a Prospective Observational Study.,"Ranjan Y, Althobiani M, Jacob J, Orini M, Dobson RJ, Porter J, Hurst J, Folarin AA.",,JMIR research protocols,2021,2021-10-07,Y,Lung diseases; Mental health; Remote Monitoring; Respiratory Health; Internet Of Things; Mhealth; Mobile Health; Wearables; Cardiopulmonary Diseases; Covid-19,,,"

Background

Chronic lung disorders like chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) are characterized by exacerbations. They are unpleasant for patients and sometimes severe enough to cause hospital admission and death. Moreover, due to the COVID-19 pandemic, vulnerable populations with these disorders are at high risk, and their routine care cannot be done properly. Remote monitoring offers a low cost and safe solution for gaining visibility into the health of people in their daily lives, making it useful for vulnerable populations.

Objective

The primary objective is to assess the feasibility and acceptability of remote monitoring using wearables and mobile phones in patients with pulmonary diseases. The secondary objective is to provide power calculations for future studies centered around understanding the number of exacerbations according to sample size and duration.

Methods

Twenty participants will be recruited in each of three cohorts (COPD, IPF, and posthospitalization COVID). Data collection will be done remotely using the RADAR-Base (Remote Assessment of Disease And Relapse) mobile health (mHealth) platform for different devices, including Garmin wearable devices and smart spirometers, mobile app questionnaires, surveys, and finger pulse oximeters. Passive data include wearable-derived continuous heart rate, oxygen saturation, respiration rate, activity, and sleep. Active data include disease-specific patient-reported outcome measures, mental health questionnaires, and symptom tracking to track disease trajectory. Analyses will assess the feasibility of lung disorder remote monitoring (including data quality, data completeness, system usability, and system acceptability). We will attempt to explore disease trajectory, patient stratification, and identification of acute clinical events such as exacerbations. A key aspect is understanding the potential of real-time data collection. We will simulate an intervention to acquire responses at the time of the event to assess model performance for exacerbation identification.

Results

The Remote Assessment of Lung Disease and Impact on Physical and Mental Health (RALPMH) study provides a unique opportunity to assess the use of remote monitoring in the evaluation of lung disorders. The study started in the middle of June 2021. The data collection apparatus, questionnaires, and wearable integrations were setup and tested by the clinical teams prior to the start of recruitment. While recruitment is ongoing, real-time exacerbation identification models are currently being constructed. The models will be pretrained daily on data of previous days, but the inference will be run in real time.

Conclusions

The RALPMH study will provide a reference infrastructure for remote monitoring of lung diseases. It specifically involves information regarding the feasibility and acceptability of remote monitoring and the potential of real-time data collection and analysis in the context of chronic lung disorders. It will help plan and inform decisions in future studies in the area of respiratory health.

Trial registration

ISRCTN Registry ISRCTN16275601; https://www.isrctn.com/ISRCTN16275601.

International registered report identifier (irrid)

PRR1-10.2196/28873.",,pdf:https://jmir.org/api/download?alt_name=resprot_v10i10e28873_app2.pdf&filename=4dda9f18456291d5d5d6facee1b77a71.pdf; doi:https://doi.org/10.2196/28873; html:https://europepmc.org/articles/PMC8500349 +37474660,https://doi.org/10.1038/s41591-023-02445-x,Considerations for patient and public involvement and engagement in health research.,"Aiyegbusi OL, McMullan C, Hughes SE, Turner GM, Subramanian A, Hotham R, Davies EH, Frost C, Alder Y, Agyen L, Buckland L, Camaradou J, Chong A, Jeyes F, Kumar S, Matthews KL, Moore P, Ormerod J, Price G, Saint-Cricq M, Stanton D, Walker A, Haroon S, Denniston AK, Calvert MJ, TLC Study Group.",,Nature medicine,2023,2023-07-20,N,,,,"Patient and public involvement and engagement (PPIE) can provide valuable insights into the experiences of those living with and affected by a disease or health condition. Inclusive collaboration between patients, the public and researchers can lead to productive relationships, ensuring that health research addresses patient needs. Guidelines are available to support effective PPIE; however, evaluation of the impact of PPIE strategies in health research is limited. In this Review, we evaluate the impact of PPIE in the 'Therapies for Long COVID in non-hospitalised individuals' (TLC) Study, using a combination of group discussions and interviews with patient partners and researchers. We identify areas of good practice and reflect on areas for improvement. Using these insights and the results of a survey, we synthesize two checklists of considerations for PPIE, and we propose that research teams use these checklists to optimize the impact of PPIE for both patients and researchers in future studies.",,doi:https://doi.org/10.1038/s41591-023-02445-x 35104366,https://doi.org/10.1111/bjd.21042,Vaccine hesitancy and access to psoriasis care during the COVID-19 pandemic: findings from a global patient-reported cross-sectional survey.,"Bechman K, Cook ES, Dand N, Yiu ZZN, Tsakok T, Meynell F, Coker B, Vincent A, Bachelez H, Barbosa I, Brown MA, Capon F, Contreras CR, De La Cruz C, Meglio PD, Gisondi P, Jullien D, Kelly J, Lambert J, Lancelot C, Langan SM, Mason KJ, McAteer H, Moorhead L, Naldi L, Norton S, Puig L, Spuls PI, Torres T, Urmston D, Vesty A, Warren RB, Waweru H, Weinman J, Griffiths CEM, Barker JN, Smith CH, Galloway JB, Mahil SK, PsoProtect study group.",,The British journal of dermatology,2022,2022-05-03,Y,,,,,,pdf:https://biblio.ugent.be/publication/8757812/file/8757816.pdf; doi:https://doi.org/10.1111/bjd.21042; html:https://europepmc.org/articles/PMC9545500; pdf:https://europepmc.org/articles/PMC9545500?pdf=render 34240696,https://doi.org/10.2807/1560-7917.es.2021.26.27.2000004,"Nanopore metagenomic sequencing of influenza virus directly from respiratory samples: diagnosis, drug resistance and nosocomial transmission, United Kingdom, 2018/19 influenza season.","Xu Y, Lewandowski K, Downs LO, Kavanagh J, Hender T, Lumley S, Jeffery K, Foster D, Sanderson ND, Vaughan A, Morgan M, Vipond R, Carroll M, Peto T, Crook D, Walker AS, Matthews PC, Pullan ST.",,Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin,2021,2021-07-01,Y,Genetic diversity; Influenza; Diagnosis; Metagenomics; Antiviral Drug Resistance; Nanopore; Respiratory Viruses; Nosocomial Transmission,,,"BackgroundInfluenza virus presents a considerable challenge to public health by causing seasonal epidemics and occasional pandemics. Nanopore metagenomic sequencing has the potential to be deployed for near-patient testing, providing rapid infection diagnosis, rationalising antimicrobial therapy, and supporting infection-control interventions.AimTo evaluate the applicability of this sequencing approach as a routine laboratory test for influenza in clinical settings.MethodsWe conducted Oxford Nanopore Technologies (Oxford, United Kingdom (UK)) metagenomic sequencing for 180 respiratory samples from a UK hospital during the 2018/19 influenza season, and compared results to routine molecular diagnostic standards (Xpert Xpress Flu/RSV assay; BioFire FilmArray Respiratory Panel 2 assay). We investigated drug resistance, genetic diversity, and nosocomial transmission using influenza sequence data.ResultsCompared to standard testing, Nanopore metagenomic sequencing was 83% (75/90) sensitive and 93% (84/90) specific for detecting influenza A viruses. Of 59 samples with haemagglutinin subtype determined, 40 were H1 and 19 H3. We identified an influenza A(H3N2) genome encoding the oseltamivir resistance S331R mutation in neuraminidase, potentially associated with an emerging distinct intra-subtype reassortant. Whole genome phylogeny refuted suspicions of a transmission cluster in a ward, but identified two other clusters that likely reflected nosocomial transmission, associated with a predominant community-circulating strain. We also detected other potentially pathogenic viruses and bacteria from the metagenome.ConclusionNanopore metagenomic sequencing can detect the emergence of novel variants and drug resistance, providing timely insights into antimicrobial stewardship and vaccine design. Full genome generation can help investigate and manage nosocomial outbreaks.",,pdf:https://www.eurosurveillance.org/deliver/fulltext/eurosurveillance/26/27/eurosurv-26-27-4.pdf?itemId=%2Fcontent%2F10.2807%2F1560-7917.ES.2021.26.27.2000004&mimeType=pdf&containerItemId=content/eurosurveillance; doi:https://doi.org/10.2807/1560-7917.ES.2021.26.27.2000004; html:https://europepmc.org/articles/PMC8268652; pdf:https://europepmc.org/articles/PMC8268652?pdf=render 35634533,https://doi.org/10.12688/wellcomeopenres.17360.1,A comprehensive high cost drugs dataset from the NHS in England - An OpenSAFELY-TPP Short Data Report.,"Rowan A, Bates C, Hulme W, Evans D, Davy S, A Kennedy N, Galloway J, E Mansfield K, Bechman K, Matthewman J, Yates M, Brown J, Schultze A, Norton S, J Walker A, E Morton C, Bhaskaran K, T Rentsch C, Williamson E, Croker R, Bacon S, Hickman G, Ward T, Green A, Fisher L, J Curtis H, Tazare J, M Eggo R, Inglesby P, Cockburn J, I McDonald H, Mathur R, Ys Wong A, Forbes H, Parry J, Hester F, Harper S, J Douglas I, Smeeth L, A Tomlinson L, W Lees C, Evans S, Smith C, M Langan S, Mehkar A, MacKenna B, Goldacre B.",,Wellcome open research,2021,2021-12-22,Y,Medications; Biosimilars; Healthcare Administration; Opensafely,,,"Background: At the outset of the COVID-19 pandemic, there was no routine comprehensive hospital medicines data from the UK available to researchers. These records can be important for many analyses including the effect of certain medicines on the risk of severe COVID-19 outcomes. With the approval of NHS England, we set out to obtain data on one specific group of medicines, ""high-cost drugs"" (HCD) which are typically specialist medicines for the management of long-term conditions, prescribed by hospitals to patients. Additionally, we aimed to make these data available to all approved researchers in OpenSAFELY-TPP. This report is intended to support all studies carried out in OpenSAFELY-TPP, and those elsewhere, working with this dataset or similar data. Methods: Working with the North East Commissioning Support Unit and NHS Digital, we arranged for collation of a single national HCD dataset to help inform responses to the COVID-19 pandemic. The dataset was developed from payment submissions from hospitals to commissioners. Results: In the financial year (FY) 2018/19 there were 2.8 million submissions for 1.1 million unique patient IDs recorded in the HCD. The average number of submissions per patient over the year was 2.6. In FY 2019/20 there were 4.0 million submissions for 1.3 million unique patient IDs. The average number of submissions per patient over the year was 3.1. Of the 21 variables in the dataset, three are now available for analysis in OpenSafely-TPP: Financial year and month of drug being dispensed; drug name; and a description of the drug dispensed. Conclusions: We have described the process for sourcing a national HCD dataset, making these data available for COVID-19-related analysis through OpenSAFELY-TPP and provided information on the variables included in the dataset, data coverage and an initial descriptive analysis.",,doi:https://doi.org/10.12688/wellcomeopenres.17360.1; html:https://europepmc.org/articles/PMC9120928; pdf:https://europepmc.org/articles/PMC9120928?pdf=render @@ -710,16 +710,16 @@ PMC8855010,https://doi.org/,POS-894 PREDICTING PANDEMIC-RELATED EXCESS-DEATH USI 32685697,https://doi.org/10.12688/wellcomeopenres.15788.1,The contribution of pre-symptomatic infection to the transmission dynamics of COVID-2019.,"Liu Y, Centre for Mathematical Modelling of Infectious Diseases nCoV Working Group, Funk S, Flasche S.",,Wellcome open research,2020,2020-04-01,Y,Incubation period; Serial Interval; Covid-19; Pre-symptomatic Transmission,,,"Background: Pre-symptomatic transmission can be a key determinant of the effectiveness of containment and mitigation strategies for infectious diseases, particularly if interventions rely on syndromic case finding. For COVID-19, infections in the absence of apparent symptoms have been reported frequently alongside circumstantial evidence for asymptomatic or pre-symptomatic transmission. We estimated the potential contribution of pre-symptomatic cases to COVID-19 transmission. Methods: Using the probability for symptom onset on a given day inferred from the incubation period, we attributed the serial interval reported from Shenzen, China, into likely pre-symptomatic and symptomatic transmission. We used the serial interval derived for cases isolated more than 6 days after symptom onset as the no active case finding scenario and the unrestricted serial interval as the active case finding scenario. We reported the estimate assuming no correlation between the incubation period and the serial interval alongside a range indicating alternative assumptions of positive and negative correlation. Results: We estimated that 23% (range accounting for correlation: 12 - 28%) of transmissions in Shenzen may have originated from pre-symptomatic infections. Through accelerated case isolation following symptom onset, this percentage increased to 46% (21 - 46%), implying that about 35% of secondary infections among symptomatic cases have been prevented. These results were robust to using reported incubation periods and serial intervals from other settings. Conclusions: Pre-symptomatic transmission may be essential to consider for containment and mitigation strategies for COVID-19.",,pdf:https://wellcomeopenresearch.org/articles/5-58/v1/pdf; doi:https://doi.org/10.12688/wellcomeopenres.15788.1; html:https://europepmc.org/articles/PMC7324944; pdf:https://europepmc.org/articles/PMC7324944?pdf=render PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm during the COVID-19 pandemic: a repeat cross-sectional UK population survey","John A, Lee S, Solomon S, Crepaz-Keay D, McDaid S, Morton A, Davidson G, Van Bortel T, Kousoulis A.",,BMJ open,2021,2021-01-01,Y,Mental health; Public Health; Suicide & Self-harm; Covid-19,,,,,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8718341/?tool=EBI; pdf:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8718341/pdf/?tool=EBI; html:https://europepmc.org/articles/PMC8718341; pdf:https://europepmc.org/articles/PMC8718341?pdf=render 38479735,https://doi.org/10.1136/bmjopen-2023-081926,"HFE genotypes, haemochromatosis diagnosis and clinical outcomes at age 80 years: a prospective cohort study in the UK Biobank.","Lucas MR, Atkins JL, Pilling LC, Shearman JD, Melzer D.",,BMJ open,2024,2024-03-13,Y,"Genetics; Mortality; Hepatology; Other Metabolic, E.g. Iron, Porphyria",,,"

Objectives

HFE haemochromatosis genetic variants have an uncertain clinical penetrance, especially to older ages and in undiagnosed groups. We estimated p.C282Y and p.H63D variant cumulative incidence of multiple clinical outcomes in a large community cohort.

Design

Prospective cohort study.

Setting

22 assessment centres across England, Scotland, and Wales in the UK Biobank (2006-2010).

Participants

451 270 participants genetically similar to the 1000 Genomes European reference population, with a mean of 13.3-year follow-up through hospital inpatient, cancer registries and death certificate data.

Main outcome measures

Cox proportional HRs of incident clinical outcomes and mortality in those with HFE p.C282Y/p.H63D mutations compared with those with no variants, stratified by sex and adjusted for age, assessment centre and genetic stratification. Cumulative incidences were estimated from age 40 years to 80 years.

Results

12.1% of p.C282Y+/+ males had baseline (mean age 57 years) haemochromatosis diagnoses, with a cumulative incidence of 56.4% at age 80 years. 33.1% died vs 25.4% without HFE variants (HR 1.29, 95% CI: 1.12 to 1.48, p=4.7×10-4); 27.9% vs 17.1% had joint replacements, 20.3% vs 8.3% had liver disease, and there were excess delirium, dementia, and Parkinson's disease but not depression. Associations, including excess mortality, were similar in the group undiagnosed with haemochromatosis. 3.4% of women with p.C282Y+/+ had baseline haemochromatosis diagnoses, with a cumulative incidence of 40.5% at age 80 years. There were excess incident liver disease (8.9% vs 6.8%; HR 1.62, 95% CI: 1.27 to 2.05, p=7.8×10-5), joint replacements and delirium, with similar results in the undiagnosed. p.C282Y/p.H63D and p.H63D+/+ men or women had no statistically significant excess fatigue or depression at baseline and no excess incident outcomes.

Conclusions

Male and female p.C282Y homozygotes experienced greater excess morbidity than previously documented, including those undiagnosed with haemochromatosis in the community. As haemochromatosis diagnosis rates were low at baseline despite treatment being considered effective, trials of screening to identify people with p.C282Y homozygosity early appear justified.",,doi:https://doi.org/10.1136/bmjopen-2023-081926; html:https://europepmc.org/articles/PMC10936495; pdf:https://europepmc.org/articles/PMC10936495?pdf=render -36777997,https://doi.org/10.1016/j.xgen.2022.100181,Leveraging global multi-ancestry meta-analysis in the study of idiopathic pulmonary fibrosis genetics.,"Partanen JJ, Häppölä P, Zhou W, Lehisto AA, Ainola M, Sutinen E, Allen RJ, Stockwell AD, Leavy OC, Oldham JM, Guillen-Guio B, Cox NJ, Hirbo JB, Schwartz DA, Fingerlin TE, Flores C, Noth I, Yaspan BL, Jenkins RG, Wain LV, Ripatti S, Pirinen M, International IPF Genetics Consortium, Global Biobank Meta-Analysis Initiative (GBMI), Laitinen T, Kaarteenaho R, Myllärniemi M, Daly MJ, Koskela JT.",,Cell genomics,2022,2022-10-12,Y,Meta-analysis; idiopathic pulmonary fibrosis; Gwas; Ancestry; Muc5b; Fine-mapping; Cross-population Analysis; Covid-19; Global Biobank Meta-Analysis Initiative,,,"The research of rare and devastating orphan diseases, such as idiopathic pulmonary fibrosis (IPF) has been limited by the rarity of the disease itself. The prognosis is poor-the prevalence of IPF is only approximately four times the incidence, limiting the recruitment of patients to trials and studies of the underlying biology. Global biobanking efforts can dramatically alter the future of IPF research. We describe a large-scale meta-analysis of IPF, with 8,492 patients and 1,355,819 population controls from 13 biobanks around the globe. Finally, we combine this meta-analysis with the largest available meta-analysis of IPF, reaching 11,160 patients and 1,364,410 population controls. We identify seven novel genome-wide significant loci, only one of which would have been identified if the analysis had been limited to European ancestry individuals. We observe notable pleiotropy across IPF susceptibility and severe COVID-19 infection and note an unexplained sex-heterogeneity effect at the strongest IPF locus MUC5B.",,pdf:https://helda.helsinki.fi/bitstream/10138/355828/1/Leveraging_global_multi_ancestry_meta_a...pdf; doi:https://doi.org/10.1016/j.xgen.2022.100181; html:https://europepmc.org/articles/PMC9903787; pdf:https://europepmc.org/articles/PMC9903787?pdf=render 34693751,https://doi.org/10.1177/14799731211053332,The diagnosis of asthma. Can physiological tests of small airways function help?,"Almeshari MA, Stockley J, Sapey E.",,Chronic respiratory disease,2021,2021-01-01,Y,Diagnosis; Asthma; Spirometry; Oscillometry; Small Airways Function,,,"Asthma is a common, chronic, and heterogeneous disease with a global impact and substantial economic costs. It is also associated with significant mortality and morbidity and the burden of undiagnosed asthma is significant. Asthma can be difficult to diagnose as there is no gold standard test and, while spirometry is central in diagnosing asthma, it may not be sufficient to confirm or exclude the diagnosis. The most commonly reported spirometric measures (forced expiratory volume in one second (FEV1) and forced vital capacity assess function in the larger airways. However, small airway dysfunction is highly prevalent in asthma and some studies suggest small airway involvement is one of the earliest disease manifestations. Moreover, there are new inhaled therapies with ultrafine particles that are specifically designed to target the small airways. Potentially, tests of small airways may more accurately diagnose early or mild asthma and assess the response to treatment than spirometry. Furthermore, some assessment techniques do not rely on forced ventilatory manoeuvres and may, therefore, be easier for certain groups to perform. This review discusses the current evidence of small airways tests in asthma and future research that may be needed to further assess their utility.",,pdf:https://journals.sagepub.com/doi/pdf/10.1177/14799731211053332; doi:https://doi.org/10.1177/14799731211053332; html:https://europepmc.org/articles/PMC8543738; pdf:https://europepmc.org/articles/PMC8543738?pdf=render +36777997,https://doi.org/10.1016/j.xgen.2022.100181,Leveraging global multi-ancestry meta-analysis in the study of idiopathic pulmonary fibrosis genetics.,"Partanen JJ, Häppölä P, Zhou W, Lehisto AA, Ainola M, Sutinen E, Allen RJ, Stockwell AD, Leavy OC, Oldham JM, Guillen-Guio B, Cox NJ, Hirbo JB, Schwartz DA, Fingerlin TE, Flores C, Noth I, Yaspan BL, Jenkins RG, Wain LV, Ripatti S, Pirinen M, International IPF Genetics Consortium, Global Biobank Meta-Analysis Initiative (GBMI), Laitinen T, Kaarteenaho R, Myllärniemi M, Daly MJ, Koskela JT.",,Cell genomics,2022,2022-10-12,Y,Meta-analysis; idiopathic pulmonary fibrosis; Gwas; Ancestry; Muc5b; Fine-mapping; Cross-population Analysis; Covid-19; Global Biobank Meta-Analysis Initiative,,,"The research of rare and devastating orphan diseases, such as idiopathic pulmonary fibrosis (IPF) has been limited by the rarity of the disease itself. The prognosis is poor-the prevalence of IPF is only approximately four times the incidence, limiting the recruitment of patients to trials and studies of the underlying biology. Global biobanking efforts can dramatically alter the future of IPF research. We describe a large-scale meta-analysis of IPF, with 8,492 patients and 1,355,819 population controls from 13 biobanks around the globe. Finally, we combine this meta-analysis with the largest available meta-analysis of IPF, reaching 11,160 patients and 1,364,410 population controls. We identify seven novel genome-wide significant loci, only one of which would have been identified if the analysis had been limited to European ancestry individuals. We observe notable pleiotropy across IPF susceptibility and severe COVID-19 infection and note an unexplained sex-heterogeneity effect at the strongest IPF locus MUC5B.",,pdf:https://helda.helsinki.fi/bitstream/10138/355828/1/Leveraging_global_multi_ancestry_meta_a...pdf; doi:https://doi.org/10.1016/j.xgen.2022.100181; html:https://europepmc.org/articles/PMC9903787; pdf:https://europepmc.org/articles/PMC9903787?pdf=render 36050271,https://doi.org/10.1016/s2589-7500(22)00151-0,CODE-EHR best-practice framework for the use of structured electronic health-care records in clinical research.,"Kotecha D, Asselbergs FW, Achenbach S, Anker SD, Atar D, Baigent C, Banerjee A, Beger B, Brobert G, Casadei B, Ceccarelli C, Cowie MR, Crea F, Cronin M, Denaxas S, Derix A, Fitzsimons D, Fredriksson M, Gale CP, Gkoutos GV, Goettsch W, Hemingway H, Ingvar M, Jonas A, Kazmierski R, Løgstrup S, Lumbers RT, Lüscher TF, McGreavy P, Piña IL, Roessig L, Steinbeisser C, Sundgren M, Tyl B, Thiel GV, Bochove KV, Vardas PE, Villanueva T, Vrana M, Weber W, Weidinger F, Windecker S, Wood A, Grobbee DE, Innovative Medicines Initiative BigData@Heart Consortium, European Society of Cardiology, and CODE-EHR International Consensus Group.",,The Lancet. Digital health,2022,2022-08-29,N,,,,"Big data is important to new developments in global clinical science that aim to improve the lives of patients. Technological advances have led to the regular use of structured electronic health-care records with the potential to address key deficits in clinical evidence that could improve patient care. The COVID-19 pandemic has shown this potential in big data and related analytics but has also revealed important limitations. Data verification, data validation, data privacy, and a mandate from the public to conduct research are important challenges to effective use of routine health-care data. The European Society of Cardiology and the BigData@Heart consortium have brought together a range of international stakeholders, including representation from patients, clinicians, scientists, regulators, journal editors, and industry members. In this Review, we propose the CODE-EHR minimum standards framework to be used by researchers and clinicians to improve the design of studies and enhance transparency of study methods. The CODE-EHR framework aims to develop robust and effective utilisation of health-care data for research purposes.",,doi:https://doi.org/10.1016/s2589-7500(22)00151-0; doi:https://doi.org/10.1016/S2589-7500(22)00151-0 37596262,https://doi.org/10.1038/s41467-023-40679-y,A genome-wide association study of blood cell morphology identifies cellular proteins implicated in disease aetiology.,"Akbari P, Vuckovic D, Stefanucci L, Jiang T, Kundu K, Kreuzhuber R, Bao EL, Collins JH, Downes K, Grassi L, Guerrero JA, Kaptoge S, Knight JC, Meacham S, Sambrook J, Seyres D, Stegle O, Verboon JM, Walter K, Watkins NA, Danesh J, Roberts DJ, Di Angelantonio E, Sankaran VG, Frontini M, Burgess S, Kuijpers T, Peters JE, Butterworth AS, Ouwehand WH, Soranzo N, Astle WJ.",,Nature communications,2023,2023-08-18,Y,,,,"Blood cells contain functionally important intracellular structures, such as granules, critical to immunity and thrombosis. Quantitative variation in these structures has not been subjected previously to large-scale genetic analysis. We perform genome-wide association studies of 63 flow-cytometry derived cellular phenotypes-including cell-type specific measures of granularity, nucleic acid content and reactivity-in 41,515 participants in the INTERVAL study. We identify 2172 distinct variant-trait associations, including associations near genes coding for proteins in organelles implicated in inflammatory and thrombotic diseases. By integrating with epigenetic data we show that many intracellular structures are likely to be determined in immature precursor cells. By integrating with proteomic data we identify the transcription factor FOG2 as an early regulator of platelet formation and α-granularity. Finally, we show that colocalisation of our associations with disease risk signals can suggest aetiological cell-types-variants in IL2RA and ITGA4 respectively mirror the known effects of daclizumab in multiple sclerosis and vedolizumab in inflammatory bowel disease.",,doi:https://doi.org/10.1038/s41467-023-40679-y; html:https://europepmc.org/articles/PMC10439125; pdf:https://europepmc.org/articles/PMC10439125?pdf=render 38198570,https://doi.org/10.1126/scitranslmed.adf4428,Prospective study design and data analysis in UK Biobank.,"Allen NE, Lacey B, Lawlor DA, Pell JP, Gallacher J, Smeeth L, Elliott P, Matthews PM, Lyons RA, Whetton AD, Lucassen A, Hurles ME, Chapman M, Roddam AW, Fitzpatrick NK, Hansell AL, Hardy R, Marioni RE, O'Donnell VB, Williams J, Lindgren CM, Effingham M, Sellors J, Danesh J, Collins R.",,Science translational medicine,2024,2024-01-10,N,,,,"Population-based prospective studies, such as UK Biobank, are valuable for generating and testing hypotheses about the potential causes of human disease. We describe how UK Biobank's study design, data access policies, and approaches to statistical analysis can help to minimize error and improve the interpretability of research findings, with implications for other population-based prospective studies being established worldwide.",,pdf:https://www.pure.ed.ac.uk/ws/files/405264227/scitranslmed.adf4428.pdf; doi:https://doi.org/10.1126/scitranslmed.adf4428; html:https://europepmc.org/articles/PMC11127744; pdf:https://europepmc.org/articles/PMC11127744?pdf=render; doi:https://doi.org/10.1126/scitranslmed.adf4428 37817277,https://doi.org/10.1186/s13063-023-07656-8,"e-Consent in UK academic-led clinical trials: current practice, challenges and the need for more evidence.","Mitchell EJ, Appelbe D, Bravery A, Culliford L, Evans H, Farrin AJ, Gillies K, Hood K, Love SB, Sydes MR, Williamson PR, Wakefield N, as part of the e-Consent collaborative group.",,Trials,2023,2023-10-10,Y,Consent; Clinical Trial; E-consent,,,"

Background

During the COVID-19 pandemic, in-person healthcare visits were reduced. Consequently, trial teams needed to consider implementing remote methods for conducting clinical trials, including e-Consent. Although some clinical trials may have implemented e-Consent prior to the pandemic, anecdotes of uptake for this method increased within academic-led trials. When the increased use of this process emerged, representatives from several large academic clinical trial groups within the UK collaborated to discuss ways in which trialists can learn from one another when implementing e-Consent.

Methods

A survey of UKCRC-registered Clinical Trials Units (CTUs) was undertaken in April-June 2021 to understand the implementation of and their views on the use of e-Consent and experiences from the perspectives of systems programmers and quality assurance staff on the use of e-Consent. CTUs not using e-Consent were asked to provide any reasons/barriers (including no suitable trials) and any plans for implementing it in the future. Two events for trialists and patient and public involvement (PPI) representatives were then held to disseminate findings, foster discussion, share experiences and aid in the identification of areas that the academic CTU community felt required more research.

Results

Thirty-four (64%) of 53 CTUs responded to the survey, with good geographical representation across the UK. Twenty-one (62%) of the responding CTUs had implemented e-Consent in at least one of their trials, across different types of trials, including CTIMPs (Clinical Trial of Investigational Medicinal Product), ATIMPs (Advanced Therapy Medicinal Products) and non-CTIMPs. One hundred ninety-seven participants attended the two workshops for wide-ranging discussions.

Conclusion

e-Consent is increasingly used in academic-led trials, yet uncertainties remain amongst trialists, patients and members of the public. Uncertainties include a lack of formal, practical guidance and a lack of evidence to demonstrate optimal or appropriate methods to use. We strongly encourage trialists to continue to share their own experiences of the implementation of e-Consent.",,doi:https://doi.org/10.1186/s13063-023-07656-8; html:https://europepmc.org/articles/PMC10565982; pdf:https://europepmc.org/articles/PMC10565982?pdf=render 38633019,https://doi.org/10.1002/lrh2.10391,ROAD2H: Development and evaluation of an open-source explainable artificial intelligence approach for managing co-morbidity and clinical guidelines.,"Domínguez J, Prociuk D, Marović B, Čyras K, Cocarascu O, Ruiz F, Mi E, Mi E, Ramtale C, Rago A, Darzi A, Toni F, Curcin V, Delaney B.",,Learning health systems,2024,2023-09-12,Y,Clinical Decision Support Systems; Argumentation; Fhir; Cds Hooks; Co‐morbidity; Transition‐based Medical Recommendation Model,,,"

Introduction

Clinical decision support (CDS) systems (CDSSs) that integrate clinical guidelines need to reflect real-world co-morbidity. In patient-specific clinical contexts, transparent recommendations that allow for contraindications and other conflicts arising from co-morbidity are a requirement. In this work, we develop and evaluate a non-proprietary, standards-based approach to the deployment of computable guidelines with explainable argumentation, integrated with a commercial electronic health record (EHR) system in Serbia, a middle-income country in West Balkans.

Methods

We used an ontological framework, the Transition-based Medical Recommendation (TMR) model, to represent, and reason about, guideline concepts, and chose the 2017 International global initiative for chronic obstructive lung disease (GOLD) guideline and a Serbian hospital as the deployment and evaluation site, respectively. To mitigate potential guideline conflicts, we used a TMR-based implementation of the Assumptions-Based Argumentation framework extended with preferences and Goals (ABA+G). Remote EHR integration of computable guidelines was via a microservice architecture based on HL7 FHIR and CDS Hooks. A prototype integration was developed to manage chronic obstructive pulmonary disease (COPD) with comorbid cardiovascular or chronic kidney diseases, and a mixed-methods evaluation was conducted with 20 simulated cases and five pulmonologists.

Results

Pulmonologists agreed 97% of the time with the GOLD-based COPD symptom severity assessment assigned to each patient by the CDSS, and 98% of the time with one of the proposed COPD care plans. Comments were favourable on the principles of explainable argumentation; inclusion of additional co-morbidities was suggested in the future along with customisation of the level of explanation with expertise.

Conclusion

An ontological model provided a flexible means of providing argumentation and explainable artificial intelligence for a long-term condition. Extension to other guidelines and multiple co-morbidities is needed to test the approach further.",,doi:https://doi.org/10.1002/lrh2.10391; html:https://europepmc.org/articles/PMC11019374; pdf:https://europepmc.org/articles/PMC11019374?pdf=render 37650026,https://doi.org/10.23889/ijpds.v7i1.1727,An overview of synthetic administrative data for research.,"Kokosi T, De Stavola B, Mitra R, Frayling L, Doherty A, Dove I, Sonnenberg P, Harron K.",,International journal of population data science,2022,2022-05-23,Y,Data Linkage; Statistical Disclosure Control; Data Utility; Synthetic Data; Data Confidentiality; Administrative Datasets,,,"Use of administrative data for research and for planning services has increased over recent decades due to the value of the large, rich information available. However, concerns about the release of sensitive or personal data and the associated disclosure risk can lead to lengthy approval processes and restricted data access. This can delay or prevent the production of timely evidence. A promising solution to facilitate more efficient data access is to create synthetic versions of the original datasets which are less likely to hold confidential information and can minimise disclosure risk. Such data may be used as an interim solution, allowing researchers to develop their analysis plans on non-disclosive data, whilst waiting for access to the real data. We aim to provide an overview of the background and uses of synthetic data and describe common methods used to generate synthetic data in the context of UK administrative research. We propose a simplified terminology for categories of synthetic data (univariate, multivariate, and complex modality synthetic data) as well as a more comprehensive description of the terminology used in the existing literature and illustrate challenges and future directions for research.",,pdf:https://ijpds.org/article/download/1727/3395; doi:https://doi.org/10.23889/ijpds.v7i1.1727; html:https://europepmc.org/articles/PMC10464868; pdf:https://europepmc.org/articles/PMC10464868?pdf=render -37043172,https://doi.org/10.1007/s12325-023-02511-3,Commentary: Patient Perspectives on Artificial Intelligence; What have We Learned and How Should We Move Forward?,"Camaradou JCL, Hogg HDJ.",,Advances in therapy,2023,2023-04-12,Y,Development; Artificial intelligence; Technology; Product; Clinical; Innovation; Patient; Perspectives; Engagement; Involvement; Acceptability; Public; Multi-stakeholder; Start-ups; Small Medium-sized Enterprises,,,"Artificial intelligence (AI) in healthcare has now begun to make its contributions to real-world patient care with varying degrees of both public and clinical acceptability around it. The heavy investment from governments, industry and academia needed to reach this point has helped to surface different perspectives on AI. As clinical AI applications become a reality, however, there is an increasing need to harness and integrate patient perspectives, which address the distinct needs of different populations, healthcare systems and clinical problems more closely. Despite this need, patient perspectives on AI implementation have little presence in academic literature and within implementation science and are not sufficiently considered throughout the MedTech and eHealthtech product development cycle, which brings its own challenges and opportunities. This joint patient expert/clinician commentary aims to briefly summarise views on AI. It reflects upon recommendations on how stakeholders such as clinicians and Health & MedTech small and medium-sized enterprises (SMEs) can make practical usage of these views. The recommendations of the authors centre around how to work better with patients to enable both product centric and patient centric innovation and person-centred care.",,pdf:https://link.springer.com/content/pdf/10.1007/s12325-023-02511-3.pdf; doi:https://doi.org/10.1007/s12325-023-02511-3; html:https://europepmc.org/articles/PMC10092909; pdf:https://europepmc.org/articles/PMC10092909?pdf=render 35304633,https://doi.org/10.1007/s00520-022-06976-w,An exploration of wellbeing in men diagnosed with prostate cancer undergoing active surveillance: a qualitative study.,"Eymech O, Brunckhorst O, Fox L, Jawaid A, Van Hemelrijck M, Stewart R, Dasgupta P, Ahmed K.",,Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer,2022,2022-03-19,Y,Quality of life; Mental health; prostate cancer; Active Surveillance; Mental Wellbeing; Psa Anxiety,,,"

Purpose

There is a growing emphasis on improving quality of life of people with prostate cancer. However, those undergoing active surveillance remain underrepresented in the literature with less known about their unique challenges. Therefore, we aimed to explore their lived experiences post diagnosis and its effect on their mental, social, and physical wellbeing.

Methods

Qualitative semi-structured interviews were conducted with 13 men undergoing active surveillance for low-risk disease. Thematic analysis was used to inductively co-construct themes through the lens of the biopsychosocial model.

Results

Mental wellbeing was strongly affected in our participants due to the overwhelming emotional impact of their diagnosis resulting in an 'Emotional Diagnostic Disequilibrium'. Informational awareness and education about prostate cancer helped patients with 'Recognition of the Impact'. Patients experienced an 'Unsettling Monitoring Cycle' due to the increased fear and anxiety around PSA monitoring appointments, with some men ignoring their mental wellbeing needs as their disease is 'A Future Problem'. 'Concealment of Diagnosis' left many feeling isolated and highlighted an important coping mechanisms in the 'Importance of a Social Support Network' theme. Finally, physical health mostly changed through alterations in health behaviour, leading to 'A Healthier Lifestyle' with increasing attribution of physical symptoms to age through 'Symptomatic Overshadowing'.

Conclusion

The greatest disease impact on men's wellbeing was at the time of diagnosis, with a subsequent cyclical anxiety and fear of disease progression prominent around monitoring appointments. Future research should explore ways to better support patients with these issues and at these times, improving their quality of life.",,pdf:https://link.springer.com/content/pdf/10.1007/s00520-022-06976-w.pdf; doi:https://doi.org/10.1007/s00520-022-06976-w; html:https://europepmc.org/articles/PMC8933126; pdf:https://europepmc.org/articles/PMC8933126?pdf=render +37043172,https://doi.org/10.1007/s12325-023-02511-3,Commentary: Patient Perspectives on Artificial Intelligence; What have We Learned and How Should We Move Forward?,"Camaradou JCL, Hogg HDJ.",,Advances in therapy,2023,2023-04-12,Y,Development; Artificial intelligence; Technology; Product; Clinical; Innovation; Patient; Perspectives; Engagement; Involvement; Acceptability; Public; Multi-stakeholder; Start-ups; Small Medium-sized Enterprises,,,"Artificial intelligence (AI) in healthcare has now begun to make its contributions to real-world patient care with varying degrees of both public and clinical acceptability around it. The heavy investment from governments, industry and academia needed to reach this point has helped to surface different perspectives on AI. As clinical AI applications become a reality, however, there is an increasing need to harness and integrate patient perspectives, which address the distinct needs of different populations, healthcare systems and clinical problems more closely. Despite this need, patient perspectives on AI implementation have little presence in academic literature and within implementation science and are not sufficiently considered throughout the MedTech and eHealthtech product development cycle, which brings its own challenges and opportunities. This joint patient expert/clinician commentary aims to briefly summarise views on AI. It reflects upon recommendations on how stakeholders such as clinicians and Health & MedTech small and medium-sized enterprises (SMEs) can make practical usage of these views. The recommendations of the authors centre around how to work better with patients to enable both product centric and patient centric innovation and person-centred care.",,pdf:https://link.springer.com/content/pdf/10.1007/s12325-023-02511-3.pdf; doi:https://doi.org/10.1007/s12325-023-02511-3; html:https://europepmc.org/articles/PMC10092909; pdf:https://europepmc.org/articles/PMC10092909?pdf=render 34173574,https://doi.org/10.1016/j.puhip.2020.100039,Schools and COVID-19: Reopening Pandora's box?,"Ziauddeen N, Woods-Townsend K, Saxena S, Gilbert R, Alwan NA.",,"Public health in practice (Oxford, England)",2020,2020-11-01,Y,Safety; Covid-19; School Re-Opening,,,"Schools in countries across the world are reopening as lockdown to slow progression of COVID-19 is eased. The UK government ordered school closures in England from March 20, 2020, later than the rest of Europe. A temporary and limited return for some year groups was trialled from June 2020. Teachers, school governors, the public and doctors have openly challenged the decision. The UK government has struggled to provide enough detailed information to convince the public, teachers and health practitioners, that effective systems for protection, including test, trace and isolate, are in place to prevent and manage outbreaks in schools. Risks of infection on reopening to children, staff and families must be weighed against the harms of closure to children's education and social development. The potential consequences, if the re-opening of schools is managed badly, is subsequent waves of COVID-19 infection leading to more deaths, further school closures and prolonged restrictions, losing any ground gained thus far. This article weighs the evidence for risks and benefits of reopening schools during the pandemic.",,doi:https://doi.org/10.1016/j.puhip.2020.100039; doi:https://doi.org/10.1016/j.puhip.2020.100039; html:https://europepmc.org/articles/PMC7486860; pdf:https://europepmc.org/articles/PMC7486860?pdf=render 36706770,https://doi.org/10.1016/s2214-109x(23)00007-4,Global investments in pandemic preparedness and COVID-19: development assistance and domestic spending on health between 1990 and 2026.,Global Burden of Disease 2021 Health Financing Collaborator Network.,,The Lancet. Global health,2023,2023-01-24,Y,,,,"

Background

The COVID-19 pandemic highlighted gaps in health surveillance systems, disease prevention, and treatment globally. Among the many factors that might have led to these gaps is the issue of the financing of national health systems, especially in low-income and middle-income countries (LMICs), as well as a robust global system for pandemic preparedness. We aimed to provide a comparative assessment of global health spending at the onset of the pandemic; characterise the amount of development assistance for pandemic preparedness and response disbursed in the first 2 years of the COVID-19 pandemic; and examine expectations for future health spending and put into context the expected need for investment in pandemic preparedness.

Methods

In this analysis of global health spending between 1990 and 2021, and prediction from 2021 to 2026, we estimated four sources of health spending: development assistance for health (DAH), government spending, out-of-pocket spending, and prepaid private spending across 204 countries and territories. We used the Organisation for Economic Co-operation and Development (OECD)'s Creditor Reporting System (CRS) and the WHO Global Health Expenditure Database (GHED) to estimate spending. We estimated development assistance for general health, COVID-19 response, and pandemic preparedness and response using a keyword search. Health spending estimates were combined with estimates of resources needed for pandemic prevention and preparedness to analyse future health spending patterns, relative to need.

Findings

In 2019, at the onset of the COVID-19 pandemic, US$9·2 trillion (95% uncertainty interval [UI] 9·1-9·3) was spent on health worldwide. We found great disparities in the amount of resources devoted to health, with high-income countries spending $7·3 trillion (95% UI 7·2-7·4) in 2019; 293·7 times the $24·8 billion (95% UI 24·3-25·3) spent by low-income countries in 2019. That same year, $43·1 billion in development assistance was provided to maintain or improve health. The pandemic led to an unprecedented increase in development assistance targeted towards health; in 2020 and 2021, $1·8 billion in DAH contributions was provided towards pandemic preparedness in LMICs, and $37·8 billion was provided for the health-related COVID-19 response. Although the support for pandemic preparedness is 12·2% of the recommended target by the High-Level Independent Panel (HLIP), the support provided for the health-related COVID-19 response is 252·2% of the recommended target. Additionally, projected spending estimates suggest that between 2022 and 2026, governments in 17 (95% UI 11-21) of the 137 LMICs will observe an increase in national government health spending equivalent to an addition of 1% of GDP, as recommended by the HLIP.

Interpretation

There was an unprecedented scale-up in DAH in 2020 and 2021. We have a unique opportunity at this time to sustain funding for crucial global health functions, including pandemic preparedness. However, historical patterns of underfunding of pandemic preparedness suggest that deliberate effort must be made to ensure funding is maintained.

Funding

Bill & Melinda Gates Foundation.",,pdf:http://www.thelancet.com/article/S2214109X23000074/pdf; doi:https://doi.org/10.1016/S2214-109X(23)00007-4; html:https://europepmc.org/articles/PMC9998276 35908569,https://doi.org/10.1016/s0140-6736(22)01109-6,"Baricitinib in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial and updated meta-analysis.",RECOVERY Collaborative Group.,,"Lancet (London, England)",2022,2022-07-01,Y,,,,"

Background

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

Methods

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

Findings

Between Feb 2 and Dec 29, 2021, from 10 852 enrolled, 8156 patients were randomly allocated to receive usual care plus baricitinib versus usual care alone. At randomisation, 95% of patients were receiving corticosteroids and 23% were receiving tocilizumab (with planned use within the next 24 h recorded for a further 9%). Overall, 514 (12%) of 4148 patients allocated to baricitinib versus 546 (14%) of 4008 patients allocated to usual care died within 28 days (age-adjusted rate ratio 0·87; 95% CI 0·77-0·99; p=0·028). This 13% proportional reduction in mortality was somewhat smaller than that seen in a meta-analysis of eight previous trials of a JAK inhibitor (involving 3732 patients and 425 deaths), in which allocation to a JAK inhibitor was associated with a 43% proportional reduction in mortality (rate ratio 0·57; 95% CI 0·45-0·72). Including the results from RECOVERY in an updated meta-analysis of all nine completed trials (involving 11 888 randomly assigned patients and 1485 deaths) allocation to baricitinib or another JAK inhibitor was associated with a 20% proportional reduction in mortality (rate ratio 0·80; 95% CI 0·72-0·89; p<0·0001). In RECOVERY, there was no significant excess in death or infection due to non-COVID-19 causes and no significant excess of thrombosis, or other safety outcomes.

Interpretation

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

Funding

UK Research and Innovation (Medical Research Council) and National Institute of Health Research.",,pdf:http://www.thelancet.com/article/S0140673622011096/pdf; doi:https://doi.org/10.1016/S0140-6736(22)01109-6; html:https://europepmc.org/articles/PMC9333998; pdf:https://europepmc.org/articles/PMC9333998?pdf=render @@ -746,11 +746,11 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 34468322,https://doi.org/10.2196/30083,An Early Warning Risk Prediction Tool (RECAP-V1) for Patients Diagnosed With COVID-19: Protocol for a Statistical Analysis Plan.,"Fiorentino F, Prociuk D, Espinosa Gonzalez AB, Neves AL, Husain L, Ramtale SC, Mi E, Mi E, Macartney J, Anand SN, Sherlock J, Saravanakumar K, Mayer E, de Lusignan S, Greenhalgh T, Delaney BC.",,JMIR research protocols,2021,2021-10-05,Y,Modeling; Early warning; Risk Score; Remote Assessment; Covid-19,,,"

Background

Since the start of the COVID-19 pandemic, efforts have been made to develop early warning risk scores to help clinicians decide which patient is likely to deteriorate and require hospitalization. The RECAP (Remote COVID-19 Assessment in Primary Care) study investigates the predictive risk of hospitalization, deterioration, and death of patients with confirmed COVID-19, based on a set of parameters chosen through a Delphi process performed by clinicians. We aim to use rich data collected remotely through the use of electronic data templates integrated in the electronic health systems of several general practices across the United Kingdom to construct accurate predictive models. The models will be based on preexisting conditions and monitoring data of a patient's clinical parameters (eg, blood oxygen saturation) to make reliable predictions as to the patient's risk of hospital admission, deterioration, and death.

Objective

This statistical analysis plan outlines the statistical methods to build the prediction model to be used in the prioritization of patients in the primary care setting. The statistical analysis plan for the RECAP study includes the development and validation of the RECAP-V1 prediction model as a primary outcome. This prediction model will be adapted as a three-category risk score split into red (high risk), amber (medium risk), and green (low risk) for any patient with suspected COVID-19. The model will predict the risk of deterioration and hospitalization.

Methods

After the data have been collected, we will assess the degree of missingness and use a combination of traditional data imputation using multiple imputation by chained equations, as well as more novel machine-learning approaches to impute the missing data for the final analysis. For predictive model development, we will use multiple logistic regression analyses to construct the model. We aim to recruit a minimum of 1317 patients for model development and validation. We will then externally validate the model on an independent dataset of 1400 patients. The model will also be applied for multiple different datasets to assess both its performance in different patient groups and its applicability for different methods of data collection.

Results

As of May 10, 2021, we have recruited 3732 patients. A further 2088 patients have been recruited through the National Health Service Clinical Assessment Service, and approximately 5000 patients have been recruited through the DoctalyHealth platform.

Conclusions

The methodology for the development of the RECAP-V1 prediction model as well as the risk score will provide clinicians with a statistically robust tool to help prioritize COVID-19 patients.

Trial registration

ClinicalTrials.gov NCT04435041; https://clinicaltrials.gov/ct2/show/NCT04435041.

International registered report identifier (irrid)

DERR1-10.2196/30083.",,pdf:https://www.researchprotocols.org/2021/10/e30083/PDF; doi:https://doi.org/10.2196/30083; html:https://europepmc.org/articles/PMC8494068 36001371,https://doi.org/10.2196/38122,Deployment of a Free-Text Analytics Platform at a UK National Health Service Research Hospital: CogStack at University College London Hospitals.,"Noor K, Roguski L, Bai X, Handy A, Klapaukh R, Folarin A, Romao L, Matteson J, Lea N, Zhu L, Asselbergs FW, Wong WK, Shah A, Dobson RJ.",,JMIR medical informatics,2022,2022-08-24,Y,Information Retrieval; Natural Language Processing; Text Mining; Electronic Health Record System; Clinical Support,,,"

Background

As more health care organizations transition to using electronic health record (EHR) systems, it is important for these organizations to maximize the secondary use of their data to support service improvement and clinical research. These organizations will find it challenging to have systems capable of harnessing the unstructured data fields in the record (clinical notes, letters, etc) and more practically have such systems interact with all of the hospital data systems (legacy and current).

Objective

We describe the deployment of the EHR interfacing information extraction and retrieval platform CogStack at University College London Hospitals (UCLH).

Methods

At UCLH, we have deployed the CogStack platform, an information retrieval platform with natural language processing capabilities. The platform addresses the problem of data ingestion and harmonization from multiple data sources using the Apache NiFi module for managing complex data flows. The platform also facilitates the extraction of structured data from free-text records through use of the MedCAT natural language processing library. Finally, data science tools are made available to support data scientists and the development of downstream applications dependent upon data ingested and analyzed by CogStack.

Results

The platform has been deployed at the hospital, and in particular, it has facilitated a number of research and service evaluation projects. To date, we have processed over 30 million records, and the insights produced from CogStack have informed a number of clinical research use cases at the hospital.

Conclusions

The CogStack platform can be configured to handle the data ingestion and harmonization challenges faced by a hospital. More importantly, the platform enables the hospital to unlock important clinical information from the unstructured portion of the record using natural language processing technology.",,pdf:https://medinform.jmir.org/2022/8/e38122/PDF; doi:https://doi.org/10.2196/38122; html:https://europepmc.org/articles/PMC9453582 37954687,https://doi.org/10.1177/20552076231211551,"Moving from development to implementation of digital innovations within the NHS: myHealthE, a remote monitoring system for tracking patient outcomes in child and adolescent mental health services.","Morris AC, Ibrahim Z, Moghraby OS, Stringaris A, Grant IM, Zalewski L, McClellan S, Moriarty G, Simonoff E, Dobson RJ, Downs J.",,Digital health,2023,2023-01-01,Y,Health; Medicine; Psychology; Mental health; general; Studies; Paediatrics; Outcomes; Wellbeing; Mixed Methods; Online; Personalised Medicine; Mhealth; Electronic; Digital Health,,,"

Objective

This paper aims to report our experience of developing, implementing, and evaluating myHealthE (MHE), a digital innovation for Child and Adolescents Mental Health Services (CAMHS), which automates the remote collection and reporting of Patient-Reported Outcome Measures (PROMs) into National Health Services (NHS) electronic healthcare records.

Methods

We describe the logistical and governance issues encountered in developing the MHE interface with patient-identifiable information, and the steps taken to overcome these development barriers. We describe the application's architecture and hosting environment to enable its operability within the NHS, as well as the capabilities needed within the technical team to bridge the gap between academic development and NHS operational teams.

Results

We present evidence on the feasibility and acceptability of this system within clinical services and the process of iterative development, highlighting additional functions that were incorporated to increase system utility.

Conclusion

This article provides a framework with which to plan, develop, and implement automated PROM collection from remote devices back to NHS infrastructure. The challenges and solutions described in this paper will be pertinent to other digital health innovation researchers aspiring to deploy interoperable systems within NHS clinical systems.",,doi:https://doi.org/10.1177/20552076231211551; html:https://europepmc.org/articles/PMC10638880; pdf:https://europepmc.org/articles/PMC10638880?pdf=render -36962407,https://doi.org/10.1371/journal.pgph.0000292,Health worker experiences of implementing TB infection prevention and control: A qualitative evidence synthesis to inform implementation recommendations.,"van der Westhuizen HM, Dorward J, Roberts N, Greenhalgh T, Ehrlich R, Butler CC, Tonkin-Crine S.",,PLOS global public health,2022,2022-07-07,Y,,,,"Implementation of TB infection prevention and control (IPC) measures in health facilities is frequently inadequate, despite nosocomial TB transmission to patients and health workers causing harm. We aimed to review qualitative evidence of the complexity associated with implementing TB IPC, to help guide the development of TB IPC implementation plans. We undertook a qualitative evidence synthesis of studies that used qualitative methods to explore the experiences of health workers implementing TB IPC in health facilities. We searched eight databases in November 2021, complemented by citation tracking. Two reviewers screened titles and abstracts and reviewed full texts of potentially eligible papers. We used the Critical Appraisals Skills Programme checklist for quality appraisal, thematic synthesis to identify key findings and the GRADE-CERQual method to appraise the certainty of review findings. The review protocol was pre-registered on PROSPERO, ID CRD42020165314. We screened 1062 titles and abstracts and reviewed 102 full texts, with 37 studies included in the synthesis. We developed 10 key findings, five of which we had high confidence in. We describe several components of TB IPC as a complex intervention. Health workers were influenced by their personal occupational TB risk perceptions when deciding whether to implement TB IPC and neglected the contribution of TB IPC to patient safety. Health workers and researchers expressed multiple uncertainties (for example the duration of infectiousness of people with TB), assumptions and misconceptions about what constitutes effective TB IPC, including focussing TB IPC on patients known with TB on treatment who pose a small risk of transmission. Instead, TB IPC resources should target high risk areas for transmission (crowded, poorly ventilated spaces). Furthermore, TB IPC implementation plans should support health workers to translate TB IPC guidelines to local contexts, including how to navigate unintended stigma caused by IPC, and using limited IPC resources effectively.",,pdf:https://journals.plos.org/globalpublichealth/article/file?id=10.1371/journal.pgph.0000292&type=printable; doi:https://doi.org/10.1371/journal.pgph.0000292; html:https://europepmc.org/articles/PMC10021216; pdf:https://europepmc.org/articles/PMC10021216?pdf=render 32838035,https://doi.org/10.1002/lrh2.10236,Rapid translation of clinical guidelines into executable knowledge: A case study of COVID-19 and online demonstration.,"Fox J, Khan O, Curtis H, Wright A, Pal C, Cockburn N, Cooper J, Chandan JS, Nirantharakumar K.",,Learning health systems,2021,2020-07-14,Y,Artificial intelligence; Covid‐19; Rapid Learning Systems,,,"

Introduction

We report a pathfinder study of AI/knowledge engineering methods to rapidly formalise COVID-19 guidelines into an executable model of decision making and care pathways. The knowledge source for the study was material published by BMJ Best Practice in March 2020.

Methods

The PROforma guideline modelling language and OpenClinical.net authoring and publishing platform were used to create a data model for care of COVID-19 patients together with executable models of rules, decisions and plans that interpret patient data and give personalised care advice.

Results

PROforma and OpenClinical.net proved to be an effective combination for rapidly creating the COVID-19 model; the Pathfinder 1 demonstrator is available for assessment at https://www.openclinical.net/index.php?id=746.

Conclusions

This is believed to be the first use of AI/knowledge engineering methods for disseminating best-practice in COVID-19 care. It demonstrates a novel and promising approach to the rapid translation of clinical guidelines into point of care services, and a foundation for rapid learning systems in many areas of healthcare.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/lrh2.10236; doi:https://doi.org/10.1002/lrh2.10236; html:https://europepmc.org/articles/PMC7323421; pdf:https://europepmc.org/articles/PMC7323421?pdf=render +36962407,https://doi.org/10.1371/journal.pgph.0000292,Health worker experiences of implementing TB infection prevention and control: A qualitative evidence synthesis to inform implementation recommendations.,"van der Westhuizen HM, Dorward J, Roberts N, Greenhalgh T, Ehrlich R, Butler CC, Tonkin-Crine S.",,PLOS global public health,2022,2022-07-07,Y,,,,"Implementation of TB infection prevention and control (IPC) measures in health facilities is frequently inadequate, despite nosocomial TB transmission to patients and health workers causing harm. We aimed to review qualitative evidence of the complexity associated with implementing TB IPC, to help guide the development of TB IPC implementation plans. We undertook a qualitative evidence synthesis of studies that used qualitative methods to explore the experiences of health workers implementing TB IPC in health facilities. We searched eight databases in November 2021, complemented by citation tracking. Two reviewers screened titles and abstracts and reviewed full texts of potentially eligible papers. We used the Critical Appraisals Skills Programme checklist for quality appraisal, thematic synthesis to identify key findings and the GRADE-CERQual method to appraise the certainty of review findings. The review protocol was pre-registered on PROSPERO, ID CRD42020165314. We screened 1062 titles and abstracts and reviewed 102 full texts, with 37 studies included in the synthesis. We developed 10 key findings, five of which we had high confidence in. We describe several components of TB IPC as a complex intervention. Health workers were influenced by their personal occupational TB risk perceptions when deciding whether to implement TB IPC and neglected the contribution of TB IPC to patient safety. Health workers and researchers expressed multiple uncertainties (for example the duration of infectiousness of people with TB), assumptions and misconceptions about what constitutes effective TB IPC, including focussing TB IPC on patients known with TB on treatment who pose a small risk of transmission. Instead, TB IPC resources should target high risk areas for transmission (crowded, poorly ventilated spaces). Furthermore, TB IPC implementation plans should support health workers to translate TB IPC guidelines to local contexts, including how to navigate unintended stigma caused by IPC, and using limited IPC resources effectively.",,pdf:https://journals.plos.org/globalpublichealth/article/file?id=10.1371/journal.pgph.0000292&type=printable; doi:https://doi.org/10.1371/journal.pgph.0000292; html:https://europepmc.org/articles/PMC10021216; pdf:https://europepmc.org/articles/PMC10021216?pdf=render 37798805,https://doi.org/10.1186/s13063-023-07576-7,"Medicines and Healthcare products Regulatory Agency's ""Consultation on proposals for legislative changes for clinical trials"": a response from the Trials Methodology Research Partnership Adaptive Designs Working Group, with a focus on data sharing.","Law M, Couturier DL, Choodari-Oskooei B, Crout P, Gamble C, Jacko P, Pallmann P, Pilling M, Robertson DS, Robling M, Sydes MR, Villar SS, Wason J, Wheeler G, Williamson SF, Yap C, Jaki T.",,Trials,2023,2023-10-05,Y,Legislation; data sharing; Consultation,,,"In the UK, the Medicines and Healthcare products Regulatory Agency consulted on proposals ""to improve and strengthen the UK clinical trials legislation to help us make the UK the best place to research and develop safe and innovative medicines"". The purpose of the consultation was to help finalise the proposals and contribute to the drafting of secondary legislation. We discussed these proposals as members of the Trials Methodology Research Partnership Adaptive Designs Working Group, which is jointly funded by the Medical Research Council and the National Institute for Health and Care Research. Two topics arose frequently in the discussion: the emphasis on legislation, and the absence of questions on data sharing. It is our opinion that the proposals rely heavily on legislation to change practice. However, clinical trials are heterogeneous, and as a result some trials will struggle to comply with all of the proposed legislation. Furthermore, adaptive design clinical trials are even more heterogeneous than their non-adaptive counterparts, and face more challenges. Consequently, it is possible that increased legislation could have a greater negative impact on adaptive designs than non-adaptive designs. Overall, we are sceptical that the introduction of legislation will achieve the desired outcomes, with some exceptions. Meanwhile the topic of data sharing - making anonymised individual-level clinical trial data available to other investigators for further use - is entirely absent from the proposals and the consultation in general. However, as an aspect of the wider concept of open science and reproducible research, data sharing is an increasingly important aspect of clinical trials. The benefits of data sharing include faster innovation, improved surveillance of drug safety and effectiveness and decreasing participant exposure to unnecessary risk. There are already a number of UK-focused documents that discuss and encourage data sharing, for example, the Concordat on Open Research Data and the Medical Research Council's Data Sharing Policy. We strongly suggest that data sharing should be the norm rather than the exception, and hope that the forthcoming proposals on clinical trials invite discussion on this important topic.",,pdf:https://trialsjournal.biomedcentral.com/counter/pdf/10.1186/s13063-023-07576-7; doi:https://doi.org/10.1186/s13063-023-07576-7; html:https://europepmc.org/articles/PMC10552399; pdf:https://europepmc.org/articles/PMC10552399?pdf=render -36810190,https://doi.org/10.1136/bmjebm-2023-112253,Digitally enabled decentralised research: opportunities to improve the efficiency of clinical trials and observational studies.,"Aiyegbusi OL, Davies EH, Myles P, Williams T, Frost C, Haroon S, Hughes SE, Wilson R, McMullan C, Subramanian A, Nirantharakumar K, Calvert MJ.",,BMJ evidence-based medicine,2023,2023-02-21,Y,information technology; drug discovery; Drug Development; Covid-19,,,,,pdf:https://ebm.bmj.com/content/ebmed/early/2023/02/20/bmjebm-2023-112253.full.pdf; doi:https://doi.org/10.1136/bmjebm-2023-112253; html:https://europepmc.org/articles/PMC10579468; pdf:https://europepmc.org/articles/PMC10579468?pdf=render 33939619,https://doi.org/10.2196/29072,Predicting Risk of Hospital Admission in Patients With Suspected COVID-19 in a Community Setting: Protocol for Development and Validation of a Multivariate Risk Prediction Tool.,"Espinosa-Gonzalez AB, Neves AL, Fiorentino F, Prociuk D, Husain L, Ramtale SC, Mi E, Mi E, Macartney J, Anand SN, Sherlock J, Saravanakumar K, Mayer E, de Lusignan S, Greenhalgh T, Delaney BC.",,JMIR research protocols,2021,2021-05-25,Y,Primary Care; Hospital Admission; Electronic Health Records; Early Warning Score; Risk Prediction Tool; Covid-19 Severity,,,"

Background

During the pandemic, remote consultations have become the norm for assessing patients with signs and symptoms of COVID-19 to decrease the risk of transmission. This has intensified the clinical uncertainty already experienced by primary care clinicians when assessing patients with suspected COVID-19 and has prompted the use of risk prediction scores, such as the National Early Warning Score (NEWS2), to assess severity and guide treatment. However, the risk prediction tools available have not been validated in a community setting and are not designed to capture the idiosyncrasies of COVID-19 infection.

Objective

The objective of this study is to produce a multivariate risk prediction tool, RECAP-V1 (Remote COVID-19 Assessment in Primary Care), to support primary care clinicians in the identification of those patients with COVID-19 that are at higher risk of deterioration and facilitate the early escalation of their treatment with the aim of improving patient outcomes.

Methods

The study follows a prospective cohort observational design, whereby patients presenting in primary care with signs and symptoms suggestive of COVID-19 will be followed and their data linked to hospital outcomes (hospital admission and death). Data collection will be carried out by primary care clinicians in four arms: North West London Clinical Commissioning Groups (NWL CCGs), Oxford-Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC), Covid Clinical Assessment Service (CCAS), and South East London CCGs (Doctaly platform). The study involves the use of an electronic template that incorporates a list of items (known as RECAP-V0) thought to be associated with disease outcome according to previous qualitative work. Data collected will be linked to patient outcomes in highly secure environments. We will then use multivariate logistic regression analyses for model development and validation.

Results

Recruitment of participants started in October 2020. Initially, only the NWL CCGs and RCGP RSC arms were active. As of March 24, 2021, we have recruited a combined sample of 3827 participants in these two arms. CCAS and Doctaly joined the study in February 2021, with CCAS starting the recruitment process on March 15, 2021. The first part of the analysis (RECAP-V1 model development) is planned to start in April 2021 using the first half of the NWL CCGs and RCGP RSC combined data set. Posteriorly, the model will be validated with the rest of the NWL CCGs and RCGP RSC data as well as the CCAS and Doctaly data sets. The study was approved by the Research Ethics Committee on May 27, 2020 (Integrated Research Application System number: 283024, Research Ethics Committee reference number: 20/NW/0266) and badged as National Institute of Health Research Urgent Public Health Study on October 14, 2020.

Conclusions

We believe the validated RECAP-V1 early warning score will be a valuable tool for the assessment of severity in patients with suspected COVID-19 in the community, either in face-to-face or remote consultations, and will facilitate the timely escalation of treatment with the potential to improve patient outcomes.

Trial registration

ISRCTN registry ISRCTN13953727; https://www.isrctn.com/ISRCTN13953727.

International registered report identifier (irrid)

DERR1-10.2196/29072.",,pdf:https://jmir.org/api/download?alt_name=resprot_v10i5e29072_app1.pdf&filename=e079f888f9036dd40808005eb7b49b6f.pdf; doi:https://doi.org/10.2196/29072; html:https://europepmc.org/articles/PMC8153031 +36810190,https://doi.org/10.1136/bmjebm-2023-112253,Digitally enabled decentralised research: opportunities to improve the efficiency of clinical trials and observational studies.,"Aiyegbusi OL, Davies EH, Myles P, Williams T, Frost C, Haroon S, Hughes SE, Wilson R, McMullan C, Subramanian A, Nirantharakumar K, Calvert MJ.",,BMJ evidence-based medicine,2023,2023-02-21,Y,information technology; drug discovery; Drug Development; Covid-19,,,,,pdf:https://ebm.bmj.com/content/ebmed/early/2023/02/20/bmjebm-2023-112253.full.pdf; doi:https://doi.org/10.1136/bmjebm-2023-112253; html:https://europepmc.org/articles/PMC10579468; pdf:https://europepmc.org/articles/PMC10579468?pdf=render 37367415,https://doi.org/10.3390/jcdd10060250,Risk Factors of Secondary Cardiovascular Events in a Multi-Ethnic Asian Population with Acute Myocardial Infarction: A Retrospective Cohort Study from Malaysia.,"Ismail SR, Mohammad MSF, Butterworth AS, Chowdhury R, Danesh J, Di Angelantonio E, Griffin SJ, Pennells L, Wood AM, Md Noh MF, Shah SA.",,Journal of cardiovascular development and disease,2023,2023-06-09,Y,Myocardial infarction; risk factors; Asian; Cardiovascular Mortality; Major Adverse Cardiovascular Events,,,"This retrospective cohort study investigated the incidence and risk factors of major adverse cardiovascular events (MACE) after 1 year of first-documented myocardial infarctions (MIs) in a multi-ethnic Asian population. Secondary MACE were observed in 231 (14.3%) individuals, including 92 (5.7%) cardiovascular-related deaths. Both histories of hypertension and diabetes were associated with secondary MACE after adjustment for age, sex, and ethnicity (HR 1.60 [95%CI 1.22-2.12] and 1.46 [95%CI 1.09-1.97], respectively). With further adjustments for traditional risk factors, individuals with conduction disturbances demonstrated higher risks of MACE: new left-bundle branch block (HR 2.86 [95%CI 1.15-6.55]), right-bundle branch block (HR 2.09 [95%CI 1.02-4.29]), and second-degree heart block (HR 2.45 [95%CI 0.59-10.16]). These associations were broadly similar across different age, sex, and ethnicity groups, although somewhat greater for history of hypertension and BMI among women versus men, for HbA1c control in individuals aged >50 years, and for LVEF ≤ 40% in those with Indian versus Chinese or Bumiputera ethnicities. Several traditional and cardiac risk factors are associated with a higher risk of secondary major adverse cardiovascular events. In addition to hypertension and diabetes, the identification of conduction disturbances in individuals with first-onset MI may be useful for the risk stratification of high-risk individuals.",,pdf:https://www.mdpi.com/2308-3425/10/6/250/pdf?version=1686288586; doi:https://doi.org/10.3390/jcdd10060250; html:https://europepmc.org/articles/PMC10299045; pdf:https://europepmc.org/articles/PMC10299045?pdf=render 33602244,https://doi.org/10.1186/s12916-021-01924-7,The impact of local and national restrictions in response to COVID-19 on social contacts in England: a longitudinal natural experiment.,"Jarvis CI, Gimma A, van Zandvoort K, Wong KLM, CMMID COVID-19 working group, Edmunds WJ.",,BMC medicine,2021,2021-02-19,Y,Pandemic; England; United Kingdom; Disease Outbreak; Non-pharmaceutical Interventions; Covid-19; Contact Survey; Lockdowns,,,"

Background

England's COVID-19 response transitioned from a national lockdown to localised interventions. In response to rising cases, these were supplemented by national restrictions on contacts (the Rule of Six), then 10 pm closing for bars and restaurants, and encouragement to work from home. These were quickly followed by a 3-tier system applying different restrictions in different localities. As cases continued to rise, a second national lockdown was declared. We used a national survey to quantify the impact of these restrictions on epidemiologically relevant contacts.

Methods

We compared paired measures on setting-specific contacts before and after each restriction started and tested for differences using paired permutation tests on the mean change in contacts and the proportion of individuals decreasing their contacts.

Results

Following the imposition of each measure, individuals tended to report fewer contacts than they had before. However, the magnitude of the changes was relatively small and variable. For instance, although early closure of bars and restaurants appeared to have no measurable effect on contacts, the work from home directive reduced mean daily work contacts by 0.99 (95% confidence interval CI] 0.03-1.94), and the Rule of Six reduced non-work and school contacts by a mean of 0.25 (0.01-0.5) per day. Whilst Tier 3 appeared to also reduce non-work and school contacts, the evidence for an effect of the lesser restrictions (Tiers 1 and 2) was much weaker. There may also have been some evidence of saturation of effects, with those who were in Tier 1 (least restrictive) reducing their contacts markedly when they entered lockdown, which was not reflected in similar changes in those who were already under tighter restrictions (Tiers 2 and 3).

Conclusions

The imposition of various local and national measures in England during the summer and autumn of 2020 has gradually reduced contacts. However, these changes are smaller than the initial lockdown in March. This may partly be because many individuals were already starting from a lower number of contacts.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-021-01924-7; doi:https://doi.org/10.1186/s12916-021-01924-7; html:https://europepmc.org/articles/PMC7892289; pdf:https://europepmc.org/articles/PMC7892289?pdf=render 37456658,https://doi.org/10.12688/hrbopenres.13667.1,Qualitative data sharing practices in clinical trials in the UK and Ireland: towards the production of good practice guidance.,"McCarthy M, Gillies K, Rousseau N, Wade J, Gamble C, Toomey E, Matvienko-Sikar K, Sydes M, Dowling M, Bryant V, Biesty L, Houghton C.",,HRB open research,2023,2023-02-06,Y,data sharing; Qualitative; trials; Focus Groups,,,"Background: Data sharing enables researchers to conduct novel research with previously collected datasets, thus maximising scientific findings and cost effectiveness, and reducing research waste. The value of sharing, even de-identified, quantitative data from clinical trials is well recognised with a moderated access approach recommended. While substantial challenges to sharing quantitative data remain, there are additional challenges for sharing qualitative data in trials. Incorporating the necessary information about how qualitative data will be shared into already complex trial recruitment and consent processes proves challenging. The aim of this study was to explore whether and how trial teams share qualitative data collected as part of the design, conduct, analysis, or delivery of clinical trials. Methods: Phase 1 involved semi-structured, in-depth qualitative interviews and focus groups with key trial stakeholder groups including trial managers and clinical trialists (n=3), qualitative researchers in trials (n=9), members of research funding bodies (n=2) and trial participants (n=1). Data were analysed using thematic analysis. In Phase 2, we conducted a content analysis of 16 participant information leaflets (PIL) and consent forms (CF) for trials that collected qualitative data. Results: Three key themes were identified from our Phase 1 findings: ' Understanding and experiences of the potential benefits of sharing qualitative data from trials', 'Concerns about qualitative data sharing', and ' Future guidance and funding'. In phase 2, the PILs and CFs received revealed that the benefits of data sharing for participants were only explained in two of the study documents. Conclusions: The value of sharing qualitative data was acknowledged, but there are many uncertainties as to how, when, and where to share this data. In addition, there were ethical concerns in relation to the consent process required for qualitative data sharing in trials. This study provides insight into the existing practice of qualitative data sharing in trials.",,pdf:https://hrbopenresearch.org/articles/6-10/pdf; doi:https://doi.org/10.12688/hrbopenres.13667.1; html:https://europepmc.org/articles/PMC10345597; pdf:https://europepmc.org/articles/PMC10345597?pdf=render @@ -772,8 +772,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 35297548,https://doi.org/10.1002/humu.24369,"Beacon v2 and Beacon networks: A ""lingua franca"" for federated data discovery in biomedical genomics, and beyond.","Rambla J, Baudis M, Ariosa R, Beck T, Fromont LA, Navarro A, Paloots R, Rueda M, Saunders G, Singh B, Spalding JD, Törnroos J, Vasallo C, Veal CD, Brookes AJ.",,Human mutation,2022,2022-04-08,Y,data sharing; Clinical Genomics; Beacon; Data Discovery; Rest Api; Ga4gh,,,"Beacon is a basic data discovery protocol issued by the Global Alliance for Genomics and Health (GA4GH). The main goal addressed by version 1 of the Beacon protocol was to test the feasibility of broadly sharing human genomic data, through providing simple ""yes"" or ""no"" responses to queries about the presence of a given variant in datasets hosted by Beacon providers. The popularity of this concept has fostered the design of a version 2, that better serves real-world requirements and addresses the needs of clinical genomics research and healthcare, as assessed by several contributing projects and organizations. Particularly, rare disease genetics and cancer research will benefit from new case level and genomic variant level requests and the enabling of richer phenotype and clinical queries as well as support for fuzzy searches. Beacon is designed as a ""lingua franca"" to bridge data collections hosted in software solutions with different and rich interfaces. Beacon version 2 works alongside popular standards like Phenopackets, OMOP, or FHIR, allowing implementing consortia to return matches in beacon responses and provide a handover to their preferred data exchange format. The protocol is being explored by other research domains and is being tested in several international projects.",,pdf:http://repositori.upf.edu/bitstream/10230/53310/1/Rambla_2022.pdf; doi:https://doi.org/10.1002/humu.24369; html:https://europepmc.org/articles/PMC9322265; pdf:https://europepmc.org/articles/PMC9322265?pdf=render 36764723,https://doi.org/10.1136/bmjopen-2022-067254,Associations of remote mental healthcare with clinical outcomes: a natural language processing enriched electronic health record data study protocol.,"Ahmed MS, Kornblum D, Oliver D, Fusar-Poli P, Patel R.",,BMJ open,2023,2023-02-10,Y,Psychiatry; epidemiology; Telemedicine; Health Informatics,,,"

Introduction

People often experience significant difficulties in receiving mental healthcare due to insufficient resources, stigma and lack of access to care. Remote care technology has the potential to overcome these barriers by reducing travel time and increasing frequency of contact with patients. However, the safe delivery of remote mental healthcare requires evidence on which aspects of care are suitable for remote delivery and which are better served by in-person care. We aim to investigate clinical and demographic associations with remote mental healthcare in a large electronic health record (EHR) dataset and the degree to which remote care is associated with differences in clinical outcomes using natural language processing (NLP) derived EHR data.

Methods and analysis

Deidentified EHR data, derived from the South London and Maudsley (SLaM) National Health Service Foundation Trust Biomedical Research Centre (BRC) Case Register, will be extracted using the Clinical Record Interactive Search tool for all patients receiving mental healthcare between 1 January 2019 and 31 March 2022. First, data on a retrospective, longitudinal cohort of around 80 000 patients will be analysed using descriptive statistics to investigate clinical and demographic associations with remote mental healthcare and multivariable Cox regression to compare clinical outcomes of remote versus in-person assessments. Second, NLP models that have been previously developed to extract mental health symptom data will be applied to around 5 million documents to analyse the variation in content of remote versus in-person assessments.

Ethics and dissemination

The SLaM BRC Case Register and Clinical Record Interactive Search (CRIS) tool have received ethical approval as a deidentified dataset (including NLP-derived data from unstructured free text documents) for secondary mental health research from Oxfordshire REC C (Ref: 18/SC/0372). The study has received approval from the SLaM CRIS Oversight Committee. Study findings will be disseminated through peer-reviewed, open access journal articles and service user and carer advisory groups.",,pdf:https://bmjopen.bmj.com/content/bmjopen/13/2/e067254.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-067254; html:https://europepmc.org/articles/PMC9923317; pdf:https://europepmc.org/articles/PMC9923317?pdf=render 35477868,https://doi.org/10.1136/bmjopen-2021-057579,Public opinion on sharing data from health services for clinical and research purposes without explicit consent: an anonymous online survey in the UK.,"Jones LA, Nelder JR, Fryer JM, Alsop PH, Geary MR, Prince M, Cardinal RN.",,BMJ open,2022,2022-04-27,Y,Information management; Mental health; Health Policy; Health Informatics,,,"

Objectives

UK National Health Service/Health and Social Care (NHS/HSC) data are variably shared between healthcare organisations for direct care, and increasingly de-identified for research. Few large-scale studies have examined public opinion on sharing, including of mental health (MH) versus physical health (PH) data. We measured data sharing preferences.

Design/setting/interventions/outcomes

Pre-registered anonymous online survey, measuring expressed preferences, recruiting February to September 2020. Participants were randomised to one of three framing statements regarding MH versus PH data.

Participants

Open to all UK residents. Participants numbered 29 275; 40% had experienced an MH condition.

Results

Most (76%) supported identifiable data sharing for direct clinical care without explicit consent, but 20% opposed this. Preference for clinical/identifiable sharing decreased with geographical distance and was slightly less for MH than PH data, with small framing effects. Preference for research/de-identified data sharing without explicit consent showed the same small PH/MH and framing effects, plus greater preference for sharing structured data than de-identified free text. There was net support for research sharing to the NHS, academic institutions, and national research charities, net ambivalence about sharing to profit-making companies researching treatments, and net opposition to sharing to other companies (similar to sharing publicly). De-identified linkage to non-health data was generally supported, except to data held by private companies. We report demographic influences on preference. A majority (89%) supported a single NHS mechanism to choose uses of their data. Support for data sharing increased during COVID-19.

Conclusions

Support for healthcare data sharing for direct care without explicit consent is broad but not universal. There is net support for the sharing of de-identified data for research to the NHS, academia, and the charitable sector, but not the commercial sector. A single national NHS-hosted system for patients to control the use of their NHS data for clinical purposes and for research would have broad support.

Trial registration number

ISRCTN37444142.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/4/e057579.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-057579; html:https://europepmc.org/articles/PMC9058801; pdf:https://europepmc.org/articles/PMC9058801?pdf=render -38595770,https://doi.org/10.2147/clep.s437937,"A Harmonised Approach to Curating Research-Ready Datasets for Asthma, Chronic Obstructive Pulmonary Disease (COPD) and Interstitial Lung Disease (ILD) in England, Wales and Scotland Using Clinical Practice Research Datalink (CPRD), Secure Anonymised Information Linkage (SAIL) Databank and DataLoch.","Hatam S, Scully ST, Cook S, Evans HT, Hume A, Kallis C, Farr I, Orton C, Sheikh A, Quint JK.",,Clinical epidemiology,2024,2024-04-04,Y,Asthma; COPD; Harmonisation; Data Curation; Her; Ild,,,"

Background

Electronic healthcare records (EHRs) are an important resource for health research that can be used to improve patient outcomes in chronic respiratory diseases. However, consistent approaches in the analysis of these datasets are needed for coherent messaging, and when undertaking comparative studies across different populations.

Methods and results

We developed a harmonised curation approach to generate comparable patient cohorts for asthma, chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD) using datasets from within Clinical Practice Research Datalink (CPRD; for England), Secure Anonymised Information Linkage (SAIL; for Wales) and DataLoch (for Scotland) by defining commonly derived variables consistently between the datasets. By working in parallel on the curation methodology used for CPRD, SAIL and DataLoch for asthma, COPD and ILD, we were able to highlight key differences in coding and recording between the databases and identify solutions to enable valid comparisons.

Conclusion

Codelists and metadata generated have been made available to help re-create the asthma, COPD and ILD cohorts in CPRD, SAIL and DataLoch for different time periods, and provide a starting point for the curation of respiratory datasets in other EHR databases, expediting further comparable respiratory research.",,doi:https://doi.org/10.2147/CLEP.S437937; html:https://europepmc.org/articles/PMC11002787; pdf:https://europepmc.org/articles/PMC11002787?pdf=render 35130878,https://doi.org/10.1186/s12916-022-02234-2,"Lifetime risk of cardiovascular-renal disease in type 2 diabetes: a population-based study in 473,399 individuals.","Zhang R, Mamza JB, Morris T, Godfrey G, Asselbergs FW, Denaxas S, Hemingway H, Banerjee A.",,BMC medicine,2022,2022-02-07,Y,Kidney; Type 2 diabetes; lifetime; Attributable Risk; Population Health; cardiovascular,,,"

Background

Cardiovascular and renal diseases (CVRD) are major causes of mortality in individuals with type 2 diabetes (T2D). Studies of lifetime risk have neither considered all CVRD together nor the relative contribution of major risk factors to combined disease burden.

Methods

In a population-based cohort study using national electronic health records, we studied 473,399 individuals with T2D in England 2007-2018. Lifetime risk of individual and combined major adverse renal cardiovascular events, MARCE (including CV death and CVRD: heart failure; chronic kidney disease; myocardial infarction; stroke or peripheral artery disease), were estimated, accounting for baseline CVRD status and competing risk of death. We calculated population attributable risk for individual CVRD components. Ideal cardiovascular health was defined by blood pressure, cholesterol, glucose, smoking, physical activity, diet, and body mass index (i.e. modifiable risk factors).

Results

In individuals with T2D, lifetime risk of MARCE was 80% in those free from CVRD and was 97%, 93%, 98%, 89% and 91% in individuals with heart failure, chronic kidney disease, myocardial infarction, stroke and peripheral arterial disease, respectively at baseline. Among CVRD-free individuals, lifetime risk of chronic kidney disease was highest (54%), followed by CV death (41%), heart failure (29%), stroke (20%), myocardial infarction (19%) and peripheral arterial disease (9%). In those with HF only, 75% of MARCE after index T2D can be attributed to HF after adjusting for age, gender, and comorbidities. Compared with those with > 1, < 3 and ≥3 modifiable health risk behaviours, achieving ideal cardiovascular health could reduce MARCE by approximately 41.5%, 23.6% and 17.2%, respectively, in the T2D population.

Conclusions

Four out of five individuals with T2D free from CVRD, and nearly all those with history of CVRD, will develop MARCE over their lifetime. Early preventive measures in T2D patients are clinical, public health and policy priorities.",,pdf:https://bmcmedicine.biomedcentral.com/track/pdf/10.1186/s12916-022-02234-2; doi:https://doi.org/10.1186/s12916-022-02234-2; html:https://europepmc.org/articles/PMC8822817; pdf:https://europepmc.org/articles/PMC8822817?pdf=render +38595770,https://doi.org/10.2147/clep.s437937,"A Harmonised Approach to Curating Research-Ready Datasets for Asthma, Chronic Obstructive Pulmonary Disease (COPD) and Interstitial Lung Disease (ILD) in England, Wales and Scotland Using Clinical Practice Research Datalink (CPRD), Secure Anonymised Information Linkage (SAIL) Databank and DataLoch.","Hatam S, Scully ST, Cook S, Evans HT, Hume A, Kallis C, Farr I, Orton C, Sheikh A, Quint JK.",,Clinical epidemiology,2024,2024-04-04,Y,Asthma; COPD; Harmonisation; Data Curation; Her; Ild,,,"

Background

Electronic healthcare records (EHRs) are an important resource for health research that can be used to improve patient outcomes in chronic respiratory diseases. However, consistent approaches in the analysis of these datasets are needed for coherent messaging, and when undertaking comparative studies across different populations.

Methods and results

We developed a harmonised curation approach to generate comparable patient cohorts for asthma, chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD) using datasets from within Clinical Practice Research Datalink (CPRD; for England), Secure Anonymised Information Linkage (SAIL; for Wales) and DataLoch (for Scotland) by defining commonly derived variables consistently between the datasets. By working in parallel on the curation methodology used for CPRD, SAIL and DataLoch for asthma, COPD and ILD, we were able to highlight key differences in coding and recording between the databases and identify solutions to enable valid comparisons.

Conclusion

Codelists and metadata generated have been made available to help re-create the asthma, COPD and ILD cohorts in CPRD, SAIL and DataLoch for different time periods, and provide a starting point for the curation of respiratory datasets in other EHR databases, expediting further comparable respiratory research.",,doi:https://doi.org/10.2147/CLEP.S437937; html:https://europepmc.org/articles/PMC11002787; pdf:https://europepmc.org/articles/PMC11002787?pdf=render 34508578,https://doi.org/10.1093/gigascience/giab059,Desiderata for the development of next-generation electronic health record phenotype libraries.,"Chapman M, Mumtaz S, Rasmussen LV, Karwath A, Gkoutos GV, Gao C, Thayer D, Pacheco JA, Parkinson H, Richesson RL, Jefferson E, Denaxas S, Curcin V.",,GigaScience,2021,2021-09-01,Y,Electronic Health Records; Computable Phenotype; Ehr-based Phenotyping; Phenotype Library,,,"

Background

High-quality phenotype definitions are desirable to enable the extraction of patient cohorts from large electronic health record repositories and are characterized by properties such as portability, reproducibility, and validity. Phenotype libraries, where definitions are stored, have the potential to contribute significantly to the quality of the definitions they host. In this work, we present a set of desiderata for the design of a next-generation phenotype library that is able to ensure the quality of hosted definitions by combining the functionality currently offered by disparate tooling.

Methods

A group of researchers examined work to date on phenotype models, implementation, and validation, as well as contemporary phenotype libraries developed as a part of their own phenomics communities. Existing phenotype frameworks were also examined. This work was translated and refined by all the authors into a set of best practices.

Results

We present 14 library desiderata that promote high-quality phenotype definitions, in the areas of modelling, logging, validation, and sharing and warehousing.

Conclusions

There are a number of choices to be made when constructing phenotype libraries. Our considerations distil the best practices in the field and include pointers towards their further development to support portable, reproducible, and clinically valid phenotype design. The provision of high-quality phenotype definitions enables electronic health record data to be more effectively used in medical domains.",,pdf:https://academic.oup.com/gigascience/article-pdf/10/9/giab059/40348225/giab059.pdf; doi:https://doi.org/10.1093/gigascience/giab059; html:https://europepmc.org/articles/PMC8434766; pdf:https://europepmc.org/articles/PMC8434766?pdf=render 36729586,https://doi.org/10.2196/42965,Assessing the Feasibility of a Text-Based Conversational Agent for Asthma Support: Protocol for a Mixed Methods Observational Study.,"Calvo RA, Peters D, Moradbakhti L, Cook D, Rizos G, Schuller B, Kallis C, Wong E, Quint J.",,JMIR research protocols,2023,2023-02-02,Y,Artificial intelligence; Health; Asthma; Health education; Well-being; Behavior Change; Conversational Agent; Chatbot,,,"

Background

Despite efforts, the UK death rate from asthma is the highest in Europe, and 65% of people with asthma in the United Kingdom do not receive the professional care they are entitled to. Experts have recommended the use of digital innovations to help address the issues of poor outcomes and lack of care access. An automated SMS text messaging-based conversational agent (ie, chatbot) created to provide access to asthma support in a familiar format via a mobile phone has the potential to help people with asthma across demographics and at scale. Such a chatbot could help improve the accuracy of self-assessed risk, improve asthma self-management, increase access to professional care, and ultimately reduce asthma attacks and emergencies.

Objective

The aims of this study are to determine the feasibility and usability of a text-based conversational agent that processes a patient's text responses and short sample voice recordings to calculate an estimate of their risk for an asthma exacerbation and then offers follow-up information for lowering risk and improving asthma control; assess the levels of engagement for different groups of users, particularly those who do not access professional services and those with poor asthma control; and assess the extent to which users of the chatbot perceive it as helpful for improving their understanding and self-management of their condition.

Methods

We will recruit 300 adults through four channels for broad reach: Facebook, YouGov, Asthma + Lung UK social media, and the website Healthily (a health self-management app). Participants will be screened, and those who meet inclusion criteria (adults diagnosed with asthma and who use WhatsApp) will be provided with a link to access the conversational agent through WhatsApp on their mobile phones. Participants will be sent scheduled and randomly timed messages to invite them to engage in dialogue about their asthma risk during the period of study. After a data collection period (28 days), participants will respond to questionnaire items related to the quality of the interaction. A pre- and postquestionnaire will measure asthma control before and after the intervention.

Results

This study was funded in March 2021 and started in January 2022. We developed a prototype conversational agent, which was iteratively improved with feedback from people with asthma, asthma nurses, and specialist doctors. Fortnightly reviews of iterations by the clinical team began in September 2022 and are ongoing. This feasibility study will start recruitment in January 2023. The anticipated completion of the study is July 2023. A future randomized controlled trial will depend on the outcomes of this study and funding.

Conclusions

This feasibility study will inform a follow-up pilot and larger randomized controlled trial to assess the impact of a conversational agent on asthma outcomes, self-management, behavior change, and access to care.

International registered report identifier (irrid)

PRR1-10.2196/42965.",,pdf:https://www.researchprotocols.org/2023/1/e42965/PDF; doi:https://doi.org/10.2196/42965; html:https://europepmc.org/articles/PMC9936366 38355192,https://doi.org/10.1136/bmjopen-2023-080678,How far back do we need to look to capture diagnoses in electronic health records? A retrospective observational study of hospital electronic health record data.,"Lewis J, Evison F, Doal R, Field J, Gallier S, Harris S, le Roux P, Osman M, Plummer C, Sapey E, Singer M, Sayer AA, Witham MD, ADMISSION Research Collaborative.",,BMJ open,2024,2024-02-13,Y,Hospitals; Electronic Health Records; Information Extraction,,,"

Objectives

Analysis of routinely collected electronic health data is a key tool for long-term condition research and practice for hospitalised patients. This requires accurate and complete ascertainment of a broad range of diagnoses, something not always recorded on an admission document at a single point in time. This study aimed to ascertain how far back in time electronic hospital records need to be interrogated to capture long-term condition diagnoses.

Design

Retrospective observational study of routinely collected hospital electronic health record data.

Setting

Queen Elizabeth Hospital Birmingham (UK)-linked data held by the PIONEER acute care data hub.

Participants

Patients whose first recorded admission for chronic obstructive pulmonary disease (COPD) exacerbation (n=560) or acute stroke (n=2142) was between January and December 2018 and who had a minimum of 10 years of data prior to the index date.

Outcome measures

We identified the most common International Classification of Diseases version 10-coded diagnoses received by patients with COPD and acute stroke separately. For each diagnosis, we derived the number of patients with the diagnosis recorded at least once over the full 10-year lookback period, and then compared this with shorter lookback periods from 1 year to 9 years prior to the index admission.

Results

Seven of the top 10 most common diagnoses in the COPD dataset reached >90% completeness by 6 years of lookback. Atrial fibrillation and diabetes were >90% coded with 2-3 years of lookback, but hypertension and asthma completeness continued to rise all the way out to 10 years of lookback. For stroke, 4 of the top 10 reached 90% completeness by 5 years of lookback; angina pectoris was >90% coded at 7 years and previous transient ischaemic attack completeness continued to rise out to 10 years of lookback.

Conclusion

A 7-year lookback captures most, but not all, common diagnoses. Lookback duration should be tailored to the conditions being studied.",,pdf:https://bmjopen.bmj.com/content/bmjopen/14/2/e080678.full.pdf; doi:https://doi.org/10.1136/bmjopen-2023-080678; html:https://europepmc.org/articles/PMC10868273; pdf:https://europepmc.org/articles/PMC10868273?pdf=render @@ -830,8 +830,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 33591566,https://doi.org/10.1007/s43441-021-00263-2,Advancing UK Regulatory Science Strategy in the Context of Global Regulation: a Stakeholder Survey.,"Cruz Rivera S, Torlinska B, Marston E, Denniston AK, Oliver K, Hoare S, Calvert MJ.",,Therapeutic innovation & regulatory science,2021,2021-02-16,Y,Regulatory Science; Health Products; Medicines And Devices,,,"

Background

The UK's transition from the European Union creates both an urgent need and key opportunity for the UK and its global collaborators to consider new approaches to the regulation of emerging technologies, underpinned by regulatory science. This survey aimed to identify the most accurate definition of regulatory science, to define strategic areas of the regulation of healthcare innovation which can be informed through regulatory science and to explore the training and infrastructure needed to advance UK and international regulatory science.

Methods

A survey was distributed to UK healthcare professionals, academics, patients, health technology assessment agencies, ethicists and trade associations, as well as international regulators, pharmaceutical companies and small or medium enterprises which have expertise in regulatory science and in developing or applying regulation in healthcare. Subsequently, a descriptive quantitative analyses of survey results and directed thematic analysis of free-text comments were applied.

Results

Priority areas for UK regulatory science identified by 145 participants included the following: flexibility: the capability of regulations to adapt to novel products and target patient outcomes; co-development: collaboration across sectors, e.g. patients, manufacturers, regulators, and educators working together to develop appropriate training for novel product deployment; responsiveness: the preparation of frameworks which enable timely innovation required by emerging events; speed: the rate at which new products can reach the market; reimbursement: developing effective tools to track and evaluate outcomes for ""pay for performance"" products; and education and professional development.

Conclusions

The UK has a time-critical opportunity to establish its national and international strategy for regulatory science leadership by harnessing broader academic input, developing strategic cross-sector collaborations, incorporating patients' experiences and perspectives, and investing in a skilled workforce.",,pdf:https://link.springer.com/content/pdf/10.1007/s43441-021-00263-2.pdf; doi:https://doi.org/10.1007/s43441-021-00263-2; html:https://europepmc.org/articles/PMC7885762; pdf:https://europepmc.org/articles/PMC7885762?pdf=render 36355406,https://doi.org/10.2196/40707,Effectiveness of a Web-Based Intervention to Prevent Anxiety in the Children of Parents With Anxiety: Protocol for a Randomized Controlled Trial.,"Dunn A, Alvarez J, Arbon A, Bremner S, Elsby-Pearson C, Emsley R, Jones C, Lawrence P, Lester KJ, Majdandžić M, Morson N, Perry N, Simner J, Thomson A, Cartwright-Hatton S.",,JMIR research protocols,2022,2022-11-10,Y,Child; Parent; Youth; Anxiety; Pediatric; Mental health; Randomized controlled trial; Parenting; Rct; Online; Mental Well-being; Online Intervention; Digital Intervention,,,"

Background

Anxiety is the most common childhood mental health condition and is associated with impaired child outcomes, including increased risk of mental health difficulties in adulthood. Anxiety runs in families: when a parent has anxiety, their child has a 50% higher chance of developing it themselves. Environmental factors are predominant in the intergenerational transmission of anxiety and, of these, parenting processes play a major role. Interventions that target parents to support them to limit the impact of any anxiogenic parenting behaviors are associated with reduced anxiety in their children. A brief UK-based group intervention delivered to parents within the UK National Health Service led to a 16% reduction in children meeting the criteria for an anxiety disorder. However, this intervention is not widely accessible. To widen access, a 9-module web-based version of this intervention has been developed. This course comprises psychoeducation and home practice delivered through text, video, animations, and practice tasks.

Objective

This study seeks to evaluate the feasibility of delivering this web-based intervention and assess its effectiveness in reducing child anxiety symptoms.

Methods

 This is the protocol for a randomized controlled trial (RCT) of a community sample of 1754 parents with self-identified high levels of anxiety with a child aged 2-11 years. Parents in the intervention arm will receive access to the web-based course, which they undertake at a self-determined rate. The control arm receives no intervention. Follow-up data collection is at months 6 and months 9-21. Intention-to-treat analysis will be conducted on outcomes including child anxiety, child mental health symptoms, and well-being; parental anxiety and well-being; and parenting behaviors.

Results

Funding was received in April 2020, and recruitment started in February 2021 and is projected to end in October 2022. A total of 1350 participants have been recruited as of May 2022.

Conclusions

The results of this RCT will provide evidence on the utility of a web-based course in preventing intergenerational transmission of anxiety and increase the understanding of familial anxiety.

Trial registration

ClinicalTrials.gov NCT04755933; https://clinicaltrials.gov/ct2/show/NCT04755933.

International registered report identifier (irrid)

DERR1-10.2196/40707.",,pdf:https://jmir.org/api/download?alt_name=resprot_v11i11e40707_app2.pdf&filename=4e6914231a45b12439d1932b760a7c34.pdf; doi:https://doi.org/10.2196/40707; html:https://europepmc.org/articles/PMC9693706 35477354,https://doi.org/10.1186/s12877-022-03077-5,Performance of the SarQoL quality of life tool in a UK population of older people with probable sarcopenia and implications for use in clinical trials: findings from the SarcNet registry.,"Witham MD, Heslop P, Dodds RM, Clegg AP, Hope SV, McDonald C, Smithard D, Storey B, Tan AL, Thornhill A, Sayer AA.",,BMC geriatrics,2022,2022-04-27,Y,Quality of life; Validity; Sarcopenia; Responsiveness; Minimum Clinical Important Difference,,,"

Background

The Sarcopenia Quality of Life (SarQoL) questionnaire is a disease-specific sarcopenia quality of life tool. We aimed to independently assess SarQoL with a particular focus on its suitability as a clinical trial outcome measure.

Methods

We analysed data from the UK Sarcopenia Network and Registry. Measures of physical performance and lean mass were collected at baseline. SarQoL and the Strength, Assistance, Rise, Climb - Falls (SARC-F) questionnaire (to assess functional ability) were collected at both baseline and six-month follow-up. Global changes in fitness and quality of life at 6 months were elicited on seven-point Likert scales. Internal consistency was assessed using Cronbach's alpha. Responsiveness (Cohen's d and Guyatt coefficients) and minimum clinically important differences were calculated for participants reporting slight improvement or worsening in their global scores. Concurrent validity was assessed by correlating baseline SarQoL scores with measures of physical performance and functional ability.

Results

We analysed data from 147 participants, 125 of whom underwent follow up assessment; mean age 78 years; 72 (49%) were women. Internal consistency was good; Cronbach's alpha was 0.944 at baseline and 0.732 at telephone follow-up. Correlation between baseline and follow-up SarQoL was weak (r = 0.27; p = 0.03). The minimum clinically important improvement ranged from 5 to 21 points giving trial sample size estimates of 25-100 participants. SarQoL scores were moderately correlated with handgrip (r = 0.37; p < 0.001), SARC-F (r = - 0.45; p < 0.001), short physical performance battery (r = 0.48; p < 0.001) and 4-m walk speed (r = 0.48; p < 0.001).

Conclusions

SarQoL has acceptable performance in older UK participants with probable sarcopenia and is sufficiently responsive for use in clinical trials for sarcopenia.",,pdf:https://bmcgeriatr.biomedcentral.com/track/pdf/10.1186/s12877-022-03077-5; doi:https://doi.org/10.1186/s12877-022-03077-5; html:https://europepmc.org/articles/PMC9043890; pdf:https://europepmc.org/articles/PMC9043890?pdf=render -34788413,https://doi.org/10.1093/ije/dyab149,Data Resource Profile: The Education and Child Health Insights from Linked Data (ECHILD) Database.,"Mc Grath-Lone L, Libuy N, Harron K, Jay MA, Wijlaars L, Etoori D, Lilliman M, Gilbert R, Blackburn R.",,International journal of epidemiology,2022,2022-02-01,Y,Education; Social Care; Adolescent Health; Administrative Data; Linked Data; Key Words: Child Health,,,,,pdf:https://academic.oup.com/ije/article-pdf/51/1/17/42555483/dyab149.pdf; doi:https://doi.org/10.1093/ije/dyab149; html:https://europepmc.org/articles/PMC8856003; pdf:https://europepmc.org/articles/PMC8856003?pdf=render 33627748,https://doi.org/10.1038/s41746-021-00406-7,Real-time clinician text feeds from electronic health records.,"Teo JTH, Dinu V, Bernal W, Davidson P, Oliynyk V, Breen C, Barker RD, Dobson RJB.",,NPJ digital medicine,2021,2021-02-24,Y,,,,"Analyses of search engine and social media feeds have been attempted for infectious disease outbreaks, but have been found to be susceptible to artefactual distortions from health scares or keyword spamming in social media or the public internet. We describe an approach using real-time aggregation of keywords and phrases of freetext from real-time clinician-generated documentation in electronic health records to produce a customisable real-time viral pneumonia signal providing up to 4 days warning for secondary care capacity planning. This low-cost approach is open-source, is locally customisable, is not dependent on any specific electronic health record system and can provide an ensemble of signals if deployed at multiple organisational scales.",,pdf:https://www.nature.com/articles/s41746-021-00406-7.pdf; doi:https://doi.org/10.1038/s41746-021-00406-7; html:https://europepmc.org/articles/PMC7904856; pdf:https://europepmc.org/articles/PMC7904856?pdf=render +34788413,https://doi.org/10.1093/ije/dyab149,Data Resource Profile: The Education and Child Health Insights from Linked Data (ECHILD) Database.,"Mc Grath-Lone L, Libuy N, Harron K, Jay MA, Wijlaars L, Etoori D, Lilliman M, Gilbert R, Blackburn R.",,International journal of epidemiology,2022,2022-02-01,Y,Education; Social Care; Adolescent Health; Administrative Data; Linked Data; Key Words: Child Health,,,,,pdf:https://academic.oup.com/ije/article-pdf/51/1/17/42555483/dyab149.pdf; doi:https://doi.org/10.1093/ije/dyab149; html:https://europepmc.org/articles/PMC8856003; pdf:https://europepmc.org/articles/PMC8856003?pdf=render 36060542,https://doi.org/10.3389/fdgth.2022.939292,Clinical deployment environments: Five pillars of translational machine learning for health.,"Harris S, Bonnici T, Keen T, Lilaonitkul W, White MJ, Swanepoel N.",,Frontiers in digital health,2022,2022-08-19,Y,Safety; Artificial intelligence; Machine Learning; Health Informatics; Translational Medicine; Ml-ops,,,"Machine Learning for Health (ML4H) has demonstrated efficacy in computer imaging and other self-contained digital workflows, but has failed to substantially impact routine clinical care. This is no longer because of poor adoption of Electronic Health Records Systems (EHRS), but because ML4H needs an infrastructure for development, deployment and evaluation within the healthcare institution. In this paper, we propose a design pattern called a Clinical Deployment Environment (CDE). We sketch the five pillars of the CDE: (1) real world development supported by live data where ML4H teams can iteratively build and test at the bedside (2) an ML-Ops platform that brings the rigour and standards of continuous deployment to ML4H (3) design and supervision by those with expertise in AI safety (4) the methods of implementation science that enable the algorithmic insights to influence the behaviour of clinicians and patients and (5) continuous evaluation that uses randomisation to avoid bias but in an agile manner. The CDE is intended to answer the same requirements that bio-medicine articulated in establishing the translational medicine domain. It envisions a transition from ""real-world"" data to ""real-world"" development.",,pdf:https://www.frontiersin.org/articles/10.3389/fdgth.2022.939292/pdf; doi:https://doi.org/10.3389/fdgth.2022.939292; html:https://europepmc.org/articles/PMC9437594; pdf:https://europepmc.org/articles/PMC9437594?pdf=render 36137640,https://doi.org/10.1136/bmjopen-2022-064586,Myocardial infarction and stroke subsequent to urinary tract infection (MISSOURI): protocol for a self-controlled case series using linked electronic health records.,"Reeve NF, Best V, Gillespie D, Hughes K, Lugg-Widger FV, Cannings-John R, Torabi F, Wootton M, Akbari A, Ahmed H.",,BMJ open,2022,2022-09-22,Y,Myocardial infarction; Stroke; Urinary tract infections,,,"

Introduction

There is increasing interest in the relationship between acute infections and acute cardiovascular events. Most previous research has focused on understanding whether the risk of acute cardiovascular events increases following a respiratory tract infection. The relationship between urinary tract infections (UTIs) and acute cardiovascular events is less well studied. Therefore, the aim of this study is to determine whether there is a causal relationship between UTI and acute myocardial infarction (MI) or stroke.

Methods and analysis

We will undertake a self-controlled case series study using linked anonymised general practice, hospital admission and microbiology data held within the Secure Anonymised Information Linkage (SAIL) Databank. Self-controlled case series is a relatively novel study design where individuals act as their own controls, thereby inherently controlling for time-invariant confounders. Only individuals who experience an exposure and outcome of interest are included.We will identify individuals in the SAIL Databank who have a hospital admission record for acute MI or stroke during the study period of 2010-2020. Individuals will need to be aged 30-100 during the study period and be Welsh residents for inclusion. UTI will be identified using general practice, microbiology and hospital admissions data. We will calculate the incidence of MI and stroke in predefined risk periods following an UTI and in 'baseline' periods (without UTI exposure) and use conditional Poisson regression models to derive incidence rate ratios.

Ethics and dissemination

Data access, research permissions and approvals have been obtained from the SAIL independent Information Governance Review Panel, project number 0972. Findings will be disseminated through conferences, blogs, social media threads and peer-reviewed journals. Results will be of interest internationally to primary and secondary care clinicians who manage UTIs and may inform future clinical trials of preventative therapy.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/9/e064586.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-064586; html:https://europepmc.org/articles/PMC9511592; pdf:https://europepmc.org/articles/PMC9511592?pdf=render 36691123,https://doi.org/10.1136/bmjopen-2022-063199,Feasibility of a new electronic patient-reported outcome (ePRO) system for an advanced therapy clinical trial in immune-mediated inflammatory disease (PROmics): protocol for a qualitative feasibility study.,"Hughes SE, McMullan C, Rowe A, Retzer A, Malpass R, Bathurst C, Davies EH, Frost C, McNamara G, Harding R, Price G, Wilson R, Walker A, Newsome PN, Calvert M.",,BMJ open,2022,2022-09-06,Y,information technology; immunology; Hepatology; Inflammatory Bowel Disease; Rheumatology,,,"

Introduction

The use of electronic patient-reported outcome (ePRO) systems to capture PRO data in clinical trials is increasing; however, their feasibility, acceptability and utility in clinical trials of advanced therapy medicinal products (ATMPs) are not yet well understood. This protocol describes a qualitative study that aims to evaluate the feasibility and acceptability of ePRO data capture using a trial-specific ePRO system (the PROmics system) within an advanced therapy trial involving patients with immune-mediated inflammatory disease (rheumatoid arthritis, lupus, primary sclerosing cholangitis (PSC) and Crohn's disease).

Methods and analysis

This protocol for a remote, qualitative, interview-based feasibility study is embedded within the POLARISE trial, a single-arm, phase II, multisite ATMP basket trial in the UK. 10-15 patients enrolled in the POLARISE trial and 10-15 research team members at the trial sites will be recruited. Participants will take part in semistructured interviews which will be transcribed verbatim and analysed thematically according to the framework method. Data collection and analysis will occur concurrently and iteratively. Researcher triangulation will be used to achieve a consensus-based analysis, enhancing rigour and trustworthiness.

Ethics and dissemination

This study was approved by the London-West London and GTAC Research Ethics Committee (Ref: 21/LO/0475). Informed consent will be obtained from all participants prior to data collection. The study findings will be published in peer-review journals and disseminated via conference presentations and other media. Our patient and public involvement and engagement group and ATMP stakeholder networks will be consulted to maximise dissemination and impact.

Trial registration number

ISRCTN80103507.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/9/e063199.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-063199; html:https://europepmc.org/articles/PMC9453996; pdf:https://europepmc.org/articles/PMC9453996?pdf=render diff --git a/data/papers.csv b/data/papers.csv index c2e710d8..3ab2d912 100644 --- a/data/papers.csv +++ b/data/papers.csv @@ -43,8 +43,8 @@ PMC10929454,https://doi.org/,Optimising data curation pipelines for population-l 35038629,https://doi.org/10.1016/j.puhe.2021.12.010,Investigating the association between COVID-19 vaccination and care home outbreak frequency and duration.,"Bradley DT, Murphy S, McWilliams P, Arnold S, Lavery S, Murphy J, de Lusignan S, Hobbs R, Tsang RSM, Akbari A, Torabi F, Beggs J, Chuter A, Shi T, Vasileiou E, Robertson C, Sheikh A, Reid H, O'Reilly D.",,Public health,2022,2021-12-18,Y,Vaccination; outbreak; Care Homes; Covid-19; Sars-cov-2,,,"

Objectives

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

Study design

We undertook an ecological study using routinely available national data.

Methods

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

Results

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

Conclusions

These findings describe the association of the vaccination with a reduction in outbreak frequency and duration across NI care homes. This indicates probable reduced harm and disruption from COVID-19 in social care settings following vaccination. Future research using individual level data from care home residents will be needed to investigate the effectiveness of the vaccines and the duration of their effects.",,pdf:https://cronfa.swan.ac.uk/Record/cronfa59048/Download/59048__22075__e4bbc8a7cad6434abac5984eb2422e06.pdf; doi:https://doi.org/10.1016/j.puhe.2021.12.010; html:https://europepmc.org/articles/PMC8683272; pdf:https://europepmc.org/articles/PMC8683272?pdf=render 37587102,https://doi.org/10.1038/s41467-023-40643-w,"SARS-CoV-2 rapid antibody test results and subsequent risk of hospitalisation and death in 361,801 people.","Whitaker M, Davies B, Atchison C, Barclay W, Ashby D, Darzi A, Riley S, Cooke G, Donnelly CA, Chadeau-Hyam M, Elliott P, Ward H.",,Nature communications,2023,2023-08-16,Y,,,,"The value of SARS-CoV-2 lateral flow immunoassay (LFIA) tests for estimating individual disease risk is unclear. The REACT-2 study in England, UK, obtained self-administered SARS-CoV-2 LFIA test results from 361,801 adults in January-May 2021. Here, we link to routine data on subsequent hospitalisation (to September 2021), and death (to December 2021). Among those who had received one or more vaccines, a negative LFIA is associated with increased risk of hospitalisation with COVID-19 (HR: 2.73 [95% confidence interval: 1.15,6.48]), death (all-cause) (HR: 1.59, 95% CI:1.07, 2.37), and death with COVID-19 as underlying cause (20.6 [1.83,232]). For people designated at high risk from COVID-19, who had received one or more vaccines, there is an additional risk of all-cause mortality of 1.9 per 1000 for those testing antibody negative compared to positive. However, the LFIA does not provide substantial predictive information over and above that which is available from detailed sociodemographic and health-related variables. Nonetheless, this simple test provides a marker which could be a valuable addition to understanding population and individual-level risk.",,doi:https://doi.org/10.1038/s41467-023-40643-w; html:https://europepmc.org/articles/PMC10432566; pdf:https://europepmc.org/articles/PMC10432566?pdf=render 35715992,https://doi.org/10.1002/cam4.4941,Associating transcriptomics data with inflammatory markers to understand tumour microenvironment in hepatocellular carcinoma.,"Bahcivanci B, Shafiha R, Gkoutos GV, Acharjee A.",,Cancer medicine,2023,2022-06-18,Y,Hepatocellular carcinoma; Tumor Microenvironment; Gene Signature; Immune Deconvolution,,,"

Background

Liver cancer is the fourth leading cause of cancer-related death globally which is estimated to reach more than 1 million deaths a year by 2030. Among liver cancer types, hepatocellular carcinoma (HCC) accounts for approximately 90% of the cases and is known to have a tumour promoting inflammation regardless of its underlying aetiology. However, current promising treatment approaches, such as immunotherapy, are partially effective for most of the patients due to the immunosuppressive nature of the tumour microenvironment (TME). Therefore, there is an urgent need to fully understand TME in HCC and discover new immune markers to eliminate resistance to immunotherapy.

Methods

We analyse three microarray datasets, using unsupervised and supervised methods, in an effort to discover signature genes. First, univariate, and multivariate, feature selection methods, such as the Boruta algorithm, are applied. Subsequently, an optimisation procedure, which utilises random forest algorithm with three dataset pairs combinations, is performed. The resulting optimal gene sets are then combined and further subjected to network analysis and pathway enrichment analysis so as to obtain information related to their biological relevance. The microarray datasets were analysed via the MCP-counter, CIBERSORT, TIMER, EPIC, and quanTIseq deconvolution methods and an estimation of cell type abundances for each dataset sample were identified. The differences in the cell type abundances, between the adjacent and tumour sample groups, were then assessed using a Wilcoxon Rank Sum test (p-value < 0.05).

Results

The optimal gene signature sets, derived from each of the data pairs combination, achieved AUC values ranging from 0.959 to 0.988 in external validation sets using Random Forest model. CLEC1B and PTTG1 genes are retrieved across each optimal set. Among the signature genes, PTTG1, AURKA, and UBE2C genes are found to be involved in the regulation of mitotic sister chromatid separation and anaphase-promoting complex (APC) dependent catabolic process (adjusted p-value < 0.001). Additionally, the application of deconvolution algorithms revealed significant changes in cell type abundances of Regulatory T (Treg) cells, M0 and M1 macrophages, and T CD8+ cells between adjacent and tumour samples.

Conclusion

We identified ECM1 gene as a potential immune-related marker acting through immune cell migration and macrophage polarisation. Our results indicate that macrophages, such as M0 macrophage and M1 macrophage cells, undergo significant changes in HCC TME. Moreover, our immune deconvolution approach revealed significant infiltration of Treg cells and M0 macrophages, and a significant decrease in T CD8+ cells and M1 macrophages in tumour samples.",,pdf:http://pure-oai.bham.ac.uk/ws/files/172896799/Cancer_Medicine_2022_Bahcivanci_Associating_transcriptomics_data_with_inflammatory_markers_to_understand_tumour.pdf; doi:https://doi.org/10.1002/cam4.4941; html:https://europepmc.org/articles/PMC9844659; pdf:https://europepmc.org/articles/PMC9844659?pdf=render -38630417,https://doi.org/10.1007/s44192-024-00066-5,Cerebrospinal fluid metabolomes of treatment-resistant depression subtypes and ketamine response: a pilot study.,"Berner J, Acharjee A.",,Discover mental health,2024,2024-04-17,Y,,,,"Depression is a disorder with variable presentation. Selecting treatments and dose-finding is, therefore, challenging and time-consuming. In addition, novel antidepressants such as ketamine have sparse optimization evidence. Insights obtained from metabolomics may improve the management of patients. The objective of this study was to determine whether compounds in the cerebrospinal fluid (CSF) metabolome correlate with scores on questionnaires and response to medication. We performed a retrospective pilot study to evaluate phenotypic and metabolomic variability in patients with treatment-resistant depression using multivariate data compression algorithms. Twenty-nine patients with treatment-resistant depression provided fasting CSF samples. Over 300 metabolites were analyzed in these samples with liquid chromatography-mass spectrometry. Chart review provided basic demographic information, clinical status with self-reported questionnaires, and response to medication. Of the 300 metabolites analyzed, 151 were present in all CSF samples and used in the analyses. Hypothesis-free multivariate analysis compressed the resultant data set into two dimensions using Principal Component (PC) analysis, accounting for ~ 32% of the variance. PC1 accounted for 16.9% of the variance and strongly correlated with age in one direction and 5-methyltetrahydrofolate, homocarnosine, and depression and anxiety scores in the opposite direction. PC2 accounted for 15.4% of the variance, with one end strongly correlated with autism scores, male gender, and cognitive fatigue scores, and the other end with bipolar diagnosis, lithium use, and ethylmalonate disturbance. This small pilot study suggests that complex treatment-resistant depression can be mapped onto a 2-dimensional pathophysiological domain. The results may have implications for treatment selection for depression subtypes.",,pdf:https://link.springer.com/content/pdf/10.1007/s44192-024-00066-5.pdf; doi:https://doi.org/10.1007/s44192-024-00066-5; html:https://europepmc.org/articles/PMC11024073; pdf:https://europepmc.org/articles/PMC11024073?pdf=render 36647111,https://doi.org/10.1186/s12911-022-02093-0,"Harmonising electronic health records for reproducible research: challenges, solutions and recommendations from a UK-wide COVID-19 research collaboration.","Abbasizanjani H, Torabi F, Bedston S, Bolton T, Davies G, Denaxas S, Griffiths R, Herbert L, Hollings S, Keene S, Khunti K, Lowthian E, Lyons J, Mizani MA, Nolan J, Sudlow C, Walker V, Whiteley W, Wood A, Akbari A, CVD-COVID-UK/COVID-IMPACT Consortium.",,BMC medical informatics and decision making,2023,2023-01-16,Y,Population Health; Electronic Health Record; Reproducible Research; Common Data Model; Data Harmonisation; Covid-19; Trusted Research Environments; Nhs Digital Tre For England; Sail Databank,,,"

Background

The CVD-COVID-UK consortium was formed to understand the relationship between COVID-19 and cardiovascular diseases through analyses of harmonised electronic health records (EHRs) across the four UK nations. Beyond COVID-19, data harmonisation and common approaches enable analysis within and across independent Trusted Research Environments. Here we describe the reproducible harmonisation method developed using large-scale EHRs in Wales to accommodate the fast and efficient implementation of cross-nation analysis in England and Wales as part of the CVD-COVID-UK programme. We characterise current challenges and share lessons learnt.

Methods

Serving the scope and scalability of multiple study protocols, we used linked, anonymised individual-level EHR, demographic and administrative data held within the SAIL Databank for the population of Wales. The harmonisation method was implemented as a four-layer reproducible process, starting from raw data in the first layer. Then each of the layers two to four is framed by, but not limited to, the characterised challenges and lessons learnt. We achieved curated data as part of our second layer, followed by extracting phenotyped data in the third layer. We captured any project-specific requirements in the fourth layer.

Results

Using the implemented four-layer harmonisation method, we retrieved approximately 100 health-related variables for the 3.2 million individuals in Wales, which are harmonised with corresponding variables for > 56 million individuals in England. We processed 13 data sources into the first layer of our harmonisation method: five of these are updated daily or weekly, and the rest at various frequencies providing sufficient data flow updates for frequent capturing of up-to-date demographic, administrative and clinical information.

Conclusions

We implemented an efficient, transparent, scalable, and reproducible harmonisation method that enables multi-nation collaborative research. With a current focus on COVID-19 and its relationship with cardiovascular outcomes, the harmonised data has supported a wide range of research activities across the UK.",,pdf:https://bmcmedinformdecismak.biomedcentral.com/counter/pdf/10.1186/s12911-022-02093-0; doi:https://doi.org/10.1186/s12911-022-02093-0; html:https://europepmc.org/articles/PMC9842203; pdf:https://europepmc.org/articles/PMC9842203?pdf=render +38630417,https://doi.org/10.1007/s44192-024-00066-5,Cerebrospinal fluid metabolomes of treatment-resistant depression subtypes and ketamine response: a pilot study.,"Berner J, Acharjee A.",,Discover mental health,2024,2024-04-17,Y,,,,"Depression is a disorder with variable presentation. Selecting treatments and dose-finding is, therefore, challenging and time-consuming. In addition, novel antidepressants such as ketamine have sparse optimization evidence. Insights obtained from metabolomics may improve the management of patients. The objective of this study was to determine whether compounds in the cerebrospinal fluid (CSF) metabolome correlate with scores on questionnaires and response to medication. We performed a retrospective pilot study to evaluate phenotypic and metabolomic variability in patients with treatment-resistant depression using multivariate data compression algorithms. Twenty-nine patients with treatment-resistant depression provided fasting CSF samples. Over 300 metabolites were analyzed in these samples with liquid chromatography-mass spectrometry. Chart review provided basic demographic information, clinical status with self-reported questionnaires, and response to medication. Of the 300 metabolites analyzed, 151 were present in all CSF samples and used in the analyses. Hypothesis-free multivariate analysis compressed the resultant data set into two dimensions using Principal Component (PC) analysis, accounting for ~ 32% of the variance. PC1 accounted for 16.9% of the variance and strongly correlated with age in one direction and 5-methyltetrahydrofolate, homocarnosine, and depression and anxiety scores in the opposite direction. PC2 accounted for 15.4% of the variance, with one end strongly correlated with autism scores, male gender, and cognitive fatigue scores, and the other end with bipolar diagnosis, lithium use, and ethylmalonate disturbance. This small pilot study suggests that complex treatment-resistant depression can be mapped onto a 2-dimensional pathophysiological domain. The results may have implications for treatment selection for depression subtypes.",,pdf:https://link.springer.com/content/pdf/10.1007/s44192-024-00066-5.pdf; doi:https://doi.org/10.1007/s44192-024-00066-5; html:https://europepmc.org/articles/PMC11024073; pdf:https://europepmc.org/articles/PMC11024073?pdf=render 38645891,https://doi.org/10.1136/bmjmed-2023-000807,Identification of patients undergoing chronic kidney replacement therapy in primary and secondary care data: validation study based on OpenSAFELY and UK Renal Registry.,"Santhakumaran S, Fisher L, Zheng B, Mahalingasivam V, Plumb L, Parker EP, Steenkamp R, Morton C, Mehrkar A, Bacon S, Lyon S, Konstant-Hambling R, Goldacre B, MacKenna B, Tomlinson LA, Nitsch D.",,BMJ medicine,2024,2024-04-18,Y,"Dialysis; Kidney transplantation; Kidney failure, chronic; epidemiology; Covid-19",,,"

Objective

To validate primary and secondary care codes in electronic health records to identify people receiving chronic kidney replacement therapy based on gold standard registry data.

Design

Validation study using data from OpenSAFELY and the UK Renal Registry, with the approval of NHS England.

Setting

Primary and secondary care electronic health records from people registered at 45% of general practices in England on 1 January 2020, linked to data from the UK Renal Registry (UKRR) within the OpenSAFELY-TPP platform, part of the NHS England OpenSAFELY covid-19 service.

Participants

38 745 prevalent patients (recorded as receiving kidney replacement therapy on 1 January 2020 in UKRR data, or primary or secondary care data) and 10 730 incident patients (starting kidney replacement therapy during 2020), from a population of 19 million people alive and registered with a general practice in England on 1 January 2020.

Main outcome measures

Sensitivity and positive predictive values of primary and secondary care code lists for identifying prevalent and incident kidney replacement therapy cohorts compared with the gold standard UKRR data on chronic kidney replacement therapy. Agreement across the data sources overall, and by treatment modality (transplantation or dialysis) and personal characteristics.

Results

Primary and secondary care code lists were sensitive for identifying the UKRR prevalent cohort (91.2% (95% confidence interval (CI) 90.8% to 91.6%) and 92.0% (91.6% to 92.4%), respectively), but not the incident cohort (52.3% (50.3% to 54.3%) and 67.9% (66.1% to 69.7%)). Positive predictive values were low (77.7% (77.2% to 78.2%) for primary care data and 64.7% (64.1% to 65.3%) for secondary care data), particularly for chronic dialysis (53.7% (52.9% to 54.5%) for primary care data and 49.1% (48.0% to 50.2%) for secondary care data). Sensitivity decreased with age and index of multiple deprivation in primary care data, but the opposite was true in secondary care data. Agreement was lower in children, with 30% (295/980) featuring in all three datasets. Half (1165/2315) of the incident patients receiving dialysis in UKRR data had a kidney replacement therapy code in the primary care data within three months of the start date of the kidney replacement therapy. No codes existed whose exclusion would substantially improve the positive predictive value without a decrease in sensitivity.

Conclusions

Codes used in primary and secondary care data failed to identify a small proportion of prevalent patients receiving kidney replacement therapy. Codes also identified many patients who were not recipients of chronic kidney replacement therapy in UKRR data, particularly dialysis codes. Linkage with UKRR kidney replacement therapy data facilitated more accurate identification of incident and prevalent kidney replacement therapy cohorts for research into this vulnerable population. Poor coding has implications for any patient care (including eligibility for vaccination, resourcing, and health policy responses in future pandemics) that relies on accurate reporting of kidney replacement therapy in primary and secondary care data.",,doi:https://doi.org/10.1136/bmjmed-2023-000807; html:https://europepmc.org/articles/PMC11029353; pdf:https://europepmc.org/articles/PMC11029353?pdf=render 34301672,https://doi.org/10.1136/bmjopen-2021-053402,Sociodemographic inequality in COVID-19 vaccination coverage among elderly adults in England: a national linked data study.,"Nafilyan V, Dolby T, Razieh C, Gaughan CH, Morgan J, Ayoubkhani D, Walker S, Khunti K, Glickman M, Yates T.",,BMJ open,2021,2021-07-23,Y,Infection control; epidemiology; Covid-19,,,"

Objective

To examine inequalities in COVID-19 vaccination rates among elderly adults in England.

Design

Cohort study.

Setting

People living in private households and communal establishments in England.

Participants

6 655 672 adults aged ≥70 years (mean 78.8 years, 55.2% women) who were alive on 15 March 2021.

Main outcome measures

Having received the first dose of a vaccine against COVID-19 by 15 March 2021. We calculated vaccination rates and estimated unadjusted and adjusted ORs using logistic regression models.

Results

By 15 March 2021, 93.2% of people living in England aged 70 years and over had received at least one dose of a COVID-19 vaccine. While vaccination rates differed across all factors considered apart from sex, the greatest disparities were seen between ethnic and religious groups. The lowest rates were in people of black African and black Caribbean ethnic backgrounds, where only 67.2% and 73.8% had received a vaccine, with adjusted odds of not being vaccinated at 5.01 (95% CI 4.86 to 5.16) and 4.85 (4.75 to 4.96) times greater than the white British group. The proportion of individuals self-identifying as Muslim and Buddhist who had received a vaccine was 79.1% and 84.1%, respectively. Older age, greater area deprivation, less advantaged socioeconomic position (proxied by living in a rented home), being disabled and living either alone or in a multigenerational household were also associated with higher odds of not having received the vaccine.

Conclusion

Research is now urgently needed to understand why disparities exist in these groups and how they can best be addressed through public health policy and community engagement.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/7/e053402.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-053402; html:https://europepmc.org/articles/PMC8313303; pdf:https://europepmc.org/articles/PMC8313303?pdf=render 35724769,https://doi.org/10.1016/j.kint.2022.05.015,A retrospective cohort study predicting and validating impact of the COVID-19 pandemic in individuals with chronic kidney disease.,"Dashtban A, Mizani MA, Denaxas S, Nitsch D, Quint J, Corbett R, Mamza JB, Morris T, Mamas M, Lawlor DA, Khunti K, CVD-COVID-UK Consortium, Sudlow C, Hemingway H, Banerjee A.",,Kidney international,2022,2022-06-17,Y,Mortality; Chronic Kidney Disease; Sars-cov-2,,,"Chronic kidney disease (CKD) is associated with increased risk of baseline mortality and severe COVID-19, but analyses across CKD stages, and comorbidities are lacking. In prevalent and incident CKD, we investigated comorbidities, baseline risk, COVID-19 incidence, and predicted versus observed one-year excess death. In a national dataset (NHS Digital Trusted Research Environment [NHSD TRE]) for England encompassing 56 million individuals), we conducted a retrospective cohort study (March 2020 to March 2021) for prevalence of comorbidities by incident and prevalent CKD, SARS-CoV-2 infection and mortality. Baseline mortality risk, incidence and outcome of infection by comorbidities, controlling for age, sex and vaccination were assessed. Observed versus predicted one-year mortality at varying population infection rates and pandemic-related relative risks using our published model in pre-pandemic CKD cohorts (NHSD TRE and Clinical Practice Research Datalink [CPRD]) were compared. Among individuals with CKD (prevalent:1,934,585, incident:144,969), comorbidities were common (73.5% and 71.2% with one or more condition[s] in respective data sets, and 13.2% and 11.2% with three or more conditions, in prevalent and incident CKD), and associated with SARS-CoV-2 infection, particularly dialysis/transplantation (odds ratio 2.08, 95% confidence interval 2.04-2.13) and heart failure (1.73, 1.71-1.76), but not cancer (1.01, 1.01-1.04). One-year all-cause mortality varied by age, sex, multi-morbidity and CKD stage. Compared with 34,265 observed excess deaths, in the NHSD-TRE and CPRD databases respectively, we predicted 28,746 and 24,546 deaths (infection rates 10% and relative risks 3.0), and 23,754 and 20,283 deaths (observed infection rates 6.7% and relative risks 3.7). Thus, in this largest, national-level study, individuals with CKD have a high burden of comorbidities and multi-morbidity, and high risk of pre-pandemic and pandemic mortality. Hence, treatment of comorbidities, non-pharmaceutical measures, and vaccination are priorities for people with CKD and management of long-term conditions is important during and beyond the pandemic.",,doi:https://doi.org/10.1016/j.kint.2022.05.015; doi:https://doi.org/10.1016/j.kint.2022.05.015; html:https://europepmc.org/articles/PMC9212366; pdf:https://europepmc.org/articles/PMC9212366?pdf=render @@ -126,16 +126,16 @@ PMC10929454,https://doi.org/,Optimising data curation pipelines for population-l 35275994,https://doi.org/10.2337/dc21-1709,Admission Blood Glucose Level and Its Association With Cardiovascular and Renal Complications in Patients Hospitalized With COVID-19.,"Norris T, Razieh C, Yates T, Zaccardi F, Gillies CL, Chudasama YV, Rowlands A, Davies MJ, McCann GP, Banerjee A, Docherty AB, Openshaw PJM, Baillie JK, Semple MG, Lawson CA, Khunti K.",,Diabetes care,2022,2022-05-01,N,,,,"

Objective

To investigate the association between admission blood glucose levels and risk of in-hospital cardiovascular and renal complications.

Research design and methods

In this multicenter prospective study of 36,269 adults hospitalized with COVID-19 between 6 February 2020 and 16 March 2021 (N = 143,266), logistic regression models were used to explore associations between admission glucose level (mmol/L and mg/dL) and odds of in-hospital complications, including heart failure, arrhythmia, cardiac ischemia, cardiac arrest, coagulation complications, stroke, and renal injury. Nonlinearity was investigated using restricted cubic splines. Interaction models explored whether associations between glucose levels and complications were modified by clinically relevant factors.

Results

Cardiovascular and renal complications occurred in 10,421 (28.7%) patients; median admission glucose level was 6.7 mmol/L (interquartile range 5.8-8.7) (120.6 mg/dL [104.4-156.6]). While accounting for confounders, for all complications except cardiac ischemia and stroke, there was a nonlinear association between glucose and cardiovascular and renal complications. For example, odds of heart failure, arrhythmia, coagulation complications, and renal injury decreased to a nadir at 6.4 mmol/L (115 mg/dL), 4.9 mmol/L (88.2 mg/dL), 4.7 mmol/L (84.6 mg/dL), and 5.8 mmol/L (104.4 mg/dL), respectively, and increased thereafter until 26.0 mmol/L (468 mg/dL), 50.0 mmol/L (900 mg/dL), 8.5 mmol/L (153 mg/dL), and 32.4 mmol/L (583.2 mg/dL). Compared with 5 mmol/L (90 mg/dL), odds ratios at these glucose levels were 1.28 (95% CI 0.96, 1.69) for heart failure, 2.23 (1.03, 4.81) for arrhythmia, 1.59 (1.36, 1.86) for coagulation complications, and 2.42 (2.01, 2.92) for renal injury. For most complications, a modifying effect of age was observed, with higher odds of complications at higher glucose levels for patients age <69 years. Preexisting diabetes status had a similar modifying effect on odds of complications, but evidence was strongest for renal injury, cardiac ischemia, and any cardiovascular/renal complication.

Conclusions

Increased odds of cardiovascular or renal complications were observed for admission glucose levels indicative of both hypo- and hyperglycemia. Admission glucose could be used as a marker for risk stratification of high-risk patients. Further research should evaluate interventions to optimize admission glucose on improving COVID-19 outcomes.",,pdf:https://diabetesjournals.org/care/article-pdf/45/5/1132/678515/dc211709.pdf; doi:https://doi.org/10.2337/dc21-1709; html:https://europepmc.org/articles/PMC9174963; pdf:https://europepmc.org/articles/PMC9174963?pdf=render; doi:https://doi.org/10.2337/dc21-1709 37726825,https://doi.org/10.1186/s13063-023-07606-4,Correction: Development and evaluation of rapid data-enabled access to routine clinical information to enhance early recruitment to the national clinical platform trial of COVID-19 community treatments.,"Cake C, Ogburn E, Pinches H, Coleman G, Seymour D, Woodard F, Manohar S, Monsur M, Landray M, Dalton G, Morris AD, Chinnery PF, UK COVID-19 National Core Studies Consortium, Hobbs FDR, Butler C.",,Trials,2023,2023-09-19,Y,,,,,,pdf:https://trialsjournal.biomedcentral.com/counter/pdf/10.1186/s13063-023-07606-4; doi:https://doi.org/10.1186/s13063-023-07606-4; html:https://europepmc.org/articles/PMC10507817; pdf:https://europepmc.org/articles/PMC10507817?pdf=render 35501391,https://doi.org/10.1038/s41416-022-01830-6,"Impact of the SARS-CoV-2 pandemic on female breast, colorectal and non-small cell lung cancer incidence, stage and healthcare pathway to diagnosis during 2020 in Wales, UK, using a national cancer clinical record system.","Greene G, Griffiths R, Han J, Akbari A, Jones M, Lyons J, Lyons RA, Rolles M, Torabi F, Warlow J, Morris ERA, Lawler M, Huws DW.",,British journal of cancer,2022,2022-05-02,Y,,,,"

Background

COVID-19 pandemic responses impacted behaviour and health services. We estimated the impact on incidence, stage and healthcare pathway to diagnosis for female breast, colorectal and non-small cell lung cancers at population level in Wales.

Methods

Cancer e-record and hospital admission data linkage identified adult cases, stage and healthcare pathway to diagnosis (population ~2.5 million). Using multivariate Poisson regressions, we compared 2019 and 2020 counts and estimated incidence rate ratios (IRR).

Results

Cases decreased 15.2% (n = -1011) overall. Female breast annual IRR was 0.81 (95% CI: 0.76-0.86, p < 0.001), colorectal 0.80 (95% CI: 0.79-0.81, p < 0.001) and non-small cell lung 0.91 (95% CI: 0.90-0.92, p < 0.001). Decreases were largest in 50-69 year olds for female breast and 80+ year olds for all cancers. Stage I female breast cancer declined 41.6%, but unknown stage increased 55.8%. Colorectal stages I-IV declined (range 26.6-29.9%), while unknown stage increased 803.6%. Colorectal Q2-2020 GP-urgent suspected cancer diagnoses decreased 50.0%, and 53.9% for non-small cell lung cancer. Annual screen-detected female breast and colorectal cancers fell 47.8% and 13.3%, respectively. Non-smal -cell lung cancer emergency presentation diagnoses increased 9.5% (Q2-2020) and 16.3% (Q3-2020).

Conclusion

Significantly fewer cases of three common cancers were diagnosed in 2020. Detrimental impacts on outcomes varied between cancers. Ongoing surveillance with health service optimisation will be needed to mitigate impacts.",,pdf:https://www.nature.com/articles/s41416-022-01830-6.pdf; doi:https://doi.org/10.1038/s41416-022-01830-6; html:https://europepmc.org/articles/PMC9060409; pdf:https://europepmc.org/articles/PMC9060409?pdf=render -37193316,https://doi.org/10.1016/j.xops.2023.100293,"A Datasheet for the INSIGHT Birmingham, Solihull, and Black Country Diabetic Retinopathy Screening Dataset.","Kale AU, Mills A, Guggenheim E, Gee D, Bodza S, Anumakonda A, Doal R, Williams R, Gallier S, Lee WH, Galsworthy P, Benning M, Fanning H, Keane PA, Denniston AK, Mollan SP.",,Ophthalmology science,2023,2023-02-26,Y,Diabetes mellitus; Diabetic retinopathy; Imaging; Dataset; Biomedical Data,,,"

Purpose

Diabetic retinopathy (DR) is the most common microvascular complication associated with diabetes mellitus (DM), affecting approximately 40% of this patient population. Early detection of DR is vital to ensure monitoring of disease progression and prompt sight saving treatments as required. This article describes the data contained within the INSIGHT Birmingham, Solihull, and Black Country Diabetic Retinopathy Dataset.

Design

Dataset descriptor for routinely collected eye screening data.

Participants

All diabetic patients aged 12 years and older, attending annual digital retinal photography-based screening within the Birmingham, Solihull, and Black Country Eye Screening Programme.

Methods

The INSIGHT Health Data Research Hub for Eye Health is a National Health Service (NHS)-led ophthalmic bioresource that provides researchers with safe access to anonymized, routinely collected data from contributing NHS hospitals to advance research for patient benefit. This report describes the INSIGHT Birmingham, Solihull, and Black Country DR Screening Dataset, a dataset of anonymized images and linked screening data derived from the United Kingdom's largest regional DR screening program.

Main outcome measures

This dataset consists of routinely collected data from the eye screening program. The data primarily include retinal photographs with the associated DR grading data. Additional data such as corresponding demographic details, information regarding patients' diabetic status, and visual acuity data are also available. Further details regarding available data points are available in the supplementary information, in addition to the INSIGHT webpage included below.

Results

At the time point of this analysis (December 31, 2019), the dataset comprised 6 202 161 images from 246 180 patients, with a dataset inception date of January 1, 2007. The dataset includes 1 360 547 grading episodes between R0M0 and R3M1.

Conclusions

This dataset descriptor article summarizes the content of the dataset, how it has been curated, and what its potential uses are. Data are available through a structured application process for research studies that support discovery, clinical evidence analyses, and innovation in artificial intelligence technologies for patient benefit. Further information regarding the data repository and contact details can be found at https://www.insight.hdrhub.org/.

Financial disclosures

Proprietary or commercial disclosure may be found after the references.",,pdf:http://www.ophthalmologyscience.org/article/S2666914523000258/pdf; doi:https://doi.org/10.1016/j.xops.2023.100293; html:https://europepmc.org/articles/PMC10182318; pdf:https://europepmc.org/articles/PMC10182318?pdf=render 33484944,https://doi.org/10.1016/j.compbiomed.2021.104216,"A fast, accurate, and generalisable heuristic-based negation detection algorithm for clinical text.","Slater K, Bradlow W, Motti DF, Hoehndorf R, Ball S, Gkoutos GV.",,Computers in biology and medicine,2021,2021-01-16,Y,Text Mining Negation Detection Context Disambiguation Clinical Information Extraction,,,"Negation detection is an important task in biomedical text mining. Particularly in clinical settings, it is of critical importance to determine whether findings mentioned in text are present or absent. Rule-based negation detection algorithms are a common approach to the task, and more recent investigations have resulted in the development of rule-based systems utilising the rich grammatical information afforded by typed dependency graphs. However, interacting with these complex representations inevitably necessitates complex rules, which are time-consuming to develop and do not generalise well. We hypothesise that a heuristic approach to determining negation via dependency graphs could offer a powerful alternative. We describe and implement an algorithm for negation detection based on grammatical distance from a negatory construct in a typed dependency graph. To evaluate the algorithm, we develop two testing corpora comprised of sentences of clinical text extracted from the MIMIC-III database and documents related to hypertrophic cardiomyopathy patients routinely collected at University Hospitals Birmingham NHS trust. Gold-standard validation datasets were built by a combination of human annotation and examination of algorithm error. Finally, we compare the performance of our approach with four other rule-based algorithms on both gold-standard corpora. The presented algorithm exhibits the best performance by f-measure over the MIMIC-III dataset, and a similar performance to the syntactic negation detection systems over the HCM dataset. It is also the fastest of the dependency-based negation systems explored in this study. Our results show that while a single heuristic approach to dependency-based negation detection is ignorant to certain advanced cases, it nevertheless forms a powerful and stable method, requiring minimal training and adaptation between datasets. As such, it could present a drop-in replacement or augmentation for many-rule negation approaches in clinical text-mining pipelines, particularly for cases where adaptation and rule development is not required or possible.",,doi:https://doi.org/10.1016/j.compbiomed.2021.104216; doi:https://doi.org/10.1016/j.compbiomed.2021.104216; html:https://europepmc.org/articles/PMC7910278 +37193316,https://doi.org/10.1016/j.xops.2023.100293,"A Datasheet for the INSIGHT Birmingham, Solihull, and Black Country Diabetic Retinopathy Screening Dataset.","Kale AU, Mills A, Guggenheim E, Gee D, Bodza S, Anumakonda A, Doal R, Williams R, Gallier S, Lee WH, Galsworthy P, Benning M, Fanning H, Keane PA, Denniston AK, Mollan SP.",,Ophthalmology science,2023,2023-02-26,Y,Diabetes mellitus; Diabetic retinopathy; Imaging; Dataset; Biomedical Data,,,"

Purpose

Diabetic retinopathy (DR) is the most common microvascular complication associated with diabetes mellitus (DM), affecting approximately 40% of this patient population. Early detection of DR is vital to ensure monitoring of disease progression and prompt sight saving treatments as required. This article describes the data contained within the INSIGHT Birmingham, Solihull, and Black Country Diabetic Retinopathy Dataset.

Design

Dataset descriptor for routinely collected eye screening data.

Participants

All diabetic patients aged 12 years and older, attending annual digital retinal photography-based screening within the Birmingham, Solihull, and Black Country Eye Screening Programme.

Methods

The INSIGHT Health Data Research Hub for Eye Health is a National Health Service (NHS)-led ophthalmic bioresource that provides researchers with safe access to anonymized, routinely collected data from contributing NHS hospitals to advance research for patient benefit. This report describes the INSIGHT Birmingham, Solihull, and Black Country DR Screening Dataset, a dataset of anonymized images and linked screening data derived from the United Kingdom's largest regional DR screening program.

Main outcome measures

This dataset consists of routinely collected data from the eye screening program. The data primarily include retinal photographs with the associated DR grading data. Additional data such as corresponding demographic details, information regarding patients' diabetic status, and visual acuity data are also available. Further details regarding available data points are available in the supplementary information, in addition to the INSIGHT webpage included below.

Results

At the time point of this analysis (December 31, 2019), the dataset comprised 6 202 161 images from 246 180 patients, with a dataset inception date of January 1, 2007. The dataset includes 1 360 547 grading episodes between R0M0 and R3M1.

Conclusions

This dataset descriptor article summarizes the content of the dataset, how it has been curated, and what its potential uses are. Data are available through a structured application process for research studies that support discovery, clinical evidence analyses, and innovation in artificial intelligence technologies for patient benefit. Further information regarding the data repository and contact details can be found at https://www.insight.hdrhub.org/.

Financial disclosures

Proprietary or commercial disclosure may be found after the references.",,pdf:http://www.ophthalmologyscience.org/article/S2666914523000258/pdf; doi:https://doi.org/10.1016/j.xops.2023.100293; html:https://europepmc.org/articles/PMC10182318; pdf:https://europepmc.org/articles/PMC10182318?pdf=render 37228015,https://doi.org/10.1371/journal.pbio.3002118,Dynamics of SARS-CoV-2 infection hospitalisation and infection fatality ratios over 23 months in England.,"Eales O, Haw D, Wang H, Atchison C, Ashby D, Cooke GS, Barclay W, Ward H, Darzi A, Donnelly CA, Chadeau-Hyam M, Elliott P, Riley S.",,PLoS biology,2023,2023-05-25,Y,,,,"The relationship between prevalence of infection and severe outcomes such as hospitalisation and death changed over the course of the COVID-19 pandemic. Reliable estimates of the infection fatality ratio (IFR) and infection hospitalisation ratio (IHR) along with the time-delay between infection and hospitalisation/death can inform forecasts of the numbers/timing of severe outcomes and allow healthcare services to better prepare for periods of increased demand. The REal-time Assessment of Community Transmission-1 (REACT-1) study estimated swab positivity for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection in England approximately monthly from May 2020 to March 2022. Here, we analyse the changing relationship between prevalence of swab positivity and the IFR and IHR over this period in England, using publicly available data for the daily number of deaths and hospitalisations, REACT-1 swab positivity data, time-delay models, and Bayesian P-spline models. We analyse data for all age groups together, as well as in 2 subgroups: those aged 65 and over and those aged 64 and under. Additionally, we analysed the relationship between swab positivity and daily case numbers to estimate the case ascertainment rate of England's mass testing programme. During 2020, we estimated the IFR to be 0.67% and the IHR to be 2.6%. By late 2021/early 2022, the IFR and IHR had both decreased to 0.097% and 0.76%, respectively. The average case ascertainment rate over the entire duration of the study was estimated to be 36.1%, but there was some significant variation in continuous estimates of the case ascertainment rate. Continuous estimates of the IFR and IHR of the virus were observed to increase during the periods of Alpha and Delta's emergence. During periods of vaccination rollout, and the emergence of the Omicron variant, the IFR and IHR decreased. During 2020, we estimated a time-lag of 19 days between hospitalisation and swab positivity, and 26 days between deaths and swab positivity. By late 2021/early 2022, these time-lags had decreased to 7 days for hospitalisations and 18 days for deaths. Even though many populations have high levels of immunity to SARS-CoV-2 from vaccination and natural infection, waning of immunity and variant emergence will continue to be an upwards pressure on the IHR and IFR. As investments in community surveillance of SARS-CoV-2 infection are scaled back, alternative methods are required to accurately track the ever-changing relationship between infection, hospitalisation, and death and hence provide vital information for healthcare provision and utilisation.",,pdf:https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3002118&type=printable; doi:https://doi.org/10.1371/journal.pbio.3002118; html:https://europepmc.org/articles/PMC10212114; pdf:https://europepmc.org/articles/PMC10212114?pdf=render -38237625,https://doi.org/10.1016/s0140-6736(23)02467-4,"Undervaccination and severe COVID-19 outcomes: meta-analysis of national cohort studies in England, Northern Ireland, Scotland, and Wales.",HDR UK COALESCE Consortium.,,"Lancet (London, England)",2024,2024-01-15,N,,,,"

Background

Undervaccination (receiving fewer than the recommended number of SARS-CoV-2 vaccine doses) could be associated with increased risk of severe COVID-19 outcomes-ie, COVID-19 hospitalisation or death-compared with full vaccination (receiving the recommended number of SARS-CoV-2 vaccine doses). We sought to determine the factors associated with undervaccination, and to investigate the risk of severe COVID-19 outcomes in people who were undervaccinated in each UK nation and across the UK.

Methods

We used anonymised, harmonised electronic health record data with whole population coverage to carry out cohort studies in England, Northern Ireland, Scotland, and Wales. Participants were required to be at least 5 years of age to be included in the cohorts. We estimated adjusted odds ratios for undervaccination as of June 1, 2022. We also estimated adjusted hazard ratios (aHRs) for severe COVID-19 outcomes during the period June 1 to Sept 30, 2022, with undervaccination as a time-dependent exposure. We combined results from nation-specific analyses in a UK-wide fixed-effect meta-analysis. We estimated the reduction in severe COVID-19 outcomes associated with a counterfactual scenario in which everyone in the UK was fully vaccinated on June 1, 2022.

Findings

The numbers of people undervaccinated on June 1, 2022 were 26 985 570 (45·8%) of 58 967 360 in England, 938 420 (49·8%) of 1 885 670 in Northern Ireland, 1 709 786 (34·2%) of 4 992 498 in Scotland, and 773 850 (32·8%) of 2 358 740 in Wales. People who were younger, from more deprived backgrounds, of non-White ethnicity, or had a lower number of comorbidities were less likely to be fully vaccinated. There was a total of 40 393 severe COVID-19 outcomes in the cohorts, with 14 156 of these in undervaccinated participants. We estimated the reduction in severe COVID-19 outcomes in the UK over 4 months of follow-up associated with a counterfactual scenario in which everyone was fully vaccinated on June 1, 2022 as 210 (95% CI 94-326) in the 5-15 years age group, 1544 (1399-1689) in those aged 16-74 years, and 5426 (5340-5512) in those aged 75 years or older. aHRs for severe COVID-19 outcomes in the meta-analysis for the age group of 75 years or older were 2·70 (2·61-2·78) for one dose fewer than recommended, 3·13 (2·93-3·34) for two fewer, 3·61 (3·13-4·17) for three fewer, and 3·08 (2·89-3·29) for four fewer.

Interpretation

Rates of undervaccination against COVID-19 ranged from 32·8% to 49·8% across the four UK nations in summer, 2022. Undervaccination was associated with an elevated risk of severe COVID-19 outcomes.

Funding

UK Research and Innovation National Core Studies: Data and Connectivity.",,pdf:http://www.thelancet.com/article/S0140673623024674/pdf; doi:https://doi.org/10.1016/S0140-6736(23)02467-4 34706900,https://doi.org/10.1136/emermed-2021-211706,Comparative analysis of major incident triage tools in children: a UK population-based analysis.,"Vassallo J, Chernbumroong S, Malik N, Xu Y, Keene D, Gkoutos G, Lyttle MD, Smith J, in collaboration with PERUKI (Paediatric Emergency Research in the UK and Ireland).",,Emergency medicine journal : EMJ,2021,2021-10-27,Y,Planning; Paediatrics; Major Incident; Clinical Care; Triage; Major Incidents,,,"

Introduction

Triage is a key principle in the effective management of major incidents. There is currently a paucity of evidence to guide the triage of children. The aim of this study was to perform a comparative analysis of nine adult and paediatric triage tools, including the novel 'Sheffield Paediatric Triage Tool' (SPTT), assessing their ability in identifying patients needing life-saving interventions (LSIs).

Methods

A 10-year (2008-2017) retrospective database review of the Trauma Audit Research Network (TARN) Database for paediatric patients (<16 years) was performed. Primary outcome was identification of patients receiving one or more LSIs from a previously defined list. Secondary outcomes included mortality and prediction of Injury Severity Score (ISS) >15. Primary analysis was conducted on patients with complete prehospital physiological data with planned secondary analyses using first recorded data. Performance characteristics were evaluated using sensitivity, specificity, undertriage and overtriage.

Results

15 133 patients met TARN inclusion criteria. 4962 (32.8%) had complete prehospital physiological data and 8255 (54.5%) had complete first recorded physiological data. The majority of patients were male (69.5%), with a median age of 11.9 years. The overwhelming majority of patients (95.4%) sustained blunt trauma, yielding a median ISS of 9 and overall, 875 patients (17.6%) received at least one LSI. The SPTT demonstrated the greatest sensitivity of all triage tools at identifying need for LSI (92.2%) but was associated with the highest rate of overtriage (75.0%). Both the Paediatric Triage Tape (sensitivity 34.1%) and JumpSTART (sensitivity 45.0%) performed less well at identifying LSI. By contrast, the adult Modified Physiological Triage Tool-24 (MPTT-24) triage tool had the second highest sensitivity (80.8%) with tolerable rates of overtriage (70.2%).

Conclusion

The SPTT and MPTT-24 outperform existing paediatric triage tools at identifying those patients requiring LSIs. This may necessitate a change in recommended practice. Further work is needed to determine the optimum method of paediatric major incident triage, but consideration should be given to simplifying major incident triage by the use of one generic tool (the MPTT-24) for adults and children.",,pdf:https://emj.bmj.com/content/emermed/early/2022/04/27/emermed-2021-211706.full.pdf; doi:https://doi.org/10.1136/emermed-2021-211706; html:https://europepmc.org/articles/PMC9510399; pdf:https://europepmc.org/articles/PMC9510399?pdf=render +38237625,https://doi.org/10.1016/s0140-6736(23)02467-4,"Undervaccination and severe COVID-19 outcomes: meta-analysis of national cohort studies in England, Northern Ireland, Scotland, and Wales.",HDR UK COALESCE Consortium.,,"Lancet (London, England)",2024,2024-01-15,N,,,,"

Background

Undervaccination (receiving fewer than the recommended number of SARS-CoV-2 vaccine doses) could be associated with increased risk of severe COVID-19 outcomes-ie, COVID-19 hospitalisation or death-compared with full vaccination (receiving the recommended number of SARS-CoV-2 vaccine doses). We sought to determine the factors associated with undervaccination, and to investigate the risk of severe COVID-19 outcomes in people who were undervaccinated in each UK nation and across the UK.

Methods

We used anonymised, harmonised electronic health record data with whole population coverage to carry out cohort studies in England, Northern Ireland, Scotland, and Wales. Participants were required to be at least 5 years of age to be included in the cohorts. We estimated adjusted odds ratios for undervaccination as of June 1, 2022. We also estimated adjusted hazard ratios (aHRs) for severe COVID-19 outcomes during the period June 1 to Sept 30, 2022, with undervaccination as a time-dependent exposure. We combined results from nation-specific analyses in a UK-wide fixed-effect meta-analysis. We estimated the reduction in severe COVID-19 outcomes associated with a counterfactual scenario in which everyone in the UK was fully vaccinated on June 1, 2022.

Findings

The numbers of people undervaccinated on June 1, 2022 were 26 985 570 (45·8%) of 58 967 360 in England, 938 420 (49·8%) of 1 885 670 in Northern Ireland, 1 709 786 (34·2%) of 4 992 498 in Scotland, and 773 850 (32·8%) of 2 358 740 in Wales. People who were younger, from more deprived backgrounds, of non-White ethnicity, or had a lower number of comorbidities were less likely to be fully vaccinated. There was a total of 40 393 severe COVID-19 outcomes in the cohorts, with 14 156 of these in undervaccinated participants. We estimated the reduction in severe COVID-19 outcomes in the UK over 4 months of follow-up associated with a counterfactual scenario in which everyone was fully vaccinated on June 1, 2022 as 210 (95% CI 94-326) in the 5-15 years age group, 1544 (1399-1689) in those aged 16-74 years, and 5426 (5340-5512) in those aged 75 years or older. aHRs for severe COVID-19 outcomes in the meta-analysis for the age group of 75 years or older were 2·70 (2·61-2·78) for one dose fewer than recommended, 3·13 (2·93-3·34) for two fewer, 3·61 (3·13-4·17) for three fewer, and 3·08 (2·89-3·29) for four fewer.

Interpretation

Rates of undervaccination against COVID-19 ranged from 32·8% to 49·8% across the four UK nations in summer, 2022. Undervaccination was associated with an elevated risk of severe COVID-19 outcomes.

Funding

UK Research and Innovation National Core Studies: Data and Connectivity.",,pdf:http://www.thelancet.com/article/S0140673623024674/pdf; doi:https://doi.org/10.1016/S0140-6736(23)02467-4 37644002,https://doi.org/10.1038/s41467-023-40965-9,Neonatal and maternal outcomes following SARS-CoV-2 infection and COVID-19 vaccination: a population-based matched cohort study.,"Lindsay L, Calvert C, Shi T, Carruthers J, Denny C, Donaghy J, Hopcroft LEM, Hopkins L, Goulding A, McLaughlin T, Moore E, Taylor B, Bhaskaran K, Katikireddi SV, McCabe R, McCowan C, Simpson CR, Robertson C, Sheikh A, Wood R, Stock SJ.",,Nature communications,2023,2023-08-29,Y,,,,"Understanding the impact of SARS-CoV-2 infection and COVID-19 vaccination in pregnancy on neonatal and maternal outcomes informs clinical decision-making. Here we report a national, population-based, matched cohort study to investigate associations between SARS-CoV-2 infection and, separately, COVID-19 vaccination just before or during pregnancy and the risk of adverse neonatal and maternal outcomes among women in Scotland with a singleton pregnancy ending at ≥20 weeks gestation. Neonatal outcomes are stillbirth, neonatal death, extended perinatal mortality, preterm birth (overall, spontaneous, and provider-initiated), small-for-gestational age, and low Apgar score. Maternal outcomes are admission to critical care or death, venous thromboembolism, hypertensive disorders of pregnancy, and pregnancy-related bleeding. We use conditional logistic regression to derive odds ratios adjusted for socio-demographic and clinical characteristics (aORs). We find that infection is associated with an increased risk of preterm (aOR=1.36, 95% Confidence Interval [CI] = 1.16-1.59) and very preterm birth (aOR = 1.90, 95% CI 1.20-3.02), maternal admission to critical care or death (aOR=1.72, 95% CI = 1.39-2.12), and venous thromboembolism (aOR = 2.53, 95% CI = 1.47-4.35). We find no evidence of increased risk for any of our outcomes following vaccination. These data suggest SARS-CoV-2 infection during pregnancy is associated with adverse neonatal and maternal outcomes, and COVID-19 vaccination remains a safe way for pregnant women to protect themselves and their babies against infection.",,pdf:https://www.nature.com/articles/s41467-023-40965-9.pdf; doi:https://doi.org/10.1038/s41467-023-40965-9; html:https://europepmc.org/articles/PMC10465539; pdf:https://europepmc.org/articles/PMC10465539?pdf=render 38280379,https://doi.org/10.1016/j.xcrm.2023.101391,Evidence for a causal link between intra-pancreatic fat deposition and pancreatic cancer: A prospective cohort and Mendelian randomization study.,"Yamazaki H, Streicher SA, Wu L, Fukuhara S, Wagner R, Heni M, Grossman SR, Lenz HJ, Setiawan VW, Le Marchand L, Huang BZ.",,Cell reports. Medicine,2024,2024-01-26,Y,Pancreatic adenocarcinoma; Pancreas Cancer; Fatty Pancreas; Pancreatic Fat; Pancreatic Steatosis; Pancreas Fat,,,"Prior observational studies suggest an association between intra-pancreatic fat deposition (IPFD) and pancreatic ductal adenocarcinoma (PDAC); however, the causal relationship is unclear. To elucidate causality, we conduct a prospective observational study using magnetic resonance imaging (MRI)-measured IPFD data and also perform a Mendelian randomization study using genetic instruments for IPFD. In the observational study, we use UK Biobank data (N = 29,463, median follow-up: 4.5 years) and find that high IPFD (>10%) is associated with PDAC risk (adjusted hazard ratio [HR]: 3.35, 95% confidence interval [95% CI]: 1.60-7.00). In the Mendelian randomization study, we leverage eight out of nine IPFD-associated genetic variants (p < 5 × 10-8) from a genome-wide association study in the UK Biobank (N = 25,617) and find that genetically determined IPFD is associated with PDAC (odds ratio [OR] per 1-standard deviation [SD] increase in IPFD: 2.46, 95% CI: 1.38-4.40) in the Pancreatic Cancer Cohort Consortium I, II, III (PanScan I-III)/Pancreatic Cancer Case-Control Consortium (PanC4) dataset (8,275 PDAC cases and 6,723 non-cases). This study provides evidence for a potential causal role of IPFD in the pathogenesis of PDAC. Thus, reducing IPFD may lower PDAC risk.",,doi:https://doi.org/10.1016/j.xcrm.2023.101391; html:https://europepmc.org/articles/PMC10897551; pdf:https://europepmc.org/articles/PMC10897551?pdf=render 38086891,https://doi.org/10.1038/s41598-023-48894-9,surviveR: a flexible shiny application for patient survival analysis.,"Sessler T, Quinn GP, Wappett M, Rogan E, Sharkey D, Ahmaderaghi B, Lawler M, Longley DB, McDade SS.",,Scientific reports,2023,2023-12-13,Y,,,,"Kaplan-Meier (KM) survival analyses based on complex patient categorization due to the burgeoning volumes of genomic, molecular and phenotypic data, are an increasingly important aspect of the biomedical researcher's toolkit. Commercial statistics and graphing packages for such analyses are functionally limited, whereas open-source tools have a high barrier-to-entry in terms of understanding of methodologies and computational expertise. We developed surviveR to address this unmet need for a survival analysis tool that can enable users with limited computational expertise to conduct routine but complex analyses. surviveR is a cloud-based Shiny application, that addresses our identified unmet need for an easy-to-use web-based tool that can plot and analyse survival based datasets. Integrated customization options allows a user with limited computational expertise to easily filter patients to enable custom cohort generation, automatically calculate log-rank test and Cox hazard ratios. Continuous datasets can be integrated, such as RNA or protein expression measurements which can be then used as categories for survival plotting. We further demonstrate the utility through exemplifying its application to a clinically relevant colorectal cancer patient dataset. surviveR is a cloud-based web application available at https://generatr.qub.ac.uk/app/surviveR , that can be used by non-experts users to perform complex custom survival analysis.",,pdf:https://www.nature.com/articles/s41598-023-48894-9.pdf; doi:https://doi.org/10.1038/s41598-023-48894-9; html:https://europepmc.org/articles/PMC10716386; pdf:https://europepmc.org/articles/PMC10716386?pdf=render -36102210,https://doi.org/10.1002/prp2.1007,What is the evidence that a pharmacy team working in an acute or emergency medicine department improves outcomes for patients: A systematic review.,"Punj E, Collins A, Agravedi N, Marriott J, Sapey E.",,Pharmacology research & perspectives,2022,2022-10-01,Y,Emergency Medicine; Medication Errors; Medication Reconciliation; Pharmac*,,,"Pharmacy services within hospitals are changing, with more taking on medication reconciliation activities. This systematic review was conducted to determine the measured impacts of Pharmacy teams working in an acute or emergency medicine department. The protocol followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and was prospectively registered on PROSPERO, National Institute for Health and Care Research, UK registration number: CRD42020187487. The systematic review had two co-primary aims: a reduction in the number of incorrect prescriptions on admission by comparing the medication list from primary care to secondary care, and a reduction in the severity of harm caused by these incorrect prescriptions; chosen to determine the impact of pharmacy-led medication reconciliation services in the emergency and acute medicine setting. Seventeen articles were included. Fifteen were non-randomized controlled trials and two were randomized controlled trials. The number of patients combined for all studies was 7630. No studies included were based within the UK. All studies showed benefits in terms of a reduction in medicine errors and patient harm, compared to control arms. Nine articles were included in a statistical analysis comparing the pharmacy intervention arm with the non-pharmacy control arm, with a Chi2 of 101.10 and I2 value = 92%. However, studies were heterogenous with different outcome measures and many showed evidence of bias. The included studies consistently indicated that pharmacy services based within acute or emergency medicine departments in hospitals were associated with fewer medication errors. Further studies are needed to understand the health and economic impact of deploying a pharmacy service in acute medical settings including out-of-hours working.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9471999; doi:https://doi.org/10.1002/prp2.1007; html:https://europepmc.org/articles/PMC9471999; pdf:https://europepmc.org/articles/PMC9471999?pdf=render 33045103,https://doi.org/10.1002/gps.5446,Socio-economic predictors of time to care home admission in people living with dementia in Wales: A routine data linkage study.,"Giebel C, Hollinghurst J, Akbari A, Schnier C, Wilkinson T, North L, Gabbay M, Rodgers S.",,International journal of geriatric psychiatry,2021,2020-10-19,Y,Dementia; Care Homes; Socio-economic Status; Health Inequalities; Routine Data,,,"

Objectives

Limited research has shown that people with dementia (PwD) from lower socio-economic backgrounds can face difficulties in accessing the right care at the right time. This study examined whether socio-economic status (SES) and rural versus urban living location are associated with the time between diagnosis and care home admission in PwD living in Wales, UK.

Methods/design

This study linked routine health data and an e-cohort of PwD who have been admitted into a care home between 2000 and 2018 living in Wales. Survival analysis explored the effects of SES, living location, living situation, and frailty on the time between diagnosis and care home admission.

Results

In 34,514 PwD, the average time between diagnosis and care home admission was 1.5 (±1.4) years. Cox regression analysis showed that increased age, living alone, frailty, and living in less disadvantaged neighbourhoods were associated with faster rate to care home admission. Living in rural regions predicted a slower rate until care home admission.

Conclusions

This is one of the first studies to show a link between socio-economic factors on time to care home admission in dementia. Future research needs to address variations in care needs between PwD from different socio-economic and geographical backgrounds.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/gps.5446; doi:https://doi.org/10.1002/gps.5446; html:https://europepmc.org/articles/PMC7984448; pdf:https://europepmc.org/articles/PMC7984448?pdf=render +36102210,https://doi.org/10.1002/prp2.1007,What is the evidence that a pharmacy team working in an acute or emergency medicine department improves outcomes for patients: A systematic review.,"Punj E, Collins A, Agravedi N, Marriott J, Sapey E.",,Pharmacology research & perspectives,2022,2022-10-01,Y,Emergency Medicine; Medication Errors; Medication Reconciliation; Pharmac*,,,"Pharmacy services within hospitals are changing, with more taking on medication reconciliation activities. This systematic review was conducted to determine the measured impacts of Pharmacy teams working in an acute or emergency medicine department. The protocol followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and was prospectively registered on PROSPERO, National Institute for Health and Care Research, UK registration number: CRD42020187487. The systematic review had two co-primary aims: a reduction in the number of incorrect prescriptions on admission by comparing the medication list from primary care to secondary care, and a reduction in the severity of harm caused by these incorrect prescriptions; chosen to determine the impact of pharmacy-led medication reconciliation services in the emergency and acute medicine setting. Seventeen articles were included. Fifteen were non-randomized controlled trials and two were randomized controlled trials. The number of patients combined for all studies was 7630. No studies included were based within the UK. All studies showed benefits in terms of a reduction in medicine errors and patient harm, compared to control arms. Nine articles were included in a statistical analysis comparing the pharmacy intervention arm with the non-pharmacy control arm, with a Chi2 of 101.10 and I2 value = 92%. However, studies were heterogenous with different outcome measures and many showed evidence of bias. The included studies consistently indicated that pharmacy services based within acute or emergency medicine departments in hospitals were associated with fewer medication errors. Further studies are needed to understand the health and economic impact of deploying a pharmacy service in acute medical settings including out-of-hours working.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9471999; doi:https://doi.org/10.1002/prp2.1007; html:https://europepmc.org/articles/PMC9471999; pdf:https://europepmc.org/articles/PMC9471999?pdf=render 34238721,https://doi.org/10.1016/s2589-7500(21)00105-9,Temporal trends and forecasting of COVID-19 hospitalisations and deaths in Scotland using a national real-time patient-level data platform: a statistical modelling study.,"Simpson CR, Robertson C, Vasileiou E, Moore E, McCowan C, Agrawal U, Stagg HR, Docherty A, Mulholland R, Murray JLK, Ritchie LD, McMenamin J, Sheikh A.",,The Lancet. Digital health,2021,2021-07-05,Y,,,,"

Background

As the COVID-19 pandemic continues, national-level surveillance platforms with real-time individual person-level data are required to monitor and predict the epidemiological and clinical profile of COVID-19 and inform public health policy. We aimed to create a national dataset of patient-level data in Scotland to identify temporal trends and COVID-19 risk factors, and to develop a novel statistical prediction model to forecast COVID-19-related deaths and hospitalisations during the second wave.

Methods

We established a surveillance platform to monitor COVID-19 temporal trends using person-level primary care data (including age, sex, socioeconomic status, urban or rural residence, care home residence, and clinical risk factors) linked to data on SARS-CoV-2 RT-PCR tests, hospitalisations, and deaths for all individuals resident in Scotland who were registered with a general practice on Feb 23, 2020. A Cox proportional hazards model was used to estimate the association between clinical risk groups and time to hospitalisation and death. A survival prediction model derived from data from March 1 to June 23, 2020, was created to forecast hospital admissions and deaths from October to December, 2020. We fitted a generalised additive spline model to daily SARS-CoV-2 cases over the previous 10 weeks and used this to create a 28-day forecast of the number of daily cases. The age and risk group pattern of cases in the previous 3 weeks was then used to select a stratified sample of individuals from our cohort who had not previously tested positive, with future cases in each group sampled from a multinomial distribution. We then used their patient characteristics (including age, sex, comorbidities, and socioeconomic status) to predict their probability of hospitalisation or death.

Findings

Our cohort included 5 384 819 people, representing 98·6% of the entire estimated population residing in Scotland during 2020. Hospitalisation and death among those testing positive for SARS-CoV-2 between March 1 and June 23, 2020, were associated with several patient characteristics, including male sex (hospitalisation hazard ratio [HR] 1·47, 95% CI 1·38-1·57; death HR 1·62, 1·49-1·76) and various comorbidities, with the highest hospitalisation HR found for transplantation (4·53, 1·87-10·98) and the highest death HR for myoneural disease (2·33, 1·46-3·71). For those testing positive, there were decreasing temporal trends in hospitalisation and death rates. The proportion of positive tests among older age groups (>40 years) and those with at-risk comorbidities increased during October, 2020. On Nov 10, 2020, the projected number of hospitalisations for Dec 8, 2020 (28 days later) was 90 per day (95% prediction interval 55-125) and the projected number of deaths was 21 per day (12-29).

Interpretation

The estimated incidence of SARS-CoV-2 infection based on positive tests recorded in this unique data resource has provided forecasts of hospitalisation and death rates for the whole of Scotland. These findings were used by the Scottish Government to inform their response to reduce COVID-19-related morbidity and mortality.

Funding

Medical Research Council, National Institute for Health Research Health Technology Assessment Programme, UK Research and Innovation Industrial Strategy Challenge Fund, Health Data Research UK, Scottish Government Director General Health and Social Care.",,doi:https://doi.org/10.1016/s2589-7500(21)00105-9; doi:https://doi.org/10.1016/S2589-7500(21)00105-9; html:https://europepmc.org/articles/PMC8257056 36083213,https://doi.org/10.1093/jamia/ocac158,Translating and evaluating historic phenotyping algorithms using SNOMED CT.,"Elkheder M, Gonzalez-Izquierdo A, Qummer Ul Arfeen M, Kuan V, Lumbers RT, Denaxas S, Shah AD.",,Journal of the American Medical Informatics Association : JAMIA,2023,2023-01-01,Y,Terminology; Phenotype; Ontology; Electronic Health Records; Snomed Ct,,,"

Objective

Patient phenotype definitions based on terminologies are required for the computational use of electronic health records. Within UK primary care research databases, such definitions have typically been represented as flat lists of Read terms, but Systematized Nomenclature of Medicine-Clinical Terms (SNOMED CT) (a widely employed international reference terminology) enables the use of relationships between concepts, which could facilitate the phenotyping process. We implemented SNOMED CT-based phenotyping approaches and investigated their performance in the CPRD Aurum primary care database.

Materials and methods

We developed SNOMED CT phenotype definitions for 3 exemplar diseases: diabetes mellitus, asthma, and heart failure, using 3 methods: ""primary"" (primary concept and its descendants), ""extended"" (primary concept, descendants, and additional relations), and ""value set"" (based on text searches of term descriptions). We also derived SNOMED CT codelists in a semiautomated manner for 276 disease phenotypes used in a study of health across the lifecourse. Cohorts selected using each codelist were compared to ""gold standard"" manually curated Read codelists in a sample of 500 000 patients from CPRD Aurum.

Results

SNOMED CT codelists selected a similar set of patients to Read, with F1 scores exceeding 0.93, and age and sex distributions were similar. The ""value set"" and ""extended"" codelists had slightly greater recall but lower precision than ""primary"" codelists. We were able to represent 257 of the 276 phenotypes by a single concept hierarchy, and for 135 phenotypes, the F1 score was greater than 0.9.

Conclusions

SNOMED CT provides an efficient way to define disease phenotypes, resulting in similar patient populations to manually curated codelists.",,pdf:https://discovery.ucl.ac.uk/id/eprint/10155637/1/ocac158.pdf; doi:https://doi.org/10.1093/jamia/ocac158; html:https://europepmc.org/articles/PMC9846670; pdf:https://europepmc.org/articles/PMC9846670?pdf=render 36189425,https://doi.org/10.1016/j.lanepe.2022.100513,"BNT162b2 COVID-19 vaccination uptake, safety, effectiveness and waning in children and young people aged 12-17 years in Scotland.","Rudan I, Millington T, Antal K, Grange Z, Fenton L, Sullivan C, Buelo A, Wood R, Woolford L, Swann OV, Murray JLK, Cullen LA, Moore E, Haider F, Almaghrabi F, McMenamin J, Agrawal U, Shah SA, Kerr S, Simpson CR, Katikireddi SV, Ritchie SLD, Robertson C, Sheikh SA.",,The Lancet regional health. Europe,2022,2022-09-28,Y,Scotland; United Kingdom; Children And Young People; Vaccine Effectiveness; Vaccine Uptake; Vaccine Safety; Vaccine Waning; Age Group 12-15 Years; Covid-19; Bnt162b2 Covid-19 Vaccination; Age Group 16-17 Years; National Prospective Cohort Study,,,"

Background

The two-dose BNT162b2 (Pfizer-BioNTech) vaccine has demonstrated high efficacy against COVID-19 disease in clinical trials of children and young people (CYP). Consequently, we investigated the uptake, safety, effectiveness and waning of the protective effect of the BNT162b2 against symptomatic COVID-19 in CYP aged 12-17 years in Scotland.

Methods

The analysis of the vaccine uptake was based on information from the Turas Vaccination Management Tool, inclusive of Mar 1, 2022. Vaccine safety was evaluated using national data on hospital admissions and General Practice (GP) consultations, through a self-controlled case series (SCCS) design, investigating 17 health outcomes of interest. Vaccine effectiveness (VE) against symptomatic COVID-19 disease for Delta and Omicron variants was estimated using a test-negative design (TND) and S-gene status in a prospective cohort study using the Scotland-wide Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II) surveillance platform. The waning of the VE following each dose of BNT162b2 was assessed using a matching process followed by conditional logistic regression.

Findings

Between Aug 6, 2021 and Mar 1, 2022, 75.9% of the 112,609 CYP aged 16-17 years received the first and 49.0% the second COVID-19 vaccine dose. Among 237,681 CYP aged 12-15 years, the uptake was 64.5% and 37.2%, respectively. For 12-17-year-olds, BNT162b2 showed an excellent safety record, with no increase in hospital stays following vaccination for any of the 17 investigated health outcomes. In the 16-17-year-old group, VE against symptomatic COVID-19 during the Delta period was 64.2% (95% confidence interval [CI] 59.2-68.5) at 2-5 weeks after the first dose and 95.6% (77.0-99.1) at 2-5 weeks after the second dose. The respective VEs against symptomatic COVID-19 in the Omicron period were 22.8% (95% CI -6.4-44.0) and 65.5% (95% CI 56.0-73.0). In children aged 12-15 years, VE against symptomatic COVID-19 during the Delta period was 65.4% (95% CI 61.5-68.8) at 2-5 weeks after the first dose, with no observed cases at 2-5 weeks after the second dose. The corresponding VE against symptomatic COVID-19 during the Omicron period were 30.2% (95% CI 18.4-40.3) and 81.2% (95% CI 77.7-84.2). The waning of the protective effect against the symptomatic disease began after five weeks post-first and post-second dose.

Interpretation

During the study period, uptake of BNT162b2 in Scotland has covered more than two-thirds of CYP aged 12-17 years with the first dose and about 40% with the second dose. We found no increased likelihood of admission to hospital with a range of health outcomes in the period after vaccination. Vaccination with both doses was associated with a substantial reduction in the risk of COVID-19 symptomatic disease during both the Delta and Omicron periods, but this protection began to wane after five weeks.

Funding

UK Research and Innovation (Medical Research Council); Research and Innovation Industrial Strategy Challenge Fund; Chief Scientist's Office of the Scottish Government; Health Data Research UK; National Core Studies - Data and Connectivity.",,pdf:https://aura.abdn.ac.uk/bitstream/2164/19244/1/Rudan_etal_LRHE_BNT162b2_COVID_19_VOR.pdf; doi:https://doi.org/10.1016/j.lanepe.2022.100513; html:https://europepmc.org/articles/PMC9514975; pdf:https://europepmc.org/articles/PMC9514975?pdf=render @@ -169,8 +169,8 @@ PMC10929454,https://doi.org/,Optimising data curation pipelines for population-l 37347268,https://doi.org/10.1177/01410768231181268,"Trends in SARS-CoV-2 infection and vaccination in school staff, students and their household members from 2020 to 2022 in Wales, UK: an electronic cohort study.","Lowthian E, Abbasizanjani H, Bedston S, Akbari A, Cowley L, Fry R, Owen RK, Hollinghurst J, Rudan I, Beggs J, Marchant E, Torabi F, Lusignan S, Crick T, Moore G, Sheikh A, Lyons RA.",,Journal of the Royal Society of Medicine,2023,2023-06-22,Y,Pandemic; Schools; Population Health; Covid-19; Social Restrictions,,,"

Objectives

We investigated SARS-CoV-2 infection trends, risk of SARS-CoV-2 infection and COVID-19 vaccination uptake among school staff, students and their household members in Wales, UK.

Design

Seven-day average of SARS-CoV-2 infections and polymerase chain reaction tests per 1000 people daily, cumulative incidence of COVID-19 vaccination uptake and multi-level Poisson models with time-varying covariates.

Setting

National electronic cohort between September 2020 and May 2022 when several variants were predominant in the UK (Alpha, Delta and Omicron).

Participants

School students aged 4 to 10/11 years (primary school and younger middle school, n = 238,163), and 11 to 15/16 years (secondary school and older middle school, n = 182,775), school staff in Wales (n = 47,963) and the household members of students and staff (n = 697,659).

Main outcome measures

SARS-CoV-2 infection and COVID-19 vaccination uptake.

Results

School students had a sustained period of high infection rates compared with household members after August 2021. Primary schedule vaccination uptake was highest among staff (96.3%) but lower for household members (72.2%), secondary and older middle school students (59.8%), and primary and younger middle school students (3.3%). Multi-level Poisson models showed that vaccination was associated with a lower risk of SARS-CoV-2 infection. The Delta variant posed a greater infection risk for students than the Alpha variant. However, Omicron was a larger risk for staff and household members.

Conclusions

Public health bodies should be informed of the protection COVID-19 vaccines afford, with more research being required for younger populations. Furthermore, schools require additional support in managing new, highly transmissible variants. Further research should examine the mechanisms between child deprivation and SARS-CoV-2 infection.",,pdf:https://journals.sagepub.com/doi/pdf/10.1177/01410768231181268; doi:https://doi.org/10.1177/01410768231181268; html:https://europepmc.org/articles/PMC10767617; pdf:https://europepmc.org/articles/PMC10767617?pdf=render 35915784,https://doi.org/10.1016/j.lanepe.2022.100462,Omicron SARS-CoV-2 epidemic in England during February 2022: A series of cross-sectional community surveys.,"Chadeau-Hyam M, Tang D, Eales O, Bodinier B, Wang H, Jonnerby J, Whitaker M, Elliott J, Haw D, Walters CE, Atchison C, Diggle PJ, Page AJ, Ashby D, Barclay W, Taylor G, Cooke G, Ward H, Darzi A, Donnelly CA, Elliott P.",,The Lancet regional health. Europe,2022,2022-07-28,Y,"Rt-pcr, Reverse Transcription Polymerase Chain Reaction; Ct, Cycle Threshold; Nhs, National Health Service; Covid-19; Sars-cov-2; Omicron Variant; Ba.2 Sublineage; Random Community Surveys; Ltla, Lower-tier Local Authority; P-spline, Penalised Spline; Ukhsa, Uk Health Security Agency; B-spline, Basis Spline; Rim, Random Iterative Method",,,"

Background

The Omicron wave of COVID-19 in England peaked in January 2022 resulting from the rapid transmission of the Omicron BA.1 variant. We investigate the spread and dynamics of the SARS-CoV-2 epidemic in the population of England during February 2022, by region, age and main SARS-CoV-2 sub-lineage.

Methods

In the REal-time Assessment of Community Transmission-1 (REACT-1) study we obtained data from a random sample of 94,950 participants with valid throat and nose swab results by RT-PCR during round 18 (8 February to 1 March 2022).

Findings

We estimated a weighted mean SARS-CoV-2 prevalence of 2.88% (95% credible interval [CrI] 2.76-3.00), with a within-round effective reproduction number (R) overall of 0.94 (0·91-0.96). While within-round weighted prevalence fell among children (aged 5 to 17 years) and adults aged 18 to 54 years, we observed a level or increasing weighted prevalence among those aged 55 years and older with an R of 1.04 (1.00-1.09). Among 1,616 positive samples with sublineages determined, one (0.1% [0.0-0.3]) corresponded to XE BA.1/BA.2 recombinant and the remainder were Omicron: N=1047, 64.8% (62.4-67.2) were BA.1; N=568, 35.2% (32.8-37.6) were BA.2. We estimated an R additive advantage for BA.2 (vs BA.1) of 0.38 (0.34-0.41). The highest proportion of BA.2 among positives was found in London.

Interpretation

In February 2022, infection prevalence in England remained high with level or increasing rates of infection in older people and an uptick in hospitalisations. Ongoing surveillance of both survey and hospitalisations data is required.

Funding

Department of Health and Social Care, England.",,doi:https://doi.org/10.1016/j.lanepe.2022.100462; doi:https://doi.org/10.1016/j.lanepe.2022.100462; html:https://europepmc.org/articles/PMC9330654; pdf:https://europepmc.org/articles/PMC9330654?pdf=render 36860174,https://doi.org/10.1093/ije/dyad022,Proxy gene-by-environment Mendelian randomization study of the association between cigarette smoking during pregnancy and offspring mental health.,"Sallis HM, Wootton RE, Davey Smith G, Munafò MR.",,International journal of epidemiology,2023,2023-10-01,Y,Schizophrenia; Depression; Smoking; Mendelian Randomization,,,"

Background

Smoking prevalence is higher among individuals with schizophrenia or depression, and previous work has suggested this relationship is causal. However, this may be due to dynastic effects, for example reflecting maternal smoking during pregnancy rather than a direct effect of smoking. We used a proxy gene-by-environment Mendelian randomization approach to investigate whether there is a causal effect of maternal heaviness of smoking during pregnancy on offspring mental health.

Methods

Analyses were performed in the UK Biobank cohort. Individuals with data on smoking status, maternal smoking during pregnancy, a diagnosis of schizophrenia or depression, and genetic data were included. We used participants' genotype (rs16969968 in the CHRNA5 gene) as a proxy for their mothers' genotype. Analyses were stratified on participants' own smoking status in order to estimate the effect of maternal smoking heaviness during pregnancy independently of offspring smoking.

Results

The effect of maternal smoking on offspring schizophrenia was in opposing directions when stratifying on offspring smoking status. Among offspring of never smokers, each additional risk allele for maternal smoking heaviness appeared to have a protective effect [odds ratio (OR) = 0.77, 95% confidence interval (CI) 0.62 to 0.95, P = 0.015], whereas among ever smokers the effect of maternal smoking was in the reverse direction (OR = 1.23, 95% CI 1.05 to 1.45, P = 0.011, Pinteraction <0.001). There was no clear evidence of an association between maternal smoking heaviness and offspring depression.

Conclusions

These findings do not provide clear evidence of an effect of maternal smoking during pregnancy on offspring schizophrenia or depression, which implies that any causal effect of smoking on schizophrenia or depression is direct.",,pdf:https://academic.oup.com/ije/advance-article-pdf/doi/10.1093/ije/dyad022/49393500/dyad022.pdf; doi:https://doi.org/10.1093/ije/dyad022; html:https://europepmc.org/articles/PMC10555861; pdf:https://europepmc.org/articles/PMC10555861?pdf=render -38539097,https://doi.org/10.1186/s12877-024-04804-w,'In the shower crying…but we came back in the following day and did it all again'. Distress and resilience in care home staff during the COVID-19 pandemic- A qualitative interview study.,"Cockshott Z, Russell S, Stocker R, Knight J, Mason S, Hanratty B, Preston N.",,BMC geriatrics,2024,2024-03-27,Y,Resilience; Nursing Homes; Care Homes; Coping; Long-term Care Facilities; Staff Well-being; Covid-19; Staff Mental Health,,,"

Background

Care homes (long-term care facilities) were profoundly impacted early in the COVID-19 pandemic, both in terms of resident mortality and restrictions for infection control. This study investigated the impact on the emotional well-being of care home staff of challenges faced at this time, and the strategies used to manage them.

Methods

Semi-structured interviews conducted October 2020-June 2021 with care home staff and health service staff working with them explored the impact of the early waves of the COVID-19 pandemic (March 2020-June 2021). Interview data were analysed using reflexive thematic analysis.

Results

Interview participants were 16 care home staff and 10 health service staff. Analysis generated four key themes: 1)Anxiety and distress, 2)Overwhelming workload, 3)Pulling through; and 4)Resilience in a time of crisis. Care home staff experienced Anxiety and distress due to uncertainty of what to expect; witnessing illness and deaths of residents; concerns regarding their own health, and sometimes feeling their work was under-recognised. They also experienced an Overwhelming workload due to infection control measures, caring for sick residents and reduction in external healthcare support. Our theme of Pulling through reflects the peer support and problem-solving strategies with which care home staff managed the impact of the pandemic, along with a sense of responsibility and meaning towards their work. An overarching theme of Resilience in a time of crisis drew on the other three themes and describes how many staff managed, maintained, and often increased their work despite the challenges of the pandemic. Participants also described increasing emotional fatigue as the pandemic continued.

Conclusions

This paper builds on literature on the emotional impact of the pandemic on care home staff, also exploring ways that staff responded to this impact. These findings can help inform planning for future crises including disease outbreaks, and raise important questions for further work to develop pandemic preparedness in care homes and beyond. They also raise wider questions about the current cultural status of care work, which may have exposed care home staff to greater risk of distress, and which contrasts with the professionalism and responsibility shown by staff in response to pandemic challenges.",,pdf:https://bmcgeriatr.biomedcentral.com/counter/pdf/10.1186/s12877-024-04804-w; doi:https://doi.org/10.1186/s12877-024-04804-w; html:https://europepmc.org/articles/PMC10967173; pdf:https://europepmc.org/articles/PMC10967173?pdf=render 37126810,https://doi.org/10.7326/m21-4269,Challenges in Estimating the Effectiveness of COVID-19 Vaccination Using Observational Data.,"Hulme WJ, Williamson E, Horne EMF, Green A, McDonald HI, Walker AJ, Curtis HJ, Morton CE, MacKenna B, Croker R, Mehrkar A, Bacon S, Evans D, Inglesby P, Davy S, Bhaskaran K, Schultze A, Rentsch CT, Tomlinson L, Douglas IJ, Evans SJW, Smeeth L, Palmer T, Goldacre B, Hernán MA, Sterne JAC.",,Annals of internal medicine,2023,2023-05-02,N,,,,"The COVID-19 vaccines were developed and rigorously evaluated in randomized trials during 2020. However, important questions, such as the magnitude and duration of protection, their effectiveness against new virus variants, and the effectiveness of booster vaccination, could not be answered by randomized trials and have therefore been addressed in observational studies. Analyses of observational data can be biased because of confounding and because of inadequate design that does not consider the evolution of the pandemic over time and the rapid uptake of vaccination. Emulating a hypothetical ""target trial"" using observational data assembled during vaccine rollouts can help manage such potential sources of bias. This article describes 2 approaches to target trial emulation. In the sequential approach, on each day, eligible persons who have not yet been vaccinated are matched to a vaccinated person. The single-trial approach sets a single baseline at the start of the rollout and considers vaccination as a time-varying variable. The nature of the confounding depends on the analysis strategy: Estimating ""per-protocol"" effects (accounting for vaccination of initially unvaccinated persons after baseline) may require adjustment for both baseline and ""time-varying"" confounders. These issues are illustrated by using observational data from 2 780 931 persons in the United Kingdom aged 70 years or older to estimate the effect of a first dose of a COVID-19 vaccine. Addressing the issues discussed in this article should help authors of observational studies provide robust evidence to guide clinical and policy decisions.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10152408; doi:https://doi.org/10.7326/M21-4269; html:https://europepmc.org/articles/PMC10152408; pdf:https://europepmc.org/articles/PMC10152408?pdf=render; doi:https://doi.org/10.7326/m21-4269 +38539097,https://doi.org/10.1186/s12877-024-04804-w,'In the shower crying…but we came back in the following day and did it all again'. Distress and resilience in care home staff during the COVID-19 pandemic- A qualitative interview study.,"Cockshott Z, Russell S, Stocker R, Knight J, Mason S, Hanratty B, Preston N.",,BMC geriatrics,2024,2024-03-27,Y,Resilience; Nursing Homes; Care Homes; Coping; Long-term Care Facilities; Staff Well-being; Covid-19; Staff Mental Health,,,"

Background

Care homes (long-term care facilities) were profoundly impacted early in the COVID-19 pandemic, both in terms of resident mortality and restrictions for infection control. This study investigated the impact on the emotional well-being of care home staff of challenges faced at this time, and the strategies used to manage them.

Methods

Semi-structured interviews conducted October 2020-June 2021 with care home staff and health service staff working with them explored the impact of the early waves of the COVID-19 pandemic (March 2020-June 2021). Interview data were analysed using reflexive thematic analysis.

Results

Interview participants were 16 care home staff and 10 health service staff. Analysis generated four key themes: 1)Anxiety and distress, 2)Overwhelming workload, 3)Pulling through; and 4)Resilience in a time of crisis. Care home staff experienced Anxiety and distress due to uncertainty of what to expect; witnessing illness and deaths of residents; concerns regarding their own health, and sometimes feeling their work was under-recognised. They also experienced an Overwhelming workload due to infection control measures, caring for sick residents and reduction in external healthcare support. Our theme of Pulling through reflects the peer support and problem-solving strategies with which care home staff managed the impact of the pandemic, along with a sense of responsibility and meaning towards their work. An overarching theme of Resilience in a time of crisis drew on the other three themes and describes how many staff managed, maintained, and often increased their work despite the challenges of the pandemic. Participants also described increasing emotional fatigue as the pandemic continued.

Conclusions

This paper builds on literature on the emotional impact of the pandemic on care home staff, also exploring ways that staff responded to this impact. These findings can help inform planning for future crises including disease outbreaks, and raise important questions for further work to develop pandemic preparedness in care homes and beyond. They also raise wider questions about the current cultural status of care work, which may have exposed care home staff to greater risk of distress, and which contrasts with the professionalism and responsibility shown by staff in response to pandemic challenges.",,pdf:https://bmcgeriatr.biomedcentral.com/counter/pdf/10.1186/s12877-024-04804-w; doi:https://doi.org/10.1186/s12877-024-04804-w; html:https://europepmc.org/articles/PMC10967173; pdf:https://europepmc.org/articles/PMC10967173?pdf=render 38467603,https://doi.org/10.1038/s41467-024-46497-0,Impact of vaccination on the association of COVID-19 with cardiovascular diseases: An OpenSAFELY cohort study.,"Cezard GI, Denholm RE, Knight R, Wei Y, Teece L, Toms R, Forbes HJ, Walker AJ, Fisher L, Massey J, Hopcroft LEM, Horne EMF, Taylor K, Palmer T, Arab MA, Cuitun Coronado JI, Ip SHY, Davy S, Dillingham I, Bacon S, Mehrkar A, Morton CE, Greaves F, Hyams C, Davey Smith G, Macleod J, Chaturvedi N, Goldacre B, Whiteley WN, Wood AM, Sterne JAC, Walker V, Longitudinal Health and Wellbeing and Data and Connectivity UK COVID-19 National Core Studies, CONVALESCENCE study and the OpenSAFELY collaborative.",,Nature communications,2024,2024-03-11,Y,,,,"Infection with SARS-CoV-2 is associated with an increased risk of arterial and venous thrombotic events, but the implications of vaccination for this increased risk are uncertain. With the approval of NHS England, we quantified associations between COVID-19 diagnosis and cardiovascular diseases in different vaccination and variant eras using linked electronic health records for ~40% of the English population. We defined a 'pre-vaccination' cohort (18,210,937 people) in the wild-type/Alpha variant eras (January 2020-June 2021), and 'vaccinated' and 'unvaccinated' cohorts (13,572,399 and 3,161,485 people respectively) in the Delta variant era (June-December 2021). We showed that the incidence of each arterial thrombotic, venous thrombotic and other cardiovascular outcomes was substantially elevated during weeks 1-4 after COVID-19, compared with before or without COVID-19, but less markedly elevated in time periods beyond week 4. Hazard ratios were higher after hospitalised than non-hospitalised COVID-19 and higher in the pre-vaccination and unvaccinated cohorts than the vaccinated cohort. COVID-19 vaccination reduces the risk of cardiovascular events after COVID-19 infection. People who had COVID-19 before or without being vaccinated are at higher risk of cardiovascular events for at least two years.",,pdf:https://www.nature.com/articles/s41467-024-46497-0.pdf; doi:https://doi.org/10.1038/s41467-024-46497-0; html:https://europepmc.org/articles/PMC10928172; pdf:https://europepmc.org/articles/PMC10928172?pdf=render 38763986,https://doi.org/10.1038/s41467-024-48568-8,Medical history predicts phenome-wide disease onset and enables the rapid response to emerging health threats.,"Steinfeldt J, Wild B, Buergel T, Pietzner M, Upmeier Zu Belzen J, Vauvelle A, Hegselmann S, Denaxas S, Hemingway H, Langenberg C, Landmesser U, Deanfield J, Eils R.",,Nature communications,2024,2024-05-20,Y,,,,"The COVID-19 pandemic exposed a global deficiency of systematic, data-driven guidance to identify high-risk individuals. Here, we illustrate the utility of routinely recorded medical history to predict the risk for 1883 diseases across clinical specialties and support the rapid response to emerging health threats such as COVID-19. We developed a neural network to learn from health records of 502,460 UK Biobank. Importantly, we observed discriminative improvements over basic demographic predictors for 1774 (94.3%) endpoints. After transferring the unmodified risk models to the All of US cohort, we replicated these improvements for 1347 (89.8%) of 1500 investigated endpoints, demonstrating generalizability across healthcare systems and historically underrepresented groups. Ultimately, we showed how this approach could have been used to identify individuals vulnerable to severe COVID-19. Our study demonstrates the potential of medical history to support guidance for emerging pandemics by systematically estimating risk for thousands of diseases at once at minimal cost.",,pdf:https://www.nature.com/articles/s41467-024-48568-8.pdf; doi:https://doi.org/10.1038/s41467-024-48568-8; html:https://europepmc.org/articles/PMC11102902; pdf:https://europepmc.org/articles/PMC11102902?pdf=render 37544968,https://doi.org/10.1007/s11357-023-00890-7,"Does physical activity moderate the association between shorter leukocyte telomere length and incident coronary heart disease? Data from 54,180 UK Biobank participants.","Xiang M, Pilling LC, Melzer D, Kirk B, Duque G, Liu R, Kuchel GA, Wood AR, Metcalf B, Diniz BS, Hillsdon M, Kuo CL.",,GeroScience,2024,2023-08-07,Y,Interaction; epidemiology; Population-based Study; Prospective Cohort Study; Accelerometer; Moderation; Accelerometry; Time To Event Survival Data,,,"Telomere shortening is a biological aging hallmark. The effect of short telomere length may be targeted by increased physical activity to reduce the risk of multiple aging-related diseases, including coronary heart disease (CHD). The objective was to assess the moderation effect of accelerometer-based physical activity (aPA) on the association between shorter leukocyte telomere length (LTL) relatively in the population sample and incident CHD. Data were from the UK Biobank participants with well-calibrated accelerometer data for at least 6.5 days (n = 54,180). Relative mean LTL at baseline (5-6 years prior to aPA assessment) was measured in T/S ratio, using a multiplex quantitative polymerase chain reaction (qPCR) technology, by comparing the amount of the telomere amplification product (T) to that of a single-copy gene (S). aPA measures included total number of events (at least 10-s continued physical activity > 32 milligravities [mg]), total volume, mean duration, mean intensity, and peak intensity of all events. LTL, aPA measures, and their interactions were associated with incident CHD (mean follow-up 6.8 years) using Cox proportional hazards models adjusting for covariates. Longer LTL (relative to the sample distribution) was associated with reduced incidence of CHD (adjusted hazard ratio [aHR] = 0.94 per standard deviation [SD] increase in LTL, [95% CI, 0.90 to 0.99], P = .010). Incidence of CHD was reduced by higher total volume of aPA (aHR = 0.82 per SD increase in LTL, [95% CI, 0.71 to 0.95], P = .010) but increased by higher total number of events (aHR = 1.11 per SD increase in LTL, [95% CI, 1.02 to 1.21], P = .020) after controlling for other aPA measures and covariates. However, none of the interactions between LTL and aPA measures was statistically significant (P = .171).",,pdf:https://link.springer.com/content/pdf/10.1007/s11357-023-00890-7.pdf; doi:https://doi.org/10.1007/s11357-023-00890-7; html:https://europepmc.org/articles/PMC10828302; pdf:https://europepmc.org/articles/PMC10828302?pdf=render @@ -180,8 +180,8 @@ PMC10929454,https://doi.org/,Optimising data curation pipelines for population-l 36121907,https://doi.org/10.1161/circulationaha.122.060785,Association of COVID-19 With Major Arterial and Venous Thrombotic Diseases: A Population-Wide Cohort Study of 48 Million Adults in England and Wales.,"Knight R, Walker V, Ip S, Cooper JA, Bolton T, Keene S, Denholm R, Akbari A, Abbasizanjani H, Torabi F, Omigie E, Hollings S, North TL, Toms R, Jiang X, Angelantonio ED, Denaxas S, Thygesen JH, Tomlinson C, Bray B, Smith CJ, Barber M, Khunti K, Davey Smith G, Chaturvedi N, Sudlow C, Whiteley WN, Wood AM, Sterne JAC, CVD-COVID-UK/COVID-IMPACT Consortium and the Longitudinal Health and Wellbeing COVID-19 National Core Study.",,Circulation,2022,2022-09-19,Y,Thrombosis; Myocardial infarction; Stroke; Pulmonary embolism; Venous thrombosis; Electronic Health Records; Covid-19,,,"

Background

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces a prothrombotic state, but long-term effects of COVID-19 on incidence of vascular diseases are unclear.

Methods

We studied vascular diseases after COVID-19 diagnosis in population-wide anonymized linked English and Welsh electronic health records from January 1 to December 7, 2020. We estimated adjusted hazard ratios comparing the incidence of arterial thromboses and venous thromboembolic events (VTEs) after diagnosis of COVID-19 with the incidence in people without a COVID-19 diagnosis. We conducted subgroup analyses by COVID-19 severity, demographic characteristics, and previous history.

Results

Among 48 million adults, 125 985 were hospitalized and 1 319 789 were not hospitalized within 28 days of COVID-19 diagnosis. In England, there were 260 279 first arterial thromboses and 59 421 first VTEs during 41.6 million person-years of follow-up. Adjusted hazard ratios for first arterial thrombosis after COVID-19 diagnosis compared with no COVID-19 diagnosis declined from 21.7 (95% CI, 21.0-22.4) in week 1 after COVID-19 diagnosis to 1.34 (95% CI, 1.21-1.48) during weeks 27 to 49. Adjusted hazard ratios for first VTE after COVID-19 diagnosis declined from 33.2 (95% CI, 31.3-35.2) in week 1 to 1.80 (95% CI, 1.50-2.17) during weeks 27 to 49. Adjusted hazard ratios were higher, for longer after diagnosis, after hospitalized versus nonhospitalized COVID-19, among Black or Asian versus White people, and among people without versus with a previous event. The estimated whole-population increases in risk of arterial thromboses and VTEs 49 weeks after COVID-19 diagnosis were 0.5% and 0.25%, respectively, corresponding to 7200 and 3500 additional events, respectively, after 1.4 million COVID-19 diagnoses.

Conclusions

High relative incidence of vascular events soon after COVID-19 diagnosis declines more rapidly for arterial thromboses than VTEs. However, incidence remains elevated up to 49 weeks after COVID-19 diagnosis. These results support policies to prevent severe COVID-19 by means of COVID-19 vaccines, early review after discharge, risk factor control, and use of secondary preventive agents in high-risk patients.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCULATIONAHA.122.060785; doi:https://doi.org/10.1161/CIRCULATIONAHA.122.060785; html:https://europepmc.org/articles/PMC9484653; pdf:https://europepmc.org/articles/PMC9484653?pdf=render 35501368,https://doi.org/10.1038/s41431-022-01107-9,"Genetic analysis of the PCSK9 locus in psychological, psychiatric, metabolic and cardiovascular traits in UK Biobank.","Hay R, Cullen B, Graham N, Lyall DM, Aman A, Pell JP, Ward J, Smith DJ, Strawbridge RJ.",,European journal of human genetics : EJHG,2022,2022-05-02,Y,,,,"The association between severe mental illness (SMI) and cardiovascular and metabolic disease (CMD) is poorly understood. PCSK9 is expressed in systems critical to both SMI and CMD and influences lipid homeostasis and brain function. We systematically investigated relationships between genetic variation within the PCSK9 locus and risk for both CMD and SMI. UK Biobank recruited ~500,000 volunteers and assessed a wide range of SMI and CMD phenotypes. We used genetic data from white British ancestry individuals of UK Biobank. Genetic association analyses were conducted in PLINK, with statistical significance defined by the number of independent SNPs. Conditional analyses and linkage disequilibrium assessed the independence of SNPs and the presence of multiple signals. Two genetic risk scores of lipid-lowering alleles were calculated and used as proxies for putative lipid-lowering effects of PCSK9. PCSK9 variants were associated with central adiposity, venous thrombosis embolism, systolic blood pressure, mood instability, and neuroticism (all p < 1.16 × 10-4). No secondary signals were identified. Conditional analyses and high linkage disequilibrium (r2 = 0.98) indicated that mood instability and central obesity may share a genetic signal. Genetic risk scores suggested that the lipid-lowering effects of PCSK9 may be causal for greater mood instability and higher neuroticism. This is the first study to implicate the PCSK9 locus in mood-disorder symptoms and related traits, as well as the shared pathology of SMI and CMD. PCSK9 effects on mood may occur via lipid-lowering mechanisms. Further work is needed to understand whether repurposing PCSK9-targeting therapies might improve SMI symptoms and prevent CMD.",,pdf:https://www.nature.com/articles/s41431-022-01107-9.pdf; doi:https://doi.org/10.1038/s41431-022-01107-9; html:https://europepmc.org/articles/PMC9712543; pdf:https://europepmc.org/articles/PMC9712543?pdf=render 37056776,https://doi.org/10.3389/fimmu.2023.1146702,"SARS-CoV-2 antibody responses associate with sex, age and disease severity in previously uninfected people admitted to hospital with COVID-19: An ISARIC4C prospective study.","Parker E, Thomas J, Roper KJ, Ijaz S, Edwards T, Marchesin F, Katsanovskaja K, Lett L, Jones C, Hardwick HE, Davis C, Vink E, McDonald SE, Moore SC, Dicks S, Jegatheesan K, Cook NJ, Hope J, Cherepanov P, McClure MO, Baillie JK, Openshaw PJM, Turtle L, Ho A, Semple MG, Paxton WA, Tedder RS, Pollakis G, ISARIC4C Investigators.",,Frontiers in immunology,2023,2023-03-15,Y,Serology; Virus; Disease; immunology; Neutralisation; Covid-19; Sars-cov-2,,,"The SARS-CoV-2 pandemic enables the analysis of immune responses induced against a novel coronavirus infecting immunologically naïve individuals. This provides an opportunity for analysis of immune responses and associations with age, sex and disease severity. Here we measured an array of solid-phase binding antibody and viral neutralising Ab (nAb) responses in participants (n=337) of the ISARIC4C cohort and characterised their correlation with peak disease severity during acute infection and early convalescence. Overall, the responses in a Double Antigen Binding Assay (DABA) for antibody to the receptor binding domain (anti-RBD) correlated well with IgM as well as IgG responses against viral spike, S1 and nucleocapsid protein (NP) antigens. DABA reactivity also correlated with nAb. As we and others reported previously, there is greater risk of severe disease and death in older men, whilst the sex ratio was found to be equal within each severity grouping in younger people. In older males with severe disease (mean age 68 years), peak antibody levels were found to be delayed by one to two weeks compared with women, and nAb responses were delayed further. Additionally, we demonstrated that solid-phase binding antibody responses reached higher levels in males as measured via DABA and IgM binding against Spike, NP and S1 antigens. In contrast, this was not observed for nAb responses. When measuring SARS-CoV-2 RNA transcripts (as a surrogate for viral shedding) in nasal swabs at recruitment, we saw no significant differences by sex or disease severity status. However, we have shown higher antibody levels associated with low nasal viral RNA indicating a role of antibody responses in controlling viral replication and shedding in the upper airway. In this study, we have shown discernible differences in the humoral immune responses between males and females and these differences associate with age as well as with resultant disease severity.",,pdf:https://www.frontiersin.org/articles/10.3389/fimmu.2023.1146702/pdf; doi:https://doi.org/10.3389/fimmu.2023.1146702; html:https://europepmc.org/articles/PMC10087108; pdf:https://europepmc.org/articles/PMC10087108?pdf=render -37368589,https://doi.org/10.3390/toxics11060489,Association between Residential Exposure to Air Pollution and Incident Coronary Heart Disease Is Not Mediated by Leukocyte Telomere Length: A UK Biobank Study.,"Kuo CL, Liu R, Godoy LDC, Pilling LC, Fortinsky RH, Brugge D.",,Toxics,2023,2023-05-28,Y,Pm10; Pm2.5; No2; Nox; Pm2.5 Absorbance; Pm2.5–10,,,"Higher air pollution exposure and shorter leukocyte telomere length (LTL) are both associated with increased risk of coronary heart disease (CHD), and share plausible mechanisms, including inflammation. LTL may serve as a biomarker of air pollution exposure and may be intervened with to reduce the risk of CHD. To the best of our knowledge, we are the first to test the mediation effect of LTL in the relationship between air pollution exposure and incident CHD. Using the UK Biobank (UKB) data (n = 317,601), we conducted a prospective study linking residential air pollution exposure (PM2.5, PM10, NO2, NOx) and LTL to incident CHD during a mean follow-up of 12.6 years. Cox proportional hazards models and generalized additive models with penalized spline functions were used to model the associations of pollutant concentrations and LTL with incident CHD. We found non-linear associations of air pollution exposure with LTL and CHD. Pollutant concentrations in the lower range were decreasingly associated with longer LTL and reduced risk of CHD. The associations between lower pollutant concentrations and reduced risk of CHD, however, were minimally mediated by LTL (<3%). Our findings suggest that air pollution influences CHD through pathways that do not involve LTL. Replication is needed with improved measurements of air pollution that more accurately assesses personal exposure.",,doi:https://doi.org/10.3390/toxics11060489; html:https://europepmc.org/articles/PMC10301073; pdf:https://europepmc.org/articles/PMC10301073?pdf=render 34864250,https://doi.org/10.1016/j.seizure.2021.11.017,Epilepsy mortality in Wales during COVID-19.,"Daniels H, Lacey AS, Mikadze D, Akbari A, Fonferko-Shadrach B, Hollinghurst J, Lyons RA, Rees MI, Sawhney IM, Powell RH, Kerr MP, Pickrell WO.",,Seizure,2022,2021-11-27,Y,Pandemic; Data Linkage; Electronic Health Records; Covid-19,,,"

Purpose

The COVID-19 pandemic has increased mortality worldwide and those with chronic conditions may have been disproportionally affected. However, it is unknown whether the pandemic has changed mortality rates for people with epilepsy. We aimed to compare mortality rates in people with epilepsy in Wales during the pandemic with pre-pandemic rates.

Methods

We performed a retrospective study using individual-level linked population-scale anonymised electronic health records. We identified deaths in people with epilepsy (DPWE), i.e. those with a diagnosis of epilepsy, and deaths associated with epilepsy (DAE), where epilepsy was recorded as a cause of death on death certificates. We compared death rates in 2020 with average rates in 2015-2019 using Poisson models to calculate death rate ratios.

Results

There were 188 DAE and 628 DPWE in Wales in 2020 (death rates: 7.7/100,000/year and 25.7/100,000/year). The average rates for DAE and DPWE from 2015 to 2019 were 5.8/100,000/year and 23.8/100,000/year, respectively. Death rate ratios (2020 compared to 2015-2019) for DAE were 1.34 (95%CI 1.14-1.57, p<0.001) and for DPWE were 1.08 (0.99-1.17, p = 0.09). The death rate ratios for non-COVID deaths (deaths without COVID mentioned on death certificates) for DAE were 1.17 (0.99-1.39, p = 0.06) and for DPWE were 0.96 (0.87-1.05, p = 0.37).

Conclusions

The significant increase in DAE in Wales during 2020 could be explained by the direct effect of COVID-19 infection. Non-COVID-19 deaths have not increased significantly but further work is needed to assess the longer-term impact.",,pdf:http://www.seizure-journal.com/article/S1059131121003757/pdf; doi:https://doi.org/10.1016/j.seizure.2021.11.017; html:https://europepmc.org/articles/PMC8626872 +37368589,https://doi.org/10.3390/toxics11060489,Association between Residential Exposure to Air Pollution and Incident Coronary Heart Disease Is Not Mediated by Leukocyte Telomere Length: A UK Biobank Study.,"Kuo CL, Liu R, Godoy LDC, Pilling LC, Fortinsky RH, Brugge D.",,Toxics,2023,2023-05-28,Y,Pm10; Pm2.5; No2; Nox; Pm2.5 Absorbance; Pm2.5–10,,,"Higher air pollution exposure and shorter leukocyte telomere length (LTL) are both associated with increased risk of coronary heart disease (CHD), and share plausible mechanisms, including inflammation. LTL may serve as a biomarker of air pollution exposure and may be intervened with to reduce the risk of CHD. To the best of our knowledge, we are the first to test the mediation effect of LTL in the relationship between air pollution exposure and incident CHD. Using the UK Biobank (UKB) data (n = 317,601), we conducted a prospective study linking residential air pollution exposure (PM2.5, PM10, NO2, NOx) and LTL to incident CHD during a mean follow-up of 12.6 years. Cox proportional hazards models and generalized additive models with penalized spline functions were used to model the associations of pollutant concentrations and LTL with incident CHD. We found non-linear associations of air pollution exposure with LTL and CHD. Pollutant concentrations in the lower range were decreasingly associated with longer LTL and reduced risk of CHD. The associations between lower pollutant concentrations and reduced risk of CHD, however, were minimally mediated by LTL (<3%). Our findings suggest that air pollution influences CHD through pathways that do not involve LTL. Replication is needed with improved measurements of air pollution that more accurately assesses personal exposure.",,doi:https://doi.org/10.3390/toxics11060489; html:https://europepmc.org/articles/PMC10301073; pdf:https://europepmc.org/articles/PMC10301073?pdf=render 35858680,https://doi.org/10.1136/bmj-2021-068946,Comparative effectiveness of ChAdOx1 versus BNT162b2 covid-19 vaccines in health and social care workers in England: cohort study using OpenSAFELY.,"Hulme WJ, Williamson EJ, Green ACA, Bhaskaran K, McDonald HI, Rentsch CT, Schultze A, Tazare J, Curtis HJ, Walker AJ, Tomlinson LA, Palmer T, Horne EMF, MacKenna B, Morton CE, Mehrkar A, Morley J, Fisher L, Bacon SCJ, Evans D, Inglesby P, Hickman G, Davy S, Ward T, Croker R, Eggo RM, Wong AYS, Mathur R, Wing K, Forbes H, Grint DJ, Douglas IJ, Evans SJW, Smeeth L, Bates C, Cockburn J, Parry J, Hester F, Harper S, Sterne JAC, Hernán MA, Goldacre B.",,BMJ (Clinical research ed.),2022,2022-07-20,Y,,,,"

Objective

To compare the effectiveness of the BNT162b2 mRNA (Pfizer-BioNTech) and the ChAdOx1 (Oxford-AstraZeneca) covid-19 vaccines against infection and covid-19 disease in health and social care workers.

Design

Cohort study, emulating a comparative effectiveness trial, on behalf of NHS England.

Setting

Linked primary care, hospital, and covid-19 surveillance records available within the OpenSAFELY-TPP research platform, covering a period when the SARS-CoV-2 Alpha variant was dominant.

Participants

317 341 health and social care workers vaccinated between 4 January and 28 February 2021, registered with a general practice using the TPP SystmOne clinical information system in England, and not clinically extremely vulnerable.

Interventions

Vaccination with either BNT162b2 or ChAdOx1 administered as part of the national covid-19 vaccine roll-out.

Main outcome measures

Recorded SARS-CoV-2 positive test, or covid-19 related attendance at an accident and emergency (A&E) department or hospital admission occurring within 20 weeks of receipt of the first vaccine dose.

Results

Over the duration of 118 771 person-years of follow-up there were 6962 positive SARS-CoV-2 tests, 282 covid-19 related A&E attendances, and 166 covid-19 related hospital admissions. The cumulative incidence of each outcome was similar for both vaccines during the first 20 weeks after vaccination. The cumulative incidence of recorded SARS-CoV-2 infection 20 weeks after first-dose vaccination with BNT162b2 was 21.7 per 1000 people (95% confidence interval 20.9 to 22.4) and with ChAdOx1 was 23.7 (21.8 to 25.6), representing a difference of 2.04 per 1000 people (0.04 to 4.04). The difference in the cumulative incidence per 1000 people of covid-19 related A&E attendance at 20 weeks was 0.06 per 1000 people (95% CI -0.31 to 0.43). For covid-19 related hospital admission, this difference was 0.11 per 1000 people (-0.22 to 0.44).

Conclusions

In this cohort of healthcare workers where we would not anticipate vaccine type to be related to health status, we found no substantial differences in the incidence of SARS-CoV-2 infection or covid-19 disease up to 20 weeks after vaccination. Incidence dropped sharply at 3-4 weeks after vaccination, and there were few covid-19 related hospital attendance and admission events after this period. This is in line with expected onset of vaccine induced immunity and suggests strong protection against Alpha variant covid-19 disease for both vaccines in this relatively young and healthy population of healthcare workers.",,pdf:https://www.bmj.com/content/bmj/378/bmj-2021-068946.full.pdf; doi:https://doi.org/10.1136/bmj-2021-068946; html:https://europepmc.org/articles/PMC9295078; pdf:https://europepmc.org/articles/PMC9295078?pdf=render 34850818,https://doi.org/10.1093/ageing/afab223,"COVID-19 infection risk amongst 14,104 vaccinated care home residents: a national observational longitudinal cohort study in Wales, UK, December 2020-March 2021.","Hollinghurst J, North L, Perry M, Akbari A, Gravenor MB, Lyons RA, Fry R.",,Age and ageing,2022,2022-01-01,Y,Vaccination; Older People; Care Homes; Covid-19; Sars-cov-2,,,"

Background

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

Aim

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

Study design and setting

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

Methods

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

Results

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

Conclusions

increased risk of infection after 21 days was associated with frailty. We found most infections occurred within 28 days of vaccination, suggesting extra precautions to reduce transmission risk should be taken in this time frame.",,pdf:https://academic.oup.com/ageing/article-pdf/51/1/afab223/42083726/afab223.pdf; doi:https://doi.org/10.1093/ageing/afab223; html:https://europepmc.org/articles/PMC8690013; pdf:https://europepmc.org/articles/PMC8690013?pdf=render 34713086,https://doi.org/10.3389/fdgth.2021.598916,Markup: A Web-Based Annotation Tool Powered by Active Learning.,"Dobbie S, Strafford H, Pickrell WO, Fonferko-Shadrach B, Jones C, Akbari A, Thompson S, Lacey A.",,Frontiers in digital health,2021,2021-07-26,Y,Active Learning; Annotation; Natural Language Processing; Unstructured Text; Sequence-to-sequence Learning,,,"Across various domains, such as health and social care, law, news, and social media, there are increasing quantities of unstructured texts being produced. These potential data sources often contain rich information that could be used for domain-specific and research purposes. However, the unstructured nature of free-text data poses a significant challenge for its utilisation due to the necessity of substantial manual intervention from domain-experts to label embedded information. Annotation tools can assist with this process by providing functionality that enables the accurate capture and transformation of unstructured texts into structured annotations, which can be used individually, or as part of larger Natural Language Processing (NLP) pipelines. We present Markup (https://www.getmarkup.com/) an open-source, web-based annotation tool that is undergoing continued development for use across all domains. Markup incorporates NLP and Active Learning (AL) technologies to enable rapid and accurate annotation using custom user configurations, predictive annotation suggestions, and automated mapping suggestions to both domain-specific ontologies, such as the Unified Medical Language System (UMLS), and custom, user-defined ontologies. We demonstrate a real-world use case of how Markup has been used in a healthcare setting to annotate structured information from unstructured clinic letters, where captured annotations were used to build and test NLP applications.",,pdf:https://www.frontiersin.org/articles/10.3389/fdgth.2021.598916/pdf; doi:https://doi.org/10.3389/fdgth.2021.598916; html:https://europepmc.org/articles/PMC8521860; pdf:https://europepmc.org/articles/PMC8521860?pdf=render @@ -200,8 +200,8 @@ PMC10929454,https://doi.org/,Optimising data curation pipelines for population-l 34497074,https://doi.org/10.1136/bmjopen-2020-042483,Modelling the impact of lockdown-easing measures on cumulative COVID-19 cases and deaths in England.,"Ziauddeen H, Subramaniam N, Gurdasani D.",,BMJ open,2021,2021-09-08,Y,Infection control; epidemiology; Public Health; Health Policy,,,"

Objectives

To assess the potential impacts of successive lockdown-easing measures in England, at a point in the COVID-19 pandemic when community transmission levels were relatively high.

Design

We developed a Bayesian model to infer incident cases and reproduction number (R) in England, from incident death data. We then used this to forecast excess cases and deaths in multiple plausible scenarios in which R increases at one or more time points.

Setting

England.

Participants

Publicly available national incident death data for COVID-19 were examined.

Primary outcome

Excess cumulative cases and deaths forecast at 90 days, in simulated scenarios of plausible increases in R after successive easing of lockdown in England, compared with a baseline scenario where R remained constant.

Results

Our model inferred an R of 0.75 on 13 May when England first started easing lockdown. In the most conservative scenario modelled where R increased to 0.80 as lockdown was eased further on 1 June and then remained constant, the model predicted an excess 257 (95% CI 108 to 492) deaths and 26 447 (95% CI 11 105 to 50 549) cumulative cases over 90 days. In the scenario with maximal increases in R (but staying ≤1), the model predicts 3174 (95% CI 1334 to 6060) excess cumulative deaths and 421 310 (95% CI 177 012 to 804 811) cases. Observed data from the forecasting period aligned most closely to the scenario in which R increased to 0.85 on 1 June, and 0.9 on 4 July.

Conclusions

When levels of transmission are high, even small changes in R with easing of lockdown can have significant impacts on expected cases and deaths, even if R remains ≤1. This will have a major impact on population health, tracing systems and healthcare services in England. Following an elimination strategy rather than one of maintenance of R ≤1 would substantially mitigate the impact of the COVID-19 epidemic within England.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/9/e042483.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-042483; html:https://europepmc.org/articles/PMC8438582; pdf:https://europepmc.org/articles/PMC8438582?pdf=render 38332132,https://doi.org/10.1038/s41467-024-45445-2,Disease clusters subsequent to anxiety and stress-related disorders and their genetic determinants.,"Han X, Shen Q, Hou C, Yang H, Chen W, Zeng Y, Qu Y, Suo C, Ye W, Fang F, Valdimarsdóttir UA, Song H.",,Nature communications,2024,2024-02-08,Y,,,,"Anxiety/stress-related disorders have been associated with multiple diseases, whereas a comprehensive assessment of the structure and interplay of subsequent associated diseases and their genetic underpinnings is lacking. Here, we first identify 136, out of 454 tested, medical conditions associated with incident anxiety/stress-related disorders attended in specialized care using a population-based cohort from the nationwide Swedish Patient Register, comprising 70,026 patients with anxiety/stress-related disorders and 1:10 birth year- and sex-matched unaffected individuals. By combining findings from the comorbidity network and disease trajectory analyses, we identify five robust disease clusters to be associated with a prior diagnosis of anxiety/stress-related disorders, featured by predominance of psychiatric disorders, eye diseases, ear diseases, cardiovascular diseases, and skin and genitourinary diseases. These five clusters and their featured diseases are largely validated in the UK Biobank. GWAS analyses based on the UK Biobank identify 3, 33, 40, 4, and 16 significantly independent single nucleotide polymorphisms for the link to the five disease clusters, respectively, which are mapped to several distinct risk genes and biological pathways. These findings motivate further mechanistic explorations and aid early risk assessment for cluster-based disease prevention among patients with newly diagnosed anxiety/stress-related disorders in specialized care.",,pdf:https://www.nature.com/articles/s41467-024-45445-2.pdf; doi:https://doi.org/10.1038/s41467-024-45445-2; html:https://europepmc.org/articles/PMC10853285; pdf:https://europepmc.org/articles/PMC10853285?pdf=render 34799365,https://doi.org/10.1136/bmjopen-2021-054861,Retrospective cohort study to evaluate medication use in patients hospitalised with COVID-19 in Scotland: protocol for a national observational study.,"Mueller T, Kerr S, McTaggart S, Kurdi A, Vasileiou E, Docherty A, Fraser K, Shi T, Simpson CR, Bennie M, Sheikh A.",,BMJ open,2021,2021-11-19,Y,Therapeutics; clinical pharmacology; Covid-19,,,"

Introduction

COVID-19 has caused millions of hospitalisations and deaths globally. A range of vaccines have been developed and are being deployed at scale in the UK to prevent SARS-CoV-2 infection, which have reduced risk of infection and severe COVID-19 outcomes. Those with COVID-19 are now being treated with several repurposed drugs based on evidence emerging from recent clinical trials. However, there is currently limited real-world data available related to the use of these drugs in routine clinical practice. The purpose of this study is to address the prevailing knowledge gaps regarding the use of dexamethasone, remdesivir and tocilizumab by conducting an exploratory drug utilisation study, aimed at providing in-depth descriptions of patients receiving these drugs as well as the treatment patterns observed in Scotland.

Methods and analysis

Retrospective cohort study, comprising adult patients admitted to hospital with confirmed or suspected COVID-19 across five Scottish Health Boards using data from in-hospital ePrescribing linked to the Early Estimation of Vaccine and Anti-Viral Effectiveness (EAVE II) COVID-19 surveillance platform. The primary outcome will be exposure to the medicines of interest (dexamethasone, remdesivir, tocilizumab), either alone or in combination; exposure will be described in terms of drug(s) of choice; prescribed and administered dose; treatment duration; and any changes in treatment, for example, dose escalation and/or switching to an alternative drug. Analyses will primarily be descriptive in nature.

Ethics and dissemination

Ethical and information governance approvals have been obtained by the National Research Ethics Service Committee, South East Scotland 02 and the Public Benefit and Privacy Panel for Health and Social Care, respectively. Findings from this study will be presented at academic and clinical conferences, and to the funders and other interested parties as appropriate; study findings will also be published in peer-reviewed journals. Publications will be available on the EAVE II website (https://www.ed.ac.uk/usher/eave-ii/key-outputs/our-publications), alongside lay summaries and infographics aimed at the general public. Press releases will also be considered, if appropriate.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/11/e054861.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-054861; html:https://europepmc.org/articles/PMC8609490; pdf:https://europepmc.org/articles/PMC8609490?pdf=render -38429771,https://doi.org/10.1186/s13643-024-02477-5,Accuracy of heart failure ascertainment using routinely collected healthcare data: a systematic review and meta-analysis.,"Goonasekera MA, Offer A, Karsan W, El-Nayir M, Mallorie AE, Parish S, Haynes RJ, Mafham MM.",,Systematic reviews,2024,2024-03-01,Y,"Meta-analysis; Systematic Review,; Methods Comparison,; Outcome Ascertainment,; Randomized Trials,; Streamlined Clinical Trials,",,,"

Background

Ascertainment of heart failure (HF) hospitalizations in cardiovascular trials is costly and complex, involving processes that could be streamlined by using routinely collected healthcare data (RCD). The utility of coded RCD for HF outcome ascertainment in randomized trials requires assessment. We systematically reviewed studies assessing RCD-based HF outcome ascertainment against ""gold standard"" (GS) methods to study the feasibility of using such methods in clinical trials.

Methods

Studies assessing International Classification of Disease (ICD) coded RCD-based HF outcome ascertainment against GS methods and reporting at least one agreement statistic were identified by searching MEDLINE and Embase from inception to May 2021. Data on study characteristics, details of RCD and GS data sources and definitions, and test statistics were reviewed. Summary sensitivities and specificities for studies ascertaining acute and prevalent HF were estimated using a bivariate random effects meta-analysis. Heterogeneity was evaluated using I2 statistics and hierarchical summary receiver operating characteristic (HSROC) curves.

Results

A total of 58 studies of 48,643 GS-adjudicated HF events were included in this review. Strategies used to improve case identification included the use of broader coding definitions, combining multiple data sources, and using machine learning algorithms to search free text data, but these methods were not always successful and at times reduced specificity in individual studies. Meta-analysis of 17 acute HF studies showed that RCD algorithms have high specificity (96.2%, 95% confidence interval [CI] 91.5-98.3), but lacked sensitivity (63.5%, 95% CI 51.3-74.1) with similar results for 21 prevalent HF studies. There was considerable heterogeneity between studies.

Conclusions

RCD can correctly identify HF outcomes but may miss approximately one-third of events. Methods used to improve case identification should also focus on minimizing false positives.",,pdf:https://systematicreviewsjournal.biomedcentral.com/counter/pdf/10.1186/s13643-024-02477-5; doi:https://doi.org/10.1186/s13643-024-02477-5; html:https://europepmc.org/articles/PMC10905869; pdf:https://europepmc.org/articles/PMC10905869?pdf=render 36543718,https://doi.org/10.1016/j.ebiom.2022.104402,SARS-CoV-2-specific nasal IgA wanes 9 months after hospitalisation with COVID-19 and is not induced by subsequent vaccination.,"Liew F, Talwar S, Cross A, Willett BJ, Scott S, Logan N, Siggins MK, Swieboda D, Sidhu JK, Efstathiou C, Moore SC, Davis C, Mohamed N, Nunag J, King C, Thompson AAR, Rowland-Jones SL, Docherty AB, Chalmers JD, Ho LP, Horsley A, Raman B, Poinasamy K, Marks M, Kon OM, Howard L, Wootton DG, Dunachie S, Quint JK, Evans RA, Wain LV, Fontanella S, de Silva TI, Ho A, Harrison E, Baillie JK, Semple MG, Brightling C, Thwaites RS, Turtle L, Openshaw PJM, ISARIC4C Investigators, PHOSP-COVID collaborative group.",,EBioMedicine,2023,2022-12-19,Y,Vaccination; Mucosal immunity; Convalescent; Covid-19; Sars-cov-2 Immunity; Sars-cov-2 Variants; Nasal Antibody,,,"

Background

Most studies of immunity to SARS-CoV-2 focus on circulating antibody, giving limited insights into mucosal defences that prevent viral replication and onward transmission. We studied nasal and plasma antibody responses one year after hospitalisation for COVID-19, including a period when SARS-CoV-2 vaccination was introduced.

Methods

In this follow up study, plasma and nasosorption samples were prospectively collected from 446 adults hospitalised for COVID-19 between February 2020 and March 2021 via the ISARIC4C and PHOSP-COVID consortia. IgA and IgG responses to NP and S of ancestral SARS-CoV-2, Delta and Omicron (BA.1) variants were measured by electrochemiluminescence and compared with plasma neutralisation data.

Findings

Strong and consistent nasal anti-NP and anti-S IgA responses were demonstrated, which remained elevated for nine months (p < 0.0001). Nasal and plasma anti-S IgG remained elevated for at least 12 months (p < 0.0001) with plasma neutralising titres that were raised against all variants compared to controls (p < 0.0001). Of 323 with complete data, 307 were vaccinated between 6 and 12 months; coinciding with rises in nasal and plasma IgA and IgG anti-S titres for all SARS-CoV-2 variants, although the change in nasal IgA was minimal (1.46-fold change after 10 months, p = 0.011) and the median remained below the positive threshold determined by pre-pandemic controls. Samples 12 months after admission showed no association between nasal IgA and plasma IgG anti-S responses (R = 0.05, p = 0.18), indicating that nasal IgA responses are distinct from those in plasma and minimally boosted by vaccination.

Interpretation

The decline in nasal IgA responses 9 months after infection and minimal impact of subsequent vaccination may explain the lack of long-lasting nasal defence against reinfection and the limited effects of vaccination on transmission. These findings highlight the need to develop vaccines that enhance nasal immunity.

Funding

This study has been supported by ISARIC4C and PHOSP-COVID consortia. ISARIC4C is supported by grants from the National Institute for Health and Care Research and the Medical Research Council. Liverpool Experimental Cancer Medicine Centre provided infrastructure support for this research. The PHOSP-COVD study is jointly funded by UK Research and Innovation and National Institute of Health and Care Research. The funders were not involved in the study design, interpretation of data or the writing of this manuscript.",,pdf:http://bura.brunel.ac.uk/bitstream/2438/26835/1/FullText.pdf; doi:https://doi.org/10.1016/j.ebiom.2022.104402; html:https://europepmc.org/articles/PMC9762734; pdf:https://europepmc.org/articles/PMC9762734?pdf=render +38429771,https://doi.org/10.1186/s13643-024-02477-5,Accuracy of heart failure ascertainment using routinely collected healthcare data: a systematic review and meta-analysis.,"Goonasekera MA, Offer A, Karsan W, El-Nayir M, Mallorie AE, Parish S, Haynes RJ, Mafham MM.",,Systematic reviews,2024,2024-03-01,Y,"Meta-analysis; Systematic Review,; Methods Comparison,; Outcome Ascertainment,; Randomized Trials,; Streamlined Clinical Trials,",,,"

Background

Ascertainment of heart failure (HF) hospitalizations in cardiovascular trials is costly and complex, involving processes that could be streamlined by using routinely collected healthcare data (RCD). The utility of coded RCD for HF outcome ascertainment in randomized trials requires assessment. We systematically reviewed studies assessing RCD-based HF outcome ascertainment against ""gold standard"" (GS) methods to study the feasibility of using such methods in clinical trials.

Methods

Studies assessing International Classification of Disease (ICD) coded RCD-based HF outcome ascertainment against GS methods and reporting at least one agreement statistic were identified by searching MEDLINE and Embase from inception to May 2021. Data on study characteristics, details of RCD and GS data sources and definitions, and test statistics were reviewed. Summary sensitivities and specificities for studies ascertaining acute and prevalent HF were estimated using a bivariate random effects meta-analysis. Heterogeneity was evaluated using I2 statistics and hierarchical summary receiver operating characteristic (HSROC) curves.

Results

A total of 58 studies of 48,643 GS-adjudicated HF events were included in this review. Strategies used to improve case identification included the use of broader coding definitions, combining multiple data sources, and using machine learning algorithms to search free text data, but these methods were not always successful and at times reduced specificity in individual studies. Meta-analysis of 17 acute HF studies showed that RCD algorithms have high specificity (96.2%, 95% confidence interval [CI] 91.5-98.3), but lacked sensitivity (63.5%, 95% CI 51.3-74.1) with similar results for 21 prevalent HF studies. There was considerable heterogeneity between studies.

Conclusions

RCD can correctly identify HF outcomes but may miss approximately one-third of events. Methods used to improve case identification should also focus on minimizing false positives.",,pdf:https://systematicreviewsjournal.biomedcentral.com/counter/pdf/10.1186/s13643-024-02477-5; doi:https://doi.org/10.1186/s13643-024-02477-5; html:https://europepmc.org/articles/PMC10905869; pdf:https://europepmc.org/articles/PMC10905869?pdf=render 37494295,https://doi.org/10.1371/journal.pone.0286840,"Educational outcomes in childhood cancer survivors: A Scotland-wide record-linkage study of 766,217 schoolchildren.","Baughan N, Pell JP, Mackay DF, Clark D, King A, Fleming M.",,PloS one,2023,2023-07-26,Y,,,,"

Background

A cancer diagnosis during childhood greatly disrupts the lives of those affected, causing physical and psychological challenges. We aim to investigate educational outcomes among schoolchildren with a previous cancer diagnosis compared to their peers.

Methods

Individual records from four national education databases and three national health databases were linked to construct a cohort of all singleton schoolchildren born in Scotland attending Scottish local-authority schools between 2009-2013. Pupils previously diagnosed with any cancer, haematological cancers, and central nervous system (CNS) cancers, were compared to their unaffected peers with respect to five educational outcomes: special educational need (SEN), absenteeism, school exclusion, academic attainment, and unemployment. Analyses were adjusted for sociodemographic and maternity factors and chronic conditions.

Results

Of 766,217 pupils, 1,313 (0.17%) had a previous cancer diagnosis. Children with any cancer had increased odds of SEN (OR 3.26, 95% CI 2.86-3.71), absenteeism (IRR 1.82, 95% CI 1.70-1.94), and low attainment (OR 2.15, 95% CI 1.52-3.03) compared to their peers. Similar findings were observed for haematological (SEN OR 2.62, 95% CI 2.12-3.24; absenteeism IRR 2.04, 95% CI 1.85-2.25; low attainment OR 2.17, 95% CI 1.31-3.61) and CNS (SEN OR 6.44, 95% CI 4.91-8.46; absenteeism IRR 1.75, 95% CI 1.51-2.04; low attainment OR 3.33, 95% CI 1.52-7.30) cancers. Lower exclusions were observed among children with any cancer (IRR 0.51, 95% CI 0.31-0.83) and CNS cancer (IRR 0.20, 95% CI 0.06-0.61). No associations were observed with unemployment.

Conclusions

This study highlights the wider impacts of childhood cancer on educational outcomes. These children need to be supported, as poor educational outcomes can further impact later health.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0286840&type=printable; doi:https://doi.org/10.1371/journal.pone.0286840; html:https://europepmc.org/articles/PMC10370705; pdf:https://europepmc.org/articles/PMC10370705?pdf=render 38036541,https://doi.org/10.1038/s41467-023-43661-w,"True prevalence of long-COVID in a nationwide, population cohort study.","Hastie CE, Lowe DJ, McAuley A, Mills NL, Winter AJ, Black C, Scott JT, O'Donnell CA, Blane DN, Browne S, Ibbotson TR, Pell JP.",,Nature communications,2023,2023-11-30,Y,,,,"Long-COVID prevalence estimates vary widely and should take account of symptoms that would have occurred anyway. Here we determine the prevalence of symptoms attributable to SARS-CoV-2 infection, taking account of background rates and confounding, in a nationwide population cohort study of 198,096 Scottish adults. 98,666 (49.8%) had symptomatic laboratory-confirmed SARS-CoV-2 infections and 99,430 (50.2%) were age-, sex-, and socioeconomically-matched and never-infected. While 41,775 (64.5%) reported at least one symptom 6 months following SARS-CoV-2 infection, this was also true of 34,600 (50.8%) of those never-infected. The crude prevalence of one or more symptom attributable to SARS-CoV-2 infection was 13.8% (13.2%,14.3%), 12.8% (11.9%,13.6%), and 16.3% (14.4%,18.2%) at 6, 12, and 18 months respectively. Following adjustment for potential confounders, these figures were 6.6% (6.3%, 6.9%), 6.5% (6.0%, 6.9%) and 10.4% (9.1%, 11.6%) respectively. Long-COVID is characterised by a wide range of symptoms that, apart from altered taste and smell, are non-specific. Care should be taken in attributing symptoms to previous SARS-CoV-2 infection.",,pdf:https://www.nature.com/articles/s41467-023-43661-w.pdf; doi:https://doi.org/10.1038/s41467-023-43661-w; html:https://europepmc.org/articles/PMC10689486; pdf:https://europepmc.org/articles/PMC10689486?pdf=render 37303488,https://doi.org/10.1136/bmjmed-2022-000392,"Changes in medication safety indicators in England throughout the covid-19 pandemic using OpenSAFELY: population based, retrospective cohort study of 57 million patients using federated analytics.","Fisher L, Hopcroft LE, Rodgers S, Barrett J, Oliver K, Avery AJ, Evans D, Curtis H, Croker R, Macdonald O, Morley J, Mehrkar A, Bacon S, Davy S, Dillingham I, Evans D, Hickman G, Inglesby P, Morton CE, Smith B, Ward T, Hulme W, Green A, Massey J, Walker AJ, Bates C, Cockburn J, Parry J, Hester F, Harper S, O'Hanlon S, Eavis A, Jarvis R, Avramov D, Griffiths P, Fowles A, Parkes N, Goldacre B, MacKenna B.",,BMJ medicine,2023,2023-05-11,Y,Primary Health Care; Medical Informatics; Covid-19,,,"

Objective

To implement complex, PINCER (pharmacist led information technology intervention) prescribing indicators, on a national scale with general practice data to describe the impact of the covid-19 pandemic on safe prescribing.

Design

Population based, retrospective cohort study using federated analytics.

Setting

Electronic general practice health record data from 56.8 million NHS patients by use of the OpenSAFELY platform, with the approval of the National Health Service (NHS) England.

Participants

NHS patients (aged 18-120 years) who were alive and registered at a general practice that used TPP or EMIS computer systems and were recorded as at risk of at least one potentially hazardous PINCER indicator.

Main outcome measure

Between 1 September 2019 and 1 September 2021, monthly trends and between practice variation for compliance with 13 PINCER indicators, as calculated on the first of every month, were reported. Prescriptions that do not adhere to these indicators are potentially hazardous and can cause gastrointestinal bleeds; are cautioned against in specific conditions (specifically heart failure, asthma, and chronic renal failure); or require blood test monitoring. The percentage for each indicator is formed of a numerator of patients deemed to be at risk of a potentially hazardous prescribing event and the denominator is of patients for which assessment of the indicator is clinically meaningful. Higher indicator percentages represent potentially poorer performance on medication safety.

Results

The PINCER indicators were successfully implemented across general practice data for 56.8 million patient records from 6367 practices in OpenSAFELY. Hazardous prescribing remained largely unchanged during the covid-19 pandemic, with no evidence of increases in indicators of harm as captured by the PINCER indicators. The percentage of patients at risk of potentially hazardous prescribing, as defined by each PINCER indicator, at mean quarter 1 (Q1) 2020 (representing before the pandemic) ranged from 1.11% (age ≥65 years and non-steroidal anti-inflammatory drugs) to 36.20% (amiodarone and no thyroid function test), while Q1 2021 (representing after the pandemic) percentages ranged from 0.75% (age ≥65 years and non-steroidal anti-inflammatory drugs) to 39.23% (amiodarone and no thyroid function test). Transient delays occurred in blood test monitoring for some medications, particularly angiotensin-converting enzyme inhibitors (where blood monitoring worsened from a mean of 5.16% in Q1 2020 to 12.14% in Q1 2021, and began to recover in June 2021). All indicators substantially recovered by September 2021. We identified 1 813 058 patients (3.1%) at risk of at least one potentially hazardous prescribing event.

Conclusion

NHS data from general practices can be analysed at national scale to generate insights into service delivery. Potentially hazardous prescribing was largely unaffected by the covid-19 pandemic in primary care health records in England.",,pdf:https://bmjmedicine.bmj.com/content/bmjmed/2/1/e000392.full.pdf; doi:https://doi.org/10.1136/bmjmed-2022-000392; html:https://europepmc.org/articles/PMC10254692; pdf:https://europepmc.org/articles/PMC10254692?pdf=render @@ -326,19 +326,19 @@ PMC10929454,https://doi.org/,Optimising data curation pipelines for population-l 35197114,https://doi.org/10.1186/s41512-022-00120-2,Comparison of methods for predicting COVID-19-related death in the general population using the OpenSAFELY platform.,"OpenSAFELY Collaborative, Williamson EJ, Tazare J, Bhaskaran K, McDonald HI, Walker AJ, Tomlinson L, Wing K, Bacon S, Bates C, Curtis HJ, Forbes HJ, Minassian C, Morton CE, Nightingale E, Mehrkar A, Evans D, Nicholson BD, Leon DA, Inglesby P, MacKenna B, Davies NG, DeVito NJ, Drysdale H, Cockburn J, Hulme WJ, Morley J, Douglas I, Rentsch CT, Mathur R, Wong A, Schultze A, Croker R, Parry J, Hester F, Harper S, Grieve R, Harrison DA, Steyerberg EW, Eggo RM, Diaz-Ordaz K, Keogh R, Evans SJW, Smeeth L, Goldacre B.",,Diagnostic and prognostic research,2022,2022-02-24,Y,Mortality; Infectious disease; Risk stratification; Statistical methodology; Risk Prediction; Covid-19,,,"

Background

Obtaining accurate estimates of the risk of COVID-19-related death in the general population is challenging in the context of changing levels of circulating infection.

Methods

We propose a modelling approach to predict 28-day COVID-19-related death which explicitly accounts for COVID-19 infection prevalence using a series of sub-studies from new landmark times incorporating time-updating proxy measures of COVID-19 infection prevalence. This was compared with an approach ignoring infection prevalence. The target population was adults registered at a general practice in England in March 2020. The outcome was 28-day COVID-19-related death. Predictors included demographic characteristics and comorbidities. Three proxies of local infection prevalence were used: model-based estimates, rate of COVID-19-related attendances in emergency care, and rate of suspected COVID-19 cases in primary care. We used data within the TPP SystmOne electronic health record system linked to Office for National Statistics mortality data, using the OpenSAFELY platform, working on behalf of NHS England. Prediction models were developed in case-cohort samples with a 100-day follow-up. Validation was undertaken in 28-day cohorts from the target population. We considered predictive performance (discrimination and calibration) in geographical and temporal subsets of data not used in developing the risk prediction models. Simple models were contrasted to models including a full range of predictors.

Results

Prediction models were developed on 11,972,947 individuals, of whom 7999 experienced COVID-19-related death. All models discriminated well between individuals who did and did not experience the outcome, including simple models adjusting only for basic demographics and number of comorbidities: C-statistics 0.92-0.94. However, absolute risk estimates were substantially miscalibrated when infection prevalence was not explicitly modelled.

Conclusions

Our proposed models allow absolute risk estimation in the context of changing infection prevalence but predictive performance is sensitive to the proxy for infection prevalence. Simple models can provide excellent discrimination and may simplify implementation of risk prediction tools.",,pdf:https://diagnprognres.biomedcentral.com/track/pdf/10.1186/s41512-022-00120-2; doi:https://doi.org/10.1186/s41512-022-00120-2; html:https://europepmc.org/articles/PMC8865947; pdf:https://europepmc.org/articles/PMC8865947?pdf=render 35918110,https://doi.org/10.1136/bmjopen-2021-057433,"Investigating the relationship between thought interference, somatic passivity and outcomes in patients with psychosis: a natural language processing approach using a clinical records search platform in south London.","Magrangeas TT, Kolliakou A, Sanyal J, Patel R, Stewart R.",,BMJ open,2022,2022-08-02,Y,Health Informatics; Adult Psychiatry; Schizophrenia & Psychotic Disorders,,,"

Objectives

We aimed to apply natural language processing algorithms in routine healthcare records to identify reported somatic passivity (external control of sensations, actions and impulses) and thought interference symptoms (thought broadcasting, insertion, withdrawal), first-rank symptoms traditionally central to diagnosing schizophrenia, and determine associations with prognosis by analysing routine outcomes.

Design

Four algorithms were developed on deidentified mental healthcare data and applied to ascertain recorded symptoms over the 3 months following first presentation to a mental healthcare provider in a cohort of patients with a primary schizophreniform disorder (ICD-10 F20-F29) diagnosis.

Setting and participants

From the electronic health records of a large secondary mental healthcare provider in south London, 9323 patients were ascertained from 2007 to the data extraction date (25 February 2020).

Outcomes

The primary binary dependent variable for logistic regression analyses was any negative outcome (Mental Health Act section, >2 antipsychotics prescribed, >22 days spent in crisis care) over the subsequent 2 years.

Results

Final adjusted models indicated significant associations of this composite outcome with baseline somatic passivity (prevalence 4.9%; adjusted OR 1.61, 95% CI 1.37 to 1.88), thought insertion (10.7%; 1.24, 95% CI 1.15 to 1.55) and thought withdrawal (4.9%; 1.36, 95% CI 1.10 to 1.69), but not independently with thought broadcast (10.3%; 1.05, 95% CI 0.91 to 1.22).

Conclusions

Symptoms traditionally central to the diagnosis of schizophrenia, but under-represented in current diagnostic frameworks, were thus identified as important predictors of short-term to medium-term prognosis in schizophreniform disorders.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/8/e057433.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-057433; html:https://europepmc.org/articles/PMC9351333; pdf:https://europepmc.org/articles/PMC9351333?pdf=render 37198478,https://doi.org/10.1038/s41586-023-06034-3,GWAS and meta-analysis identifies 49 genetic variants underlying critical COVID-19.,"Pairo-Castineira E, Rawlik K, Bretherick AD, Qi T, Wu Y, Nassiri I, McConkey GA, Zechner M, Klaric L, Griffiths F, Oosthuyzen W, Kousathanas A, Richmond A, Millar J, Russell CD, Malinauskas T, Thwaites R, Morrice K, Keating S, Maslove D, Nichol A, Semple MG, Knight J, Shankar-Hari M, Summers C, Hinds C, Horby P, Ling L, McAuley D, Montgomery H, Openshaw PJM, Begg C, Walsh T, Tenesa A, Flores C, Riancho JA, Rojas-Martinez A, Lapunzina P, GenOMICC Investigators, SCOURGE Consortium, ISARICC Investigators, 23andMe COVID-19 Team, Yang J, Ponting CP, Wilson JF, Vitart V, Abedalthagafi M, Luchessi AD, Parra EJ, Cruz R, Carracedo A, Fawkes A, Murphy L, Rowan K, Pereira AC, Law A, Fairfax B, Hendry SC, Baillie JK.",,Nature,2023,2023-05-17,Y,,,,"Critical illness in COVID-19 is an extreme and clinically homogeneous disease phenotype that we have previously shown1 to be highly efficient for discovery of genetic associations2. Despite the advanced stage of illness at presentation, we have shown that host genetics in patients who are critically ill with COVID-19 can identify immunomodulatory therapies with strong beneficial effects in this group3. Here we analyse 24,202 cases of COVID-19 with critical illness comprising a combination of microarray genotype and whole-genome sequencing data from cases of critical illness in the international GenOMICC (11,440 cases) study, combined with other studies recruiting hospitalized patients with a strong focus on severe and critical disease: ISARIC4C (676 cases) and the SCOURGE consortium (5,934 cases). To put these results in the context of existing work, we conduct a meta-analysis of the new GenOMICC genome-wide association study (GWAS) results with previously published data. We find 49 genome-wide significant associations, of which 16 have not been reported previously. To investigate the therapeutic implications of these findings, we infer the structural consequences of protein-coding variants, and combine our GWAS results with gene expression data using a monocyte transcriptome-wide association study (TWAS) model, as well as gene and protein expression using Mendelian randomization. We identify potentially druggable targets in multiple systems, including inflammatory signalling (JAK1), monocyte-macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).",,pdf:https://www.nature.com/articles/s41586-023-06034-3.pdf; doi:https://doi.org/10.1038/s41586-023-06034-3; html:https://europepmc.org/articles/PMC10208981; pdf:https://europepmc.org/articles/PMC10208981?pdf=render -38106617,https://doi.org/10.1016/j.patter.2023.100892,Mortality prediction with adaptive feature importance recalibration for peritoneal dialysis patients.,"Ma L, Zhang C, Gao J, Jiao X, Yu Z, Zhu Y, Wang T, Ma X, Wang Y, Tang W, Zhao X, Ruan W, Wang T.",,"Patterns (New York, N.Y.)",2023,2023-12-08,Y,Peritoneal dialysis; PD; End-stage Renal Disease; Electronic Medical Record; Emr; Esrd; Mortality Prediction; Deep Learning; Model Interpretability,,,"The study aims to develop AICare, an interpretable mortality prediction model, using electronic medical records (EMR) from follow-up visits for end-stage renal disease (ESRD) patients. AICare includes a multichannel feature extraction module and an adaptive feature importance recalibration module. It integrates dynamic records and static features to perform personalized health context representation learning. The dataset encompasses 13,091 visits and demographic data of 656 peritoneal dialysis (PD) patients spanning 12 years. An additional public dataset of 4,789 visits from 1,363 hemodialysis (HD) patients is also considered. AICare outperforms traditional deep learning models in mortality prediction while retaining interpretability. It uncovers mortality-feature relationships and variations in feature importance and provides reference values. An AI-doctor interaction system is developed for visualizing patients' health trajectories and risk indicators.",,doi:https://doi.org/10.1016/j.patter.2023.100892; html:https://europepmc.org/articles/PMC10724364; pdf:https://europepmc.org/articles/PMC10724364?pdf=render 36629015,https://doi.org/10.1177/17407745221143449,Lack of transparent reporting of trial monitoring approaches in randomised controlled trials: A systematic review of contemporary protocol papers.,"Hsieh SF, Yorke-Edwards V, Murray ML, Diaz-Montana C, Love SB, Sydes MR.",,"Clinical trials (London, England)",2023,2023-01-11,Y,Systematic review; Randomised Controlled Trial; On-site Monitoring; Risk-based Monitoring; Protocol Paper; Central Monitoring; Trial Monitoring; Reporting Monitoring,,,"

Background

Monitoring is essential to ensure patient safety and data integrity in clinical trials as per Good Clinical Practice. The Standard Protocol Items: Recommendations for Interventional Trials Statement and its checklist guides authors to include monitoring in their protocols. We investigated how well monitoring was reported in published 'protocol papers' for contemporary randomised controlled trials.

Methods

A systematic search was conducted in PubMed to identify eligible protocol papers published in selected journals between 1 January 2020 and 31 May 2020. Protocol papers were classified by whether they reported monitoring and, if so, by the details of monitoring. Data were summarised descriptively.

Results

Of 811 protocol papers for randomised controlled trials, 386 (48%; 95% CI: 44%-51%) explicitly reported some monitoring information. Of these, 20% (77/386) reported monitoring information consistent with an on-site monitoring approach, and 39% (152/386) with central monitoring, 26% (101/386) with a mixed approach, while 14% (54/386) did not provide sufficient information to specify an approach. Only 8% (30/386) of randomised controlled trials reported complete details about all of scope, frequency and organisation of monitoring; frequency of monitoring was the least reported. However, 6% (25/386) of papers used the term 'audit' to describe 'monitoring'.

Discussion

Monitoring information was reported in only approximately half of the protocol papers. Suboptimal reporting of monitoring hinders the clinical community from having the full information on which to judge the validity of a trial and jeopardises the value of protocol papers and the credibility of the trial itself. Greater efforts are needed to promote the transparent reporting of monitoring to journal editors and authors.",,pdf:https://journals.sagepub.com/doi/pdf/10.1177/17407745221143449; doi:https://doi.org/10.1177/17407745221143449; html:https://europepmc.org/articles/PMC10021127; pdf:https://europepmc.org/articles/PMC10021127?pdf=render +38106617,https://doi.org/10.1016/j.patter.2023.100892,Mortality prediction with adaptive feature importance recalibration for peritoneal dialysis patients.,"Ma L, Zhang C, Gao J, Jiao X, Yu Z, Zhu Y, Wang T, Ma X, Wang Y, Tang W, Zhao X, Ruan W, Wang T.",,"Patterns (New York, N.Y.)",2023,2023-12-08,Y,Peritoneal dialysis; PD; End-stage Renal Disease; Electronic Medical Record; Emr; Esrd; Mortality Prediction; Deep Learning; Model Interpretability,,,"The study aims to develop AICare, an interpretable mortality prediction model, using electronic medical records (EMR) from follow-up visits for end-stage renal disease (ESRD) patients. AICare includes a multichannel feature extraction module and an adaptive feature importance recalibration module. It integrates dynamic records and static features to perform personalized health context representation learning. The dataset encompasses 13,091 visits and demographic data of 656 peritoneal dialysis (PD) patients spanning 12 years. An additional public dataset of 4,789 visits from 1,363 hemodialysis (HD) patients is also considered. AICare outperforms traditional deep learning models in mortality prediction while retaining interpretability. It uncovers mortality-feature relationships and variations in feature importance and provides reference values. An AI-doctor interaction system is developed for visualizing patients' health trajectories and risk indicators.",,doi:https://doi.org/10.1016/j.patter.2023.100892; html:https://europepmc.org/articles/PMC10724364; pdf:https://europepmc.org/articles/PMC10724364?pdf=render 34446426,https://doi.org/10.1136/bmj.n1931,Risk of thrombocytopenia and thromboembolism after covid-19 vaccination and SARS-CoV-2 positive testing: self-controlled case series study.,"Hippisley-Cox J, Patone M, Mei XW, Saatci D, Dixon S, Khunti K, Zaccardi F, Watkinson P, Shankar-Hari M, Doidge J, Harrison DA, Griffin SJ, Sheikh A, Coupland CAC.",,BMJ (Clinical research ed.),2021,2021-08-26,Y,,,,"

Objective

To assess the association between covid-19 vaccines and risk of thrombocytopenia and thromboembolic events in England among adults.

Design

Self-controlled case series study using national data on covid-19 vaccination and hospital admissions.

Setting

Patient level data were obtained for approximately 30 million people vaccinated in England between 1 December 2020 and 24 April 2021. Electronic health records were linked with death data from the Office for National Statistics, SARS-CoV-2 positive test data, and hospital admission data from the United Kingdom's health service (NHS).

Participants

29 121 633 people were vaccinated with first doses (19 608 008 with Oxford-AstraZeneca (ChAdOx1 nCoV-19) and 9 513 625 with Pfizer-BioNTech (BNT162b2 mRNA)) and 1 758 095 people had a positive SARS-CoV-2 test. People aged ≥16 years who had first doses of the ChAdOx1 nCoV-19 or BNT162b2 mRNA vaccines and any outcome of interest were included in the study.

Main outcome measures

The primary outcomes were hospital admission or death associated with thrombocytopenia, venous thromboembolism, and arterial thromboembolism within 28 days of three exposures: first dose of the ChAdOx1 nCoV-19 vaccine; first dose of the BNT162b2 mRNA vaccine; and a SARS-CoV-2 positive test. Secondary outcomes were subsets of the primary outcomes: cerebral venous sinus thrombosis (CVST), ischaemic stroke, myocardial infarction, and other rare arterial thrombotic events.

Results

The study found increased risk of thrombocytopenia after ChAdOx1 nCoV-19 vaccination (incidence rate ratio 1.33, 95% confidence interval 1.19 to 1.47 at 8-14 days) and after a positive SARS-CoV-2 test (5.27, 4.34 to 6.40 at 8-14 days); increased risk of venous thromboembolism after ChAdOx1 nCoV-19 vaccination (1.10, 1.02 to 1.18 at 8-14 days) and after SARS-CoV-2 infection (13.86, 12.76 to 15.05 at 8-14 days); and increased risk of arterial thromboembolism after BNT162b2 mRNA vaccination (1.06, 1.01 to 1.10 at 15-21 days) and after SARS-CoV-2 infection (2.02, 1.82 to 2.24 at 15-21 days). Secondary analyses found increased risk of CVST after ChAdOx1 nCoV-19 vaccination (4.01, 2.08 to 7.71 at 8-14 days), after BNT162b2 mRNA vaccination (3.58, 1.39 to 9.27 at 15-21 days), and after a positive SARS-CoV-2 test; increased risk of ischaemic stroke after BNT162b2 mRNA vaccination (1.12, 1.04 to 1.20 at 15-21 days) and after a positive SARS-CoV-2 test; and increased risk of other rare arterial thrombotic events after ChAdOx1 nCoV-19 vaccination (1.21, 1.02 to 1.43 at 8-14 days) and after a positive SARS-CoV-2 test.

Conclusion

Increased risks of haematological and vascular events that led to hospital admission or death were observed for short time intervals after first doses of the ChAdOx1 nCoV-19 and BNT162b2 mRNA vaccines. The risks of most of these events were substantially higher and more prolonged after SARS-CoV-2 infection than after vaccination in the same population.",,pdf:https://www.bmj.com/content/bmj/374/bmj.n1931.full.pdf; doi:https://doi.org/10.1136/bmj.n1931; html:https://europepmc.org/articles/PMC8388189; pdf:https://europepmc.org/articles/PMC8388189?pdf=render 36051279,https://doi.org/10.3389/fcvm.2022.894503,Predicting post-contrast information from contrast agent free cardiac MRI using machine learning: Challenges and methods.,"Abdulkareem M, Kenawy AA, Rauseo E, Lee AM, Sojoudi A, Amir-Khalili A, Lekadir K, Young AA, Barnes MR, Barckow P, Khanji MY, Aung N, Petersen SE.",,Frontiers in cardiovascular medicine,2022,2022-07-27,Y,contrast; Decision tree; Machine Learning; Cmr; support vector machines; Deep Learning; Contrast-free,,,"

Objectives

Currently, administering contrast agents is necessary for accurately visualizing and quantifying presence, location, and extent of myocardial infarction (MI) with cardiac magnetic resonance (CMR). In this study, our objective is to investigate and analyze pre- and post-contrast CMR images with the goal of predicting post-contrast information using pre-contrast information only. We propose methods and identify challenges.

Methods

The study population consists of 272 retrospectively selected CMR studies with diagnoses of MI (n = 108) and healthy controls (n = 164). We describe a pipeline for pre-processing this dataset for analysis. After data feature engineering, 722 cine short-axis (SAX) images and segmentation mask pairs were used for experimentation. This constitutes 506, 108, and 108 pairs for the training, validation, and testing sets, respectively. We use deep learning (DL) segmentation (UNet) and classification (ResNet50) models to discover the extent and location of the scar and classify between the ischemic cases and healthy cases (i.e., cases with no regional myocardial scar) from the pre-contrast cine SAX image frames, respectively. We then capture complex data patterns that represent subtle signal and functional changes in the cine SAX images due to MI using optical flow, rate of change of myocardial area, and radiomics data. We apply this dataset to explore two supervised learning methods, namely, the support vector machines (SVM) and the decision tree (DT) methods, to develop predictive models for classifying pre-contrast cine SAX images as being a case of MI or healthy.

Results

Overall, for the UNet segmentation model, the performance based on the mean Dice score for the test set (n = 108) is 0.75 (±0.20) for the endocardium, 0.51 (±0.21) for the epicardium and 0.20 (±0.17) for the scar. For the classification task, the accuracy, F1 and precision scores of 0.68, 0.69, and 0.64, respectively, were achieved with the SVM model, and of 0.62, 0.63, and 0.72, respectively, with the DT model.

Conclusion

We have presented some promising approaches involving DL, SVM, and DT methods in an attempt to accurately predict contrast information from non-contrast images. While our initial results are modest for this challenging task, this area of research still poses several open problems.",,pdf:https://www.frontiersin.org/articles/10.3389/fcvm.2022.894503/pdf; doi:https://doi.org/10.3389/fcvm.2022.894503; html:https://europepmc.org/articles/PMC9426684; pdf:https://europepmc.org/articles/PMC9426684?pdf=render 37561812,https://doi.org/10.1371/journal.pcbi.1011368,Call detail record aggregation methodology impacts infectious disease models informed by human mobility.,"Gibbs H, Musah A, Seidu O, Ampofo W, Asiedu-Bekoe F, Gray J, Adewole WA, Cheshire J, Marks M, Eggo RM.",,PLoS computational biology,2023,2023-08-10,Y,,,,"This paper demonstrates how two different methods used to calculate population-level mobility from Call Detail Records (CDR) produce varying predictions of the spread of epidemics informed by these data. Our findings are based on one CDR dataset describing inter-district movement in Ghana in 2021, produced using two different aggregation methodologies. One methodology, ""all pairs,"" is designed to retain long distance network connections while the other, ""sequential"" methodology is designed to accurately reflect the volume of travel between locations. We show how the choice of methodology feeds through models of human mobility to the predictions of a metapopulation SEIR model of disease transmission. We also show that this impact varies depending on the location of pathogen introduction and the transmissibility of infections. For central locations or highly transmissible diseases, we do not observe significant differences between aggregation methodologies on the predicted spread of disease. For less transmissible diseases or those introduced into remote locations, we find that the choice of aggregation methodology influences the speed of spatial spread as well as the size of the peak number of infections in individual districts. Our findings can help researchers and users of epidemiological models to understand how methodological choices at the level of model inputs may influence the results of models of infectious disease transmission, as well as the circumstances in which these choices do not alter model predictions.",,pdf:https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1011368&type=printable; doi:https://doi.org/10.1371/journal.pcbi.1011368; html:https://europepmc.org/articles/PMC10443843; pdf:https://europepmc.org/articles/PMC10443843?pdf=render 35473737,https://doi.org/10.1136/bmjopen-2021-060413,"Therapies for Long COVID in non-hospitalised individuals: from symptoms, patient-reported outcomes and immunology to targeted therapies (The TLC Study).","Haroon S, Nirantharakumar K, Hughes SE, Subramanian A, Aiyegbusi OL, Davies EH, Myles P, Williams T, Turner G, Chandan JS, McMullan C, Lord J, Wraith DC, McGee K, Denniston AK, Taverner T, Jackson LJ, Sapey E, Gkoutos G, Gokhale K, Leggett E, Iles C, Frost C, McNamara G, Bamford A, Marshall T, Zemedikun DT, Price G, Marwaha S, Simms-Williams N, Brown K, Walker A, Jones K, Matthews K, Camaradou J, Saint-Cricq M, Kumar S, Alder Y, Stanton DE, Agyen L, Baber M, Blaize H, Calvert M.",,BMJ open,2022,2022-04-26,Y,Therapeutics; immunology; Public Health; Covid-19,,,"

Introduction

Individuals with COVID-19 frequently experience symptoms and impaired quality of life beyond 4-12 weeks, commonly referred to as Long COVID. Whether Long COVID is one or several distinct syndromes is unknown. Establishing the evidence base for appropriate therapies is needed. We aim to evaluate the symptom burden and underlying pathophysiology of Long COVID syndromes in non-hospitalised individuals and evaluate potential therapies.

Methods and analysis

A cohort of 4000 non-hospitalised individuals with a past COVID-19 diagnosis and 1000 matched controls will be selected from anonymised primary care records from the Clinical Practice Research Datalink, and invited by their general practitioners to participate on a digital platform (Atom5). Individuals will report symptoms, quality of life, work capability and patient-reported outcome measures. Data will be collected monthly for 1 year.Statistical clustering methods will be used to identify distinct Long COVID-19 symptom clusters. Individuals from the four most prevalent clusters and two control groups will be invited to participate in the BioWear substudy which will further phenotype Long COVID symptom clusters by measurement of immunological parameters and actigraphy.We will review existing evidence on interventions for postviral syndromes and Long COVID to map and prioritise interventions for each newly characterised Long COVID syndrome. Recommendations will be made using the cumulative evidence in an expert consensus workshop. A virtual supportive intervention will be coproduced with patients and health service providers for future evaluation.Individuals with lived experience of Long COVID will be involved throughout this programme through a patient and public involvement group.

Ethics and dissemination

Ethical approval was obtained from the Solihull Research Ethics Committee, West Midlands (21/WM/0203). Research findings will be presented at international conferences, in peer-reviewed journals, to Long COVID patient support groups and to policymakers.

Trial registration number

1567490.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/4/e060413.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-060413; html:https://europepmc.org/articles/PMC9044550; pdf:https://europepmc.org/articles/PMC9044550?pdf=render 34445233,https://doi.org/10.3390/ijms22168527,The Contribution of Autophagy and LncRNAs to MYC-Driven Gene Regulatory Networks in Cancers.,"Jahangiri L, Pucci P, Ishola T, Trigg RM, Williams JA, Pereira J, Cavanagh ML, Turner SD, Gkoutos GV, Tsaprouni L.",,International journal of molecular sciences,2021,2021-08-08,Y,MYC; Autophagy; Lncrnas; Gene Regulatory Networks (Grns),,,"MYC is a target of the Wnt signalling pathway and governs numerous cellular and developmental programmes hijacked in cancers. The amplification of MYC is a frequently occurring genetic alteration in cancer genomes, and this transcription factor is implicated in metabolic reprogramming, cell death, and angiogenesis in cancers. In this review, we analyse MYC gene networks in solid cancers. We investigate the interaction of MYC with long non-coding RNAs (lncRNAs). Furthermore, we investigate the role of MYC regulatory networks in inducing changes to cellular processes, including autophagy and mitophagy. Finally, we review the interaction and mutual regulation between MYC and lncRNAs, and autophagic processes and analyse these networks as unexplored areas of targeting and manipulation for therapeutic gain in MYC-driven malignancies.",,pdf:https://www.mdpi.com/1422-0067/22/16/8527/pdf?version=1628431894; doi:https://doi.org/10.3390/ijms22168527; html:https://europepmc.org/articles/PMC8395220; pdf:https://europepmc.org/articles/PMC8395220?pdf=render -35165107,https://doi.org/10.1136/bmjopen-2021-050062,"Investigating the uptake, effectiveness and safety of COVID-19 vaccines: protocol for an observational study using linked UK national data.","Vasileiou E, Shi T, Kerr S, Robertson C, Joy M, Tsang R, McGagh D, Williams J, Hobbs R, de Lusignan S, de Lusignan S, Bradley D, OReilly D, Murphy S, Chuter A, Beggs J, Ford D, Orton C, Akbari A, Bedston S, Davies G, Griffiths LJ, Griffiths R, Lowthian E, Lyons J, Lyons RA, North L, Perry M, Torabi F, Pickett J, McMenamin J, McCowan C, Agrawal U, Wood R, Stock SJ, Moore E, Henery P, Simpson CR, Sheikh A.",,BMJ open,2022,2022-02-14,Y,epidemiology; Public Health; Respiratory Infections; Covid-19,,,"

Introduction

The novel coronavirus SARS-CoV-2, which emerged in December 2019, has caused millions of deaths and severe illness worldwide. Numerous vaccines are currently under development of which a few have now been authorised for population-level administration by several countries. As of 20 September 2021, over 48 million people have received their first vaccine dose and over 44 million people have received their second vaccine dose across the UK. We aim to assess the uptake rates, effectiveness, and safety of all currently approved COVID-19 vaccines in the UK.

Methods and analysis

We will use prospective cohort study designs to assess vaccine uptake, effectiveness and safety against clinical outcomes and deaths. Test-negative case-control study design will be used to assess vaccine effectiveness (VE) against laboratory confirmed SARS-CoV-2 infection. Self-controlled case series and retrospective cohort study designs will be carried out to assess vaccine safety against mild-to-moderate and severe adverse events, respectively. Individual-level pseudonymised data from primary care, secondary care, laboratory test and death records will be linked and analysed in secure research environments in each UK nation. Univariate and multivariate logistic regression models will be carried out to estimate vaccine uptake levels in relation to various population characteristics. VE estimates against laboratory confirmed SARS-CoV-2 infection will be generated using a generalised additive logistic model. Time-dependent Cox models will be used to estimate the VE against clinical outcomes and deaths. The safety of the vaccines will be assessed using logistic regression models with an offset for the length of the risk period. Where possible, data will be meta-analysed across the UK nations.

Ethics and dissemination

We obtained approvals from the National Research Ethics Service Committee, Southeast Scotland 02 (12/SS/0201), the Secure Anonymised Information Linkage independent Information Governance Review Panel project number 0911. Concerning English data, University of Oxford is compliant with the General Data Protection Regulation and the National Health Service (NHS) Digital Data Security and Protection Policy. This is an approved study (Integrated Research Application ID 301740, Health Research Authority (HRA) Research Ethics Committee 21/HRA/2786). The Oxford-Royal College of General Practitioners Clinical Informatics Digital Hub meets NHS Digital's Data Security and Protection Toolkit requirements. In Northern Ireland, the project was approved by the Honest Broker Governance Board, project number 0064. Findings will be made available to national policy-makers, presented at conferences and published in peer-reviewed journals.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/2/e050062.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-050062; html:https://europepmc.org/articles/PMC8844955; pdf:https://europepmc.org/articles/PMC8844955?pdf=render 34829865,https://doi.org/10.3390/biomedicines9111636,Machine Learning-Based Identification of Potentially Novel Non-Alcoholic Fatty Liver Disease Biomarkers.,"Shafiha R, Bahcivanci B, Gkoutos GV, Acharjee A.",,Biomedicines,2021,2021-11-07,Y,Biomarker; Machine Learning; Lipidomics; Transcriptomics; Nafld,,,"Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease that presents a great challenge for treatment and prevention.. This study aims to implement a machine learning approach that employs such datasets to identify potential biomarker targets. We developed a pipeline to identify potential biomarkers for NAFLD that includes five major processes, namely, a pre-processing step, a feature selection and a generation of a random forest model and, finally, a downstream feature analysis and a provision of a potential biological interpretation. The pre-processing step includes data normalising and variable extraction accompanied by appropriate annotations. A feature selection based on a differential gene expression analysis is then conducted to identify significant features and then employ them to generate a random forest model whose performance is assessed based on a receiver operating characteristic curve. Next, the features are subjected to a downstream analysis, such as univariate analysis, a pathway enrichment analysis, a network analysis and a generation of correlation plots, boxplots and heatmaps. Once the results are obtained, the biological interpretation and the literature validation is conducted over the identified features and results. We applied this pipeline to transcriptomics and lipidomic datasets and concluded that the C4BPA gene could play a role in the development of NAFLD. The activation of the complement pathway, due to the downregulation of the C4BPA gene, leads to an increase in triglyceride content, which might further render the lipid metabolism. This approach identified the C4BPA gene, an inhibitor of the complement pathway, as a potential biomarker for the development of NAFLD.",,pdf:https://www.mdpi.com/2227-9059/9/11/1636/pdf?version=1637024773; doi:https://doi.org/10.3390/biomedicines9111636; html:https://europepmc.org/articles/PMC8615894; pdf:https://europepmc.org/articles/PMC8615894?pdf=render +35165107,https://doi.org/10.1136/bmjopen-2021-050062,"Investigating the uptake, effectiveness and safety of COVID-19 vaccines: protocol for an observational study using linked UK national data.","Vasileiou E, Shi T, Kerr S, Robertson C, Joy M, Tsang R, McGagh D, Williams J, Hobbs R, de Lusignan S, de Lusignan S, Bradley D, OReilly D, Murphy S, Chuter A, Beggs J, Ford D, Orton C, Akbari A, Bedston S, Davies G, Griffiths LJ, Griffiths R, Lowthian E, Lyons J, Lyons RA, North L, Perry M, Torabi F, Pickett J, McMenamin J, McCowan C, Agrawal U, Wood R, Stock SJ, Moore E, Henery P, Simpson CR, Sheikh A.",,BMJ open,2022,2022-02-14,Y,epidemiology; Public Health; Respiratory Infections; Covid-19,,,"

Introduction

The novel coronavirus SARS-CoV-2, which emerged in December 2019, has caused millions of deaths and severe illness worldwide. Numerous vaccines are currently under development of which a few have now been authorised for population-level administration by several countries. As of 20 September 2021, over 48 million people have received their first vaccine dose and over 44 million people have received their second vaccine dose across the UK. We aim to assess the uptake rates, effectiveness, and safety of all currently approved COVID-19 vaccines in the UK.

Methods and analysis

We will use prospective cohort study designs to assess vaccine uptake, effectiveness and safety against clinical outcomes and deaths. Test-negative case-control study design will be used to assess vaccine effectiveness (VE) against laboratory confirmed SARS-CoV-2 infection. Self-controlled case series and retrospective cohort study designs will be carried out to assess vaccine safety against mild-to-moderate and severe adverse events, respectively. Individual-level pseudonymised data from primary care, secondary care, laboratory test and death records will be linked and analysed in secure research environments in each UK nation. Univariate and multivariate logistic regression models will be carried out to estimate vaccine uptake levels in relation to various population characteristics. VE estimates against laboratory confirmed SARS-CoV-2 infection will be generated using a generalised additive logistic model. Time-dependent Cox models will be used to estimate the VE against clinical outcomes and deaths. The safety of the vaccines will be assessed using logistic regression models with an offset for the length of the risk period. Where possible, data will be meta-analysed across the UK nations.

Ethics and dissemination

We obtained approvals from the National Research Ethics Service Committee, Southeast Scotland 02 (12/SS/0201), the Secure Anonymised Information Linkage independent Information Governance Review Panel project number 0911. Concerning English data, University of Oxford is compliant with the General Data Protection Regulation and the National Health Service (NHS) Digital Data Security and Protection Policy. This is an approved study (Integrated Research Application ID 301740, Health Research Authority (HRA) Research Ethics Committee 21/HRA/2786). The Oxford-Royal College of General Practitioners Clinical Informatics Digital Hub meets NHS Digital's Data Security and Protection Toolkit requirements. In Northern Ireland, the project was approved by the Honest Broker Governance Board, project number 0064. Findings will be made available to national policy-makers, presented at conferences and published in peer-reviewed journals.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/2/e050062.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-050062; html:https://europepmc.org/articles/PMC8844955; pdf:https://europepmc.org/articles/PMC8844955?pdf=render 34879829,https://doi.org/10.1186/s12911-021-01693-6,Identifying and evaluating clinical subtypes of Alzheimer's disease in care electronic health records using unsupervised machine learning.,"Alexander N, Alexander DC, Barkhof F, Denaxas S.",,BMC medical informatics and decision making,2021,2021-12-08,Y,Alzheimer's disease; Clustering; Subtyping; Ehr; K-means,,,"

Background

Alzheimer's disease (AD) is a highly heterogeneous disease with diverse trajectories and outcomes observed in clinical populations. Understanding this heterogeneity can enable better treatment, prognosis and disease management. Studies to date have mainly used imaging or cognition data and have been limited in terms of data breadth and sample size. Here we examine the clinical heterogeneity of Alzheimer's disease patients using electronic health records (EHR) to identify and characterise disease subgroups using multiple clustering methods, identifying clusters which are clinically actionable.

Methods

We identified AD patients in primary care EHR from the Clinical Practice Research Datalink (CPRD) using a previously validated rule-based phenotyping algorithm. We extracted and included a range of comorbidities, symptoms and demographic features as patient features. We evaluated four different clustering methods (k-means, kernel k-means, affinity propagation and latent class analysis) to cluster Alzheimer's disease patients. We compared clusters on clinically relevant outcomes and evaluated each method using measures of cluster structure, stability, efficiency of outcome prediction and replicability in external data sets.

Results

We identified 7,913 AD patients, with a mean age of 82 and 66.2% female. We included 21 features in our analysis. We observed 5, 2, 5 and 6 clusters in k-means, kernel k-means, affinity propagation and latent class analysis respectively. K-means was found to produce the most consistent results based on four evaluative measures. We discovered a consistent cluster found in three of the four methods composed of predominantly female, younger disease onset (43% between ages 42-73) diagnosed with depression and anxiety, with a quicker rate of progression compared to the average across other clusters.

Conclusion

Each clustering approach produced substantially different clusters and K-Means performed the best out of the four methods based on the four evaluative criteria. However, the consistent appearance of one particular cluster across three of the four methods potentially suggests the presence of a distinct disease subtype that merits further exploration. Our study underlines the variability of the results obtained from different clustering approaches and the importance of systematically evaluating different approaches for identifying disease subtypes in complex EHR.",,pdf:https://bmcmedinformdecismak.biomedcentral.com/track/pdf/10.1186/s12911-021-01693-6; doi:https://doi.org/10.1186/s12911-021-01693-6; html:https://europepmc.org/articles/PMC8653614; pdf:https://europepmc.org/articles/PMC8653614?pdf=render 37463814,https://doi.org/10.1136/bmjopen-2022-069635,HbA1c recording in patients following a first diagnosis of serious mental illness: the South London and Maudsley Biomedical Research Centre case register.,"Bell N, Perera G, Chandran D, Stubbs B, Gaughran F, Stewart R.",,BMJ open,2023,2023-07-18,Y,Psychiatry; Mental health; epidemiology; Health Informatics; General Diabetes; Quality In Health Care,,,"

Objectives

To investigate factors associated with the recording of glycated haemoglobin (HbA1c) in people with first diagnoses of serious mental illness (SMI) in a large mental healthcare provider, and factors associated with HbA1c levels, when recorded. To our knowledge this is the first such investigation, although attention to dysglycaemia in SMI is an increasing priority in mental healthcare.

Design

The study was primarily descriptive in nature, seeking to ascertain the frequency of HbA1c recording in the mental healthcare sector for people following first SMI diagnosis.

Settings

A large mental healthcare provider, the South London and Maudsley National Health Service Trust.

Participants

Using electronic mental health records data, we ascertained patients with first SMI diagnoses (schizophrenia, schizoaffective disorder, bipolar disorder) from 2008 to 2018.

Outcome measures

Recording or not of HbA1c level was ascertained from routine local laboratory data and supplemented by a natural language processing (NLP) algorithm for extracting recorded values in text fields (precision 0.89%, recall 0.93%). Age, gender, ethnic group, year of diagnosis, and SMI diagnosis were investigated as covariates in relation to recording or not of HbA1c and first recorded levels.

Results

Of 21 462 patients in the sample (6546 bipolar disorder; 14 916 schizophrenia or schizoaffective disorder; mean age 38.8 years, 49% female), 4106 (19.1%) had at least one HbA1c result recorded from laboratory data, increasing to 6901 (32.2%) following NLP. HbA1c recording was independently more likely in non-white ethnic groups (black compared with white: OR 2.45, 95% CI 2.29 to 2.62), and was negatively associated with age (OR per year increase 0.93, 0.92-0.95), female gender (0.83, 0.78-0.88) and bipolar disorder (0.49, 0.45-0.52).

Conclusions

Over a 10-year period, relatively low level of recording of HbA1c was observed, although this has increased over time and ascertainment was increased with text extraction. It remains important to improve the routine monitoring of dysglycaemia in these at-risk disorders.",,pdf:https://bmjopen.bmj.com/content/bmjopen/13/7/e069635.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-069635; html:https://europepmc.org/articles/PMC10357777; pdf:https://europepmc.org/articles/PMC10357777?pdf=render -38177425,https://doi.org/10.1038/s43588-023-00461-y,GREENER principles for environmentally sustainable computational science.,"Lannelongue L, Aronson HG, Bateman A, Birney E, Caplan T, Juckes M, McEntyre J, Morris AD, Reilly G, Inouye M.",,Nature computational science,2023,2023-06-26,N,,,,"The carbon footprint of scientific computing is substantial, but environmentally sustainable computational science (ESCS) is a nascent field with many opportunities to thrive. To realize the immense green opportunities and continued, yet sustainable, growth of computer science, we must take a coordinated approach to our current challenges, including greater awareness and transparency, improved estimation and wider reporting of environmental impacts. Here, we present a snapshot of where ESCS stands today and introduce the GREENER set of principles, as well as guidance for best practices moving forward.",,doi:https://doi.org/10.1038/s43588-023-00461-y 31799783,https://doi.org/10.1002/cnm.3267,Personalising cardiovascular network models in pregnancy: A two-tiered parameter estimation approach.,"Carson J, Warrander L, Johnstone E, van Loon R.",,International journal for numerical methods in biomedical engineering,2021,2020-01-13,Y,Pregnancy; Parameter estimation; Pre-eclampsia; Personalised Haemodynamic Model; Uterine Artery Waveform,,,"Uterine artery Doppler waveforms are often studied to determine whether a patient is at risk of developing pathologies such as pre-eclampsia. Many uterine waveform indices have been developed, which attempt to relate characteristics of the waveform with the physiological adaptation of the maternal cardiovascular system, and are often suggested to be an indicator of increased placenta resistance and arterial stiffness. Doppler waveforms of four patients, two of whom developed pre-eclampsia, are compared with a comprehensive closed-loop model of pregnancy. The closed-loop model has been previously validated but has been extended to include an improved parameter estimation technique that utilises systolic and diastolic blood pressure, cardiac output, heart rate, and pulse wave velocity measurements to adapt model resistances, compliances, blood volume, and the mean vessel areas in the main systemic arteries. The shape of the model-predicted uterine artery velocity waveforms showed good agreement with the characteristics observed in the patient Doppler waveforms. The personalised models obtained now allow a prediction of the uterine pressure waveforms in addition to the uterine velocity. This allows for a more detailed mechanistic analysis of the waveforms, eg, wave intensity analysis, to study existing clinical indices. The findings indicate that to accurately estimate arterial stiffness, both pulse pressure and pulse wave velocities are required. In addition, the results predict that patients who developed pre-eclampsia later in pregnancy have larger vessel areas in the main systemic arteries compared with the two patients who had normal pregnancy outcomes.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/cnm.3267; doi:https://doi.org/10.1002/cnm.3267; html:https://europepmc.org/articles/PMC9286682; pdf:https://europepmc.org/articles/PMC9286682?pdf=render +38177425,https://doi.org/10.1038/s43588-023-00461-y,GREENER principles for environmentally sustainable computational science.,"Lannelongue L, Aronson HG, Bateman A, Birney E, Caplan T, Juckes M, McEntyre J, Morris AD, Reilly G, Inouye M.",,Nature computational science,2023,2023-06-26,N,,,,"The carbon footprint of scientific computing is substantial, but environmentally sustainable computational science (ESCS) is a nascent field with many opportunities to thrive. To realize the immense green opportunities and continued, yet sustainable, growth of computer science, we must take a coordinated approach to our current challenges, including greater awareness and transparency, improved estimation and wider reporting of environmental impacts. Here, we present a snapshot of where ESCS stands today and introduce the GREENER set of principles, as well as guidance for best practices moving forward.",,doi:https://doi.org/10.1038/s43588-023-00461-y 37346822,https://doi.org/10.12688/wellcomeopenres.18735.2,First dose COVID-19 vaccine coverage amongst adolescents and children in England: an analysis of 3.21 million patients' primary care records in situ using OpenSAFELY.,"Hopcroft LE, Curtis HJ, Brown AD, Hulme WJ, Andrews CD, Morton CE, Inglesby P, Morley J, Mehrkar A, Bacon SC, Eggo RM, Mahalingasivam V, Parker EPK, Tomlinson LA, Bates C, Cockburn J, Parry J, Hester F, Harper S, Goldacre B, Walker AJ, MacKenna B.",,Wellcome open research,2023,2023-06-09,Y,Vaccine; Primary Health Care; Public Health; Covid-19,,,"Background: The coronavirus disease 2019 (COVID-19) vaccination programme in England was extended to include all adolescents and children by April 2022. The aim of this paper is to describe trends and variation in vaccine coverage in different clinical and demographic groups amongst adolescents and children in England by August 2022. Methods: With the approval of NHS England, a cohort study was conducted of 3.21 million children and adolescents' records in general practice in England,  in situ and within the infrastructure of the electronic health record software vendor TPP using OpenSAFELY. Vaccine coverage across various demographic (sex, deprivation index and ethnicity) and clinical (risk status) populations is described. Results: Coverage is higher amongst adolescents than it is amongst children, with 53.5% adolescents and 10.8% children having received their first dose of the COVID-19 vaccine. Within those groups, coverage varies by ethnicity, deprivation index and risk status; there is no evidence of variation by sex. Conclusion: First dose COVID-19 vaccine coverage is shown to vary amongst various demographic and clinical groups of children and adolescents.",,doi:https://doi.org/10.12688/wellcomeopenres.18735.2; html:https://europepmc.org/articles/PMC10280033; pdf:https://europepmc.org/articles/PMC10280033?pdf=render 31088492,https://doi.org/10.1186/s12967-019-1912-5,-Omics biomarker identification pipeline for translational medicine.,"Bravo-Merodio L, Williams JA, Gkoutos GV, Acharjee A.",,Journal of translational medicine,2019,2019-05-14,Y,Biomarker; Feature Selection; Regularization; -omics; Translational Medicine,,,"

Background

Translational medicine (TM) is an emerging domain that aims to facilitate medical or biological advances efficiently from the scientist to the clinician. Central to the TM vision is to narrow the gap between basic science and applied science in terms of time, cost and early diagnosis of the disease state. Biomarker identification is one of the main challenges within TM. The identification of disease biomarkers from -omics data will not only help the stratification of diverse patient cohorts but will also provide early diagnostic information which could improve patient management and potentially prevent adverse outcomes. However, biomarker identification needs to be robust and reproducible. Hence a robust unbiased computational framework that can help clinicians identify those biomarkers is necessary.

Methods

We developed a pipeline (workflow) that includes two different supervised classification techniques based on regularization methods to identify biomarkers from -omics or other high dimension clinical datasets. The pipeline includes several important steps such as quality control and stability of selected biomarkers. The process takes input files (outcome and independent variables or -omics data) and pre-processes (normalization, missing values) them. After a random division of samples into training and test sets, Least Absolute Shrinkage and Selection Operator and Elastic Net feature selection methods are applied to identify the most important features representing potential biomarker candidates. The penalization parameters are optimised using 10-fold cross validation and the process undergoes 100 iterations and a combinatorial analysis to select the best performing multivariate model. An empirical unbiased assessment of their quality as biomarkers for clinical use is performed through a Receiver Operating Characteristic curve and its Area Under the Curve analysis on both permuted and real data for 1000 different randomized training and test sets. We validated this pipeline against previously published biomarkers.

Results

We applied this pipeline to three different datasets with previously published biomarkers: lipidomics data by Acharjee et al. (Metabolomics 13:25, 2017) and transcriptomics data by Rajamani and Bhasin (Genome Med 8:38, 2016) and Mills et al. (Blood 114:1063-1072, 2009). Our results demonstrate that our method was able to identify both previously published biomarkers as well as new variables that add value to the published results.

Conclusions

We developed a robust pipeline to identify clinically relevant biomarkers that can be applied to different -omics datasets. Such identification reveals potentially novel drug targets and can be used as a part of a machine-learning based patient stratification framework in the translational medicine settings.",,pdf:https://translational-medicine.biomedcentral.com/track/pdf/10.1186/s12967-019-1912-5; doi:https://doi.org/10.1186/s12967-019-1912-5; html:https://europepmc.org/articles/PMC6518609; pdf:https://europepmc.org/articles/PMC6518609?pdf=render 33114263,https://doi.org/10.3390/ijms21217886,Biomarker Prioritisation and Power Estimation Using Ensemble Gene Regulatory Network Inference.,"Aziz F, Acharjee A, Williams JA, Russ D, Bravo-Merodio L, Gkoutos GV.",,International journal of molecular sciences,2020,2020-10-23,Y,Experimental design; Gene Regulatory Network; Causal Modelling; Omics Integration,,,"Inferring the topology of a gene regulatory network (GRN) from gene expression data is a challenging but important undertaking for gaining a better understanding of gene regulation. Key challenges include working with noisy data and dealing with a higher number of genes than samples. Although a number of different methods have been proposed to infer the structure of a GRN, there are large discrepancies among the different inference algorithms they adopt, rendering their meaningful comparison challenging. In this study, we used two methods, namely the MIDER (Mutual Information Distance and Entropy Reduction) and the PLSNET (Partial least square based feature selection) methods, to infer the structure of a GRN directly from data and computationally validated our results. Both methods were applied to different gene expression datasets resulting from inflammatory bowel disease (IBD), pancreatic ductal adenocarcinoma (PDAC), and acute myeloid leukaemia (AML) studies. For each case, gene regulators were successfully identified. For example, for the case of the IBD dataset, the UGT1A family genes were identified as key regulators while upon analysing the PDAC dataset, the SULF1 and THBS2 genes were depicted. We further demonstrate that an ensemble-based approach, that combines the output of the MIDER and PLSNET algorithms, can infer the structure of a GRN from data with higher accuracy. We have also estimated the number of the samples required for potential future validation studies. Here, we presented our proposed analysis framework that caters not only to candidate regulator genes prediction for potential validation experiments but also an estimation of the number of samples required for these experiments.",,pdf:https://www.mdpi.com/1422-0067/21/21/7886/pdf?version=1604329387; doi:https://doi.org/10.3390/ijms21217886; html:https://europepmc.org/articles/PMC7660606; pdf:https://europepmc.org/articles/PMC7660606?pdf=render @@ -347,8 +347,8 @@ PMC10929454,https://doi.org/,Optimising data curation pipelines for population-l 32851419,https://doi.org/10.1007/s00394-020-02372-4,Vitamin D and COVID-19 infection and mortality in UK Biobank.,"Hastie CE, Pell JP, Sattar N.",,European journal of nutrition,2021,2020-08-26,Y,Vitamin D; Mortality; Covid-19,,,"

Purpose

Low blood 25-hydroxyvitamin D (25(OH)D) concentration has been proposed as a potential causal factor in COVID-19 risk. We aimed to establish whether baseline serum 25(OH)D concentration was associated with COVID-19 mortality, and inpatient confirmed COVID-19 infection, in UK Biobank participants.

Methods

UK Biobank recruited 502,624 participants aged 37-73 years between 2006 and 2010. Baseline exposure data, including serum 25(OH)D concentration, were linked to COVID-19 mortality. Univariable and multivariable Cox proportional hazards regression analyses were performed for the association between 25(OH)D and COVID-19 death, and Poisson regression analyses for the association between 25(OH)D and severe COVID-19 infection.

Results

Complete data were available for 341,484 UK Biobank participants, of which 656 had inpatient confirmed COVID-19 infection and 203 died of COVID-19 infection. 25(OH)D concentration was associated with severe COVID-19 infection and mortality univariably (mortality per 10 nmol/L 25(OH)D HR  0.92; 95% CI 0.86-0.98; p = 0.016), but not after adjustment for confounders (mortality per 10 nmol/L 25(OH)D HR 0.98; 95% CI = 0.91-1.06; p = 0.696). Vitamin D insufficiency or deficiency was also not independently associated with either COVID-19 infection or linked mortality.

Conclusions

Our findings do not support a potential link between 25(OH)D concentrations and risk of severe COVID-19 infection and mortality. Randomised trials are needed to prove a beneficial role for vitamin D in the prevention of severe COVID-19 reactions or death.",,pdf:https://link.springer.com/content/pdf/10.1007/s00394-020-02372-4.pdf; doi:https://doi.org/10.1007/s00394-020-02372-4; html:https://europepmc.org/articles/PMC7449523; pdf:https://europepmc.org/articles/PMC7449523?pdf=render 38151278,https://doi.org/10.1136/bmjopen-2023-075958,External validation of the QCovid 2 and 3 risk prediction algorithms for risk of COVID-19 hospitalisation and mortality in adults: a national cohort study in Scotland.,"Kerr S, Millington T, Rudan I, McCowan C, Tibble H, Jeffrey K, Fagbamigbe AF, Simpson CR, Robertson C, Hippisley-Cox J, Sheikh A.",,BMJ open,2023,2023-12-27,Y,epidemiology; Health Informatics; Respiratory Medicine (See Thoracic Medicine),,,"

Objective

The QCovid 2 and 3 algorithms are risk prediction tools developed during the second wave of the COVID-19 pandemic that can be used to predict the risk of COVID-19 hospitalisation and mortality, taking vaccination status into account. In this study, we assess their performance in Scotland.

Methods

We used the Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 national data platform consisting of individual-level data for the population of Scotland (5.4 million residents). Primary care data were linked to reverse-transcription PCR virology testing, hospitalisation and mortality data. We assessed the discrimination and calibration of the QCovid 2 and 3 algorithms in predicting COVID-19 hospitalisations and deaths between 8 December 2020 and 15 June 2021.

Results

Our validation dataset comprised 465 058 individuals, aged 19-100. We found the following performance metrics (95% CIs) for QCovid 2 and 3: Harrell's C 0.84 (0.82 to 0.86) for hospitalisation, and 0.92 (0.90 to 0.94) for death, observed-expected ratio of 0.24 for hospitalisation and 0.26 for death (ie, both the number of hospitalisations and the number of deaths were overestimated), and a Brier score of 0.0009 (0.00084 to 0.00096) for hospitalisation and 0.00036 (0.00032 to 0.0004) for death.

Conclusions

We found good discrimination of the QCovid 2 and 3 algorithms in Scotland, although performance was worse in higher age groups. Both the number of hospitalisations and the number of deaths were overestimated.",,pdf:https://bmjopen.bmj.com/content/bmjopen/13/12/e075958.full.pdf; doi:https://doi.org/10.1136/bmjopen-2023-075958; html:https://europepmc.org/articles/PMC10753764; pdf:https://europepmc.org/articles/PMC10753764?pdf=render 37815053,https://doi.org/10.1161/jaha.123.029552,Lipoprotein Characteristics and Incident Coronary Heart Disease: Prospective Cohort of Nearly 90 000 Individuals in UK Biobank.,"Jin D, Trichia E, Islam N, Bešević J, Lewington S, Lacey B.",,Journal of the American Heart Association,2023,2023-10-10,Y,Apolipoproteins; Cholesterol; Nuclear magnetic resonance; Lipoproteins; Triglycerides; Coronary Heart Disease; Uk biobank,,,"Background Associations of coronary heart disease (CHD) with plasma lipids are well described, but the associations with characteristics of lipoproteins (which transport lipids) remain unclear. Methods and Results UK Biobank is a prospective study of 0.5 million adults. Analyses were restricted to 89 422 participants with plasma lipoprotein and apolipoprotein measures from Nightingale nuclear magnetic resonance spectroscopy and without CHD at baseline. CHD risk was positively associated with concentrations of very-low-density lipoproteins, intermediate-density lipoproteins, and low-density lipoproteins (LDL), and inversely associated with high-density lipoproteins. Hazard ratios (99% CIs) per SD were 1.22 (1.17-1.28), 1.16 (1.11-1.21), 1.20 (1.15-1.25), and 0.90 (0.86-0.95), respectively. Larger subclasses of very-low-density lipoproteins were less strongly associated with CHD risk, but associations did not materially vary by size of LDL or high-density lipoprotein. Given lipoprotein particle concentrations, lipid composition (including cholesterol) was not strongly related to CHD risk, except for triglyceride in LDL particles. Apolipoprotein B was highly correlated with LDL concentration (r=0.99), but after adjustment for apolipoprotein B, concentrations of very-low-density lipoprotein and high-density lipoprotein particles remained strongly related to CHD risk. Conclusions This large-scale study reliably quantifies the associations of nuclear magnetic resonance-defined lipoprotein characteristics with CHD risk. CHD risk was most strongly related to particle concentrations, and separate measurements of lipoprotein concentrations may be of greater value than the measurement by apolipoprotein B, which was largely determined by LDL concentration alone. Furthermore, there was strong evidence of positive association with mean triglyceride molecules per LDL particle but little evidence of associations with total triglycerides or other lipid and lipoprotein fractions after accounting for lipoprotein concentrations.",,doi:https://doi.org/10.1161/JAHA.123.029552; html:https://europepmc.org/articles/PMC10757541; pdf:https://europepmc.org/articles/PMC10757541?pdf=render -38355631,https://doi.org/10.1186/s12916-024-03284-4,Association between pregnancy-related complications and development of type 2 diabetes and hypertension in women: an umbrella review.,"Wambua S, Singh M, Okoth K, Snell KIE, Riley RD, Yau C, Thangaratinam S, Nirantharakumar K, Crowe FL, MuM-PreDiCT Group.",,BMC medicine,2024,2024-02-14,Y,Hypertension; Type 2 diabetes; Pregnancy complications; Obstetrics And Gynaecology; Umbrella Review,,,"

Background

Despite many systematic reviews and meta-analyses examining the associations of pregnancy complications with risk of type 2 diabetes mellitus (T2DM) and hypertension, previous umbrella reviews have only examined a single pregnancy complication. Here we have synthesised evidence from systematic reviews and meta-analyses on the associations of a wide range of pregnancy-related complications with risk of developing T2DM and hypertension.

Methods

Medline, Embase and Cochrane Database of Systematic Reviews were searched from inception until 26 September 2022 for systematic reviews and meta-analysis examining the association between pregnancy complications and risk of T2DM and hypertension. Screening of articles, data extraction and quality appraisal (AMSTAR2) were conducted independently by two reviewers using Covidence software. Data were extracted for studies that examined the risk of T2DM and hypertension in pregnant women with the pregnancy complication compared to pregnant women without the pregnancy complication. Summary estimates of each review were presented using tables, forest plots and narrative synthesis and reported following Preferred Reporting Items for Overviews of Reviews (PRIOR) guidelines.

Results

Ten systematic reviews were included. Two pregnancy complications were identified. Gestational diabetes mellitus (GDM): One review showed GDM was associated with a 10-fold higher risk of T2DM at least 1 year after pregnancy (relative risk (RR) 9.51 (95% confidence interval (CI) 7.14 to 12.67) and although the association differed by ethnicity (white: RR 16.28 (95% CI 15.01 to 17.66), non-white: RR 10.38 (95% CI 4.61 to 23.39), mixed: RR 8.31 (95% CI 5.44 to 12.69)), the between subgroups difference were not statistically significant at 5% significance level. Another review showed GDM was associated with higher mean blood pressure at least 3 months postpartum (mean difference in systolic blood pressure: 2.57 (95% CI 1.74 to 3.40) mmHg and mean difference in diastolic blood pressure: 1.89 (95% CI 1.32 to 2.46) mmHg). Hypertensive disorders of pregnancy (HDP): Three reviews showed women with a history of HDP were 3 to 6 times more likely to develop hypertension at least 6 weeks after pregnancy compared to women without HDP (meta-analysis with largest number of studies: odds ratio (OR) 4.33 (3.51 to 5.33)) and one review reported a higher rate of T2DM after HDP (hazard ratio (HR) 2.24 (1.95 to 2.58)) at least a year after pregnancy. One of the three reviews and five other reviews reported women with a history of preeclampsia were 3 to 7 times more likely to develop hypertension at least 6 weeks postpartum (meta-analysis with the largest number of studies: OR 3.90 (3.16 to 4.82) with one of these reviews reporting the association was greatest in women from Asia (Asia: OR 7.54 (95% CI 2.49 to 22.81), Europe: OR 2.19 (95% CI 0.30 to 16.02), North and South America: OR 3.32 (95% CI 1.26 to 8.74)).

Conclusions

GDM and HDP are associated with a greater risk of developing T2DM and hypertension. Common confounders adjusted for across the included studies in the reviews were maternal age, body mass index (BMI), socioeconomic status, smoking status, pre-pregnancy and current BMI, parity, family history of T2DM or cardiovascular disease, ethnicity, and time of delivery. Further research is needed to evaluate the value of embedding these pregnancy complications as part of assessment for future risk of T2DM and chronic hypertension.",,doi:https://doi.org/10.1186/s12916-024-03284-4; html:https://europepmc.org/articles/PMC10865714; pdf:https://europepmc.org/articles/PMC10865714?pdf=render 34108714,https://doi.org/10.1038/s41591-021-01408-4,"First-dose ChAdOx1 and BNT162b2 COVID-19 vaccines and thrombocytopenic, thromboembolic and hemorrhagic events in Scotland.","Simpson CR, Shi T, Vasileiou E, Katikireddi SV, Kerr S, Moore E, McCowan C, Agrawal U, Shah SA, Ritchie LD, Murray J, Pan J, Bradley DT, Stock SJ, Wood R, Chuter A, Beggs J, Stagg HR, Joy M, Tsang RSM, de Lusignan S, Hobbs R, Lyons RA, Torabi F, Bedston S, O'Leary M, Akbari A, McMenamin J, Robertson C, Sheikh A.",,Nature medicine,2021,2021-06-09,Y,,,,"Reports of ChAdOx1 vaccine-associated thrombocytopenia and vascular adverse events have led to some countries restricting its use. Using a national prospective cohort, we estimated associations between exposure to first-dose ChAdOx1 or BNT162b2 vaccination and hematological and vascular adverse events using a nested incident-matched case-control study and a confirmatory self-controlled case series (SCCS) analysis. An association was found between ChAdOx1 vaccination and idiopathic thrombocytopenic purpura (ITP) (0-27 d after vaccination; adjusted rate ratio (aRR) = 5.77, 95% confidence interval (CI), 2.41-13.83), with an estimated incidence of 1.13 (0.62-1.63) cases per 100,000 doses. An SCCS analysis confirmed that this was unlikely due to bias (RR = 1.98 (1.29-3.02)). There was also an increased risk for arterial thromboembolic events (aRR = 1.22, 1.12-1.34) 0-27 d after vaccination, with an SCCS RR of 0.97 (0.93-1.02). For hemorrhagic events 0-27 d after vaccination, the aRR was 1.48 (1.12-1.96), with an SCCS RR of 0.95 (0.82-1.11). A first dose of ChAdOx1 was found to be associated with small increased risks of ITP, with suggestive evidence of an increased risk of arterial thromboembolic and hemorrhagic events. The attenuation of effect found in the SCCS analysis means that there is the potential for overestimation of the reported results, which might indicate the presence of some residual confounding or confounding by indication. Public health authorities should inform their jurisdictions of these relatively small increased risks associated with ChAdOx1. No positive associations were seen between BNT162b2 and thrombocytopenic, thromboembolic and hemorrhagic events.",,pdf:https://www.nature.com/articles/s41591-021-01408-4.pdf; doi:https://doi.org/10.1038/s41591-021-01408-4; html:https://europepmc.org/articles/PMC8282499; pdf:https://europepmc.org/articles/PMC8282499?pdf=render +38355631,https://doi.org/10.1186/s12916-024-03284-4,Association between pregnancy-related complications and development of type 2 diabetes and hypertension in women: an umbrella review.,"Wambua S, Singh M, Okoth K, Snell KIE, Riley RD, Yau C, Thangaratinam S, Nirantharakumar K, Crowe FL, MuM-PreDiCT Group.",,BMC medicine,2024,2024-02-14,Y,Hypertension; Type 2 diabetes; Pregnancy complications; Obstetrics And Gynaecology; Umbrella Review,,,"

Background

Despite many systematic reviews and meta-analyses examining the associations of pregnancy complications with risk of type 2 diabetes mellitus (T2DM) and hypertension, previous umbrella reviews have only examined a single pregnancy complication. Here we have synthesised evidence from systematic reviews and meta-analyses on the associations of a wide range of pregnancy-related complications with risk of developing T2DM and hypertension.

Methods

Medline, Embase and Cochrane Database of Systematic Reviews were searched from inception until 26 September 2022 for systematic reviews and meta-analysis examining the association between pregnancy complications and risk of T2DM and hypertension. Screening of articles, data extraction and quality appraisal (AMSTAR2) were conducted independently by two reviewers using Covidence software. Data were extracted for studies that examined the risk of T2DM and hypertension in pregnant women with the pregnancy complication compared to pregnant women without the pregnancy complication. Summary estimates of each review were presented using tables, forest plots and narrative synthesis and reported following Preferred Reporting Items for Overviews of Reviews (PRIOR) guidelines.

Results

Ten systematic reviews were included. Two pregnancy complications were identified. Gestational diabetes mellitus (GDM): One review showed GDM was associated with a 10-fold higher risk of T2DM at least 1 year after pregnancy (relative risk (RR) 9.51 (95% confidence interval (CI) 7.14 to 12.67) and although the association differed by ethnicity (white: RR 16.28 (95% CI 15.01 to 17.66), non-white: RR 10.38 (95% CI 4.61 to 23.39), mixed: RR 8.31 (95% CI 5.44 to 12.69)), the between subgroups difference were not statistically significant at 5% significance level. Another review showed GDM was associated with higher mean blood pressure at least 3 months postpartum (mean difference in systolic blood pressure: 2.57 (95% CI 1.74 to 3.40) mmHg and mean difference in diastolic blood pressure: 1.89 (95% CI 1.32 to 2.46) mmHg). Hypertensive disorders of pregnancy (HDP): Three reviews showed women with a history of HDP were 3 to 6 times more likely to develop hypertension at least 6 weeks after pregnancy compared to women without HDP (meta-analysis with largest number of studies: odds ratio (OR) 4.33 (3.51 to 5.33)) and one review reported a higher rate of T2DM after HDP (hazard ratio (HR) 2.24 (1.95 to 2.58)) at least a year after pregnancy. One of the three reviews and five other reviews reported women with a history of preeclampsia were 3 to 7 times more likely to develop hypertension at least 6 weeks postpartum (meta-analysis with the largest number of studies: OR 3.90 (3.16 to 4.82) with one of these reviews reporting the association was greatest in women from Asia (Asia: OR 7.54 (95% CI 2.49 to 22.81), Europe: OR 2.19 (95% CI 0.30 to 16.02), North and South America: OR 3.32 (95% CI 1.26 to 8.74)).

Conclusions

GDM and HDP are associated with a greater risk of developing T2DM and hypertension. Common confounders adjusted for across the included studies in the reviews were maternal age, body mass index (BMI), socioeconomic status, smoking status, pre-pregnancy and current BMI, parity, family history of T2DM or cardiovascular disease, ethnicity, and time of delivery. Further research is needed to evaluate the value of embedding these pregnancy complications as part of assessment for future risk of T2DM and chronic hypertension.",,doi:https://doi.org/10.1186/s12916-024-03284-4; html:https://europepmc.org/articles/PMC10865714; pdf:https://europepmc.org/articles/PMC10865714?pdf=render 36243955,https://doi.org/10.1093/ndt/gfac287,Self-reported health change in haemodialysis recipients modulates the effect of frailty upon mortality and hospital admissions: outcomes from a large prospective UK cohort.,"Anderson BM, Qasim M, Correa G, Evison F, Gallier S, Ferro CJ, Jackson TA, Sharif A.",,"Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association",2023,2023-05-01,N,Survival analysis; Frailty; Haemodialysis; epidemiology; Hospitalization,,,"

Background

Frailty among haemodialysis patients is associated with hospitalization and mortality, but high frailty prevalence suggests further discrimination of risk is required. We hypothesized that incorporation of self-reported health with frailty measurement may aid risk stratification.

Methods

Prospective cohort study of 485 prevalent haemodialysis recipients linked to English national datasets. Frailty Phenotype (FP), Frailty Index (FI), Edmonton Frail Scale (EFS), Clinical Frailty Scale (CFS) and self-reported health change were assessed. Mortality was explored using Fine and Gray regression, and admissions by negative binomial regression.

Results

Over a median 678 (interquartile range 531-812) days, there were 111 deaths, and 1241 hospitalizations. Increasing frailty was associated with mortality on adjusted analyses for FP [subdistribution hazard ratio (SHR) 1.26, 95% confidence interval (CI) 1.05-1.53, P = .01], FI (SHR 1.21, 95% CI 1.09-1.35, P = .001) and CFS (SHR 1.32, 95% CI 1.11-1.58, P = .002), but not EFS (HR 1.08, 95% CI 0.99-1.18, P = .1). Health change interacted with frailty tools to modify association with mortality; only those who rated their health as the same or worse experienced increased mortality hazard associated with frailty by FP (Pinteraction = .001 and 0.035, respectively), FI (Pinteraction = .002 and .007, respectively) and CFS (Pinteraction = .009 and 0.02, respectively). CFS was the only frailty tool associated with hospitalization (incidence rate ratio 1.12, 95% CI 1.02-1.23, P = .02).

Conclusions

We confirm the high burden of hospitalization and mortality associated with haemodialysis patients regardless of frailty tool utilized and introduce the discriminatory ability of self-reported health to identify the most at-risk frail individuals.",,doi:https://doi.org/10.1093/ndt/gfac287 36583230,https://doi.org/10.1002/cam4.5556,Circulating gamma-glutamyl transpeptidase and risk of pancreatic cancer: A prospective cohort study in the UK Biobank.,"Liao W, Yang Y, Yang H, Qu Y, Song H, Li Q.",,Cancer medicine,2023,2022-12-29,Y,Prevention; Pancreatic cancer; Gamma-glutamyl Transpeptidase; European Ancestry,,,"

Background

To determine whether serum gamma-glutamyl transpeptidase (GGT) level is associated with pancreatic cancer risk in a large prospective cohort.

Methods

The study analyzed serum GGT concentration at baseline of 421,032 participants recruited in the UK Biobank since 2006 through 2010. Information on incidence of pancreatic cancer was obtained from cancer and death registers, updated until 2015 in Scotland or 2016 in England and Wales. Adjusted Cox proportional hazards models were used to measure the association between serum GGT and pancreatic cancer risk.

Results

The study identified 586 cases of pancreatic cancer over a median follow-up period of 7.16 years. In the multivariable-adjusted Cox model, serum GGT level was associated with 14% higher pancreatic cancer risk (hazard ratio (HR) per one standard deviation increment of log2 GGT level = 1.14, 95% confidence interval (CI) 1.02-1.28, p = 0.025). In the total population, the HR for the highest GGT group was 1.68 (95%CI: 1.22-2.30) versus the lowest GGT group. The HR for the highest GGT group in men (≥50.2 U/L) was 1.72 (95%CI: 1.14-2.61) and that in women (≥31.6 U/L) was 1.75 (95%CI: 1.06-2.88) versus the lowest GGT group.

Conclusion

Our findings suggested a positive association of serum GGT in pancreatic cancer etiology, implying the potential of monitoring GGT level for identifying at-risk individuals for pancreatic cancer.",,doi:https://doi.org/10.1002/cam4.5556; doi:https://doi.org/10.1002/cam4.5556; html:https://europepmc.org/articles/PMC10134379; pdf:https://europepmc.org/articles/PMC10134379?pdf=render 34440368,https://doi.org/10.3390/genes12081194,"Genetic Variation in the ASTN2 Locus in Cardiovascular, Metabolic and Psychiatric Traits: Evidence for Pleiotropy Rather Than Shared Biology.","Burt O, Johnston KJA, Graham N, Cullen B, Lyall DM, Lyall LM, Pell JP, Ward J, Smith DJ, Strawbridge RJ.",,Genes,2021,2021-07-31,Y,Blood pressure; BMI; Cardiovascular disease; Metabolic Disease; Psychiatric Illness; Mood Instability; Neuroticism; Central Obesity; Anhedonia; Astn2,,,"

Background

The link between cardiometabolic and psychiatric illness has long been attributed to human behaviour, however recent research highlights shared biological mechanisms. The ASTN2 locus has been previously implicated in psychiatric and cardiometabolic traits, therefore this study aimed to systematically investigate the genetic architecture of ASTN2 in relation to a wide range of relevant traits.

Methods

Baseline questionnaire, assessment and genetic data of 402111 unrelated white British ancestry individuals from the UK Biobank was analysed. Genetic association analyses were conducted using PLINK 1.07, assuming an additive genetic model and adjusting for age, sex, genotyping chip, and population structure. Conditional analyses and linkage disequilibrium assessment were used to determine whether cardiometabolic and psychiatric signals were independent.

Results

Associations between genetic variants in the ASTN2 locus and blood pressure, total and central obesity, neuroticism, anhedonia and mood instability were identified. All analyses support the independence of the cardiometabolic traits from the psychiatric traits. In silico analyses provide support for the central obesity signal acting through ASTN2, however most of the other signals are likely acting through other genes in the locus.

Conclusions

Our systematic analysis demonstrates that ASTN2 has pleiotropic effects on cardiometabolic and psychiatric traits, rather than contributing to shared pathology.",,pdf:https://www.mdpi.com/2073-4425/12/8/1194/pdf?version=1627984735; doi:https://doi.org/10.3390/genes12081194; html:https://europepmc.org/articles/PMC8391428; pdf:https://europepmc.org/articles/PMC8391428?pdf=render @@ -387,10 +387,10 @@ PMC10910267,https://doi.org/,Development and evaluation of a tool to optimise in 37480048,https://doi.org/10.1186/s12872-023-03394-6,"Associations of circulating fatty acids with incident coronary heart disease: a prospective study of 89,242 individuals in UK Biobank.","Jin D, Trichia E, Islam N, Lewington S, Lacey B.",,BMC cardiovascular disorders,2023,2023-07-21,Y,Fatty acids; Lipids; Nuclear magnetic resonance; Coronary Heart Disease; Uk Biobank,,,"

Background

The role of fatty acids in coronary heart disease (CHD) remains uncertain. There is little evidence from large-scale epidemiological studies on the relevance of circulating fatty acids levels to CHD risk. This study aims to examine the independent associations of the major circulating types of fatty acids with CHD risk.

Methods

UK Biobank is a prospective study of adults aged 40-69 in 2006-2010; in 2012-2013, a subset of the participants were resurveyed. Analyses were restricted to 89,242 participants with baseline plasma fatty acids (measured using nuclear magnetic resonance spectroscopy) and without prior CHD. Cox proportional hazards models were used to estimate hazard ratios (HRs) for the associations with incidence CHD, defined as the first-ever myocardial infarction, unstable angina pectoris, coronary-related death, or relevant procedure. And the major types of fatty acids were mutually adjusted to examine the independent associations. Hazard ratios were corrected for regression dilution using the correlation of baseline and resurvey fatty acids measures.

Results

During a median follow-up of 11.8 years, 3,815 incident cases of CHD occurred. Independently of other fatty acids, CHD risk was positively associated with saturated fatty acids (SFA) and monounsaturated fatty acids (MUFA), inversely associated with omega-3 polyunsaturated fatty acids (PUFA), but there was no strong evidence of an association with omega-6 PUFA: HR per standard deviation higher were 1.14 (95% CI, 1.09-1.20), 1.15 (1.10-1.21), 0.91 (0.87-0.94), and 1.04 (0.99-1.09) respectively. Independently of triglycerides and cholesterol, the inverse association with omega-3 PUFA was not materially changed, but the positive associations with SFA and MUFA attenuated to null after adjusting for triglycerides levels.

Conclusions

This large-scale study has quantitated the independent associations of circulating fatty acids with CHD risk. Omega-3 PUFA was inversely related to CHD risk, independently of other fatty acids and major lipid fractions. By contrast, independently of other fatty acids, the positive associations of circulating SFA and MUFA with CHD risk were mostly attributed to their relationship with triglycerides.",,pdf:https://bmccardiovascdisord.biomedcentral.com/counter/pdf/10.1186/s12872-023-03394-6; doi:https://doi.org/10.1186/s12872-023-03394-6; html:https://europepmc.org/articles/PMC10362581; pdf:https://europepmc.org/articles/PMC10362581?pdf=render 37171130,https://doi.org/10.1093/gigascience/giad030,Strategies and techniques for quality control and semantic enrichment with multimodal data: a case study in colorectal cancer with eHDPrep.,"Toner TM, Pancholi R, Miller P, Forster T, Coleman HG, Overton IM.",,GigaScience,2022,2022-12-01,Y,Quality control; Bioinformatics; Data integration; Quality assessment; Colorectal Cancer; Medical Informatics; Ontology; Health Data; Semantic Enrichment,,,"

Background

Integration of data from multiple domains can greatly enhance the quality and applicability of knowledge generated in analysis workflows. However, working with health data is challenging, requiring careful preparation in order to support meaningful interpretation and robust results. Ontologies encapsulate relationships between variables that can enrich the semantic content of health datasets to enhance interpretability and inform downstream analyses.

Findings

We developed an R package for electronic health data preparation, ""eHDPrep,"" demonstrated upon a multimodal colorectal cancer dataset (661 patients, 155 variables; Colo-661); a further demonstrator is taken from The Cancer Genome Atlas (459 patients, 94 variables; TCGA-COAD). eHDPrep offers user-friendly methods for quality control, including internal consistency checking and redundancy removal with information-theoretic variable merging. Semantic enrichment functionality is provided, enabling generation of new informative ""meta-variables"" according to ontological common ancestry between variables, demonstrated with SNOMED CT and the Gene Ontology in the current study. eHDPrep also facilitates numerical encoding, variable extraction from free text, completeness analysis, and user review of modifications to the dataset.

Conclusions

eHDPrep provides effective tools to assess and enhance data quality, laying the foundation for robust performance and interpretability in downstream analyses. Application to multimodal colorectal cancer datasets resulted in improved data quality, structuring, and robust encoding, as well as enhanced semantic information. We make eHDPrep available as an R package from CRAN (https://cran.r-project.org/package = eHDPrep) and GitHub (https://github.com/overton-group/eHDPrep).",,pdf:https://academic.oup.com/gigascience/article-pdf/doi/10.1093/gigascience/giad030/50383140/giad030.pdf; doi:https://doi.org/10.1093/gigascience/giad030; html:https://europepmc.org/articles/PMC10176503; pdf:https://europepmc.org/articles/PMC10176503?pdf=render 37607793,https://doi.org/10.1136/bmjopen-2023-076296,"Knowledge support for optimising antibiotic prescribing for common infections in general practices: evaluation of the effectiveness of periodic feedback, decision support during consultations and peer comparisons in a cluster randomised trial (BRIT2) - study protocol.","van Staa T, Sharma A, Palin V, Fahmi A, Cant H, Zhong X, Jury F, Gold N, Welfare W, Ashcroft D, Tsang JY, Elliott RA, Sutton C, Armitage C, Couch P, Moulton G, Tempest E, Buchan IE.",,BMJ open,2023,2023-08-22,Y,Infectious diseases; Randomized controlled trial; Primary Care; Electronic Health Records,,,"

Introduction

This project applies a Learning Healthcare System (LHS) approach to antibiotic prescribing for common infections in primary care. The approach involves iterations of data analysis, feedback to clinicians and implementation of quality improvement activities by the clinicians. The main research question is, can a knowledge support system (KSS) intervention within an LHS implementation improve antibiotic prescribing without increasing the risk of complications?

Methods and analysis

A pragmatic cluster randomised controlled trial will be conducted, with randomisation of at least 112 general practices in North-West England. General practices participating in the trial will be randomised to the following interventions: periodic practice-level and individual prescriber feedback using dashboards; or the same dashboards plus a KSS. Data from large databases of healthcare records are used to characterise heterogeneity in antibiotic uses, and to calculate risk scores for clinical outcomes and for the effectiveness of different treatment strategies. The results provide the baseline content for the dashboards and KSS. The KSS comprises a display within the electronic health record used during the consultation; the prescriber (general practitioner or allied health professional) will answer standard questions about the patient's presentation and will then be presented with information (eg, patient's risk of complications from the infection) to guide decision making. The KSS can generate information sheets for patients, conveyed by the clinicians during consultations. The primary outcome is the practice-level rate of antibiotic prescribing (per 1000 patients) with secondary safety outcomes. The data from practices participating in the trial and the dashboard infrastructure will be held within regional shared care record systems of the National Health Service in the UK.

Ethics and dissemination

Approved by National Health Service Ethics Committee IRAS 290050. The research results will be published in peer-reviewed journals and also disseminated to participating clinical staff and policy and guideline developers.

Trial registration number

ISRCTN16230629.",,doi:https://doi.org/10.1136/bmjopen-2023-076296; doi:https://doi.org/10.1136/bmjopen-2023-076296; html:https://europepmc.org/articles/PMC10445367; pdf:https://europepmc.org/articles/PMC10445367?pdf=render -38096890,https://doi.org/10.1016/s1470-2045(23)00530-2,"Mortality from leading cancers in districts of England from 2002 to 2019: a population-based, spatiotemporal study.","Rashid T, Bennett JE, Muller DC, Cross AJ, Pearson-Stuttard J, Asaria P, Daby HI, Fecht D, Davies B, Ezzati M.",,The Lancet. Oncology,2024,2023-12-11,Y,,,,"

Background

Cancers are the leading cause of death in England. We aimed to estimate trends in mortality from leading cancers from 2002 to 2019 for the 314 districts in England.

Methods

We did a high-resolution spatiotemporal analysis of vital registration data from the UK Office for National Statistics using data on all deaths from the ten leading cancers in England from 2002 to 2019. We used a Bayesian hierarchical model to obtain robust estimates of age-specific and cause-specific death rates. We used life table methods to calculate the primary outcome, the unconditional probability of dying between birth and age 80 years by sex, cancer cause of death, local district, and year. We reported Spearman rank correlations between the probability of dying from a cancer and district-level poverty in 2019.

Findings

In 2019, the probability of dying from a cancer before age 80 years ranged from 0·10 (95% credible interval [CrI] 0·10-0·11) to 0·17 (0·16-0·18) for women and from 0·12 (0·12-0·13) to 0·22 (0·21-0·23) for men. Variation in the probability of dying was largest for lung cancer among women, being 3·7 times (95% CrI 3·2-4·4) higher in the district with the highest probability than in the district with the lowest probability; and for stomach cancer for men, being 3·2 times (2·6-4·1) higher in the district with the highest probability than in the one with the lowest probability. The variation in the probability of dying was smallest across districts for lymphoma and multiple myeloma (95% CrI 1·2 times [1·1-1·4] higher in the district with the highest probability than the lowest probability for women and 1·2 times [1·0-1·4] for men), and leukaemia (1·1 times [1·0-1·4] for women and 1·2 times [1·0-1·5] for men). The Spearman rank correlation between probability of dying from a cancer and district poverty was 0·74 (95% CrI 0·72-0·76) for women and 0·79 (0·78-0·81) for men. From 2002 to 2019, the overall probability of dying from a cancer declined in all districts: the reductions ranged from 6·6% (95% CrI 0·3-13·1) to 30·1% (25·6-34·5) for women and from 12·8% (7·1-18·8) to 36·7% (32·2-41·2) for men. However, there were increases in mortality for liver cancer among men, lung cancer and corpus uteri cancer among women, and pancreatic cancer in both sexes in some or all districts with posterior probability greater than 0·80.

Interpretation

Cancers with modifiable risk factors and potential for screening for precancerous lesions had heterogeneous trends and the greatest geographical inequality. To reduce these inequalities, factors affecting both incidence and survival need to be addressed at the local level.

Funding

Wellcome Trust, Imperial College London, UK Medical Research Council, and the National Institute of Health Research.",,pdf:http://www.thelancet.com/article/S1470204523005302/pdf; doi:https://doi.org/10.1016/S1470-2045(23)00530-2; html:https://europepmc.org/articles/PMC7615518; pdf:https://europepmc.org/articles/PMC7615518?pdf=render 35793922,https://doi.org/10.1136/bmjopen-2021-059385,Deriving and validating a risk prediction model for long COVID-19: protocol for an observational cohort study using linked Scottish data.,"Daines L, Mulholland RH, Vasileiou E, Hammersley V, Weatherill D, Katikireddi SV, Kerr S, Moore E, Pesenti E, Quint JK, Shah SA, Shi T, Simpson CR, Robertson C, Sheikh A.",,BMJ open,2022,2022-07-06,Y,Public Health; Protocols & Guidelines; Covid-19,,,"

Introduction

COVID-19 is commonly experienced as an acute illness, yet some people continue to have symptoms that persist for weeks, or months (commonly referred to as 'long-COVID'). It remains unclear which patients are at highest risk of developing long-COVID. In this protocol, we describe plans to develop a prediction model to identify individuals at risk of developing long-COVID.

Methods and analysis

We will use the national Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II) platform, a population-level linked dataset of routine electronic healthcare data from 5.4 million individuals in Scotland. We will identify potential indicators for long-COVID by identifying patterns in primary care data linked to information from out-of-hours general practitioner encounters, accident and emergency visits, hospital admissions, outpatient visits, medication prescribing/dispensing and mortality. We will investigate the potential indicators of long-COVID by performing a matched analysis between those with a positive reverse transcriptase PCR (RT-PCR) test for SARS-CoV-2 infection and two control groups: (1) individuals with at least one negative RT-PCR test and never tested positive; (2) the general population (everyone who did not test positive) of Scotland. Cluster analysis will then be used to determine the final definition of the outcome measure for long-COVID. We will then derive, internally and externally validate a prediction model to identify the epidemiological risk factors associated with long-COVID.

Ethics and dissemination

The EAVE II study has obtained approvals from the Research Ethics Committee (reference: 12/SS/0201), and the Public Benefit and Privacy Panel for Health and Social Care (reference: 1920-0279). Study findings will be published in peer-reviewed journals and presented at conferences. Understanding the predictors for long-COVID and identifying the patient groups at greatest risk of persisting symptoms will inform future treatments and preventative strategies for long-COVID.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/7/e059385.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-059385; html:https://europepmc.org/articles/PMC9260199; pdf:https://europepmc.org/articles/PMC9260199?pdf=render -36530697,https://doi.org/10.3389/fpubh.2022.1035415,Associations between air pollution and multimorbidity in the UK Biobank: A cross-sectional study.,"Ronaldson A, Arias de la Torre J, Ashworth M, Hansell AL, Hotopf M, Mudway I, Stewart R, Dregan A, Bakolis I.",,Frontiers in public health,2022,2022-12-02,Y,Air pollution; Nitrogen dioxide; particulate matter; Health Status; Exploratory Factor Analysis; Multimorbidity,,,"

Background

Long-term exposure to air pollution concentrations is known to be adversely associated with a broad range of single non-communicable diseases, but its role in multimorbidity has not been investigated in the UK. We aimed to assess associations between long-term air pollution exposure and multimorbidity status, severity, and patterns using the UK Biobank cohort.

Methods

Multimorbidity status was calculated based on 41 physical and mental conditions. We assessed cross-sectional associations between annual modeled particulate matter (PM)2.5, PMcoarse, PM10, and nitrogen dioxide (NO2) concentrations (μg/m3-modeled to residential address) and multimorbidity status at the baseline assessment (2006-2010) in 364,144 people (mean age: 52.2 ± 8.1 years, 52.6% female). Air pollutants were categorized into quartiles to assess dose-response associations. Among those with multimorbidity (≥2 conditions; n = 156,395) we assessed associations between air pollutant exposure levels and multimorbidity severity and multimorbidity patterns, which were identified using exploratory factor analysis. Associations were explored using generalized linear models adjusted for sociodemographic, behavioral, and environmental indicators.

Results

Higher exposures to PM2.5, and NO2 were associated with multimorbidity status in a dose-dependent manner. These associations were strongest when we compared the highest air pollution quartile (quartile 4: Q4) with the lowest quartile (Q1) [PM2.5: adjusted odds ratio (adjOR) = 1.21 (95% CI = 1.18, 1.24); NO2: adjOR = 1.19 (95 % CI = 1.16, 1.23)]. We also observed dose-response associations between air pollutant exposures and multimorbidity severity scores. We identified 11 multimorbidity patterns. Air pollution was associated with several multimorbidity patterns with strongest associations (Q4 vs. Q1) observed for neurological (stroke, epilepsy, alcohol/substance dependency) [PM2.5: adjOR = 1.31 (95% CI = 1.14, 1.51); NO2: adjOR = 1.33 (95% CI = 1.11, 1.60)] and respiratory patterns (COPD, asthma) [PM2.5: adjOR = 1.24 (95% CI = 1.16, 1.33); NO2: adjOR = 1.26 (95% CI = 1.15, 1.38)].

Conclusions

This cross-sectional study provides evidence that exposure to air pollution might be associated with having multimorbid, multi-organ conditions. Longitudinal studies are needed to further explore these associations.",,pdf:https://www.frontiersin.org/articles/10.3389/fpubh.2022.1035415/pdf; doi:https://doi.org/10.3389/fpubh.2022.1035415; html:https://europepmc.org/articles/PMC9755180; pdf:https://europepmc.org/articles/PMC9755180?pdf=render +38096890,https://doi.org/10.1016/s1470-2045(23)00530-2,"Mortality from leading cancers in districts of England from 2002 to 2019: a population-based, spatiotemporal study.","Rashid T, Bennett JE, Muller DC, Cross AJ, Pearson-Stuttard J, Asaria P, Daby HI, Fecht D, Davies B, Ezzati M.",,The Lancet. Oncology,2024,2023-12-11,Y,,,,"

Background

Cancers are the leading cause of death in England. We aimed to estimate trends in mortality from leading cancers from 2002 to 2019 for the 314 districts in England.

Methods

We did a high-resolution spatiotemporal analysis of vital registration data from the UK Office for National Statistics using data on all deaths from the ten leading cancers in England from 2002 to 2019. We used a Bayesian hierarchical model to obtain robust estimates of age-specific and cause-specific death rates. We used life table methods to calculate the primary outcome, the unconditional probability of dying between birth and age 80 years by sex, cancer cause of death, local district, and year. We reported Spearman rank correlations between the probability of dying from a cancer and district-level poverty in 2019.

Findings

In 2019, the probability of dying from a cancer before age 80 years ranged from 0·10 (95% credible interval [CrI] 0·10-0·11) to 0·17 (0·16-0·18) for women and from 0·12 (0·12-0·13) to 0·22 (0·21-0·23) for men. Variation in the probability of dying was largest for lung cancer among women, being 3·7 times (95% CrI 3·2-4·4) higher in the district with the highest probability than in the district with the lowest probability; and for stomach cancer for men, being 3·2 times (2·6-4·1) higher in the district with the highest probability than in the one with the lowest probability. The variation in the probability of dying was smallest across districts for lymphoma and multiple myeloma (95% CrI 1·2 times [1·1-1·4] higher in the district with the highest probability than the lowest probability for women and 1·2 times [1·0-1·4] for men), and leukaemia (1·1 times [1·0-1·4] for women and 1·2 times [1·0-1·5] for men). The Spearman rank correlation between probability of dying from a cancer and district poverty was 0·74 (95% CrI 0·72-0·76) for women and 0·79 (0·78-0·81) for men. From 2002 to 2019, the overall probability of dying from a cancer declined in all districts: the reductions ranged from 6·6% (95% CrI 0·3-13·1) to 30·1% (25·6-34·5) for women and from 12·8% (7·1-18·8) to 36·7% (32·2-41·2) for men. However, there were increases in mortality for liver cancer among men, lung cancer and corpus uteri cancer among women, and pancreatic cancer in both sexes in some or all districts with posterior probability greater than 0·80.

Interpretation

Cancers with modifiable risk factors and potential for screening for precancerous lesions had heterogeneous trends and the greatest geographical inequality. To reduce these inequalities, factors affecting both incidence and survival need to be addressed at the local level.

Funding

Wellcome Trust, Imperial College London, UK Medical Research Council, and the National Institute of Health Research.",,pdf:http://www.thelancet.com/article/S1470204523005302/pdf; doi:https://doi.org/10.1016/S1470-2045(23)00530-2; html:https://europepmc.org/articles/PMC7615518; pdf:https://europepmc.org/articles/PMC7615518?pdf=render 32635913,https://doi.org/10.1186/s12911-020-01169-z,Application of standardised effect sizes to hospital discharge outcomes for people with diabetes.,"Robbins T, Lim Choi Keung SN, Sankar S, Randeva H, Arvanitis TN.",,BMC medical informatics and decision making,2020,2020-07-07,Y,Mortality; Diabetes; Readmission; Effect Size,,,"

Background

Patients with diabetes are at an increased risk of readmission and mortality when discharged from hospital. Existing research identifies statistically significant risk factors that are thought to underpin these outcomes. Increasingly, these risk factors are being used to create risk prediction models, and target risk modifying interventions. These risk factors are typically reported in the literature accompanied by unstandardized effect sizes, which makes comparisons difficult. We demonstrate an assessment of variation between standardised effect sizes for such risk factors across care outcomes and patient cohorts. Such an approach will support development of more rigorous risk stratification tools and better targeting of intervention measures.

Methods

Data was extracted from the electronic health record of a major tertiary referral centre, over a 3-year period, for all patients discharged from hospital with a concurrent diagnosis of diabetes mellitus. Risk factors selected for extraction were pre-specified according to a systematic review of the research literature. Standardised effect sizes were calculated for all statistically significant risk factors, and compared across patient cohorts and both readmission & mortality outcome measures.

Results

Data was extracted for 46,357 distinct admissions patients, creating a large dataset of approximately 10,281,400 data points. The calculation of standardized effect size measures allowed direct comparison. Effect sizes were noted to be larger for mortality compared to readmission, as well as for being larger for surgical and type 1 diabetes cohorts of patients.

Conclusions

The calculation of standardised effect sizes is an important step in evaluating risk factors for healthcare events. This will improve our understanding of risk and support the development of more effective risk stratification tools to support patients to make better informed decisions at discharge from hospital.",,pdf:https://bmcmedinformdecismak.biomedcentral.com/track/pdf/10.1186/s12911-020-01169-z; doi:https://doi.org/10.1186/s12911-020-01169-z; html:https://europepmc.org/articles/PMC7339522; pdf:https://europepmc.org/articles/PMC7339522?pdf=render +36530697,https://doi.org/10.3389/fpubh.2022.1035415,Associations between air pollution and multimorbidity in the UK Biobank: A cross-sectional study.,"Ronaldson A, Arias de la Torre J, Ashworth M, Hansell AL, Hotopf M, Mudway I, Stewart R, Dregan A, Bakolis I.",,Frontiers in public health,2022,2022-12-02,Y,Air pollution; Nitrogen dioxide; particulate matter; Health Status; Exploratory Factor Analysis; Multimorbidity,,,"

Background

Long-term exposure to air pollution concentrations is known to be adversely associated with a broad range of single non-communicable diseases, but its role in multimorbidity has not been investigated in the UK. We aimed to assess associations between long-term air pollution exposure and multimorbidity status, severity, and patterns using the UK Biobank cohort.

Methods

Multimorbidity status was calculated based on 41 physical and mental conditions. We assessed cross-sectional associations between annual modeled particulate matter (PM)2.5, PMcoarse, PM10, and nitrogen dioxide (NO2) concentrations (μg/m3-modeled to residential address) and multimorbidity status at the baseline assessment (2006-2010) in 364,144 people (mean age: 52.2 ± 8.1 years, 52.6% female). Air pollutants were categorized into quartiles to assess dose-response associations. Among those with multimorbidity (≥2 conditions; n = 156,395) we assessed associations between air pollutant exposure levels and multimorbidity severity and multimorbidity patterns, which were identified using exploratory factor analysis. Associations were explored using generalized linear models adjusted for sociodemographic, behavioral, and environmental indicators.

Results

Higher exposures to PM2.5, and NO2 were associated with multimorbidity status in a dose-dependent manner. These associations were strongest when we compared the highest air pollution quartile (quartile 4: Q4) with the lowest quartile (Q1) [PM2.5: adjusted odds ratio (adjOR) = 1.21 (95% CI = 1.18, 1.24); NO2: adjOR = 1.19 (95 % CI = 1.16, 1.23)]. We also observed dose-response associations between air pollutant exposures and multimorbidity severity scores. We identified 11 multimorbidity patterns. Air pollution was associated with several multimorbidity patterns with strongest associations (Q4 vs. Q1) observed for neurological (stroke, epilepsy, alcohol/substance dependency) [PM2.5: adjOR = 1.31 (95% CI = 1.14, 1.51); NO2: adjOR = 1.33 (95% CI = 1.11, 1.60)] and respiratory patterns (COPD, asthma) [PM2.5: adjOR = 1.24 (95% CI = 1.16, 1.33); NO2: adjOR = 1.26 (95% CI = 1.15, 1.38)].

Conclusions

This cross-sectional study provides evidence that exposure to air pollution might be associated with having multimorbid, multi-organ conditions. Longitudinal studies are needed to further explore these associations.",,pdf:https://www.frontiersin.org/articles/10.3389/fpubh.2022.1035415/pdf; doi:https://doi.org/10.3389/fpubh.2022.1035415; html:https://europepmc.org/articles/PMC9755180; pdf:https://europepmc.org/articles/PMC9755180?pdf=render 35050151,https://doi.org/10.3390/metabo12010029,Integration of Metabolomic and Clinical Data Improves the Prediction of Intensive Care Unit Length of Stay Following Major Traumatic Injury.,"Acharjee A, Hazeldine J, Bazarova A, Deenadayalu L, Zhang J, Bentley C, Russ D, Lord JM, Gkoutos GV, Young SP, Foster MA.",,Metabolites,2021,2021-12-31,Y,Inflammation; Metabolomics; Omics Integration; Icu Length Of Stay,,,"Recent advances in emergency medicine and the co-ordinated delivery of trauma care mean more critically-injured patients now reach the hospital alive and survive life-saving operations. Indeed, between 2008 and 2017, the odds of surviving a major traumatic injury in the UK increased by nineteen percent. However, the improved survival rates of severely-injured patients have placed an increased burden on the healthcare system, with major trauma a common cause of intensive care unit (ICU) admissions that last ≥10 days. Improved understanding of the factors influencing patient outcomes is now urgently needed. We investigated the serum metabolomic profile of fifty-five major trauma patients across three post-injury phases: acute (days 0-4), intermediate (days 5-14) and late (days 15-112). Using ICU length of stay (LOS) as a clinical outcome, we aimed to determine whether the serum metabolome measured at days 0-4 post-injury for patients with an extended (≥10 days) ICU LOS differed from that of patients with a short (<10 days) ICU LOS. In addition, we investigated whether combining metabolomic profiles with clinical scoring systems would generate a variable that would identify patients with an extended ICU LOS with a greater degree of accuracy than models built on either variable alone. The number of metabolites unique to and shared across each time segment varied across acute, intermediate and late segments. A one-way ANOVA revealed the most variation in metabolite levels across the different time-points was for the metabolites lactate, glucose, anserine and 3-hydroxybutyrate. A total of eleven features were selected to differentiate between <10 days ICU LOS vs. >10 days ICU LOS. New Injury Severity Score (NISS), testosterone, and the metabolites cadaverine, urea, isoleucine, acetoacetate, dimethyl sulfone, syringate, creatinine, xylitol, and acetone form the integrated biomarker set. Using metabolic enrichment analysis, we found valine, leucine and isoleucine biosynthesis, glutathione metabolism, and glycine, serine and threonine metabolism were the top three pathways differentiating ICU LOS with a p < 0.05. A combined model of NISS and testosterone and all nine selected metabolites achieved an AUROC of 0.824. Differences exist in the serum metabolome of major trauma patients who subsequently experience a short or prolonged ICU LOS in the acute post-injury setting. Combining metabolomic data with anatomical scoring systems allowed us to discriminate between these two groups with a greater degree of accuracy than that of either variable alone.",,pdf:https://www.mdpi.com/2218-1989/12/1/29/pdf?version=1642410547; doi:https://doi.org/10.3390/metabo12010029; html:https://europepmc.org/articles/PMC8780653; pdf:https://europepmc.org/articles/PMC8780653?pdf=render 38269898,https://doi.org/10.3233/shti231054,Identifying Mentions of Pain in Mental Health Records Text: A Natural Language Processing Approach.,"Chaturvedi J, Velupillai S, Stewart R, Roberts A.",,Studies in health technology and informatics,2024,2024-01-01,N,Pain; Mental health; Electronic Health Records; Natural Language Processing; Transformers,,,"Pain is a common reason for accessing healthcare resources and is a growing area of research, especially in its overlap with mental health. Mental health electronic health records are a good data source to study this overlap. However, much information on pain is held in the free text of these records, where mentions of pain present a unique natural language processing problem due to its ambiguous nature. This project uses data from an anonymised mental health electronic health records database. A machine learning based classification algorithm is trained to classify sentences as discussing patient pain or not. This will facilitate the extraction of relevant pain information from large databases. 1,985 documents were manually triple-annotated for creation of gold standard training data, which was used to train four classification algorithms. The best performing model achieved an F1-score of 0.98 (95% CI 0.98-0.99).",,pdf:https://ebooks.iospress.nl/pdf/doi/10.3233/SHTI231054; doi:https://doi.org/10.3233/SHTI231054 36217535,https://doi.org/10.1038/s43856-022-00185-6,"Multi-omic phenotyping reveals host-microbe responses to bariatric surgery, glycaemic control and obesity.","Penney NC, Yeung DKT, Garcia-Perez I, Posma JM, Kopytek A, Garratt B, Ashrafian H, Frost G, Marchesi JR, Purkayastha S, Hoyles L, Darzi A, Holmes E.",,Communications medicine,2022,2022-10-07,Y,Obesity; Type 2 diabetes; Dynamical Systems; Microbiome,,,"

Background

Resolution of type 2 diabetes (T2D) is common following bariatric surgery, particularly Roux-en-Y gastric bypass. However, the underlying mechanisms have not been fully elucidated.

Methods

To address this we compare the integrated serum, urine and faecal metabolic profiles of participants with obesity ± T2D (n = 80, T2D = 42) with participants who underwent Roux-en-Y gastric bypass or sleeve gastrectomy (pre and 3-months post-surgery; n = 27), taking diet into account. We co-model these data with shotgun metagenomic profiles of the gut microbiota to provide a comprehensive atlas of host-gut microbe responses to bariatric surgery, weight-loss and glycaemic control at the systems level.

Results

Here we show that bariatric surgery reverses several disrupted pathways characteristic of T2D. The differential metabolite set representative of bariatric surgery overlaps with both diabetes (19.3% commonality) and body mass index (18.6% commonality). However, the percentage overlap between diabetes and body mass index is minimal (4.0% commonality), consistent with weight-independent mechanisms of T2D resolution. The gut microbiota is more strongly correlated to body mass index than T2D, although we identify some pathways such as amino acid metabolism that correlate with changes to the gut microbiota and which influence glycaemic control.

Conclusion

We identify multi-omic signatures associated with responses to surgery, body mass index, and glycaemic control. Improved understanding of gut microbiota - host co-metabolism may lead to novel therapies for weight-loss or diabetes. However, further experiments are required to provide mechanistic insight into the role of the gut microbiota in host metabolism and establish proof of causality.",,pdf:https://www.nature.com/articles/s43856-022-00185-6.pdf; doi:https://doi.org/10.1038/s43856-022-00185-6; html:https://europepmc.org/articles/PMC9546886; pdf:https://europepmc.org/articles/PMC9546886?pdf=render @@ -410,8 +410,8 @@ PMC10910267,https://doi.org/,Development and evaluation of a tool to optimise in 34598993,https://doi.org/10.1136/bmjopen-2021-054410,"Changes in neonatal admissions, care processes and outcomes in England and Wales during the COVID-19 pandemic: a whole population cohort study.","Greenbury SF, Longford N, Ougham K, Angelini ED, Battersby C, Uthaya S, Modi N.",,BMJ open,2021,2021-10-01,Y,Public Health; Neonatology; Neonatal Intensive & Critical Care,,,"

Objectives

The COVID-19 pandemic instigated multiple societal and healthcare interventions with potential to affect perinatal practice. We evaluated population-level changes in preterm and full-term admissions to neonatal units, care processes and outcomes.

Design

Observational cohort study using the UK National Neonatal Research Database.

Setting

England and Wales.

Participants

Admissions to National Health Service neonatal units from 2012 to 2020.

Main outcome measures

Admissions by gestational age, ethnicity and Index of Multiple Deprivation, and key care processes and outcomes.

Methods

We calculated differences in numbers and rates between April and June 2020 (spring), the first 3 months of national lockdown (COVID-19 period), and December 2019-February 2020 (winter), prior to introduction of mitigation measures, and compared them with the corresponding differences in the previous 7 years. We considered the COVID-19 period highly unusual if the spring-winter difference was smaller or larger than all previous corresponding differences, and calculated the level of confidence in this conclusion.

Results

Marked fluctuations occurred in all measures over the 8 years with several highly unusual changes during the COVID-19 period. Total admissions fell, having risen over all previous years (COVID-19 difference: -1492; previous 7-year difference range: +100, +1617; p<0.001); full-term black admissions rose (+66; -64, +35; p<0.001) whereas Asian (-137; -14, +101; p<0.001) and white (-319; -235, +643: p<0.001) admissions fell. Transfers to higher and lower designation neonatal units increased (+129; -4, +88; p<0.001) and decreased (-47; -25, +12; p<0.001), respectively. Total preterm admissions decreased (-350; -26, +479; p<0.001). The fall in extremely preterm admissions was most marked in the two lowest socioeconomic quintiles.

Conclusions

Our findings indicate substantial changes occurred in care pathways and clinical thresholds, with disproportionate effects on black ethnic groups, during the immediate COVID-19 period, and raise the intriguing possibility that non-healthcare interventions may reduce extremely preterm births.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/10/e054410.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-054410; html:https://europepmc.org/articles/PMC8488283; pdf:https://europepmc.org/articles/PMC8488283?pdf=render 36544046,https://doi.org/10.1038/s41746-022-00730-6,A survey on clinical natural language processing in the United Kingdom from 2007 to 2022.,"Wu H, Wang M, Wu J, Francis F, Chang YH, Shavick A, Dong H, Poon MTC, Fitzpatrick N, Levine AP, Slater LT, Handy A, Karwath A, Gkoutos GV, Chelala C, Shah AD, Stewart R, Collier N, Alex B, Whiteley W, Sudlow C, Roberts A, Dobson RJB.",,NPJ digital medicine,2022,2022-12-21,Y,,,,"Much of the knowledge and information needed for enabling high-quality clinical research is stored in free-text format. Natural language processing (NLP) has been used to extract information from these sources at scale for several decades. This paper aims to present a comprehensive review of clinical NLP for the past 15 years in the UK to identify the community, depict its evolution, analyse methodologies and applications, and identify the main barriers. We collect a dataset of clinical NLP projects (n = 94; £ = 41.97 m) funded by UK funders or the European Union's funding programmes. Additionally, we extract details on 9 funders, 137 organisations, 139 persons and 431 research papers. Networks are created from timestamped data interlinking all entities, and network analysis is subsequently applied to generate insights. 431 publications are identified as part of a literature review, of which 107 are eligible for final analysis. Results show, not surprisingly, clinical NLP in the UK has increased substantially in the last 15 years: the total budget in the period of 2019-2022 was 80 times that of 2007-2010. However, the effort is required to deepen areas such as disease (sub-)phenotyping and broaden application domains. There is also a need to improve links between academia and industry and enable deployments in real-world settings for the realisation of clinical NLP's great potential in care delivery. The major barriers include research and development access to hospital data, lack of capable computational resources in the right places, the scarcity of labelled data and barriers to sharing of pretrained models.",,pdf:https://www.nature.com/articles/s41746-022-00730-6.pdf; doi:https://doi.org/10.1038/s41746-022-00730-6; html:https://europepmc.org/articles/PMC9770568; pdf:https://europepmc.org/articles/PMC9770568?pdf=render 35413949,https://doi.org/10.1038/s41467-022-29521-z,"Persistent COVID-19 symptoms in a community study of 606,434 people in England.","Whitaker M, Elliott J, Chadeau-Hyam M, Riley S, Darzi A, Cooke G, Ward H, Elliott P.",,Nature communications,2022,2022-04-12,Y,,,,"Long COVID remains a broadly defined syndrome, with estimates of prevalence and duration varying widely. We use data from rounds 3-5 of the REACT-2 study (n = 508,707; September 2020 - February 2021), a representative community survey of adults in England, and replication data from round 6 (n = 97,717; May 2021) to estimate the prevalence and identify predictors of persistent symptoms lasting 12 weeks or more; and unsupervised learning to cluster individuals by reported symptoms. At 12 weeks in rounds 3-5, 37.7% experienced at least one symptom, falling to 21.6% in round 6. Female sex, increasing age, obesity, smoking, vaping, hospitalisation with COVID-19, deprivation, and being a healthcare worker are associated with higher probability of persistent symptoms in rounds 3-5, and Asian ethnicity with lower probability. Clustering analysis identifies a subset of participants with predominantly respiratory symptoms. Managing the long-term sequelae of COVID-19 will remain a major challenge for affected individuals and their families and for health services.",,pdf:https://www.nature.com/articles/s41467-022-29521-z.pdf; doi:https://doi.org/10.1038/s41467-022-29521-z; html:https://europepmc.org/articles/PMC9005552; pdf:https://europepmc.org/articles/PMC9005552?pdf=render -37400731,https://doi.org/10.1007/s10802-023-01086-5,Maternal Mental Health and Children's Problem Behaviours: A Bi-directional Relationship?,"Lowthian E, Bedston S, Kristensen SM, Akbari A, Fry R, Huxley K, Johnson R, Kim HS, Owen RK, Taylor C, Griffiths L.",,Research on child and adolescent psychopathology,2023,2023-07-04,Y,Child Development; Bayesian analysis; Structural Equation Modelling; Maternal Mental Health; Millennium Cohort Study,,,"Transactional theory and the coercive family process model have illustrated how the parent-child relationship is reciprocal. Emerging research using advanced statistical methods has examined these theories, but further investigations are necessary. In this study, we utilised linked health data on maternal mental health disorders and explored their relationship with child problem behaviours via the Strengths and Difficulties Questionnaire for over 13 years. We accessed data from the Millennium Cohort Study, linked to anonymised individual-level population-scale health and administrative data within the Secure Anonymised Information Linkage (SAIL) Databank. We used Bayesian Structural Equation Modelling, specifically Random-Intercept Cross-Lagged Panel Models, to analyse the relationships between mothers and their children. We then explored these models with the addition of time-invariant covariates. We found that a mother's mental health was strongly associated over time, as were children's problem behaviours. We found mixed evidence for bi-directional relationships, with only emotional problems showing bi-directional associations in mid to late childhood. Only child-to-mother pathways were identified for the overall problem behaviour score and peer problems; no associations were found for conduct problems or hyperactivity. All models had strong between-effects and clear socioeconomic and sex differences. We encourage the use of whole family-based support for mental health and problem behaviours, and recommend that socioeconomic, sex and wider differences should be considered as factors in tailoring family-based interventions and support.",,pdf:https://link.springer.com/content/pdf/10.1007/s10802-023-01086-5.pdf; doi:https://doi.org/10.1007/s10802-023-01086-5; html:https://europepmc.org/articles/PMC10628040; pdf:https://europepmc.org/articles/PMC10628040?pdf=render 33948220,https://doi.org/10.1177/20552076211007661,Association between glycosylated haemoglobin and outcomes for patients discharged from hospital with diabetes: A health informatics approach.,"Robbins T, Sankaranarayanan S, Randeva H, Keung SNLC, Arvanitis TN.",,Digital health,2021,2021-01-01,Y,Biochemistry; Diabetes; Hospital Discharge; Readmission; Health Informatics,,,"

Aims/objectives

Extensive research considers associations between inpatient glycaemic control and outcomes during hospital admission; this cautions against overly tight glycaemic targets. Little research considers glycaemic control following hospital discharge. This is despite a clear understanding that people with diabetes are at increased risk of negative outcomes, following discharge. We evaluate absolute and relative Hba1c values, and frequency of Hba1c monitoring, on readmission and mortality rates for people discharged from hospital with diabetes.

Methods

All discharges (n = 46,357) with diabetes from a major tertiary referral centre over 3 years were extracted, including biochemistry data. We conducted an evaluation of association between Hba1c, mortality and readmission, statistical significance and standardised Cohen's D effect size calculations.

Results

399 patients had a Hba1c performed during their admission. 3,138 patients had a Hba1c within 1 year of discharge. Mean average Hba1c for readmissions was 57.82 vs 60.39 for not readmitted (p = 0.009, Cohen's D 0.28). Mean average number of days to Hba1c testing in readmitted was 97 vs 113 for those not readmitted (p = 0.00006, Cohen's D 0.39). Further evaluation of mortality outcomes, cohorts of T1DM and T2DM and association of relative change in Hba1c was performed.

Conclusions

Lower Hba1c values following discharge from hospital are significantly associated with increased risk of readmission, as is a shorter duration until testing. Similar patterns observed for mortality. Findings particularly prominent for T1DM. Further research needed to consider underlying causation and design of appropriate risk stratification models.",,pdf:https://journals.sagepub.com/doi/pdf/10.1177/20552076211007661; doi:https://doi.org/10.1177/20552076211007661; html:https://europepmc.org/articles/PMC8054217; pdf:https://europepmc.org/articles/PMC8054217?pdf=render +37400731,https://doi.org/10.1007/s10802-023-01086-5,Maternal Mental Health and Children's Problem Behaviours: A Bi-directional Relationship?,"Lowthian E, Bedston S, Kristensen SM, Akbari A, Fry R, Huxley K, Johnson R, Kim HS, Owen RK, Taylor C, Griffiths L.",,Research on child and adolescent psychopathology,2023,2023-07-04,Y,Child Development; Bayesian analysis; Structural Equation Modelling; Maternal Mental Health; Millennium Cohort Study,,,"Transactional theory and the coercive family process model have illustrated how the parent-child relationship is reciprocal. Emerging research using advanced statistical methods has examined these theories, but further investigations are necessary. In this study, we utilised linked health data on maternal mental health disorders and explored their relationship with child problem behaviours via the Strengths and Difficulties Questionnaire for over 13 years. We accessed data from the Millennium Cohort Study, linked to anonymised individual-level population-scale health and administrative data within the Secure Anonymised Information Linkage (SAIL) Databank. We used Bayesian Structural Equation Modelling, specifically Random-Intercept Cross-Lagged Panel Models, to analyse the relationships between mothers and their children. We then explored these models with the addition of time-invariant covariates. We found that a mother's mental health was strongly associated over time, as were children's problem behaviours. We found mixed evidence for bi-directional relationships, with only emotional problems showing bi-directional associations in mid to late childhood. Only child-to-mother pathways were identified for the overall problem behaviour score and peer problems; no associations were found for conduct problems or hyperactivity. All models had strong between-effects and clear socioeconomic and sex differences. We encourage the use of whole family-based support for mental health and problem behaviours, and recommend that socioeconomic, sex and wider differences should be considered as factors in tailoring family-based interventions and support.",,pdf:https://link.springer.com/content/pdf/10.1007/s10802-023-01086-5.pdf; doi:https://doi.org/10.1007/s10802-023-01086-5; html:https://europepmc.org/articles/PMC10628040; pdf:https://europepmc.org/articles/PMC10628040?pdf=render 36944118,https://doi.org/10.2337/dc22-1238,Cardiovascular Safety in Type 2 Diabetes With Sulfonylureas as Second-line Drugs: A Nationwide Population-Based Comparative Safety Study.,"Wang H, Cordiner RLM, Huang Y, Donnelly L, Hapca S, Collier A, McKnight J, Kennon B, Gibb F, McKeigue P, Wild SH, Colhoun H, Chalmers J, Petrie J, Sattar N, MacDonald T, McCrimmon RJ, Morales DR, Pearson ER, Scottish Diabetes Research Network Epidemiology Group.",,Diabetes care,2023,2023-05-01,Y,,,,"

Objective

To assess the real-world cardiovascular (CV) safety for sulfonylureas (SU), in comparison with dipeptidyl peptidase 4 inhibitors (DPP4i) and thiazolidinediones (TZD), through development of robust methodology for causal inference in a whole nation study.

Research design and methods

A cohort study was performed including people with type 2 diabetes diagnosed in Scotland before 31 December 2017, who failed to reach HbA1c 48 mmol/mol despite metformin monotherapy and initiated second-line pharmacotherapy (SU/DPP4i/TZD) on or after 1 January 2010. The primary outcome was composite major adverse cardiovascular events (MACE), including hospitalization for myocardial infarction, ischemic stroke, heart failure, and CV death. Secondary outcomes were each individual end point and all-cause death. Multivariable Cox proportional hazards regression and an instrumental variable (IV) approach were used to control confounding in a similar way to the randomization process in a randomized control trial.

Results

Comparing SU to non-SU (DPP4i/TZD), the hazard ratio (HR) for MACE was 1.00 (95% CI: 0.91-1.09) from the multivariable Cox regression and 1.02 (0.91-1.13) and 1.03 (0.91-1.16) using two different IVs. For all-cause death, the HR from Cox regression and the two IV analyses was 1.03 (0.94-1.13), 1.04 (0.93-1.17), and 1.03 (0.90-1.17).

Conclusions

Our findings contribute to the understanding that second-line SU for glucose lowering are unlikely to increase CV risk or all-cause mortality. Given their potent efficacy, microvascular benefits, cost effectiveness, and widespread use, this study supports that SU should remain a part of the global diabetes treatment portfolio.",,pdf:https://diabetesjournals.org/care/article-pdf/46/5/967/702262/dc221238.pdf; doi:https://doi.org/10.2337/dc22-1238; html:https://europepmc.org/articles/PMC10154665; pdf:https://europepmc.org/articles/PMC10154665?pdf=render 33087383,https://doi.org/10.1136/bmjopen-2020-043010,Understanding and responding to COVID-19 in Wales: protocol for a privacy-protecting data platform for enhanced epidemiology and evaluation of interventions.,"Lyons J, Akbari A, Torabi F, Davies GI, North L, Griffiths R, Bailey R, Hollinghurst J, Fry R, Turner SL, Thompson D, Rafferty J, Mizen A, Orton C, Thompson S, Au-Yeung L, Cross L, Gravenor MB, Brophy S, Lucini B, John A, Szakmany T, Davies J, Davies C, Thomas DR, Williams C, Emmerson C, Cottrell S, Connor TR, Taylor C, Pugh RJ, Diggle P, John G, Scourfield S, Hunt J, Cunningham AM, Helliwell K, Lyons R.",,BMJ open,2020,2020-10-21,Y,epidemiology; Public Health; Health Informatics; Covid-19,,,"

Introduction

The emergence of the novel respiratory SARS-CoV-2 and subsequent COVID-19 pandemic have required rapid assimilation of population-level data to understand and control the spread of infection in the general and vulnerable populations. Rapid analyses are needed to inform policy development and target interventions to at-risk groups to prevent serious health outcomes. We aim to provide an accessible research platform to determine demographic, socioeconomic and clinical risk factors for infection, morbidity and mortality of COVID-19, to measure the impact of COVID-19 on healthcare utilisation and long-term health, and to enable the evaluation of natural experiments of policy interventions.

Methods and analysis

Two privacy-protecting population-level cohorts have been created and derived from multisourced demographic and healthcare data. The C20 cohort consists of 3.2 million people in Wales on the 1 January 2020 with follow-up until 31 May 2020. The complete cohort dataset will be updated monthly with some individual datasets available daily. The C16 cohort consists of 3 million people in Wales on the 1 January 2016 with follow-up to 31 December 2019. C16 is designed as a counterfactual cohort to provide contextual comparative population data on disease, health service utilisation and mortality. Study outcomes will: (a) characterise the epidemiology of COVID-19, (b) assess socioeconomic and demographic influences on infection and outcomes, (c) measure the impact of COVID-19 on short -term and longer-term population outcomes and (d) undertake studies on the transmission and spatial spread of infection.

Ethics and dissemination

The Secure Anonymised Information Linkage-independent Information Governance Review Panel has approved this study. The study findings will be presented to policy groups, public meetings, national and international conferences, and published in peer-reviewed journals.",,pdf:https://bmjopen.bmj.com/content/bmjopen/10/10/e043010.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-043010; html:https://europepmc.org/articles/PMC7580065; pdf:https://europepmc.org/articles/PMC7580065?pdf=render 38233744,https://doi.org/10.1186/s12874-024-02143-3,Novel linkage approach to join community-acquired and national data.,"Tochel C, Pead E, McTrusty A, Buckmaster F, MacGillivray T, Tatham AJ, Strang NC, Dhillon B, Bernabeu MO.",,BMC medical research methodology,2024,2024-01-17,Y,Image analysis; Longitudinal data; Data Linkage; Early Disease Detection; Community Optometry,,,"

Background

Community optometrists in Scotland have performed regular free-at-point-of-care eye examinations for all, for over 15 years. Eye examinations include retinal imaging but image storage is fragmented and they are not used for research. The Scottish Collaborative Optometry-Ophthalmology Network e-research project aimed to collect these images and create a repository linked to routinely collected healthcare data, supporting the development of pre-symptomatic diagnostic tools.

Methods

As the image record was usually separate from the patient record and contained minimal patient information, we developed an efficient matching algorithm using a combination of deterministic and probabilistic steps which minimised the risk of false positives, to facilitate national health record linkage. We visited two practices and assessed the data contained in their image device and Practice Management Systems. Practice activities were explored to understand the context of data collection processes. Iteratively, we tested a series of matching rules which captured a high proportion of true positive records compared to manual matches. The approach was validated by testing manual matching against automated steps in three further practices.

Results

A sequence of deterministic rules successfully matched 95% of records in the three test practices compared to manual matching. Adding two probabilistic rules to the algorithm successfully matched 99% of records.

Conclusions

The potential value of community-acquired retinal images can be harnessed only if they are linked to centrally-held healthcare care data. Despite the lack of interoperability between systems within optometry practices and inconsistent use of unique identifiers, data linkage is possible using robust, almost entirely automated processes.",,pdf:https://bmcmedresmethodol.biomedcentral.com/counter/pdf/10.1186/s12874-024-02143-3; doi:https://doi.org/10.1186/s12874-024-02143-3; html:https://europepmc.org/articles/PMC10792819; pdf:https://europepmc.org/articles/PMC10792819?pdf=render @@ -423,14 +423,14 @@ PMC10910267,https://doi.org/,Development and evaluation of a tool to optimise in 34232969,https://doi.org/10.23889/ijpds.v5i1.1151,How effective are population health surveys for estimating prevalence of chronic conditions compared to anonymised clinical data?,"Whiffen T, Akbari A, Paget T, Lowe S, Lyons R.",,International journal of population data science,2020,2020-06-12,Y,,,,"

Introduction

Population health surveys are used to record person-reported outcome measures for chronic health conditions and provide a useful source of data when evaluating potential disease burdens. The reliability of survey-based prevalence estimates for chronic diseases is unclear nonetheless. This study applied methodological triangulation via a data linkage method to validate prevalence of selected chronic conditions (angina, myocardial infarction, heart failure, and asthma).

Methods

Linked healthcare records were used for a combined cohort of 11,323 adults from the 2013 and 2014 sweeps of the Welsh Health Survey (WHS). The approach utilised consented survey data linked to primary and secondary care electronic health record (EHR) data back to 2002 within the Secure Anonymised Information Linkage (SAIL) Databank.

Results

This descriptive study demonstrates validation of survey and clinical data using data linkage for selected chronic cardiovascular conditions and asthma with varied success. The results indicate that identifying cases for separate cardiovascular conditions was limited without specific medication codes for each condition, but more straightforward for asthma, where there was an extensive list of medications available. For asthma there was better agreement between prevalence estimates based on survey and clinical data as a result.

Conclusion

Whilst the results provide external validity for the WHS as an instrument for estimating the burden of chronic disease, they also indicate that a data linkage appproach can be used to produce comparable prevalence estimates using clinical data if a defined condition-specific set of clinical codes are available.",,pdf:https://ijpds.org/article/download/1151/2553; doi:https://doi.org/10.23889/ijpds.v5i1.1151; html:https://europepmc.org/articles/PMC7473295; pdf:https://europepmc.org/articles/PMC7473295?pdf=render 34746717,https://doi.org/10.1016/j.eclinm.2021.101100,Paediatric major incident triage: UK military tool offers best performance in predicting the need for time-critical major surgical and resuscitative intervention.,"Malik NS, Chernbumroong S, Xu Y, Vassallo J, Lee J, Moran CG, Newton T, Arul GS, Lord JM, Belli A, Keene D, Foster M, Hodgetts T, Bowley DM, Gkoutos GV.",,EClinicalMedicine,2021,2021-08-23,Y,,,,"

Background

Children are frequently injured during major incidents (MI), including terrorist attacks, conflict and natural disasters. Triage facilitates healthcare resource allocation in order to maximise overall survival. A critical function of MI triage tools is to identify patients needing time-critical major resuscitative and surgical intervention (Priority 1 (P1) status). This study compares the performance of 11 MI triage tools in predicting P1 status in children from the UK Trauma Audit and Research Network (TARN) registry.

Methods

Patients aged <16 years within TARN (January 2008-December 2017) were included. 11 triage tools were applied to patients' first recorded pre-hospital physiology. Patients were retrospectively assigned triage categories (P1, P2, P3, Expectant or Dead) using predefined intervention-based criteria. Tools' performance in <16s were evaluated within four-yearly age subgroups, comparing tool-predicted and intervention-based priority status.

Findings

Amongst 4962 patients, mortality was 1.1% (n = 53); median Injury Severity Score (ISS) was 9 (IQR 9-16). Blunt injuries predominated (94.4%). 1343 (27.1%) met intervention-based criteria for P1, exhibiting greater intensive care requirement (60.2% vs. 8.5%, p < 0.01) and ISS (median 17 vs 9, p < 0.01) compared with P2 patients. The Battlefield Casualty Drills (BCD) Triage Sieve had greatest sensitivity (75.7%) in predicting P1 status in children <16 years, demonstrating a 38.4-49.8% improvement across all subgroups of children <12 years compared with the UK's current Paediatric Triage Tape (PTT). JumpSTART demonstrated low sensitivity in predicting P1 status in 4 to 8 year olds (35.5%) and 0 to 4 year olds (28.5%), and was outperformed by its adult counterpart START (60.6% and 59.6%).

Interpretation

The BCD Triage Sieve had greatest sensitivity in predicting P1 status in this paediatric trauma registry population: we recommend it replaces the PTT in UK practice. Users of JumpSTART may consider alternative tools. We recommend Lerner's triage category definitions when conducting MI evaluations.",,pdf:http://www.thelancet.com/article/S2589537021003801/pdf; doi:https://doi.org/10.1016/j.eclinm.2021.101100; html:https://europepmc.org/articles/PMC8548919; pdf:https://europepmc.org/articles/PMC8548919?pdf=render 38769347,https://doi.org/10.1038/s41746-024-01065-0,Self-supervised learning of accelerometer data provides new insights for sleep and its association with mortality.,"Yuan H, Plekhanova T, Walmsley R, Reynolds AC, Maddison KJ, Bucan M, Gehrman P, Rowlands A, Ray DW, Bennett D, McVeigh J, Straker L, Eastwood P, Kyle SD, Doherty A.",,NPJ digital medicine,2024,2024-05-20,Y,,,,"Sleep is essential to life. Accurate measurement and classification of sleep/wake and sleep stages is important in clinical studies for sleep disorder diagnoses and in the interpretation of data from consumer devices for monitoring physical and mental well-being. Existing non-polysomnography sleep classification techniques mainly rely on heuristic methods developed in relatively small cohorts. Thus, we aimed to establish the accuracy of wrist-worn accelerometers for sleep stage classification and subsequently describe the association between sleep duration and efficiency (proportion of total time asleep when in bed) with mortality outcomes. We developed a self-supervised deep neural network for sleep stage classification using concurrent laboratory-based polysomnography and accelerometry. After exclusion, 1448 participant nights of data were used for training. The difference between polysomnography and the model classifications on the external validation was 34.7 min (95% limits of agreement (LoA): -37.8-107.2 min) for total sleep duration, 2.6 min for REM duration (95% LoA: -68.4-73.4 min) and 32.1 min (95% LoA: -54.4-118.5 min) for NREM duration. The sleep classifier was deployed in the UK Biobank with 100,000 participants to study the association of sleep duration and sleep efficiency with all-cause mortality. Among 66,214 UK Biobank participants, 1642 mortality events were observed. Short sleepers (<6 h) had a higher risk of mortality compared to participants with normal sleep duration of 6-7.9 h, regardless of whether they had low sleep efficiency (Hazard ratios (HRs): 1.58; 95% confidence intervals (CIs): 1.19-2.11) or high sleep efficiency (HRs: 1.45; 95% CIs: 1.16-1.81). Deep-learning-based sleep classification using accelerometers has a fair to moderate agreement with polysomnography. Our findings suggest that having short overnight sleep confers mortality risk irrespective of sleep continuity.",,pdf:https://www.nature.com/articles/s41746-024-01065-0.pdf; doi:https://doi.org/10.1038/s41746-024-01065-0; html:https://europepmc.org/articles/PMC11106264; pdf:https://europepmc.org/articles/PMC11106264?pdf=render -38642997,https://doi.org/10.1136/bmjopen-2023-079923,Distributions of recorded pain in mental health records: a natural language processing based study.,"Chaturvedi J, Stewart R, Ashworth M, Roberts A.",,BMJ open,2024,2024-04-19,Y,Chronic pain; Mental health; epidemiology; Electronic Health Records; Natural Language Processing,,,"

Objective

The objective of this study is to determine demographic and diagnostic distributions of physical pain recorded in clinical notes of a mental health electronic health records database by using natural language processing and examine the overlap in recorded physical pain between primary and secondary care.

Design, setting and participants

The data were extracted from an anonymised version of the electronic health records of a large secondary mental healthcare provider serving a catchment of 1.3 million residents in south London. These included patients under active referral, aged 18+ at the index date of 1 July 2018 and having at least one clinical document (≥30 characters) between 1 July 2017 and 1 July 2019. This cohort was compared with linked primary care records from one of the four local government areas.

Outcome

The primary outcome of interest was the presence of recorded physical pain within the clinical notes of the patients, not including psychological or metaphorical pain.

Results

A total of 27 211 patients were retrieved. Of these, 52% (14,202) had narrative text containing relevant mentions of physical pain. Older patients (OR 1.17, 95% CI 1.15 to 1.19), females (OR 1.42, 95% CI 1.35 to 1.49), Asians (OR 1.30, 95% CI 1.16 to 1.45) or black (OR 1.49, 95% CI 1.40 to 1.59) ethnicities, living in deprived neighbourhoods (OR 1.64, 95% CI 1.55 to 1.73) showed higher odds of recorded pain. Patients with severe mental illnesses were found to be less likely to report pain (OR 0.43, 95% CI 0.41 to 0.46, p<0.001). 17% of the cohort from secondary care also had records from primary care.

Conclusion

The findings of this study show sociodemographic and diagnostic differences in recorded pain. Specifically, lower documentation across certain groups indicates the need for better screening protocols and training on recognising varied pain presentations. Additionally, targeting improved detection of pain for minority and disadvantaged groups by care providers can promote health equity.",,doi:https://doi.org/10.1136/bmjopen-2023-079923; html:https://europepmc.org/articles/PMC11033644; pdf:https://europepmc.org/articles/PMC11033644?pdf=render 33079204,https://doi.org/10.1093/ehjqcco/qcaa079,Impact of COVID-19 on cardiac procedure activity in England and associated 30-day mortality.,"Mohamed MO, Banerjee A, Clarke S, de Belder M, Patwala A, Goodwin AT, Kwok CS, Rashid M, Gale CP, Curzen N, Mamas MA.",,European heart journal. Quality of care & clinical outcomes,2021,2021-05-01,Y,Mortality; Cardiac; England; Procedures; Covid-19,,,"

Aims

Limited data exist on the impact of COVID-19 on national changes in cardiac procedure activity, including patient characteristics and clinical outcomes before and during the COVID-19 pandemic.

Methods and results

All major cardiac procedures (n = 374 899) performed between 1 January and 31 May for the years 2018, 2019, and 2020 were analysed, stratified by procedure type and time-period (pre-COVID: January-May 2018 and 2019 and January-February 2020 and COVID: March-May 2020). Multivariable logistic regression was performed to examine the odds ratio (OR) of 30-day mortality for procedures performed in the COVID period. Overall, there was a deficit of 45 501 procedures during the COVID period compared to the monthly averages (March-May) in 2018-2019. Cardiac catheterization and device implantations were the most affected in terms of numbers (n = 19 637 and n = 10 453), whereas surgical procedures such as mitral valve replacement, other valve replacement/repair, atrioseptal defect/ventriculoseptal defect repair, and coronary artery bypass grafting were the most affected as a relative percentage difference (Δ) to previous years' averages. Transcatheter aortic valve replacement was the least affected (Δ -10.6%). No difference in 30-day mortality was observed between pre-COVID and COVID time-periods for all cardiac procedures except cardiac catheterization [OR 1.25 95% confidence interval (CI) 1.07-1.47, P = 0.006] and cardiac device implantation (OR 1.35 95% CI 1.15-1.58, P < 0.001).

Conclusion

Cardiac procedural activity has significantly declined across England during the COVID-19 pandemic, with a deficit in excess of 45 000 procedures, without an increase in risk of mortality for most cardiac procedures performed during the pandemic. Major restructuring of cardiac services is necessary to deal with this deficit, which would inevitably impact long-term morbidity and mortality.",,pdf:https://academic.oup.com/ehjqcco/article-pdf/7/3/247/37776880/qcaa079.pdf; doi:https://doi.org/10.1093/ehjqcco/qcaa079; html:https://europepmc.org/articles/PMC7665465; pdf:https://europepmc.org/articles/PMC7665465?pdf=render +38642997,https://doi.org/10.1136/bmjopen-2023-079923,Distributions of recorded pain in mental health records: a natural language processing based study.,"Chaturvedi J, Stewart R, Ashworth M, Roberts A.",,BMJ open,2024,2024-04-19,Y,Chronic pain; Mental health; epidemiology; Electronic Health Records; Natural Language Processing,,,"

Objective

The objective of this study is to determine demographic and diagnostic distributions of physical pain recorded in clinical notes of a mental health electronic health records database by using natural language processing and examine the overlap in recorded physical pain between primary and secondary care.

Design, setting and participants

The data were extracted from an anonymised version of the electronic health records of a large secondary mental healthcare provider serving a catchment of 1.3 million residents in south London. These included patients under active referral, aged 18+ at the index date of 1 July 2018 and having at least one clinical document (≥30 characters) between 1 July 2017 and 1 July 2019. This cohort was compared with linked primary care records from one of the four local government areas.

Outcome

The primary outcome of interest was the presence of recorded physical pain within the clinical notes of the patients, not including psychological or metaphorical pain.

Results

A total of 27 211 patients were retrieved. Of these, 52% (14,202) had narrative text containing relevant mentions of physical pain. Older patients (OR 1.17, 95% CI 1.15 to 1.19), females (OR 1.42, 95% CI 1.35 to 1.49), Asians (OR 1.30, 95% CI 1.16 to 1.45) or black (OR 1.49, 95% CI 1.40 to 1.59) ethnicities, living in deprived neighbourhoods (OR 1.64, 95% CI 1.55 to 1.73) showed higher odds of recorded pain. Patients with severe mental illnesses were found to be less likely to report pain (OR 0.43, 95% CI 0.41 to 0.46, p<0.001). 17% of the cohort from secondary care also had records from primary care.

Conclusion

The findings of this study show sociodemographic and diagnostic differences in recorded pain. Specifically, lower documentation across certain groups indicates the need for better screening protocols and training on recognising varied pain presentations. Additionally, targeting improved detection of pain for minority and disadvantaged groups by care providers can promote health equity.",,doi:https://doi.org/10.1136/bmjopen-2023-079923; html:https://europepmc.org/articles/PMC11033644; pdf:https://europepmc.org/articles/PMC11033644?pdf=render 37558806,https://doi.org/10.1038/s41598-023-40215-4,"Associations of the serotonin transporter gene polymorphism, 5-HTTLPR, and adverse life events with late life depression in the elderly Lithuanian population.","Simonyte S, Grabauskyte I, Macijauskiene J, Lesauskaite V, Lesauskaite V, Kvaal KS, Stewart R.",,Scientific reports,2023,2023-08-09,Y,,,,"Late-life depression (LLD) is a multifactorial disorder, with susceptibility and vulnerability potentially influenced by gene-environment interaction. The aim of this study was to investigate whether the 5-HTTLPR polymorphism is associated with LLD. The sample of 353 participants aged 65 years and over was randomly selected from the list of Kaunas city inhabitants by Residents' Register Service of Lithuania. Depressive symptoms were ascertained using the EURO-D scale. The List of Threatening Events Questionnaire was used to identify stressful life events that happened over the last 6 months and during lifetime. A 5-HTTLPR and lifetime stressful events interaction was indicated by higher odds of depression in those with s/s genotype who experienced high stress compared to l/l carriers with low or medium stress, while 5-HTTLPR and current stressful events interaction analysis revealed that carriers of either one or two copies of the s allele had increased odds of depressive symptoms associated with stress compared to participants with the l/l genotype not exposed to stressful situations. Although no significant direct association was found between the 5-HTTLPR short allele and depression, our findings demonstrated that lifetime or current stressful life events and their modification by 5-HTTLPR genotype are risk factors for late-life depression.",,pdf:https://www.nature.com/articles/s41598-023-40215-4.pdf; doi:https://doi.org/10.1038/s41598-023-40215-4; html:https://europepmc.org/articles/PMC10412533; pdf:https://europepmc.org/articles/PMC10412533?pdf=render 36529825,https://doi.org/10.1007/s40258-022-00777-2,The False Economy of Seeking to Eliminate Delayed Transfers of Care: Some Lessons from Queueing Theory.,"Wood RM, Harper AL, Onen-Dumlu Z, Forte PG, Pitt M, Vasilakis C.",,Applied health economics and health policy,2023,2022-12-18,Y,,,,"

Background

It is a stated ambition of many healthcare systems to eliminate delayed transfers of care (DTOCs) between acute and step-down community services.

Objective

This study aims to demonstrate how, counter to intuition, pursual of such a policy is likely to be uneconomical, as it would require large amounts of community capacity to accommodate even the rarest of demand peaks, leaving much capacity unused for much of the time.

Methods

Some standard results from queueing theory-a mathematical discipline for considering the dynamics of queues and queueing systems-are used to provide a model of patient flow from the acute to community setting. While queueing models have a track record of application in healthcare, they have not before been used to address this question.

Results

Results show that 'eliminating' DTOCs is a false economy: the additional community costs required are greater than the possible acute cost saving. While a substantial proportion of DTOCs can be attributed to inefficient use of resources, the remainder can be considered economically essential to ensuring cost-efficient service operation. For England's National Health Service (NHS), our modelling estimates annual cost savings of £117m if DTOCs are reduced to the 12% of current levels that can be regarded as economically essential.

Conclusion

This study discourages the use of 'zero DTOC' targets and instead supports an assessment based on the specific characteristics of the healthcare system considered.",,pdf:https://link.springer.com/content/pdf/10.1007/s40258-022-00777-2.pdf; doi:https://doi.org/10.1007/s40258-022-00777-2; html:https://europepmc.org/articles/PMC9760184; pdf:https://europepmc.org/articles/PMC9760184?pdf=render 34474011,https://doi.org/10.1016/s0140-6736(21)01638-x,Redefining β-blocker response in heart failure patients with sinus rhythm and atrial fibrillation: a machine learning cluster analysis.,"Karwath A, Bunting KV, Gill SK, Tica O, Pendleton S, Aziz F, Barsky AD, Chernbumroong S, Duan J, Mobley AR, Cardoso VR, Slater K, Williams JA, Bruce EJ, Wang X, Flather MD, Coats AJS, Gkoutos GV, Kotecha D, card AIc group and the Beta-blockers in Heart Failure Collaborative Group.",,"Lancet (London, England)",2021,2021-08-30,Y,,,,"

Background

Mortality remains unacceptably high in patients with heart failure and reduced left ventricular ejection fraction (LVEF) despite advances in therapeutics. We hypothesised that a novel artificial intelligence approach could better assess multiple and higher-dimension interactions of comorbidities, and define clusters of β-blocker efficacy in patients with sinus rhythm and atrial fibrillation.

Methods

Neural network-based variational autoencoders and hierarchical clustering were applied to pooled individual patient data from nine double-blind, randomised, placebo-controlled trials of β blockers. All-cause mortality during median 1·3 years of follow-up was assessed by intention to treat, stratified by electrocardiographic heart rhythm. The number of clusters and dimensions was determined objectively, with results validated using a leave-one-trial-out approach. This study was prospectively registered with ClinicalTrials.gov (NCT00832442) and the PROSPERO database of systematic reviews (CRD42014010012).

Findings

15 659 patients with heart failure and LVEF of less than 50% were included, with median age 65 years (IQR 56-72) and LVEF 27% (IQR 21-33). 3708 (24%) patients were women. In sinus rhythm (n=12 822), most clusters demonstrated a consistent overall mortality benefit from β blockers, with odds ratios (ORs) ranging from 0·54 to 0·74. One cluster in sinus rhythm of older patients with less severe symptoms showed no significant efficacy (OR 0·86, 95% CI 0·67-1·10; p=0·22). In atrial fibrillation (n=2837), four of five clusters were consistent with the overall neutral effect of β blockers versus placebo (OR 0·92, 0·77-1·10; p=0·37). One cluster of younger atrial fibrillation patients at lower mortality risk but similar LVEF to average had a statistically significant reduction in mortality with β blockers (OR 0·57, 0·35-0·93; p=0·023). The robustness and consistency of clustering was confirmed for all models (p<0·0001 vs random), and cluster membership was externally validated across the nine independent trials.

Interpretation

An artificial intelligence-based clustering approach was able to distinguish prognostic response from β blockers in patients with heart failure and reduced LVEF. This included patients in sinus rhythm with suboptimal efficacy, as well as a cluster of patients with atrial fibrillation where β blockers did reduce mortality.

Funding

Medical Research Council, UK, and EU/EFPIA Innovative Medicines Initiative BigData@Heart.",,doi:https://doi.org/10.1016/s0140-6736(21)01638-x; doi:https://doi.org/10.1016/S0140-6736(21)01638-X; html:https://europepmc.org/articles/PMC8542730 37798357,https://doi.org/10.1038/s41598-023-42331-7,"An angiopoietin 2, FGF23, and BMP10 biomarker signature differentiates atrial fibrillation from other concomitant cardiovascular conditions.","Chua W, Cardoso VR, Guasch E, Sinner MF, Al-Taie C, Brady P, Casadei B, Crijns HJGM, Dudink EAMP, Hatem SN, Kääb S, Kastner P, Mont L, Nehaj F, Purmah Y, Reyat JS, Schotten U, Sommerfeld LC, Zeemering S, Ziegler A, Gkoutos GV, Kirchhof P, Fabritz L.",,Scientific reports,2023,2023-10-05,Y,,,,"Early detection of atrial fibrillation (AF) enables initiation of anticoagulation and early rhythm control therapy to reduce stroke, cardiovascular death, and heart failure. In a cross-sectional, observational study, we aimed to identify a combination of circulating biomolecules reflecting different biological processes to detect prevalent AF in patients with cardiovascular conditions presenting to hospital. Twelve biomarkers identified by reviewing literature and patents were quantified on a high-precision, high-throughput platform in 1485 consecutive patients with cardiovascular conditions (median age 69 years [Q1, Q3 60, 78]; 60% male). Patients had either known AF (45%) or AF ruled out by 7-day ECG-monitoring. Logistic regression with backward elimination and a neural network approach considering 7 key clinical characteristics and 12 biomarker concentrations were applied to a randomly sampled discovery cohort (n = 933) and validated in the remaining patients (n = 552). In addition to age, sex, and body mass index (BMI), BMP10, ANGPT2, and FGF23 identified patients with prevalent AF (AUC 0.743 [95% CI 0.712, 0.775]). These circulating biomolecules represent distinct pathways associated with atrial cardiomyopathy and AF. Neural networks identified the same variables as the regression-based approach. The validation using regression yielded an AUC of 0.719 (95% CI 0.677, 0.762), corroborated using deep neural networks (AUC 0.784 [95% CI 0.745, 0.822]). Age, sex, BMI and three circulating biomolecules (BMP10, ANGPT2, FGF23) are associated with prevalent AF in unselected patients presenting to hospital. Findings should be externally validated. Results suggest that age and different disease processes approximated by these three biomolecules contribute to AF in patients. Our findings have the potential to improve screening programs for AF after external validation.",,pdf:https://www.nature.com/articles/s41598-023-42331-7.pdf; doi:https://doi.org/10.1038/s41598-023-42331-7; html:https://europepmc.org/articles/PMC10556075; pdf:https://europepmc.org/articles/PMC10556075?pdf=render -36333839,https://doi.org/10.1002/gps.5834,The impact of the first UK COVID-19 lockdown on presentations with psychosis to mental health services for older adults: An electronic health records study in South London.,"Simkin L, Yung P, Greig F, Perera G, Tsamakis K, Rizos E, Stewart R, Velayudhan L, Mueller C.",,International journal of geriatric psychiatry,2022,2022-10-24,Y,Dementia; Hallucinations; Delusions; Psychosis; Older Adults; Lockdown; Covid-19; Non-white Ethnicity,,,"

Objectives

Social distancing restrictions in the COVID-19 pandemic may have had adverse effects on older adults' mental health. Whereby the impact on mood is well-described, less is known about psychotic symptoms. The aim of this study was to compare characteristics associated with psychotic symptoms during the first UK lockdown and a pre-pandemic comparison period.

Methods

In this retrospective observational study we analysed anonymised records from patients referred to mental health services for older adults in South London in the 16-week period of the UK lockdown starting in March 2020, and in the comparable pre-pandemic period in 2019. We used logistic regression models to compare the associations of different patient characteristics with increased odds of presenting with any psychotic symptom (defined as hallucinations and/or delusion), hallucinations, or delusions, during lockdown and the corresponding pre-pandemic period.

Results

1991 referrals were identified. There were fewer referrals during lockdown but a higher proportion of presentations with any psychotic symptom (48.7% vs. 42.8%, p = 0.018), particularly hallucinations (41.0% vs. 27.8%, p < 0.001). Patients of non-White ethnicity (adjusted odds ratio (OR): 1.83; 95% confidence interval (CI): 1.13-2.99) and patients with dementia (adjusted OR: 3.09; 95% CI: 1.91-4.99) were more likely to be referred with psychotic symptoms during lockdown. While a weaker association between dementia and psychotic symptoms was found in the pre-COVID period (adjusted OR: 1.55; 95% CI: 1.19-2.03), interaction terms indicated higher odds of patients of non-White ethnicity or dementia to present with psychosis during the lockdown period.

Conclusions

During lockdown, referrals to mental health services for adults decreased, but contained a higher proportion with psychotic symptoms. The stronger association with psychotic symptoms in non-White ethnic groups and patients with dementia during lockdown suggests that barriers in accessing care might have increased during the COVID-19 pandemic.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/gps.5834; doi:https://doi.org/10.1002/gps.5834; html:https://europepmc.org/articles/PMC9828419; pdf:https://europepmc.org/articles/PMC9828419?pdf=render 35607618,https://doi.org/10.1016/j.patter.2022.100471,"Relevance, redundancy, and complementarity trade-off (RRCT): A principled, generic, robust feature-selection tool.",Tsanas A.,,"Patterns (New York, N.Y.)",2022,2022-03-31,Y,Information theory; Variable selection; Feature Selection; Statistical Learning; Dimensionality Reduction; Curse Of Dimensionality; Principle Of Parsimony,,,"We present a new heuristic feature-selection (FS) algorithm that integrates in a principled algorithmic framework the three key FS components: relevance, redundancy, and complementarity. Thus, we call it relevance, redundancy, and complementarity trade-off (RRCT). The association strength between each feature and the response and between feature pairs is quantified via an information theoretic transformation of rank correlation coefficients, and the feature complementarity is quantified using partial correlation coefficients. We empirically benchmark the performance of RRCT against 19 FS algorithms across four synthetic and eight real-world datasets in indicative challenging settings evaluating the following: (1) matching the true feature set and (2) out-of-sample performance in binary and multi-class classification problems when presenting selected features into a random forest. RRCT is very competitive in both tasks, and we tentatively make suggestions on the generalizability and application of the best-performing FS algorithms across settings where they may operate effectively.",,pdf:http://www.cell.com/article/S2666389922000514/pdf; doi:https://doi.org/10.1016/j.patter.2022.100471; html:https://europepmc.org/articles/PMC9122960; pdf:https://europepmc.org/articles/PMC9122960?pdf=render +36333839,https://doi.org/10.1002/gps.5834,The impact of the first UK COVID-19 lockdown on presentations with psychosis to mental health services for older adults: An electronic health records study in South London.,"Simkin L, Yung P, Greig F, Perera G, Tsamakis K, Rizos E, Stewart R, Velayudhan L, Mueller C.",,International journal of geriatric psychiatry,2022,2022-10-24,Y,Dementia; Hallucinations; Delusions; Psychosis; Older Adults; Lockdown; Covid-19; Non-white Ethnicity,,,"

Objectives

Social distancing restrictions in the COVID-19 pandemic may have had adverse effects on older adults' mental health. Whereby the impact on mood is well-described, less is known about psychotic symptoms. The aim of this study was to compare characteristics associated with psychotic symptoms during the first UK lockdown and a pre-pandemic comparison period.

Methods

In this retrospective observational study we analysed anonymised records from patients referred to mental health services for older adults in South London in the 16-week period of the UK lockdown starting in March 2020, and in the comparable pre-pandemic period in 2019. We used logistic regression models to compare the associations of different patient characteristics with increased odds of presenting with any psychotic symptom (defined as hallucinations and/or delusion), hallucinations, or delusions, during lockdown and the corresponding pre-pandemic period.

Results

1991 referrals were identified. There were fewer referrals during lockdown but a higher proportion of presentations with any psychotic symptom (48.7% vs. 42.8%, p = 0.018), particularly hallucinations (41.0% vs. 27.8%, p < 0.001). Patients of non-White ethnicity (adjusted odds ratio (OR): 1.83; 95% confidence interval (CI): 1.13-2.99) and patients with dementia (adjusted OR: 3.09; 95% CI: 1.91-4.99) were more likely to be referred with psychotic symptoms during lockdown. While a weaker association between dementia and psychotic symptoms was found in the pre-COVID period (adjusted OR: 1.55; 95% CI: 1.19-2.03), interaction terms indicated higher odds of patients of non-White ethnicity or dementia to present with psychosis during the lockdown period.

Conclusions

During lockdown, referrals to mental health services for adults decreased, but contained a higher proportion with psychotic symptoms. The stronger association with psychotic symptoms in non-White ethnic groups and patients with dementia during lockdown suggests that barriers in accessing care might have increased during the COVID-19 pandemic.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/gps.5834; doi:https://doi.org/10.1002/gps.5834; html:https://europepmc.org/articles/PMC9828419; pdf:https://europepmc.org/articles/PMC9828419?pdf=render 37006328,https://doi.org/10.1093/braincomms/fcad065,"Infections among individuals with multiple sclerosis, Alzheimer's disease and Parkinson's disease.","Hu Y, Hu K, Song H, Pawitan Y, Piehl F, Fang F.",,Brain communications,2023,2023-03-16,Y,Multiple sclerosis; Alzheimer’s disease; Infections; Parkinson’s Disease,,,"A link between neurodegenerative diseases and infections has been previously reported. However, it is not clear to what extent such link is caused by confounding factors or to what extent it is intimately connected with the underlying conditions. Further, studies on the impact of infections on mortality risk following neurodegenerative diseases are rare. We analysed two data sets with different characteristics: (i) a community-based cohort from the UK Biobank with 2023 patients with multiple sclerosis, 2200 patients with Alzheimer's disease, 3050 patients with Parkinson's disease diagnosed before 1 March 2020 and 5 controls per case who were randomly selected and individually matched to the case; (ii) a Swedish Twin Registry cohort with 230 patients with multiple sclerosis, 885 patients with Alzheimer's disease and 626 patients with Parkinson's disease diagnosed before 31 December 2016 and their disease-free co-twins. The relative risk of infections after a diagnosis of neurodegenerative disease was estimated using stratified Cox models, with adjustment for differences in baseline characteristics. Causal mediation analyses of survival outcomes based on Cox models were performed to assess the impact of infections on mortality. Compared with matched controls or unaffected co-twins, we observed an elevated infection risk after diagnosis of neurodegenerative diseases, with a fully adjusted hazard ratio (95% confidence interval) of 2.45 (2.24-2.69) for multiple sclerosis, 5.06 (4.58-5.59) for Alzheimer's disease and 3.72 (3.44-4.01) for Parkinson's disease in the UK Biobank cohort, and 1.78 (1.21-2.62) for multiple sclerosis, 1.50 (1.19-1.88) for Alzheimer's disease and 2.30 (1.79-2.95) for Parkinson's disease in the twin cohort. Similar risk increases were observed when we analysed infections during the 5 years before diagnosis of the respective disease. Occurrence of infections after diagnosis had, however, relatively little impact on mortality, as mediation of infections on mortality (95% confidence interval) was estimated as 31.89% (26.83-37.11%) for multiple sclerosis, 13.38% (11.49-15.29%) for Alzheimer's disease and 18.85% (16.95-20.97%) for Parkinson's disease in the UK Biobank cohort, whereas it was 6.56% (-3.59 to 16.88%) for multiple sclerosis, -2.21% (-0.21 to 4.65%) for Parkinson's disease and -3.89% (-7.27 to -0.51%) for Alzheimer's disease in the twin cohort. Individuals with studied neurodegenerative diseases display an increased risk of infections independently of genetic and familial environment factors. A similar magnitude of risk increase is present prior to confirmed diagnosis, which may indicate a modulating effect of the studied neurological conditions on immune defences.",,pdf:https://academic.oup.com/braincomms/advance-article-pdf/doi/10.1093/braincomms/fcad065/49588224/fcad065.pdf; doi:https://doi.org/10.1093/braincomms/fcad065; html:https://europepmc.org/articles/PMC10053639; pdf:https://europepmc.org/articles/PMC10053639?pdf=render 38806176,https://doi.org/10.1177/00045632241261274,A SARS-CoV-2 minimum data standard to support national serology reporting.,"Urwin EN, Martin J, Sebire N, Harris A, Johnston J, Masood E, Milligan G, Mairs L, Chuter A, Ferguson M, Quinlan P, Jefferson E.",,Annals of clinical biochemistry,2024,2024-05-28,N,Computers; Laboratory Management; Laboratory Methods; Analytical Systems,,,"

Background

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

Method

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

Results

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

Conclusions

This paper puts forward a minimum viable standard for COVID-19 serology data attributes to enhance its granularity and augment the national reporting of COVID-19 serology laboratory results, with implications for future pandemics.",,doi:https://doi.org/10.1177/00045632241261274 36992188,https://doi.org/10.3390/vaccines11030604,"Household Composition and Inequalities in COVID-19 Vaccination in Wales, UK.","Lench A, Perry M, Johnson RD, Fry R, Richardson G, Lyons RA, Akbari A, Edwards A, Collins B, Joseph-Williams N, Cooper A, Cottrell S.",,Vaccines,2023,2023-03-07,Y,Vaccines; Vaccination; Households; Inequalities; Immunisation; Household Composition; Inequities; Covid-19,,,"The uptake of COVID-19 vaccination in Wales is high at a population level but many inequalities exist. Household composition may be an important factor in COVID-19 vaccination uptake due to the practical, social, and psychological implications associated with different living arrangements. In this study, the role of household composition in the uptake of COVID-19 vaccination in Wales was examined with the aim of identifying areas for intervention to address inequalities. Records within the Wales Immunisation System (WIS) COVID-19 vaccination register were linked to the Welsh Demographic Service Dataset (WDSD; a population register for Wales) held within the Secure Anonymised Information Linkage (SAIL) databank. Eight household types were defined based on household size, the presence or absence of children, and the presence of single or multiple generations. Uptake of the second dose of any COVID-19 vaccine was analysed using logistic regression. Gender, age group, health board, rural/urban residential classification, ethnic group, and deprivation quintile were included as covariates for multivariable regression. Compared to two-adult households, all other household types were associated with lower uptake. The most significantly reduced uptake was observed for large, multigenerational, adult group households (aOR 0.45, 95%CI 0.43-0.46). Comparing multivariable regression with and without incorporation of household composition as a variable produced significant differences in odds of vaccination for health board, age group, and ethnic group categories. These results indicate that household composition is an important factor for the uptake of COVID-19 vaccination and consideration of differences in household composition is necessary to mitigate vaccination inequalities.",,pdf:https://www.mdpi.com/2076-393X/11/3/604/pdf?version=1678670919; doi:https://doi.org/10.3390/vaccines11030604; html:https://europepmc.org/articles/PMC10055803; pdf:https://europepmc.org/articles/PMC10055803?pdf=render @@ -454,16 +454,16 @@ PMC10910267,https://doi.org/,Development and evaluation of a tool to optimise in 37340474,https://doi.org/10.1186/s12916-023-02877-9,Antidepressant drug prescription and incidence of COVID-19 in mental health outpatients: a retrospective cohort study.,"Glebov OO, Mueller C, Stewart R, Aarsland D, Perera G.",,BMC medicine,2023,2023-06-21,Y,Antidepressants; Ssri; respiratory infection; Drug Repurposing; Covid-19; Sars-cov-2,,,"

Background

Currently, the main pharmaceutical intervention for COVID-19 is vaccination. While antidepressant (AD) drugs have shown some efficacy in treatment of symptomatic COVID-19, their preventative potential remains largely unexplored. Analysis of association between prescription of ADs and COVID-19 incidence in the population would be beneficial for assessing the utility of ADs in COVID-19 prevention.

Methods

Retrospective study of association between AD prescription and COVID-19 diagnosis was performed in a cohort of community-dwelling adult mental health outpatients during the 1st wave of COVID-19 pandemic in the UK. Clinical record interactive search (CRIS) was performed for mentions of ADs within 3 months preceding admission to inpatient care of the South London and Maudsley (SLaM) NHS Foundation Trust. Incidence of positive COVID-19 tests upon admission and during inpatient treatment was the primary outcome measure.

Results

AD mention was associated with approximately 40% lower incidence of positive COVID-19 test results when adjusted for socioeconomic parameters and physical health. This association was also observed for prescription of ADs of the selective serotonin reuptake inhibitor (SSRI) class.

Conclusions

This preliminary study suggests that ADs, and SSRIs in particular, may be of benefit for preventing COVID-19 infection spread in the community. The key limitations of the study are its retrospective nature and the focus on a mental health patient cohort. A more definitive assessment of AD and SSRI preventative potential warrants prospective studies in the wider demographic.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-023-02877-9; doi:https://doi.org/10.1186/s12916-023-02877-9; html:https://europepmc.org/articles/PMC10283271; pdf:https://europepmc.org/articles/PMC10283271?pdf=render 36332942,https://doi.org/10.1136/openhrt-2022-002142,Development of algorithms for determining heart failure with reduced and preserved ejection fraction using nationwide electronic healthcare records in the UK.,"Sundaram V, Zakeri R, Witte KK, Quint JK.",,Open heart,2022,2022-11-01,Y,epidemiology; Heart Failure; Electronic Health Records,,,"

Background

Determining heart failure (HF) phenotypes in routine electronic health records (EHR) is challenging. We aimed to develop and validate EHR algorithms for identification of specific HF phenotypes, using Read codes in combination with selected patient characteristics.

Methods

We used The Healthcare Improvement Network (THIN). The study population included a random sample of individuals with HF diagnostic codes (HF with reduced ejection fraction (HFrEF), HF with preserved ejection fraction (HFpEF) and non-specific HF) selected from all participants registered in the THIN database between 1 January 2015 and 30 September 2017. Confirmed diagnoses were determined in a randomly selected subgroup of 500 patients via GP questionnaires including a review of all available cardiovascular investigations. Confirmed diagnoses of HFrEF and HFpEF were based on four criteria. Based on these data, we calculated a positive predictive value (PPV) of predefined algorithms which consisted of a combination of Read codes and additional information such as echocardiogram results and HF medication records.

Results

The final cohort from which we drew the 500 patient random sample consisted of 10 275 patients. Response rate to the questionnaire was 77.2%. A small proportion (18%) of the overall HF patient population were coded with specific HF phenotype Read codes. For HFrEF, algorithms achieving over 80% PPV included definite, possible or non-specific HF HFrEF codes when combined with at least two of the drugs used to treat HFrEF. Only in non-specific HF coding did the use of three drugs (rather than two) contribute to an improvement of the PPV for HFrEF. HFpEF was only accurately defined with specific codes. In the absence of specific coding for HFpEF, the PPV was consistently below 50%.

Conclusions

Prescription for HF medication can reliably be used to find HFrEF patients in the UK, even in the absence of a specific Read code for HFrEF. Algorithms using non-specific coding could not reliably find HFpEF patients.",,pdf:https://openheart.bmj.com/content/openhrt/9/2/e002142.full.pdf; doi:https://doi.org/10.1136/openhrt-2022-002142; html:https://europepmc.org/articles/PMC9639145; pdf:https://europepmc.org/articles/PMC9639145?pdf=render 37200350,https://doi.org/10.1371/journal.pone.0285979,"An external validation of the QCOVID3 risk prediction algorithm for risk of hospitalisation and death from COVID-19: An observational, prospective cohort study of 1.66m vaccinated adults in Wales, UK.","Lyons J, Nafilyan V, Akbari A, Bedston S, Harrison E, Hayward A, Hippisley-Cox J, Kee F, Khunti K, Rahman S, Sheikh A, Torabi F, Lyons RA.",,PloS one,2023,2023-05-18,Y,,,,"

Introduction

At the start of the COVID-19 pandemic there was an urgent need to identify individuals at highest risk of severe outcomes, such as hospitalisation and death following infection. The QCOVID risk prediction algorithms emerged as key tools in facilitating this which were further developed during the second wave of the COVID-19 pandemic to identify groups of people at highest risk of severe COVID-19 related outcomes following one or two doses of vaccine.

Objectives

To externally validate the QCOVID3 algorithm based on primary and secondary care records for Wales, UK.

Methods

We conducted an observational, prospective cohort based on electronic health care records for 1.66m vaccinated adults living in Wales on 8th December 2020, with follow-up until 15th June 2021. Follow-up started from day 14 post vaccination to allow the full effect of the vaccine.

Results

The scores produced by the QCOVID3 risk algorithm showed high levels of discrimination for both COVID-19 related deaths and hospital admissions and good calibration (Harrell C statistic: ≥ 0.828).

Conclusion

This validation of the updated QCOVID3 risk algorithms in the adult vaccinated Welsh population has shown that the algorithms are valid for use in the Welsh population, and applicable on a population independent of the original study, which has not been previously reported. This study provides further evidence that the QCOVID algorithms can help inform public health risk management on the ongoing surveillance and intervention to manage COVID-19 related risks.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0285979&type=printable; doi:https://doi.org/10.1371/journal.pone.0285979; html:https://europepmc.org/articles/PMC10194890; pdf:https://europepmc.org/articles/PMC10194890?pdf=render -37263602,https://doi.org/10.1093/eurpub/ckad075,"Community factors and excess mortality in the COVID-19 pandemic in England, Italy and Sweden.","Parkes B, Stafoggia M, Fecht D, Davies B, Bonander C, De' Donato F, Michelozzi P, Piel FB, Strömberg U, Blangiardo M.",,European journal of public health,2023,2023-08-01,Y,,,,"

Background

Analyses of coronavirus disease 19 suggest specific risk factors make communities more or less vulnerable to pandemic-related deaths within countries. What is unclear is whether the characteristics affecting vulnerability of small communities within countries produce similar patterns of excess mortality across countries with different demographics and public health responses to the pandemic. Our aim is to quantify community-level variations in excess mortality within England, Italy and Sweden and identify how such spatial variability was driven by community-level characteristics.

Methods

We applied a two-stage Bayesian model to quantify inequalities in excess mortality in people aged 40 years and older at the community level in England, Italy and Sweden during the first year of the pandemic (March 2020-February 2021). We used community characteristics measuring deprivation, air pollution, living conditions, population density and movement of people as covariates to quantify their associations with excess mortality.

Results

We found just under half of communities in England (48.1%) and Italy (45.8%) had an excess mortality of over 300 per 100 000 males over the age of 40, while for Sweden that covered 23.1% of communities. We showed that deprivation is a strong predictor of excess mortality across the three countries, and communities with high levels of overcrowding were associated with higher excess mortality in England and Sweden.

Conclusion

These results highlight some international similarities in factors affecting mortality that will help policy makers target public health measures to increase resilience to the mortality impacts of this and future pandemics.",,pdf:https://academic.oup.com/eurpub/advance-article-pdf/doi/10.1093/eurpub/ckad075/50504334/ckad075.pdf; doi:https://doi.org/10.1093/eurpub/ckad075; html:https://europepmc.org/articles/PMC10393497; pdf:https://europepmc.org/articles/PMC10393497?pdf=render 38222382,https://doi.org/,Development of a Knowledge Graph Embeddings Model for Pain.,"Chaturvedi J, Wang T, Velupillai S, Stewart R, Roberts A.",,AMIA ... Annual Symposium proceedings. AMIA Symposium,2023,2023-01-01,N,,,,"Pain is a complex concept that can interconnect with other concepts such as a disorder that might cause pain, a medication that might relieve pain, and so on. To fully understand the context of pain experienced by either an individual or across a population, we may need to examine all concepts related to pain and the relationships between them. This is especially useful when modeling pain that has been recorded in electronic health records. Knowledge graphs represent concepts and their relations by an interlinked network, enabling semantic and context-based reasoning in a computationally tractable form. These graphs can, however, be too large for efficient computation. Knowledge graph embeddings help to resolve this by representing the graphs in a low-dimensional vector space. These embeddings can then be used in various downstream tasks such as classification and link prediction. The various relations associated with pain which are required to construct such a knowledge graph can be obtained from external medical knowledge bases such as SNOMED CT, a hierarchical systematic nomenclature of medical terms. A knowledge graph built in this way could be further enriched with real-world examples of pain and its relations extracted from electronic health records. This paper describes the construction of such knowledge graph embedding models of pain concepts, extracted from the unstructured text of mental health electronic health records, combined with external knowledge created from relations described in SNOMED CT, and their evaluation on a subject-object link prediction task. The performance of the models was compared with other baseline models.",,html:https://europepmc.org/articles/PMC10785867; pdf:https://europepmc.org/articles/PMC10785867?pdf=render +37263602,https://doi.org/10.1093/eurpub/ckad075,"Community factors and excess mortality in the COVID-19 pandemic in England, Italy and Sweden.","Parkes B, Stafoggia M, Fecht D, Davies B, Bonander C, De' Donato F, Michelozzi P, Piel FB, Strömberg U, Blangiardo M.",,European journal of public health,2023,2023-08-01,Y,,,,"

Background

Analyses of coronavirus disease 19 suggest specific risk factors make communities more or less vulnerable to pandemic-related deaths within countries. What is unclear is whether the characteristics affecting vulnerability of small communities within countries produce similar patterns of excess mortality across countries with different demographics and public health responses to the pandemic. Our aim is to quantify community-level variations in excess mortality within England, Italy and Sweden and identify how such spatial variability was driven by community-level characteristics.

Methods

We applied a two-stage Bayesian model to quantify inequalities in excess mortality in people aged 40 years and older at the community level in England, Italy and Sweden during the first year of the pandemic (March 2020-February 2021). We used community characteristics measuring deprivation, air pollution, living conditions, population density and movement of people as covariates to quantify their associations with excess mortality.

Results

We found just under half of communities in England (48.1%) and Italy (45.8%) had an excess mortality of over 300 per 100 000 males over the age of 40, while for Sweden that covered 23.1% of communities. We showed that deprivation is a strong predictor of excess mortality across the three countries, and communities with high levels of overcrowding were associated with higher excess mortality in England and Sweden.

Conclusion

These results highlight some international similarities in factors affecting mortality that will help policy makers target public health measures to increase resilience to the mortality impacts of this and future pandemics.",,pdf:https://academic.oup.com/eurpub/advance-article-pdf/doi/10.1093/eurpub/ckad075/50504334/ckad075.pdf; doi:https://doi.org/10.1093/eurpub/ckad075; html:https://europepmc.org/articles/PMC10393497; pdf:https://europepmc.org/articles/PMC10393497?pdf=render 33240522,https://doi.org/10.1177/2055207620965046,Electronic-prescribing tools improve N-acetylcysteine prescription accuracy and timeliness for patients who present following a paracetamol overdose: A digital innovation quality-improvement project.,"McCulloch A, Sarwar A, Bate T, Thompson D, McDowell P, Sharif Q, Sapey E, Seccombe A.",,Digital health,2020,2020-01-01,Y,Antidote; Digital; paracetamol; Prescription Errors; Electronic Health Systems,,,"

Objectives

Prescription error rates and delays in treatment provision are high for N-acetylcysteine (NAC) when prescribed for paracetamol overdose (POD). We hypothesised that an electronic tool which proposed the complete NAC regimen would reduce prescription errors and improve the timeliness of NAC provision. Error rates and delays in the provision of NAC were assessed following POD, before and after the implementation of an electronic prescribing tool.

Methods

The NAC electronic prescribing tool proposed the three NAC infusions (dosed for weight) following entry of the patient's weight. All NAC prescriptions were reviewed during a three-month period prior to and after the tool's implementation. Error rates were divided into dose, infusion volume or infusion rate. Delays in NAC provision were identified using national Emergency Medicine guidelines.

Results

108 NAC prescriptions were analysed for all adult patients admitted to the emergency department of a secondary care hospital in the UK between July-September 2017 and August-October 2018, respectively. There were no differences in the demographics of patients or the seniority of the prescribing clinician before or after the introduction of the electronic tool. The electronic prescribing tool was associated with a decrease in prescribing errors (25% to 0%, p < 0.0071) and an increase in the provision of NAC within recommended times (11.1% to 47.4%, p = 0.029).

Conclusions

An electronic prescribing tool improved prescription errors and the timeliness of NAC provision following POD. Further studies will determine the effect of this on length of stay and the benefit of wider implementation in other secondary care hospitals.",,pdf:https://journals.sagepub.com/doi/pdf/10.1177/2055207620965046; doi:https://doi.org/10.1177/2055207620965046; html:https://europepmc.org/articles/PMC7675911; pdf:https://europepmc.org/articles/PMC7675911?pdf=render -36193673,https://doi.org/10.1192/j.eurpsy.2022.2324,Cardiac surgery receipt and outcomes for people using secondary mental healthcare services: Retrospective cohort study using a large mental healthcare database in South London.,"Brooks G, Weerakkody R, Harris M, Harris M, Stewart R, Perera G.",,European psychiatry : the journal of the Association of European Psychiatrists,2022,2022-10-04,Y,Cardiac surgery; Length Of Stay; Emergency Admissions; Mental Healthcare Services,,,"

Background

Patients diagnosed with mental health problems are more predisposed to cardiovascular disease, including cardiac surgery. Nevertheless, health outcomes after cardiac surgery for patients with mental health problems as a discrete group are unknown. This study examined the association between secondary care mental health service use and postoperative health outcomes following cardiac surgery.

Methods

We conducted a retrospective observational research, utilizing data from a large South London mental healthcare supplier linked to national hospitalization data. OPCS-4 codes were applied to classify cardiac surgery. Health results were compared between those individuals with a mental health disorder diagnosis from secondary care and other local residents, including the length of hospital stay (LOS), inpatient mortality, and 30-day emergency hospital readmission.

Results

Twelve thousand three hundred and eighty-four patients received cardiac surgery, including 1,481 with a mental disorder diagnosis. Patients with mental health diagnosis were at greater risk of emergency admissions for cardiac surgery (odds ratio [OR] 1.60; 1.43, 1.79), longer index LOS (incidence rate ratio 1.28; 1.26, 1.30), and at higher risk of 30-day emergency readmission (OR 1.53; 1.31, 1.78). Those who underwent pacemaker insertion and major open surgery had worse postoperative outcomes during index surgery hospital admission while those who had major endovascular surgery had worse health outcomes subsequent 30-day emergency hospital readmission.

Conclusion

People with a mental health disorder diagnosis undertaking cardiac surgery have significantly worse health outcomes. Personalized guidelines and policies to manage preoperative risk factors require consideration and evaluation.",,pdf:https://www.cambridge.org/core/services/aop-cambridge-core/content/view/63FA124CF816896E02CAEE14215D590E/S0924933822023240a.pdf/div-class-title-cardiac-surgery-receipt-and-outcomes-for-people-using-secondary-mental-health-care-services-retrospective-cohort-study-using-a-large-mental-healthcare-database-in-south-london-div.pdf; doi:https://doi.org/10.1192/j.eurpsy.2022.2324; html:https://europepmc.org/articles/PMC9677442; pdf:https://europepmc.org/articles/PMC9677442?pdf=render 31757986,https://doi.org/10.1038/s41598-019-53454-1,Ontology-based prediction of cancer driver genes.,"Althubaiti S, Karwath A, Dallol A, Noor A, Alkhayyat SS, Alwassia R, Mineta K, Gojobori T, Beggs AD, Schofield PN, Gkoutos GV, Hoehndorf R.",,Scientific reports,2019,2019-11-22,Y,,Applied Analytics,,"Identifying and distinguishing cancer driver genes among thousands of candidate mutations remains a major challenge. Accurate identification of driver genes and driver mutations is critical for advancing cancer research and personalizing treatment based on accurate stratification of patients. Due to inter-tumor genetic heterogeneity many driver mutations within a gene occur at low frequencies, which make it challenging to distinguish them from non-driver mutations. We have developed a novel method for identifying cancer driver genes. Our approach utilizes multiple complementary types of information, specifically cellular phenotypes, cellular locations, functions, and whole body physiological phenotypes as features. We demonstrate that our method can accurately identify known cancer driver genes and distinguish between their role in different types of cancer. In addition to confirming known driver genes, we identify several novel candidate driver genes. We demonstrate the utility of our method by validating its predictions in nasopharyngeal cancer and colorectal cancer using whole exome and whole genome sequencing.",This study investigated which genes encourage cancer tumors to grow. The study identifies genes and distinguishes their role in different types of cancers. Their method is validated using whole exome and whole genome sequencing,pdf:https://www.nature.com/articles/s41598-019-53454-1.pdf; doi:https://doi.org/10.1038/s41598-019-53454-1; html:https://europepmc.org/articles/PMC6874647; pdf:https://europepmc.org/articles/PMC6874647?pdf=render +36193673,https://doi.org/10.1192/j.eurpsy.2022.2324,Cardiac surgery receipt and outcomes for people using secondary mental healthcare services: Retrospective cohort study using a large mental healthcare database in South London.,"Brooks G, Weerakkody R, Harris M, Harris M, Stewart R, Perera G.",,European psychiatry : the journal of the Association of European Psychiatrists,2022,2022-10-04,Y,Cardiac surgery; Length Of Stay; Emergency Admissions; Mental Healthcare Services,,,"

Background

Patients diagnosed with mental health problems are more predisposed to cardiovascular disease, including cardiac surgery. Nevertheless, health outcomes after cardiac surgery for patients with mental health problems as a discrete group are unknown. This study examined the association between secondary care mental health service use and postoperative health outcomes following cardiac surgery.

Methods

We conducted a retrospective observational research, utilizing data from a large South London mental healthcare supplier linked to national hospitalization data. OPCS-4 codes were applied to classify cardiac surgery. Health results were compared between those individuals with a mental health disorder diagnosis from secondary care and other local residents, including the length of hospital stay (LOS), inpatient mortality, and 30-day emergency hospital readmission.

Results

Twelve thousand three hundred and eighty-four patients received cardiac surgery, including 1,481 with a mental disorder diagnosis. Patients with mental health diagnosis were at greater risk of emergency admissions for cardiac surgery (odds ratio [OR] 1.60; 1.43, 1.79), longer index LOS (incidence rate ratio 1.28; 1.26, 1.30), and at higher risk of 30-day emergency readmission (OR 1.53; 1.31, 1.78). Those who underwent pacemaker insertion and major open surgery had worse postoperative outcomes during index surgery hospital admission while those who had major endovascular surgery had worse health outcomes subsequent 30-day emergency hospital readmission.

Conclusion

People with a mental health disorder diagnosis undertaking cardiac surgery have significantly worse health outcomes. Personalized guidelines and policies to manage preoperative risk factors require consideration and evaluation.",,pdf:https://www.cambridge.org/core/services/aop-cambridge-core/content/view/63FA124CF816896E02CAEE14215D590E/S0924933822023240a.pdf/div-class-title-cardiac-surgery-receipt-and-outcomes-for-people-using-secondary-mental-health-care-services-retrospective-cohort-study-using-a-large-mental-healthcare-database-in-south-london-div.pdf; doi:https://doi.org/10.1192/j.eurpsy.2022.2324; html:https://europepmc.org/articles/PMC9677442; pdf:https://europepmc.org/articles/PMC9677442?pdf=render 34599903,https://doi.org/10.1016/s2213-2600(21)00380-5,COVID-19 hospital admissions and deaths after BNT162b2 and ChAdOx1 nCoV-19 vaccinations in 2·57 million people in Scotland (EAVE II): a prospective cohort study.,"Agrawal U, Katikireddi SV, McCowan C, Mulholland RH, Azcoaga-Lorenzo A, Amele S, Fagbamigbe AF, Vasileiou E, Grange Z, Shi T, Kerr S, Moore E, Murray JLK, Shah SA, Ritchie L, O'Reilly D, Stock SJ, Beggs J, Chuter A, Torabi F, Akbari A, Bedston S, McMenamin J, Wood R, Tang RSM, de Lusignan S, Hobbs FDR, Woolhouse M, Simpson CR, Robertson C, Sheikh A.",,The Lancet. Respiratory medicine,2021,2021-09-29,Y,,,,"

Background

The UK COVID-19 vaccination programme has prioritised vaccination of those at the highest risk of COVID-19 mortality and hospitalisation. The programme was rolled out in Scotland during winter 2020-21, when SARS-CoV-2 infection rates were at their highest since the pandemic started, despite social distancing measures being in place. We aimed to estimate the frequency of COVID-19 hospitalisation or death in people who received at least one vaccine dose and characterise these individuals.

Methods

We conducted a prospective cohort study using the Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II) national surveillance platform, which contained linked vaccination, primary care, RT-PCR testing, hospitalisation, and mortality records for 5·4 million people (around 99% of the population) in Scotland. Individuals were followed up from receiving their first dose of the BNT162b2 (Pfizer-BioNTech) or ChAdOx1 nCoV-19 (Oxford-AstraZeneca) COVID-19 vaccines until admission to hospital for COVID-19, death, or the end of the study period on April 18, 2021. We used a time-dependent Poisson regression model to estimate rate ratios (RRs) for demographic and clinical factors associated with COVID-19 hospitalisation or death 14 days or more after the first vaccine dose, stratified by vaccine type.

Findings

Between Dec 8, 2020, and April 18, 2021, 2 572 008 individuals received their first dose of vaccine-841 090 (32·7%) received BNT162b2 and 1 730 918 (67·3%) received ChAdOx1. 1196 (<0·1%) individuals were admitted to hospital or died due to COVID-19 illness (883 hospitalised, of whom 228 died, and 313 who died due to COVID-19 without hospitalisation) 14 days or more after their first vaccine dose. These severe COVID-19 outcomes were associated with older age (≥80 years vs 18-64 years adjusted RR 4·75, 95% CI 3·85-5·87), comorbidities (five or more risk groups vs less than five risk groups 4·24, 3·34-5·39), hospitalisation in the previous 4 weeks (3·00, 2·47-3·65), high-risk occupations (ten or more previous COVID-19 tests vs less than ten previous COVID-19 tests 2·14, 1·62-2·81), care home residence (1·63, 1·32-2·02), socioeconomic deprivation (most deprived quintile vs least deprived quintile 1·57, 1·30-1·90), being male (1·27, 1·13-1·43), and being an ex-smoker (ex-smoker vs non-smoker 1·18, 1·01-1·38). A history of COVID-19 before vaccination was protective (0·40, 0·29-0·54).

Interpretation

COVID-19 hospitalisations and deaths were uncommon 14 days or more after the first vaccine dose in this national analysis in the context of a high background incidence of SARS-CoV-2 infection and with extensive social distancing measures in place. Sociodemographic and clinical features known to increase the risk of severe disease in unvaccinated populations were also associated with severe outcomes in people receiving their first dose of vaccine and could help inform case management and future vaccine policy formulation.

Funding

UK Research and Innovation (Medical Research Council), Research and Innovation Industrial Strategy Challenge Fund, Scottish Government, and Health Data Research UK.",,pdf:http://www.thelancet.com/article/S2213260021003805/pdf; doi:https://doi.org/10.1016/S2213-2600(21)00380-5; html:https://europepmc.org/articles/PMC8480963 38373998,https://doi.org/10.1186/s13073-024-01304-9,"Recent advances in polygenic scores: translation, equitability, methods and FAIR tools.","Xiang R, Kelemen M, Xu Y, Harris LW, Parkinson H, Inouye M, Lambert SA.",,Genome medicine,2024,2024-02-19,Y,transferability; Clinical Utility; Genome-wide Association Studies (Gwas); Open-access; Accessible; Interoperable; Responsible Use; Polygenic Score (Pgs); Fair (Findable; And Reusable),,,"Polygenic scores (PGS) can be used for risk stratification by quantifying individuals' genetic predisposition to disease, and many potentially clinically useful applications have been proposed. Here, we review the latest potential benefits of PGS in the clinic and challenges to implementation. PGS could augment risk stratification through combined use with traditional risk factors (demographics, disease-specific risk factors, family history, etc.), to support diagnostic pathways, to predict groups with therapeutic benefits, and to increase the efficiency of clinical trials. However, there exist challenges to maximizing the clinical utility of PGS, including FAIR (Findable, Accessible, Interoperable, and Reusable) use and standardized sharing of the genomic data needed to develop and recalculate PGS, the equitable performance of PGS across populations and ancestries, the generation of robust and reproducible PGS calculations, and the responsible communication and interpretation of results. We outline how these challenges may be overcome analytically and with more diverse data as well as highlight sustained community efforts to achieve equitable, impactful, and responsible use of PGS in healthcare.",,pdf:https://genomemedicine.biomedcentral.com/counter/pdf/10.1186/s13073-024-01304-9; doi:https://doi.org/10.1186/s13073-024-01304-9; html:https://europepmc.org/articles/PMC10875792; pdf:https://europepmc.org/articles/PMC10875792?pdf=render 36987388,https://doi.org/10.1177/08862605231163885,Characterizing the Differences in Descriptions of Violence on Reddit During the COVID-19 Pandemic.,"Li L, Neubauer L, Stewart R, Roberts A.",,Journal of interpersonal violence,2023,2023-03-28,Y,Increase rate; Data Classification; Reddit; Violence Types,,,"Concerns have been raised over the experiences of violence such as domestic violence (DV) and intimate partner violence (IPV) during the COVID-19 pandemic. Social media such as Reddit represent an alternative outlet for reporting experiences of violence where healthcare access has been limited. This study analyzed seven violence-related subreddits to investigate the trends of different violence patterns from January 2018 to February 2022 to enhance the health-service providers' existing service or provide some new perspective for existing violence research. Specifically, we collected violence-related texts from Reddit using keyword searching and identified six major types with supervised machine learning classifiers: DV, IPV, physical violence, sexual violence, emotional violence, and nonspecific violence or others. The increase rate (IR) of each violence type was calculated and temporally compared in five phases of the pandemic. The phases include one pre-pandemic phase (Phase 0, the date before February 26, 2020) and four pandemic phases (Phases 1-4) with separation dates of June 17, 2020, September 7, 2020, and June 4, 2021. We found that the number of IPV-related posts increased most in the earliest phase; however, that for COVID-citing IPV was highest in the mid-pandemic phase. IRs for DV, IPV, and emotional violence also showed increases across all pandemic phases, with IRs of 26.9%, 58.8%, and 28.8%, respectively, from the pre-pandemic to the first pandemic phase. In the other three pandemic phases, all the IRs for these three types of violence were positive, though lower than the IRs in the first pandemic phase. The findings highlight the importance of identifying and providing help to those who suffer from such violent experiences and support the role of social media site monitoring as a means of informative surveillance for help-providing authorities and violence research groups.",,doi:https://doi.org/10.1177/08862605231163885; doi:https://doi.org/10.1177/08862605231163885; html:https://europepmc.org/articles/PMC10064198; pdf:https://europepmc.org/articles/PMC10064198?pdf=render -38200587,https://doi.org/10.1093/bioinformatics/btae012,Pitfalls of machine learning models for protein-protein interaction networks.,"Lannelongue L, Inouye M.",,"Bioinformatics (Oxford, England)",2024,2024-02-01,Y,,,,"

Motivation

Protein-protein interactions (PPIs) are essential to understanding biological pathways as well as their roles in development and disease. Computational tools, based on classic machine learning, have been successful at predicting PPIs in silico, but the lack of consistent and reliable frameworks for this task has led to network models that are difficult to compare and discrepancies between algorithms that remain unexplained.

Results

To better understand the underlying inference mechanisms that underpin these models, we designed an open-source framework for benchmarking that accounts for a range of biological and statistical pitfalls while facilitating reproducibility. We use it to shed light on the impact of network topology and how different algorithms deal with highly connected proteins. By studying functional genomics-based and sequence-based models on human PPIs, we show their complementarity as the former performs best on lone proteins while the latter specializes in interactions involving hubs. We also show that algorithm design has little impact on performance with functional genomic data. We replicate our results between both human and S. cerevisiae data and demonstrate that models using functional genomics are better suited to PPI prediction across species. With rapidly increasing amounts of sequence and functional genomics data, our study provides a principled foundation for future construction, comparison, and application of PPI networks.

Availability and implementation

The code and data are available on GitHub: https://github.com/Llannelongue/B4PPI.",,pdf:https://academic.oup.com/bioinformatics/advance-article-pdf/doi/10.1093/bioinformatics/btae012/55399607/btae012.pdf; doi:https://doi.org/10.1093/bioinformatics/btae012; html:https://europepmc.org/articles/PMC10868344; pdf:https://europepmc.org/articles/PMC10868344?pdf=render 34461893,https://doi.org/10.1186/s12916-021-02096-0,The association between mechanical ventilator compatible bed occupancy and mortality risk in intensive care patients with COVID-19: a national retrospective cohort study.,"Wilde H, Mellan T, Hawryluk I, Dennis JM, Denaxas S, Pagel C, Duncan A, Bhatt S, Flaxman S, Mateen BA, Vollmer SJ.",,BMC medicine,2021,2021-08-30,Y,Critical Care; Hospital Mortality; Quality Of Healthcare; Public Health Surveillance; Coronavirus Infection,,,"

Background

The literature paints a complex picture of the association between mortality risk and ICU strain. In this study, we sought to determine if there is an association between mortality risk in intensive care units (ICU) and occupancy of beds compatible with mechanical ventilation, as a proxy for strain.

Methods

A national retrospective observational cohort study of 89 English hospital trusts (i.e. groups of hospitals functioning as single operational units). Seven thousand one hundred thirty-three adults admitted to an ICU in England between 2 April and 1 December, 2020 (inclusive), with presumed or confirmed COVID-19, for whom data was submitted to the national surveillance programme and met study inclusion criteria. A Bayesian hierarchical approach was used to model the association between hospital trust level (mechanical ventilation compatible), bed occupancy, and in-hospital all-cause mortality. Results were adjusted for unit characteristics (pre-pandemic size), individual patient-level demographic characteristics (age, sex, ethnicity, deprivation index, time-to-ICU admission), and recorded chronic comorbidities (obesity, diabetes, respiratory disease, liver disease, heart disease, hypertension, immunosuppression, neurological disease, renal disease).

Results

One hundred thirty-five thousand six hundred patient days were observed, with a mortality rate of 19.4 per 1000 patient days. Adjusting for patient-level factors, mortality was higher for admissions during periods of high occupancy (> 85% occupancy versus the baseline of 45 to 85%) [OR 1.23 (95% posterior credible interval (PCI): 1.08 to 1.39)]. In contrast, mortality was decreased for admissions during periods of low occupancy (< 45% relative to the baseline) [OR 0.83 (95% PCI 0.75 to 0.94)].

Conclusion

Increasing occupancy of beds compatible with mechanical ventilation, a proxy for operational strain, is associated with a higher mortality risk for individuals admitted to ICU. Further research is required to establish if this is a causal relationship or whether it reflects strain on other operational factors such as staff. If causal, the result highlights the importance of strategies to keep ICU occupancy low to mitigate the impact of this type of resource saturation.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-021-02096-0; doi:https://doi.org/10.1186/s12916-021-02096-0; html:https://europepmc.org/articles/PMC8404408; pdf:https://europepmc.org/articles/PMC8404408?pdf=render +38200587,https://doi.org/10.1093/bioinformatics/btae012,Pitfalls of machine learning models for protein-protein interaction networks.,"Lannelongue L, Inouye M.",,"Bioinformatics (Oxford, England)",2024,2024-02-01,Y,,,,"

Motivation

Protein-protein interactions (PPIs) are essential to understanding biological pathways as well as their roles in development and disease. Computational tools, based on classic machine learning, have been successful at predicting PPIs in silico, but the lack of consistent and reliable frameworks for this task has led to network models that are difficult to compare and discrepancies between algorithms that remain unexplained.

Results

To better understand the underlying inference mechanisms that underpin these models, we designed an open-source framework for benchmarking that accounts for a range of biological and statistical pitfalls while facilitating reproducibility. We use it to shed light on the impact of network topology and how different algorithms deal with highly connected proteins. By studying functional genomics-based and sequence-based models on human PPIs, we show their complementarity as the former performs best on lone proteins while the latter specializes in interactions involving hubs. We also show that algorithm design has little impact on performance with functional genomic data. We replicate our results between both human and S. cerevisiae data and demonstrate that models using functional genomics are better suited to PPI prediction across species. With rapidly increasing amounts of sequence and functional genomics data, our study provides a principled foundation for future construction, comparison, and application of PPI networks.

Availability and implementation

The code and data are available on GitHub: https://github.com/Llannelongue/B4PPI.",,pdf:https://academic.oup.com/bioinformatics/advance-article-pdf/doi/10.1093/bioinformatics/btae012/55399607/btae012.pdf; doi:https://doi.org/10.1093/bioinformatics/btae012; html:https://europepmc.org/articles/PMC10868344; pdf:https://europepmc.org/articles/PMC10868344?pdf=render 36649943,https://doi.org/10.1136/bmjoq-2021-001704,Benefits of electronic charts in intensive care and during a world health pandemic: advantages of the technology age.,"Pankhurst T, Lucas L, Ryan S, Ragdale C, Gyves H, Denner L, Young I, Rathbone L, Shah A, McKee D, Coleman JJ, Evison F, Atia J, Rosser D, Garrick M, Baker R, Gallier S, Ball S.",,BMJ open quality,2023,2023-01-01,Y,Evaluation Methodology; Critical Care; Electronic Health Records,,,"

Aims and objectives

This study sets out to describe benefits from the implementation of electronic observation charting in intensive care units (ICU). This was an extension to the existing hospital wide digital health system. We evaluated error reduction, time-savings and the costs associated with conversion from paper to digital records. The world health emergency of COVID-19 placed extraordinary strain on ICU and staff opinion was evaluated to test how well the electronic system performed.

Methods

A clinically led project group working directly with programmers developed an electronic patient record for intensive care. Data error rates, time to add data and to make calculations were studied before and after the introduction of electronic charts. User feedback was sought pre and post go-live (during the COVID-19 pandemic) and financial implications were calculated by the hospital finance teams.

Results

Error rates equating to 219 000/year were avoided by conversion to electronic charts. Time saved was the equivalent of a nursing shift each day. Recurrent cost savings per year were estimated to be £257k. Staff were overwhelmingly positive about electronic charts in ICU, even during a health pandemic and despite redeployment into intensive care where they were using the electronic charts for the first time.

Discussion

Electronic ICU charts have been successfully introduced into our institution with benefits in terms of patient safety through error reduction and improved care through release of nursing time. Costs have been reduced. Staff feel supported by the digital system and report it to be helpful even during redeployment and in the unfamiliar environment of intensive care.",,pdf:https://bmjopenquality.bmj.com/content/bmjqir/12/1/e001704.full.pdf; doi:https://doi.org/10.1136/bmjoq-2021-001704; html:https://europepmc.org/articles/PMC9853220; pdf:https://europepmc.org/articles/PMC9853220?pdf=render 35671273,https://doi.org/10.1371/journal.pone.0268837,Optimising the balance of acute and intermediate care capacity for the complex discharge pathway: Computer modelling study during COVID-19 recovery in England.,"Onen-Dumlu Z, Harper AL, Forte PG, Powell AL, Pitt M, Vasilakis C, Wood RM.",,PloS one,2022,2022-06-07,Y,,,,"

Objectives

While there has been significant research on the pressures facing acute hospitals during the COVID-19 pandemic, there has been less interest in downstream community services which have also been challenged in meeting demand. This study aimed to estimate the theoretical cost-optimal capacity requirement for 'step down' intermediate care services within a major healthcare system in England, at a time when considerable uncertainty remained regarding vaccination uptake and the easing of societal restrictions.

Methods

Demand for intermediate care was projected using an epidemiological model (for COVID-19 demand) and regressing upon public mobility (for non-COVID-19 demand). These were inputted to a computer simulation model of patient flow from acute discharge readiness to bedded and home-based Discharge to Assess (D2A) intermediate care services. Cost-optimal capacity was defined as that which yielded the lowest total cost of intermediate care provision and corresponding acute discharge delays.

Results

Increased intermediate care capacity is likely to bring about lower system-level costs, with the additional D2A investment more than offset by substantial reductions in costly acute discharge delays (leading also to improved patient outcome and experience). Results suggest that completely eliminating acute 'bed blocking' is unlikely economical (requiring large amounts of downstream capacity), and that health systems should instead target an appropriate tolerance based upon the specific characteristics of the pathway.

Conclusions

Computer modelling can be a valuable asset for determining optimal capacity allocation along the complex care pathway. With results supporting a Business Case for increased downstream capacity, this study demonstrates how modelling can be applied in practice and provides a blueprint for use alongside the freely-available model code.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0268837&type=printable; doi:https://doi.org/10.1371/journal.pone.0268837; html:https://europepmc.org/articles/PMC9173611; pdf:https://europepmc.org/articles/PMC9173611?pdf=render 36145196,https://doi.org/10.3390/nu14183821,Vitamin D Supplementation Does Not Influence SARS-CoV-2 Vaccine Efficacy or Immunogenicity: Sub-Studies Nested within the CORONAVIT Randomised Controlled Trial.,"Jolliffe DA, Vivaldi G, Chambers ES, Cai W, Li W, Faustini SE, Gibbons JM, Pade C, Coussens AK, Richter AG, McKnight Á, Martineau AR.",,Nutrients,2022,2022-09-16,Y,Interferon gamma; Vitamin D; Antibody; Randomised Controlled Trial; Breakthrough Sars-cov-2 Infection; Bnt162b2 Pfizer; Chadox1 Ncov-19 Oxford–astrazeneca,,,"Vitamin D deficiency has been reported to associate with the impaired development of antigen-specific responses following vaccination. We aimed to determine whether vitamin D supplements might boost the immunogenicity and efficacy of SARS-CoV-2 vaccination by conducting three sub-studies nested within the CORONAVIT randomised controlled trial, which investigated the effects of offering vitamin D supplements at a dose of 800 IU/day or 3200 IU/day vs. no offer on risk of acute respiratory infections in UK adults with circulating 25-hydroxyvitamin D concentrations <75 nmol/L. Sub-study 1 (n = 2808) investigated the effects of vitamin D supplementation on the risk of breakthrough SARS-CoV-2 infection following two doses of SARS-CoV-2 vaccine. Sub-study 2 (n = 1853) investigated the effects of vitamin D supplementation on titres of combined IgG, IgA and IgM (IgGAM) anti-Spike antibodies in eluates of dried blood spots collected after SARS-CoV-2 vaccination. Sub-study 3 (n = 100) investigated the effects of vitamin D supplementation on neutralising antibody and cellular responses in venous blood samples collected after SARS-CoV-2 vaccination. In total, 1945/2808 (69.3%) sub-study 1 participants received two doses of ChAdOx1 nCoV-19 (Oxford−AstraZeneca); the remainder received two doses of BNT162b2 (Pfizer). Mean follow-up 25(OH)D concentrations were significantly elevated in the 800 IU/day vs. no-offer group (82.5 vs. 53.6 nmol/L; mean difference 28.8 nmol/L, 95% CI 22.8−34.8) and in the 3200 IU/day vs. no offer group (105.4 vs. 53.6 nmol/L; mean difference 51.7 nmol/L, 45.1−58.4). Vitamin D supplementation did not influence the risk of breakthrough SARS-CoV-2 infection in vaccinated participants (800 IU/day vs. no offer: adjusted hazard ratio 1.28, 95% CI 0.89 to 1.84; 3200 IU/day vs. no offer: 1.17, 0.81 to 1.70). Neither did it influence IgGAM anti-Spike titres, neutralising antibody titres or IFN-γ concentrations in the supernatants of S peptide-stimulated whole blood. In conclusion, vitamin D replacement at a dose of 800 or 3200 IU/day effectively elevated 25(OH)D concentrations, but it did not influence the protective efficacy or immunogenicity of SARS-CoV-2 vaccination when given to adults who had a sub-optimal vitamin D status at baseline.",,pdf:https://www.mdpi.com/2072-6643/14/18/3821/pdf?version=1663570353; doi:https://doi.org/10.3390/nu14183821; html:https://europepmc.org/articles/PMC9506404; pdf:https://europepmc.org/articles/PMC9506404?pdf=render @@ -501,8 +501,8 @@ PMC10910267,https://doi.org/,Development and evaluation of a tool to optimise in 35927670,https://doi.org/10.1186/s12882-022-02902-8,Pre-operative Waterlow score and outcomes after kidney transplantation.,"Brotherton A, Evison F, Gallier S, Sharif A.",,BMC nephrology,2022,2022-08-04,Y,Mortality; Kidney transplantation; Length Of Stay; Readmission; Surrogate; Waterlow,,,"

Background

Waterlow scoring was introduced in the 1980s as a nursing tool to risk stratify for development of decubitus ulcers (pressure sores) and is commonly used in UK hospitals. Recent interest has focussed on its value as a pre-op surrogate marker for adverse surgical outcomes, but utility after kidney transplantation has never been explored.

Methods

In this single-centre observational study, data was extracted from hospital informatics systems for all kidney allograft recipients transplanted between 1st January 2007 and 30th June 2020. Waterlow scores were categorised as per national standards; 0-9 (low risk), 10-14 (at risk), 15-19 (high risk) and ≥ 20 (very high risk). Multiple imputation was used to replace missing data with substituted values. Primary outcomes of interest were post-operative length of stay, emergency re-admission within 90-days and mortality analysed by linear, logistic or Cox regression models respectively.

Results

Data was available for 2,041 kidney transplant patients, with baseline demographics significantly different across Waterlow categories. As a continuous variable, the median Waterlow score across the study cohort was 10 (interquartile range 8-13). As a categorical variable, Waterlow scores pre-operatively were classified as low risk (n = 557), at risk (n = 543), high risk (n = 120), very high risk (n = 27) and a large proportion of missing data (n = 794). Median length of stay in days varied significantly with pre-op Waterlow category scores, progressively getting longer with increasing severity of Waterlow category. However, no difference was observed in risk for emergency readmission within 90-days of surgery with severity of Waterlow category. Patients with 'very high risk' Waterlow scores had increased risk for mortality at 41.9% versus high risk (23.7%), at risk (17.4%) and low risk (13.4%). In adjusted analyses, 'very high risk' Waterlow group (as a categorical variable) or Waterlow score (as a continuous variable) had an independent association with increase length of stay after transplant surgery only. No association was observed between any Waterlow risk group/score with emergency 90-day readmission rates or post-transplant mortality after adjustment.

Conclusions

Pre-operative Waterlow scoring is a poor surrogate marker to identify kidney transplant patients at risk of emergency readmission or death and should not be utilised outside its intended use.",,pdf:https://bmcnephrol.biomedcentral.com/counter/pdf/10.1186/s12882-022-02902-8; doi:https://doi.org/10.1186/s12882-022-02902-8; html:https://europepmc.org/articles/PMC9351155; pdf:https://europepmc.org/articles/PMC9351155?pdf=render 37248229,https://doi.org/10.1038/s41467-023-38756-3,Evidence-driven spatiotemporal COVID-19 hospitalization prediction with Ising dynamics.,"Gao J, Heintz J, Mack C, Glass L, Cross A, Sun J.",,Nature communications,2023,2023-05-29,Y,,,,"In this work, we aim to accurately predict the number of hospitalizations during the COVID-19 pandemic by developing a spatiotemporal prediction model. We propose HOIST, an Ising dynamics-based deep learning model for spatiotemporal COVID-19 hospitalization prediction. By drawing the analogy between locations and lattice sites in statistical mechanics, we use the Ising dynamics to guide the model to extract and utilize spatial relationships across locations and model the complex influence of granular information from real-world clinical evidence. By leveraging rich linked databases, including insurance claims, census information, and hospital resource usage data across the U.S., we evaluate the HOIST model on the large-scale spatiotemporal COVID-19 hospitalization prediction task for 2299 counties in the U.S. In the 4-week hospitalization prediction task, HOIST achieves 368.7 mean absolute error, 0.6 [Formula: see text] and 0.89 concordance correlation coefficient score on average. Our detailed number needed to treat (NNT) and cost analysis suggest that future COVID-19 vaccination efforts may be most impactful in rural areas. This model may serve as a resource for future county and state-level vaccination efforts.",,doi:https://doi.org/10.1038/s41467-023-38756-3; doi:https://doi.org/10.1038/s41467-023-38756-3; html:https://europepmc.org/articles/PMC10226446; pdf:https://europepmc.org/articles/PMC10226446?pdf=render 37927438,https://doi.org/10.1016/j.lanepe.2023.100741,Comparative effectiveness of nirmatrelvir/ritonavir versus sotrovimab and molnupiravir for preventing severe COVID-19 outcomes in non-hospitalised high-risk patients during Omicron waves: observational cohort study using the OpenSAFELY platform.,"Zheng B, Tazare J, Nab L, Green AC, Curtis HJ, Mahalingasivam V, Herrett EL, Costello RE, Eggo RM, Speed V, Bacon SC, Bates C, Parry J, Cockburn J, Hester F, Harper S, Schaffer AL, Hulme WJ, Mehrkar A, Evans SJ, MacKenna B, Goldacre B, Douglas IJ, Tomlinson LA, OpenSAFELY Collaborative.",,The Lancet regional health. Europe,2023,2023-10-08,Y,Comparative Effectiveness; Real-world Data; Covid-19; Sotrovimab; Paxlovid,,,"

Background

Timely evidence of the comparative effectiveness between COVID-19 therapies in real-world settings is needed to inform clinical care. This study aimed to compare the effectiveness of nirmatrelvir/ritonavir versus sotrovimab and molnupiravir in preventing severe COVID-19 outcomes in non-hospitalised high-risk COVID-19 adult patients during Omicron waves.

Methods

With the approval of NHS England, we conducted a real-world cohort study using the OpenSAFELY-TPP platform. Patient-level primary care data were obtained from 24 million people in England and were securely linked with data on COVID-19 infection and therapeutics, hospital admission, and death, covering a period where both nirmatrelvir/ritonavir and sotrovimab were first-line treatment options in community settings (February 10, 2022-November 27, 2022). Molnupiravir (third-line option) was used as an exploratory comparator to nirmatrelvir/ritonavir, both of which were antivirals. Cox proportional hazards model stratified by area was used to compare the risk of 28-day COVID-19 related hospitalisation/death across treatment groups.

Findings

A total of 9026 eligible patients treated with nirmatrelvir/ritonavir (n = 5704) and sotrovimab (n = 3322) were included in the main analysis. The mean age was 52.7 (SD = 14.9) years and 93% (8436/9026) had three or more COVID-19 vaccinations. Within 28 days after treatment initiation, 55/9026 (0.61%) COVID-19 related hospitalisations/deaths were observed (34/5704 [0.60%] treated with nirmatrelvir/ritonavir and 21/3322 [0.63%] with sotrovimab). After adjusting for demographics, high-risk cohort categories, vaccination status, calendar time, body mass index and other comorbidities, we observed no significant difference in outcome risk between nirmatrelvir/ritonavir and sotrovimab users (HR = 0.89, 95% CI: 0.48-1.63; P = 0.698). Results from propensity score weighted model also showed non-significant difference between treatment groups (HR = 0.82, 95% CI: 0.45-1.52; P = 0.535). The exploratory analysis comparing nirmatrelvir/ritonavir users with 1041 molnupiravir users (13/1041 [1.25%] COVID-19 related hospitalisations/deaths) showed an association in favour of nirmatrelvir/ritonavir (HR = 0.45, 95% CI: 0.22-0.94; P = 0.033).

Interpretation

In routine care of non-hospitalised high-risk adult patients with COVID-19 in England, no substantial difference in the risk of severe COVID-19 outcomes was observed between those who received nirmatrelvir/ritonavir and sotrovimab between February and November 2022, when Omicron subvariants BA.2, BA.5, or BQ.1 were dominant.

Funding

UK Research and Innovation, Wellcome Trust, UK Medical Research Council, National Institute for Health and Care Research, and Health Data Research UK.",,doi:https://doi.org/10.1016/j.lanepe.2023.100741; doi:https://doi.org/10.1016/j.lanepe.2023.100741; html:https://europepmc.org/articles/PMC10624988; pdf:https://europepmc.org/articles/PMC10624988?pdf=render -37311808,https://doi.org/10.1038/s41467-023-39193-y,"Natural history of long-COVID in a nationwide, population cohort study.","Hastie CE, Lowe DJ, McAuley A, Mills NL, Winter AJ, Black C, Scott JT, O'Donnell CA, Blane DN, Browne S, Ibbotson TR, Pell JP.",,Nature communications,2023,2023-06-13,Y,,,,"Previous studies on the natural history of long-COVID have been few and selective. Without comparison groups, disease progression cannot be differentiated from symptoms originating from other causes. The Long-COVID in Scotland Study (Long-CISS) is a Scotland-wide, general population cohort of adults who had laboratory-confirmed SARS-CoV-2 infection matched to PCR-negative adults. Serial, self-completed, online questionnaires collected information on pre-existing health conditions and current health six, 12 and 18 months after index test. Of those with previous symptomatic infection, 35% reported persistent incomplete/no recovery, 12% improvement and 12% deterioration. At six and 12 months, one or more symptom was reported by 71.5% and 70.7% respectively of those previously infected, compared with 53.5% and 56.5% of those never infected. Altered taste, smell and confusion improved over time compared to the never infected group and adjusted for confounders. Conversely, late onset dry and productive cough, and hearing problems were more likely following SARS-CoV-2 infection.",,pdf:https://www.nature.com/articles/s41467-023-39193-y.pdf; doi:https://doi.org/10.1038/s41467-023-39193-y; html:https://europepmc.org/articles/PMC10263377; pdf:https://europepmc.org/articles/PMC10263377?pdf=render 32877922,https://doi.org/10.1093/gerona/glaa216,Frailty Is Associated With Neutrophil Dysfunction Which Is Correctable With Phosphoinositol-3-Kinase Inhibitors.,"Wilson D, Drew W, Jasper A, Crisford H, Nightingale P, Newby P, Jackson T, Lord JM, Sapey E.",,"The journals of gerontology. Series A, Biological sciences and medical sciences",2020,2020-11-01,Y,Inflammation; Proteinases; innate immunity; Comorbidity,,,"Neutrophil dysfunction has been described with age, appears exaggerated in infection, with altered phosphoinositol signaling a potential mechanism. However, functional aging is heterogeneous. Frailty is a negative health status and is more common in older adults. We hypothesized that neutrophil migration may be compromised in frailty, associated with the degree of frailty experienced by the older person. We compared measures of frailty, neutrophil function, and systemic inflammation in 40 young and 77 older community-dwelling adults in the United Kingdom. Systemic neutrophils exhibited an age-associated reduction in the accuracy of migration (chemotaxis) which was further blunted with frailty. The degree of migratory inaccuracy correlated with physical (adjusted hand grip strength) and cognitive (Stroop test) markers of frailty. Regression analysis demonstrated that age, Charlson comorbidity index, and frailty index were able to predict neutrophil chemotaxis. Reduced chemotaxis of neutrophils from frail adults could be reversed using selective PI3K inhibitors. Exposure of neutrophils from young adults to plasma from chronically inflamed frail older adults could not recapitulate the migratory deficit in vitro, and there were no relationships with systemic inflammation and neutrophil dysfunction. Frailty exaggerated the neutrophil deficits seen with advanced age but aspects of the frailty-associated deficit in neutrophil function are rescuable and thus potentially form a therapeutic target to improve outcomes from infection in older adults.",,pdf:https://academic.oup.com/biomedgerontology/article-pdf/75/12/2320/34289886/glaa216.pdf; doi:https://doi.org/10.1093/gerona/glaa216; html:https://europepmc.org/articles/PMC7662170; pdf:https://europepmc.org/articles/PMC7662170?pdf=render +37311808,https://doi.org/10.1038/s41467-023-39193-y,"Natural history of long-COVID in a nationwide, population cohort study.","Hastie CE, Lowe DJ, McAuley A, Mills NL, Winter AJ, Black C, Scott JT, O'Donnell CA, Blane DN, Browne S, Ibbotson TR, Pell JP.",,Nature communications,2023,2023-06-13,Y,,,,"Previous studies on the natural history of long-COVID have been few and selective. Without comparison groups, disease progression cannot be differentiated from symptoms originating from other causes. The Long-COVID in Scotland Study (Long-CISS) is a Scotland-wide, general population cohort of adults who had laboratory-confirmed SARS-CoV-2 infection matched to PCR-negative adults. Serial, self-completed, online questionnaires collected information on pre-existing health conditions and current health six, 12 and 18 months after index test. Of those with previous symptomatic infection, 35% reported persistent incomplete/no recovery, 12% improvement and 12% deterioration. At six and 12 months, one or more symptom was reported by 71.5% and 70.7% respectively of those previously infected, compared with 53.5% and 56.5% of those never infected. Altered taste, smell and confusion improved over time compared to the never infected group and adjusted for confounders. Conversely, late onset dry and productive cough, and hearing problems were more likely following SARS-CoV-2 infection.",,pdf:https://www.nature.com/articles/s41467-023-39193-y.pdf; doi:https://doi.org/10.1038/s41467-023-39193-y; html:https://europepmc.org/articles/PMC10263377; pdf:https://europepmc.org/articles/PMC10263377?pdf=render 33611594,https://doi.org/10.1093/eurjpc/zwaa155,Excess deaths in people with cardiovascular diseases during the COVID-19 pandemic.,"Banerjee A, Chen S, Pasea L, Lai AG, Katsoulis M, Denaxas S, Nafilyan V, Williams B, Wong WK, Bakhai A, Khunti K, Pillay D, Noursadeghi M, Wu H, Pareek N, Bromage D, McDonagh TA, Byrne J, Teo JTH, Shah AM, Humberstone B, Tang LV, Shah ASV, Rubboli A, Guo Y, Hu Y, Sudlow CLM, Lip GYH, Hemingway H.",,European journal of preventive cardiology,2021,2021-12-01,Y,Cardiovascular disease; Public Health; Health Policy; Global Health; Coronavirus-2019,,,"

Aims

Cardiovascular diseases (CVDs) increase mortality risk from coronavirus infection (COVID-19). There are also concerns that the pandemic has affected supply and demand of acute cardiovascular care. We estimated excess mortality in specific CVDs, both 'direct', through infection, and 'indirect', through changes in healthcare.

Methods and results

We used (i) national mortality data for England and Wales to investigate trends in non-COVID-19 and CVD excess deaths; (ii) routine data from hospitals in England (n = 2), Italy (n = 1), and China (n = 5) to assess indirect pandemic effects on referral, diagnosis, and treatment services for CVD; and (iii) population-based electronic health records from 3 862 012 individuals in England to investigate pre- and post-COVID-19 mortality for people with incident and prevalent CVD. We incorporated pre-COVID-19 risk (by age, sex, and comorbidities), estimated population COVID-19 prevalence, and estimated relative risk (RR) of mortality in those with CVD and COVID-19 compared with CVD and non-infected (RR: 1.2, 1.5, 2.0, and 3.0).Mortality data suggest indirect effects on CVD will be delayed rather than contemporaneous (peak RR 1.14). CVD service activity decreased by 60-100% compared with pre-pandemic levels in eight hospitals across China, Italy, and England. In China, activity remained below pre-COVID-19 levels for 2-3 months even after easing lockdown and is still reduced in Italy and England. For total CVD (incident and prevalent), at 10% COVID-19 prevalence, we estimated direct impact of 31 205 and 62 410 excess deaths in England (RR 1.5 and 2.0, respectively), and indirect effect of 49 932 to 99 865 deaths.

Conclusion

Supply and demand for CVD services have dramatically reduced across countries with potential for substantial, but avoidable, excess mortality during and after the pandemic.",,pdf:https://academic.oup.com/eurjpc/article-pdf/28/14/1599/41827245/zwaa155.pdf; doi:https://doi.org/10.1093/eurjpc/zwaa155; html:https://europepmc.org/articles/PMC7928969; pdf:https://europepmc.org/articles/PMC7928969?pdf=render 35332197,https://doi.org/10.1038/s41598-022-08690-3,Identifying multimorbidity clusters in an unselected population of hospitalised patients.,"Robertson L, Vieira R, Butler J, Johnston M, Sawhney S, Black C.",,Scientific reports,2022,2022-03-24,Y,,,,"Multimorbidity (multiple coexisting chronic health conditions) is common and increasing worldwide, and makes care challenging for both patients and healthcare systems. To ensure care is patient-centred rather than specialty-centred, it is important to know which conditions commonly occur together and identify the corresponding patient profile. To date, no studies have described multimorbidity clusters within an unselected hospital population. Our aim was to identify and characterise multimorbidity clusters, in a large, unselected hospitalised patient population. Linked inpatient hospital episode data were used to identify adults admitted to hospital in Grampian, Scotland in 2014 who had ≥ 2 of 30 chronic conditions diagnosed in the 5 years prior. Cluster analysis (Gower distance and Partitioning around Medoids) was used to identify groups of patients with similar conditions. Clusters of conditions were defined based on clinical review and assessment of prevalence within patient groups and labelled according to the most prevalent condition. Patient profiles for each group were described by age, sex, admission type, deprivation and urban-rural area of residence. 11,389 of 41,545 hospitalised patients (27%) had ≥ 2 conditions. Ten clusters of conditions were identified: hypertension; asthma; alcohol misuse; chronic kidney disease and diabetes; chronic kidney disease; chronic pain; cancer; chronic heart failure; diabetes; hypothyroidism. Age ranged from 51 (alcohol misuse) to 79 (chronic heart failure). Women were a higher proportion in the chronic pain and hypothyroidism clusters. The proportion of patients from the most deprived quintile of the population ranged from 6% (hypertension) to 14% (alcohol misuse). Identifying clusters of conditions in hospital patients is a first step towards identifying opportunities to target patient-centred care towards people with unmet needs, leading to improved outcomes and increased efficiency. Here we have demonstrated the face validity of cluster analysis as an exploratory method for identifying clusters of conditions in hospitalised patients with multimorbidity.",,pdf:https://www.nature.com/articles/s41598-022-08690-3.pdf; doi:https://doi.org/10.1038/s41598-022-08690-3; html:https://europepmc.org/articles/PMC8948299; pdf:https://europepmc.org/articles/PMC8948299?pdf=render 33243817,https://doi.org/10.1136/bmjopen-2020-042813,COVID-19 in Pregnancy in Scotland (COPS): protocol for an observational study using linked Scottish national data.,"Stock SJ, McAllister D, Vasileiou E, Simpson CR, Stagg HR, Agrawal U, McCowan C, Hopkins L, Donaghy J, Ritchie L, Robertson C, Sheikh A, Wood R.",,BMJ open,2020,2020-11-26,Y,Obstetrics; epidemiology; Neonatology; Perinatology; Covid-19,,,"

Introduction

The effects of SARS-CoV-2 in pregnancy are not fully delineated. We will describe the incidence of COVID-19 in pregnancy at population level in Scotland, in a prospective cohort study using linked data. We will determine associations between COVID-19 and adverse pregnancy, neonatal and maternal outcomes and the proportion of confirmed cases of SARS-CoV-2 infection in neonates associated with maternal COVID-19.

Methods and analysis

Prospective cohort study using national linked data sets. We will include all women in Scotland, UK, who were pregnant on or became pregnant after, 1 March 2020 (the date of the first confirmed case of SARS-CoV-2 infection in Scotland) and all births in Scotland from 1 March 2020 onwards. Individual-level data will be extracted from data sets containing details of all livebirths, stillbirth, terminations of pregnancy and miscarriages and ectopic pregnancies treated in hospital or attending general practice. Records will be linked within the Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II) platform, which includes primary care records, virology and serology results and details of COVID-19 Community Hubs and Assessment Centre contacts and deaths. We will perform analyses using definitions for confirmed, probable and possible COVID-19 and report serology results (where available). Outcomes will include congenital anomaly, miscarriage, stillbirth, termination of pregnancy, preterm birth, neonatal infection, severe maternal disease and maternal deaths. We will perform descriptive analyses and appropriate modelling, adjusting for demographic and pregnancy characteristics and the presence of comorbidities. The cohort will provide a platform for future studies of the effectiveness and safety of therapeutic interventions and immunisations for COVID-19 and their effects on childhood and developmental outcomes.

Ethics and dissemination

COVID-19 in Pregnancy in Scotland is a substudy of EAVE II(, which has approval from the National Research Ethics Service Committee. Findings will be reported to Scottish Government, Public Health Scotland and published in peer-reviewed journals.",,pdf:https://bmjopen.bmj.com/content/bmjopen/10/11/e042813.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-042813; html:https://europepmc.org/articles/PMC7691999; pdf:https://europepmc.org/articles/PMC7691999?pdf=render @@ -524,18 +524,18 @@ PMC10910267,https://doi.org/,Development and evaluation of a tool to optimise in 38177344,https://doi.org/10.1038/s41588-023-01585-7,A compendium of genetic regulatory effects across pig tissues.,"Teng J, Gao Y, Yin H, Bai Z, Liu S, Zeng H, PigGTEx Consortium, Bai L, Cai Z, Zhao B, Li X, Xu Z, Lin Q, Pan Z, Yang W, Yu X, Guan D, Hou Y, Keel BN, Rohrer GA, Lindholm-Perry AK, Oliver WT, Ballester M, Crespo-Piazuelo D, Quintanilla R, Canela-Xandri O, Rawlik K, Xia C, Yao Y, Zhao Q, Yao W, Yang L, Li H, Zhang H, Liao W, Chen T, Karlskov-Mortensen P, Fredholm M, Amills M, Clop A, Giuffra E, Wu J, Cai X, Diao S, Pan X, Wei C, Li J, Cheng H, Wang S, Su G, Sahana G, Lund MS, Dekkers JCM, Kramer L, Tuggle CK, Corbett R, Groenen MAM, Madsen O, Gòdia M, Rocha D, Charles M, Li CJ, Pausch H, Hu X, Frantz L, Luo Y, Lin L, Zhou Z, Zhang Z, Chen Z, Cui L, Xiang R, Shen X, Li P, Huang R, Tang G, Li M, Zhao Y, Yi G, Tang Z, Jiang J, Zhao F, Yuan X, Liu X, Chen Y, Xu X, Zhao S, Zhao P, Haley C, Zhou H, Wang Q, Pan Y, Ding X, Ma L, Li J, Navarro P, Zhang Q, Li B, Tenesa A, Li K, Liu GE, Zhang Z, Fang L.",,Nature genetics,2024,2024-01-04,Y,,,,"The Farm Animal Genotype-Tissue Expression (FarmGTEx) project has been established to develop a public resource of genetic regulatory variants in livestock, which is essential for linking genetic polymorphisms to variation in phenotypes, helping fundamental biological discovery and exploitation in animal breeding and human biomedicine. Here we show results from the pilot phase of PigGTEx by processing 5,457 RNA-sequencing and 1,602 whole-genome sequencing samples passing quality control from pigs. We build a pig genotype imputation panel and associate millions of genetic variants with five types of transcriptomic phenotypes in 34 tissues. We evaluate tissue specificity of regulatory effects and elucidate molecular mechanisms of their action using multi-omics data. Leveraging this resource, we decipher regulatory mechanisms underlying 207 pig complex phenotypes and demonstrate the similarity of pigs to humans in gene expression and the genetic regulation behind complex phenotypes, supporting the importance of pigs as a human biomedical model.",,pdf:https://www.nature.com/articles/s41588-023-01585-7.pdf; doi:https://doi.org/10.1038/s41588-023-01585-7; html:https://europepmc.org/articles/PMC10786720; pdf:https://europepmc.org/articles/PMC10786720?pdf=render 38569874,https://doi.org/10.1136/jnnp-2024-333530,"Trends in the prevalence and pharmacological management of migraine during pregnancy in the UK, 2000-2018.","Phillips K, Nirantharakumar K, Wakerley BR, Crowe FL.",,"Journal of neurology, neurosurgery, and psychiatry",2024,2024-04-03,N,Migraine,,,"

Background

Migraine is common in women of reproductive age. This study aimed to (1) describe the prevalence of migraine in pregnant women in the UK, (2) identify drugs commonly prescribed for migraine during pregnancy and (3) identify characteristics associated with being prescribed medication for migraine during pregnancy.

Methods

The Clinical Practice Research Datalink pregnancy register, a database of pregnancy episodes identified in anonymised primary care health records, was used.Crude and age-standardised prevalence of migraine during pregnancy and the proportion of women with migraine prescribed drugs used for migraine management were calculated for each year between 2000 and 2018.Logistic regression was used to describe the relationship between patient characteristics and being prescribed migraine medication during pregnancy.

Results

1 377 053 pregnancies were included, of which 187 328 were in women with a history of migraine. The age-adjusted prevalence increased from 11.4% in 2000 to 17.2% in 2018. There was an increase in the rates of prescription for numerous medications for the management of migraine.Older women (adjusted OR (aOR) 1.41 (1.20 to 1.66)), women of black (aOR 1.40 (1.32 to 1.48)) and South Asian ethnicity (aOR 1.48 (1.38 to 1.59)), those living in the most deprived areas (aOR 1.60 (1.54 to 1.66)), women who were obese (aOR 1.39 (1.35 to 1.43)), smokers (aOR 1.15 (1.12 to 1.18)) and those with comorbid conditions were more likely to receive a prescription during pregnancy.

Conclusions

Rates of recorded migraine have increased over the past two decades as well as rates of prescribing in women with migraine. Higher prescribing rates are seen in certain groups, which has the potential to exacerbate health inequalities.",,pdf:https://jnnp.bmj.com/content/jnnp/early/2024/04/03/jnnp-2024-333530.full.pdf; doi:https://doi.org/10.1136/jnnp-2024-333530 37159441,https://doi.org/10.1371/journal.pdig.0000218,Hospital-wide natural language processing summarising the health data of 1 million patients.,"Bean DM, Kraljevic Z, Shek A, Teo J, Dobson RJB.",,PLOS digital health,2023,2023-05-09,Y,,,,"Electronic health records (EHRs) represent a major repository of real world clinical trajectories, interventions and outcomes. While modern enterprise EHR's try to capture data in structured standardised formats, a significant bulk of the available information captured in the EHR is still recorded only in unstructured text format and can only be transformed into structured codes by manual processes. Recently, Natural Language Processing (NLP) algorithms have reached a level of performance suitable for large scale and accurate information extraction from clinical text. Here we describe the application of open-source named-entity-recognition and linkage (NER+L) methods (CogStack, MedCAT) to the entire text content of a large UK hospital trust (King's College Hospital, London). The resulting dataset contains 157M SNOMED concepts generated from 9.5M documents for 1.07M patients over a period of 9 years. We present a summary of prevalence and disease onset as well as a patient embedding that captures major comorbidity patterns at scale. NLP has the potential to transform the health data lifecycle, through large-scale automation of a traditionally manual task.",,doi:https://doi.org/10.1371/journal.pdig.0000218; doi:https://doi.org/10.1371/journal.pdig.0000218; html:https://europepmc.org/articles/PMC10168555; pdf:https://europepmc.org/articles/PMC10168555?pdf=render -36841835,https://doi.org/10.1038/s41541-023-00614-0,Incidence determinants and serological correlates of reactive symptoms following SARS-CoV-2 vaccination.,"Holt H, Jolliffe DA, Talaei M, Faustini S, Vivaldi G, Greenig M, Richter AG, Lyons RA, Griffiths CJ, Kee F, Sheikh A, Davies GA, Shaheen SO, Martineau AR.",,NPJ vaccines,2023,2023-02-25,Y,,,,"Prospective population-based studies investigating associations between reactive symptoms following SARS-CoV-2 vaccination and serologic responses to vaccination are lacking. We therefore conducted a study in 9003 adults from the UK general population receiving SARS-CoV-2 vaccines as part of the national vaccination programme. Titres of combined IgG/IgA/IgM responses to SARS-CoV-2 spike (S) glycoprotein were determined in eluates of dried blood spots collected from all participants before and after vaccination. 4262 (47.3%) participants experienced systemic reactive symptoms after a first vaccine dose. Factors associating with lower risk of such symptoms included older age (aOR per additional 10 years of age 0.85, 95% CI: 0.81-0.90), male vs. female sex (0.59, 0.53-0.65) and receipt of an mRNA vaccine vs. ChAdOx1 nCoV-19 (0.29, 0.26-0.32 for BNT162b2; 0.06, 0.01-0.26 for mRNA-1273). Higher risk of such symptoms was associated with SARS-CoV-2 seropositivity and COVID-19 symptoms prior to vaccination (2.23, 1.78-2.81), but not with SARS-CoV-2 seropositivity in the absence of COVID-19 symptoms (0.94, 0.81-1.09). Presence vs. absence of self-reported anxiety or depression at enrolment associated with higher risk of such symptoms (1.24, 1.12-1.39). Post-vaccination anti-S titres were higher among participants who experienced reactive symptoms after vaccination vs. those who did not (P < 0.001). We conclude that factors influencing risk of systemic symptoms after SARS-CoV-2 vaccination include demographic characteristics, pre-vaccination SARS-CoV-2 serostatus and vaccine type. Participants experiencing reactive symptoms following SARS-CoV-2 vaccination had higher post-vaccination titres of IgG/A/M anti-S antibodies. Improved public understanding of the frequency of reactogenic symptoms and their positive association with vaccine immunogenicity could potentially increase vaccine uptake.",,pdf:https://www.nature.com/articles/s41541-023-00614-0.pdf; doi:https://doi.org/10.1038/s41541-023-00614-0; html:https://europepmc.org/articles/PMC9959934; pdf:https://europepmc.org/articles/PMC9959934?pdf=render 36224173,https://doi.org/10.1038/s41467-022-33415-5,Outcomes among confirmed cases and a matched comparison group in the Long-COVID in Scotland study.,"Hastie CE, Lowe DJ, McAuley A, Winter AJ, Mills NL, Black C, Scott JT, O'Donnell CA, Blane DN, Browne S, Ibbotson TR, Pell JP.",,Nature communications,2022,2022-10-12,Y,,,,"With increasing numbers infected by SARS-CoV-2, understanding long-COVID is essential to inform health and social care support. A Scottish population cohort of 33,281 laboratory-confirmed SARS-CoV-2 infections and 62,957 never-infected individuals were followed-up via 6, 12 and 18-month questionnaires and linkage to hospitalization and death records. Of the 31,486 symptomatic infections,1,856 (6%) had not recovered and 13,350 (42%) only partially. No recovery was associated with hospitalized infection, age, female sex, deprivation, respiratory disease, depression and multimorbidity. Previous symptomatic infection was associated with poorer quality of life, impairment across all daily activities and 24 persistent symptoms including breathlessness (OR 3.43, 95% CI 3.29-3.58), palpitations (OR 2.51, OR 2.36-2.66), chest pain (OR 2.09, 95% CI 1.96-2.23), and confusion (OR 2.92, 95% CI 2.78-3.07). Asymptomatic infection was not associated with adverse outcomes. Vaccination was associated with reduced risk of seven symptoms. Here we describe the nature of long-COVID and the factors associated with it.",,pdf:https://researchonline.gcu.ac.uk/files/64233779/s41467_022_33415_5.pdf; doi:https://doi.org/10.1038/s41467-022-33415-5; html:https://europepmc.org/articles/PMC9556711; pdf:https://europepmc.org/articles/PMC9556711?pdf=render +36841835,https://doi.org/10.1038/s41541-023-00614-0,Incidence determinants and serological correlates of reactive symptoms following SARS-CoV-2 vaccination.,"Holt H, Jolliffe DA, Talaei M, Faustini S, Vivaldi G, Greenig M, Richter AG, Lyons RA, Griffiths CJ, Kee F, Sheikh A, Davies GA, Shaheen SO, Martineau AR.",,NPJ vaccines,2023,2023-02-25,Y,,,,"Prospective population-based studies investigating associations between reactive symptoms following SARS-CoV-2 vaccination and serologic responses to vaccination are lacking. We therefore conducted a study in 9003 adults from the UK general population receiving SARS-CoV-2 vaccines as part of the national vaccination programme. Titres of combined IgG/IgA/IgM responses to SARS-CoV-2 spike (S) glycoprotein were determined in eluates of dried blood spots collected from all participants before and after vaccination. 4262 (47.3%) participants experienced systemic reactive symptoms after a first vaccine dose. Factors associating with lower risk of such symptoms included older age (aOR per additional 10 years of age 0.85, 95% CI: 0.81-0.90), male vs. female sex (0.59, 0.53-0.65) and receipt of an mRNA vaccine vs. ChAdOx1 nCoV-19 (0.29, 0.26-0.32 for BNT162b2; 0.06, 0.01-0.26 for mRNA-1273). Higher risk of such symptoms was associated with SARS-CoV-2 seropositivity and COVID-19 symptoms prior to vaccination (2.23, 1.78-2.81), but not with SARS-CoV-2 seropositivity in the absence of COVID-19 symptoms (0.94, 0.81-1.09). Presence vs. absence of self-reported anxiety or depression at enrolment associated with higher risk of such symptoms (1.24, 1.12-1.39). Post-vaccination anti-S titres were higher among participants who experienced reactive symptoms after vaccination vs. those who did not (P < 0.001). We conclude that factors influencing risk of systemic symptoms after SARS-CoV-2 vaccination include demographic characteristics, pre-vaccination SARS-CoV-2 serostatus and vaccine type. Participants experiencing reactive symptoms following SARS-CoV-2 vaccination had higher post-vaccination titres of IgG/A/M anti-S antibodies. Improved public understanding of the frequency of reactogenic symptoms and their positive association with vaccine immunogenicity could potentially increase vaccine uptake.",,pdf:https://www.nature.com/articles/s41541-023-00614-0.pdf; doi:https://doi.org/10.1038/s41541-023-00614-0; html:https://europepmc.org/articles/PMC9959934; pdf:https://europepmc.org/articles/PMC9959934?pdf=render 34282121,https://doi.org/10.1038/s41398-021-01522-4,Phenotypic and genetic associations between anhedonia and brain structure in UK Biobank.,"Zhu X, Ward J, Cullen B, Lyall DM, Strawbridge RJ, Lyall LM, Smith DJ.",,Translational psychiatry,2021,2021-07-16,Y,,,,"Anhedonia is a core symptom of multiple psychiatric disorders and has been associated with alterations in brain structure. Genome-wide association studies suggest that anhedonia is heritable, with a polygenic architecture, but few studies have explored the association between genetic loading for anhedonia-indexed by polygenic risk scores for anhedonia (PRS-anhedonia)-and structural brain imaging phenotypes. Here, we investigated how anhedonia and PRS-anhedonia were associated with brain structure within the UK Biobank cohort. Brain measures (including total grey/white matter volumes, subcortical volumes, cortical thickness (CT) and white matter integrity) were analysed using linear mixed models in relation to anhedonia and PRS-anhedonia in 19,592 participants (9225 males; mean age = 62.6 years, SD = 7.44). We found that state anhedonia was significantly associated with reduced total grey matter volume (GMV); increased total white matter volume (WMV); smaller volumes in thalamus and nucleus accumbens; reduced CT within the paracentral cortex, the opercular part of inferior frontal gyrus, precentral cortex, insula and rostral anterior cingulate cortex; and poorer integrity of many white matter tracts. PRS-anhedonia was associated with reduced total GMV; increased total WMV; reduced white matter integrity; and reduced CT within the parahippocampal cortex, superior temporal gyrus and insula. Overall, both state anhedonia and PRS-anhedonia were associated with individual differences in multiple brain structures, including within reward-related circuits. These associations may represent vulnerability markers for psychopathology relevant to a range of psychiatric disorders.",,pdf:https://www.nature.com/articles/s41398-021-01522-4.pdf; doi:https://doi.org/10.1038/s41398-021-01522-4; html:https://europepmc.org/articles/PMC8289859; pdf:https://europepmc.org/articles/PMC8289859?pdf=render 37185201,https://doi.org/10.1136/bmjopen-2022-067337,Prevalence of HIV in mental health service users: a retrospective cohort study.,"Heslin M, Jewell A, Croxford S, Chau C, Smith S, Pittrof R, Covshoff E, Sullivan A, Delpech V, Brown A, King HP, Kakaiya M, Campbell L, Hughes E, Stewart R.",,BMJ open,2023,2023-04-25,Y,Mental health; Hiv & Aids; Sexual Medicine,,,"

Objective

To examine the prevalence of HIV in a cohort of people who have used secondary mental health services in the UK.

Design

Retrospective cohort study.

Setting

Routinely collected clinical data from secondary mental health services in South London, UK available for research through the Clinical Record Interactive Search tool at the National Institute for Health and Care Research Maudsley Biomedical Research Centre were matched with pseudonymised national HIV surveillance data held by the UK Health Security Agency using a deterministic matching algorithm.

Participants

All adults aged 16+ who presented for the first time to mental health services in the South London and Maudsley (SLaM) National Health Service Trust between 1 January 2007 and 31 December 2018 were included.

Primary outcome

Point prevalence of HIV.

Results

There were 181 177 people who had contact with mental health services for the first time between 2007 and 2018 in SLaM. Overall, 2.47% (n=4481) of those had a recorded HIV diagnosis in national HIV surveillance data at any time (before, during or after contact with mental health services), 24.73 people per 1000. HIV point prevalence was highest in people with a diagnosed substance use disorder at 3.77% (n=784). A substantial percentage of the sample did not have a formal mental health diagnosis (27%), but even with those excluded, the point prevalence remained high at 2.31%. Around two-thirds of people had their diagnosis of HIV before contact with mental health services (67%; n=1495).

Conclusions

The prevalence of HIV in people who have had contact with mental health services was approximately 2.5 times higher than the general population in the same geographical area. Future work should investigate risk factors and disparities in HIV outcomes between those with and without mental health service contact.",,pdf:https://bmjopen.bmj.com/content/bmjopen/13/4/e067337.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-067337; html:https://europepmc.org/articles/PMC10186409; pdf:https://europepmc.org/articles/PMC10186409?pdf=render 34356905,https://doi.org/10.3390/biomedicines9070841,Relationship between Circulating PCSK9 and Markers of Subclinical Atherosclerosis-The IMPROVE Study.,"Coggi D, Frigerio B, Bonomi A, Ruscica M, Ferri N, Sansaro D, Ravani A, Ferrante P, Damigella M, Veglia F, Capra N, Lupo MG, Macchi C, Savonen K, Silveira A, Kurl S, Giral P, Pirro M, Strawbridge RJ, Gigante B, Smit AJ, Tremoli E, Amato M, Baldassarre D, On Behalf Of The Improve Study Group.",,Biomedicines,2021,2021-07-19,Y,Intima-media thickness; carotid artery; Pcsk9; Subclinical Atherosclerosis; Echolucency,,,"(1) Background and purpose: circulating proprotein convertase subtilisin/kexin type 9 (PCSK9) is one of the key regulators of cholesterol metabolism. Despite this, its role as a player in atherosclerosis development is still matter of debate. Here, we investigated the relationships between this protein and several markers of subclinical atherosclerosis. (2) Methods: the IMPROVE study enrolled 3703 European subjects (54-79 years; 48% men; with ≥3 vascular risk factors), asymptomatic for cardiovascular diseases. PCSK9 levels were measured by ELISA. B-mode ultrasound was used to measure markers of carotid subclinical atherosclerosis. (3) Results: in the crude analysis, PCSK9 levels were associated with several baseline measures of carotid intima-media thickness (cIMT) (all p < 0.0001); with cIMT change over time (Fastest-IMTmax-progr) (p = 0.01); with inter-adventitia common carotid artery diameter (ICCAD) (p < 0.0001); and with the echolucency (Grey Scale Median; GSM) of both carotid plaque and plaque-free common carotid IMT (both p < 0.0001). However, after adjustment for age, sex, latitude, and pharmacological treatment, all the afore-mentioned correlations were no longer statistically significant. The lack of correlation was also observed after stratification for sex, latitude, and pharmacological treatments. (4) Conclusions: in subjects who are asymptomatic for cardiovascular diseases, PCSK9 plasma levels do not correlate with vascular damage and/or subclinical atherosclerosis of extracranial carotid arteries.",,pdf:https://www.mdpi.com/2227-9059/9/7/841/pdf?version=1626837519; doi:https://doi.org/10.3390/biomedicines9070841; html:https://europepmc.org/articles/PMC8301759; pdf:https://europepmc.org/articles/PMC8301759?pdf=render -37068951,https://doi.org/10.1136/thorax-2022-219901,Asthma hospitalisations and heat exposure in England: a case-crossover study during 2002-2019.,"Konstantinoudis G, Minelli C, Lam HCY, Fuertes E, Ballester J, Davies B, Vicedo-Cabrera AM, Gasparrini A, Blangiardo M.",,Thorax,2023,2023-04-17,Y,Asthma Epidemiology,,,"

Background

Previous studies have reported an association between warm temperature and asthma hospitalisation. They have reported different sex-related and age-related vulnerabilities; nevertheless, little is known about how this effect has changed over time and how it varies in space. This study aims to evaluate the association between asthma hospitalisation and warm temperature and investigate vulnerabilities by age, sex, time and space.

Methods

We retrieved individual-level data on summer asthma hospitalisation at high temporal (daily) and spatial (postcodes) resolutions during 2002-2019 in England from the NHS Digital. Daily mean temperature at 1 km×1 km resolution was retrieved from the UK Met Office. We focused on lag 0-3 days. We employed a case-crossover study design and fitted Bayesian hierarchical Poisson models accounting for possible confounders (rainfall, relative humidity, wind speed and national holidays).

Results

After accounting for confounding, we found an increase of 1.11% (95% credible interval: 0.88% to 1.34%) in the asthma hospitalisation risk for every 1°C increase in the ambient summer temperature. The effect was highest for males aged 16-64 (2.10%, 1.59% to 2.61%) and during the early years of our analysis. We also found evidence of a decreasing linear trend of the effect over time. Populations in Yorkshire and the Humber and East and West Midlands were the most vulnerable.

Conclusion

This study provides evidence of an association between warm temperature and hospital admission for asthma. The effect has decreased over time with potential explanations including temporal differences in patterns of heat exposure, adaptive mechanisms, asthma management, lifestyle, comorbidities and occupation.",,pdf:https://thorax.bmj.com/content/thoraxjnl/early/2023/04/17/thorax-2022-219901.full.pdf; doi:https://doi.org/10.1136/thorax-2022-219901; html:https://europepmc.org/articles/PMC10447396; pdf:https://europepmc.org/articles/PMC10447396?pdf=render 33838587,https://doi.org/10.1016/j.epidem.2021.100460,Competition between RSV and influenza: Limits of modelling inference from surveillance data.,"Waterlow NR, Flasche S, Minter A, Eggo RM.",,Epidemics,2021,2021-03-26,Y,Interaction; Competition; Influenza; Respiratory syncytial virus; Inference,,,"Respiratory Syncytial Virus (RSV) and Influenza cause a large burden of disease. Evidence of their interaction via temporary cross-protection implies that prevention of one could inadvertently lead to an increase in the burden of the other. However, evidence for the public health impact of such interaction is sparse and largely derives from ecological analyses of peak shifts in surveillance data. To test the robustness of estimates of interaction parameters between RSV and Influenza from surveillance data we conducted a simulation and back-inference study. We developed a two-pathogen interaction model, parameterised to simulate RSV and Influenza epidemiology in the UK. Using the infection model in combination with a surveillance-like stochastic observation process we generated a range of possible RSV and Influenza trajectories and then used Markov Chain Monte Carlo (MCMC) methods to back-infer parameters including those describing competition. We find that in most scenarios both the strength and duration of RSV and Influenza interaction could be estimated from the simulated surveillance data reasonably well. However, the robustness of inference declined towards the extremes of the plausible parameter ranges, with misleading results. It was for instance not possible to tell the difference between low/moderate interaction and no interaction. In conclusion, our results illustrate that in a plausible parameter range, the strength of RSV and Influenza interaction can be estimated from a single season of high-quality surveillance data but also highlights the importance to test parameter identifiability a priori in such situations.",,doi:https://doi.org/10.1016/j.epidem.2021.100460; doi:https://doi.org/10.1016/j.epidem.2021.100460; html:https://europepmc.org/articles/PMC8193815 +37068951,https://doi.org/10.1136/thorax-2022-219901,Asthma hospitalisations and heat exposure in England: a case-crossover study during 2002-2019.,"Konstantinoudis G, Minelli C, Lam HCY, Fuertes E, Ballester J, Davies B, Vicedo-Cabrera AM, Gasparrini A, Blangiardo M.",,Thorax,2023,2023-04-17,Y,Asthma Epidemiology,,,"

Background

Previous studies have reported an association between warm temperature and asthma hospitalisation. They have reported different sex-related and age-related vulnerabilities; nevertheless, little is known about how this effect has changed over time and how it varies in space. This study aims to evaluate the association between asthma hospitalisation and warm temperature and investigate vulnerabilities by age, sex, time and space.

Methods

We retrieved individual-level data on summer asthma hospitalisation at high temporal (daily) and spatial (postcodes) resolutions during 2002-2019 in England from the NHS Digital. Daily mean temperature at 1 km×1 km resolution was retrieved from the UK Met Office. We focused on lag 0-3 days. We employed a case-crossover study design and fitted Bayesian hierarchical Poisson models accounting for possible confounders (rainfall, relative humidity, wind speed and national holidays).

Results

After accounting for confounding, we found an increase of 1.11% (95% credible interval: 0.88% to 1.34%) in the asthma hospitalisation risk for every 1°C increase in the ambient summer temperature. The effect was highest for males aged 16-64 (2.10%, 1.59% to 2.61%) and during the early years of our analysis. We also found evidence of a decreasing linear trend of the effect over time. Populations in Yorkshire and the Humber and East and West Midlands were the most vulnerable.

Conclusion

This study provides evidence of an association between warm temperature and hospital admission for asthma. The effect has decreased over time with potential explanations including temporal differences in patterns of heat exposure, adaptive mechanisms, asthma management, lifestyle, comorbidities and occupation.",,pdf:https://thorax.bmj.com/content/thoraxjnl/early/2023/04/17/thorax-2022-219901.full.pdf; doi:https://doi.org/10.1136/thorax-2022-219901; html:https://europepmc.org/articles/PMC10447396; pdf:https://europepmc.org/articles/PMC10447396?pdf=render 37587484,https://doi.org/10.1186/s12874-023-02000-9,Implementation of the trial emulation approach in medical research: a scoping review.,"Scola G, Chis Ster A, Bean D, Pareek N, Emsley R, Landau S.",,BMC medical research methodology,2023,2023-08-16,Y,Causal Inference; Observational Data; Target Trial; Trial Emulation,,,"

Background

When conducting randomised controlled trials is impractical, an alternative is to carry out an observational study. However, making valid causal inferences from observational data is challenging because of the risk of several statistical biases. In 2016 Hernán and Robins put forward the 'target trial framework' as a guide to best design and analyse observational studies whilst preventing the most common biases. This framework consists of (1) clearly defining a causal question about an intervention, (2) specifying the protocol of the hypothetical trial, and (3) explaining how the observational data will be used to emulate it.

Methods

The aim of this scoping review was to identify and review all explicit attempts of trial emulation studies across all medical fields. Embase, Medline and Web of Science were searched for trial emulation studies published in English from database inception to February 25, 2021. The following information was extracted from studies that were deemed eligible for review: the subject area, the type of observational data that they leveraged, and the statistical methods they used to address the following biases: (A) confounding bias, (B) immortal time bias, and (C) selection bias.

Results

The search resulted in 617 studies, 38 of which we deemed eligible for review. Of those 38 studies, most focused on cardiology, infectious diseases or oncology and the majority used electronic health records/electronic medical records data and cohort studies data. Different statistical methods were used to address confounding at baseline and selection bias, predominantly conditioning on the confounders (N = 18/49, 37%) and inverse probability of censoring weighting (N = 7/20, 35%) respectively. Different approaches were used to address immortal time bias, assigning individuals to treatment strategies at start of follow-up based on their data available at that specific time (N = 21, 55%), using the sequential trial emulations approach (N = 11, 29%) or the cloning approach (N = 6, 16%).

Conclusion

Different methods can be leveraged to address (A) confounding bias, (B) immortal time bias, and (C) selection bias. When working with observational data, and if possible, the 'target trial' framework should be used as it provides a structured conceptual approach to observational research.",,doi:https://doi.org/10.1186/s12874-023-02000-9; html:https://europepmc.org/articles/PMC10428565; pdf:https://europepmc.org/articles/PMC10428565?pdf=render 33879450,https://doi.org/10.1136/heartjnl-2021-319118,Sex differences in investigations and outcomes among patients with type 2 myocardial infarction.,"Kimenai DM, Lindahl B, Chapman AR, Baron T, Gard A, Wereski R, Meex SJR, Jernberg T, Mills NL, Eggers KM.",,Heart (British Cardiac Society),2021,2021-04-20,Y,Myocardial infarction; acute coronary syndrome; risk factors,,,"

Objectives

Type 2 myocardial infarction (MI) is a heterogenous condition and whether there are differences between women and men is unknown. We evaluated sex differences in clinical characteristics, investigations and outcomes in patients with type 2 MI.

Methods

In the Swedish Web based system for Enhancement and Development of Evidence based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART) registry, we compared patients admitted to coronary care units with a diagnosis of type 1 or type 2 MI. Sex-stratified Cox regression models evaluated the association with all-cause death in men and women separately.

Results

We included 57 264 (median age 73 years, 65% men) and 6485 (median age 78 years, 50% men) patients with type 1 and type 2 MI, respectively. No differences were observed in the proportion of men and women with type 2 MI who underwent echocardiography and coronary angiography, but women were less likely than men to have left ventricular (LV) impairment and obstructive coronary artery disease (CAD). Compared with type 1 MI, patients with type 2 MI had higher risk of death regardless of sex (men: adjusted HR 1.55 (95% CI 1.44 to 1.67); women: adjusted HR 1.34 (95% CI 1.24 to 1.45)). In those with type 2 MI, the risk of death was lower for women than men (adjusted HR 0.85 (95% CI 0.76 to 0.92) (men, reference)).

Conclusions

Type 2 MI occurred in men and women equally and we found no evidence of sex bias in the selection of patients for cardiac investigations. Patients with type 2 MI had worse outcomes, but women were less likely to have obstructive CAD or severe LV impairment and were more likely to survive than men.",,pdf:https://heart.bmj.com/content/heartjnl/107/18/1480.full.pdf; doi:https://doi.org/10.1136/heartjnl-2021-319118; html:https://europepmc.org/articles/PMC8408584; pdf:https://europepmc.org/articles/PMC8408584?pdf=render 36735963,https://doi.org/10.1080/09553002.2023.2173823,Machine intelligence for radiation science: summary of the Radiation Research Society 67th annual meeting symposium.,"Wilson LJ, Kiffer FC, Berrios DC, Bryce-Atkinson A, Costes SV, Gevaert O, Matarèse BFE, Miller J, Mukherjee P, Peach K, Schofield PN, Slater LT, Langen B.",,International journal of radiation biology,2023,2023-02-06,N,Artificial intelligence; Lung cancer; Radiotherapy; Radiobiology; Ontology; Machine Learning; Voxel-based Analysis,,,"The era of high-throughput techniques created big data in the medical field and research disciplines. Machine intelligence (MI) approaches can overcome critical limitations on how those large-scale data sets are processed, analyzed, and interpreted. The 67th Annual Meeting of the Radiation Research Society featured a symposium on MI approaches to highlight recent advancements in the radiation sciences and their clinical applications. This article summarizes three of those presentations regarding recent developments for metadata processing and ontological formalization, data mining for radiation outcomes in pediatric oncology, and imaging in lung cancer.",,doi:https://doi.org/10.1080/09553002.2023.2173823; doi:https://doi.org/10.1080/09553002.2023.2173823 -38552327,https://doi.org/10.1093/bioinformatics/btae172,shinyExprPortal: a configurable 'shiny' portal for sharing analysis of molecular expression data.,"Henkin R, Goldmann K, Lewis M, Barnes MR.",,"Bioinformatics (Oxford, England)",2024,2024-03-01,Y,,,,"

Motivation

The scale of omics research presents many obstacles to full sharing and access to analysis results. Current publication models impose limits on the number of pages and figures, requiring careful preparation and selection of content. At the same time, depositing data in open repositories significantly shifts the burden of access and reproduction to readers, who may include people who are not programmers or analysts.

Results

We introduce shinyExprPortal, an R package that implements omics web portals with minimal coding effort. The portals allow exploration of transcriptomic or proteomic expression data and phenotypes, showcasing results of various types of analysis including differential expression, co-expression and pathways analysis. The integration with bioinformatics workflows enables researchers to focus on their results and share findings using interactive and publication-quality plots.

Availability and implementation

The shinyExprPortal package is available to download and install from CRAN and https://github.com/C4TB/shinyExprPortal.",,pdf:https://academic.oup.com/bioinformatics/advance-article-pdf/doi/10.1093/bioinformatics/btae172/57122310/btae172.pdf; doi:https://doi.org/10.1093/bioinformatics/btae172; html:https://europepmc.org/articles/PMC11021805; pdf:https://europepmc.org/articles/PMC11021805?pdf=render 30474191,https://doi.org/10.1111/dme.13870,Utility of HbA1c assessment in people with diabetes awaiting liver transplantation.,"Bhattacharjee D, Vracar S, Round RA, Nightingale PG, Williams JA, Gkoutos GV, Stratton IM, Parker R, Luzio SD, Webber J, Manley SE, Roberts GA, Ghosh S.",,Diabetic medicine : a journal of the British Diabetic Association,2019,2019-04-30,Y,,The Human Phenome,,"

Aims

To investigate the relationship between HbA1c and glucose in people with co-existing liver disease and diabetes awaiting transplant, and in those with diabetes but no liver disease.

Methods

HbA1c and random plasma glucose data were collected for 125 people with diabetes without liver disease and for 29 people awaiting liver transplant with diabetes and cirrhosis. Cirrhosis was caused by non-alcoholic fatty liver disease, hepatitis C, alcoholic liver disease, hereditary haemochromatosis, polycystic liver/kidneys, cryptogenic/non-cirrhotic portal hypertension and α-1-antitrypsin-related disease.

Results

The median (interquartile range) age of the diabetes with cirrhosis group was 55 (49-63) years compared to 60 (50-71) years (P=0.13) in the group without cirrhosis. In the diabetes with cirrhosis group there were 21 men (72%) compared with 86 men (69%) in the group with diabetes and no cirrhosis (P=0.82). Of the group with diabetes and cirrhosis, 27 people (93%) were of white European ethnicity, two (7%) were South Asian and none was of Afro-Caribbean/other ethnicity compared with 94 (75%), 16 (13%), 10 (8%)/5 (4%), respectively, in the group with diabetes and no cirrhosis (P=0.20). Median (interquartile range) HbA1c was 41 (32-56) mmol/mol [5.9 (5.1-7.3)%] vs 61 (52-70) mmol/mol [7.7 (6.9-8.6)%] (P<0.001), respectively, in the diabetes with cirrhosis group vs the diabetes without cirrhosis group. The glucose concentrations were 8.4 (7.0-11.2) mmol/l vs 7.3 (5.2-11.5) mmol/l (P=0.17). HbA1c was depressed by 20 mmol/mol (1.8%; P<0.001) in 28 participants with cirrhosis but elevated by 28 mmol/mol (2.6%) in the participant with α-1-antitrypsin disorder. Those with cirrhosis and depressed HbA1c had fewer larger erythrocytes, and higher red cell distribution width and reticulocyte count. This was reflected in the positive association of glucose with mean cell volume (r=0.39) and haemoglobin level (r=0.49) and the negative association for HbA1c (r=-0.28 and r=-0.26, respectively) in the diabetes group with cirrhosis.

Conclusion

HbA1c is not an appropriate test for blood glucose in people with cirrhosis and diabetes awaiting transplant as it reflects altered erythrocyte presentation.","The aim of this article was to investigate the relationship between HbA1c and glucose in patients with diabetes awaiting transplant due to a co-existing liver disease, and in those with diabetes but no liver disease. Statistical analyses results indicated that HbA1c is not an appropriate test for blood glucose in people with cirrhosis and diabetes awaiting transplant, and it might cause misdiagnosis of diabetes and inappropirate clinical care in people with cirrhotic liver disease.",pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/dme.13870; doi:https://doi.org/10.1111/dme.13870; html:https://europepmc.org/articles/PMC6850030; pdf:https://europepmc.org/articles/PMC6850030?pdf=render +38552327,https://doi.org/10.1093/bioinformatics/btae172,shinyExprPortal: a configurable 'shiny' portal for sharing analysis of molecular expression data.,"Henkin R, Goldmann K, Lewis M, Barnes MR.",,"Bioinformatics (Oxford, England)",2024,2024-03-01,Y,,,,"

Motivation

The scale of omics research presents many obstacles to full sharing and access to analysis results. Current publication models impose limits on the number of pages and figures, requiring careful preparation and selection of content. At the same time, depositing data in open repositories significantly shifts the burden of access and reproduction to readers, who may include people who are not programmers or analysts.

Results

We introduce shinyExprPortal, an R package that implements omics web portals with minimal coding effort. The portals allow exploration of transcriptomic or proteomic expression data and phenotypes, showcasing results of various types of analysis including differential expression, co-expression and pathways analysis. The integration with bioinformatics workflows enables researchers to focus on their results and share findings using interactive and publication-quality plots.

Availability and implementation

The shinyExprPortal package is available to download and install from CRAN and https://github.com/C4TB/shinyExprPortal.",,pdf:https://academic.oup.com/bioinformatics/advance-article-pdf/doi/10.1093/bioinformatics/btae172/57122310/btae172.pdf; doi:https://doi.org/10.1093/bioinformatics/btae172; html:https://europepmc.org/articles/PMC11021805; pdf:https://europepmc.org/articles/PMC11021805?pdf=render 34514500,https://doi.org/10.1093/infdis/jiab459,The Impact of Cocirculating Pathogens on Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)/Coronavirus Disease 2019 Surveillance: How Concurrent Epidemics May Introduce Bias and Decrease the Observed SARS-CoV-2 Percentage Positivity.,"Kovacevic A, Eggo RM, Baguelin M, Domenech de Cellès M, Opatowski L.",,The Journal of infectious diseases,2022,2022-01-01,Y,Mathematical Modeling; Multiplex Testing; Sars-cov-2; Covid-19 Surveillance; Cocirculating Respiratory Viruses,,,"

Background

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

Methods

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

Results

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

Conclusions

This study showed that cocirculating respiratory viruses can distort SARS-CoV-2 surveillance. Correction of the positivity rate can be achieved by using multiplex polymerase chain reaction tests, and a low number of samples is sufficient to avoid bias in SARS-CoV-2 surveillance.",,pdf:https://academic.oup.com/jid/article-pdf/225/2/199/42224165/jiab459.pdf; doi:https://doi.org/10.1093/infdis/jiab459; html:https://europepmc.org/articles/PMC8763960; pdf:https://europepmc.org/articles/PMC8763960?pdf=render 34957254,https://doi.org/10.3389/fcvm.2021.766287,Radiomics Analysis Derived From LGE-MRI Predict Sudden Cardiac Death in Participants With Hypertrophic Cardiomyopathy.,"Wang J, Bravo L, Zhang J, Liu W, Wan K, Sun J, Zhu Y, Han Y, Gkoutos GV, Chen Y.",,Frontiers in cardiovascular medicine,2021,2021-12-10,Y,hypertrophic cardiomyopathy; Sudden Cardiac Death; Machine Learning; Late Gadolinium Enhancement; Radiomics,,,"Objectives: To identify significant radiomics features derived from late gadolinium enhancement (LGE) images in participants with hypertrophic cardiomyopathy (HCM) and assess their prognostic value in predicting sudden cardiac death (SCD) endpoint. Method: The 157 radiomic features of 379 sequential participants with HCM who underwent cardiovascular magnetic resonance imaging (MRI) were extracted. CoxNet (Least Absolute Shrinkage and Selection Operator (LASSO) and Elastic Net) and Random Forest models were applied to optimize feature selection for the SCD risk prediction and cross-validation was performed. Results: During a median follow-up of 29 months (interquartile range, 20-42 months), 27 participants with HCM experienced SCD events. Cox analysis revealed that two selected features, local binary patterns (LBP) (19) (hazard ratio (HR), 1.028, 95% CI: 1.032-1.134; P = 0.001) and Moment (1) (HR, 1.212, 95%CI: 1.032-1.423; P = 0.02) provided significant prognostic value to predict the SCD endpoints after adjustment for the clinical risk predictors and late gadolinium enhancement. Furthermore, the univariately significant risk predictor was improved by the addition of the selected radiomics features, LBP (19) and Moment (1), to predict SCD events (P < 0.05). Conclusion: The radiomics features of LBP (19) and Moment (1) extracted from LGE images, reflecting scar heterogeneity, have independent prognostic value in identifying high SCD risk patients with HCM.",,pdf:https://www.frontiersin.org/articles/10.3389/fcvm.2021.766287/pdf; doi:https://doi.org/10.3389/fcvm.2021.766287; html:https://europepmc.org/articles/PMC8702805; pdf:https://europepmc.org/articles/PMC8702805?pdf=render 36936594,https://doi.org/10.1136/bmjmed-2022-000247,Measuring multimorbidity in research: Delphi consensus study.,"Ho ISS, Azcoaga-Lorenzo A, Akbari A, Davies J, Khunti K, Kadam UT, Lyons RA, McCowan C, Mercer SW, Nirantharakumar K, Staniszewska S, Guthrie B.",,BMJ medicine,2022,2022-07-27,Y,Medicine; epidemiology; Primary Health Care; Public Health; Research Design,,,"

Objective

To develop international consensus on the definition and measurement of multimorbidity in research.

Design

Delphi consensus study.

Setting

International consensus; data collected in three online rounds from participants between 30 November 2020 and 18 May 2021.

Participants

Professionals interested in multimorbidity and people with long term conditions were recruited to professional and public panels.

Results

150 professional and 25 public participants completed the first survey round. Response rates for rounds 2/3 were 83%/92% for professionals and 88%/93% in the public panel, respectively. Across both panels, the consensus was that multimorbidity should be defined as two or more long term conditions. Complex multimorbidity was perceived to be a useful concept, but the panels were unable to agree on how to define it. Both panels agreed that conditions should be included in a multimorbidity measure if they were one or more of the following: currently active; permanent in their effects; requiring current treatment, care, or therapy; requiring surveillance; or relapsing-remitting conditions requiring ongoing care. Consensus was reached for 24 conditions to always include in multimorbidity measures, and 35 conditions to usually include unless a good reason not to existed. Simple counts were preferred for estimating prevalence and examining clustering or trajectories, and weighted measures were preferred for risk adjustment and outcome prediction.

Conclusions

Previous multimorbidity research is limited by inconsistent definitions and approaches to measuring multimorbidity. This Delphi study identifies professional and public panel consensus guidance to facilitate consistency of definition and measurement, and to improve study comparability and reproducibility.",,pdf:https://bmjmedicine.bmj.com/content/bmjmed/1/1/e000247.full.pdf; doi:https://doi.org/10.1136/bmjmed-2022-000247; html:https://europepmc.org/articles/PMC9978673; pdf:https://europepmc.org/articles/PMC9978673?pdf=render @@ -554,8 +554,8 @@ PMC10910267,https://doi.org/,Development and evaluation of a tool to optimise in 35505353,https://doi.org/10.1186/s12916-022-02349-6,Predictive performance of a competing risk cardiovascular prediction tool CRISK compared to QRISK3 in older people and those with comorbidity: population cohort study.,"Livingstone SJ, Guthrie B, Donnan PT, Thompson A, Morales DR.",,BMC medicine,2022,2022-05-04,Y,Primary Prevention; Cardiovascular Risk; Risk Prediction; Competing Risk; Qrisk3,,,"

Background

Recommended cardiovascular disease (CVD) prediction tools do not account for competing mortality risk and over-predict incident CVD in older and multimorbid people. The aim of this study was to derive and validate a competing risk model (CRISK) to predict incident CVD and compare its performance to that of QRISK3 in UK primary care.

Methods

We used UK linked primary care data from the Clinical Practice Research Datalink (CPRD) GOLD to identify people aged 25-84 years with no previous CVD or statin treatment split into derivation and validation cohorts. In the derivation cohort, we derived models using the same covariates as QRISK3 with Fine-Gray competing risk modelling alone (CRISK) and with Charlson Comorbidity score (CRISK-CCI) as an additional predictor of non-CVD death. In a separate validation cohort, we examined discrimination and calibration compared to QRISK3. Reclassification analysis examined the number of patients recommended for treatment and the estimated number needed to treat (NNT) to prevent a new CVD event.

Results

The derivation and validation cohorts included 989,732 and 494,865 women and 946,784 and 473,392 men respectively. Overall discrimination of CRISK and CRISK-CCI were excellent and similar to QRISK3 (for women, C-statistic = 0.863/0.864/0.863 respectively; for men 0.833/0.819/0.832 respectively). CRISK and CRISK-CCI calibration overall and in younger people was excellent. CRISK over-predicted in older and multimorbid people although performed better than QRISK3, whilst CRISK-CCI performed the best. The proportion of people reclassified by CRISK-CCI varied by QRISK3 risk score category, with 0.7-9.7% of women and 2.8-25.2% of men reclassified as higher risk and 21.0-69.1% of women and 27.1-57.4% of men reclassified as lower risk. Overall, CRISK-CCI recommended fewer people for treatment and had a lower estimated NNT at 10% risk threshold. Patients reclassified as higher risk were younger, had lower SBP and higher BMI, and were more likely to smoke.

Conclusions

CRISK and CRISK-CCI performed better than QRISK3. CRISK-CCI recommends fewer people for treatment and has a lower NNT to prevent a new CVD event compared to QRISK3. Competing risk models should be recommended for CVD primary prevention treatment recommendations.",,pdf:https://bmcmedicine.biomedcentral.com/track/pdf/10.1186/s12916-022-02349-6; doi:https://doi.org/10.1186/s12916-022-02349-6; html:https://europepmc.org/articles/PMC9066924; pdf:https://europepmc.org/articles/PMC9066924?pdf=render 38576109,https://doi.org/10.1111/nbu.12670,The double burden of malnutrition in individuals: Identifying key challenges and re-thinking research focus.,"Kiosia A, Dagbasi A, Berkley JA, Wilding JPH, Prendergast AJ, Li JV, Swann J, Mathers JC, Kerac M, Morrison D, Drake L, Briend A, Maitland K, Frost G.",,Nutrition bulletin,2024,2024-04-04,N,Obesity; Children; Adults; Undernutrition; Double Burden Of Malnutrition; Low To Middle‐income Countries,,,"The 'double burden of malnutrition' is a global health challenge that increasingly affects populations in both low- and middle-income countries (LMICs). This phenomenon refers to the coexistence of undernutrition and overweight or obesity, as well as other diet-related non-communicable diseases, in the same population, household or even individual. While noteworthy progress has been made in reducing undernutrition in some parts of the world, in many of these areas, the prevalence of overweight and obesity is increasing, particularly in urban areas, resulting in greater numbers of people who were undernourished in childhood and have overweight or obesity in adulthood. This creates a complex and challenging situation for research experts and policymakers who must simultaneously address the public health burdens of undernutrition and overweight/obesity. This review identifies key challenges and limitations in the current research on the double burden of malnutrition in individuals, including the need for a more comprehensive and nuanced understanding of the drivers of malnutrition, the importance of context-specific interventions and the need for greater attention to the food environment and food systems. We advocate for the re-evaluation of research strategies and focus, with a greater emphasis on multidisciplinary and systems approaches and greater attention to the synergistic relationship between the biological, environmental, commercial and socio-economic determinants of malnutrition. Addressing these key challenges can enable us to better comprehend and tackle the multifaceted and dynamic issues of the double burden of malnutrition, particularly in individuals and work towards more effective and sustainable solutions.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/nbu.12670; doi:https://doi.org/10.1111/nbu.12670 38834334,https://doi.org/10.1136/bmjdrc-2024-004191,"Identifying subtypes of type 2 diabetes mellitus with machine learning: development, internal validation, prognostic validation and medication burden in linked electronic health records in 420 448 individuals.","Mizani MA, Dashtban A, Pasea L, Zeng Q, Khunti K, Valabhji J, Mamza JB, Gao H, Morris T, Banerjee A.",,BMJ open diabetes research & care,2024,2024-06-04,N,"Diabetes mellitus, type 2; epidemiology; Informatics; Electronic Health Records",,,"

Introduction

None of the studies of type 2 diabetes (T2D) subtyping to date have used linked population-level data for incident and prevalent T2D, incorporating a diverse set of variables, explainable methods for cluster characterization, or adhered to an established framework. We aimed to develop and validate machine learning (ML)-informed subtypes for type 2 diabetes mellitus (T2D) using nationally representative data.

Research design and methods

In population-based electronic health records (2006-2020; Clinical Practice Research Datalink) in individuals ≥18 years with incident T2D (n=420 448), we included factors (n=3787), including demography, history, examination, biomarkers and medications. Using a published framework, we identified subtypes through nine unsupervised ML methods (K-means, K-means++, K-mode, K-prototype, mini-batch, agglomerative hierarchical clustering, Birch, Gaussian mixture models, and consensus clustering). We characterized clusters using intracluster distributions and explainable artificial intelligence (AI) techniques. We evaluated subtypes for (1) internal validity (within dataset; across methods); (2) prognostic validity (prediction for 5-year all-cause mortality, hospitalization and new chronic diseases); and (3) medication burden.

Results

Development: We identified four T2D subtypes: metabolic, early onset, late onset and cardiometabolic. Internal validity: Subtypes were predicted with high accuracy (F1 score >0.98). Prognostic validity: 5-year all-cause mortality, hospitalization, new chronic disease incidence and medication burden differed across T2D subtypes. Compared with the metabolic subtype, 5-year risks of mortality and hospitalization in incident T2D were highest in late-onset subtype (HR 1.95, 1.85-2.05 and 1.66, 1.58-1.75) and lowest in early-onset subtype (1.18, 1.11-1.27 and 0.85, 0.80-0.90). Incidence of chronic diseases was highest in late-onset subtype and lowest in early-onset subtype. Medications: Compared with the metabolic subtype, after adjusting for age, sex, and pre-T2D medications, late-onset subtype (1.31, 1.28-1.35) and early-onset subtype (0.83, 0.81-0.85) were most and least likely, respectively, to be prescribed medications within 5 years following T2D onset.

Conclusions

In the largest study using ML to date in incident T2D, we identified four distinct subtypes, with potential future implications for etiology, therapeutics, and risk prediction.",,doi:https://doi.org/10.1136/bmjdrc-2024-004191; doi:https://doi.org/10.1136/bmjdrc-2024-004191 -37144149,https://doi.org/10.3389/fped.2023.1148975,The psychosocial impact of microtia and ear reconstruction: A national data-linkage study.,"Jovic TH, Gibson JAG, Jovic M, Dobbs TD, Griffiths R, Akbari A, Whitaker IS.",,Frontiers in pediatrics,2023,2023-04-18,Y,Depression; Anxiety; Education; Microtia; Data Science,,,"

Introduction

Children with visible facial differences are believed to be at increased risk of negative psychosocial behaviours which may manifest as affective disorders. The aim of this study was to determine whether a diagnosis of microtia, and the associated surgical intervention, is associated with psychosocial implications including impaired educational attainment and a diagnosis of an affective disorder.

Methods

A retrospective case-control study was conducted using data linkage to identify patients in Wales with a diagnosis of microtia. Matched controls were sought on the basis of age, gender and socioeconomic deprivation status to yield a total sample size of 709. incidence was calculated using annual and geographic birth rates. Surgical operation codes were used to classify patients into those that had no surgery, autologous reconstruction or prosthetic reconstruction. Educational attainment at 11 years of age, plus a diagnosis of depression or anxiety were used as markers of adverse psychosocial outcomes and the relative risk was attained using logistic regression analyses.

Results

There were no significant associations between a diagnosis of microtia and an increased risk of adverse educational attainment or a risk of an affective disorder diagnosis. Male gender and higher deprivation scores were significantly associated with poorer educational attainment, irrespective of a diagnosis of microtia. Surgical intervention of any nature was also not associated with any increased risk of adverse educational or psychosocial outcomes in microtia patients.

Discussion

Microtia patients in Wales do not appear to be at greater risk of developing affective disorders or impaired academic performance as a result of their diagnosis or associated surgical intervention. Whilst reassuring, the need for appropriate support mechanisms to maintain positive psychosocial wellbeing and academic achievement in this patient cohort is reinforced.",,pdf:https://www.frontiersin.org/articles/10.3389/fped.2023.1148975/pdf; doi:https://doi.org/10.3389/fped.2023.1148975; html:https://europepmc.org/articles/PMC10152550; pdf:https://europepmc.org/articles/PMC10152550?pdf=render 32180562,https://doi.org/10.1016/j.molmet.2020.01.009,Genome-wide association study of adipocyte lipolysis in the GENetics of adipocyte lipolysis (GENiAL) cohort.,"Kulyté A, Lundbäck V, Lindgren CM, Luan J, Lotta LA, Langenberg C, Arner P, Strawbridge RJ, Dahlman I.",,Molecular metabolism,2020,2020-01-25,Y,Adipocytes; Gene Expression; Subcutaneous; Genetic Variants; Lipolysis,The Human Phenome,,"

Objectives

Lipolysis, hydrolysis of triglycerides to fatty acids in adipocytes, is tightly regulated, poorly understood, and, if perturbed, can lead to metabolic diseases including obesity and type 2 diabetes. The goal of this study was to identify the genetic regulators of lipolysis and elucidate their molecular mechanisms.

Methods

Adipocytes from abdominal subcutaneous adipose tissue biopsies were isolated and were incubated without (spontaneous lipolysis) or with a catecholamine (stimulated lipolysis) to analyze lipolysis. DNA was extracted and genome-wide genotyping and imputation conducted. After quality control, 939 samples with genetic and lipolysis data were available. Genome-wide association studies of spontaneous and stimulated lipolysis were conducted. Subsequent in vitro gene expression analyses were used to identify candidate genes and explore their regulation of adipose tissue biology.

Results

One locus on chromosome 19 demonstrated genome-wide significance with spontaneous lipolysis. 60 loci showed suggestive associations with spontaneous or stimulated lipolysis, of which many influenced both traits. In the chromosome 19 locus, only HIF3A was expressed in the adipocytes and displayed genotype-dependent gene expression. HIF3A knockdown in vitro increased lipolysis and the expression of key lipolysis-regulating genes.

Conclusions

In conclusion, we identified a genetic regulator of spontaneous lipolysis and provided evidence of HIF3A as a novel key regulator of lipolysis in subcutaneous adipocytes as the mechanism through which the locus influences adipose tissue biology.","How the body breaks down fat is poorly understood, and, if this mechanism does not happen effiently in the body it can lead to metabolic diseases including obesity and type 2 diabetes. The goal of this study was to identify the genetic regulators of how the body break down fat and explain their molecular mechanisms.",doi:https://doi.org/10.1016/j.molmet.2020.01.009; doi:https://doi.org/10.1016/j.molmet.2020.01.009; html:https://europepmc.org/articles/PMC7021539; pdf:https://europepmc.org/articles/PMC7021539?pdf=render +37144149,https://doi.org/10.3389/fped.2023.1148975,The psychosocial impact of microtia and ear reconstruction: A national data-linkage study.,"Jovic TH, Gibson JAG, Jovic M, Dobbs TD, Griffiths R, Akbari A, Whitaker IS.",,Frontiers in pediatrics,2023,2023-04-18,Y,Depression; Anxiety; Education; Microtia; Data Science,,,"

Introduction

Children with visible facial differences are believed to be at increased risk of negative psychosocial behaviours which may manifest as affective disorders. The aim of this study was to determine whether a diagnosis of microtia, and the associated surgical intervention, is associated with psychosocial implications including impaired educational attainment and a diagnosis of an affective disorder.

Methods

A retrospective case-control study was conducted using data linkage to identify patients in Wales with a diagnosis of microtia. Matched controls were sought on the basis of age, gender and socioeconomic deprivation status to yield a total sample size of 709. incidence was calculated using annual and geographic birth rates. Surgical operation codes were used to classify patients into those that had no surgery, autologous reconstruction or prosthetic reconstruction. Educational attainment at 11 years of age, plus a diagnosis of depression or anxiety were used as markers of adverse psychosocial outcomes and the relative risk was attained using logistic regression analyses.

Results

There were no significant associations between a diagnosis of microtia and an increased risk of adverse educational attainment or a risk of an affective disorder diagnosis. Male gender and higher deprivation scores were significantly associated with poorer educational attainment, irrespective of a diagnosis of microtia. Surgical intervention of any nature was also not associated with any increased risk of adverse educational or psychosocial outcomes in microtia patients.

Discussion

Microtia patients in Wales do not appear to be at greater risk of developing affective disorders or impaired academic performance as a result of their diagnosis or associated surgical intervention. Whilst reassuring, the need for appropriate support mechanisms to maintain positive psychosocial wellbeing and academic achievement in this patient cohort is reinforced.",,pdf:https://www.frontiersin.org/articles/10.3389/fped.2023.1148975/pdf; doi:https://doi.org/10.3389/fped.2023.1148975; html:https://europepmc.org/articles/PMC10152550; pdf:https://europepmc.org/articles/PMC10152550?pdf=render 33842409,https://doi.org/10.3389/fped.2021.630036,Microtia: A Data Linkage Study of Epidemiology and Implications for Service Delivery.,"Jovic TH, Gibson JAG, Griffiths R, Dobbs TD, Akbari A, Wilson-Jones N, Costello R, Evans P, Cooper M, Key S, Lyons R, Whitaker IS.",,Frontiers in pediatrics,2021,2021-03-26,Y,epidemiology; congenital; Otology; Reconstructive Surgery; Microtia,,,"Introduction: Previous studies of microtia epidemiology globally have demonstrated significant geographical and ethnic variation, cited broadly as affecting 3-5 in 10,000 live births. The aim of this study was to determine the incidence of microtia in a largely homogeneous ethnic population in the United Kingdom (Wales) and to identify factors, such as distance and socioeconomic status, which may influence the access to surgical intervention. Materials and Methods: A retrospective cohort study was conducted using data linkage to identify patients born between 2000 and 2018 with a diagnosis of microtia. Microtia incidence was calculated using annual and geographic birth rates. Surgical operation codes were used to classify patients into those that had no surgery, autologous reconstruction or prosthetic reconstruction. Sociodemographic attributes were compared using descriptive statistics to determine differences in access to each type of surgical intervention. Results: A total of 101 patients were identified, 64.4% were male and the median age was 12 (8-16). The mean annual incidence was 2.13 microtia cases per 10,000 births over the 19-year study period. Both temporal and geographic variation was noted. The majority of patients undergoing surgery opted for autologous reconstruction (72.9%) at a median age of 9 (7-10) compared to 7 (5-8) for prosthetic reconstruction. Autologous reconstruction had a higher median number of surgeries (2, 1-3) than prosthetic (1.5, 1-2) and a higher median socioeconomic status of 3 (2-4) compared to 2 (1-4) for the prosthetic cohort. There were no statistically significant differences in the distance traveled for surgery. Discussion: This study highlights a role for data linkage in epidemiological analyses and provides a revised incidence of microtia in Wales. Although the majority of patients opted for autologous reconstruction, demographic disparities in socioeconomic status warrant further investigation, emphasizing the importance of striving for equity in accessibility to surgical intervention.",,pdf:https://www.frontiersin.org/articles/10.3389/fped.2021.630036/pdf; doi:https://doi.org/10.3389/fped.2021.630036; html:https://europepmc.org/articles/PMC8033003; pdf:https://europepmc.org/articles/PMC8033003?pdf=render 34632260,https://doi.org/10.1093/rap/rkab042,"Biologic use in psoriatic arthritis and ankylosing spondylitis patients: a descriptive epidemiological study using linked, routine data in Wales, UK.","Cooksey R, Rahman MA, Kennedy J, Brophy S, Choy E.",,Rheumatology advances in practice,2021,2021-06-27,Y,Ankylosing spondylitis; Psoriatic Arthritis; Outcomes; Biologics; Electronic Health Records; Treatment Pathways,,,"

Objectives

PsA and AS are chronic diseases associated with significant morbidities. National and international management guidelines include treatment with biologic therapies to improve outcomes and quality of life. There are limited real-world data on the patients' journey from symptom onset to diagnosis and treatment in the UK. We use real-life, linked health data to explore patient pathways and the impact of biologics on patient outcomes.

Methods

Data from the Secure Anonymised Information Linkage databank in Wales were used to assess diagnosis and treatment of patients ≥18 years of age with at least one International Classification of Diseases, Tenth Revision code present for PsA/AS in rheumatology clinic data and at least one Read code present in primary care records. We investigated the use of biologics while exploring demographics, comorbidities and surgical procedures of 641 AS patients and 1312 PsA patients.

Results

AS patients were significantly younger at diagnosis and were predominantly male. The average time from presenting symptoms to diagnosis of AS and PsA was 7.9 (s.d. 5.5) and 9.3 (s.d. 5.5) years, respectively. The proportion of patients receiving biologic treatment was significantly higher in AS (46%) compared with PsA patients (28.8%); of these, 23.1% of AS and 22.2% of PsA patients stopped/switched a biologic. There was a significant reduction in primary care involvement, sick notes and disability living allowance for both AS and PsA patients following biologic initiation.

Conclusion

This real-world descriptive study confirms that patients treated with biologics have reduced disability and time off work despite being initiated ∼13 years after the first symptoms and 6 years after diagnosis.",,pdf:https://academic.oup.com/rheumap/article-pdf/5/2/rkab042/39307450/rkab042.pdf; doi:https://doi.org/10.1093/rap/rkab042; html:https://europepmc.org/articles/PMC8496109; pdf:https://europepmc.org/articles/PMC8496109?pdf=render 35291009,https://doi.org/10.1093/ageing/afac072,Intensity of COVID-19 in care homes following hospital discharge in the early stages of the UK epidemic.,"Hollinghurst J, North L, Emmerson C, Akbari A, Torabi F, Williams C, Lyons RA, Hawkes AG, Bennett E, Gravenor MB, Fry R.",,Age and ageing,2022,2022-05-01,Y,Older People; Care Homes; Hospital Discharge; Linked Data; Hawkes Process; Multi-level Model; Covid-19,,,"

Background

defining features of the COVID-19 pandemic in many countries were the tragic extent to which care home residents were affected and the difficulty in preventing the introduction and subsequent spread of infection. Management of risk in care homes requires good evidence on the most important transmission pathways. One hypothesised route at the start of the pandemic, prior to widespread testing, was the transfer of patients from hospitals that were experiencing high levels of nosocomial events.

Methods

we tested the hypothesis that hospital discharge events increased the intensity of care home cases using a national individually linked health record cohort in Wales, UK. We monitored 186,772 hospital discharge events over the period from March to July 2020, tracking individuals to 923 care homes and recording the daily case rate in the homes populated by 15,772 residents. We estimated the risk of an increase in case rates following exposure to a hospital discharge using multi-level hierarchical logistic regression and a novel stochastic Hawkes process outbreak model.

Findings

in regression analysis, after adjusting for care home size, we found no significant association between hospital discharge and subsequent increases in care home case numbers (odds ratio: 0.99, 95% CI: 0.82, 1.90). Risk factors for increased cases included care home size, care home resident density and provision of nursing care. Using our outbreak model, we found a significant effect of hospital discharge on the subsequent intensity of cases. However, the effect was small and considerably less than the effect of care home size, suggesting the highest risk of introduction came from interaction with the community. We estimated that approximately 1.8% of hospital discharged patients may have been infected.

Interpretation

there is growing evidence in the UK that the risk of transfer of COVID-19 from the high-risk hospital setting to the high-risk care home setting during the early stages of the pandemic was relatively small. Although access to testing was limited to initial symptomatic cases in each care home at this time, our results suggest that reduced numbers of discharges, selection of patients and action taken within care homes following transfer all may have contributed to the mitigation. The precise key transmission routes from the community remain to be quantified.",,pdf:https://academic.oup.com/ageing/article-pdf/51/5/afac072/43616755/afac072.pdf; doi:https://doi.org/10.1093/ageing/afac072; html:https://europepmc.org/articles/PMC8992303; pdf:https://europepmc.org/articles/PMC8992303?pdf=render @@ -564,8 +564,8 @@ PMC10910267,https://doi.org/,Development and evaluation of a tool to optimise in 37658166,https://doi.org/10.1007/s00392-023-02295-0,Efficacy and safety of intravenous beta-blockers in acute atrial fibrillation and flutter is dependent on beta-1 selectivity: a systematic review and meta-analysis of randomised trials.,"Perrett M, Gohil N, Tica O, Bunting KV, Kotecha D.",,Clinical research in cardiology : official journal of the German Cardiac Society,2024,2023-09-01,Y,Meta-analysis; Atrial fibrillation; Acute; Atrial flutter; Systematic review; Beta-blockers,,,"

Background

Intravenous beta-blockers are commonly used to manage patients with acute atrial fibrillation (AF) and atrial flutter (AFl), but the choice of specific agent is often not evidence-based.

Methods

A prospectively-registered systematic review and meta-analysis of randomised trials (PROSPERO: CRD42020204772) to compare the safety and efficacy of intravenous beta-blockers against alternative pharmacological agents.

Results

Twelve trials comparing beta-blockers with diltiazem, digoxin, verapamil, anti-arrhythmic drugs and placebo were included, with variable risk of bias and 1152 participants. With high heterogeneity (I2 = 87%; p < 0.001), there was no difference in the primary outcomes of heart rate reduction (standardised mean difference - 0.65 beats/minute compared to control, 95% CI - 1.63 to 0.32; p = 0.19) or the proportion that achieved target heart rate (risk ratio [RR] 0.85, 95% CI 0.36-1.97; p = 0.70). Conventional selective beta-1 blockers were inferior for target heart rate reduction versus control (RR 0.33, 0.17-0.64; p < 0.001), whereas super-selective beta-1 blockers were superior (RR 1.98, 1.54-2.54; p < 0.001). There was no significant difference between beta-blockers and comparators for secondary outcomes of conversion to sinus rhythm (RR 1.15, 0.90-1.46; p = 0.28), hypotension (RR 1.85, 0.87-3.93; p = 0.11), bradycardia (RR 1.29, 0.25-6.82; p = 0.76) or adverse events leading to drug discontinuation (RR 1.03, 0.49-2.17; p = 0.93). The incidence of hypotension and bradycardia were greater with non-selective beta-blockers (p = 0.031 and p < 0.001).

Conclusions

Across all intravenous beta-blockers, there was no difference with other medications for acute heart rate control in atrial fibrillation and flutter. Efficacy and safety may be improved by choosing beta-blockers with higher beta-1 selectivity.",,doi:https://doi.org/10.1007/s00392-023-02295-0; html:https://europepmc.org/articles/PMC11108934; pdf:https://europepmc.org/articles/PMC11108934?pdf=render 38254067,https://doi.org/10.1186/s12916-023-03187-w,NHS Health Check attendance is associated with reduced multiorgan disease risk: a matched cohort study in the UK Biobank.,"McCracken C, Raisi-Estabragh Z, Szabo L, Robson J, Raman B, Topiwala A, Roca-Fernández A, Husain M, Petersen SE, Neubauer S, Nichols TE.",,BMC medicine,2024,2024-01-23,Y,Public Health; Preventive Medicine; Primary Care; General Medicine; Nhs Health Check,,,"

Background

The NHS Health Check is a preventive programme in the UK designed to screen for cardiovascular risk and to aid in primary disease prevention. Despite its widespread implementation, the effectiveness of the NHS Health Check for longer-term disease prevention is unclear. In this study, we measured the rate of new diagnoses in UK Biobank participants who underwent the NHS Health Check compared with those who did not.

Methods

Within the UK Biobank prospective study, 48,602 NHS Health Check recipients were identified from linked primary care records. These participants were then covariate-matched on an extensive range of socio-demographic, lifestyle, and medical factors with 48,602 participants without record of the check. Follow-up diagnoses were ascertained from health records over an average of 9 years (SD 2 years) including hypertension, diabetes, hypercholesterolaemia, stroke, dementia, myocardial infarction, atrial fibrillation, heart failure, fatty liver disease, alcoholic liver disease, liver cirrhosis, liver failure, acute kidney injury, chronic kidney disease (stage 3 +), cardiovascular mortality, and all-cause mortality. Time-varying survival modelling was used to compare adjusted outcome rates between the groups.

Results

In the immediate 2 years after the NHS Health Check, higher diagnosis rates were observed for hypertension, high cholesterol, and chronic kidney disease among health check recipients compared to their matched counterparts. However, in the longer term, NHS Health Check recipients had significantly lower risk across all multiorgan disease outcomes and reduced rates of cardiovascular and all-cause mortality.

Conclusions

The NHS Health Check is linked to reduced incidence of disease across multiple organ systems, which may be attributed to risk modification through earlier detection and treatment of key risk factors such as hypertension and high cholesterol. This work adds important evidence to the growing body of research supporting the effectiveness of preventative interventions in reducing longer-term multimorbidity.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-023-03187-w; doi:https://doi.org/10.1186/s12916-023-03187-w; html:https://europepmc.org/articles/PMC10804500; pdf:https://europepmc.org/articles/PMC10804500?pdf=render 35581158,https://doi.org/10.1093/ageing/afac098,Patterns of unplanned hospital admissions among people with dementia: from diagnosis to the end of life.,"Yorganci E, Stewart R, Sampson EL, Sleeman KE.",,Age and ageing,2022,2022-05-01,Y,Retrospective studies; Dementia; incidence; Older People; Hospitalisation,,,"

Background

hospitalisations are sentinel events for people with dementia. How patterns of unplanned hospital admissions change among people with dementia after diagnosis is relatively unknown.

Objective

to describe patterns of unplanned hospital admissions of people with dementia from diagnosis until death/study end.

Methods

retrospective cohort study using mental healthcare provider data of people diagnosed with dementia in London, UK (1995-2017), linked to mortality and hospital data. The primary outcome was the rate of unplanned hospital admissions after diagnosis until death/study end. We calculated the cumulative incidence of unplanned hospital admissions. The rates of unplanned hospital admissions and the percentage of time spent as an inpatient were stratified by time from first dementia diagnosis.

Results

for 19,221 people with dementia (61.4% female, mean age at diagnosis 81.0 years (standard deviation, SD 8.5)), the cumulative incidence of unplanned hospital admissions (n = 14,759) was 76.8% (95% CI 76.3%-77.3%). Individuals remained in the study for mean 3.0 (SD 2.6) years, and 12,667 (65.9%) died. Rates and lengths of unplanned hospital admissions remained relatively low and short in the months after the dementia diagnosis, increasing only as people approached the end of life. Percentage of time spent as an inpatient was <3% for people who were alive at the study end but was on average 19.6 and 13.3% for the decedents in the last 6 and 12 months of life, respectively.

Conclusions

the steep rise in hospitalisations before death highlights the need for improved community care and services for people with dementia who are approaching the end of life.",,pdf:https://discovery.ucl.ac.uk/10149895/1/afac098.pdf; doi:https://doi.org/10.1093/ageing/afac098; html:https://europepmc.org/articles/PMC9113942; pdf:https://europepmc.org/articles/PMC9113942?pdf=render -38429012,https://doi.org/10.1016/s2468-2667(24)00025-2,Social and spatial inequalities in premature mortality across Europe.,"Bragg F, Lacey B.",,The Lancet. Public health,2024,2024-03-01,N,,,,,,doi:https://doi.org/10.1016/S2468-2667(24)00025-2 34183342,https://doi.org/10.1136/bmjopen-2020-046392,"United Kingdom Research study into Ethnicity And COVID-19 outcomes in Healthcare workers (UK-REACH): a retrospective cohort study using linked routinely collected data, study protocol.","Teece L, Gray LJ, Melbourne C, Orton C, Ford DV, Martin CA, McAllister D, Khunti K, Tobin M, John C, Abrams KR, Pareek M, UK-REACH Study Collaborative Group.",,BMJ open,2021,2021-06-28,Y,epidemiology; Public Health; Adult Intensive & Critical Care; Covid-19,,,"

Introduction

COVID-19 has spread rapidly worldwide, causing significant morbidity and mortality. People from ethnic minorities, particularly those working in healthcare settings, have been disproportionately affected. Current evidence of the association between ethnicity and COVID-19 outcomes in people working in healthcare settings is insufficient to inform plans to address health inequalities.

Methods and analysis

This study combines anonymised human resource databases with professional registration and National Health Service data sets to assess associations between ethnicity and COVID-19 diagnosis, hospitalisation and death in healthcare workers in the UK. Adverse COVID-19 outcomes will be assessed between 1 February 2020 (date following first confirmed COVID-19 case in UK) and study end date (31 January 2021), allowing 1-year of follow-up. Planned analyses include multivariable Poisson, logistic and flexible parametric time-to-event regression within each country, adjusting for core predictors, followed by meta-analysis of country-specific results to produce combined effect estimates for the UK. Mediation analysis methods will be explored to examine the direct, indirect and mediated interactive effects between ethnicity, occupational group and COVID-19 outcomes.

Ethics and dissemination

Ethical approval for the UK-REACH programme has been obtained via the expedited HRA COVID-19 processes (REC ref: 20/HRA/4718, IRAS ID: 288316). Research information will be anonymised via the Secure Anonymised Information Linkage Databank before release to researchers. Study results will be submitted for publication in an open access peer-reviewed journal and made available on our dedicated website (https://uk-reach.org/).

Trial registration number

ISRCTN11811602.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/6/e046392.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-046392; html:https://europepmc.org/articles/PMC8245289; pdf:https://europepmc.org/articles/PMC8245289?pdf=render +38429012,https://doi.org/10.1016/s2468-2667(24)00025-2,Social and spatial inequalities in premature mortality across Europe.,"Bragg F, Lacey B.",,The Lancet. Public health,2024,2024-03-01,N,,,,,,doi:https://doi.org/10.1016/S2468-2667(24)00025-2 33182605,https://doi.org/10.3390/genes11111326,"Exploring the Role of Contactins across Psychological, Psychiatric and Cardiometabolic Traits within UK Biobank.","Morris J, Leung SSY, Bailey MES, Cullen B, Ferguson A, Graham N, Johnston KJA, Lyall DM, Lyall LM, Ward J, Smith DJ, Strawbridge RJ.",,Genes,2020,2020-11-10,Y,Hypertension; Genetic variation; Type 2 diabetes; Psychiatric disorders; Single Nucleotide Polymorphisms; Gene Expression; Uk Biobank; Contactins; Cardiometabolic Diseases,,,"Individuals with severe mental illness have an increased risk of cardiometabolic diseases compared to the general population. Shared risk factors and medication effects explain part of this excess risk; however, there is growing evidence to suggest that shared biology (including genetic variation) is likely to contribute to comorbidity between mental and physical illness. Contactins are a family of genes involved in development of the nervous system and implicated, though genome-wide association studies, in a wide range of psychological, psychiatric and cardiometabolic conditions. Contactins are plausible candidates for shared pathology between mental and physical health. We used data from UK Biobank to systematically assess how genetic variation in contactin genes was associated with a wide range of psychological, psychiatric and cardiometabolic conditions. We also investigated whether associations for cardiometabolic and psychological traits represented the same or distinct signals and how the genetic variation might influence the measured traits. We identified: A novel genetic association between variation in CNTN1 and current smoking; two independent signals in CNTN4 for BMI; and demonstrated that associations between CNTN5 and neuroticism were distinct from those between CNTN5 and blood pressure/HbA1c. There was no evidence that the contactin genes contributed to shared aetiology between physical and mental illness.",,pdf:https://www.mdpi.com/2073-4425/11/11/1326/pdf?version=1605520057; doi:https://doi.org/10.3390/genes11111326; html:https://europepmc.org/articles/PMC7697406; pdf:https://europepmc.org/articles/PMC7697406?pdf=render 36481043,https://doi.org/10.1016/s2468-1253(22)00389-2,Neutralising antibody potency against SARS-CoV-2 wild-type and omicron BA.1 and BA.4/5 variants in patients with inflammatory bowel disease treated with infliximab and vedolizumab after three doses of COVID-19 vaccine (CLARITY IBD): an analysis of a prospective multicentre cohort study.,"Liu Z, Le K, Zhou X, Alexander JL, Lin S, Bewshea C, Chanchlani N, Nice R, McDonald TJ, Lamb CA, Sebastian S, Kok K, Lees CW, Hart AL, Pollok RC, Boyton RJ, Altmann DM, Pollock KM, Goodhand JR, Kennedy NA, Ahmad T, Powell N, CLARITY study investigators.",,The lancet. Gastroenterology & hepatology,2023,2022-12-05,Y,,,,"

Background

Anti-TNF drugs, such as infliximab, are associated with attenuated antibody responses after SARS-CoV-2 vaccination. We aimed to determine how the anti-TNF drug infliximab and the anti-integrin drug vedolizumab affect vaccine-induced neutralising antibodies against highly transmissible omicron (B.1.1.529) BA.1, and BA.4 and BA.5 (hereafter BA.4/5) SARS-CoV-2 variants, which possess the ability to evade host immunity and, together with emerging sublineages, are now the dominating variants causing current waves of infection.

Methods

CLARITY IBD is a prospective, multicentre, observational cohort study investigating the effect of infliximab and vedolizumab on SARS-CoV-2 infection and vaccination in patients with inflammatory bowel disease (IBD). Patients aged 5 years and older with a diagnosis of IBD and being treated with infliximab or vedolizumab for 6 weeks or longer were recruited from infusion units at 92 hospitals in the UK. In this analysis, we included participants who had received uninterrupted biological therapy since recruitment and without a previous SARS-CoV-2 infection. The primary outcome was neutralising antibody responses against SARS-CoV-2 wild-type and omicron subvariants BA.1 and BA.4/5 after three doses of SARS-CoV-2 vaccine. We constructed Cox proportional hazards models to investigate the risk of breakthrough infection in relation to neutralising antibody titres. The study is registered with the ISRCTN registry, ISRCTN45176516, and is closed to accrual.

Findings

Between Sept 22 and Dec 23, 2020, 7224 patients with IBD were recruited to the CLARITY IBD study, of whom 1288 had no previous SARS-CoV-2 infection after three doses of SARS-CoV-2 vaccine and were established on either infliximab (n=871) or vedolizumab (n=417) and included in this study (median age was 46·1 years [IQR 33·6-58·2], 610 [47·4%] were female, 671 [52·1%] were male, 1209 [93·9%] were White, and 46 [3·6%] were Asian). After three doses of SARS-CoV-2 vaccine, 50% neutralising titres (NT50s) were significantly lower in patients treated with infliximab than in those treated with vedolizumab, against wild-type (geometric mean 2062 [95% CI 1720-2473] vs 3440 [2939-4026]; p<0·0001), BA.1 (107·3 [86·40-133·2] vs 648·9 [523·5-804·5]; p<0·0001), and BA.4/5 (40·63 [31·99-51·60] vs 223·0 [183·1-271·4]; p<0·0001) variants. Breakthrough infection was significantly more frequent in patients treated with infliximab (119 [13·7%; 95% CI 11·5-16·2] of 871) than in those treated with vedolizumab (29 [7·0% [4·8-10·0] of 417; p=0·00040). Cox proportional hazards models of time to breakthrough infection after the third dose of vaccine showed infliximab treatment to be associated with a higher hazard risk than treatment with vedolizumab (hazard ratio [HR] 1·71 [95% CI 1·08-2·71]; p=0·022). Among participants who had a breakthrough infection, we found that higher neutralising antibody titres against BA.4/5 were associated with a lower hazard risk and, hence, a longer time to breakthrough infection (HR 0·87 [0·79-0·95]; p=0·0028).

Interpretation

Our findings underline the importance of continued SARS-CoV-2 vaccination programmes, including second-generation bivalent vaccines, especially in patient subgroups where vaccine immunogenicity and efficacy might be reduced, such as those on anti-TNF therapies.

Funding

Royal Devon University Healthcare NHS Foundation Trust; Hull University Teaching Hospital NHS Trust; NIHR Imperial Biomedical Research Centre; Crohn's and Colitis UK; Guts UK; National Core Studies Immunity Programme, UK Research and Innovation; and unrestricted educational grants from F Hoffmann-La Roche, Biogen, Celltrion Healthcare, Takeda, and Galapagos.",,doi:https://doi.org/10.1016/s2468-1253(22)00389-2; doi:https://doi.org/10.1016/S2468-1253(22)00389-2; html:https://europepmc.org/articles/PMC9757903; pdf:https://europepmc.org/articles/PMC9757903?pdf=render 34145260,https://doi.org/10.1038/s41467-021-23935-x,Community factors and excess mortality in first wave of the COVID-19 pandemic in England.,"Davies B, Parkes BL, Bennett J, Fecht D, Blangiardo M, Ezzati M, Elliott P.",,Nature communications,2021,2021-06-18,Y,,,,"Risk factors for increased risk of death from COVID-19 have been identified, but less is known on characteristics that make communities resilient or vulnerable to the mortality impacts of the pandemic. We applied a two-stage Bayesian spatial model to quantify inequalities in excess mortality in people aged 40 years and older at the community level during the first wave of the pandemic in England, March-May 2020 compared with 2015-2019. Here we show that communities with an increased risk of excess mortality had a high density of care homes, and/or high proportion of residents on income support, living in overcrowded homes and/or with a non-white ethnicity. We found no association between population density or air pollution and excess mortality. Effective and timely public health and healthcare measures that target the communities at greatest risk are urgently needed to avoid further widening of inequalities in mortality patterns as the pandemic progresses.",,pdf:https://www.nature.com/articles/s41467-021-23935-x.pdf; doi:https://doi.org/10.1038/s41467-021-23935-x; html:https://europepmc.org/articles/PMC8213785; pdf:https://europepmc.org/articles/PMC8213785?pdf=render @@ -590,8 +590,8 @@ PMC10910267,https://doi.org/,Development and evaluation of a tool to optimise in 37203546,https://doi.org/10.3233/shti230319,On the Difficulty of Predicting Engagement with Digital Health for Substance Use.,"Günther F, Yau C, Elison-Davies S, Wong D.",,Studies in health technology and informatics,2023,2023-05-01,N,Prediction; Engagement; Substance Use; Digital Health,,,"Digital interventions can be an important instrument in treating substance use disorder. However, most digital mental health interventions suffer from early, frequent user dropout. Early prediction of engagement would allow identification of individuals whose engagement with digital interventions may be too limited to support behaviour change, and subsequently offering them support. To investigate this, we used machine learning models to predict different metrics of real-world engagement with a digital cognitive behavioural therapy intervention widely available in UK addiction services. Our predictor set consisted of baseline data from routinely-collected standardised psychometric measures. Areas under the ROC curve, and correlations between predicted and observed values indicated that baseline data do not contain sufficient information about individual patterns of engagement.",,pdf:https://ebooks.iospress.nl/pdf/doi/10.3233/SHTI230319; doi:https://doi.org/10.3233/SHTI230319 36036238,https://doi.org/10.1002/clt2.12180,Mixed-methods evaluation of a nurse-led allergy clinic model in primary care: Feasibility trial.,"Hammersley V, Kelman M, Morrice L, Kendall M, Mukerjhee M, Harley S, Schwarze J, Sheikh A.",,Clinical and translational allergy,2022,2022-08-01,Y,Allergy; Quality of life; Primary Care,,,"

Introduction

It is now widely acknowledged that there are serious shortcomings in allergy care provision for patients seen in primary care. We sought to assess the feasibility of delivering and evaluating a new nurse-led allergy service in primary care, measured by recruitment, retention and estimates of the potential impact of the intervention on disease-specific quality of life.

Methods

Mixed-methods evaluation of a nurse-led primary care-based allergy clinic in Edinburgh, UK undertaken during the period 2017-2021 with a focus on suspected food allergy and atopic eczema in young children, allergic rhinitis in children and young people, and suspected anaphylaxis in adults. Prior to March 2020, patients were seen face-to-face (Phase 1). Due to COVID-19 pandemic restrictions, recruitment was halted between March-August 2020, and a remote clinic was restarted in September 2020 (Phase 2). Disease-specific quality of life was measured at baseline and 6-12 weeks post intervention using validated instruments. Quantitative data were descriptively analysed. We undertook interviews with 16 carers/patients and nine healthcare professionals, which were thematically analysed.

Results

During Phase 1, 426/506 (84%) referred patients met the eligibility criteria; 40/46 (87%) of Phase 2 referrals were eligible. Males and females were recruited in approximately equal numbers. The majority (83%) of referrals were for possible food allergy or anaphylaxis. Complete data were available for 338/426 (79%) patients seen in Phase 1 and 30/40 (75%) in Phase 2. Compared with baseline assessments, there were improvements in disease-specific quality of life for most categories of patients. Patients/carers and healthcare professionals reported high levels of satisfaction, this being reinforced by the qualitative interviews in which convenience and speed of access to expert opinion, the quality of the consultation, and patient/care empowerment were particularly emphasised.

Conclusion

This large feasibility trial has demonstrated that it is possible to recruit, deliver and retain individuals into a nurse-led allergy clinic with both face-to-face and remote consultations. Our data indicate that the intervention was considered acceptable to patients/carers and healthcare professionals. The before-after data of disease-specific quality of life suggest that the intervention may prove effective, but this now needs to be confirmed through a formal randomised controlled trial.

Trial registration

ClinicalTrials.gov reference NCT03826953.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9362986; doi:https://doi.org/10.1002/clt2.12180; html:https://europepmc.org/articles/PMC9362986; pdf:https://europepmc.org/articles/PMC9362986?pdf=render 38735523,https://doi.org/10.1016/j.ejvs.2024.05.010,Challenges of Using Routinely Collected Healthcare System Data in Randomised Trials.,"Twine CP, Ahmed H, Lugg-Widger FV, Waldron CA, Bown MJ, Sydes MR.",,European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery,2024,2024-05-10,N,Diseases; Cohort; Analyses; Randomised Clinical Trials; Peripheral Arterial; Clinical Research Methodology,,,,,doi:https://doi.org/10.1016/j.ejvs.2024.05.010 -38505485,https://doi.org/10.1093/ehjdh/ztae001,Explainable machine learning using echocardiography to improve risk prediction in patients with chronic coronary syndrome.,"Molenaar MA, Bouma BJ, Asselbergs FW, Verouden NJ, Selder JL, Chamuleau SAJ, Schuuring MJ.",,European heart journal. Digital health,2024,2024-01-22,Y,Artificial intelligence; Mortality; Prognosis; coronary artery disease; risk; Machine Learning,,,"

Aims

The European Society of Cardiology guidelines recommend risk stratification with limited clinical parameters such as left ventricular (LV) function in patients with chronic coronary syndrome (CCS). Machine learning (ML) methods enable an analysis of complex datasets including transthoracic echocardiography (TTE) studies. We aimed to evaluate the accuracy of ML using clinical and TTE data to predict all-cause 5-year mortality in patients with CCS and to compare its performance with traditional risk stratification scores.

Methods and results

Data of consecutive patients with CCS were retrospectively collected if they attended the outpatient clinic of Amsterdam UMC location AMC between 2015 and 2017 and had a TTE assessment of the LV function. An eXtreme Gradient Boosting (XGBoost) model was trained to predict all-cause 5-year mortality. The performance of this ML model was evaluated using data from the Amsterdam UMC location VUmc and compared with the reference standard of traditional risk scores. A total of 1253 patients (775 training set and 478 testing set) were included, of which 176 patients (105 training set and 71 testing set) died during the 5-year follow-up period. The ML model demonstrated a superior performance [area under the receiver operating characteristic curve (AUC) 0.79] compared with traditional risk stratification tools (AUC 0.62-0.76) and showed good external performance. The most important TTE risk predictors included in the ML model were LV dysfunction and significant tricuspid regurgitation.

Conclusion

This study demonstrates that an explainable ML model using TTE and clinical data can accurately identify high-risk CCS patients, with a prognostic value superior to traditional risk scores.",,doi:https://doi.org/10.1093/ehjdh/ztae001; html:https://europepmc.org/articles/PMC10944683; pdf:https://europepmc.org/articles/PMC10944683?pdf=render 33419870,https://doi.org/10.1136/bmjhci-2020-100254,Network graph representation of COVID-19 scientific publications to aid knowledge discovery.,"Cernile G, Heritage T, Sebire NJ, Gordon B, Schwering T, Kazemlou S, Borecki Y.",,BMJ health & care informatics,2021,2021-01-01,Y,Health care; Medical Informatics; Information Science; Bmj Health Informatics,,,"

Introduction

Numerous scientific journal articles related to COVID-19 have been rapidly published, making navigation and understanding of relationships difficult.

Methods

A graph network was constructed from the publicly available COVID-19 Open Research Dataset (CORD-19) of COVID-19-related publications using an engine leveraging medical knowledge bases to identify discrete medical concepts and an open-source tool (Gephi) to visualise the network.

Results

The network shows connections between diseases, medications and procedures identified from the title and abstract of 195 958 COVID-19-related publications (CORD-19 Dataset). Connections between terms with few publications, those unconnected to the main network and those irrelevant were not displayed. Nodes were coloured by knowledge base and the size of the node related to the number of publications containing the term. The data set and visualisations were made publicly accessible via a webtool.

Conclusion

Knowledge management approaches (text mining and graph networks) can effectively allow rapid navigation and exploration of entity inter-relationships to improve understanding of diseases such as COVID-19.",,pdf:https://informatics.bmj.com/content/bmjhci/28/1/e100254.full.pdf; doi:https://doi.org/10.1136/bmjhci-2020-100254; html:https://europepmc.org/articles/PMC7798427; pdf:https://europepmc.org/articles/PMC7798427?pdf=render +38505485,https://doi.org/10.1093/ehjdh/ztae001,Explainable machine learning using echocardiography to improve risk prediction in patients with chronic coronary syndrome.,"Molenaar MA, Bouma BJ, Asselbergs FW, Verouden NJ, Selder JL, Chamuleau SAJ, Schuuring MJ.",,European heart journal. Digital health,2024,2024-01-22,Y,Artificial intelligence; Mortality; Prognosis; coronary artery disease; risk; Machine Learning,,,"

Aims

The European Society of Cardiology guidelines recommend risk stratification with limited clinical parameters such as left ventricular (LV) function in patients with chronic coronary syndrome (CCS). Machine learning (ML) methods enable an analysis of complex datasets including transthoracic echocardiography (TTE) studies. We aimed to evaluate the accuracy of ML using clinical and TTE data to predict all-cause 5-year mortality in patients with CCS and to compare its performance with traditional risk stratification scores.

Methods and results

Data of consecutive patients with CCS were retrospectively collected if they attended the outpatient clinic of Amsterdam UMC location AMC between 2015 and 2017 and had a TTE assessment of the LV function. An eXtreme Gradient Boosting (XGBoost) model was trained to predict all-cause 5-year mortality. The performance of this ML model was evaluated using data from the Amsterdam UMC location VUmc and compared with the reference standard of traditional risk scores. A total of 1253 patients (775 training set and 478 testing set) were included, of which 176 patients (105 training set and 71 testing set) died during the 5-year follow-up period. The ML model demonstrated a superior performance [area under the receiver operating characteristic curve (AUC) 0.79] compared with traditional risk stratification tools (AUC 0.62-0.76) and showed good external performance. The most important TTE risk predictors included in the ML model were LV dysfunction and significant tricuspid regurgitation.

Conclusion

This study demonstrates that an explainable ML model using TTE and clinical data can accurately identify high-risk CCS patients, with a prognostic value superior to traditional risk scores.",,doi:https://doi.org/10.1093/ehjdh/ztae001; html:https://europepmc.org/articles/PMC10944683; pdf:https://europepmc.org/articles/PMC10944683?pdf=render 29992526,https://doi.org/10.1007/s11906-018-0877-8,An Overview of Metabolic Phenotyping in Blood Pressure Research.,"Tzoulaki I, Iliou A, Mikros E, Elliott P.",,Current hypertension reports,2018,2018-07-10,Y,Hypertension; Blood pressure; Metabolomics; Microbiome; Epidemiological Studies; Metabolic Phenotyping,,,"

Purpose of the review

This review presents the analytical techniques, processing and analytical steps used in metabolomics phenotyping studies, as well as the main results from epidemiological studies on the associations between metabolites and high blood pressure.

Recent findings

A variety of metabolomic approaches have been applied to a range of epidemiological studies to uncover the pathophysiology of high blood pressure. Several pathways have been suggested in relation to blood pressure including the possible role of the gut microflora, inflammatory, oxidative stress, and lipid pathways. Metabolic changes have also been identified associated with blood pressure lowering effects of diets high in fruits and vegetables and low in meat intake. However, the current body of literature on metabolic profiling and blood pressure is still in its infancy, not fully consistent and requires careful interpretation. Metabolic phenotyping is a promising approach to uncover metabolic pathways associated with high blood pressure and throw light into the complex pathophysiology of hypertension.",,pdf:https://link.springer.com/content/pdf/10.1007%2Fs11906-018-0877-8.pdf; doi:https://doi.org/10.1007/s11906-018-0877-8; html:https://europepmc.org/articles/PMC6061189; pdf:https://europepmc.org/articles/PMC6061189?pdf=render 34489241,https://doi.org/10.1136/bjsports-2021-104050,Reallocation of time between device-measured movement behaviours and risk of incident cardiovascular disease.,"Walmsley R, Chan S, Smith-Byrne K, Ramakrishnan R, Woodward M, Rahimi K, Dwyer T, Bennett D, Doherty A.",,British journal of sports medicine,2021,2021-09-06,Y,Cardiovascular diseases; Sleep; Methods; Physical Activity; Sedentary Behavior,,,"

Objective

To improve classification of movement behaviours in free-living accelerometer data using machine-learning methods, and to investigate the association between machine-learned movement behaviours and risk of incident cardiovascular disease (CVD) in adults.

Methods

Using free-living data from 152 participants, we developed a machine-learning model to classify movement behaviours (moderate-to-vigorous physical activity behaviours (MVPA), light physical activity behaviours, sedentary behaviour, sleep) in wrist-worn accelerometer data. Participants in UK Biobank, a prospective cohort, were asked to wear an accelerometer for 7 days, and we applied our machine-learning model to classify their movement behaviours. Using compositional data analysis Cox regression, we investigated how reallocating time between movement behaviours was associated with CVD incidence.

Results

In leave-one-participant-out analysis, our machine-learning method classified free-living movement behaviours with mean accuracy 88% (95% CI 87% to 89%) and Cohen's kappa 0.80 (95% CI 0.79 to 0.82). Among 87 498 UK Biobank participants, there were 4105 incident CVD events. Reallocating time from any behaviour to MVPA, or reallocating time from sedentary behaviour to any behaviour, was associated with lower CVD risk. For an average individual, reallocating 20 min/day to MVPA from all other behaviours proportionally was associated with 9% (95% CI 7% to 10%) lower risk, while reallocating 1 hour/day to sedentary behaviour from all other behaviours proportionally was associated with 5% (95% CI 3% to 7%) higher risk.

Conclusion

Machine-learning methods classified movement behaviours accurately in free-living accelerometer data. Reallocating time from other behaviours to MVPA, and from sedentary behaviour to other behaviours, was associated with lower risk of incident CVD, and should be promoted by interventions and guidelines.",,pdf:https://bjsm.bmj.com/content/bjsports/early/2022/02/15/bjsports-2021-104050.full.pdf; doi:https://doi.org/10.1136/bjsports-2021-104050; html:https://europepmc.org/articles/PMC9484395; pdf:https://europepmc.org/articles/PMC9484395?pdf=render 33801002,https://doi.org/10.3390/s21062190,A Novel Coupled Reaction-Diffusion System for Explainable Gene Expression Profiling.,"Farouq MW, Boulila W, Hussain Z, Rashid A, Shah M, Hussain S, Ng N, Ng D, Hanif H, Shaikh MG, Sheikh A, Hussain A.",,"Sensors (Basel, Switzerland)",2021,2021-03-21,Y,Non-small cell lung cancer; Gene Expression; Diffusion Equation; Explainable Machine Learning; Coupled Reaction Pde,,,"Machine learning (ML)-based algorithms are playing an important role in cancer diagnosis and are increasingly being used to aid clinical decision-making. However, these commonly operate as 'black boxes' and it is unclear how decisions are derived. Recently, techniques have been applied to help us understand how specific ML models work and explain the rational for outputs. This study aims to determine why a given type of cancer has a certain phenotypic characteristic. Cancer results in cellular dysregulation and a thorough consideration of cancer regulators is required. This would increase our understanding of the nature of the disease and help discover more effective diagnostic, prognostic, and treatment methods for a variety of cancer types and stages. Our study proposes a novel explainable analysis of potential biomarkers denoting tumorigenesis in non-small cell lung cancer. A number of these biomarkers are known to appear following various treatment pathways. An enhanced analysis is enabled through a novel mathematical formulation for the regulators of mRNA, the regulators of ncRNA, and the coupled mRNA-ncRNA regulators. Temporal gene expression profiles are approximated in a two-dimensional spatial domain for the transition states before converging to the stationary state, using a system comprised of coupled-reaction partial differential equations. Simulation experiments demonstrate that the proposed mathematical gene-expression profile represents a best fit for the population abundance of these oncogenes. In future, our proposed solution can lead to the development of alternative interpretable approaches, through the application of ML models to discover unknown dynamics in gene regulatory systems.",,pdf:https://www.mdpi.com/1424-8220/21/6/2190/pdf?version=1616388230; doi:https://doi.org/10.3390/s21062190; html:https://europepmc.org/articles/PMC8003942; pdf:https://europepmc.org/articles/PMC8003942?pdf=render @@ -611,11 +611,11 @@ PMC9644982,https://doi.org/,Assessing the impacts of COVID-19 on Care Homes in W 36992264,https://doi.org/10.3390/vaccines11030680,"Determinants of Equity in Coverage of Measles-Containing Vaccines in Wales, UK, during the Elimination Era.","Perry M, Cottrell S, Gravenor MB, Griffiths L.",,Vaccines,2023,2023-03-17,Y,"Vaccination; Measles; Socioeconomic Factors; Immunisation; Mmr; Measles, Mumps And Rubella Vaccine",,,"In the context of the WHO's measles and rubella elimination targets and European Immunization Agenda 2030, this large cross-sectional study aimed to identify inequalities in measles vaccination coverage in Wales, UK. The vaccination status of individuals aged 2 to 25 years of age, alive and resident in Wales as of 31 August 2021, was ascertained through linkage of the National Community Child Health Database and primary care data. A series of predictor variables were derived from five national datasets and all analysis was carried out in the Secure Anonymised Information Linkage Databank at Swansea University. In these 648,895 individuals, coverage of the first dose of measles-containing vaccine (due at 12-13 months of age) was 97.1%, and coverage of the second dose (due at 3 years and 4 months) in 4 to 25-year-olds was 93.8%. In multivariable analysis, excluding 0.7% with known refusal, the strongest association with being unvaccinated was birth order (families with six or more children) and being born outside of the UK. Living in a deprived area, being eligible for free school meals, a lower level of maternal education, and having a recorded language other than English or Welsh were also associated with lower coverage. Some of these factors may also be associated with refusal. This knowledge can be used to target future interventions and prioritise areas for catch up in a time of limited resource.",,pdf:https://www.mdpi.com/2076-393X/11/3/680/pdf?version=1679031223; doi:https://doi.org/10.3390/vaccines11030680; html:https://europepmc.org/articles/PMC10057771; pdf:https://europepmc.org/articles/PMC10057771?pdf=render 34847950,https://doi.org/10.1186/s12916-021-02190-3,Models of COVID-19 vaccine prioritisation: a systematic literature search and narrative review.,"Saadi N, Chi YL, Ghosh S, Eggo RM, McCarthy CV, Quaife M, Dawa J, Jit M, Vassall A.",,BMC medicine,2021,2021-12-01,Y,"Covid-19, Vaccination, Mathematical Modelling",,,"

Background

How best to prioritise COVID-19 vaccination within and between countries has been a public health and an ethical challenge for decision-makers globally. We reviewed epidemiological and economic modelling evidence on population priority groups to minimise COVID-19 mortality, transmission, and morbidity outcomes.

Methods

We searched the National Institute of Health iSearch COVID-19 Portfolio (a database of peer-reviewed and pre-print articles), Econlit, the Centre for Economic Policy Research, and the National Bureau of Economic Research for mathematical modelling studies evaluating the impact of prioritising COVID-19 vaccination to population target groups. The first search was conducted on March 3, 2021, and an updated search on the LMIC literature was conducted from March 3, 2021, to September 24, 2021. We narratively synthesised the main study conclusions on prioritisation and the conditions under which the conclusions changed.

Results

The initial search identified 1820 studies and 36 studies met the inclusion criteria. The updated search on LMIC literature identified 7 more studies. 43 studies in total were narratively synthesised. 74% of studies described outcomes in high-income countries (single and multi-country). We found that for countries seeking to minimise deaths, prioritising vaccination of senior adults was the optimal strategy and for countries seeking to minimise cases the young were prioritised. There were several exceptions to the main conclusion, notably that reductions in deaths could be increased if groups at high risk of both transmission and death could be further identified. Findings were also sensitive to the level of vaccine coverage.

Conclusion

The evidence supports WHO SAGE recommendations on COVID-19 vaccine prioritisation. There is, however, an evidence gap on optimal prioritisation for low- and middle-income countries, studies that included an economic evaluation, and studies that explore prioritisation strategies if the aim is to reduce overall health burden including morbidity.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-021-02190-3; doi:https://doi.org/10.1186/s12916-021-02190-3; html:https://europepmc.org/articles/PMC8632563; pdf:https://europepmc.org/articles/PMC8632563?pdf=render 30928998,https://doi.org/10.4193/rhin18.237,Risk of mortality and cardiovascular events following macrolide prescription in chronic rhinosinusitis patients: a cohort study using linked primary care electronic health records.,"Williamson E, Denaxas S, Morris S, Clarke CS, Thomas M, Evans H, Direk K, Gonzalez-Izquierdo A, Little P, Lund V, Blackshaw H, Schilder A, Philpott C, Hopkins C, Carpenter J, Programme Team OBOTM.",,Rhinology,2019,2019-08-01,N,,,,"

Background

Macrolide antibiotics have demonstrated important anti-inflammatory and immunomodulatory properties in chronic rhinosinusitis (CRS) patients. However, reports of increased risks of cardiovascular events have led to safety concerns. We investigated the risk of all-cause and cardiac death, and cardiovascular outcomes, associated with macrolide use.

Methodology

Observational cohort (1997-2016) using linked data from the Clinical Practice Research Datalink, Hospital Episodes Statistics, and the Office for National Statistics. Patients aged 16-80 years with CRS prescribed a macrolide antibiotic or penicillin were included, comparing prescriptions for macrolide antibiotics to penicillin. Outcomes were all-cause mortality, cardiac death, myocardial infarction, stroke, diagnosis of peripheral vascular disease, and cardiac arrhythmia.

Results

Analysis included 320,798 prescriptions received by 66,331 patients. There were 3,251 deaths, 815 due to cardiovascular causes, 925 incident myocardial infarctions, 859 strokes, 637 diagnoses of peripheral vascular disease, and 1,436 cardiac arrhythmias. A non-statistically significant trend towards increased risk of myocardial infarction during the first 30 days following macrolide prescription was observed. No statistically significant short- or long-term risks were observed for macrolide prescription. No significant risks were identified for clarithromycin in particular.

Conclusions

Although not statistically significant, our best estimates suggest an increased short-term risk of myocardial infarction in patients with CRS following macrolide prescription, supporting previous observational evidence. However, confounding by indication remains a possible explanation for this apparent increased risk. We found no evidence of longer term increased risks.",,pdf:https://www.rhinologyjournal.com/download.php?id=1882; doi:https://doi.org/10.4193/Rhin18.237 -37185641,https://doi.org/10.1136/bmjopen-2022-070022,EXAcerbations of COPD and their OutcomeS on CardioVascular diseases (EXACOS-CV) Programme: protocol of multicountry observational cohort studies.,"Nordon C, Rhodes K, Quint JK, Vogelmeier CF, Simons SO, Hawkins NM, Marshall J, Ouwens M, Garbe E, Müllerová H.",,BMJ open,2023,2023-04-26,Y,epidemiology; Cardiology; Vascular Medicine; Chronic Airways Disease,,,"

Introduction

In patients with chronic obstructive pulmonary disease (COPD), the risk of certain cardiovascular (CV) events is increased by threefold to fivefold in the year following acute exacerbation of COPD (AECOPD), compared with a non-exacerbation period. While the effect of severe AECOPD is well established, the relationship of moderate exacerbation or prior exacerbation to elevated risk of CV events is less clear. We will conduct cohort studies in multiple countries to further characterise the association between AECOPD and CV events.

Methods and analysis

Retrospective longitudinal cohort studies will be conducted within routinely collected electronic healthcare records or claims databases. The study cohorts will include patients meeting inclusion criteria for COPD between 1 January 2014 and 31 December 2018. Moderate exacerbation is defined as an outpatient visit and/or medication dispensation/prescription for exacerbation; severe exacerbation is defined as hospitalisation for COPD. The primary outcomes of interest are the time to (1) first hospitalisation for a CV event (including acute coronary syndrome, heart failure, arrhythmias or cerebral ischaemia) since cohort entry or (2) death. Time-dependent Cox proportional hazards models will compare the hazard of a CV event between exposed periods following exacerbation (split into these periods: 1-7, 8-14, 15-30, 31-180 and 181-365 days) and the unexposed reference time period, adjusted on time-fixed and time-varying confounders.

Ethics and dissemination

Studies have been approved in Canada, Japan, the Netherlands, Spain and the UK, where an institutional review board is mandated. For each study, the results will be published in peer-reviewed journals.",,pdf:https://bmjopen.bmj.com/content/bmjopen/13/4/e070022.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-070022; html:https://europepmc.org/articles/PMC10151875; pdf:https://europepmc.org/articles/PMC10151875?pdf=render 35151397,https://doi.org/10.1016/s0140-6736(22)00163-5,"Casirivimab and imdevimab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial.",RECOVERY Collaborative Group.,,"Lancet (London, England)",2022,2022-02-01,Y,,,,"

Background

Casirivimab and imdevimab are non-competing monoclonal antibodies that bind to two different sites on the receptor binding domain of the SARS-CoV-2 spike glycoprotein, blocking viral entry into host cells. We aimed to evaluate the efficacy and safety of casirivimab and imdevimab administered in combination in patients admitted to hospital with COVID-19.

Methods

RECOVERY is a randomised, controlled, open-label platform trial comparing several possible treatments with usual care in patients admitted to hospital with COVID-19. 127 UK hospitals took part in the evaluation of casirivimab and imdevimab. Eligible participants were any patients aged at least 12 years admitted to hospital with clinically suspected or laboratory-confirmed SARS-CoV-2 infection. Participants were randomly assigned (1:1) to either usual standard of care alone or usual care plus casirivimab 4 g and imdevimab 4 g administered together in a single intravenous infusion. Investigators and data assessors were masked to analyses of the outcome data during the trial. The primary outcome was 28-day all-cause mortality assessed by intention to treat, first only in patients without detectable antibodies to SARS-CoV-2 infection at randomisation (ie, those who were seronegative) and then in the overall population. Safety was assessed in all participants who received casirivimab and imdevimab. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936).

Findings

Between Sept 18, 2020, and May 22, 2021, 9785 patients enrolled in RECOVERY were eligible for casirivimab and imdevimab, of which 4839 were randomly assigned to casirivimab and imdevimab plus usual care and 4946 to usual care alone. 3153 (32%) of 9785 patients were seronegative, 5272 (54%) were seropositive, and 1360 (14%) had unknown baseline antibody status. 812 (8%) patients were known to have received at least one dose of a SARS-CoV-2 vaccine. In the primary efficacy population of seronegative patients, 396 (24%) of 1633 patients allocated to casirivimab and imdevimab versus 452 (30%) of 1520 patients allocated to usual care died within 28 days (rate ratio [RR] 0·79, 95% CI 0·69-0·91; p=0·0009). In an analysis of all randomly assigned patients (regardless of baseline antibody status), 943 (19%) of 4839 patients allocated to casirivimab and imdevimab versus 1029 (21%) of 4946 patients allocated to usual care died within 28 days (RR 0·94, 95% CI 0·86-1·02; p=0·14). The proportional effect of casirivimab and imdevimab on mortality differed significantly between seropositive and seronegative patients (p value for heterogeneity=0·002). There were no deaths attributed to the treatment, or meaningful between-group differences in the pre-specified safety outcomes of cause-specific mortality, cardiac arrhythmia, thrombosis, or major bleeding events. Serious adverse reactions reported in seven (<1%) participants were believed by the local investigator to be related to treatment with casirivimab and imdevimab.

Interpretation

In patients admitted to hospital with COVID-19, the monoclonal antibody combination of casirivimab and imdevimab reduced 28-day mortality in patients who were seronegative (and therefore had not mounted their own humoral immune response) at baseline but not in those who were seropositive at baseline.

Funding

UK Research and Innovation (Medical Research Council) and National Institute of Health Research.",,pdf:http://spiral.imperial.ac.uk/bitstream/10044/1/95149/5/1-s2.0-S0140673622001635-main.pdf; doi:https://doi.org/10.1016/S0140-6736(22)00163-5; html:https://europepmc.org/articles/PMC8830904 +37185641,https://doi.org/10.1136/bmjopen-2022-070022,EXAcerbations of COPD and their OutcomeS on CardioVascular diseases (EXACOS-CV) Programme: protocol of multicountry observational cohort studies.,"Nordon C, Rhodes K, Quint JK, Vogelmeier CF, Simons SO, Hawkins NM, Marshall J, Ouwens M, Garbe E, Müllerová H.",,BMJ open,2023,2023-04-26,Y,epidemiology; Cardiology; Vascular Medicine; Chronic Airways Disease,,,"

Introduction

In patients with chronic obstructive pulmonary disease (COPD), the risk of certain cardiovascular (CV) events is increased by threefold to fivefold in the year following acute exacerbation of COPD (AECOPD), compared with a non-exacerbation period. While the effect of severe AECOPD is well established, the relationship of moderate exacerbation or prior exacerbation to elevated risk of CV events is less clear. We will conduct cohort studies in multiple countries to further characterise the association between AECOPD and CV events.

Methods and analysis

Retrospective longitudinal cohort studies will be conducted within routinely collected electronic healthcare records or claims databases. The study cohorts will include patients meeting inclusion criteria for COPD between 1 January 2014 and 31 December 2018. Moderate exacerbation is defined as an outpatient visit and/or medication dispensation/prescription for exacerbation; severe exacerbation is defined as hospitalisation for COPD. The primary outcomes of interest are the time to (1) first hospitalisation for a CV event (including acute coronary syndrome, heart failure, arrhythmias or cerebral ischaemia) since cohort entry or (2) death. Time-dependent Cox proportional hazards models will compare the hazard of a CV event between exposed periods following exacerbation (split into these periods: 1-7, 8-14, 15-30, 31-180 and 181-365 days) and the unexposed reference time period, adjusted on time-fixed and time-varying confounders.

Ethics and dissemination

Studies have been approved in Canada, Japan, the Netherlands, Spain and the UK, where an institutional review board is mandated. For each study, the results will be published in peer-reviewed journals.",,pdf:https://bmjopen.bmj.com/content/bmjopen/13/4/e070022.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-070022; html:https://europepmc.org/articles/PMC10151875; pdf:https://europepmc.org/articles/PMC10151875?pdf=render 34518162,https://doi.org/10.1136/bjophthalmol-2021-319383,Predicting the immediate impact of national lockdown on neovascular age-related macular degeneration and associated visual morbidity: an INSIGHT Health Data Research Hub for Eye Health report.,"Mollan SP, Fu DJ, Chuo CY, Gannon JG, Lee WH, Hopkins JJ, Hughes C, Denniston AK, Keane PA, Cantrell R.",,The British journal of ophthalmology,2023,2021-09-13,Y,Clinical Trial; Neovascularisation; Covid-19,,,"

Objective

Predicting the impact of neovascular age-related macular degeneration (nAMD) service disruption on visual outcomes following national lockdown in the UK to contain SARS-CoV-2.

Methods and analysis

This retrospective cohort study includes deidentified data from 2229 UK patients from the INSIGHT Health Data Research digital hub. We forecasted the number of treatment-naïve nAMD patients requiring anti-vascular endothelial growth factor (anti-VEGF) initiation during UK lockdown (16 March 2020 through 31 July 2020) at Moorfields Eye Hospital (MEH) and University Hospitals Birmingham (UHB). Best-measured visual acuity (VA) changes without anti-VEGF therapy were predicted using post hoc analysis of Minimally Classic/Occult Trial of the Anti-VEGF Antibody Ranibizumab in the Treatment of Neovascular AMD trial sham-control arm data (n=238).

Results

At our centres, 376 patients were predicted to require anti-VEGF initiation during lockdown (MEH: 325; UHB: 51). Without treatment, mean VA was projected to decline after 12 months. The proportion of eyes in the MEH cohort predicted to maintain the key positive visual outcome of ≥70 ETDRS letters (Snellen equivalent 6/12) fell from 25.5% at baseline to 5.8% at 12 months (UHB: 9.8%-7.8%). Similarly, eyes with VA <25 ETDRS letters (6/96) were predicted to increase from 4.3% to 14.2% at MEH (UHB: 5.9%-7.8%) after 12 months without treatment.

Conclusions

Here, we demonstrate how combining data from a recently founded national digital health data repository with historical industry-funded clinical trial data can enhance predictive modelling in nAMD. The demonstrated detrimental effects of prolonged treatment delay should incentivise healthcare providers to support nAMD patients accessing care in safe environments.

Trial registration number

NCT00056836.",,pdf:https://discovery.ucl.ac.uk/10164981/1/267.full.pdf; doi:https://doi.org/10.1136/bjophthalmol-2021-319383; html:https://europepmc.org/articles/PMC9887382; pdf:https://europepmc.org/articles/PMC9887382?pdf=render -38053867,https://doi.org/10.1016/j.heliyon.2023.e21734,Wastewater-based surveillance models for COVID-19: A focused review on spatio-temporal models.,"Torabi F, Li G, Mole C, Nicholson G, Rowlingson B, Smith CR, Jersakova R, Diggle PJ, Blangiardo M.",,Heliyon,2023,2023-11-08,Y,Wastewater-based Epidemiology; Covid-19; Wastewater-Based Surveillance; Spatio-Temporal Statistical Modelling,,,"The evident shedding of the SARS-CoV-2 RNA particles from infected individuals into the wastewater opened up a tantalizing array of possibilities for prediction of COVID-19 prevalence prior to symptomatic case identification through community testing. Many countries have therefore explored the use of wastewater metrics as a surveillance tool, replacing traditional direct measurement of prevalence with cost-effective approaches based on SARS-CoV-2 RNA concentrations in wastewater samples. Two important aspects in building prediction models are: time over which the prediction occurs and space for which the predicted case numbers is shown. In this review, our main focus was on finding mathematical models which take into the account both the time-varying and spatial nature of wastewater-based metrics into account. We used six main characteristics as our assessment criteria: i) modelling approach; ii) temporal coverage; iii) spatial coverage; iv) sample size; v) wastewater sampling method; and vi) covariates included in the modelling. The majority of studies in the early phases of the pandemic recognized the temporal association of SARS-CoV-2 RNA concentration level in wastewater with the number of COVID-19 cases, ignoring their spatial context. We examined 15 studies up to April 2023, focusing on models considering both temporal and spatial aspects of wastewater metrics. Most early studies correlated temporal SARS-CoV-2 RNA levels with COVID-19 cases but overlooked spatial factors. Linear regression and SEIR models were commonly used (n = 10, 66.6 % of studies), along with machine learning (n = 1, 6.6 %) and Bayesian approaches (n = 1, 6.6 %) in some cases. Three studies employed spatio-temporal modelling approach (n = 3, 20.0 %). We conclude that the development, validation and calibration of further spatio-temporally explicit models should be done in parallel with the advancement of wastewater metrics before the potential of wastewater as a surveillance tool can be fully realised.",,doi:https://doi.org/10.1016/j.heliyon.2023.e21734; html:https://europepmc.org/articles/PMC10694161; pdf:https://europepmc.org/articles/PMC10694161?pdf=render 35749561,https://doi.org/10.1371/journal.pcbi.1010234,"Evidence for influenza and RSV interaction from 10 years of enhanced surveillance in Nha Trang, Vietnam, a modelling study.","Waterlow NR, Toizumi M, van Leeuwen E, Thi Nguyen HA, Myint-Yoshida L, Eggo RM, Flasche S.",,PLoS computational biology,2022,2022-06-24,Y,,,,"Influenza and Respiratory Syncytial Virus (RSV) interact within their host posing the concern for impacts on heterologous viruses following vaccination. We aimed to estimate the population level impact of their interaction. We developed a dynamic age-stratified two-pathogen mathematical model that includes pathogen interaction through competition for infection and enhanced severity of dual infections. We used parallel tempering to fit its parameters to 11 years of enhanced hospital-based surveillance for acute respiratory illnesses (ARI) in children under 5 years old in Nha Trang, Vietnam. The data supported either a 41% (95%CrI: 36-54) reduction in susceptibility following infection and for 10.0 days (95%CrI 7.1-12.8) thereafter, or no change in susceptibility following infection. We estimate that co-infection increased the probability for an infection in <2y old children to be reported 7.2 fold (95%CrI 5.0-11.4); or 16.6 fold (95%CrI 14.5-18.4) in the moderate or low interaction scenarios. Absence of either pathogen was not to the detriment of the other. We find stronger evidence for severity enhancing than for acquisition limiting interaction. In this setting vaccination against either pathogen is unlikely to have a major detrimental effect on the burden of disease caused by the other.",,pdf:https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1010234&type=printable; doi:https://doi.org/10.1371/journal.pcbi.1010234; html:https://europepmc.org/articles/PMC9262224; pdf:https://europepmc.org/articles/PMC9262224?pdf=render +38053867,https://doi.org/10.1016/j.heliyon.2023.e21734,Wastewater-based surveillance models for COVID-19: A focused review on spatio-temporal models.,"Torabi F, Li G, Mole C, Nicholson G, Rowlingson B, Smith CR, Jersakova R, Diggle PJ, Blangiardo M.",,Heliyon,2023,2023-11-08,Y,Wastewater-based Epidemiology; Covid-19; Wastewater-Based Surveillance; Spatio-Temporal Statistical Modelling,,,"The evident shedding of the SARS-CoV-2 RNA particles from infected individuals into the wastewater opened up a tantalizing array of possibilities for prediction of COVID-19 prevalence prior to symptomatic case identification through community testing. Many countries have therefore explored the use of wastewater metrics as a surveillance tool, replacing traditional direct measurement of prevalence with cost-effective approaches based on SARS-CoV-2 RNA concentrations in wastewater samples. Two important aspects in building prediction models are: time over which the prediction occurs and space for which the predicted case numbers is shown. In this review, our main focus was on finding mathematical models which take into the account both the time-varying and spatial nature of wastewater-based metrics into account. We used six main characteristics as our assessment criteria: i) modelling approach; ii) temporal coverage; iii) spatial coverage; iv) sample size; v) wastewater sampling method; and vi) covariates included in the modelling. The majority of studies in the early phases of the pandemic recognized the temporal association of SARS-CoV-2 RNA concentration level in wastewater with the number of COVID-19 cases, ignoring their spatial context. We examined 15 studies up to April 2023, focusing on models considering both temporal and spatial aspects of wastewater metrics. Most early studies correlated temporal SARS-CoV-2 RNA levels with COVID-19 cases but overlooked spatial factors. Linear regression and SEIR models were commonly used (n = 10, 66.6 % of studies), along with machine learning (n = 1, 6.6 %) and Bayesian approaches (n = 1, 6.6 %) in some cases. Three studies employed spatio-temporal modelling approach (n = 3, 20.0 %). We conclude that the development, validation and calibration of further spatio-temporally explicit models should be done in parallel with the advancement of wastewater metrics before the potential of wastewater as a surveillance tool can be fully realised.",,doi:https://doi.org/10.1016/j.heliyon.2023.e21734; html:https://europepmc.org/articles/PMC10694161; pdf:https://europepmc.org/articles/PMC10694161?pdf=render PMC9644860,https://doi.org/,Maternal mental health and children’s development: a bi-directional relationship?,"Lowthian E, Bedston S, Akbari A, Katz A, Huxley K, Johnson R, Kristensen S, Owen R, Taylor C, Griffiths L.",,International journal of population data science,,2022-11-21,Y,,,,,,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9644860/?tool=EBI; pdf:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9644860/pdf/?tool=EBI; html:https://europepmc.org/articles/PMC9644860; pdf:https://europepmc.org/articles/PMC9644860?pdf=render 35868811,https://doi.org/10.1016/s2589-7500(22)00122-4,Data provenance and integrity of health-care systems data for clinical trials.,"Murray ML, Love SB, Carpenter JR, Hartley S, Landray MJ, Mafham M, Parmar MKB, Pinches H, Sydes MR, Healthcare Systems Data for Clinical Trials Collaborative Group.",,The Lancet. Digital health,2022,2022-08-01,Y,,,,,,pdf:http://www.thelancet.com/article/S2589750022001224/pdf; doi:https://doi.org/10.1016/S2589-7500(22)00122-4; html:https://europepmc.org/articles/PMC9296098; pdf:https://europepmc.org/articles/PMC9296098?pdf=render 36211555,https://doi.org/10.3389/fcvm.2022.983091,Cardiac aging synthesis from cross-sectional data with conditional generative adversarial networks.,"Campello VM, Xia T, Liu X, Sanchez P, Martín-Isla C, Petersen SE, Seguí S, Tsaftaris SA, Lekadir K.",,Frontiers in cardiovascular medicine,2022,2022-09-23,Y,Synthesis; Magnetic Resonance Imaging; Data Augmentation; Aging Heart; Generative Adversarial Network,,,"Age has important implications for health, and understanding how age manifests in the human body is the first step for a potential intervention. This becomes especially important for cardiac health, since age is the main risk factor for development of cardiovascular disease. Data-driven modeling of age progression has been conducted successfully in diverse applications such as face or brain aging. While longitudinal data is the preferred option for training deep learning models, collecting such a dataset is usually very costly, especially in medical imaging. In this work, a conditional generative adversarial network is proposed to synthesize older and younger versions of a heart scan by using only cross-sectional data. We train our model with more than 14,000 different scans from the UK Biobank. The induced modifications focused mainly on the interventricular septum and the aorta, which is consistent with the existing literature in cardiac aging. We evaluate the results by measuring image quality, the mean absolute error for predicted age using a pre-trained regressor, and demonstrate the application of synthetic data for counter-balancing biased datasets. The results suggest that the proposed approach is able to model realistic changes in the heart using only cross-sectional data and that these data can be used to correct age bias in a dataset.",,pdf:https://www.frontiersin.org/articles/10.3389/fcvm.2022.983091/pdf; doi:https://doi.org/10.3389/fcvm.2022.983091; html:https://europepmc.org/articles/PMC9537599; pdf:https://europepmc.org/articles/PMC9537599?pdf=render @@ -629,8 +629,8 @@ PMC9644860,https://doi.org/,Maternal mental health and children’s development: 36384890,https://doi.org/10.1136/bmj-2022-071932,Comparative effectiveness of sotrovimab and molnupiravir for prevention of severe covid-19 outcomes in patients in the community: observational cohort study with the OpenSAFELY platform.,"Zheng B, Green ACA, Tazare J, Curtis HJ, Fisher L, Nab L, Schultze A, Mahalingasivam V, Parker EPK, Hulme WJ, Bacon SCJ, DeVito NJ, Bates C, Evans D, Inglesby P, Drysdale H, Davy S, Cockburn J, Morton CE, Hickman G, Ward T, Smith RM, Parry J, Hester F, Harper S, Mehrkar A, Eggo RM, Walker AJ, Evans SJW, Douglas IJ, MacKenna B, Goldacre B, Tomlinson LA.",,BMJ (Clinical research ed.),2022,2022-11-16,Y,,,,"

Objective

To compare the effectiveness of sotrovimab (a neutralising monoclonal antibody) with molnupiravir (an antiviral) in preventing severe outcomes of covid-19 in adult patients infected with SARS-CoV-2 in the community and at high risk of severe outcomes from covid-19.

Design

Observational cohort study with the OpenSAFELY platform.

Setting

With the approval of NHS England, a real world cohort study was conducted with the OpenSAFELY-TPP platform (a secure, transparent, open source software platform for analysis of NHS electronic health records), and patient level electronic health record data were obtained from 24 million people registered with a general practice in England that uses TPP software. The primary care data were securely linked with data on SARS-CoV-2 infection and treatments, hospital admission, and death, over a period when both drug treatments were frequently prescribed in community settings.

Participants

Adult patients with covid-19 in the community at high risk of severe outcomes from covid-19, treated with sotrovimab or molnupiravir from 16 December 2021.

Interventions

Sotrovimab or molnupiravir given in the community by covid-19 medicine delivery units.

Main outcome measures

Admission to hospital with covid-19 (ie, with covid-19 as the primary diagnosis) or death from covid-19 (ie, with covid-19 as the underlying or contributing cause of death) within 28 days of the start of treatment.

Results

Between 16 December 2021 and 10 February 2022, 3331 and 2689 patients were treated with sotrovimab and molnupiravir, respectively, with no substantial differences in baseline characteristics. Mean age of all 6020 patients was 52 (standard deviation 16) years; 59% were women, 89% were white, and 88% had received three or more covid-19 vaccinations. Within 28 days of the start of treatment, 87 (1.4%) patients were admitted to hospital or died of infection from SARS-CoV-2 (32 treated with sotrovimab and 55 with molnupiravir). Cox proportional hazards models stratified by area showed that after adjusting for demographic information, high risk cohort categories, vaccination status, calendar time, body mass index, and other comorbidities, treatment with sotrovimab was associated with a substantially lower risk than treatment with molnupiravir (hazard ratio 0.54, 95% confidence interval 0.33 to 0.88, P=0.01). Consistent results were found from propensity score weighted Cox models (0.50, 0.31 to 0.81, P=0.005) and when restricted to people who were fully vaccinated (0.53, 0.31 to 0.90, P=0.02). No substantial effect modifications by other characteristics were detected (all P values for interaction >0.10). The findings were similar in an exploratory analysis of patients treated between 16 February and 1 May 2022 when omicron BA.2 was the predominant variant in England.

Conclusions

In routine care of adult patients in England with covid-19 in the community, at high risk of severe outcomes from covid-19, those who received sotrovimab were at lower risk of severe outcomes of covid-19 than those treated with molnupiravir.",,pdf:https://www.bmj.com/content/bmj/379/bmj-2022-071932.full.pdf; doi:https://doi.org/10.1136/bmj-2022-071932; html:https://europepmc.org/articles/PMC9667468 34308125,https://doi.org/10.1136/bmjnph-2020-000225,Effect of ultraprocessed food intake on cardiometabolic risk is mediated by diet quality: a cross-sectional study.,"Griffin J, Albaloul A, Kopytek A, Elliott P, Frost G.",,"BMJ nutrition, prevention & health",2021,2021-04-07,Y,metabolic syndrome; Dietary Patterns,,,"

Objective

To examine the effect of the consumption of ultraprocessed food on diet quality, and cardiometabolic risk (CMR) in an occupational cohort.

Design

Cross-sectional.

Setting

Occupational cohort.

Participants

53 163 British police force employees enrolled (2004-2012) into the Airwave Health Monitoring Study. A total of 28 forces across the UK agreed to participate. 9009 participants with available 7-day diet record data and complete co-variate data are reported in this study.

Main outcome measures

A CMR and Dietary Approaches to Stop Hypertension score were treated as continuous variables and used to generate measures of cardiometabolic health and diet quality. Secondary outcome measures include percentage of energy from fat, saturated fat, carbohydrate, protein and non-milk extrinsic sugars (NMES) and fibre grams per 1000 kcal of energy intake.

Results

In this cohort, 58.3%±11.6 of total energy intake was derived from ultraprocessed (NOVA 4) foods. Ultraprocessed food intake was negatively correlated with diet quality (r=-0.32, p<0.001), fibre (r=-0.20, p<0.001) and protein (r = -0.40, p<0.001) and positively correlated with fat (r=0.18, p<0.001), saturated fat (r=0.14, p<0.001) and nmes (r=0.10, p<0.001) intake. Multivariable analysis suggests a positive association between ultraprocessed food (NOVA 4) consumption and CMR. However, this main effect was no longer observed after adjustment for diet quality (p=0.209). Findings from mediation analysis indicate that the effect of ultraprocessed food (NOVA 4) intake on CMR is mediated by diet quality (p<0.001).

Conclusions

Ultraprocessed food consumption is associated with a deterioration in diet quality and positively associated with CMR, although this association is mediated by and dependent on the quality of the diet. The negative impact of ultraprocessed food consumption on diet quality needs to be addressed and controlled studies are needed to fully comprehend whether the relationship between ultraprocessed food consumption and health is independent to its relationship with poor diet quality.",,pdf:https://nutrition.bmj.com/content/bmjnph/4/1/174.full.pdf; doi:https://doi.org/10.1136/bmjnph-2020-000225; html:https://europepmc.org/articles/PMC8258022; pdf:https://europepmc.org/articles/PMC8258022?pdf=render 36472984,https://doi.org/10.1371/journal.pmed.1004124,Association between antidementia medication use and mortality in people diagnosed with dementia with Lewy bodies in the UK: A retrospective cohort study.,"Chen S, Price AC, Cardinal RN, Moylett S, Kershenbaum AD, Fitzgerald J, Mueller C, Stewart R, O'Brien JT.",,PLoS medicine,2022,2022-12-06,Y,,,,"

Background

Dementia with Lewy bodies (DLBs) is a common cause of dementia but has higher mortality than Alzheimer's disease (AD). The reasons for this are unclear, but antidementia drugs (including acetylcholinesterase inhibitors [AChEIs] and memantine) symptomatically benefit people with DLB and might improve outcomes. We investigated whether AChEIs and/or memantine were associated with reduced hospital admissions and mortality.

Methods and findings

We performed a retrospective cohort study of those diagnosed with DLB between 1 January 2005 and 31 December 2019, using data from electronic clinical records of secondary care mental health services in Cambridgeshire and Peterborough NHS Foundation Trust (CPFT), United Kingdom (catchment area population approximately 0.86 million), as well as linked records from national Hospital Episode Statistics (HES) data. Eligible patients were those who started AChEIs or memantine within 3 months of their diagnosis (cases) and those who never used AChEIs or memantine (controls). Outcomes included admission, length of stay, and mortality. Cox proportional hazard and linear regression models were used. Of 592 patients with DLB, 219 never took AChEIs or memantine, 100 took AChEIs only, and 273 took both AChEIs and memantine. The cohorts were followed up for an average of 896 days, 981 days, and 1,004 days, respectively. There were no significant differences in the cohorts' baseline characteristics, except for socioeconomic status that was lower in patients who never took AChEIs or memantine (χ2 = 23.34, P = 0.003). After controlling for confounding by sociodemographic factors (age, sex, marital status, ethnicity, socioeconomic status), antipsychotic use, antidepressant use, cognitive status, physical comorbidity, anticholinergic burden, and global health performance, compared with patients who never took AChEIs or memantine, patients taking AChEIs only or taking both had a significantly lower risk of death (adjusted hazard ratio (HR) = 0.67, 95% CI = 0.48 to 0.93, p = 0.02; adjusted HR = 0.64, 95% CI = 0.50 to 0.83, P = 0.001, respectively). Those taking AChEIs or both AChEIs and memantine had significantly shorter periods of unplanned hospital admission for physical disorders (adjusted coefficient -13.48, 95% CI = [-26.87, -0.09], P = 0.049; adjusted coefficient -14.21, 95% CI = [-24.58, -3.85], P = 0.007, respectively), but no difference in length of stay for planned admissions for physical disorders, or for admissions for mental health disorders. No significant additional associations of memantine on admission, length of stay, and mortality were found (all P > 0.05). The main limitation was that this was a naturalistic study and possible confounds cannot be fully controlled, and there may be selection bias resulting from nonrandom prescription behaviour in clinical practice. However, we mimicked the intention-to-treat design of clinical trials, and the majority of baseline characters were balanced between cohorts. In addition, our series of sensitivity analyses confirmed the consistency of our results.

Conclusion

In this study, we observed that use of AChEIs with or without memantine in DLB was associated with shorter duration of hospital admissions and decreased risk of mortality. Although our study was naturalistic, it supports further the use of AChEIs in DLB.",,pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1004124&type=printable; doi:https://doi.org/10.1371/journal.pmed.1004124; html:https://europepmc.org/articles/PMC9725132; pdf:https://europepmc.org/articles/PMC9725132?pdf=render -38479735,https://doi.org/10.1136/bmjopen-2023-081926,"HFE genotypes, haemochromatosis diagnosis and clinical outcomes at age 80 years: a prospective cohort study in the UK Biobank.","Lucas MR, Atkins JL, Pilling LC, Shearman JD, Melzer D.",,BMJ open,2024,2024-03-13,Y,"Genetics; Mortality; Hepatology; Other Metabolic, E.g. Iron, Porphyria",,,"

Objectives

HFE haemochromatosis genetic variants have an uncertain clinical penetrance, especially to older ages and in undiagnosed groups. We estimated p.C282Y and p.H63D variant cumulative incidence of multiple clinical outcomes in a large community cohort.

Design

Prospective cohort study.

Setting

22 assessment centres across England, Scotland, and Wales in the UK Biobank (2006-2010).

Participants

451 270 participants genetically similar to the 1000 Genomes European reference population, with a mean of 13.3-year follow-up through hospital inpatient, cancer registries and death certificate data.

Main outcome measures

Cox proportional HRs of incident clinical outcomes and mortality in those with HFE p.C282Y/p.H63D mutations compared with those with no variants, stratified by sex and adjusted for age, assessment centre and genetic stratification. Cumulative incidences were estimated from age 40 years to 80 years.

Results

12.1% of p.C282Y+/+ males had baseline (mean age 57 years) haemochromatosis diagnoses, with a cumulative incidence of 56.4% at age 80 years. 33.1% died vs 25.4% without HFE variants (HR 1.29, 95% CI: 1.12 to 1.48, p=4.7×10-4); 27.9% vs 17.1% had joint replacements, 20.3% vs 8.3% had liver disease, and there were excess delirium, dementia, and Parkinson's disease but not depression. Associations, including excess mortality, were similar in the group undiagnosed with haemochromatosis. 3.4% of women with p.C282Y+/+ had baseline haemochromatosis diagnoses, with a cumulative incidence of 40.5% at age 80 years. There were excess incident liver disease (8.9% vs 6.8%; HR 1.62, 95% CI: 1.27 to 2.05, p=7.8×10-5), joint replacements and delirium, with similar results in the undiagnosed. p.C282Y/p.H63D and p.H63D+/+ men or women had no statistically significant excess fatigue or depression at baseline and no excess incident outcomes.

Conclusions

Male and female p.C282Y homozygotes experienced greater excess morbidity than previously documented, including those undiagnosed with haemochromatosis in the community. As haemochromatosis diagnosis rates were low at baseline despite treatment being considered effective, trials of screening to identify people with p.C282Y homozygosity early appear justified.",,doi:https://doi.org/10.1136/bmjopen-2023-081926; html:https://europepmc.org/articles/PMC10936495; pdf:https://europepmc.org/articles/PMC10936495?pdf=render 36921681,https://doi.org/10.1016/j.cca.2023.117271,"Letter to the editor regarding: ""A haemochromatosis-causing HFE mutation is associated with SARS-CoV-2 susceptibility in the Czech population"" clinica chimica acta 538 (2023) 211-215.","Atkins JL, Lucas MR, Pilling LC, Melzer D.",,Clinica chimica acta; international journal of clinical chemistry,2023,2023-03-13,Y,Iron; Haemochromatosis; Hfe; Covd-19,,,,,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10009995; doi:https://doi.org/10.1016/j.cca.2023.117271; html:https://europepmc.org/articles/PMC10009995; pdf:https://europepmc.org/articles/PMC10009995?pdf=render +38479735,https://doi.org/10.1136/bmjopen-2023-081926,"HFE genotypes, haemochromatosis diagnosis and clinical outcomes at age 80 years: a prospective cohort study in the UK Biobank.","Lucas MR, Atkins JL, Pilling LC, Shearman JD, Melzer D.",,BMJ open,2024,2024-03-13,Y,"Genetics; Mortality; Hepatology; Other Metabolic, E.g. Iron, Porphyria",,,"

Objectives

HFE haemochromatosis genetic variants have an uncertain clinical penetrance, especially to older ages and in undiagnosed groups. We estimated p.C282Y and p.H63D variant cumulative incidence of multiple clinical outcomes in a large community cohort.

Design

Prospective cohort study.

Setting

22 assessment centres across England, Scotland, and Wales in the UK Biobank (2006-2010).

Participants

451 270 participants genetically similar to the 1000 Genomes European reference population, with a mean of 13.3-year follow-up through hospital inpatient, cancer registries and death certificate data.

Main outcome measures

Cox proportional HRs of incident clinical outcomes and mortality in those with HFE p.C282Y/p.H63D mutations compared with those with no variants, stratified by sex and adjusted for age, assessment centre and genetic stratification. Cumulative incidences were estimated from age 40 years to 80 years.

Results

12.1% of p.C282Y+/+ males had baseline (mean age 57 years) haemochromatosis diagnoses, with a cumulative incidence of 56.4% at age 80 years. 33.1% died vs 25.4% without HFE variants (HR 1.29, 95% CI: 1.12 to 1.48, p=4.7×10-4); 27.9% vs 17.1% had joint replacements, 20.3% vs 8.3% had liver disease, and there were excess delirium, dementia, and Parkinson's disease but not depression. Associations, including excess mortality, were similar in the group undiagnosed with haemochromatosis. 3.4% of women with p.C282Y+/+ had baseline haemochromatosis diagnoses, with a cumulative incidence of 40.5% at age 80 years. There were excess incident liver disease (8.9% vs 6.8%; HR 1.62, 95% CI: 1.27 to 2.05, p=7.8×10-5), joint replacements and delirium, with similar results in the undiagnosed. p.C282Y/p.H63D and p.H63D+/+ men or women had no statistically significant excess fatigue or depression at baseline and no excess incident outcomes.

Conclusions

Male and female p.C282Y homozygotes experienced greater excess morbidity than previously documented, including those undiagnosed with haemochromatosis in the community. As haemochromatosis diagnosis rates were low at baseline despite treatment being considered effective, trials of screening to identify people with p.C282Y homozygosity early appear justified.",,doi:https://doi.org/10.1136/bmjopen-2023-081926; html:https://europepmc.org/articles/PMC10936495; pdf:https://europepmc.org/articles/PMC10936495?pdf=render 38383380,https://doi.org/10.1186/s12939-024-02114-6,Rapid systematic review on risks and outcomes of sepsis: the influence of risk factors associated with health inequalities.,"Bladon S, Ashiru-Oredope D, Cunningham N, Pate A, Martin GP, Zhong X, Gilham EL, Brown CS, Mirfenderesky M, Palin V, van Staa TP.",,International journal for equity in health,2024,2024-02-21,Y,Sepsis; Antimicrobial resistance; communities; Socioeconomic status; Ethnicity; Deprivation; Health Inequalities; Maternal,,,"

Background and aims

Sepsis is a serious and life-threatening condition caused by a dysregulated immune response to an infection. Recent guidance issued in the UK gave recommendations around recognition and antibiotic treatment of sepsis, but did not consider factors relating to health inequalities. The aim of this study was to summarise the literature investigating associations between health inequalities and sepsis.

Methods

Searches were conducted in Embase for peer-reviewed articles published since 2010 that included sepsis in combination with one of the following five areas: socioeconomic status, race/ethnicity, community factors, medical needs and pregnancy/maternity.

Results

Five searches identified 1,402 studies, with 50 unique studies included in the review after screening (13 sociodemographic, 14 race/ethnicity, 3 community, 3 care/medical needs and 20 pregnancy/maternity; 3 papers examined multiple health inequalities). Most of the studies were conducted in the USA (31/50), with only four studies using UK data (all pregnancy related). Socioeconomic factors associated with increased sepsis incidence included lower socioeconomic status, unemployment and lower education level, although findings were not consistent across studies. For ethnicity, mixed results were reported. Living in a medically underserved area or being resident in a nursing home increased risk of sepsis. Mortality rates after sepsis were found to be higher in people living in rural areas or in those discharged to skilled nursing facilities while associations with ethnicity were mixed. Complications during delivery, caesarean-section delivery, increased deprivation and black and other ethnic minority race were associated with post-partum sepsis.

Conclusion

There are clear correlations between sepsis morbidity and mortality and the presence of factors associated with health inequalities. To inform local guidance and drive public health measures, there is a need for studies conducted across more diverse setting and countries.",,doi:https://doi.org/10.1186/s12939-024-02114-6; html:https://europepmc.org/articles/PMC10882893; pdf:https://europepmc.org/articles/PMC10882893?pdf=render 37663407,https://doi.org/10.1093/jamiaopen/ooad072,Identifying factors associated with user retention and outcomes of a digital intervention for substance use disorder: a retrospective analysis of real-world data.,"Günther F, Wong D, Elison-Davies S, Yau C.",,JAMIA open,2023,2023-09-02,Y,Substance Use Disorder; Secondary Use; Digital Health Intervention; Real-World Data Exploration; Real-World Uptake,,,"

Objectives

Successful delivery of digital health interventions is affected by multiple real-world factors. These factors may be identified in routinely collected, ecologically valid data from these interventions. We propose ideas for exploring these data, focusing on interventions targeting complex, comorbid conditions.

Materials and methods

This study retrospectively explores pre-post data collected between 2016 and 2019 from users of digital cognitive behavioral therapy (CBT)-containing psychoeducation and practical exercises-for substance use disorder (SUD) at UK addiction services. To identify factors associated with heterogenous user responses to the technology, we employed multivariable and multivariate regressions and random forest models of user-reported questionnaire data.

Results

The dataset contained information from 14 078 individuals of which 12 529 reported complete data at baseline and 2925 did so again after engagement with the CBT. Ninety-three percent screened positive for dependence on 1 of 43 substances at baseline, and 73% screened positive for anxiety or depression. Despite pre-post improvements independent of user sociodemographics, women reported more frequent and persistent symptoms of SUD, anxiety, and depression. Retention-minimum 2 use events recorded-was associated more with deployment environment than user characteristics. Prediction accuracy of post-engagement outcomes was acceptable (Area Under Curve [AUC]: 0.74-0.79), depending non-trivially on user characteristics.

Discussion

Traditionally, performance of digital health interventions is determined in controlled trials. Our analysis showcases multivariate models with which real-world data from these interventions can be explored and sources of user heterogeneity in retention and symptom reduction uncovered.

Conclusion

Real-world data from digital health interventions contain information on natural user-technology interactions which could enrich results from controlled trials.",,pdf:https://academic.oup.com/jamiaopen/article-pdf/6/3/ooad072/51335405/ooad072.pdf; doi:https://doi.org/10.1093/jamiaopen/ooad072; html:https://europepmc.org/articles/PMC10474970; pdf:https://europepmc.org/articles/PMC10474970?pdf=render 36434299,https://doi.org/10.1007/s00127-022-02393-w,Adverse outcomes associated with recorded victimization in mental health electronic records during the first UK COVID-19 lockdown.,"Kadra-Scalzo G, Kornblum D, Stewart R, Howard LM.",,Social psychiatry and psychiatric epidemiology,2023,2022-11-24,Y,Mental health; Domestic Violence; Victimisation; Adverse Outcomes; Covid-19,,,"

Purpose

The impact of COVID-19 pandemic policies on vulnerable groups such as people with mental health problems who experience violence remains unknown. This study aimed to investigate the prevalence of victimization recorded in mental healthcare records during the first UK lockdown, and associations with subsequent adverse outcomes.

Methods

Using a large mental healthcare database, we identified all adult patients receiving services between 16.12.2019 and 15.06.2020 and extracted records of victimisation between 16.03.2020 and 15.06.2020 (first UK COVID-19 lockdown). We investigated adverse outcomes including acute care, emergency department referrals and all-cause mortality in the year following the lockdown (16.06.2020- 01.11.2021). Multivariable Cox regressions models were constructed, adjusting for socio-demographic, socioeconomic, clinical, and service use factors.

Results

Of 21,037 adults receiving mental healthcare over the observation period, 3,610 (17.2%) had victimisation mentioned between 16.03.2020 and 15.06.2020 (first UK COVID-19 lockdown). Service users with mentions of victimisation in their records had an elevated risk for all outcomes: acute care (adjusted HR: 2.1; 95%CI 1.9-2.3, p < 0.001), emergency department referrals (aHR: 2.0; 95%CI 1.8-2.2; p < 0.001), and all-cause mortality (aHR: 1.5; 95%CI 1.1-1.9; p = 0.003), when compared to service users with no recorded victimisation. We did not observe a statistically significant interaction with gender; however, after adjusting for possible confounders, men had slightly higher hazard ratios for all-cause mortality and emergency department referrals than women.

Conclusion

Patients with documented victimisation during the first UK lockdown were at increased risk for acute care, emergency department referrals and all-cause mortality. Further research is needed into mediating mechanisms.",,pdf:https://link.springer.com/content/pdf/10.1007/s00127-022-02393-w.pdf; doi:https://doi.org/10.1007/s00127-022-02393-w; html:https://europepmc.org/articles/PMC9702612; pdf:https://europepmc.org/articles/PMC9702612?pdf=render @@ -639,8 +639,8 @@ PMC9644860,https://doi.org/,Maternal mental health and children’s development: 31612961,https://doi.org/10.1093/nar/gkz895,GWAS Central: a comprehensive resource for the discovery and comparison of genotype and phenotype data from genome-wide association studies.,"Beck T, Shorter T, Brookes AJ.",,Nucleic acids research,2020,2020-01-01,Y,,,,"The GWAS Central resource provides a toolkit for integrative access and visualization of a uniquely extensive collection of genome-wide association study data, while ensuring safe open access to prevent research participant identification. GWAS Central is the world's most comprehensive openly accessible repository of summary-level GWAS association information, providing over 70 million P-values for over 3800 studies investigating over 1400 unique phenotypes. The database content comprises direct submissions received from GWAS authors and consortia, in addition to actively gathered data sets from various public sources. GWAS data are discoverable from the perspective of genetic markers, genes, genome regions or phenotypes, via graphical visualizations and detailed downloadable data reports. Tested genetic markers and relevant genomic features can be visually interrogated across up to sixteen multiple association data sets in a single view using the integrated genome browser. The semantic standardization of phenotype descriptions with Medical Subject Headings and the Human Phenotype Ontology allows the precise identification of genetic variants associated with diseases, phenotypes and traits of interest. Harmonization of the phenotype descriptions used across several GWAS-related resources has extended the phenotype search capabilities to enable cross-database study discovery using a range of ontologies. GWAS Central is updated regularly and available at https://www.gwascentral.org.",,pdf:https://academic.oup.com/nar/article-pdf/48/D1/D933/31697824/gkz895.pdf; doi:https://doi.org/10.1093/nar/gkz895; html:https://europepmc.org/articles/PMC7145571; pdf:https://europepmc.org/articles/PMC7145571?pdf=render 35845286,https://doi.org/10.1002/jha2.182,"An open-source, expert-designed decision tree application to support accurate diagnosis of myeloid malignancies.","Coats T, Bean D, Vatopoulou T, Vijayavalli D, El-Bashir R, Panopoulou A, Wood H, Wimalachandra M, Coppell J, Medd P, Furtado M, Tucker D, Kulasakeraraj A, Pawade J, Dobson R, Ireland R.",,EJHaem,2021,2021-03-26,Y,Myeloid Leukaemia; Classifications; Diagnostic Haematology; Clinical Haematology,,,"Accurate, reproducible diagnoses can be difficult to make in haemato-oncology due to multi-parameter clinical data, complex diagnostic criteria and time-pressured environments. We have designed a decision tree application (DTA) that reflects WHO diagnostic criteria to support accurate diagnoses of myeloid malignancies. The DTA returned the correct diagnoses in 94% of clinical cases tested. The DTA maintained a high level of accuracy in a second validation using artificially generated clinical cases. Optimisations have been made to the DTA based on the validations, and the revised version is now publicly available for use at http://bit.do/ADAtool.",,pdf:https://discovery.ucl.ac.uk/10145154/1/Bean_An%20open%20source%2C%20expert%20designed%20decision%20tree%20application%20to%20support%20accurate%20diagnosis%20of%20myeloid%20malignancies_VoR.pdf; doi:https://doi.org/10.1002/jha2.182; html:https://europepmc.org/articles/PMC9175663; pdf:https://europepmc.org/articles/PMC9175663?pdf=render 33020224,https://doi.org/10.1136/heartjnl-2020-317870,Monitoring indirect impact of COVID-19 pandemic on services for cardiovascular diseases in the UK.,"Ball S, Banerjee A, Berry C, Boyle JR, Bray B, Bradlow W, Chaudhry A, Crawley R, Danesh J, Denniston A, Falter F, Figueroa JD, Hall C, Hemingway H, Jefferson E, Johnson T, King G, Lee KK, McKean P, Mason S, Mills NL, Pearson E, Pirmohamed M, Poon MTC, Priedon R, Shah A, Sofat R, Sterne JAC, Strachan FE, Sudlow CLM, Szarka Z, Whiteley W, Wyatt M, CVD-COVID-UK Consortium.",,Heart (British Cardiac Society),2020,2020-10-05,Y,epidemiology; Heart Disease; Health Care Delivery; Global Health Care Delivery; Aortic And Arterial Disease,,,"

Objective

To monitor hospital activity for presentation, diagnosis and treatment of cardiovascular diseases during the COVID-19) pandemic to inform on indirect effects.

Methods

Retrospective serial cross-sectional study in nine UK hospitals using hospital activity data from 28 October 2019 (pre-COVID-19) to 10 May 2020 (pre-easing of lockdown) and for the same weeks during 2018-2019. We analysed aggregate data for selected cardiovascular diseases before and during the epidemic. We produced an online visualisation tool to enable near real-time monitoring of trends.

Results

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

Conclusions

Substantial reductions in total and cardiovascular activities are likely to contribute to a major burden of indirect effects of the pandemic, suggesting they should be monitored and mitigated urgently.",,pdf:https://heart.bmj.com/content/heartjnl/106/24/1890.full.pdf; doi:https://doi.org/10.1136/heartjnl-2020-317870; html:https://europepmc.org/articles/PMC7536637; pdf:https://europepmc.org/articles/PMC7536637?pdf=render -36812617,https://doi.org/10.1371/journal.pdig.0000162,Informing antimicrobial stewardship with explainable AI.,"Cavallaro M, Moran E, Collyer B, McCarthy ND, Green C, Keeling MJ.",,PLOS digital health,2023,2023-01-05,Y,,,,"The accuracy and flexibility of artificial intelligence (AI) systems often comes at the cost of a decreased ability to offer an intuitive explanation of their predictions. This hinders trust and discourage adoption of AI in healthcare, exacerbated by concerns over liabilities and risks to patients' health in case of misdiagnosis. Providing an explanation for a model's prediction is possible due to recent advances in the field of interpretable machine learning. We considered a data set of hospital admissions linked to records of antibiotic prescriptions and susceptibilities of bacterial isolates. An appropriately trained gradient boosted decision tree algorithm, supplemented by a Shapley explanation model, predicts the likely antimicrobial drug resistance, with the odds of resistance informed by characteristics of the patient, admission data, and historical drug treatments and culture test results. Applying this AI-based system, we found that it substantially reduces the risk of mismatched treatment compared with the observed prescriptions. The Shapley values provide an intuitive association between observations/data and outcomes; the associations identified are broadly consistent with expectations based on prior knowledge from health specialists. The results, and the ability to attribute confidence and explanations, support the wider adoption of AI in healthcare.",,pdf:https://journals.plos.org/digitalhealth/article/file?id=10.1371/journal.pdig.0000162&type=printable; doi:https://doi.org/10.1371/journal.pdig.0000162; html:https://europepmc.org/articles/PMC9931350; pdf:https://europepmc.org/articles/PMC9931350?pdf=render 35953587,https://doi.org/10.1038/s41588-022-01153-5,A multi-tissue atlas of regulatory variants in cattle.,"Liu S, Gao Y, Canela-Xandri O, Wang S, Yu Y, Cai W, Li B, Xiang R, Chamberlain AJ, Pairo-Castineira E, D'Mellow K, Rawlik K, Xia C, Yao Y, Navarro P, Rocha D, Li X, Yan Z, Li C, Rosen BD, Van Tassell CP, Vanraden PM, Zhang S, Ma L, Cole JB, Liu GE, Tenesa A, Fang L.",,Nature genetics,2022,2022-08-11,Y,,,,"Characterization of genetic regulatory variants acting on livestock gene expression is essential for interpreting the molecular mechanisms underlying traits of economic value and for increasing the rate of genetic gain through artificial selection. Here we build a Cattle Genotype-Tissue Expression atlas (CattleGTEx) as part of the pilot phase of the Farm animal GTEx (FarmGTEx) project for the research community based on 7,180 publicly available RNA-sequencing (RNA-seq) samples. We describe the transcriptomic landscape of more than 100 tissues/cell types and report hundreds of thousands of genetic associations with gene expression and alternative splicing for 23 distinct tissues. We evaluate the tissue-sharing patterns of these genetic regulatory effects, and functionally annotate them using multiomics data. Finally, we link gene expression in different tissues to 43 economically important traits using both transcriptome-wide association and colocalization analyses to decipher the molecular regulatory mechanisms underpinning such agronomic traits in cattle.",,pdf:https://europepmc.org/articles/pmc7613894?pdf=render; doi:https://doi.org/10.1038/s41588-022-01153-5; html:https://europepmc.org/articles/PMC7613894; pdf:https://europepmc.org/articles/PMC7613894?pdf=render +36812617,https://doi.org/10.1371/journal.pdig.0000162,Informing antimicrobial stewardship with explainable AI.,"Cavallaro M, Moran E, Collyer B, McCarthy ND, Green C, Keeling MJ.",,PLOS digital health,2023,2023-01-05,Y,,,,"The accuracy and flexibility of artificial intelligence (AI) systems often comes at the cost of a decreased ability to offer an intuitive explanation of their predictions. This hinders trust and discourage adoption of AI in healthcare, exacerbated by concerns over liabilities and risks to patients' health in case of misdiagnosis. Providing an explanation for a model's prediction is possible due to recent advances in the field of interpretable machine learning. We considered a data set of hospital admissions linked to records of antibiotic prescriptions and susceptibilities of bacterial isolates. An appropriately trained gradient boosted decision tree algorithm, supplemented by a Shapley explanation model, predicts the likely antimicrobial drug resistance, with the odds of resistance informed by characteristics of the patient, admission data, and historical drug treatments and culture test results. Applying this AI-based system, we found that it substantially reduces the risk of mismatched treatment compared with the observed prescriptions. The Shapley values provide an intuitive association between observations/data and outcomes; the associations identified are broadly consistent with expectations based on prior knowledge from health specialists. The results, and the ability to attribute confidence and explanations, support the wider adoption of AI in healthcare.",,pdf:https://journals.plos.org/digitalhealth/article/file?id=10.1371/journal.pdig.0000162&type=printable; doi:https://doi.org/10.1371/journal.pdig.0000162; html:https://europepmc.org/articles/PMC9931350; pdf:https://europepmc.org/articles/PMC9931350?pdf=render 35131989,https://doi.org/10.1097/mcp.0000000000000863,A clinical review of long-COVID with a focus on the respiratory system.,"Daines L, Zheng B, Pfeffer P, Hurst JR, Sheikh A.",,Current opinion in pulmonary medicine,2022,2022-02-07,N,,,,"

Purpose of review

Persistence of symptoms after acute coronavirus disease 2019 (COVID-19), often described as long- COVID, is common and debilitating. In this article, we review the epidemiology, clinical features, and research priorities for long-COVID focusing on the respiratory system.

Recent findings

Breathlessness, cough and chest pain were the most commonly reported respiratory symptoms associated with long-COVID. In hospitalised patients, abnormalities on lung function testing or chest imaging were observed less commonly at 12 months compared to six months since discharge. Clinical assessment of patients with persisting symptoms after acute COVID-19 requires a comprehensive evaluation to exclude other possible causes for symptoms. With no robust current evidence for interventions to treat long-COVID respiratory symptoms, symptomatic treatment, supported self-management and pulmonary rehabilitation should be considered to help individuals with respiratory symptoms associated with long-COVID.

Summary

Long-COVID is a debilitating syndrome that often includes persisting respiratory symptoms and to a lesser degree, abnormalities in lung physiology or imaging. Respiratory features of long-COVID may reduce over time, yet resolution is not seen in all cases. Future research is needed to understand the natural history of long-COVID, identify factors associated with spontaneous improvement/persistence, investigate mechanisms for persisting symptoms, and test interventions to prevent and treat long-COVID.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7612723; doi:https://doi.org/10.1097/MCP.0000000000000863; html:https://europepmc.org/articles/PMC7612723; pdf:https://europepmc.org/articles/PMC7612723?pdf=render; doi:https://doi.org/10.1097/mcp.0000000000000863 34828364,https://doi.org/10.3390/genes12111758,The Influence of CYP2D6 and CYP2C19 Genetic Variation on Diabetes Mellitus Risk in People Taking Antidepressants and Antipsychotics.,"Austin-Zimmerman I, Wronska M, Wang B, Irizar H, Thygesen JH, Bhat A, Denaxas S, Fatemifar G, Finan C, Harju-Seppänen J, Giannakopoulou O, Kuchenbaecker K, Zartaloudi E, McQuillin A, Bramon E.",,Genes,2021,2021-11-03,Y,Diabetes; CYP2C19; CYP2D6; Pharmacogenetics; Hba1c; Personalized Medicine; Uk Biobank,,,"CYP2D6 and CYP2C19 enzymes are essential in the metabolism of antidepressants and antipsychotics. Genetic variation in these genes may increase risk of adverse drug reactions. Antidepressants and antipsychotics have previously been associated with risk of diabetes. We examined whether individual genetic differences in CYP2D6 and CYP2C19 contribute to these effects. We identified 31,579 individuals taking antidepressants and 2699 taking antipsychotics within UK Biobank. Participants were classified as poor, intermediate, or normal metabolizers of CYP2D6, and as poor, intermediate, normal, rapid, or ultra-rapid metabolizers of CYP2C19. Risk of diabetes mellitus represented by HbA1c level was examined in relation to the metabolic phenotypes. CYP2D6 poor metabolizers taking paroxetine had higher Hb1Ac than normal metabolizers (mean difference: 2.29 mmol/mol; p < 0.001). Among participants with diabetes who were taking venlafaxine, CYP2D6 poor metabolizers had higher HbA1c levels compared to normal metabolizers (mean differences: 10.15 mmol/mol; p < 0.001. Among participants with diabetes who were taking fluoxetine, CYP2D6 intermediate metabolizers and decreased HbA1c, compared to normal metabolizers (mean difference -7.74 mmol/mol; p = 0.017). We did not observe any relationship between CYP2D6 or CYP2C19 metabolic status and HbA1c levels in participants taking antipsychotic medication. Our results indicate that the impact of genetic variation in CYP2D6 differs depending on diabetes status. Although our findings support existing clinical guidelines, further research is essential to inform pharmacogenetic testing for people taking antidepressants and antipsychotics.",,pdf:https://www.mdpi.com/2073-4425/12/11/1758/pdf?version=1637118460; doi:https://doi.org/10.3390/genes12111758; html:https://europepmc.org/articles/PMC8620997; pdf:https://europepmc.org/articles/PMC8620997?pdf=render 35304633,https://doi.org/10.1007/s00520-022-06976-w,An exploration of wellbeing in men diagnosed with prostate cancer undergoing active surveillance: a qualitative study.,"Eymech O, Brunckhorst O, Fox L, Jawaid A, Van Hemelrijck M, Stewart R, Dasgupta P, Ahmed K.",,Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer,2022,2022-03-19,Y,Quality of life; Mental health; prostate cancer; Active Surveillance; Mental Wellbeing; Psa Anxiety,,,"

Purpose

There is a growing emphasis on improving quality of life of people with prostate cancer. However, those undergoing active surveillance remain underrepresented in the literature with less known about their unique challenges. Therefore, we aimed to explore their lived experiences post diagnosis and its effect on their mental, social, and physical wellbeing.

Methods

Qualitative semi-structured interviews were conducted with 13 men undergoing active surveillance for low-risk disease. Thematic analysis was used to inductively co-construct themes through the lens of the biopsychosocial model.

Results

Mental wellbeing was strongly affected in our participants due to the overwhelming emotional impact of their diagnosis resulting in an 'Emotional Diagnostic Disequilibrium'. Informational awareness and education about prostate cancer helped patients with 'Recognition of the Impact'. Patients experienced an 'Unsettling Monitoring Cycle' due to the increased fear and anxiety around PSA monitoring appointments, with some men ignoring their mental wellbeing needs as their disease is 'A Future Problem'. 'Concealment of Diagnosis' left many feeling isolated and highlighted an important coping mechanisms in the 'Importance of a Social Support Network' theme. Finally, physical health mostly changed through alterations in health behaviour, leading to 'A Healthier Lifestyle' with increasing attribution of physical symptoms to age through 'Symptomatic Overshadowing'.

Conclusion

The greatest disease impact on men's wellbeing was at the time of diagnosis, with a subsequent cyclical anxiety and fear of disease progression prominent around monitoring appointments. Future research should explore ways to better support patients with these issues and at these times, improving their quality of life.",,pdf:https://link.springer.com/content/pdf/10.1007/s00520-022-06976-w.pdf; doi:https://doi.org/10.1007/s00520-022-06976-w; html:https://europepmc.org/articles/PMC8933126; pdf:https://europepmc.org/articles/PMC8933126?pdf=render @@ -665,8 +665,8 @@ PMC9644860,https://doi.org/,Maternal mental health and children’s development: 38670744,https://doi.org/10.1016/s2589-7500(24)00028-1,Data challenges for international health emergencies: lessons learned from ten international COVID-19 driver projects.,"Boylan S, Arsenault C, Barreto M, Bozza FA, Fonseca A, Forde E, Hookham L, Humphreys GS, Ichihara MY, Le Doare K, Liu XF, McNamara E, Mugunga JC, Oliveira JF, Ouma J, Postlethwaite N, Retford M, Reyes LF, Morris AD, Wozencraft A.",,The Lancet. Digital health,2024,2024-05-01,N,,,,"The COVID-19 pandemic highlighted the importance of international data sharing and access to improve health outcomes for all. The International COVID-19 Data Alliance (ICODA) programme enabled 12 exemplar or driver projects to use existing health-related data to address major research questions relating to the pandemic, and developed data science approaches that helped each research team to overcome challenges, accelerate the data research cycle, and produce rapid insights and outputs. These approaches also sought to address inequity in data access and use, test approaches to ethical health data use, and make summary datasets and outputs accessible to a wider group of researchers. This Health Policy paper focuses on the challenges and lessons learned from ten of the ICODA driver projects, involving researchers from 19 countries and a range of health-related datasets. The ICODA programme reviewed the time taken for each project to complete stages of the health data research cycle and identified common challenges in areas such as data sharing agreements and data curation. Solutions included provision of standard data sharing templates, additional data curation expertise at an early stage, and a trusted research environment that facilitated data sharing across national boundaries and reduced risk. These approaches enabled the driver projects to rapidly produce research outputs, including publications, shared code, dashboards, and innovative resources, which can all be accessed and used by other research teams to address global health challenges.",,doi:https://doi.org/10.1016/S2589-7500(24)00028-1 36949447,https://doi.org/10.1186/s12889-023-15345-z,Inequalities in colorectal cancer screening uptake in Wales: an examination of the impact of the temporary suspension of the screening programme during the COVID-19 pandemic.,"Bright D, Hillier S, Song J, Huws DW, Greene G, Hodgson K, Akbari A, Griffiths R, Davies AR, Gjini A.",,BMC public health,2023,2023-03-22,Y,Colorectal Cancer; Inequalities; Bowel; Ethnicity; Cancer Screening; Covid-19,,,"

Background

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

Methods

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

Results

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

Conclusion

Our findings are encouraging with overall uptake achieving the 60% Welsh standard during the first three months after the programme restarted in 2020 despite the disruption. Inequalities did not worsen after the programme resumed activities but variations in CRC screening in Wales associated with sex, age, deprivation and ethnic group remain. This needs to be considered in targeting strategies to improve uptake and informed choice in CRC screening to avoid exacerbating disparities in CRC outcomes as screening services recover from the pandemic.",,pdf:https://bmcpublichealth.biomedcentral.com/counter/pdf/10.1186/s12889-023-15345-z; doi:https://doi.org/10.1186/s12889-023-15345-z; html:https://europepmc.org/articles/PMC10031708; pdf:https://europepmc.org/articles/PMC10031708?pdf=render 37868035,https://doi.org/10.1016/j.xgen.2023.100385,Gene expression and RNA splicing explain large proportions of the heritability for complex traits in cattle.,"Xiang R, Fang L, Liu S, Macleod IM, Liu Z, Breen EJ, Gao Y, Liu GE, Tenesa A, CattleGTEx Consortium, Mason BA, Chamberlain AJ, Wray NR, Goddard ME.",,Cell genomics,2023,2023-08-23,Y,RNA splicing; Heritability; Gene Expression; Complex Traits; Eqtl; Sqtl; Bayesr; Bayesrc,,,"Many quantitative trait loci (QTLs) are in non-coding regions. Therefore, QTLs are assumed to affect gene regulation. Gene expression and RNA splicing are primary steps of transcription, so DNA variants changing gene expression (eVariants) or RNA splicing (sVariants) are expected to significantly affect phenotypes. We quantify the contribution of eVariants and sVariants detected from 16 tissues (n = 4,725) to 37 traits of ∼120,000 cattle (average magnitude of genetic correlation between traits = 0.13). Analyzed in Bayesian mixture models, averaged across 37 traits, cis and trans eVariants and sVariants detected from 16 tissues jointly explain 69.2% (SE = 0.5%) of heritability, 44% more than expected from the same number of random variants. This 69.2% includes an average of 24% from trans e-/sVariants (14% more than expected). Averaged across 56 lipidomic traits, multi-tissue cis and trans e-/sVariants also explain 71.5% (SE = 0.3%) of heritability, demonstrating the essential role of proximal and distal regulatory variants in shaping mammalian phenotypes.",,doi:https://doi.org/10.1016/j.xgen.2023.100385; doi:https://doi.org/10.1016/j.xgen.2023.100385; html:https://europepmc.org/articles/PMC10589627; pdf:https://europepmc.org/articles/PMC10589627?pdf=render -38727134,https://doi.org/10.1002/epi4.12957,Hospital-acquired infections as a risk factor for post-traumatic epilepsy: A registry-based cohort study.,"Chen Z, Laing J, Li J, O'Brien TJ, Gabbe BJ, Semple BD.",,Epilepsia open,2024,2024-05-10,N,Epilepsy; Sepsis; Bacterial; Meningitis; Seizure; Nosocomial,,,"

Objective

Hospital-acquired infections are a common complication for patients with moderate or severe traumatic brain injury (TBI), contributing to morbidity and mortality. As infection-mediated immune responses can predispose towards epilepsy, we hypothesized that post-injury hospital-acquired infections increase the risk of post-traumatic epilepsy (PTE).

Methods

A retrospective cohort study of adults with moderate to severe TBI was conducted using data from the Victorian State Trauma Registry in Australia. Infections were identified from the International Statistical Classification of Diseases and Related Health Problems 10th Revision-Australian Modification (ICD-10-AM) codes, and diagnosis of PTE was determined by the Glasgow Outcome Scale - Extended questionnaire regarding epileptic fits at 24 months follow-up.

Results

Of all TBI patients (n = 15 152), 24% had evidence of having had any type of infection, with the most common being pneumonia, urinary tract, and respiratory infections. Of those who responded to the PTE question at 24 months (n = 1361), 11% had developed PTE. Univariable analysis found that the incidence of PTE was higher in patients who had any type of infection compared to patients without an infection (p < 0.001). After adjustment for covariates associated with both development of PTE and risk of infection, multivariable analysis found a solid association between infection and PTE (adjusted RR = 1.59; 95% CI: 1.11-2.28; p = 0.011). Having any type of complicating infection acquired during admission was also associated with poor GOSE outcomes at subsequent follow-ups (adjusted OR = 0.20; 95% CI: 0.11-0.35, p < 0.001).

Significance

These findings suggest that hospital-acquired infections contribute to PTE development after TBI. Future investigation into infections as a modifiable target to reduce poor outcomes after TBI is warranted.

Plain language summary

Hospital-acquired infections are common in patients with traumatic brain injuries. A database study of adults with moderate or severe brain injuries in Australia examined whether these infections are associated with the development of epilepsy after a brain injury. 24% of patients had infections, with pneumonia and urinary tract infections being the most common. Of those surveyed 2 years after the injury, 11% developed post-traumatic epilepsy. Patients with infections had a significantly higher risk of epilepsy, even when accounting for other known risk factors, and infections were also linked to poor outcomes more broadly. The study suggests that preventing hospital-acquired infections could be a crucial target for improving outcomes after traumatic brain injuries.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/epi4.12957; doi:https://doi.org/10.1002/epi4.12957 33845909,https://doi.org/10.1186/s13326-021-00241-5,Improved characterisation of clinical text through ontology-based vocabulary expansion.,"Slater LT, Bradlow W, Ball S, Hoehndorf R, Gkoutos GV.",,Journal of biomedical semantics,2021,2021-04-12,Y,Ontology; Text Mining; Semantic Similarity; Vocabulary Expansion,,,"

Background

Biomedical ontologies contain a wealth of metadata that constitutes a fundamental infrastructural resource for text mining. For several reasons, redundancies exist in the ontology ecosystem, which lead to the same entities being described by several concepts in the same or similar contexts across several ontologies. While these concepts describe the same entities, they contain different sets of complementary metadata. Linking these definitions to make use of their combined metadata could lead to improved performance in ontology-based information retrieval, extraction, and analysis tasks.

Results

We develop and present an algorithm that expands the set of labels associated with an ontology class using a combination of strict lexical matching and cross-ontology reasoner-enabled equivalency queries. Across all disease terms in the Disease Ontology, the approach found 51,362 additional labels, more than tripling the number defined by the ontology itself. Manual validation by a clinical expert on a random sampling of expanded synonyms over the Human Phenotype Ontology yielded a precision of 0.912. Furthermore, we found that annotating patient visits in MIMIC-III with an extended set of Disease Ontology labels led to semantic similarity score derived from those labels being a significantly better predictor of matching first diagnosis, with a mean average precision of 0.88 for the unexpanded set of annotations, and 0.913 for the expanded set.

Conclusions

Inter-ontology synonym expansion can lead to a vast increase in the scale of vocabulary available for text mining applications. While the accuracy of the extended vocabulary is not perfect, it nevertheless led to a significantly improved ontology-based characterisation of patients from text in one setting. Furthermore, where run-on error is not acceptable, the technique can be used to provide candidate synonyms which can be checked by a domain expert.",,pdf:https://jbiomedsem.biomedcentral.com/track/pdf/10.1186/s13326-021-00241-5; doi:https://doi.org/10.1186/s13326-021-00241-5; html:https://europepmc.org/articles/PMC8042947; pdf:https://europepmc.org/articles/PMC8042947?pdf=render +38727134,https://doi.org/10.1002/epi4.12957,Hospital-acquired infections as a risk factor for post-traumatic epilepsy: A registry-based cohort study.,"Chen Z, Laing J, Li J, O'Brien TJ, Gabbe BJ, Semple BD.",,Epilepsia open,2024,2024-05-10,N,Epilepsy; Sepsis; Bacterial; Meningitis; Seizure; Nosocomial,,,"

Objective

Hospital-acquired infections are a common complication for patients with moderate or severe traumatic brain injury (TBI), contributing to morbidity and mortality. As infection-mediated immune responses can predispose towards epilepsy, we hypothesized that post-injury hospital-acquired infections increase the risk of post-traumatic epilepsy (PTE).

Methods

A retrospective cohort study of adults with moderate to severe TBI was conducted using data from the Victorian State Trauma Registry in Australia. Infections were identified from the International Statistical Classification of Diseases and Related Health Problems 10th Revision-Australian Modification (ICD-10-AM) codes, and diagnosis of PTE was determined by the Glasgow Outcome Scale - Extended questionnaire regarding epileptic fits at 24 months follow-up.

Results

Of all TBI patients (n = 15 152), 24% had evidence of having had any type of infection, with the most common being pneumonia, urinary tract, and respiratory infections. Of those who responded to the PTE question at 24 months (n = 1361), 11% had developed PTE. Univariable analysis found that the incidence of PTE was higher in patients who had any type of infection compared to patients without an infection (p < 0.001). After adjustment for covariates associated with both development of PTE and risk of infection, multivariable analysis found a solid association between infection and PTE (adjusted RR = 1.59; 95% CI: 1.11-2.28; p = 0.011). Having any type of complicating infection acquired during admission was also associated with poor GOSE outcomes at subsequent follow-ups (adjusted OR = 0.20; 95% CI: 0.11-0.35, p < 0.001).

Significance

These findings suggest that hospital-acquired infections contribute to PTE development after TBI. Future investigation into infections as a modifiable target to reduce poor outcomes after TBI is warranted.

Plain language summary

Hospital-acquired infections are common in patients with traumatic brain injuries. A database study of adults with moderate or severe brain injuries in Australia examined whether these infections are associated with the development of epilepsy after a brain injury. 24% of patients had infections, with pneumonia and urinary tract infections being the most common. Of those surveyed 2 years after the injury, 11% developed post-traumatic epilepsy. Patients with infections had a significantly higher risk of epilepsy, even when accounting for other known risk factors, and infections were also linked to poor outcomes more broadly. The study suggests that preventing hospital-acquired infections could be a crucial target for improving outcomes after traumatic brain injuries.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/epi4.12957; doi:https://doi.org/10.1002/epi4.12957 36720882,https://doi.org/10.1038/s41597-023-01949-y,"Quality control and removal of technical variation of NMR metabolic biomarker data in ~120,000 UK Biobank participants.","Ritchie SC, Surendran P, Karthikeyan S, Lambert SA, Bolton T, Pennells L, Danesh J, Di Angelantonio E, Butterworth AS, Inouye M.",,Scientific data,2023,2023-01-31,Y,,,,"Metabolic biomarker data quantified by nuclear magnetic resonance (NMR) spectroscopy in approximately 121,000 UK Biobank participants has recently been released as a community resource, comprising absolute concentrations and ratios of 249 circulating metabolites, lipids, and lipoprotein sub-fractions. Here we identify and characterise additional sources of unwanted technical variation influencing individual biomarkers in the data available to download from UK Biobank. These included sample preparation time, shipping plate well, spectrometer batch effects, drift over time within spectrometer, and outlier shipping plates. We developed a procedure for removing this unwanted technical variation, and demonstrate that it increases signal for genetic and epidemiological studies of the NMR metabolic biomarker data in UK Biobank. We subsequently developed an R package, ukbnmr, which we make available to the wider research community to enhance the utility of the UK Biobank NMR metabolic biomarker data and to facilitate rapid analysis.",,pdf:https://www.nature.com/articles/s41597-023-01949-y.pdf; doi:https://doi.org/10.1038/s41597-023-01949-y; html:https://europepmc.org/articles/PMC9887579; pdf:https://europepmc.org/articles/PMC9887579?pdf=render 35305568,https://doi.org/10.1186/s12882-022-02742-6,Interaction between socioeconomic deprivation and ethnicity for likelihood of receiving living-donor kidney transplantation.,"Khalil K, Brotherton A, Moore S, Evison F, Gallier S, Hodson J, Sharif A.",,BMC nephrology,2022,2022-03-19,Y,Diversity; Kidney transplantation; Ethnicity; Deprivation; Living Kidney Donors,,,"

Background

The interplay between ethnicity and socioeconomic deprivation for living-donor kidney transplantation (LDKT) opportunities is unclear.

Methods

Data for 2040 consecutive kidney-alone transplant recipients receiving an allograft between 1st January 2007 and 30th June 2020 at a single center were retrospectively analyzed. The associations between the proportions of transplants that were LDKT (versus deceased donation) and both ethnicity and socioeconomic deprivation were assessed, with the latter quantified by the Index of Multiple Deprivation (IMD) quintile.

Results

The cohort comprised recipients of White (64.7%), South Asian (21.7%), Black (7.0%) and other (6.6%) ethnic groups. Recipients tended to be from socioeconomically deprived areas, with the most deprived quintile being the most frequently observed (quintile 1: 38.6% of patients); non-White recipients were significantly more likely to live in socioeconomically deprived areas (p < 0.001). Overall, 36.5% of transplants were LDKT, with this proportion declining progressively with socioeconomic deprivation, from 50.4 to 27.6% in the least versus most deprived IMD quintile (p < 0.001). A significant difference across recipient ethnicities was also observed, with the proportion of LDKTs ranging from 43.2% in White recipients to 17.8% in Black recipients (p < 0.001). Both socioeconomic deprivation (p < 0.001) and ethnicity (p = 0.005) remained significant predictors of LDKT on multivariable analysis, with a significant interaction between these factors also being observed (p < 0.001). Further assessment of this interaction effect found that, whilst there was a marked difference in the proportions of transplants that were LDKT between White versus non-White recipients in the most socioeconomically deprived groups (39.5% versus 19.3%), no such difference was seen in the least deprived recipients (48.5% versus 51.9%).

Conclusions

Whilst both socioeconomic deprivation and non-White ethnicity are independent predictors for lower proportions of LDKTs, the significant interaction between the two factors should be appreciated.",,pdf:https://bmcnephrol.biomedcentral.com/track/pdf/10.1186/s12882-022-02742-6; doi:https://doi.org/10.1186/s12882-022-02742-6; html:https://europepmc.org/articles/PMC8934457; pdf:https://europepmc.org/articles/PMC8934457?pdf=render 38388753,https://doi.org/10.1007/s00125-024-06099-3,Phenotype-based targeted treatment of SGLT2 inhibitors and GLP-1 receptor agonists in type 2 diabetes.,"Cardoso P, Young KG, Nair ATN, Hopkins R, McGovern AP, Haider E, Karunaratne P, Donnelly L, Mateen BA, Sattar N, Holman RR, Bowden J, Hattersley AT, Pearson ER, Jones AG, Shields BM, McKinley TJ, Dennis JM, MASTERMIND consortium.",,Diabetologia,2024,2024-02-22,Y,Type 2 diabetes; Precision Medicine; Sglt2-inhibitors; Heterogeneous Treatment Effects; Bayesian Non-parametric Modelling; Glp1-receptor Agonists,,,"

Aims/hypothesis

A precision medicine approach in type 2 diabetes could enhance targeting specific glucose-lowering therapies to individual patients most likely to benefit. We aimed to use the recently developed Bayesian causal forest (BCF) method to develop and validate an individualised treatment selection algorithm for two major type 2 diabetes drug classes, sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1-RA).

Methods

We designed a predictive algorithm using BCF to estimate individual-level conditional average treatment effects for 12-month glycaemic outcome (HbA1c) between SGLT2i and GLP1-RA, based on routine clinical features of 46,394 people with type 2 diabetes in primary care in England (Clinical Practice Research Datalink; 27,319 for model development, 19,075 for hold-out validation), with additional external validation in 2252 people with type 2 diabetes from Scotland (SCI-Diabetes [Tayside & Fife]). Differences in glycaemic outcome with GLP1-RA by sex seen in clinical data were replicated in clinical trial data (HARMONY programme: liraglutide [n=389] and albiglutide [n=1682]). As secondary outcomes, we evaluated the impacts of targeting therapy based on glycaemic response on weight change, tolerability and longer-term risk of new-onset microvascular complications, macrovascular complications and adverse kidney events.

Results

Model development identified marked heterogeneity in glycaemic response, with 4787 (17.5%) of the development cohort having a predicted HbA1c benefit >3 mmol/mol (>0.3%) with SGLT2i over GLP1-RA and 5551 (20.3%) having a predicted HbA1c benefit >3 mmol/mol with GLP1-RA over SGLT2i. Calibration was good in hold-back validation, and external validation in an independent Scottish dataset identified clear differences in glycaemic outcomes between those predicted to benefit from each therapy. Sex, with women markedly more responsive to GLP1-RA, was identified as a major treatment effect modifier in both the UK observational datasets and in clinical trial data: HARMONY-7 liraglutide (GLP1-RA): 4.4 mmol/mol (95% credible interval [95% CrI] 2.2, 6.3) (0.4% [95% CrI 0.2, 0.6]) greater response in women than men. Targeting the two therapies based on predicted glycaemic response was also associated with improvements in short-term tolerability and long-term risk of new-onset microvascular complications.

Conclusions/interpretation

Precision medicine approaches can facilitate effective individualised treatment choice between SGLT2i and GLP1-RA therapies, and the use of routinely collected clinical features for treatment selection could support low-cost deployment in many countries.",,doi:https://doi.org/10.1007/s00125-024-06099-3; html:https://europepmc.org/articles/PMC10955037; pdf:https://europepmc.org/articles/PMC10955037?pdf=render @@ -674,12 +674,12 @@ PMC9644860,https://doi.org/,Maternal mental health and children’s development: 34726481,https://doi.org/10.1126/science.abl9551,"Exponential growth, high prevalence of SARS-CoV-2, and vaccine effectiveness associated with the Delta variant.","Elliott P, Haw D, Wang H, Eales O, Walters CE, Ainslie KEC, Atchison C, Fronterre C, Diggle PJ, Page AJ, Trotter AJ, Prosolek SJ, COVID-19 Genomics UK (COG-UK) Consortium11‡, Ashby D, Donnelly CA, Barclay W, Taylor G, Cooke G, Ward H, Darzi A, Riley S.",,"Science (New York, N.Y.)",2021,2021-12-17,Y,,,,"Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections were rising during early summer 2021 in many countries as a result of the Delta variant. We assessed reverse transcription polymerase chain reaction swab positivity in the Real-time Assessment of Community Transmission–1 (REACT-1) study in England. During June and July 2021, we observed sustained exponential growth with an average doubling time of 25 days, driven by complete replacement of the Alpha variant by Delta and by high prevalence at younger, less-vaccinated ages. Prevalence among unvaccinated people [1.21% (95% credible interval 1.03%, 1.41%)] was three times that among double-vaccinated people [0.40% (95% credible interval 0.34%, 0.48%)]. However, after adjusting for age and other variables, vaccine effectiveness for double-vaccinated people was estimated at between ~50% and ~60% during this period in England. Increased social mixing in the presence of Delta had the potential to generate sustained growth in infections, even at high levels of vaccination.",,pdf:https://www.science.org/history/7d0b03b2-b465-410e-a40d-7300157d8b54/science.abl9551.v1.pdf; doi:https://doi.org/10.1126/science.abl9551; html:https://europepmc.org/articles/PMC10763627; pdf:https://europepmc.org/articles/PMC10763627?pdf=render 37004203,https://doi.org/10.1093/qjmed/hcad050,Classifying the unclassifiable-a Delphi study to reach consensus on the fibrotic nature of diseases.,"Massen GM, Allen RJ, Leavy OC, Selby NM, Aithal GP, Oliver N, Parfrey H, Wain LV, Jenkins G, Stewart I, Quint JK.",,QJM : monthly journal of the Association of Physicians,2023,2023-06-01,Y,,,,"

Background

Traditionally, clinical research has focused on individual fibrotic diseases or fibrosis in a particular organ. However, it is possible for people to have multiple fibrotic diseases. While multi-organ fibrosis may suggest shared pathogenic mechanisms, yet there is no consensus on what constitutes a fibrotic disease and therefore fibrotic multimorbidity.

Aim

A Delphi study was performed to reach consensus on which diseases may be described as fibrotic.

Methods

Participants were asked to rate a list of diseases, sub-grouped according to eight body regions, as 'fibrotic manifestation always present', 'can develop fibrotic manifestations', 'associated with fibrotic manifestations' or 'not fibrotic nor associated'. Classifications of 'fibrotic manifestation always present' and 'can develop fibrotic manifestations' were merged and termed 'fibrotic'. Clinical consensus was defined according to the interquartile range, having met a minimum number of responses. Clinical agreement was used for classification where diseases did not meet the minimum number of responses (required for consensus measure), were only classified if there was 100% consensus on disease classification.

Results

After consulting experts, searching the literature and coding dictionaries, a total of 323 non-overlapping diseases which might be considered fibrotic were identified; 92 clinical specialists responded to the first round of the survey. Over three survey rounds, 240 diseases were categorized as fibrotic via clinical consensus and 25 additional diseases through clinical agreement.

Conclusion

Using a robust methodology, an extensive list of diseases was classified. The findings lay the foundations for studies estimating the burden of fibrotic multimorbidity, as well as investigating shared mechanisms and therapies.",,pdf:https://academic.oup.com/qjmed/advance-article-pdf/doi/10.1093/qjmed/hcad050/50051055/hcad050.pdf; doi:https://doi.org/10.1093/qjmed/hcad050; html:https://europepmc.org/articles/PMC10250078; pdf:https://europepmc.org/articles/PMC10250078?pdf=render 33371011,https://doi.org/10.1136/bmjresp-2020-000770,Physiological tests of small airways function in diagnosing asthma: a systematic review.,"Almeshari MA, Alobaidi NY, Edgar RG, Stockley J, Sapey E.",,BMJ open respiratory research,2020,2020-12-01,Y,Asthma; Lung Physiology,,,"

Background

Asthma is a common, heterogeneous disease that is characterised by chronic airway inflammation and variable expiratory airflow limitation. Current guidelines use spirometric measures for asthma assessment. This systematic review aimed to assess whether the most commonly reported tests of small airways function could contribute to the diagnosis of asthma.

Methods

Standard systematic review methodology was used, and a range of electronic databases was searched (Embase, MEDLINE, CINAHL, CENTRAL, Web of Science, DARE). Studies that included physiological tests of small airways function to diagnose asthma in adults were included, with no restrictions on language or date. The risk of bias and quality assessment tools used were Agency for Healthcare Research and Quality tool for cross-sectional studies and Quality Assessment of Diagnostic Accuracy Studies 2 for diagnostic test accuracy (DTA) studies.

Results

7072 studies were identified and 10 studies met review criteria. 7 included oscillation techniques and 5 included maximal mid-expiratory flow (MMEF). Studies were small and of variable quality. In oscillometry, total resistance (R5) and reactance at 5 Hz (X5) was altered in asthma compared with healthy controls. The percentage predicted of MMEF was lower in patients with asthma compared with controls in all studies and lower than the % predicted forced expiratory volume in 1 s. In DTA of oscillometry, R5 showed a sensitivity between 69% and 72% and specificity between 61% and 86%.

Conclusion

There were differences in the results of physiological tests of small airway function in patients with asthma compared with controls. However, studies are small and heterogeneous. Further studies are needed to assess the effectiveness of these tests on a larger scale, including studies to determine which test methodology is the most useful in asthma.",,pdf:https://bmjopenrespres.bmj.com/content/bmjresp/7/1/e000770.full.pdf; doi:https://doi.org/10.1136/bmjresp-2020-000770; html:https://europepmc.org/articles/PMC7754643; pdf:https://europepmc.org/articles/PMC7754643?pdf=render -38627354,https://doi.org/10.1007/s15010-024-02235-8,"Sepsis and case fatality rates and associations with deprivation, ethnicity, and clinical characteristics: population-based case-control study with linked primary care and hospital data in England.","van Staa TP, Pate A, Martin GP, Sharma A, Dark P, Felton T, Zhong X, Bladon S, Cunningham N, Gilham EL, Brown CS, Mirfenderesky M, Palin V, Ashiru-Oredope D.",,Infection,2024,2024-04-16,N,Sepsis; RACE; Frailty; Primary Care; Deprivation,,,"

Purpose

Sepsis is a life-threatening organ dysfunction caused by dysregulated host response to infection. The purpose of the study was to measure the associations of specific exposures (deprivation, ethnicity, and clinical characteristics) with incident sepsis and case fatality.

Methods

Two research databases in England were used including anonymized patient-level records from primary care linked to hospital admission, death certificate, and small-area deprivation. Sepsis cases aged 65-100 years were matched to up to six controls. Predictors for sepsis (including 60 clinical conditions) were evaluated using logistic and random forest models; case fatality rates were analyzed using logistic models.

Results

108,317 community-acquired sepsis cases were analyzed. Severe frailty was strongly associated with the risk of developing sepsis (crude odds ratio [OR] 14.93; 95% confidence interval [CI] 14.37-15.52). The quintile with most deprived patients showed an increased sepsis risk (crude OR 1.48; 95% CI 1.45-1.51) compared to least deprived quintile. Strong predictors for sepsis included antibiotic exposure in prior 2 months, being house bound, having cancer, learning disability, and diabetes mellitus. Severely frail patients had a case fatality rate of 42.0% compared to 24.0% in non-frail patients (adjusted OR 1.53; 95% CI 1.41-1.65). Sepsis cases with recent prior antibiotic exposure died less frequently compared to non-users (adjusted OR 0.7; 95% CI 0.72-0.76). Case fatality strongly decreased over calendar time.

Conclusion

Given the variety of predictors and their level of associations for developing sepsis, there is a need for prediction models for risk of developing sepsis that can help to target preventative antibiotic therapy.",,pdf:https://link.springer.com/content/pdf/10.1007/s15010-024-02235-8.pdf; doi:https://doi.org/10.1007/s15010-024-02235-8 -37550086,https://doi.org/10.1136/bmjment-2023-300762,Associations between air pollution and mental health service use in dementia: a retrospective cohort study.,"Ronaldson A, Stewart R, Mueller C, Das-Munshi J, Newbury JB, Mudway IS, Broadbent M, Fisher HL, Beevers S, Dajnak D, Hotopf M, Hatch SL, Bakolis I.",,BMJ mental health,2023,2023-07-01,Y,Psychiatry; Adult Psychiatry; Delirium & Cognitive Disorders,,,"

Background

Little is known about the role of air pollution in how people with dementia use mental health services.

Objective

We examined longitudinal associations between air pollution exposure and mental health service use in people with dementia.

Methods

In 5024 people aged 65 years or older with dementia in South London, high resolution estimates of nitrogen dioxide (NO2) and particulate matter (PM2.5 and PM10) levels in ambient air were linked to residential addresses. Associations between air pollution and Community Mental Health Team (CMHT) events (recorded over 9 years) were examined using negative binomial regression models. Cognitive function was measured using the Mini Mental State Examination (MMSE) and health and social functioning was measured using the Health of the Nation Outcomes Scale (HoNOS65+). Associations between air pollution and both MMSE and HoNOS65+ scores were assessed using linear regression models.

Findings

In the first year of follow-up, increased exposure to all air pollutants was associated with an increase in the use of CMHTs in a dose-response manner. These associations were strongest when we compared the highest air pollution quartile (quartile 4: Q4) with the lowest quartile (Q1) (eg, NO2: adjusted incidence rate ratio (aIRR) 1.27, 95% CI 1.11 to 1.45, p<0.001). Dose-response patterns between PM2.5 and CMHT events remained at 5 and 9 years. Associations were strongest for patients with vascular dementia. NO2 levels were linked with poor functional status, but not cognitive function.

Conclusions

Residential air pollution exposure is associated with increased CMHT usage among people with dementia.

Clinical implications

Efforts to reduce pollutant exposures in urban settings might reduce the use of mental health services in people with dementia, freeing up resources in already considerably stretched psychiatric services.",,doi:https://doi.org/10.1136/bmjment-2023-300762; html:https://europepmc.org/articles/PMC10577765; pdf:https://europepmc.org/articles/PMC10577765?pdf=render 36929232,https://doi.org/10.1002/jmri.28675,Image-Based Biological Heart Age Estimation Reveals Differential Aging Patterns Across Cardiac Chambers.,"Salih AM, Pujadas ER, Campello VM, McCracken C, Harvey NC, Neubauer S, Lekadir K, Nichols TE, Petersen SE, Raisi-Estabragh Z.",,Journal of magnetic resonance imaging : JMRI,2023,2023-03-16,Y,Aging; Cardiac Imaging; Cardiac Health; Radiomics,,,"

Background

Biological heart age estimation can provide insights into cardiac aging. However, existing studies do not consider differential aging across cardiac regions.

Purpose

To estimate biological age of the left ventricle (LV), right ventricle (RV), myocardium, left atrium, and right atrium using magnetic resonance imaging radiomics phenotypes and to investigate determinants of aging by cardiac region.

Study type

Cross-sectional.

Population

A total of 18,117 healthy UK Biobank participants including 8338 men (mean age = 64.2 ± 7.5) and 9779 women (mean age = 63.0 ± 7.4).

Field strength/sequence

A 1.5 T/balanced steady-state free precession.

Assessment

An automated algorithm was used to segment the five cardiac regions, from which radiomic features were extracted. Bayesian ridge regression was used to estimate biological age of each cardiac region with radiomics features as predictors and chronological age as the output. The ""age gap"" was the difference between biological and chronological age. Linear regression was used to calculate associations of age gap from each cardiac region with socioeconomic, lifestyle, body composition, blood pressure and arterial stiffness, blood biomarkers, mental well-being, multiorgan health, and sex hormone exposures (n = 49).

Statistical test

Multiple testing correction with false discovery method (threshold = 5%).

Results

The largest model error was with RV and the smallest with LV age (mean absolute error in men: 5.26 vs. 4.96 years). There were 172 statistically significant age gap associations. Greater visceral adiposity was the strongest correlate of larger age gaps, for example, myocardial age gap in women (Beta = 0.85, P = 1.69 × 10-26 ). Poor mental health associated with large age gaps, for example, ""disinterested"" episodes and myocardial age gap in men (Beta = 0.25, P = 0.001), as did a history of dental problems (eg LV in men Beta = 0.19, P = 0.02). Higher bone mineral density was the strongest associate of smaller age gaps, for example, myocardial age gap in men (Beta = -1.52, P = 7.44 × 10-6 ).

Data conclusion

This work demonstrates image-based heart age estimation as a novel method for understanding cardiac aging.

Evidence level

1.

Technical efficacy

Stage 1.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/jmri.28675; doi:https://doi.org/10.1002/jmri.28675; html:https://europepmc.org/articles/PMC10947470; pdf:https://europepmc.org/articles/PMC10947470?pdf=render +37550086,https://doi.org/10.1136/bmjment-2023-300762,Associations between air pollution and mental health service use in dementia: a retrospective cohort study.,"Ronaldson A, Stewart R, Mueller C, Das-Munshi J, Newbury JB, Mudway IS, Broadbent M, Fisher HL, Beevers S, Dajnak D, Hotopf M, Hatch SL, Bakolis I.",,BMJ mental health,2023,2023-07-01,Y,Psychiatry; Adult Psychiatry; Delirium & Cognitive Disorders,,,"

Background

Little is known about the role of air pollution in how people with dementia use mental health services.

Objective

We examined longitudinal associations between air pollution exposure and mental health service use in people with dementia.

Methods

In 5024 people aged 65 years or older with dementia in South London, high resolution estimates of nitrogen dioxide (NO2) and particulate matter (PM2.5 and PM10) levels in ambient air were linked to residential addresses. Associations between air pollution and Community Mental Health Team (CMHT) events (recorded over 9 years) were examined using negative binomial regression models. Cognitive function was measured using the Mini Mental State Examination (MMSE) and health and social functioning was measured using the Health of the Nation Outcomes Scale (HoNOS65+). Associations between air pollution and both MMSE and HoNOS65+ scores were assessed using linear regression models.

Findings

In the first year of follow-up, increased exposure to all air pollutants was associated with an increase in the use of CMHTs in a dose-response manner. These associations were strongest when we compared the highest air pollution quartile (quartile 4: Q4) with the lowest quartile (Q1) (eg, NO2: adjusted incidence rate ratio (aIRR) 1.27, 95% CI 1.11 to 1.45, p<0.001). Dose-response patterns between PM2.5 and CMHT events remained at 5 and 9 years. Associations were strongest for patients with vascular dementia. NO2 levels were linked with poor functional status, but not cognitive function.

Conclusions

Residential air pollution exposure is associated with increased CMHT usage among people with dementia.

Clinical implications

Efforts to reduce pollutant exposures in urban settings might reduce the use of mental health services in people with dementia, freeing up resources in already considerably stretched psychiatric services.",,doi:https://doi.org/10.1136/bmjment-2023-300762; html:https://europepmc.org/articles/PMC10577765; pdf:https://europepmc.org/articles/PMC10577765?pdf=render +38627354,https://doi.org/10.1007/s15010-024-02235-8,"Sepsis and case fatality rates and associations with deprivation, ethnicity, and clinical characteristics: population-based case-control study with linked primary care and hospital data in England.","van Staa TP, Pate A, Martin GP, Sharma A, Dark P, Felton T, Zhong X, Bladon S, Cunningham N, Gilham EL, Brown CS, Mirfenderesky M, Palin V, Ashiru-Oredope D.",,Infection,2024,2024-04-16,N,Sepsis; RACE; Frailty; Primary Care; Deprivation,,,"

Purpose

Sepsis is a life-threatening organ dysfunction caused by dysregulated host response to infection. The purpose of the study was to measure the associations of specific exposures (deprivation, ethnicity, and clinical characteristics) with incident sepsis and case fatality.

Methods

Two research databases in England were used including anonymized patient-level records from primary care linked to hospital admission, death certificate, and small-area deprivation. Sepsis cases aged 65-100 years were matched to up to six controls. Predictors for sepsis (including 60 clinical conditions) were evaluated using logistic and random forest models; case fatality rates were analyzed using logistic models.

Results

108,317 community-acquired sepsis cases were analyzed. Severe frailty was strongly associated with the risk of developing sepsis (crude odds ratio [OR] 14.93; 95% confidence interval [CI] 14.37-15.52). The quintile with most deprived patients showed an increased sepsis risk (crude OR 1.48; 95% CI 1.45-1.51) compared to least deprived quintile. Strong predictors for sepsis included antibiotic exposure in prior 2 months, being house bound, having cancer, learning disability, and diabetes mellitus. Severely frail patients had a case fatality rate of 42.0% compared to 24.0% in non-frail patients (adjusted OR 1.53; 95% CI 1.41-1.65). Sepsis cases with recent prior antibiotic exposure died less frequently compared to non-users (adjusted OR 0.7; 95% CI 0.72-0.76). Case fatality strongly decreased over calendar time.

Conclusion

Given the variety of predictors and their level of associations for developing sepsis, there is a need for prediction models for risk of developing sepsis that can help to target preventative antibiotic therapy.",,pdf:https://link.springer.com/content/pdf/10.1007/s15010-024-02235-8.pdf; doi:https://doi.org/10.1007/s15010-024-02235-8 37650026,https://doi.org/10.23889/ijpds.v7i1.1727,An overview of synthetic administrative data for research.,"Kokosi T, De Stavola B, Mitra R, Frayling L, Doherty A, Dove I, Sonnenberg P, Harron K.",,International journal of population data science,2022,2022-05-23,Y,Data Linkage; Statistical Disclosure Control; Data Utility; Synthetic Data; Data Confidentiality; Administrative Datasets,,,"Use of administrative data for research and for planning services has increased over recent decades due to the value of the large, rich information available. However, concerns about the release of sensitive or personal data and the associated disclosure risk can lead to lengthy approval processes and restricted data access. This can delay or prevent the production of timely evidence. A promising solution to facilitate more efficient data access is to create synthetic versions of the original datasets which are less likely to hold confidential information and can minimise disclosure risk. Such data may be used as an interim solution, allowing researchers to develop their analysis plans on non-disclosive data, whilst waiting for access to the real data. We aim to provide an overview of the background and uses of synthetic data and describe common methods used to generate synthetic data in the context of UK administrative research. We propose a simplified terminology for categories of synthetic data (univariate, multivariate, and complex modality synthetic data) as well as a more comprehensive description of the terminology used in the existing literature and illustrate challenges and future directions for research.",,pdf:https://ijpds.org/article/download/1727/3395; doi:https://doi.org/10.23889/ijpds.v7i1.1727; html:https://europepmc.org/articles/PMC10464868; pdf:https://europepmc.org/articles/PMC10464868?pdf=render -38849195,https://doi.org/10.1136/archdischild-2023-326756,Utility and acceptability of remote 6-lead electrocardiographic monitoring in children with inherited cardiac conditions.,"Lawley CM, Luczak-Wozniak K, Chung SC, Field E, Barnes A, Starling L, Cervi E, Kaski JP.",,Archives of disease in childhood,2024,2024-06-07,N,Cardiology; Paediatrics,,,"

Objective

This pilot study sought to investigate the utility and acceptability of the KardiaMobile 6-lead ECG (KM6LECG) as a tool for remote monitoring in children with inherited cardiac conditions.

Design

A single-centre prospective cohort study. Children underwent standard clinical evaluation including a 12-lead ECG and a KM6LECG in the clinic. Participants recorded KM6LECGs monthly at home for 3 months. Families completed a questionnaire on their experience.

Setting

Great Ormond Street Hospital Centre for Inherited Cardiovascular Diseases.

Participants

64 children: 22 with hypertrophic cardiomyopathy (HCM); 22 with long QT syndrome and 20 unaffected siblings (controls).

Main outcome measures

Comparison of data extracted from the clinic 12-lead ECG and supervised KM6LECG, and the supervised and unsupervised KM6LECG recording.

Results

Of 64 children (35% female, mean age 12 years), 58 had a baseline 12-lead ECG and appropriate baseline KM6LECG. In children with HCM, abnormalities in ventricular depolarisation/repolarisation in the limb leads of the 12-lead ECG were reliably reproduced. From the whole cohort, there was a strong positive correlation between the corrected QT interval from the 12-lead ECG and baseline KM6LECG (intraclass correlation coefficient=0.839) and baseline KM6LECG with an unsupervised KM6LECG (intraclass correlation coefficient=0.736). Suspected 'lead' misplacement impacted 18% of unsupervised recordings. Overall, the acceptability of the KM6LECG to families was good.

Conclusions

The KM6LECG provides an accurate tool for assessing some ECG abnormalities associated with paediatric inherited cardiovascular disease and may provide a useful at-home adjunct to face-to-face clinical care of children requiring ECG assessment.",,doi:https://doi.org/10.1136/archdischild-2023-326756 33632765,https://doi.org/10.1136/thoraxjnl-2020-215986,"Neutrophils in asthma: the good, the bad and the bacteria.","Crisford H, Sapey E, Rogers GB, Taylor S, Nagakumar P, Lokwani R, Simpson JL.",,Thorax,2021,2021-02-25,Y,Asthma; Bacterial Infection; Paediatric Asthma; Asthma Mechanisms; Neutrophil Biology,,,"Airway inflammation plays a key role in asthma pathogenesis but is heterogeneous in nature. There has been significant scientific discovery with regard to type 2-driven, eosinophil-dominated asthma, with effective therapies ranging from inhaled corticosteroids to novel biologics. However, studies suggest that approximately 1 in 5 adults with asthma have an increased proportion of neutrophils in their airways. These patients tend to be older, have potentially pathogenic airway bacteria and do not respond well to classical therapies. Currently, there are no specific therapeutic options for these patients, such as neutrophil-targeting biologics.Neutrophils comprise 70% of the total circulatory white cells and play a critical defence role during inflammatory and infective challenges. This makes them a problematic target for therapeutics. Furthermore, neutrophil functions change with age, with reduced microbial killing, increased reactive oxygen species release and reduced production of extracellular traps with advancing age. Therefore, different therapeutic strategies may be required for different age groups of patients.The pathogenesis of neutrophil-dominated airway inflammation in adults with asthma may reflect a counterproductive response to the defective neutrophil microbial killing seen with age, resulting in bystander damage to host airway cells and subsequent mucus hypersecretion and airway remodelling. However, in children with asthma, neutrophils are less associated with adverse features of disease, and it is possible that in children, neutrophils are less pathogenic.In this review, we explore the mechanisms of neutrophil recruitment, changes in cellular function across the life course and the implications this may have for asthma management now and in the future. We also describe the prevalence of neutrophilic asthma globally, with a focus on First Nations people of Australia, New Zealand and North America.",,pdf:https://thorax.bmj.com/content/thoraxjnl/76/8/835.full.pdf; doi:https://doi.org/10.1136/thoraxjnl-2020-215986; html:https://europepmc.org/articles/PMC8311087; pdf:https://europepmc.org/articles/PMC8311087?pdf=render +38849195,https://doi.org/10.1136/archdischild-2023-326756,Utility and acceptability of remote 6-lead electrocardiographic monitoring in children with inherited cardiac conditions.,"Lawley CM, Luczak-Wozniak K, Chung SC, Field E, Barnes A, Starling L, Cervi E, Kaski JP.",,Archives of disease in childhood,2024,2024-06-07,N,Cardiology; Paediatrics,,,"

Objective

This pilot study sought to investigate the utility and acceptability of the KardiaMobile 6-lead ECG (KM6LECG) as a tool for remote monitoring in children with inherited cardiac conditions.

Design

A single-centre prospective cohort study. Children underwent standard clinical evaluation including a 12-lead ECG and a KM6LECG in the clinic. Participants recorded KM6LECGs monthly at home for 3 months. Families completed a questionnaire on their experience.

Setting

Great Ormond Street Hospital Centre for Inherited Cardiovascular Diseases.

Participants

64 children: 22 with hypertrophic cardiomyopathy (HCM); 22 with long QT syndrome and 20 unaffected siblings (controls).

Main outcome measures

Comparison of data extracted from the clinic 12-lead ECG and supervised KM6LECG, and the supervised and unsupervised KM6LECG recording.

Results

Of 64 children (35% female, mean age 12 years), 58 had a baseline 12-lead ECG and appropriate baseline KM6LECG. In children with HCM, abnormalities in ventricular depolarisation/repolarisation in the limb leads of the 12-lead ECG were reliably reproduced. From the whole cohort, there was a strong positive correlation between the corrected QT interval from the 12-lead ECG and baseline KM6LECG (intraclass correlation coefficient=0.839) and baseline KM6LECG with an unsupervised KM6LECG (intraclass correlation coefficient=0.736). Suspected 'lead' misplacement impacted 18% of unsupervised recordings. Overall, the acceptability of the KM6LECG to families was good.

Conclusions

The KM6LECG provides an accurate tool for assessing some ECG abnormalities associated with paediatric inherited cardiovascular disease and may provide a useful at-home adjunct to face-to-face clinical care of children requiring ECG assessment.",,doi:https://doi.org/10.1136/archdischild-2023-326756 35531432,https://doi.org/10.1016/s2666-7568(22)00093-9,"Outcomes of SARS-CoV-2 omicron infection in residents of long-term care facilities in England (VIVALDI): a prospective, cohort study.","Krutikov M, Stirrup O, Nacer-Laidi H, Azmi B, Fuller C, Tut G, Palmer T, Shrotri M, Irwin-Singer A, Baynton V, Hayward A, Moss P, Copas A, Shallcross L, COVID-19 Genomics UK consortium.",,The lancet. Healthy longevity,2022,2022-05-04,Y,,,,"

Background

The SARS-CoV-2 omicron variant (B.1.1.529) is highly transmissible, but disease severity appears to be reduced compared with previous variants such as alpha and delta. We investigated the risk of severe outcomes following infection in residents of long-term care facilities.

Methods

We did a prospective cohort study in residents of long-term care facilities in England who were tested regularly for SARS-CoV-2 between Sept 1, 2021, and Feb 1, 2022, and who were participants of the VIVALDI study. Residents were eligible for inclusion if they had a positive PCR or lateral flow device test during the study period, which could be linked to a National Health Service (NHS) number, enabling linkage to hospital admissions and mortality datasets. PCR or lateral flow device test results were linked to national hospital admission and mortality records using the NHS-number-based pseudo-identifier. We compared the risk of hospital admission (within 14 days following a positive SARS-CoV-2 test) or death (within 28 days) in residents who had tested positive for SARS-CoV-2 in the period shortly before omicron emerged (delta-dominant) and in the omicron-dominant period, adjusting for age, sex, primary vaccine course, past infection, and booster vaccination. Variants were confirmed by sequencing or spike-gene status in a subset of samples.

Results

795 233 tests were done in 333 long-term care facilities, of which 159 084 (20·0%) could not be linked to a pseudo-identifier and 138 012 (17·4%) were done in residents. Eight residents had two episodes of infection (>28 days apart) and in these cases the second episode was excluded from the analysis. 2264 residents in 259 long-term care facilities (median age 84·5 years, IQR 77·9-90·0) were diagnosed with SARS-CoV-2, of whom 253 (11·2%) had a previous infection and 1468 (64·8%) had received a booster vaccination. About a third of participants were male. Risk of hospital admissions was markedly lower in the 1864 residents infected in the omicron-period (4·51%, 95% CI 3·65-5·55) than in the 400 residents infected in the pre-omicron period (10·50%, 7·87-13·94), as was risk of death (5·48% [4·52-6·64] vs 10·75% [8·09-14·22]). Adjusted hazard ratios (aHR) also indicated a reduction in hospital admissions (0·64, 95% CI 0·41-1·00; p=0·051) and mortality (aHR 0·68, 0·44-1·04; p=0·076) in the omicron versus the pre-omicron period. Findings were similar in residents with a confirmed variant.

Interpretation

Observed reduced severity of the omicron variant compared with previous variants suggests that the wave of omicron infections is unlikely to lead to a major surge in severe disease in long-term care facility populations with high levels of vaccine coverage or natural immunity. Continued surveillance in this vulnerable population is important to protect residents from infection and monitor the public health effect of emerging variants.

Funding

UK Department of Health and Social Care.",,pdf:http://www.thelancet.com/article/S2666756822000939/pdf; doi:https://doi.org/10.1016/S2666-7568(22)00093-9; html:https://europepmc.org/articles/PMC9067940; pdf:https://europepmc.org/articles/PMC9067940?pdf=render 31774502,https://doi.org/10.1093/ehjcvp/pvz071,An observational study of international normalized ratio control according to NICE criteria in patients with non-valvular atrial fibrillation: the SAIL Warfarin Out of Range Descriptors Study (SWORDS).,"Harris DE, Thayer D, Wang T, Brooks C, Murley G, Gravenor M, Hill NR, Lister S, Halcox J.",,European heart journal. Cardiovascular pharmacotherapy,2021,2021-01-01,Y,Atrial fibrillation; Warfarin; Pharmacoepidemiology,Improving Public Health,,"

Aims

In patients with non-valvular atrial fibrillation prescribed warfarin, the UK National Institute of Health and Care Excellence (NICE) defines poor anticoagulation as a time in therapeutic range (TTR) of <65%, any two international normalized ratios (INRs) within a 6-month period of ≤1.5 ('low'), two INRs ≥5 within 6 months, or any INR ≥8 ('high'). Our objectives were to (i) quantify the number of patients with poor INR control and (ii) describe the demographic and clinical characteristics associated with poor INR control.

Method and results

Linked anonymized health record data for Wales, UK (2006-2017) was used to evaluate patients prescribed warfarin who had at least 6 months of INR data. 32 380 patients were included. In total, 13 913 (43.0%) patients had at least one of the NICE markers of poor INR control. Importantly, in the 24 123 (74.6%) of the cohort with an acceptable TTR (≥65%), 5676 (23.5%) had either low or high INR readings at some point in their history. In a multivariable regression female gender, age (≥75 years), excess alcohol, diabetes heart failure, ischaemic heart disease, and respiratory disease were independently associated with all markers of poor INR control.

Conclusion

Acceptable INR control according to NICE standards is poor. Of those with an acceptable TTR (>65%), one-quarter still had unacceptably low or high INR levels according to NICE criteria. Thus, only using TTR to assess effectiveness with warfarin has the potential to miss a large number of patients with non-therapeutic INRs who are likely to be at increased risk.","This retrospective observational cohort study aimed to quanitfy the number of patients with non-valvular atrial fibrillation (NVAF) prescribed warfarin who exhibit NICE-defined poor international normalised ratio (INR) control. Another objective was to describe the relationship between demographic and clinical characteristics of these patients and poor INR control. The results from statistical analyses in this study suggest a considerable opportunity to improve both embloc and bleeding risk, eben though the relationship between poor INR control and these clinical outcomes remains to be determined.",pdf:https://academic.oup.com/ehjcvp/advance-article-pdf/doi/10.1093/ehjcvp/pvz071/31700014/pvz071.pdf; doi:https://doi.org/10.1093/ehjcvp/pvz071; html:https://europepmc.org/articles/PMC7811400; pdf:https://europepmc.org/articles/PMC7811400?pdf=render 37736873,https://doi.org/10.1002/ehf2.14527,Genetically predicted androgenic profiles and adverse cardiac markers: a sex-specific Mendelian randomization study.,"Chen JY, Ardissino M, Reddy RK, Mason AM, Raisi-Estabragh Z, Di Angelantonio E, Burgess S, Ng FS.",,ESC heart failure,2023,2023-09-22,Y,Sex hormones; Testosterone; Heart Failure; Cmr; Mendelian Randomization; Shbg,,,"

Aims

Observational evidence suggests associations between sex hormone levels and heart failure (HF). We used sex-specific genetic variants associated with androgenic sex hormone profiles to investigate the causal relevance of androgenic sex hormone profiles on cardiac structure and function and HF using Mendelian randomization (MR).

Methods and results

Sex-specific uncorrelated genome-wide significant (P < 5 × 10-8 ) variants predicting sex hormone-binding globulin (SHBG), total testosterone, and bioavailable testosterone were extracted from summary statistics of genome-wide association study (GWAS) on 425 097 participants in the UK Biobank. Sex-specific gene-outcome association estimates were computed for left ventricular ejection fraction (LVEF), left ventricular end-diastolic and end-systolic volumes (LVEDV and LVESV, respectively), left ventricular stroke volume (LVSV), cardiac index, and cardiac output in 11 528 female and 14 356 male UK Biobank Imaging Study participants and for incident or prevalent HF in an external cohort of 47 309 cases and 930 014 controls. Inverse-variance weighted MR was the primary analysis method. In females, higher genetically predicted bioavailable testosterone was associated with lower LVEDV [β per nmol/L = -0.11 (-0.19 to -0.03), P = 0.006], lower LVESV [β = -0.09 (-0.17 to -0.01), P = 0.022], lower LVSV [β = -0.11 (-0.18 to -0.03), P = 0.005], lower cardiac output [β = -0.08 (-0.16 to 0.00), P = 0.046], and lower cardiac index [β = -0.08 (-0.16 to -0.01), P = 0.034] and a higher risk of HF [odds ratio 1.10 (1.01-1.19), P = 0.026] on external validation analysis in larger scale, sex-adjusted GWAS data. Higher genetically predicted SHBG was associated with higher LVEDV [β per nmol/L = 0.17 (0.08-0.25), P = 2 × 10-4 ], higher LVESV [β = 0.13 (0.05-0.22), P = 0.003], and higher LVSV [β = 0.18 (0.08-0.28), P = 2 × 10-4 ]. In males, higher genetically predicted total and bioavailable testosterone was associated with lower LVESV [β = -0.07 (-0.12 to -0.02), P = 0.007] and LVEF [β = -0.11 (-0.18 to -0.04), P = 0.003], respectively.

Conclusions

This study supports a causal effect of pro-androgenic sex hormone profiles in females on adverse markers of left ventricular structure and function typically associated with HF with preserved ejection fraction and with HF. There was weaker evidence of association in males.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ehf2.14527; doi:https://doi.org/10.1002/ehf2.14527; html:https://europepmc.org/articles/PMC10682908; pdf:https://europepmc.org/articles/PMC10682908?pdf=render @@ -688,8 +688,8 @@ PMC9644860,https://doi.org/,Maternal mental health and children’s development: 36997954,https://doi.org/10.1186/s13063-023-07251-x,A DELPHI study priority setting the remaining challenges for the use of routinely collected data in trials: COMORANT-UK.,"Williams ADN, Davies G, Farrin AJ, Mafham M, Robling M, Sydes MR, Lugg-Widger FV.",,Trials,2023,2023-03-30,Y,Priority Setting; Consensus; Routinely Collected Data; Trials Methodology,,,"

Background

Researchers are increasingly seeking to use routinely collected data to support clinical trials. This approach has the potential to transform the way clinical trials are conducted in the future. The availability of routinely collected data for research, whether healthcare or administrative, has increased, and infrastructure funding has enabled much of this. However, challenges remain at all stages of a trial life cycle. This study, COMORANT-UK, aimed to systematically identify, with key stakeholders across the UK, the ongoing challenges related to trials that seek to use routinely collected data.

Methods

This three-step Delphi method consisted of two rounds of anonymous web-based surveys and a virtual consensus meeting. Stakeholders included trialists, data infrastructures, funders of trials, regulators, data providers and the public. Stakeholders identified research questions or challenges that they considered were of particular importance and then selected their top 10 in the second survey. The ranked questions were taken forward to the consensus meeting for discussion with representatives invited from the stakeholder groups.

Results

In the first survey, 66 respondents yielded over 260 questions or challenges. These were thematically grouped and merged into a list of 40 unique questions. Eighty-eight stakeholders then ranked their top ten from the 40 questions in the second survey. The most common 14 questions were brought to the virtual consensus meeting in which stakeholders agreed a top list of seven questions. We report these seven questions which are within the following domains: trial design, Patient and Public Involvement, trial set-up, trial open and trial data. These questions address both evidence gaps (requiring further methodological research) and implementation gaps (requiring training and/or service re-organisation).

Conclusion

This prioritised list of seven questions should inform the direction of future research in this area and should direct efforts to ensure that the benefits in major infrastructure for routinely collected data are achieved and translated. Without this and future work to address these questions, the potential societal benefits of using routinely collected data to help answer important clinical questions will not be realised.",,pdf:https://trialsjournal.biomedcentral.com/counter/pdf/10.1186/s13063-023-07251-x; doi:https://doi.org/10.1186/s13063-023-07251-x; html:https://europepmc.org/articles/PMC10064573; pdf:https://europepmc.org/articles/PMC10064573?pdf=render 37478175,https://doi.org/10.1126/sciadv.adh8839,Citizen science reveals landscape-scale exposures to multiazole-resistant Aspergillus fumigatus bioaerosols.,"Shelton JMG, Rhodes J, Uzzell CB, Hemmings S, Brackin AP, Sewell TR, Alghamdi A, Dyer PS, Fraser M, Borman AM, Johnson EM, Piel FB, Singer AC, Fisher MC.",,Science advances,2023,2023-07-21,Y,,,,"Using a citizen science approach, we identify a country-wide exposure to aerosolized spores of a human fungal pathogen, Aspergillus fumigatus, that has acquired resistance to the agricultural fungicide tebuconazole and first-line azole clinical antifungal drugs. Genomic analysis shows no distinction between resistant genotypes found in the environment and in patients, indicating that at least 40% of azole-resistant A. fumigatus infections are acquired from environmental exposures. Hotspots and coldspots of aerosolized azole-resistant spores were not stable between seasonal sampling periods. This suggests a high degree of atmospheric mixing resulting in an estimated per capita cumulative annual exposure of 21 days (±2.6). Because of the ubiquity of this measured exposure, it is imperative that we determine sources of azole-resistant A. fumigatus to reduce treatment failure in patients with aspergillosis.",,doi:https://doi.org/10.1126/sciadv.adh8839; html:https://europepmc.org/articles/PMC10361594; pdf:https://europepmc.org/articles/PMC10361594?pdf=render 31398891,https://doi.org/10.3390/nu11081839,Intakes and Food Sources of Dietary Fibre and Their Associations with Measures of Body Composition and Inflammation in UK Adults: Cross-Sectional Analysis of the Airwave Health Monitoring Study.,"Gibson R, Eriksen R, Chambers E, Gao H, Aresu M, Heard A, Chan Q, Elliott P, Frost G.",,Nutrients,2019,2019-08-08,Y,Body composition; body mass index; Dietary fibre; C-reactive Protein; Waist Circumference; Uk Population; Airwave Health Monitoring Study; Food Sources Fibre,Improving Public Health,,"The purpose of this study was to investigate the associations between intakes of fibre from the main food sources of fibre in the UK diet with body mass index (BMI), percentage body fat (%BF), waist circumference (WC) and C-reactive protein (CRP). Participants enrolled in the Airwave Health Monitoring Study (2007-2012) with 7-day food records (n = 6898; 61% men) were included for cross-sectional analyses. General linear models evaluated associations across fifths of fibre intakes (total, vegetable, fruit, potato, whole grain and non-whole grain cereal) with BMI, %BF, WC and CRP. Fully adjusted analyses showed inverse linear trends across fifths of total fibre and fibre from fruit with all outcome measures (ptrend < 0.0001). Vegetable fibre intake showed an inverse association with WC (ptrend 0.0156) and CRP (ptrend 0.0005). Fibre from whole grain sources showed an inverse association with BMI (ptrend 0.0002), %BF (ptrend 0.0007) and WC (ptrend 0.0004). Non-whole grain cereal fibre showed an inverse association with BMI (Ptrend 0.0095). Direct associations observed between potato fibre intake and measures of body composition and inflammation were attenuated in fully adjusted analyses controlling for fried potato intake. Higher fibre intake has a beneficial association on body composition, however, there are differential associations based on the food source.",,pdf:https://www.mdpi.com/2072-6643/11/8/1839/pdf?version=1565745447; doi:https://doi.org/10.3390/nu11081839; html:https://europepmc.org/articles/PMC6722677; pdf:https://europepmc.org/articles/PMC6722677?pdf=render -38102763,https://doi.org/10.1177/15353702231214253,Explainable hierarchical clustering for patient subtyping and risk prediction.,"Werner E, Clark JN, Hepburn A, Bhamber RS, Ambler M, Bourdeaux CP, McWilliams CJ, Santos-Rodriguez R.",,"Experimental biology and medicine (Maywood, N.J.)",2023,2023-12-15,Y,Clinical evaluation; hierarchical clustering; Mortality Prediction; Early Warning Score; Explainability; Patient Subtypes,,,"We present a pipeline in which machine learning techniques are used to automatically identify and evaluate subtypes of hospital patients admitted between 2017 and 2021 in a large UK teaching hospital. Patient clusters are determined using routinely collected hospital data, such as those used in the UK's National Early Warning Score 2 (NEWS2). An iterative, hierarchical clustering process was used to identify the minimum set of relevant features for cluster separation. With the use of state-of-the-art explainability techniques, the identified subtypes are interpreted and assigned clinical meaning, illustrating their robustness. In parallel, clinicians assessed intracluster similarities and intercluster differences of the identified patient subtypes within the context of their clinical knowledge. For each cluster, outcome prediction models were trained and their forecasting ability was illustrated against the NEWS2 of the unclustered patient cohort. These preliminary results suggest that subtype models can outperform the established NEWS2 method, providing improved prediction of patient deterioration. By considering both the computational outputs and clinician-based explanations in patient subtyping, we aim to highlight the mutual benefit of combining machine learning techniques with clinical expertise.",,doi:https://doi.org/10.1177/15353702231214253; html:https://europepmc.org/articles/PMC10854470; pdf:https://europepmc.org/articles/PMC10854470?pdf=render 36329425,https://doi.org/10.1186/s12890-022-02189-3,Derivation of asthma severity from electronic prescription records using British thoracic society treatment steps.,"Tibble H, Sheikh A, Tsanas A.",,BMC pulmonary medicine,2022,2022-11-03,Y,Asthma; Pharmacotherapy; Severity; Pharmacoepidemiology; Electronic Health Records; Treatment Guidelines,,,"

Background

Asthma severity is typically assessed through a retrospective assessment of the treatment required to control symptoms and to prevent exacerbations. The joint British Thoracic Society and Scottish Intercollegiate Guidelines Network (BTS/SIGN) guidelines encourage a stepwise approach to pharmacotherapy, and as such, current treatment step can be considered as a severity categorisation proxy. Briefly, the steps for adults can be summarised as: no controller therapy (Step 0), low-strength Inhaled Corticosteroids (ICS; Step 1), ICS plus Long-Acting Beta-2 Agonist (LABA; Step 2), medium-dose ICS + LABA (Step 3), and finally either an increase in strength or additional therapies (Step 4). This study aimed to investigate how BTS/SIGN Steps can be estimated from across a large cohort using electronic prescription records, and to describe the incidence of each BTS/SIGN Step in a general population.

Methods

There were 41,433,707 prescriptions, for 671,304 individuals, in the Asthma Learning Health System Scottish cohort, between 1/2009 and 3/2017. Days on which an individual had a prescription for at least one asthma controller (preventer) medication were labelled prescription events. A rule-based algorithm was developed for extracting the strength and volume of medication instructed to be taken daily from free-text data fields. Asthma treatment regimens were categorised by the combination of medications prescribed in the 120 days preceding any prescription event and categorised into BTS/SIGN treatment steps.

Results

Almost 4.5 million ALHS prescriptions were for asthma controllers. 26% of prescription events had no inhaled corticosteroid prescriptions in the preceding 120 days (Step 0), 16% were assigned to BTS/SIGN Step 1, 7% to Step 2, 21% to Step 3, and 30% to Step 4. The median days spent on a treatment step before a step-down in treatment was 297 days, whereas a step-up only took a median of 134 days.

Conclusion

We developed a reproducible methodology enabling researchers to estimate BTS/SIGN asthma treatment steps in population health studies, providing valuable insights into population and patient-specific trajectories, towards improving the management of asthma.",,pdf:https://bmcpulmmed.biomedcentral.com/counter/pdf/10.1186/s12890-022-02189-3; doi:https://doi.org/10.1186/s12890-022-02189-3; html:https://europepmc.org/articles/PMC9635147; pdf:https://europepmc.org/articles/PMC9635147?pdf=render +38102763,https://doi.org/10.1177/15353702231214253,Explainable hierarchical clustering for patient subtyping and risk prediction.,"Werner E, Clark JN, Hepburn A, Bhamber RS, Ambler M, Bourdeaux CP, McWilliams CJ, Santos-Rodriguez R.",,"Experimental biology and medicine (Maywood, N.J.)",2023,2023-12-15,Y,Clinical evaluation; hierarchical clustering; Mortality Prediction; Early Warning Score; Explainability; Patient Subtypes,,,"We present a pipeline in which machine learning techniques are used to automatically identify and evaluate subtypes of hospital patients admitted between 2017 and 2021 in a large UK teaching hospital. Patient clusters are determined using routinely collected hospital data, such as those used in the UK's National Early Warning Score 2 (NEWS2). An iterative, hierarchical clustering process was used to identify the minimum set of relevant features for cluster separation. With the use of state-of-the-art explainability techniques, the identified subtypes are interpreted and assigned clinical meaning, illustrating their robustness. In parallel, clinicians assessed intracluster similarities and intercluster differences of the identified patient subtypes within the context of their clinical knowledge. For each cluster, outcome prediction models were trained and their forecasting ability was illustrated against the NEWS2 of the unclustered patient cohort. These preliminary results suggest that subtype models can outperform the established NEWS2 method, providing improved prediction of patient deterioration. By considering both the computational outputs and clinician-based explanations in patient subtyping, we aim to highlight the mutual benefit of combining machine learning techniques with clinical expertise.",,doi:https://doi.org/10.1177/15353702231214253; html:https://europepmc.org/articles/PMC10854470; pdf:https://europepmc.org/articles/PMC10854470?pdf=render 38772405,https://doi.org/10.1016/s0140-6736(24)00537-3,Post-trial monitoring of a randomised controlled trial of intensive glycaemic control in type 2 diabetes extended from 10 years to 24 years (UKPDS 91).,"Adler AI, Coleman RL, Leal J, Whiteley WN, Clarke P, Holman RR.",,"Lancet (London, England)",2024,2024-05-17,N,,,,"

Background

The 20-year UK Prospective Diabetes Study showed major clinical benefits for people with newly diagnosed type 2 diabetes randomly allocated to intensive glycaemic control with sulfonylurea or insulin therapy or metformin therapy, compared with conventional glycaemic control. 10-year post-trial follow-up identified enduring and emerging glycaemic and metformin legacy treatment effects. We aimed to determine whether these effects would wane by extending follow-up for another 14 years.

Methods

5102 patients enrolled between 1977 and 1991, of whom 4209 (82·5%) participants were originally randomly allocated to receive either intensive glycaemic control (sulfonylurea or insulin, or if overweight, metformin) or conventional glycaemic control (primarily diet). At the end of the 20-year interventional trial, 3277 surviving participants entered a 10-year post-trial monitoring period, which ran until Sept 30, 2007. Eligible participants for this study were all surviving participants at the end of the 10-year post-trial monitoring period. An extended follow-up of these participants was done by linking them to their routinely collected National Health Service (NHS) data for another 14 years. Clinical outcomes were derived from records of deaths, hospital admissions, outpatient visits, and accident and emergency unit attendances. We examined seven prespecified aggregate clinical outcomes (ie, any diabetes-related endpoint, diabetes-related death, death from any cause, myocardial infarction, stroke, peripheral vascular disease, and microvascular disease) by the randomised glycaemic control strategy on an intention-to-treat basis using Kaplan-Meier time-to-event and log-rank analyses. This study is registered with the ISRCTN registry, number ISRCTN75451837.

Findings

Between Oct 1, 2007, and Sept 30, 2021, 1489 (97·6%) of 1525 participants could be linked to routinely collected NHS administrative data. Their mean age at baseline was 50·2 years (SD 8·0), and 41·3% were female. The mean age of those still alive as of Sept 30, 2021, was 79·9 years (SD 8·0). Individual follow-up from baseline ranged from 0 to 42 years, median 17·5 years (IQR 12·3-26·8). Overall follow-up increased by 21%, from 66 972 to 80 724 person-years. For up to 24 years after trial end, the glycaemic and metformin legacy effects showed no sign of waning. Early intensive glycaemic control with sulfonylurea or insulin therapy, compared with conventional glycaemic control, showed overall relative risk reductions of 10% (95% CI 2-17; p=0·015) for death from any cause, 17% (6-26; p=0·002) for myocardial infarction, and 26% (14-36; p<0·0001) for microvascular disease. Corresponding absolute risk reductions were 2·7%, 3·3%, and 3·5%, respectively. Early intensive glycaemic control with metformin therapy, compared with conventional glycaemic control, showed overall relative risk reductions of 20% (95% CI 5-32; p=0·010) for death from any cause and 31% (12-46; p=0·003) for myocardial infarction. Corresponding absolute risk reductions were 4·9% and 6·2%, respectively. No significant risk reductions during or after the trial for stroke or peripheral vascular disease were observed for both intensive glycaemic control groups, and no significant risk reduction for microvascular disease was observed for metformin therapy.

Interpretation

Early intensive glycaemic control with sulfonylurea or insulin, or with metformin, compared with conventional glycaemic control, appears to confer a near-lifelong reduced risk of death and myocardial infarction. Achieving near normoglycaemia immediately following diagnosis might be essential to minimise the lifetime risk of diabetes-related complications to the greatest extent possible.

Funding

University of Oxford Nuffield Department of Population Health Pump Priming.",,doi:https://doi.org/10.1016/S0140-6736(24)00537-3 35443953,https://doi.org/10.1136/bmjopen-2021-056523,Can we accurately forecast non-elective bed occupancy and admissions in the NHS? A time-series MSARIMA analysis of longitudinal data from an NHS Trust.,"Eyles E, Redaniel MT, Jones T, Prat M, Keen T.",,BMJ open,2022,2022-04-20,Y,epidemiology; Statistics & Research Methods; Health Services Administration & Management; Accident & Emergency Medicine,,,"

Objectives

The main objective of the study was to develop more accurate and precise short-term forecasting models for admissions and bed occupancy for an NHS Trust located in Bristol, England. Subforecasts for the medical and surgical specialties, and for different lengths of stay were realised DESIGN: Autoregressive integrated moving average models were specified on a training dataset of daily count data, then tested on a 6-week forecast horizon. Explanatory variables were included in the models: day of the week, holiday days, lagged temperature and precipitation.

Setting

A secondary care hospital in an NHS Trust in South West England.

Participants

Hospital admissions between September 2016 and March 2020, comprising 1291 days.

Primary and secondary outcome measures

The accuracy of the forecasts was assessed through standard measures, as well as compared with the actual data using accuracy thresholds of 10% and 20% of the mean number of admissions or occupied beds.

Results

The overall Autoregressive Integrated Moving Average (ARIMA) admissions forecast was compared with the Trust's forecast, and found to be more accurate, namely, being closer to the actual value 95.6% of the time. Furthermore, it was more precise than the Trust's. The subforecasts, as well as those for bed occupancy, tended to be less accurate compared with the overall forecasts. All of the explanatory variables improved the forecasts.

Conclusions

ARIMA models can forecast non-elective admissions in an NHS Trust accurately on a 6-week horizon, which is an improvement on the current predictive modelling in the Trust. These models can be readily applied to other contexts, improving patient flow.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/4/e056523.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-056523; html:https://europepmc.org/articles/PMC9021768; pdf:https://europepmc.org/articles/PMC9021768?pdf=render 35383067,https://doi.org/10.1136/bmjopen-2021-055447,Potentially avoidable causes of hospitalisation in people with dementia: contemporaneous associations by stage of dementia in a South London clinical cohort.,"Gungabissoon U, Perera G, Galwey NW, Stewart R.",,BMJ open,2022,2022-04-05,Y,Dementia; epidemiology; Old Age Psychiatry,,,"

Objectives

To estimate the frequency of all-cause and ambulatory care sensitive condition (ACSCs)-related hospitalisations among individuals with dementia. In addition, to investigate differences by stage of dementia based on recorded cognitive function.

Setting

Data from a large London dementia care clinical case register, linked to a national hospitalisation database.

Participants

Individuals aged ≥65 years with a confirmed dementia diagnosis with recorded cognitive function.

Outcome measures

Acute general hospital admissions were evaluated within 6 months of a randomly selected cognitive function score in patients with a clinical diagnosis of dementia. To evaluate associations between ACSC-related hospital admissions (overall and individual ACSCs) and stage of dementia, an ordinal regression was performed, modelling stage of dementia as the dependant variable (to facilitate efficient model selection, with no implication concerning the direction of causality).

Results

Of the 5294 people with dementia, 2993 (56.5%) had at least one hospitalisation during a 12-month period of evaluation, and 1192 (22.5%) had an ACSC-related admission. Proportions with an all-cause or ACSC-related hospitalisation were greater in the groups with more advanced dementia (all-cause 53.9%, 57.1% and 60.9%, p 0.002; ACSC-related 19.5%, 24.0% and 25.3%, p<0.0001 in the mild, moderate and severe groups, respectively). An ACSC-related admission was associated with 1.3-fold (95% CI 1.1 to 1.5) increased odds of more severe dementia after adjusting for demographic factors. Concerning admissions for individual ACSCs, the most common ACSC was urinary tract infection /pyelonephritis (9.8% of hospitalised patients) followed by pneumonia (7.1%); in an adjusted model, these were each associated with 1.4-fold increased odds of more severe dementia (95% CI 1.2 to 1.7 and 1.1 to 1.7, respectively).

Conclusions

Potentially avoidable hospitalisations were common in people with dementia, particularly in those with greater cognitive impairment. Our results call for greater attention to the extent of cognitive status impairment, and not just dementia diagnosis, when evaluating measures to reduce the risk of potentially avoidable hospitalisations.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/4/e055447.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-055447; html:https://europepmc.org/articles/PMC8984034; pdf:https://europepmc.org/articles/PMC8984034?pdf=render @@ -711,11 +711,11 @@ PMC9645061,https://doi.org/,Using population-scale medication data to evaluate t 38216198,https://doi.org/10.1136/bmjopen-2023-080410,"Rationale and design of the THIRST Alert feasibility study: a pragmatic, single-centre, parallel-group randomised controlled trial of an interruptive alert for oral fluid restriction in patients treated with intravenous furosemide.","Chen Y, Shah A, Jani Y, Higgins D, Saleem N, Chafer K, Sydes MR, Asselbergs FW, Lumbers RT.",,BMJ open,2024,2024-01-11,Y,Randomized controlled trial; Heart Failure; Electronic Health Records; Feasibility Studies,,,"

Introduction

Acute heart failure (HF) is a major cause of unplanned hospitalisation characterised by excess body water. A restriction in oral fluid intake is commonly imposed on patients as an adjunct to pharmacological therapy with loop diuretics, but there is a lack of evidence from traditional randomised controlled trials (RCTs) to support the safety and effectiveness of this intervention in the acute setting.This study aims to explore the feasibility of using computer alerts within the electronic health record (EHR) system to invite clinical care teams to enrol patients into a pragmatic RCT at the time of clinical decision-making. It will additionally assess the effectiveness of using an alert to help address the clinical research question of whether oral fluid restriction is a safe and effective adjunct to pharmacological therapy for patients admitted with fluid overload.

Methods and analysis

THIRST (Randomised Controlled Trial within the electronic Health record of an Interruptive alert displaying a fluid Restriction Suggestion in patients with the treatable Trait of congestion) Alert is a single-centre, parallel-group, open-label pragmatic RCT embedded in the EHR system that will be conducted as a feasibility study at an National Health Service (NHS) hospital in London. The clinical care team will be invited to enrol suitable patients in the study using a point-of-care alert with a target sample size of 50 patients. Enrolled patients will then be randomised to either restricted or unrestricted oral fluid intake. Two primary outcomes will be explored (1) the proportion of eligible patients enrolled in the study and (2) the mean difference in oral fluid intake between randomised groups. A series of secondary outcomes are specified to evaluate the effectiveness of the alert, adherence to the randomised treatment allocation and the quality of data generated from routine care, relevant to the outcomes of interest.

Ethics and dissemination

This study was approved by Riverside Research Ethics Committee (Ref: 22/LO/0889) and will be published on completion.

Trial registration number

NCT05869656.",,pdf:https://bmjopen.bmj.com/content/bmjopen/14/1/e080410.full.pdf; doi:https://doi.org/10.1136/bmjopen-2023-080410; html:https://europepmc.org/articles/PMC10806795; pdf:https://europepmc.org/articles/PMC10806795?pdf=render 38434152,https://doi.org/10.5334/gh.1298,Characterization of Non-Ischemic Dilated Cardiomyopathy in a Native Tanzanian Cohort: MOYO Study.,"Fundikira LS, Chillo P, Alimohamed MZ, Mayala H, Kifai E, Aloyce GM, Kamuhabwa A, Kwesigabo G, van Laake LW, Asselbergs FW.",,Global heart,2024,2024-02-29,Y,Echocardiography; Heart Failure; Non-ischemic Dilated Cardiomyopathy,,,"

Background

Non-ischemic dilated cardiomyopathy (NIDCM) is a common cause of heart failure with progressive tendency. The disease occurs in one in every 2,500 individuals in the developed world, with high morbidity and mortality. However, detailed data on the role of NIDCM in heart failure in Tanzania is lacking.

Aim

To characterize NIDCM in a Tanzanian cohort with respect to demographics, clinical profile, imaging findings and management.

Methods

Characterization of non-ischemic dilated cardioMyOpathY in a native Tanzanian cOhort (MOYO) is a prospective cohort study of NIDCM patients seen at the Jakaya Kikwete Cardiac Institute. Patients aged ≥18 years with a clinical diagnosis of heart failure, an ejection fraction of ≤45% on echocardiography and no evidence of ischemia were enrolled. Clinical data, echocardiography, electrocardiography (ECG), coronary angiography and stress ECG information were collected from February 2020 to March 2022.

Results

Of 402 patients, n = 220 (54.7%) were males with a median (IQR) age of 55.0 (41.0, 66.0) years. Causes of NIDCM were presumably hypertensive n = 218 (54.2%), idiopathic n = 116 (28.9%), PPCM n = 45 (11.2%), alcoholic n = 10 (2.5%) and other causes n = 13 (3.2%). The most common presenting symptoms were dyspnea n = 342 (85.1%), with the majority of patients presenting with New York Heart Association (NYHA) Class III n = 195 (48.5%). The mean (SD) left ventricular ejection fraction (LVEF) was 29.4% (±7.7), and severe systolic dysfunction (LVEF <30%) was common n = 208 (51.7%). Compared with other forms of DCM, idiopathic DCM patients were significantly younger, had more advanced NYHA class (p < 0.001) and presented more often with left bundle branch block on ECG (p = 0.0042). There was suboptimal use of novel guidelines recommended medications ARNI n = 10 (2.5%) and SGLT2 2-inhibitors n = 2 (0.5%).

Conclusions

In our Tanzanian cohort, the majority of patients with NIDCM have an identified underlying cause, and they present at late stages of the disease. Patients with idiopathic DCM are younger with more severe disease compared to other forms of NIDCM.",,doi:https://doi.org/10.5334/gh.1298; html:https://europepmc.org/articles/PMC10906337; pdf:https://europepmc.org/articles/PMC10906337?pdf=render 35814295,https://doi.org/10.1038/s43856-022-00146-z,Machine learning to support visual auditing of home-based lateral flow immunoassay self-test results for SARS-CoV-2 antibodies.,"Wong NCK, Meshkinfamfard S, Turbé V, Whitaker M, Moshe M, Bardanzellu A, Dai T, Pignatelli E, Barclay W, Darzi A, Elliott P, Ward H, Tanaka RJ, Cooke GS, McKendry RA, Atchison CJ, Bharath AA.",,Communications medicine,2022,2022-07-06,Y,Databases; Public Health,,,"

Background

Lateral flow immunoassays (LFIAs) are being used worldwide for COVID-19 mass testing and antibody prevalence studies. Relatively simple to use and low cost, these tests can be self-administered at home, but rely on subjective interpretation of a test line by eye, risking false positives and false negatives. Here, we report on the development of ALFA (Automated Lateral Flow Analysis) to improve reported sensitivity and specificity.

Methods

Our computational pipeline uses machine learning, computer vision techniques and signal processing algorithms to analyse images of the Fortress LFIA SARS-CoV-2 antibody self-test, and subsequently classify results as invalid, IgG negative and IgG positive. A large image library of 595,339 participant-submitted test photographs was created as part of the REACT-2 community SARS-CoV-2 antibody prevalence study in England, UK. Alongside ALFA, we developed an analysis toolkit which could also detect device blood leakage issues.

Results

Automated analysis showed substantial agreement with human experts (Cohen's kappa 0.90-0.97) and performed consistently better than study participants, particularly for weak positive IgG results. Specificity (98.7-99.4%) and sensitivity (90.1-97.1%) were high compared with visual interpretation by human experts (ranges due to the varying prevalence of weak positive IgG tests in datasets).

Conclusions

Given the potential for LFIAs to be used at scale in the COVID-19 response (for both antibody and antigen testing), even a small improvement in the accuracy of the algorithms could impact the lives of millions of people by reducing the risk of false-positive and false-negative result read-outs by members of the public. Our findings support the use of machine learning-enabled automated reading of at-home antibody lateral flow tests as a tool for improved accuracy for population-level community surveillance.",,pdf:https://www.nature.com/articles/s43856-022-00146-z.pdf; doi:https://doi.org/10.1038/s43856-022-00146-z; html:https://europepmc.org/articles/PMC9259560; pdf:https://europepmc.org/articles/PMC9259560?pdf=render -33933206,https://doi.org/10.1016/s0140-6736(21)00676-0,"Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial.",RECOVERY Collaborative Group.,,"Lancet (London, England)",2021,2021-05-01,Y,,,,"

Background

In this study, we aimed to evaluate the effects of tocilizumab in adult patients admitted to hospital with COVID-19 with both hypoxia and systemic inflammation.

Methods

This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. Those trial participants with hypoxia (oxygen saturation <92% on air or requiring oxygen therapy) and evidence of systemic inflammation (C-reactive protein ≥75 mg/L) were eligible for random assignment in a 1:1 ratio to usual standard of care alone versus usual standard of care plus tocilizumab at a dose of 400 mg-800 mg (depending on weight) given intravenously. A second dose could be given 12-24 h later if the patient's condition had not improved. The primary outcome was 28-day mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936).

Findings

Between April 23, 2020, and Jan 24, 2021, 4116 adults of 21 550 patients enrolled into the RECOVERY trial were included in the assessment of tocilizumab, including 3385 (82%) patients receiving systemic corticosteroids. Overall, 621 (31%) of the 2022 patients allocated tocilizumab and 729 (35%) of the 2094 patients allocated to usual care died within 28 days (rate ratio 0·85; 95% CI 0·76-0·94; p=0·0028). Consistent results were seen in all prespecified subgroups of patients, including those receiving systemic corticosteroids. Patients allocated to tocilizumab were more likely to be discharged from hospital within 28 days (57% vs 50%; rate ratio 1·22; 1·12-1·33; p<0·0001). Among those not receiving invasive mechanical ventilation at baseline, patients allocated tocilizumab were less likely to reach the composite endpoint of invasive mechanical ventilation or death (35% vs 42%; risk ratio 0·84; 95% CI 0·77-0·92; p<0·0001).

Interpretation

In hospitalised COVID-19 patients with hypoxia and systemic inflammation, tocilizumab improved survival and other clinical outcomes. These benefits were seen regardless of the amount of respiratory support and were additional to the benefits of systemic corticosteroids.

Funding

UK Research and Innovation (Medical Research Council) and National Institute of Health Research.",,pdf:https://aura.abdn.ac.uk/bitstream/2164/16630/1/Recovery_etal_TL_Tocilizumab_In_Patients_VoR.pdf; doi:https://doi.org/10.1016/S0140-6736(21)00676-0; html:https://europepmc.org/articles/PMC8084355 31256764,https://doi.org/10.1192/bjp.2019.153,"Shining the light on eating disorders, incidence, prognosis and profiling of patients in primary and secondary care: national data linkage study.","Demmler JC, Brophy ST, Marchant A, John A, Tan JOA.",,The British journal of psychiatry : the journal of mental science,2020,2020-02-01,Y,epidemiology; Anorexia Nervosa; incidence; Bulimia Nervosa; Eating Disorder,,,"

Background

Diagnosing eating disorders can be difficult and few people with the disorder receive specialist services despite the associated high morbidity and mortality.

Aims

To examine the burden of eating disorders in the population in terms of incidence, comorbidities and survival.

Method

We used linked electronic health records from general practitioner and hospital admissions in Wales, UK within the Secure Anonymised Information Linkage (SAIL) databank to investigate the incidence of new eating disorder diagnoses. We examined the frequency of comorbid diagnoses and prescribed medications in cases and controls in the 2 years before and 3 years after diagnosis, and performed a survival analysis.

Results

A total of 15 558 people were diagnosed with eating disorders between 1990 and 2017. The incidence peaked at 24 per 100 000 people in 2003/04. People with eating disorders showed higher levels of other mental disorders (odds ratio 4.32, 95% CI 4.01-4.66) and external causes of morbidity and mortality (odds ratio 2.92, 95% CI 2.44-3.50). They had greater prescription of central nervous system drugs (odds ratio 3.15, 95% CI 2.97-3.33), gastrointestinal drugs (odds ratio 2.61, 95% CI 2.45-2.79) and dietetic drugs (odds ratio 2.42, 95% CI 2.24-2.62) before diagnosis. These excess diagnoses and prescriptions remained 3 years after diagnosis. Mortality was raised compared with controls for some eating disorders, particularly in females with anorexia nervosa.

Conclusions

Incidence of diagnosed eating disorders is relatively low in the population but there is a major longer term burden in morbidity and mortality to the individual.",,pdf:https://www.cambridge.org/core/services/aop-cambridge-core/content/view/A00E32E32B0FB324075CF2CF0973687F/S0007125019001533a.pdf/div-class-title-shining-the-light-on-eating-disorders-incidence-prognosis-and-profiling-of-patients-in-primary-and-secondary-care-national-data-linkage-study-div.pdf; doi:https://doi.org/10.1192/bjp.2019.153; html:https://europepmc.org/articles/PMC7557634; pdf:https://europepmc.org/articles/PMC7557634?pdf=render +33933206,https://doi.org/10.1016/s0140-6736(21)00676-0,"Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial.",RECOVERY Collaborative Group.,,"Lancet (London, England)",2021,2021-05-01,Y,,,,"

Background

In this study, we aimed to evaluate the effects of tocilizumab in adult patients admitted to hospital with COVID-19 with both hypoxia and systemic inflammation.

Methods

This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. Those trial participants with hypoxia (oxygen saturation <92% on air or requiring oxygen therapy) and evidence of systemic inflammation (C-reactive protein ≥75 mg/L) were eligible for random assignment in a 1:1 ratio to usual standard of care alone versus usual standard of care plus tocilizumab at a dose of 400 mg-800 mg (depending on weight) given intravenously. A second dose could be given 12-24 h later if the patient's condition had not improved. The primary outcome was 28-day mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936).

Findings

Between April 23, 2020, and Jan 24, 2021, 4116 adults of 21 550 patients enrolled into the RECOVERY trial were included in the assessment of tocilizumab, including 3385 (82%) patients receiving systemic corticosteroids. Overall, 621 (31%) of the 2022 patients allocated tocilizumab and 729 (35%) of the 2094 patients allocated to usual care died within 28 days (rate ratio 0·85; 95% CI 0·76-0·94; p=0·0028). Consistent results were seen in all prespecified subgroups of patients, including those receiving systemic corticosteroids. Patients allocated to tocilizumab were more likely to be discharged from hospital within 28 days (57% vs 50%; rate ratio 1·22; 1·12-1·33; p<0·0001). Among those not receiving invasive mechanical ventilation at baseline, patients allocated tocilizumab were less likely to reach the composite endpoint of invasive mechanical ventilation or death (35% vs 42%; risk ratio 0·84; 95% CI 0·77-0·92; p<0·0001).

Interpretation

In hospitalised COVID-19 patients with hypoxia and systemic inflammation, tocilizumab improved survival and other clinical outcomes. These benefits were seen regardless of the amount of respiratory support and were additional to the benefits of systemic corticosteroids.

Funding

UK Research and Innovation (Medical Research Council) and National Institute of Health Research.",,pdf:https://aura.abdn.ac.uk/bitstream/2164/16630/1/Recovery_etal_TL_Tocilizumab_In_Patients_VoR.pdf; doi:https://doi.org/10.1016/S0140-6736(21)00676-0; html:https://europepmc.org/articles/PMC8084355 35497059,https://doi.org/10.1016/j.eclinm.2022.101392,Health conditions in adults with HIV compared with the general population: A population-based cross-sectional analysis.,"Morales DR, Moreno-Martos D, Matin N, McGettigan P.",,EClinicalMedicine,2022,2022-04-21,Y,HIV; Comorbidity; Multimorbidity,,,"

Background

Life expectancy in adults with human immunodeficiency virus (HIV) has increased and managing other health conditions is increasingly important for patients and healthcare planning. The aim of this study was to examine the prevalence and association between different health conditions and HIV status.

Methods

We performed a cross-sectional analysis of adult UK Clinical Practice Research Datalink primary care electronic medical records linked to hospital admissions as of Nov 30, 2015. We examined 47 health condition groups and 304 physical and mental health conditions by HIV status, after adjustment for age, sex, social deprivation status using logistic regression.

Findings

There were 964 patients with HIV (61.7% male; 92.8% aged <65 years) and 941,113 non-HIV patients (49.4% male; 75.2% aged <65 years). Condition groups with the greatest prevalence in HIV that were also highly prevalent in adults without HIV included: lipid disorder (41.4% vs 40.2%), and hypertension (19.1% vs 24.6%). Following adjustment, 18 (37.5%) condition groups were more likely in adults with HIV and ten (20.8%) were less likely. Individual conditions that were less likely in adults with HIV included: atrial fibrillation (odds ratio [OR] 0.37 [95% CI 0.20-0.64]) and hypertension (OR_0.78 [0.65-0.94]); rheumatoid arthritis (OR 0.27 [0.05-0.84]); asthma (OR_0.65 (0.53-0.80]); and certain eye diseases such as macular degeneration (OR_0.30 [0.09-0.70]). Meanwhile individual conditions that were more likely included: liver fibrosis, sclerosis, and cirrhosis (OR_3.23 [1.85-5.20]); pulmonary embolism (OR_2.06 [1.15-3.36]); male infertility (OR_2.23 [1.50-3.16]) and female infertility (OR_2.01 [1.34-2.88]); bipolar disorder (OR_2.93 [1.52-5.05]) and depression (OR_1.49 [1.28-1.71]); cervical malignancy (OR_4.64 [1.15-12.15]); and infections.

Interpretation

Comorbidity is common in adults with HIV, with physical and mental health conditions spanning a wide spectrum. HIV management should consider multidisciplinary care models to provide optimal patient care.

Funding

The project was funded by the Bart's Charity; DRM was funded by a Wellcome Trust Clinical Research Career Development Fellowship; DRM and DMM received funding from the HDR-UK Precision therapeutics programme.",,pdf:http://www.thelancet.com/article/S2589537022001225/pdf; doi:https://doi.org/10.1016/j.eclinm.2022.101392; html:https://europepmc.org/articles/PMC9046106; pdf:https://europepmc.org/articles/PMC9046106?pdf=render -37649988,https://doi.org/10.1093/jamiaopen/ooad078,"Determining prescriptions in electronic healthcare record data: methods for development of standardized, reproducible drug codelists.","Graul EL, Stone PW, Massen GM, Hatam S, Adamson A, Denaxas S, Peters NS, Quint JK.",,JAMIA open,2023,2023-08-29,Y,epidemiology; Electronic Medical Records; Misclassification Bias; Value Sets; Health Data Science; Code Sets,,,"

Objective

To develop a standardizable, reproducible method for creating drug codelists that incorporates clinical expertise and is adaptable to other studies and databases.

Materials and methods

We developed methods to generate drug codelists and tested this using the Clinical Practice Research Datalink (CPRD) Aurum database, accounting for missing data in the database. We generated codelists for: (1) cardiovascular disease and (2) inhaled Chronic Obstructive Pulmonary Disease (COPD) therapies, applying them to a sample cohort of 335 931 COPD patients. We compared searching all drug dictionary variables (A) against searching only (B) chemical or (C) ontological variables.

Results

In Search A, we identified 165 150 patients prescribed cardiovascular drugs (49.2% of cohort), and 317 963 prescribed COPD inhalers (94.7% of cohort). Evaluating output per search strategy, Search C missed numerous prescriptions, including vasodilator anti-hypertensives (A and B:19 696 prescriptions; C:1145) and SAMA inhalers (A and B:35 310; C:564).

Discussion

We recommend the full search (A) for comprehensiveness. There are special considerations when generating adaptable and generalizable drug codelists, including fluctuating status, cohort-specific drug indications, underlying hierarchical ontology, and statistical analyses.

Conclusions

Methods must have end-to-end clinical input, and be standardizable, reproducible, and understandable to all researchers across data contexts.",,pdf:https://academic.oup.com/jamiaopen/article-pdf/6/3/ooad078/51279371/ooad078.pdf; doi:https://doi.org/10.1093/jamiaopen/ooad078; html:https://europepmc.org/articles/PMC10463548; pdf:https://europepmc.org/articles/PMC10463548?pdf=render 33545096,https://doi.org/10.1016/s0140-6736(21)00149-5,"Azithromycin in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial.",RECOVERY Collaborative Group.,,"Lancet (London, England)",2021,2021-02-02,Y,,,,"

Background

Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatory actions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.

Methods

In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospital with COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients were randomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once per day by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatment groups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment and were twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants and local study staff were not masked to the allocated treatment, but all others involved in the trial were masked to the outcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.

Findings

Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) were eligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was 65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomly allocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall, 561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days (rate ratio 0·97, 95% CI 0·87-1·07; p=0·50). No significant difference was seen in duration of hospital stay (median 10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days (rate ratio 1·04, 95% CI 0·98-1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, no significant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilation or death (risk ratio 0·95, 95% CI 0·87-1·03; p=0·24).

Interpretation

In patients admitted to hospital with COVID-19, azithromycin did not improve survival or other prespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restricted to patients in whom there is a clear antimicrobial indication.

Funding

UK Research and Innovation (Medical Research Council) and National Institute of Health Research.",,pdf:http://www.thelancet.com/article/S0140673621001495/pdf; doi:https://doi.org/10.1016/S0140-6736(21)00149-5; html:https://europepmc.org/articles/PMC7884931; pdf:https://europepmc.org/articles/PMC7884931?pdf=render +37649988,https://doi.org/10.1093/jamiaopen/ooad078,"Determining prescriptions in electronic healthcare record data: methods for development of standardized, reproducible drug codelists.","Graul EL, Stone PW, Massen GM, Hatam S, Adamson A, Denaxas S, Peters NS, Quint JK.",,JAMIA open,2023,2023-08-29,Y,epidemiology; Electronic Medical Records; Misclassification Bias; Value Sets; Health Data Science; Code Sets,,,"

Objective

To develop a standardizable, reproducible method for creating drug codelists that incorporates clinical expertise and is adaptable to other studies and databases.

Materials and methods

We developed methods to generate drug codelists and tested this using the Clinical Practice Research Datalink (CPRD) Aurum database, accounting for missing data in the database. We generated codelists for: (1) cardiovascular disease and (2) inhaled Chronic Obstructive Pulmonary Disease (COPD) therapies, applying them to a sample cohort of 335 931 COPD patients. We compared searching all drug dictionary variables (A) against searching only (B) chemical or (C) ontological variables.

Results

In Search A, we identified 165 150 patients prescribed cardiovascular drugs (49.2% of cohort), and 317 963 prescribed COPD inhalers (94.7% of cohort). Evaluating output per search strategy, Search C missed numerous prescriptions, including vasodilator anti-hypertensives (A and B:19 696 prescriptions; C:1145) and SAMA inhalers (A and B:35 310; C:564).

Discussion

We recommend the full search (A) for comprehensiveness. There are special considerations when generating adaptable and generalizable drug codelists, including fluctuating status, cohort-specific drug indications, underlying hierarchical ontology, and statistical analyses.

Conclusions

Methods must have end-to-end clinical input, and be standardizable, reproducible, and understandable to all researchers across data contexts.",,pdf:https://academic.oup.com/jamiaopen/article-pdf/6/3/ooad078/51279371/ooad078.pdf; doi:https://doi.org/10.1093/jamiaopen/ooad078; html:https://europepmc.org/articles/PMC10463548; pdf:https://europepmc.org/articles/PMC10463548?pdf=render 33577558,https://doi.org/10.1371/journal.pmed.1003497,"Association of socioeconomic deprivation with asthma care, outcomes, and deaths in Wales: A 5-year national linked primary and secondary care cohort study.","Alsallakh MA, Rodgers SE, Lyons RA, Sheikh A, Davies GA.",,PLoS medicine,2021,2021-02-12,Y,,,,"

Background

Socioeconomic deprivation is known to be associated with worse outcomes in asthma, but there is a lack of population-based evidence of its impact across all stages of patient care. We investigated the association of socioeconomic deprivation with asthma-related care and outcomes across primary and secondary care and with asthma-related death in Wales.

Methods and findings

We constructed a national cohort, identified from 76% (2.4 million) of the Welsh population, of continuously treated asthma patients between 2013 and 2017 using anonymised, person-level, linked, routinely collected primary and secondary care data in the Secure Anonymised Information Linkage (SAIL) Databank. We investigated the association between asthma-related health service utilisation, prescribing, and deaths with the 2011 Welsh Index of Multiple Deprivation (WIMD) and its domains. We studied 106,926 patients (534,630 person-years), 56.3% were female, with mean age of 47.5 years (SD = 20.3). Compared to the least deprived patients, the most deprived patients had slightly fewer total asthma-related primary care consultations per patient (incidence rate ratio [IRR] = 0.98, 95% CI 0.97-0.99, p-value < 0.001), slightly fewer routine asthma reviews (IRR = 0.98, 0.97-0.99, p-value < 0.001), lower controller-to-total asthma medication ratios (AMRs; 0.50 versus 0.56, p-value < 0.001), more asthma-related accident and emergency (A&E) attendances (IRR = 1.27, 1.10-1.46, p-value = 0.001), more asthma emergency admissions (IRR = 1.56, 1.39-1.76, p-value < 0.001), longer asthma-related hospital stay (IRR = 1.64, 1.39-1.94, p-value < 0.001), and were at higher risk of asthma-related death (risk ratio of deaths with any mention of asthma 1.56, 1.18-2.07, p-value = 0.002). Study limitations include the deprivation index being area based and the potential for residual confounders and mediators.

Conclusions

In this study, we observed that the most deprived asthma patients in Wales had different prescribing patterns, more A&E attendances, more emergency hospital admissions, and substantially higher risk of death. Interventions specifically designed to improve treatment and outcomes for these disadvantaged groups are urgently needed.",,pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1003497&type=printable; doi:https://doi.org/10.1371/journal.pmed.1003497; html:https://europepmc.org/articles/PMC7880491; pdf:https://europepmc.org/articles/PMC7880491?pdf=render 33952557,https://doi.org/10.1136/bmjopen-2021-049964,Study protocol of the Edinburgh and Lothian Virus Intervention Study in Kids: a randomised controlled trial of hypertonic saline nose drops in children with upper respiratory tract infections (ELVIS Kids).,"Ramalingam S, Graham C, Oatey K, Rayson P, Stoddart A, Sheikh A, Cunningham S, ELVIS Kids Trial Investigators.",,BMJ open,2021,2021-05-05,Y,Virology; Community Child Health; Neonatology; Primary Care; Paediatric Infectious Disease & Immunisation,,,"

Introduction

Edinburgh and Lothians' Viral Intervention Study Kids is a parallel, open-label, randomised controlled trial of hypertonic saline (HS) nose drops (~2.6% sodium chloride) vs standard care in children <7 years of age with symptoms of an upper respiratory tract infection (URTI).

Methods and analysis

Children are recruited prior to URTI or within 48 hours of developing URTI symptoms by advertising in areas such as local schools/nurseries, health centres/hospitals, recreational facilities, public events, workplaces, local/social media. Willing parents/guardians, of children <7 years of age will be asked to contact the research team at their local site. Children will be randomised to either a control arm (standard symptomatic care), or intervention arm (three drops/nostril of HS, at least four times a day, until 24 hours after asymptomatic or a maximum of 28 days). All participants are requested to provide a nasal swab at the start of the study (intervention arm: before HS drops) and then daily for four more days. Parent/guardian complete a validated daily diary, an end of illness diary, a satisfaction questionnaire and a wheeze questionnaire (day 28). The parent/guardian of a child in the intervention arm is taught to prepare HS nose drops. Parent/guardian of children asymptomatic at recruitment are requested to inform the research team within 48 hours of their child developing an URTI and follow the instructions already provided. The day 28 questionnaire determines if the child experienced a wheeze following illness. Participation in the study ends on day 28.

Ethics and dissemination

The study has been approved by the West of Scotland Research Ethics Service (18/WS/0080). It is cosponsored by Academic and Clinical Central Office for Research and Development-a partnership between the University of Edinburgh and National Health Service Lothian Health Board. The findings will be disseminated through peer-reviewed publications, conference presentations and via the study website.

Trial registration number

NCT03463694.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/5/e049964.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-049964; html:https://europepmc.org/articles/PMC8103393; pdf:https://europepmc.org/articles/PMC8103393?pdf=render 35835543,https://doi.org/10.1136/heartjnl-2022-321196,Eligibility for early rhythm control in patients with atrial fibrillation in the UK Biobank.,"Kany S, Cardoso VR, Bravo L, Williams JA, Schnabel R, Fabritz L, Gkoutos GV, Kirchhof P.",,Heart (British Cardiac Society),2022,2022-11-10,Y,Atrial fibrillation; Stroke; Catheter ablation,,,"

Objective

The Early Treatment of Atrial Fibrillation for Stroke Prevention (EAST-AFNET4) trial showed a clinical benefit of early rhythm-control therapy in patients with recently diagnosed atrial fibrillation (AF). The generalisability of the results in the general population is not known.

Methods

Participants in the population-based UK Biobank were assessed for eligibility based on the EAST-AFNET4 inclusion/exclusion criteria. Treatment of all eligible participants was classified as early rhythm-control (antiarrhythmic drug therapy or AF ablation) or usual care. To assess treatment effects, primary care data and Hospital Episode Statistics were merged with UK Biobank data.Efficacy and safety outcomes were compared between groups in the entire cohort and in a propensity-matched data set.

Results

AF was present in 35 526/502 493 (7.1%) participants, including 8340 (988 with AF <1 year) with AF at enrolment and 27 186 with incident AF during follow-up. Most participants (22 003/27 186; 80.9%) with incident AF were eligible for early rhythm-control.Eligible participants were older (70 years vs 63 years) and more likely to be female (42% vs 21%) compared with ineligible patients. Of 9004 participants with full primary care data, 874 (9.02%) received early rhythm-control. Safety outcomes were not different between patients receiving early rhythm-control and controls. The primary outcome of EAST-AFNET 4, a composite of cardiovascular death, stroke/transient ischaemic attack and hospitalisation for heart failure or acute coronary syndrome occurred less often in participants receiving early rhythm-control compared with controls in the entire cohort (HR 0.82, 95% CI 0.71 to 0.94, p=0.005). In the propensity-score matched analysis, early rhythm-control did not significantly decrease of the primary outcome compared with usual care (HR 0.87, 95% CI 0.72 to 1.04, p=0.124).

Conclusion

Around 80% of participants diagnosed with AF in the UK population are eligible for early rhythm-control. Early rhythm-control therapy was safe in routine care.",,pdf:https://heart.bmj.com/content/heartjnl/early/2022/07/13/heartjnl-2022-321196.full.pdf; doi:https://doi.org/10.1136/heartjnl-2022-321196; html:https://europepmc.org/articles/PMC9664114; pdf:https://europepmc.org/articles/PMC9664114?pdf=render @@ -737,35 +737,35 @@ PMC9645061,https://doi.org/,Using population-scale medication data to evaluate t 33875444,https://doi.org/10.1136/bmjopen-2020-045077,COVID-19 in patients with hepatobiliary and pancreatic diseases: a single-centre cross-sectional study in East London.,"Dayem Ullah AZM, Sivapalan L, Kocher HM, Chelala C.",,BMJ open,2021,2021-04-19,Y,Pancreatic Disease; Hepatobiliary Disease; Covid-19,,,"

Objective

To explore risk factors associated with COVID-19 susceptibility and survival in patients with pre-existing hepato-pancreato-biliary (HPB) conditions.

Design

Cross-sectional study.

Setting

East London Pancreatic Cancer Epidemiology (EL-PaC-Epidem) Study at Barts Health National Health Service Trust, UK. Linked electronic health records were interrogated on a cohort of participants (age ≥18 years), reported with HPB conditions between 1 April 2008 and 6 March 2020.

Participants

EL-PaC-Epidem Study participants, alive on 12 February 2020, and living in East London within the previous 6 months (n=15 440). The cohort represents a multi-ethnic population with 51.7% belonging to the non-White background.

Main outcome measure

COVID-19 incidence and mortality.

Results

Some 226 (1.5%) participants had confirmed COVID-19 diagnosis between 12 February and 12 June 2020, with increased odds for men (OR 1.56; 95% CI 1.2 to 2.04) and Black ethnicity (2.04; 1.39 to 2.95) as well as patients with moderate to severe liver disease (2.2; 1.35 to 3.59). Each additional comorbidity increased the odds of infection by 62%. Substance misusers were at more risk of infection, so were patients on vitamin D treatment. The higher ORs in patients with chronic pancreatic or mild liver conditions, age >70, and a history of smoking or obesity were due to coexisting comorbidities. Increased odds of death were observed for men (3.54; 1.68 to 7.85) and Black ethnicity (3.77; 1.38 to 10.7). Patients having respiratory complications from COVID-19 without a history of chronic respiratory disease also had higher odds of death (5.77; 1.75 to 19).

Conclusions

In this large population-based study of patients with HPB conditions, men, Black ethnicity, pre-existing moderate to severe liver conditions, six common medical multimorbidities, substance misuse and a history of vitamin D treatment independently posed higher odds of acquiring COVID-19 compared with their respective counterparts. The odds of death were significantly high for men and Black people.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/4/e045077.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-045077; html:https://europepmc.org/articles/PMC8057071; pdf:https://europepmc.org/articles/PMC8057071?pdf=render 37118449,https://doi.org/10.1038/s43587-022-00224-w,Robust SARS-CoV-2-specific and heterologous immune responses in vaccine-naïve residents of long-term care facilities who survive natural infection.,"Tut G, Lancaster T, Butler MS, Sylla P, Spalkova E, Bone D, Kaur N, Bentley C, Amin U, Jadir AT, Hulme S, Ayodel M, Dowell AC, Pearce H, Zuo J, Margielewska-Davies S, Verma K, Nicol S, Begum J, Jinks E, Tut E, Bruton R, Krutikov M, Shrotri M, Giddings R, Azmi B, Fuller C, Irwin-Singer A, Hayward A, Copas A, Shallcross L, Moss P.",,Nature aging,2022,2022-05-30,Y,,,,"We studied humoral and cellular immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 152 long-term care facility staff and 124 residents over a prospective 4-month period shortly after the first wave of infection in England. We show that residents of long-term care facilities developed high and stable levels of antibodies against spike protein and receptor-binding domain. Nucleocapsid-specific responses were also elevated but waned over time. Antibodies showed stable and equivalent levels of functional inhibition against spike-angiotensin-converting enzyme 2 binding in all age groups with comparable activity against viral variants of concern. SARS-CoV-2 seropositive donors showed high levels of antibodies to other beta-coronaviruses but serostatus did not impact humoral immunity to influenza or other respiratory syncytial viruses. SARS-CoV-2-specific cellular responses were similar across all ages but virus-specific populations showed elevated levels of activation in older donors. Thus, survivors of SARS-CoV-2 infection show a robust and stable immunity against the virus that does not negatively impact responses to other seasonal viruses.",,pdf:https://www.nature.com/articles/s43587-022-00224-w.pdf; doi:https://doi.org/10.1038/s43587-022-00224-w; html:https://europepmc.org/articles/PMC10154219; pdf:https://europepmc.org/articles/PMC10154219?pdf=render 35923560,https://doi.org/10.1016/j.lanepe.2022.100475,Equity of access to NHS-funded hip replacements in England and Wales: Trends from 2006 to 2016.,"Wyatt S, Bailey R, Moore P, Revell M.",,The Lancet regional health. Europe,2022,2022-07-29,Y,trends; Equity; Hip Replacements; Socio-economic Deprivation,,,"

Background

Elective hip replacement is a cost-effective means of improving hip function. Previous research has suggested that the supply of hip replacements in the NHS is governed by the inverse care law. We examine whether inequities in supply improved in England and Wales between 2006 and 2016.

Methods

We compare levels of need and supply of NHS funded hip replacements to adults aged 50+ years, across quintiles of deprivation in England and Wales between 2006 and 2016. We use data from routine health records and a large longitudinal study and adjust for age and sex using general additive negative-binomial regression.

Findings

The number of NHS-funded hip replacements per 100,000 population rose substantially from 272.6 and 266.7 in 2002, to 539.7 and 466.3 in 2018 in England and Wales respectively. Having adjusted for age and sex, people living in the most deprived quintile were 2.36 (95% CI, 1.69 to 3.29) times more likely to need a hip replacement in 2006 than those living in quintile 3, whereas those living in the least deprived quintile were 0.45 (95% CI, 0.39 to 0.69) as likely. Despite this, people living in the most deprived quintile were 0.81 (95% CI, 0.78 to 0.83) times as likely in England and 0.93 (95% CI, 0.84 to 1.04) as likely in Wales to receive an NHS-funded hip replacement in 2006 than those living in quintile 3. We found no evidence that these substantial inequities had reduced between 2006 and 2016.

Interpretation

With respect to hip-replacement surgery in England and Wales, policy ambitions to reduce healthcare inequities have not been realised.

Funding

This work was supported by Health Data Research UK.",,doi:https://doi.org/10.1016/j.lanepe.2022.100475; doi:https://doi.org/10.1016/j.lanepe.2022.100475; html:https://europepmc.org/articles/PMC9340533; pdf:https://europepmc.org/articles/PMC9340533?pdf=render -38198154,https://doi.org/10.1093/bjs/znad347,Natural language processing to automate a web-based model of care and modernize skin cancer multidisciplinary team meetings.,"Ali SR, Dobbs TD, Tarafdar A, Strafford H, Fonferko-Shadrach B, Lacey AS, Pickrell WO, Hutchings HA, Whitaker IS.",,The British journal of surgery,2024,2024-01-01,Y,,,,"

Background

Cancer multidisciplinary team (MDT) meetings are under intense pressure to reform given the rapidly rising incidence of cancer and national mandates for protocolized streaming of cases. The aim of this study was to validate a natural language processing (NLP)-based web platform to automate evidence-based MDT decisions for skin cancer with basal cell carcinoma as a use case.

Methods

A novel and validated NLP information extraction model was used to extract perioperative tumour and surgical factors from histopathology reports. A web application with a bespoke application programming interface used data from this model to provide an automated clinical decision support system, mapped to national guidelines and generating a patient letter to communicate ongoing management. Performance was assessed against retrospectively derived recommendations by two independent and blinded expert clinicians.

Results

There were 893 patients (1045 lesions) used to internally validate the model. High accuracy was observed when compared against human predictions, with an overall value of 0.92. Across all classifiers the virtual skin MDT was highly specific (0.96), while sensitivity was lower (0.72).

Conclusion

This study demonstrates the feasibility of a fully automated, virtual, web-based service model to host the skin MDT with good system performance. This platform could be used to support clinical decision-making during MDTs as 'human in the loop' approach to aid protocolized streaming. Future prospective studies are needed to validate the model in tumour types where guidelines are more complex.",,pdf:https://academic.oup.com/bjs/article-pdf/111/1/znad347/55374438/znad347.pdf; doi:https://doi.org/10.1093/bjs/znad347; html:https://europepmc.org/articles/PMC10782209; pdf:https://europepmc.org/articles/PMC10782209?pdf=render 32424068,https://doi.org/10.1101/gr.250704.119,Comprehensive analyses of 723 transcriptomes enhance genetic and biological interpretations for complex traits in cattle.,"Fang L, Cai W, Liu S, Canela-Xandri O, Gao Y, Jiang J, Rawlik K, Li B, Schroeder SG, Rosen BD, Li CJ, Sonstegard TS, Alexander LJ, Van Tassell CP, VanRaden PM, Cole JB, Yu Y, Zhang S, Tenesa A, Ma L, Liu GE.",,Genome research,2020,2020-05-18,Y,,,,"By uniformly analyzing 723 RNA-seq data from 91 tissues and cell types, we built a comprehensive gene atlas and studied tissue specificity of genes in cattle. We demonstrated that tissue-specific genes significantly reflected the tissue-relevant biology, showing distinct promoter methylation and evolution patterns (e.g., brain-specific genes evolve slowest, whereas testis-specific genes evolve fastest). Through integrative analyses of those tissue-specific genes with large-scale genome-wide association studies, we detected relevant tissues/cell types and candidate genes for 45 economically important traits in cattle, including blood/immune system (e.g., CCDC88C) for male fertility, brain (e.g., TRIM46 and RAB6A) for milk production, and multiple growth-related tissues (e.g., FGF6 and CCND2) for body conformation. We validated these findings by using epigenomic data across major somatic tissues and sperm. Collectively, our findings provided novel insights into the genetic and biological mechanisms underlying complex traits in cattle, and our transcriptome atlas can serve as a primary source for biological interpretation, functional validation, studies of adaptive evolution, and genomic improvement in livestock.",,pdf:https://genome.cshlp.org/content/30/5/790.full.pdf; doi:https://doi.org/10.1101/gr.250704.119; html:https://europepmc.org/articles/PMC7263193; pdf:https://europepmc.org/articles/PMC7263193?pdf=render +38198154,https://doi.org/10.1093/bjs/znad347,Natural language processing to automate a web-based model of care and modernize skin cancer multidisciplinary team meetings.,"Ali SR, Dobbs TD, Tarafdar A, Strafford H, Fonferko-Shadrach B, Lacey AS, Pickrell WO, Hutchings HA, Whitaker IS.",,The British journal of surgery,2024,2024-01-01,Y,,,,"

Background

Cancer multidisciplinary team (MDT) meetings are under intense pressure to reform given the rapidly rising incidence of cancer and national mandates for protocolized streaming of cases. The aim of this study was to validate a natural language processing (NLP)-based web platform to automate evidence-based MDT decisions for skin cancer with basal cell carcinoma as a use case.

Methods

A novel and validated NLP information extraction model was used to extract perioperative tumour and surgical factors from histopathology reports. A web application with a bespoke application programming interface used data from this model to provide an automated clinical decision support system, mapped to national guidelines and generating a patient letter to communicate ongoing management. Performance was assessed against retrospectively derived recommendations by two independent and blinded expert clinicians.

Results

There were 893 patients (1045 lesions) used to internally validate the model. High accuracy was observed when compared against human predictions, with an overall value of 0.92. Across all classifiers the virtual skin MDT was highly specific (0.96), while sensitivity was lower (0.72).

Conclusion

This study demonstrates the feasibility of a fully automated, virtual, web-based service model to host the skin MDT with good system performance. This platform could be used to support clinical decision-making during MDTs as 'human in the loop' approach to aid protocolized streaming. Future prospective studies are needed to validate the model in tumour types where guidelines are more complex.",,pdf:https://academic.oup.com/bjs/article-pdf/111/1/znad347/55374438/znad347.pdf; doi:https://doi.org/10.1093/bjs/znad347; html:https://europepmc.org/articles/PMC10782209; pdf:https://europepmc.org/articles/PMC10782209?pdf=render 35256633,https://doi.org/10.1038/s41598-022-07291-4,Shared genetic loci for body fat storage and adipocyte lipolysis in humans.,"Kulyté A, Lundbäck V, Arner P, Strawbridge RJ, Dahlman I.",,Scientific reports,2022,2022-03-07,Y,,,,"Total body fat and central fat distribution are heritable traits and well-established predictors of adverse metabolic outcomes. Lipolysis is the process responsible for the hydrolysis of triacylglycerols stored in adipocytes. To increase our understanding of the genetic regulation of body fat distribution and total body fat, we set out to determine if genetic variants associated with body mass index (BMI) or waist-hip-ratio adjusted for BMI (WHRadjBMI) in genome-wide association studies (GWAS) mediate their effect by influencing adipocyte lipolysis. We utilized data from the recent GWAS of spontaneous and isoprenaline-stimulated lipolysis in the unique GENetics of Adipocyte Lipolysis (GENiAL) cohort. GENiAL consists of 939 participants who have undergone abdominal subcutaneous adipose biopsy for the determination of spontaneous and isoprenaline-stimulated lipolysis in adipocytes. We report 11 BMI and 15 WHRadjBMI loci with SNPs displaying nominal association with lipolysis and allele-dependent gene expression in adipose tissue according to in silico analysis. Functional evaluation of candidate genes in these loci by small interfering RNAs (siRNA)-mediated knock-down in adipose-derived stem cells identified ZNF436 and NUP85 as intrinsic regulators of lipolysis consistent with the associations observed in the clinical cohorts. Furthermore, candidate genes in another BMI-locus (STX17) and two more WHRadjBMI loci (NID2, GGA3, GRB2) control lipolysis alone, or in conjunction with lipid storage, and may hereby be involved in genetic control of body fat. The findings expand our understanding of how genetic variants mediate their impact on the complex traits of fat storage and distribution.",,pdf:https://www.nature.com/articles/s41598-022-07291-4.pdf; doi:https://doi.org/10.1038/s41598-022-07291-4; html:https://europepmc.org/articles/PMC8901764; pdf:https://europepmc.org/articles/PMC8901764?pdf=render 38286672,https://doi.org/10.1136/bmjopen-2023-073582,Improving our understanding of the social determinants of mental health: a data linkage study of mental health records and the 2011 UK census.,"Cybulski L, Chilman N, Jewell A, Dewey M, Hildersley R, Morgan C, Huck R, Hotopf M, Stewart R, Pritchard M, Wuerth M, Das-Munshi J.",,BMJ open,2024,2024-01-29,Y,Psychiatry; Mental health; Schizophrenia & Psychotic Disorders,,,"

Objectives

To address the lack of individual-level socioeconomic information in electronic healthcare records, we linked the 2011 census of England and Wales to patient records from a large mental healthcare provider. This paper describes the linkage process and methods for mitigating bias due to non-matching.

Setting

South London and Maudsley NHS Foundation Trust (SLaM), a mental healthcare provider in Southeast London.

Design

Clinical records from SLaM were supplied to the Office of National Statistics for linkage to the census through a deterministic matching algorithm. We examined clinical (International Classification of Disease-10 diagnosis, history of hospitalisation, frequency of service contact) and socio-demographic (age, gender, ethnicity, deprivation) information recorded in Clinical Record Interactive Search (CRIS) as predictors of linkage success with the 2011 census. To assess and adjust for potential biases caused by non-matching, we evaluated inverse probability weighting for mortality associations.

Participants

Individuals of all ages in contact with SLaM up until December 2019 (N=459 374).

Outcome measures

Likelihood of mental health records' linkage to census.

Results

220 864 (50.4%) records from CRIS linked to the 2011 census. Young adults (prevalence ratio (PR) 0.80, 95% CI 0.80 to 0.81), individuals living in more deprived areas (PR 0.78, 95% CI 0.78 to 0.79) and minority ethnic groups (eg, Black African, PR 0.67, 0.66 to 0.68) were less likely to match to census. After implementing inverse probability weighting, we observed little change in the strength of association between clinical/demographic characteristics and mortality (eg, presence of any psychiatric disorder: unweighted PR 2.66, 95% CI 2.52 to 2.80; weighted PR 2.70, 95% CI 2.56 to 2.84).

Conclusions

Lower response rates to the 2011 census among people with psychiatric disorders may have contributed to lower match rates, a potential concern as the census informs service planning and allocation of resources. Due to its size and unique characteristics, the linked data set will enable novel investigations into the relationship between socioeconomic factors and psychiatric disorders.",,doi:https://doi.org/10.1136/bmjopen-2023-073582; html:https://europepmc.org/articles/PMC10826590; pdf:https://europepmc.org/articles/PMC10826590?pdf=render 33716109,https://doi.org/10.1016/j.jinf.2021.03.002,Short durations of corticosteroids for hospitalised COVID-19 patients are associated with a high readmission rate.,"Chaudhry Z, Shawe-Taylor M, Rampling T, Cutfield T, Bidwell G, Chan XHS, Last A, Williams B, Logan S, Marks M, Esmail H.",,The Journal of infection,2021,2021-03-11,Y,Dexamethasone; Corticosteroids; Hospital; Readmissions; Covid-19,,,"

Objective

Our objective was to describe the characteristics of patients admitted, discharged and readmitted, due to COVID-19, to a central London acute-care hospital during the second peak, in particular in relation to corticosteroids use.

Methods

We reviewed patients admitted from the community to University College Hospital (UCH) with COVID-19 as their primary diagnosis between 1st-31st December 2020. Re-attendance and readmission data were collected for patients who re-presented within 10 days following discharge. Data were retrospectively collected.

Results

196 patients were admitted from the community with a diagnosis of COVID-19 and discharged alive in December 2020. Corticosteroids were prescribed in hospital for a median of 5 days (IQR 3-8). 20 patients (10.2%) were readmitted within 10 days. 11/20 received corticosteroids in the first admission of which 10 had received 1-3 days of corticosteroids. Readmission rate in those receiving 1-3 days of corticosteroids was 25%.

Conclusions

Most international guidelines have recommended providing up to 10 days of corticosteroids for severe COVID-19 but stopping on discharge. Our findings show shorter courses of corticosteroids during admission are associated with an increased risk of being readmitted and support continuing the course of corticosteroids after hospital discharge monitored in the virtual ward setting.",,pdf:http://www.journalofinfection.com/article/S0163445321001158/pdf; doi:https://doi.org/10.1016/j.jinf.2021.03.002; html:https://europepmc.org/articles/PMC7948670; pdf:https://europepmc.org/articles/PMC7948670?pdf=render 34265229,https://doi.org/10.1177/01410768211032850,"Symptoms, complications and management of long COVID: a review.","Aiyegbusi OL, Hughes SE, Turner G, Rivera SC, McMullan C, Chandan JS, Haroon S, Price G, Davies EH, Nirantharakumar K, Sapey E, Calvert MJ, TLC Study Group.",,Journal of the Royal Society of Medicine,2021,2021-07-15,Y,Infectious diseases; epidemiology; Public Health; Respiratory Medicine; Health Service Research; Covid-19; Long Covid; Post-Covid-19 Syndrome; Persistent Covid-19 Symptoms,,,"Globally, there are now over 160 million confirmed cases of COVID-19 and more than 3 million deaths. While the majority of infected individuals recover, a significant proportion continue to experience symptoms and complications after their acute illness. Patients with 'long COVID' experience a wide range of physical and mental/psychological symptoms. Pooled prevalence data showed the 10 most prevalent reported symptoms were fatigue, shortness of breath, muscle pain, joint pain, headache, cough, chest pain, altered smell, altered taste and diarrhoea. Other common symptoms were cognitive impairment, memory loss, anxiety and sleep disorders. Beyond symptoms and complications, people with long COVID often reported impaired quality of life, mental health and employment issues. These individuals may require multidisciplinary care involving the long-term monitoring of symptoms, to identify potential complications, physical rehabilitation, mental health and social services support. Resilient healthcare systems are needed to ensure efficient and effective responses to future health challenges.",,doi:https://doi.org/10.1177/01410768211032850; doi:https://doi.org/10.1177/01410768211032850; html:https://europepmc.org/articles/PMC8450986; pdf:https://europepmc.org/articles/PMC8450986?pdf=render -36350656,https://doi.org/10.1093/nar/gkac1010,The NHGRI-EBI GWAS Catalog: knowledgebase and deposition resource.,"Sollis E, Mosaku A, Abid A, Buniello A, Cerezo M, Gil L, Groza T, Güneş O, Hall P, Hayhurst J, Ibrahim A, Ji Y, John S, Lewis E, MacArthur JAL, McMahon A, Osumi-Sutherland D, Panoutsopoulou K, Pendlington Z, Ramachandran S, Stefancsik R, Stewart J, Whetzel P, Wilson R, Hindorff L, Cunningham F, Lambert SA, Inouye M, Parkinson H, Harris LW.",,Nucleic acids research,2023,2023-01-01,Y,,,,"The NHGRI-EBI GWAS Catalog (www.ebi.ac.uk/gwas) is a FAIR knowledgebase providing detailed, structured, standardised and interoperable genome-wide association study (GWAS) data to >200 000 users per year from academic research, healthcare and industry. The Catalog contains variant-trait associations and supporting metadata for >45 000 published GWAS across >5000 human traits, and >40 000 full P-value summary statistics datasets. Content is curated from publications or acquired via author submission of prepublication summary statistics through a new submission portal and validation tool. GWAS data volume has vastly increased in recent years. We have updated our software to meet this scaling challenge and to enable rapid release of submitted summary statistics. The scope of the repository has expanded to include additional data types of high interest to the community, including sequencing-based GWAS, gene-based analyses and copy number variation analyses. Community outreach has increased the number of shared datasets from under-represented traits, e.g. cancer, and we continue to contribute to awareness of the lack of population diversity in GWAS. Interoperability of the Catalog has been enhanced through links to other resources including the Polygenic Score Catalog and the International Mouse Phenotyping Consortium, refinements to GWAS trait annotation, and the development of a standard format for GWAS data.",,pdf:https://academic.oup.com/nar/article-pdf/51/D1/D977/48440802/gkac1010.pdf; doi:https://doi.org/10.1093/nar/gkac1010; html:https://europepmc.org/articles/PMC9825413; pdf:https://europepmc.org/articles/PMC9825413?pdf=render 31315158,https://doi.org/10.1002/cnm.3235,Non-invasive coronary CT angiography-derived fractional flow reserve: A benchmark study comparing the diagnostic performance of four different computational methodologies.,"Carson JM, Pant S, Roobottom C, Alcock R, Javier Blanco P, Alberto Bulant C, Vassilevski Y, Simakov S, Gamilov T, Pryamonosov R, Liang F, Ge X, Liu Y, Nithiarasu P.",,International journal for numerical methods in biomedical engineering,2019,2019-08-16,Y,Fractional Flow Reserve; Benchmark; Haemodynamic Models,,,"Non-invasive coronary computed tomography (CT) angiography-derived fractional flow reserve (cFFR) is an emergent approach to determine the functional relevance of obstructive coronary lesions. Its feasibility and diagnostic performance has been reported in several studies. It is unclear if differences in sensitivity and specificity between these studies are due to study design, population, or ""computational methodology."" We evaluate the diagnostic performance of four different computational workflows for the prediction of cFFR using a limited data set of 10 patients, three based on reduced-order modelling and one based on a 3D rigid-wall model. The results for three of these methodologies yield similar accuracy of 6.5% to 10.5% mean absolute difference between computed and measured FFR. The main aspects of modelling which affected cFFR estimation were choice of inlet and outlet boundary conditions and estimation of flow distribution in the coronary network. One of the reduced-order models showed the lowest overall deviation from the clinical FFR measurements, indicating that reduced-order models are capable of a similar level of accuracy to a 3D model. In addition, this reduced-order model did not include a lumped pressure-drop model for a stenosis, which implies that the additional effort of isolating a stenosis and inserting a pressure-drop element in the spatial mesh may not be required for FFR estimation. The present benchmark study is the first of this kind, in which we attempt to homogenize the data required to compute FFR using mathematical models. The clinical data utilised in the cFFR workflows are made publicly available online.","Retrospective case series of 10 patients having coronary angiogram and invasive fractional flow reserve measurement. The authors used 4 different techniques to estimate coronary vessel flow rate and compared their measurement agreement with clinical FFA measurements and with each other. They found that all 4 methods gave different results, but one approach was more similar with the clinical gold standard. They propose this method with most worthy of further investigaiton.",pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/cnm.3235; doi:https://doi.org/10.1002/cnm.3235; html:https://europepmc.org/articles/PMC6851543; pdf:https://europepmc.org/articles/PMC6851543?pdf=render -34148732,https://doi.org/10.1016/j.bja.2021.05.001,Surgical activity in England and Wales during the COVID-19 pandemic: a nationwide observational cohort study.,"Dobbs TD, Gibson JAG, Fowler AJ, Abbott TE, Shahid T, Torabi F, Griffiths R, Lyons RA, Pearse RM, Whitaker IS.",,British journal of anaesthesia,2021,2021-06-18,Y,Surgery; Anaesthesia; Public Policy; Waiting List; Surgical Activity; Covid-19,,,"

Background

A significant proportion of healthcare resource has been diverted to the care of those with COVID-19. This study reports the volume of surgical activity and the number of cancelled surgical procedures during the COVID-19 pandemic.

Methods

We used hospital episode statistics for all adult patients undergoing surgery between January 1, 2020 and December 31, 2020 in England and Wales. We identified surgical procedures using a previously published list of procedure codes. Procedures were stratified by urgency of surgery as defined by NHS England. We calculated the deficit of surgical activity by comparing the expected number of procedures from 2016 to 2019 with the actual number of procedures in 2020. Using a linear regression model, we calculated the expected cumulative number of cancelled procedures by December 31, 2021.

Results

The total number of surgical procedures carried out in England and Wales in 2020 was 3 102 674 compared with the predicted number of 4 671 338 (95% confidence interval [CI]: 4 218 740-5 123 932). This represents a 33.6% reduction in the national volume of surgical activity. There were 763 730 emergency surgical procedures (13.4% reduction) compared with 2 338 944 elective surgical procedures (38.6% reduction). The cumulative number of cancelled or postponed procedures was 1 568 664 (95% CI: 1 116 066-2 021 258). We estimate that this will increase to 2 358 420 (95% CI: 1 667 587-3 100 808) up to December 31, 2021.

Conclusions

The volume of surgical activity in England and Wales was reduced by 33.6% in 2020, resulting in more than 1.5 million cancelled operations. This deficit will continue to grow in 2021.",,pdf:http://www.bjanaesthesia.org/article/S0007091221002737/pdf; doi:https://doi.org/10.1016/j.bja.2021.05.001; html:https://europepmc.org/articles/PMC8277602; pdf:https://europepmc.org/articles/PMC8277602?pdf=render +36350656,https://doi.org/10.1093/nar/gkac1010,The NHGRI-EBI GWAS Catalog: knowledgebase and deposition resource.,"Sollis E, Mosaku A, Abid A, Buniello A, Cerezo M, Gil L, Groza T, Güneş O, Hall P, Hayhurst J, Ibrahim A, Ji Y, John S, Lewis E, MacArthur JAL, McMahon A, Osumi-Sutherland D, Panoutsopoulou K, Pendlington Z, Ramachandran S, Stefancsik R, Stewart J, Whetzel P, Wilson R, Hindorff L, Cunningham F, Lambert SA, Inouye M, Parkinson H, Harris LW.",,Nucleic acids research,2023,2023-01-01,Y,,,,"The NHGRI-EBI GWAS Catalog (www.ebi.ac.uk/gwas) is a FAIR knowledgebase providing detailed, structured, standardised and interoperable genome-wide association study (GWAS) data to >200 000 users per year from academic research, healthcare and industry. The Catalog contains variant-trait associations and supporting metadata for >45 000 published GWAS across >5000 human traits, and >40 000 full P-value summary statistics datasets. Content is curated from publications or acquired via author submission of prepublication summary statistics through a new submission portal and validation tool. GWAS data volume has vastly increased in recent years. We have updated our software to meet this scaling challenge and to enable rapid release of submitted summary statistics. The scope of the repository has expanded to include additional data types of high interest to the community, including sequencing-based GWAS, gene-based analyses and copy number variation analyses. Community outreach has increased the number of shared datasets from under-represented traits, e.g. cancer, and we continue to contribute to awareness of the lack of population diversity in GWAS. Interoperability of the Catalog has been enhanced through links to other resources including the Polygenic Score Catalog and the International Mouse Phenotyping Consortium, refinements to GWAS trait annotation, and the development of a standard format for GWAS data.",,pdf:https://academic.oup.com/nar/article-pdf/51/D1/D977/48440802/gkac1010.pdf; doi:https://doi.org/10.1093/nar/gkac1010; html:https://europepmc.org/articles/PMC9825413; pdf:https://europepmc.org/articles/PMC9825413?pdf=render 30950797,https://doi.org/10.2196/12286,Applications of Machine Learning in Real-Life Digital Health Interventions: Review of the Literature.,"Triantafyllidis AK, Tsanas A.",,Journal of medical Internet research,2019,2019-04-05,Y,Artificial intelligence; Review; data mining; Telemedicine; Machine Learning; Digital Health,Applied Analytics,,"

Background

Machine learning has attracted considerable research interest toward developing smart digital health interventions. These interventions have the potential to revolutionize health care and lead to substantial outcomes for patients and medical professionals.

Objective

Our objective was to review the literature on applications of machine learning in real-life digital health interventions, aiming to improve the understanding of researchers, clinicians, engineers, and policy makers in developing robust and impactful data-driven interventions in the health care domain.

Methods

We searched the PubMed and Scopus bibliographic databases with terms related to machine learning, to identify real-life studies of digital health interventions incorporating machine learning algorithms. We grouped those interventions according to their target (ie, target condition), study design, number of enrolled participants, follow-up duration, primary outcome and whether this had been statistically significant, machine learning algorithms used in the intervention, and outcome of the algorithms (eg, prediction).

Results

Our literature search identified 8 interventions incorporating machine learning in a real-life research setting, of which 3 (37%) were evaluated in a randomized controlled trial and 5 (63%) in a pilot or experimental single-group study. The interventions targeted depression prediction and management, speech recognition for people with speech disabilities, self-efficacy for weight loss, detection of changes in biopsychosocial condition of patients with multiple morbidity, stress management, treatment of phantom limb pain, smoking cessation, and personalized nutrition based on glycemic response. The average number of enrolled participants in the studies was 71 (range 8-214), and the average follow-up study duration was 69 days (range 3-180). Of the 8 interventions, 6 (75%) showed statistical significance (at the P=.05 level) in health outcomes.

Conclusions

This review found that digital health interventions incorporating machine learning algorithms in real-life studies can be useful and effective. Given the low number of studies identified in this review and that they did not follow a rigorous machine learning evaluation methodology, we urge the research community to conduct further studies in intervention settings following evaluation principles and demonstrating the potential of machine learning in clinical practice.",,pdf:https://www.jmir.org/2019/4/e12286/PDF; doi:https://doi.org/10.2196/12286; html:https://europepmc.org/articles/PMC6473205 +34148732,https://doi.org/10.1016/j.bja.2021.05.001,Surgical activity in England and Wales during the COVID-19 pandemic: a nationwide observational cohort study.,"Dobbs TD, Gibson JAG, Fowler AJ, Abbott TE, Shahid T, Torabi F, Griffiths R, Lyons RA, Pearse RM, Whitaker IS.",,British journal of anaesthesia,2021,2021-06-18,Y,Surgery; Anaesthesia; Public Policy; Waiting List; Surgical Activity; Covid-19,,,"

Background

A significant proportion of healthcare resource has been diverted to the care of those with COVID-19. This study reports the volume of surgical activity and the number of cancelled surgical procedures during the COVID-19 pandemic.

Methods

We used hospital episode statistics for all adult patients undergoing surgery between January 1, 2020 and December 31, 2020 in England and Wales. We identified surgical procedures using a previously published list of procedure codes. Procedures were stratified by urgency of surgery as defined by NHS England. We calculated the deficit of surgical activity by comparing the expected number of procedures from 2016 to 2019 with the actual number of procedures in 2020. Using a linear regression model, we calculated the expected cumulative number of cancelled procedures by December 31, 2021.

Results

The total number of surgical procedures carried out in England and Wales in 2020 was 3 102 674 compared with the predicted number of 4 671 338 (95% confidence interval [CI]: 4 218 740-5 123 932). This represents a 33.6% reduction in the national volume of surgical activity. There were 763 730 emergency surgical procedures (13.4% reduction) compared with 2 338 944 elective surgical procedures (38.6% reduction). The cumulative number of cancelled or postponed procedures was 1 568 664 (95% CI: 1 116 066-2 021 258). We estimate that this will increase to 2 358 420 (95% CI: 1 667 587-3 100 808) up to December 31, 2021.

Conclusions

The volume of surgical activity in England and Wales was reduced by 33.6% in 2020, resulting in more than 1.5 million cancelled operations. This deficit will continue to grow in 2021.",,pdf:http://www.bjanaesthesia.org/article/S0007091221002737/pdf; doi:https://doi.org/10.1016/j.bja.2021.05.001; html:https://europepmc.org/articles/PMC8277602; pdf:https://europepmc.org/articles/PMC8277602?pdf=render 33212507,https://doi.org/10.1093/molbev/msaa279,Genomic Analysis Revealed a Convergent Evolution of LINE-1 in Coat Color: A Case Study in Water Buffaloes (Bubalus bubalis).,"Liang D, Zhao P, Si J, Fang L, Pairo-Castineira E, Hu X, Xu Q, Hou Y, Gong Y, Liang Z, Tian B, Mao H, Yindee M, Faruque MO, Kongvongxay S, Khamphoumee S, Liu GE, Wu DD, Barker JSF, Han J, Zhang Y.",,Molecular biology and evolution,2021,2021-03-01,Y,Transposon; Water buffalo; Convergent Evolution; Line-1; Asip Gene; White Coat Color,,,"Visible pigmentation phenotypes can be used to explore the regulation of gene expression and the evolution of coat color patterns in animals. Here, we performed whole-genome and RNA sequencing and applied genome-wide association study, comparative population genomics and biological experiments to show that the 2,809-bp-long LINE-1 insertion in the ASIP (agouti signaling protein) gene is the causative mutation for the white coat phenotype in swamp buffalo (Bubalus bubalis). This LINE-1 insertion (3' truncated and containing only 5' UTR) functions as a strong proximal promoter that leads to a 10-fold increase in the transcription of ASIP in white buffalo skin. The 165 bp of 5' UTR transcribed from the LINE-1 is spliced into the first coding exon of ASIP, resulting in a chimeric transcript. The increased expression of ASIP prevents melanocyte maturation, leading to the absence of pigment in white buffalo skin and hairs. Phylogenetic analyses indicate that the white buffalo-specific ASIP allele originated from a recent genetic transposition event in swamp buffalo. Interestingly, as a similar LINE-1 insertion has been identified in the cattle ASIP gene, we discuss the convergent mechanism of coat color evolution in the Bovini tribe.",,pdf:https://academic.oup.com/mbe/article-pdf/38/3/1122/36533820/msaa279.pdf; doi:https://doi.org/10.1093/molbev/msaa279; html:https://europepmc.org/articles/PMC7947781; pdf:https://europepmc.org/articles/PMC7947781?pdf=render 34534697,https://doi.org/10.1016/j.jbi.2021.103916,Ranking sets of morbidities using hypergraph centrality.,"Rafferty J, Watkins A, Lyons J, Lyons RA, Akbari A, Peek N, Jalali-Najafabadi F, Ba Dhafari T, Pate A, Martin GP, Bailey R.",,Journal of biomedical informatics,2021,2021-09-15,Y,Network Analysis; Hypergraph; Multi-morbidity,,,"Multi-morbidity, the health state of having two or more concurrent chronic conditions, is becoming more common as populations age, but is poorly understood. Identifying and understanding commonly occurring sets of diseases is important to inform clinical decisions to improve patient services and outcomes. Network analysis has been previously used to investigate multi-morbidity, but a classic application only allows for information on binary sets of diseases to contribute to the graph. We propose the use of hypergraphs, which allows for the incorporation of data on people with any number of conditions, and also allows us to obtain a quantitative understanding of the centrality, a measure of how well connected items in the network are to each other, of both single diseases and sets of conditions. Using this framework we illustrate its application with the set of conditions described in the Charlson morbidity index using data extracted from routinely collected population-scale, patient level electronic health records (EHR) for a cohort of adults in Wales, UK. Stroke and diabetes were found to be the most central single conditions. Sets of diseases featuring diabetes; diabetes with Chronic Pulmonary Disease, Renal Disease, Congestive Heart Failure and Cancer were the most central pairs of diseases. We investigated the differences between results obtained from the hypergraph and a classic binary graph and found that the centrality of diseases such as paraplegia, which are connected strongly to a single other disease is exaggerated in binary graphs compared to hypergraphs. The measure of centrality is derived from the weighting metrics calculated for disease sets and further investigation is needed to better understand the effect of the metric used in identifying the clinical significance and ranked centrality of grouped diseases. These initial results indicate that hypergraphs can be used as a valuable tool for analysing previously poorly understood relationships and information available in EHR data.",,doi:https://doi.org/10.1016/j.jbi.2021.103916; doi:https://doi.org/10.1016/j.jbi.2021.103916; html:https://europepmc.org/articles/PMC8524321 -38837310,https://doi.org/10.1002/ejhf.3306,"A nationwide, population-based study on specialized care for acute heart failure throughout the COVID-19 pandemic.","Cannata A, Mizani MA, Bromage DI, Piper SE, Hardman SMC, Sudlow C, de Belder M, Deanfield J, Gardner RS, Clark AL, Cleland JGF, McDonagh TA,  on behalf of the CVD‐COVID‐UK/COVID‐IMPACT Consortium.",,European journal of heart failure,2024,2024-06-04,N,Heart Failure; Specialist Care; Covid‐19; National Heart Failure Audit,,,"

Aims

The COVID-19 pandemic disrupted the delivery of care for patients with heart failure (HF), leading to fewer HF hospitalizations and increased mortality. However, nationwide data on quality of care and long-term outcomes across the pandemic are scarce.

Methods and results

We used data from the National Heart Failure Audit (NHFA) linked to national records for hospitalization and deaths. We compared pre-COVID (2018-2019), COVID (2020), and late/post-COVID (2021-2022) periods. Data for 227 250 patients admitted to hospital with HF were analysed and grouped according to the admission year and the presence of HF with (HFrEF) or without reduced ejection fraction (non-HFrEF). The median age at admission was 81 years (interquartile range 72-88), 55% were men (n = 125 975), 87% were of white ethnicity (n = 102 805), and 51% had HFrEF (n = 116 990). In-hospital management and specialized cardiology care were maintained throughout the pandemic with an increasing percentage of patients discharged on disease-modifying medications over time (p < 0.001). Long-term outcomes improved over time (hazard ratio [HR] 0.92, 95% confidence interval [CI] 0.90-0.95, p < 0.001), mainly driven by a reduction in cardiovascular death. Receiving specialized cardiology care was associated with better long-term outcomes both for those who had HFrEF (HR 0.79, 95% CI 0.77-0.82, p < 0.001) and for those who had non-HFrEF (HR 0.87, 95% CI 0.85-0.90, p < 0.001).

Conclusions

Despite the disruption of healthcare systems, the clinical characteristics of patients admitted with HF were similar and the overall standard of care was maintained throughout the pandemic. Long-term survival of patients hospitalized with HF continued to improve after COVID-19, especially for HFrEF.",,doi:https://doi.org/10.1002/ejhf.3306; doi:https://doi.org/10.1002/ejhf.3306 37272361,https://doi.org/10.2340/actadv.v103.5268,Relationship between Eczema and Self-reported Difficulties Keeping up with School Education: A Cross-sectional Study.,"Beckman L, Hagquist C, Svensson Å, Langan SM, Von Kobyletzki L.",,Acta dermato-venereologica,2023,2023-06-05,Y,,,,"Eczema is a common chronic disease that affects both children and adults, and may have an adverse impact on school performance, as it is characteristically pruritic, and hence may lead to poor concentration and inadequate sleep. The aim of this study was to elucidate the relationship between eczema and self-reported difficulties keeping up with school education. The study was based on cross-sectional questionnaire data collected in schools among all 9th graders (15-16 years old) within a Swedish county. Logistic regression analyses were used to assess the association between having eczema and self-reported difficulties keeping up with school education. A total of 2,620 pupils participated (50.1% female). An increased odds ratio (OR) of self-reported difficulties keeping up with school education was found in adolescents with eczema compared with those without eczema after adjustment for sex and  family residence (OR 2.13, 95% confidence interval (95% CI) 1.32-3.44), and with additional adjustment for sleeping problems, attention-deficit hyperactivity disorder, allergy, rhinitis, asthma, and alcohol consumption (adjusted OR 1.78, CI 1.05-3.00). Eczema may be a relevant risk factor for difficulty keeping up with school education in adolescents. However, studies that can assess temporality, based in different settings with objective reports of both eczema and self-reported difficulties at school, are needed to confirm these findings.",,doi:https://doi.org/10.2340/actadv.v103.5268; html:https://europepmc.org/articles/PMC10259463; pdf:https://europepmc.org/articles/PMC10259463?pdf=render +38837310,https://doi.org/10.1002/ejhf.3306,"A nationwide, population-based study on specialized care for acute heart failure throughout the COVID-19 pandemic.","Cannata A, Mizani MA, Bromage DI, Piper SE, Hardman SMC, Sudlow C, de Belder M, Deanfield J, Gardner RS, Clark AL, Cleland JGF, McDonagh TA,  on behalf of the CVD‐COVID‐UK/COVID‐IMPACT Consortium.",,European journal of heart failure,2024,2024-06-04,N,Heart Failure; Specialist Care; Covid‐19; National Heart Failure Audit,,,"

Aims

The COVID-19 pandemic disrupted the delivery of care for patients with heart failure (HF), leading to fewer HF hospitalizations and increased mortality. However, nationwide data on quality of care and long-term outcomes across the pandemic are scarce.

Methods and results

We used data from the National Heart Failure Audit (NHFA) linked to national records for hospitalization and deaths. We compared pre-COVID (2018-2019), COVID (2020), and late/post-COVID (2021-2022) periods. Data for 227 250 patients admitted to hospital with HF were analysed and grouped according to the admission year and the presence of HF with (HFrEF) or without reduced ejection fraction (non-HFrEF). The median age at admission was 81 years (interquartile range 72-88), 55% were men (n = 125 975), 87% were of white ethnicity (n = 102 805), and 51% had HFrEF (n = 116 990). In-hospital management and specialized cardiology care were maintained throughout the pandemic with an increasing percentage of patients discharged on disease-modifying medications over time (p < 0.001). Long-term outcomes improved over time (hazard ratio [HR] 0.92, 95% confidence interval [CI] 0.90-0.95, p < 0.001), mainly driven by a reduction in cardiovascular death. Receiving specialized cardiology care was associated with better long-term outcomes both for those who had HFrEF (HR 0.79, 95% CI 0.77-0.82, p < 0.001) and for those who had non-HFrEF (HR 0.87, 95% CI 0.85-0.90, p < 0.001).

Conclusions

Despite the disruption of healthcare systems, the clinical characteristics of patients admitted with HF were similar and the overall standard of care was maintained throughout the pandemic. Long-term survival of patients hospitalized with HF continued to improve after COVID-19, especially for HFrEF.",,doi:https://doi.org/10.1002/ejhf.3306; doi:https://doi.org/10.1002/ejhf.3306 38833617,https://doi.org/10.1093/cvr/cvae123,Sex inequalities in cardiovascular risk prediction.,"Elliott J, Bodinier B, Whitaker M, Wada R, Cooke G, Ward H, Tzoulaki I, Elliott P, Chadeau-Hyam M.",,Cardiovascular research,2024,2024-06-04,N,Biomarkers; Cvd Risk Prediction; Pooled Cohort Equations; Qrisk3; Sparse Variable Selection,,,"

Aims

Evaluate sex differences in cardiovascular disease (CVD) risk prediction, including use of i) optimal sex-specific risk predictors and ii) sex-specific risk thresholds.

Methods and results

Prospective cohort study using UK Biobank, including 121,724 and 182,632 healthy men and women, respectively, aged 38-73 years at baseline. There were 11,899 (men) and 9,110 (women) incident CVD cases (hospitalization or mortality) with median 12.1 years follow-up. We used recalibrated Pooled Cohort Equations (PCE, 7.5% 10-year risk threshold as per US guidelines), QRISK3 (10% 10-year risk threshold as per UK guidelines) and Cox survival models using sparse sex-specific variable sets (via LASSO stability selection) to predict CVD risk separately in men and women. LASSO stability selection included 12 variables in common between men and women, with three additional variables selected for men and one for women. C-statistics were slightly lower for PCE than QRISK3 and models using stably-selected variables, but were similar between men and women: 0.67 [0.66-0.68], 0.70 [0.69-0.71], and 0.71 [0.70-0.72] in men and 0.69 [0.68-0.70], 0.72 [0.71-0.73], and 0.72 [0.71-0.73] in women for PCE, QRISK3 and models using stably-selected variables, respectively. At current clinically implemented risk thresholds, test sensitivity was markedly lower in women than men for all models: at 7.5% 10-year risk, sensitivity was 65.1% and 68.2% in men and 24.0% and 33.4% in women for PCE and models using stably-selected variables, respectively; at 10% 10-year risk, sensitivity was 53.7% and 52.3% in men and 16.8% and 20.2% in women for QRISK3 and models using stably-selected variables, respectively. Specificity was correspondingly higher in women than men. However, the sensitivity in women at 5% 10-year risk threshold increased to 50.1%, 58.5% and 55.7% for PCE, QRISK3 and models using stably-selected variables, respectively.

Conclusions

Use of sparse sex-specific variables improved CVD risk prediction compared with PCE but not QRISK3. At current risk thresholds, PCE and QRISK3 work less well for women than men but sensitivity was improved in women using a 5% 10-year risk threshold. Use of sex-specific risk thresholds should be considered in any re-evaluation of CVD risk calculators.

Translational perspective

Cardiovascular disease (CVD) risk prediction is an important component of clinical risk management and disease prevention. We find that at risk prediction thresholds used by currently applied risk prediction algorithms (PCE 7.5% 10-year risk threshold in the US and QRISK3 10% risk threshold in the UK), sensitivity of these risk prediction tools is markedly lower in women than in men. This sex inequality implies that women are proportionately less likely to receive appropriate clinical management including lipid-lowering therapy. If the risk prediction threshold is lowered to 5% 10-year risk in women, then sensitivity in women is substantially increased.",,doi:https://doi.org/10.1093/cvr/cvae123 36921925,https://doi.org/10.1136/bmj-2022-072808,Comparative effectiveness of BNT162b2 versus mRNA-1273 covid-19 vaccine boosting in England: matched cohort study in OpenSAFELY-TPP.,"Hulme WJ, Horne EMF, Parker EPK, Keogh RH, Williamson EJ, Walker V, Palmer TM, Curtis HJ, Walker AJ, Andrews CD, Mehrkar A, Morley J, MacKenna B, Bacon SCJ, Goldacre B, Hernán MA, Sterne JAC.",,BMJ (Clinical research ed.),2023,2023-03-15,Y,,,,"

Objective

To compare the effectiveness of the BNT162b2 mRNA (Pfizer-BioNTech) and mRNA-1273 (Moderna) covid-19 vaccines during the booster programme in England.

Design

Matched cohort study, emulating a comparative effectiveness trial.

Setting

Linked primary care, hospital, and covid-19 surveillance records available within the OpenSAFELY-TPP research platform, covering a period when the SARS-CoV-2 delta and omicron variants were dominant.

Participants

3 237 918 adults who received a booster dose of either vaccine between 29 October 2021 and 25 February 2022 as part of the national booster programme in England and who received a primary course of BNT162b2 or ChAdOx1.

Intervention

Vaccination with either BNT162b2 or mRNA-1273 as a booster vaccine dose.

Main outcome measures

Recorded SARS-CoV-2 positive test, covid-19 related hospital admission, covid-19 related death, and non-covid-19 related death at 20 weeks after receipt of the booster dose.

Results

1 618 959 people were matched in each vaccine group, contributing a total 64 546 391 person weeks of follow-up. The 20 week risks per 1000 for a positive SARS-CoV-2 test were 164.2 (95% confidence interval 163.3 to 165.1) for BNT162b2 and 159.9 (159.0 to 160.8) for mRNA-1273; the hazard ratio comparing mRNA-1273 with BNT162b2 was 0.95 (95% confidence interval 0.95 to 0.96). The 20 week risks per 1000 for hospital admission with covid-19 were 0.75 (0.71 to 0.79) for BNT162b2 and 0.65 (0.61 to 0.69) for mRNA-1273; the hazard ratio was 0.89 (0.82 to 0.95). Covid-19 related deaths were rare: the 20 week risks per 1000 were 0.028 (0.021 to 0.037) for BNT162b2 and 0.024 (0.018 to 0.033) for mRNA-1273; hazard ratio 0.83 (0.58 to 1.19). Comparative effectiveness was generally similar within subgroups defined by the primary course vaccine brand, age, previous SARS-CoV-2 infection, and clinical vulnerability. Relative benefit was similar when vaccines were compared separately in the delta and omicron variant eras.

Conclusions

This matched observational study of adults estimated a modest benefit of booster vaccination with mRNA-1273 compared with BNT162b2 in preventing positive SARS-CoV-2 tests and hospital admission with covid-19 20 weeks after vaccination, during a period of delta followed by omicron variant dominance.",,pdf:https://www.bmj.com/content/bmj/380/bmj-2022-072808.full.pdf; doi:https://doi.org/10.1136/bmj-2022-072808; html:https://europepmc.org/articles/PMC10014664; pdf:https://europepmc.org/articles/PMC10014664?pdf=render 36374585,https://doi.org/10.1177/01410768221131897,Using national electronic health records for pandemic preparedness: validation of a parsimonious model for predicting excess deaths among those with COVID-19-a data-driven retrospective cohort study.,"Mizani MA, Dashtban A, Pasea L, Lai AG, Thygesen J, Tomlinson C, Handy A, Mamza JB, Morris T, Khalid S, Zaccardi F, Macleod MJ, Torabi F, Canoy D, Akbari A, Berry C, Bolton T, Nolan J, Khunti K, Denaxas S, Hemingway H, Sudlow C, Banerjee A, CVD-COVID-UK Consortium.",,Journal of the Royal Society of Medicine,2023,2022-11-14,N,Infectious diseases; Clinical; epidemiology; Public Health; Health Informatics,,,"

Objectives

To use national, pre- and post-pandemic electronic health records (EHR) to develop and validate a scenario-based model incorporating baseline mortality risk, infection rate (IR) and relative risk (RR) of death for prediction of excess deaths.

Design

An EHR-based, retrospective cohort study.

Setting

Linked EHR in Clinical Practice Research Datalink (CPRD); and linked EHR and COVID-19 data in England provided in NHS Digital Trusted Research Environment (TRE).

Participants

In the development (CPRD) and validation (TRE) cohorts, we included 3.8 million and 35.1 million individuals aged ≥30 years, respectively.

Main outcome measures

One-year all-cause excess deaths related to COVID-19 from March 2020 to March 2021.

Results

From 1 March 2020 to 1 March 2021, there were 127,020 observed excess deaths. Observed RR was 4.34% (95% CI, 4.31-4.38) and IR was 6.27% (95% CI, 6.26-6.28). In the validation cohort, predicted one-year excess deaths were 100,338 compared with the observed 127,020 deaths with a ratio of predicted to observed excess deaths of 0.79.

Conclusions

We show that a simple, parsimonious model incorporating baseline mortality risk, one-year IR and RR of the pandemic can be used for scenario-based prediction of excess deaths in the early stages of a pandemic. Our analyses show that EHR could inform pandemic planning and surveillance, despite limited use in emergency preparedness to date. Although infection dynamics are important in the prediction of mortality, future models should take greater account of underlying conditions.",,pdf:https://journals.sagepub.com/doi/pdf/10.1177/01410768221131897; doi:https://doi.org/10.1177/01410768221131897; html:https://europepmc.org/articles/PMC9909113; pdf:https://europepmc.org/articles/PMC9909113?pdf=render; doi:https://doi.org/10.1177/01410768221131897 35172999,https://doi.org/10.1136/bmjopen-2021-052911,Can natural language processing models extract and classify instances of interpersonal violence in mental healthcare electronic records: an applied evaluative study.,"Botelle R, Bhavsar V, Kadra-Scalzo G, Mascio A, Williams MV, Roberts A, Velupillai S, Stewart R.",,BMJ open,2022,2022-02-16,Y,Psychiatry; Mental health; Public Health; Health Informatics,,,"

Objective

This paper evaluates the application of a natural language processing (NLP) model for extracting clinical text referring to interpersonal violence using electronic health records (EHRs) from a large mental healthcare provider.

Design

A multidisciplinary team iteratively developed guidelines for annotating clinical text referring to violence. Keywords were used to generate a dataset which was annotated (ie, classified as affirmed, negated or irrelevant) for: presence of violence, patient status (ie, as perpetrator, witness and/or victim of violence) and violence type (domestic, physical and/or sexual). An NLP approach using a pretrained transformer model, BioBERT (Bidirectional Encoder Representations from Transformers for Biomedical Text Mining) was fine-tuned on the annotated dataset and evaluated using 10-fold cross-validation.

Setting

We used the Clinical Records Interactive Search (CRIS) database, comprising over 500 000 de-identified EHRs of patients within the South London and Maudsley NHS Foundation Trust, a specialist mental healthcare provider serving an urban catchment area.

Participants

Searches of CRIS were carried out based on 17 predefined keywords. Randomly selected text fragments were taken from the results for each keyword, amounting to 3771 text fragments from the records of 2832 patients.

Outcome measures

We estimated precision, recall and F1 score for each NLP model. We examined sociodemographic and clinical variables in patients giving rise to the text data, and frequencies for each annotated violence characteristic.

Results

Binary classification models were developed for six labels (violence presence, perpetrator, victim, domestic, physical and sexual). Among annotations affirmed for the presence of any violence, 78% (1724) referred to physical violence, 61% (1350) referred to patients as perpetrator and 33% (731) to domestic violence. NLP models' precision ranged from 89% (perpetrator) to 98% (sexual); recall ranged from 89% (victim, perpetrator) to 97% (sexual).

Conclusions

State of the art NLP models can extract and classify clinical text on violence from EHRs at acceptable levels of scale, efficiency and accuracy.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/2/e052911.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-052911; html:https://europepmc.org/articles/PMC8852656; pdf:https://europepmc.org/articles/PMC8852656?pdf=render 37954687,https://doi.org/10.1177/20552076231211551,"Moving from development to implementation of digital innovations within the NHS: myHealthE, a remote monitoring system for tracking patient outcomes in child and adolescent mental health services.","Morris AC, Ibrahim Z, Moghraby OS, Stringaris A, Grant IM, Zalewski L, McClellan S, Moriarty G, Simonoff E, Dobson RJ, Downs J.",,Digital health,2023,2023-01-01,Y,Health; Medicine; Psychology; Mental health; general; Studies; Paediatrics; Outcomes; Wellbeing; Mixed Methods; Online; Personalised Medicine; Mhealth; Electronic; Digital Health,,,"

Objective

This paper aims to report our experience of developing, implementing, and evaluating myHealthE (MHE), a digital innovation for Child and Adolescents Mental Health Services (CAMHS), which automates the remote collection and reporting of Patient-Reported Outcome Measures (PROMs) into National Health Services (NHS) electronic healthcare records.

Methods

We describe the logistical and governance issues encountered in developing the MHE interface with patient-identifiable information, and the steps taken to overcome these development barriers. We describe the application's architecture and hosting environment to enable its operability within the NHS, as well as the capabilities needed within the technical team to bridge the gap between academic development and NHS operational teams.

Results

We present evidence on the feasibility and acceptability of this system within clinical services and the process of iterative development, highlighting additional functions that were incorporated to increase system utility.

Conclusion

This article provides a framework with which to plan, develop, and implement automated PROM collection from remote devices back to NHS infrastructure. The challenges and solutions described in this paper will be pertinent to other digital health innovation researchers aspiring to deploy interoperable systems within NHS clinical systems.",,doi:https://doi.org/10.1177/20552076231211551; html:https://europepmc.org/articles/PMC10638880; pdf:https://europepmc.org/articles/PMC10638880?pdf=render 37978887,https://doi.org/10.1093/eurheartj/ehad748,Adapting cardiovascular risk prediction models to different populations: the need for recalibration.,"Pennells L, Kaptoge S, Di Angelantonio E.",,European heart journal,2024,2024-01-01,N,,,,,,pdf:https://academic.oup.com/eurheartj/advance-article-pdf/doi/10.1093/eurheartj/ehad748/53515704/ehad748.pdf; doi:https://doi.org/10.1093/eurheartj/ehad748 -35780515,https://doi.org/10.1016/j.epidem.2022.100604,Appropriately smoothing prevalence data to inform estimates of growth rate and reproduction number.,"Eales O, Ainslie KEC, Walters CE, Wang H, Atchison C, Ashby D, Donnelly CA, Cooke G, Barclay W, Ward H, Darzi A, Elliott P, Riley S.",,Epidemics,2022,2022-06-22,Y,Cross-sectional study; Reproduction Number; Covid-19; Sars-cov-2; Bayesian P-Spline,,,"The time-varying reproduction number (Rt) can change rapidly over the course of a pandemic due to changing restrictions, behaviours, and levels of population immunity. Many methods exist that allow the estimation of Rt from case data. However, these are not easily adapted to point prevalence data nor can they infer Rt across periods of missing data. We developed a Bayesian P-spline model suitable for fitting to a wide range of epidemic time-series, including point-prevalence data. We demonstrate the utility of the model by fitting to periodic daily SARS-CoV-2 swab-positivity data in England from the first 7 rounds (May 2020-December 2020) of the REal-time Assessment of Community Transmission-1 (REACT-1) study. Estimates of Rt over the period of two subsequent rounds (6-8 weeks) and single rounds (2-3 weeks) inferred using the Bayesian P-spline model were broadly consistent with estimates from a simple exponential model, with overlapping credible intervals. However, there were sometimes substantial differences in point estimates. The Bayesian P-spline model was further able to infer changes in Rt over shorter periods tracking a temporary increase above one during late-May 2020, a gradual increase in Rt over the summer of 2020 as restrictions were eased, and a reduction in Rt during England's second national lockdown followed by an increase as the Alpha variant surged. The model is robust against both under-fitting and over-fitting and is able to interpolate between periods of available data; it is a particularly versatile model when growth rate can change over small timescales, as in the current SARS-CoV-2 pandemic. This work highlights the importance of pairing robust methods with representative samples to track pandemics.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9220254; doi:https://doi.org/10.1016/j.epidem.2022.100604; html:https://europepmc.org/articles/PMC9220254; pdf:https://europepmc.org/articles/PMC9220254?pdf=render 33634312,https://doi.org/10.1093/bib/bbab006,Benchmarking network-based gene prioritization methods for cerebral small vessel disease.,"Zhang H, Ferguson A, Robertson G, Jiang M, Zhang T, Sudlow C, Smith K, Rannikmae K, Wu H.",,Briefings in bioinformatics,2021,2021-09-01,Y,Cerebral Small Vessel Disease; Protein–protein Interaction; Benchmarking; Disease Gene Association; Network-based Gene Prioritization,,,"Network-based gene prioritization algorithms are designed to prioritize disease-associated genes based on known ones using biological networks of protein interactions, gene-disease associations (GDAs) and other relationships between biological entities. Various algorithms have been developed based on different mechanisms, but it is not obvious which algorithm is optimal for a specific disease. To address this issue, we benchmarked multiple algorithms for their application in cerebral small vessel disease (cSVD). We curated protein-gene interactions (PGIs) and GDAs from databases and assembled PGI networks and disease-gene heterogeneous networks. A screening of algorithms resulted in seven representative algorithms to be benchmarked. Performance of algorithms was assessed using both leave-one-out cross-validation (LOOCV) and external validation with MEGASTROKE genome-wide association study (GWAS). We found that random walk with restart on the heterogeneous network (RWRH) showed best LOOCV performance, with median LOOCV rediscovery rank of 185.5 (out of 19 463 genes). The GenePanda algorithm had most GWAS-confirmable genes in top 200 predictions, while RWRH had best ranks for small vessel stroke-associated genes confirmed in GWAS. In conclusion, RWRH has overall better performance for application in cSVD despite its susceptibility to bias caused by degree centrality. Choice of algorithms should be determined before applying to specific disease. Current pure network-based gene prioritization algorithms are unlikely to find novel disease-associated genes that are not associated with known ones. The tools for implementing and benchmarking algorithms have been made available and can be generalized for other diseases.",,pdf:https://www.pure.ed.ac.uk/ws/files/198917679/bbab006.pdf; doi:https://doi.org/10.1093/bib/bbab006; html:https://europepmc.org/articles/PMC8425308; pdf:https://europepmc.org/articles/PMC8425308?pdf=render +35780515,https://doi.org/10.1016/j.epidem.2022.100604,Appropriately smoothing prevalence data to inform estimates of growth rate and reproduction number.,"Eales O, Ainslie KEC, Walters CE, Wang H, Atchison C, Ashby D, Donnelly CA, Cooke G, Barclay W, Ward H, Darzi A, Elliott P, Riley S.",,Epidemics,2022,2022-06-22,Y,Cross-sectional study; Reproduction Number; Covid-19; Sars-cov-2; Bayesian P-Spline,,,"The time-varying reproduction number (Rt) can change rapidly over the course of a pandemic due to changing restrictions, behaviours, and levels of population immunity. Many methods exist that allow the estimation of Rt from case data. However, these are not easily adapted to point prevalence data nor can they infer Rt across periods of missing data. We developed a Bayesian P-spline model suitable for fitting to a wide range of epidemic time-series, including point-prevalence data. We demonstrate the utility of the model by fitting to periodic daily SARS-CoV-2 swab-positivity data in England from the first 7 rounds (May 2020-December 2020) of the REal-time Assessment of Community Transmission-1 (REACT-1) study. Estimates of Rt over the period of two subsequent rounds (6-8 weeks) and single rounds (2-3 weeks) inferred using the Bayesian P-spline model were broadly consistent with estimates from a simple exponential model, with overlapping credible intervals. However, there were sometimes substantial differences in point estimates. The Bayesian P-spline model was further able to infer changes in Rt over shorter periods tracking a temporary increase above one during late-May 2020, a gradual increase in Rt over the summer of 2020 as restrictions were eased, and a reduction in Rt during England's second national lockdown followed by an increase as the Alpha variant surged. The model is robust against both under-fitting and over-fitting and is able to interpolate between periods of available data; it is a particularly versatile model when growth rate can change over small timescales, as in the current SARS-CoV-2 pandemic. This work highlights the importance of pairing robust methods with representative samples to track pandemics.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9220254; doi:https://doi.org/10.1016/j.epidem.2022.100604; html:https://europepmc.org/articles/PMC9220254; pdf:https://europepmc.org/articles/PMC9220254?pdf=render 35611160,https://doi.org/10.1016/j.eclinm.2022.101462,Impact of first UK COVID-19 lockdown on hospital admissions: Interrupted time series study of 32 million people.,"Shah SA, Brophy S, Kennedy J, Fisher L, Walker A, Mackenna B, Curtis H, Inglesby P, Davy S, Bacon S, Goldacre B, Agrawal U, Moore E, Simpson CR, Macleod J, Cooksey R, Sheikh A, Katikireddi SV.",,EClinicalMedicine,2022,2022-05-20,Y,Pandemic; Healthcare Inequalities; Healthcare Disruption; Interrupted Time Series Analysis; Covid-19; Sars-cov-2,,,"

Background

Uncontrolled infection and lockdown measures introduced in response have resulted in an unprecedented challenge for health systems internationally. Whether such unprecedented impact was due to lockdown itself and recedes when such measures are lifted is unclear. We assessed the short- and medium-term impacts of the first lockdown measures on hospital care for tracer non-COVID-19 conditions in England, Scotland and Wales across diseases, sexes, and socioeconomic and ethnic groups.

Methods

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

Findings

Our combined dataset included 32 million people who contributed over 74 million person-years. Admission rates for all three conditions fell by 34.2% (Confidence Interval (CI): -43.0, -25.3) in England, 20.9% (CI: -27.8, -14.1) in Scotland, and 24.7% (CI: -36.7, -12.7) in Wales, with falls across every stratum considered. In all three nations, cancer-related admissions fell the most while respiratory-related admissions fell the least (e.g., rates fell by 40.5% (CI: -47.4, -33.6), 21.9% (CI: -35.4, -8.4), and 19.0% (CI: -30.6, -7.4) in England for cancer, cardiovascular-related, and respiratory-related admissions respectively). Unscheduled admissions rates fell more in the most than the least deprived quintile across all three nations. Some ethnic minority groups experienced greater falls in admissions (e.g., in England, unscheduled admissions fell by 9.5% (CI: -20.2, 1.2) for Whites, but 44.3% (CI: -71.0, -17.6), 34.6% (CI: -63.8, -5.3), and 25.6% (CI: -45.0, -6.3) for Mixed, Other and Black ethnic groups respectively). Despite easing of restrictions, the overall admission rates remained lower in England, Scotland, and Wales by 20.8%, 21.6%, and 22.0%, respectively when compared to the same period (August-September) during the pre-pandemic years. This corresponds to a reduction of 26.2, 23.8 and 30.2 admissions per 100,000 people in England, Scotland, and Wales respectively.

Interpretation

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

Funding

This work was funded by the Medical Research Council as part of the Lifelong Health and Wellbeing study as part of National Core Studies (MC_PC_20030). SVK acknowledges funding from the Medical Research Council (MC_UU_00022/2), and the Scottish Government Chief Scientist Office (SPHSU17). EAVE II is funded by the Medical Research Council (MR/R008345/1) with the support of BREATHE - The Health Data Research Hub for Respiratory Health (MC_PC_19004), which is funded through the UK Research and Innovation Industrial Strategy Challenge Fund and delivered through Health Data Research UK. BG has received research funding from the NHS National Institute for Health Research (NIHR), the Wellcome Trust, Health Data Research UK, Asthma UK, the British Lung Foundation, and the Longitudinal Health and Wellbeing strand of the National Core Studies programme.",,pdf:http://www.thelancet.com/article/S2589537022001924/pdf; doi:https://doi.org/10.1016/j.eclinm.2022.101462; html:https://europepmc.org/articles/PMC9121886; pdf:https://europepmc.org/articles/PMC9121886?pdf=render 37156754,https://doi.org/10.1111/1471-0528.17531,Risk factors for a serious adverse outcome in neonates: a retrospective cohort study of vaginal births.,"Jindal S, Steer PJ, Savvidou M, Draycott T, Dixon-Woods M, Wood A, Kim LG.",,BJOG : an international journal of obstetrics and gynaecology,2023,2023-05-08,Y,risk factors; Meconium; Pyrexia; Intrapartum Fetal Monitoring; Labour Outcome; Fetal Deterioration,,,"

Objective

To investigate the hypothesis that risk factors in addition to an abnormal fetal heart rate pattern (aFHRp) are independently associated with adverse neonatal outcomes of labour.

Design

Observational prospective cohort study.

Setting

17 UK maternity units.

Sample

585 291 pregnancies between 1988 and 2000 inclusive.

Methods

Adjusted odds ratios (OR) with 95% confidence intervals (95% CI) were estimated from multivariable logistic regression.

Main outcome measures

Adverse neonatal outcome at term (5-minute Apgar score <7, and a composite measure comprising 5-minute Apgar score <7, resuscitation by intubation and/or perinatal death).

Results

Analysis was based on 302 137 vaginal births at 37-42 weeks inclusive. We found a higher odds of Apgar score at 5 minutes <7 with suspected fetal growth restriction (OR 1.34, 95% CI 1.16-1.53), induction of labour (OR 1.41, 95% CI 1.25-1.58), nulliparity (OR 1.48, 95% CI 1.34-1.63), booking body mass index ≥30 (OR 1.18, 95% CI 1.02-1.37), maternal age <25 (OR 1.23, 95% CI 1.10-1.39), black ethnicity (OR 1.21, 95% CI 1.03-1.43), early-term birth at 37-38 weeks (OR 1.13, 95% CI 1.02-1.25), late-term birth at 41-42 weeks (OR 1.14, 95% CI 1.01-1.28), use of oxytocin (OR 1.27, 95% CI 1.14-1.41), maternal pyrexia (OR 1.87, 95% CI 1.46-2.40), aFHRp and presence of meconium (aFHRp without meconium: OR 2.40, 95% CI 2.15-2.69; meconium without aFHRp: OR 2.20, 195% CI.94-2.49; both aFHRp and meconium: OR 4.26, 95% CI 3.74-4.87). The results were similar when the composite adverse outcome was considered.

Conclusions

A range of risk factors, including suspicion of fetal growth restriction, maternal pyrexia and presence of meconium, are implicated in poor birth outcomes in addition to aFHRp. Interpretation of the fetal heart rate pattern alone is insufficient as a basis for decisions about escalation and intervention.",,doi:https://doi.org/10.1111/1471-0528.17531; doi:https://doi.org/10.1111/1471-0528.17531; html:https://europepmc.org/articles/PMC10952606; pdf:https://europepmc.org/articles/PMC10952606?pdf=render 33587202,https://doi.org/10.1007/s10654-021-00722-y,COVID-19 mortality in the UK Biobank cohort: revisiting and evaluating risk factors.,"Elliott J, Bodinier B, Whitaker M, Delpierre C, Vermeulen R, Tzoulaki I, Elliott P, Chadeau-Hyam M.",,European journal of epidemiology,2021,2021-02-15,Y,Risk factor; Prospective Cohort; Uk Biobank; Sars-cov-2; Covid-19 Mortality,,,"Most studies of severe/fatal COVID-19 risk have used routine/hospitalisation data without detailed pre-morbid characterisation. Using the community-based UK Biobank cohort, we investigate risk factors for COVID-19 mortality in comparison with non-COVID-19 mortality. We investigated demographic, social (education, income, housing, employment), lifestyle (smoking, drinking, body mass index), biological (lipids, cystatin C, vitamin D), medical (comorbidities, medications) and environmental (air pollution) data from UK Biobank (N = 473,550) in relation to 459 COVID-19 and 2626 non-COVID-19 deaths to 21 September 2020. We used univariate, multivariable and penalised regression models. Age (OR = 2.76 [2.18-3.49] per S.D. [8.1 years], p = 2.6 × 10-17), male sex (OR = 1.47 [1.26-1.73], p = 1.3 × 10-6) and Black versus White ethnicity (OR = 1.21 [1.12-1.29], p = 3.0 × 10-7) were independently associated with and jointly explanatory of (area under receiver operating characteristic curve, AUC = 0.79) increased risk of COVID-19 mortality. In multivariable regression, alongside demographic covariates, being a healthcare worker, current smoker, having cardiovascular disease, hypertension, diabetes, autoimmune disease, and oral steroid use at enrolment were independently associated with COVID-19 mortality. Penalised regression models selected income, cardiovascular disease, hypertension, diabetes, cystatin C, and oral steroid use as jointly contributing to COVID-19 mortality risk; Black ethnicity, hypertension and oral steroid use contributed to COVID-19 but not non-COVID-19 mortality. Age, male sex and Black ethnicity, as well as comorbidities and oral steroid use at enrolment were associated with increased risk of COVID-19 death. Our results suggest that previously reported associations of COVID-19 mortality with body mass index, low vitamin D, air pollutants, renin-angiotensin-aldosterone system inhibitors may be explained by the aforementioned factors.",,pdf:https://link.springer.com/content/pdf/10.1007/s10654-021-00722-y.pdf; doi:https://doi.org/10.1007/s10654-021-00722-y; html:https://europepmc.org/articles/PMC7882869; pdf:https://europepmc.org/articles/PMC7882869?pdf=render 35440469,https://doi.org/10.3399/bjgp.2022.0083,"Colchicine for COVID-19 in the community (PRINCIPLE): a randomised, controlled, adaptive platform trial.","Dorward J, Yu LM, Hayward G, Saville BR, Gbinigie O, Van Hecke O, Ogburn E, Evans PH, Thomas NP, Patel MG, Richards D, Berry N, Detry MA, Saunders C, Fitzgerald M, Harris V, Shanyinde M, de Lusignan S, Andersson MI, Butler CC, Hobbs FR, PRINCIPLE Trial Collaborative Group.",,The British journal of general practice : the journal of the Royal College of General Practitioners,2022,2022-06-30,Y,Colchicine; Community; Primary Health Care; Randomised Controlled Trial; Covid-19,,,"

Background

Colchicine has been proposed as a COVID-19 treatment.

Aim

To determine whether colchicine reduces time to recovery and COVID-19-related admissions to hospital and/or deaths among people in the community.

Design and setting

Prospective, multicentre, open-label, multi-arm, randomised, controlled, adaptive platform trial (PRINCIPLE).

Method

Adults aged ≥65 years or ≥18 years with comorbidities or shortness of breath, and unwell for ≤14 days with suspected COVID-19 in the community, were randomised to usual care, usual care plus colchicine (500 µg daily for 14 days), or usual care plus other interventions. The co-primary endpoints were time to first self-reported recovery and admission to hospital/death related to COVID-19, within 28 days, analysed using Bayesian models.

Results

The trial opened on 2 April 2020. Randomisation to colchicine started on 4 March 2021 and stopped on 26 May 2021 because the prespecified time to recovery futility criterion was met. The primary analysis model included 2755 participants who were SARS-CoV-2 positive, randomised to colchicine (n = 156), usual care (n = 1145), and other treatments (n = 1454). Time to first self-reported recovery was similar in the colchicine group compared with usual care with an estimated hazard ratio of 0.92 (95% credible interval (CrI) = 0.72 to 1.16) and an estimated increase of 1.4 days in median time to self-reported recovery for colchicine versus usual care. The probability of meaningful benefit in time to recovery was very low at 1.8%. COVID-19-related admissions to hospital/deaths were similar in the colchicine group versus usual care, with an estimated odds ratio of 0.76 (95% CrI = 0.28 to 1.89) and an estimated difference of -0.4% (95% CrI = -2.7 to 2.4).

Conclusion

Colchicine did not improve time to recovery in people at higher risk of complications with COVID-19 in the community.",,pdf:https://bjgp.org/content/bjgp/72/720/e446.full.pdf; doi:https://doi.org/10.3399/BJGP.2022.0083; html:https://europepmc.org/articles/PMC9037186; pdf:https://europepmc.org/articles/PMC9037186?pdf=render 37781298,https://doi.org/10.3389/fcvm.2023.1141026,Radiomics analysis enhances the diagnostic performance of CMR stress perfusion: a proof-of-concept study using the Dan-NICAD dataset.,"Raisi-Estabragh Z, Martin-Isla C, Nissen L, Szabo L, Campello VM, Escalera S, Winther S, Bøttcher M, Lekadir K, Petersen SE.",,Frontiers in cardiovascular medicine,2023,2023-09-15,Y,Machine Learning (Ml); Radiomics; Cmr (Cardiovascular Magnetic Resonance); Stress Perfusion Cardiac Mri; Dan-nicad,,,"

Objectives

To assess the feasibility of extracting radiomics signal intensity based features from the myocardium using cardiovascular magnetic resonance (CMR) imaging stress perfusion sequences. Furthermore, to compare the diagnostic performance of radiomics models against standard-of-care qualitative visual assessment of stress perfusion images, with the ground truth stenosis label being defined by invasive Fractional Flow Reserve (FFR) and quantitative coronary angiography.

Methods

We used the Dan-NICAD 1 dataset, a multi-centre study with coronary computed tomography angiography, 1,5 T CMR stress perfusion, and invasive FFR available for a subset of 148 patients with suspected coronary artery disease. Image segmentation was performed by two independent readers. We used the Pyradiomics platform to extract radiomics first-order (n = 14) and texture (n = 75) features from the LV myocardium (basal, mid, apical) in rest and stress perfusion images.

Results

Overall, 92 patients (mean age 62 years, 56 men) were included in the study, 39 with positive FFR. We double-cross validated the model and, in each inner fold, we trained and validated a per territory model. The conventional analysis results reported sensitivity of 41% and specificity of 84%. Our final radiomics model demonstrated an improvement on these results with an average sensitivity of 53% and specificity of 86%.

Conclusion

In this proof-of-concept study from the Dan-NICAD dataset, we demonstrate the feasibility of radiomics analysis applied to CMR perfusion images with a suggestion of superior diagnostic performance of radiomics models over conventional visual analysis of perfusion images in picking up perfusion defects defined by invasive coronary angiography.",,doi:https://doi.org/10.3389/fcvm.2023.1141026; html:https://europepmc.org/articles/PMC10541220; pdf:https://europepmc.org/articles/PMC10541220?pdf=render -37053113,https://doi.org/10.1097/bot.0000000000002612,The Translated Proximal Humerus Fracture: A Comparison of Operative and Nonoperative Management.,"Cosic F, Kirzner N, Edwards E, Page R, Kimmel L, Gabbe B.",,Journal of orthopaedic trauma,2023,2023-09-01,N,,,,"

Objectives

To report on the long-term outcomes of the management of translated proximal humerus fractures.

Design

A prospective cohort study was conducted from January 2010 to December 2018.

Setting

Academic Level 1 trauma center.

Participants/patients

A total of 108 patients with a proximal humerus fracture with ≥100% translation, defined as no cortical bony contact between the shaft and humeral head fragments, were included.

Intervention

Patients were managed nonoperatively with sling immobilization or with operative management as determined by the treating surgeon.

Main outcome measures

Outcome measures were the Oxford Shoulder Score, EQ-5D-5L, return to work, and radiological outcomes. Complications recorded included further surgery, loss of position/fixation, nonunion/malunion, and avascular necrosis.

Results

Of the 108 patients, 76 underwent operative intervention and 32 were managed nonoperatively. The mean (SD) age in the operative group was 54.3 (±20.2) years and in the nonoperative group was 73.3 (±15.3) years ( P < 0.001). There was no association between Oxford Shoulder Score and management options (mean 38.5 [±9.5] operative versus mean 41.3 [±8.5] nonoperative, P = 0.48). Operative management was associated with improved health status outcomes; EQ-5D utility score adjusted mean difference was 0.16 (95% CI, 0.04-0.27; P = 0.008); EQ-5D VAS adjusted mean difference was 19.2 (95% CI, 5.2-33.2; P = 0.008). Operative management was associated with a lower odds of nonunion (adjusted OR 0.30; 95% CI, 0.09-0.97; P = 0.04), malunion (adjusted OR 0.14; 95% CI, 0.04-0.51; P = 0.003), and complications (adjusted OR 0.07; 95% CI, 0.02-0.32; P = 0.001).

Conclusion

Translated proximal humerus fractures with ≥100% displacement demonstrate improved health status and radiological outcomes after surgical fixation.

Level of evidence

Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.",,doi:https://doi.org/10.1097/BOT.0000000000002612 33635829,https://doi.org/10.1530/eje-20-1163,Increased COVID-19 infections in women with polycystic ovary syndrome: a population-based study.,"Subramanian A, Anand A, Adderley NJ, Okoth K, Toulis KA, Gokhale K, Sainsbury C, O'Reilly MW, Arlt W, Nirantharakumar K.",,European journal of endocrinology,2021,2021-05-01,Y,,,,"

Objective

Several recent observational studies have linked metabolic comorbidities to an increased risk from COVID-19. Here we investigated whether women with PCOS are at an increased risk of COVID-19 infection.

Design

Population-based closed cohort study between 31 January 2020 and 22 July 2020 in the setting of a UK primary care database (The Health Improvement Network, THIN).

Methods

The main outcome was the incidence of COVID-19 coded as suspected or confirmed by the primary care provider. We used Cox proportional hazards regression model with stepwise inclusion of explanatory variables (age, BMI, impaired glucose regulation, androgen excess, anovulation, vitamin D deficiency, hypertension, and cardiovascular disease) to provide unadjusted and adjusted hazard risks (HR) of COVID-19 infection among women with PCOS compared to women without PCOS.

Results

We identified 21 292 women with a coded diagnosis of PCO/PCOS and randomly selected 78 310 aged and general practice matched control women. The crude COVID-19 incidence was 18.1 and 11.9 per 1000 person-years among women with and without PCOS, respectively. Age-adjusted Cox regression analysis suggested a 51% higher risk of COVID-19 among women with PCOS compared to women without PCOS (HR: 1.51 (95% CI: 1.27-1.80), P < 0.001). After adjusting for age and BMI, HR reduced to 1.36 (1.14-1.63)], P = 0.001. In the fully adjusted model, women with PCOS had a 28% increased risk of COVID-19 (aHR: 1.28 (1.05-1.56), P = 0.015).

Conclusion

Women with PCOS are at an increased risk of COVID-19 infection and should be specifically encouraged to adhere to infection control measures during the COVID-19 pandemic.

Significance statement

Women with polycystic ovary syndrome (PCOS) have an increased risk of cardio-metabolic disease, which have been identified as a risk factor for COVID-19. To investigate whether the increased metabolic risk in PCOS translates into an increased risk of COVID-19 infection, we carried out a population-based closed cohort study in the UK during its first wave of the SARS-CoV-2 pandemic (January to July 2020), including 21 292 women with PCOS and 78 310 controls matched for sex, age and general practice location. Results revealed a 52% increased risk of COVID-19 infection in women with PCOS, which remained increased at 28% above controls after adjustment for age, BMI, impaired glucose regulation and other explanatory variables.",,pdf:https://academic.oup.com/ejendo/article-pdf/184/5/637/45221794/eje-20-1163.pdf; doi:https://doi.org/10.1530/EJE-20-1163; html:https://europepmc.org/articles/PMC8052516; pdf:https://europepmc.org/articles/PMC8052516?pdf=render +37053113,https://doi.org/10.1097/bot.0000000000002612,The Translated Proximal Humerus Fracture: A Comparison of Operative and Nonoperative Management.,"Cosic F, Kirzner N, Edwards E, Page R, Kimmel L, Gabbe B.",,Journal of orthopaedic trauma,2023,2023-09-01,N,,,,"

Objectives

To report on the long-term outcomes of the management of translated proximal humerus fractures.

Design

A prospective cohort study was conducted from January 2010 to December 2018.

Setting

Academic Level 1 trauma center.

Participants/patients

A total of 108 patients with a proximal humerus fracture with ≥100% translation, defined as no cortical bony contact between the shaft and humeral head fragments, were included.

Intervention

Patients were managed nonoperatively with sling immobilization or with operative management as determined by the treating surgeon.

Main outcome measures

Outcome measures were the Oxford Shoulder Score, EQ-5D-5L, return to work, and radiological outcomes. Complications recorded included further surgery, loss of position/fixation, nonunion/malunion, and avascular necrosis.

Results

Of the 108 patients, 76 underwent operative intervention and 32 were managed nonoperatively. The mean (SD) age in the operative group was 54.3 (±20.2) years and in the nonoperative group was 73.3 (±15.3) years ( P < 0.001). There was no association between Oxford Shoulder Score and management options (mean 38.5 [±9.5] operative versus mean 41.3 [±8.5] nonoperative, P = 0.48). Operative management was associated with improved health status outcomes; EQ-5D utility score adjusted mean difference was 0.16 (95% CI, 0.04-0.27; P = 0.008); EQ-5D VAS adjusted mean difference was 19.2 (95% CI, 5.2-33.2; P = 0.008). Operative management was associated with a lower odds of nonunion (adjusted OR 0.30; 95% CI, 0.09-0.97; P = 0.04), malunion (adjusted OR 0.14; 95% CI, 0.04-0.51; P = 0.003), and complications (adjusted OR 0.07; 95% CI, 0.02-0.32; P = 0.001).

Conclusion

Translated proximal humerus fractures with ≥100% displacement demonstrate improved health status and radiological outcomes after surgical fixation.

Level of evidence

Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.",,doi:https://doi.org/10.1097/BOT.0000000000002612 31857590,https://doi.org/10.1038/s41597-019-0337-6,Machine learning for the detection of early immunological markers as predictors of multi-organ dysfunction.,"Bravo-Merodio L, Acharjee A, Hazeldine J, Bentley C, Foster M, Gkoutos GV, Lord JM.",,Scientific data,2019,2019-12-19,Y,,,,"The immune response to major trauma has been analysed mainly within post-hospital admission settings where the inflammatory response is already underway and the early drivers of clinical outcome cannot be readily determined. Thus, there is a need to better understand the immediate immune response to injury and how this might influence important patient outcomes such as multi-organ dysfunction syndrome (MODS). In this study, we have assessed the immune response to trauma in 61 patients at three different post-injury time points (ultra-early (<=1 h), 4-12 h, 48-72 h) and analysed relationships with the development of MODS. We developed a pipeline using Absolute Shrinkage and Selection Operator and Elastic Net feature selection methods that were able to identify 3 physiological features (decrease in neutrophil CD62L and CD63 expression and monocyte CD63 expression and frequency) as possible biomarkers for MODS development. After univariate and multivariate analysis for each feature alongside a stability analysis, the addition of these 3 markers to standard clinical trauma injury severity scores yields a Generalized Liner Model (GLM) with an average Area Under the Curve value of 0.92 ± 0.06. This performance provides an 8% improvement over the Probability of Survival (PS14) outcome measure and a 13% improvement over the New Injury Severity Score (NISS) for identifying patients at risk of MODS.",,pdf:https://www.nature.com/articles/s41597-019-0337-6.pdf; doi:https://doi.org/10.1038/s41597-019-0337-6; html:https://europepmc.org/articles/PMC6923383; pdf:https://europepmc.org/articles/PMC6923383?pdf=render 35485805,https://doi.org/10.1017/s003329172200109x,Multimorbidity clusters among people with serious mental illness: a representative primary and secondary data linkage cohort study.,"Ma R, Romano E, Ashworth M, Yadegarfar ME, Dregan A, Ronaldson A, de Oliveira C, Jacobs R, Stewart R, Stubbs B.",,Psychological medicine,2023,2022-04-29,Y,Mortality; Schizophrenia; Psychosis; Physical Health; Multimorbidity,,,"

Background

People with serious mental illness (SMI) experience higher mortality partially attributable to higher long-term condition (LTC) prevalence. However, little is known about multiple LTCs (MLTCs) clustering in this population.

Methods

People from South London with SMI and two or more existing LTCs aged 18+ at diagnosis were included using linked primary and mental healthcare records, 2012-2020. Latent class analysis (LCA) determined MLTC classes and multinominal logistic regression examined associations between demographic/clinical characteristics and latent class membership.

Results

The sample included 1924 patients (mean (s.d.) age 48.2 (17.3) years). Five latent classes were identified: 'substance related' (24.9%), 'atopic' (24.2%), 'pure affective' (30.4%), 'cardiovascular' (14.1%), and 'complex multimorbidity' (6.4%). Patients had on average 7-9 LTCs in each cluster. Males were at increased odds of MLTCs in all four clusters, compared to the 'pure affective'. Compared to the largest cluster ('pure affective'), the 'substance related' and the 'atopic' clusters were younger [odds ratios (OR) per year increase 0.99 (95% CI 0.98-1.00) and 0.96 (0.95-0.97) respectively], and the 'cardiovascular' and 'complex multimorbidity' clusters were older (ORs 1.09 (1.07-1.10) and 1.16 (1.14-1.18) respectively). The 'substance related' cluster was more likely to be White, the 'cardiovascular' cluster more likely to be Black (compared to White; OR 1.75, 95% CI 1.10-2.79), and both more likely to have schizophrenia, compared to other clusters.

Conclusion

The current study identified five latent class MLTC clusters among patients with SMI. An integrated care model for treating MLTCs in this population is recommended to improve multimorbidity care.",,pdf:https://www.cambridge.org/core/services/aop-cambridge-core/content/view/BDE3DC6059EB59B00B2E0CD892963804/S003329172200109Xa.pdf/div-class-title-multimorbidity-clusters-among-people-with-serious-mental-illness-a-representative-primary-and-secondary-data-linkage-cohort-study-div.pdf; doi:https://doi.org/10.1017/S003329172200109X; html:https://europepmc.org/articles/PMC10388332; pdf:https://europepmc.org/articles/PMC10388332?pdf=render 34217220,https://doi.org/10.1186/s12872-021-02137-9,Pre-existing cardiovascular disease rather than cardiovascular risk factors drives mortality in COVID-19.,"O'Gallagher K, Shek A, Bean DM, Bendayan R, Papachristidis A, Teo JTH, Dobson RJB, Shah AM, Zakeri R.",,BMC cardiovascular disorders,2021,2021-07-03,Y,Hypertension; Diabetes; Cardiovascular disease; Cardiovascular risk factors; Covid-19,,,"

Background

The relative association between cardiovascular (CV) risk factors, such as diabetes and hypertension, established CV disease (CVD), and susceptibility to CV complications or mortality in COVID-19 remains unclear.

Methods

We conducted a cohort study of consecutive adults hospitalised for severe COVID-19 between 1st March and 30th June 2020. Pre-existing CVD, CV risk factors and associations with mortality and CV complications were ascertained.

Results

Among 1721 patients (median age 71 years, 57% male), 349 (20.3%) had pre-existing CVD (CVD), 888 (51.6%) had CV risk factors without CVD (RF-CVD), 484 (28.1%) had neither. Patients with CVD were older with a higher burden of non-CV comorbidities. During follow-up, 438 (25.5%) patients died: 37% with CVD, 25.7% with RF-CVD and 16.5% with neither. CVD was independently associated with in-hospital mortality among patients < 70 years of age (adjusted HR 2.43 [95% CI 1.16-5.07]), but not in those ≥ 70 years (aHR 1.14 [95% CI 0.77-1.69]). RF-CVD were not independently associated with mortality in either age group (< 70 y aHR 1.21 [95% CI 0.72-2.01], ≥ 70 y aHR 1.07 [95% CI 0.76-1.52]). Most CV complications occurred in patients with CVD (66%) versus RF-CVD (17%) or neither (11%; p < 0.001). 213 [12.4%] patients developed venous thromboembolism (VTE). CVD was not an independent predictor of VTE.

Conclusions

In patients hospitalised with COVID-19, pre-existing established CVD appears to be a more important contributor to mortality than CV risk factors in the absence of CVD. CVD-related hazard may be mediated, in part, by new CV complications. Optimal care and vigilance for destabilised CVD are essential in this patient group. Trial registration n/a.",,pdf:https://bmccardiovascdisord.biomedcentral.com/counter/pdf/10.1186/s12872-021-02137-9; doi:https://doi.org/10.1186/s12872-021-02137-9; html:https://europepmc.org/articles/PMC8254437; pdf:https://europepmc.org/articles/PMC8254437?pdf=render @@ -773,14 +773,14 @@ PMC9645061,https://doi.org/,Using population-scale medication data to evaluate t 32620158,https://doi.org/10.1186/s12915-020-00792-6,Epigenomics and genotype-phenotype association analyses reveal conserved genetic architecture of complex traits in cattle and human.,"Liu S, Yu Y, Zhang S, Cole JB, Tenesa A, Wang T, McDaneld TG, Ma L, Liu GE, Fang L.",,BMC biology,2020,2020-07-03,Y,Comparative Epigenomics; Gwas Enrichment; Human-cattle Comparison; Trait-relevant Tissues,,,"

Background

Lack of comprehensive functional annotations across a wide range of tissues and cell types severely hinders the biological interpretations of phenotypic variation, adaptive evolution, and domestication in livestock. Here we used a combination of comparative epigenomics, genome-wide association study (GWAS), and selection signature analysis, to shed light on potential adaptive evolution in cattle.

Results

We cross-mapped 8 histone marks of 1300 samples from human to cattle, covering 178 unique tissues/cell types. By uniformly analyzing 723 RNA-seq and 40 whole genome bisulfite sequencing (WGBS) datasets in cattle, we validated that cross-mapped histone marks captured tissue-specific expression and methylation, reflecting tissue-relevant biology. Through integrating cross-mapped tissue-specific histone marks with large-scale GWAS and selection signature results, we for the first time detected relevant tissues and cell types for 45 economically important traits and artificial selection in cattle. For instance, immune tissues are significantly associated with health and reproduction traits, multiple tissues for milk production and body conformation traits (reflecting their highly polygenic architecture), and thyroid for the different selection between beef and dairy cattle. Similarly, we detected relevant tissues for 58 complex traits and diseases in humans and observed that immune and fertility traits in humans significantly correlated with those in cattle in terms of relevant tissues, which facilitated the identification of causal genes for such traits. For instance, PIK3CG, a gene highly specifically expressed in mononuclear cells, was significantly associated with both age-at-menopause in human and daughter-still-birth in cattle. ICAM, a T cell-specific gene, was significantly associated with both allergic diseases in human and metritis in cattle.

Conclusion

Collectively, our results highlighted that comparative epigenomics in conjunction with GWAS and selection signature analyses could provide biological insights into the phenotypic variation and adaptive evolution. Cattle may serve as a model for human complex traits, by providing additional information beyond laboratory model organisms, particularly when more novel phenotypes become available in the near future.",,pdf:https://bmcbiol.biomedcentral.com/counter/pdf/10.1186/s12915-020-00792-6; doi:https://doi.org/10.1186/s12915-020-00792-6; html:https://europepmc.org/articles/PMC7334855; pdf:https://europepmc.org/articles/PMC7334855?pdf=render 37745706,https://doi.org/10.3389/fendo.2023.1266557,"Editorial: Integrative multi-modal, multi-omics analytics for the better understanding of metabolic diseases.","Acharjee A, Agarwal P, Gkoutos GV.",,Frontiers in endocrinology,2023,2023-09-08,Y,Biomarker; Therapeutic; Diagnostic; Metabolic Disease; Omics,,,,,doi:https://doi.org/10.3389/fendo.2023.1266557; html:https://europepmc.org/articles/PMC10516571; pdf:https://europepmc.org/articles/PMC10516571?pdf=render 33203640,https://doi.org/10.1136/bmjopen-2020-043828,"Estimated impact of the COVID-19 pandemic on cancer services and excess 1-year mortality in people with cancer and multimorbidity: near real-time data on cancer care, cancer deaths and a population-based cohort study.","Lai AG, Pasea L, Banerjee A, Hall G, Denaxas S, Chang WH, Katsoulis M, Williams B, Pillay D, Noursadeghi M, Linch D, Hughes D, Forster MD, Turnbull C, Fitzpatrick NK, Boyd K, Foster GR, Enver T, Nafilyan V, Humberstone B, Neal RD, Cooper M, Jones M, Pritchard-Jones K, Sullivan R, Davie C, Lawler M, Hemingway H.",,BMJ open,2020,2020-11-17,Y,Oncology; Health Informatics; Covid-19,,,"

Objectives

To estimate the impact of the COVID-19 pandemic on cancer care services and overall (direct and indirect) excess deaths in people with cancer.

Methods

We employed near real-time weekly data on cancer care to determine the adverse effect of the pandemic on cancer services. We also used these data, together with national death registrations until June 2020 to model deaths, in excess of background (pre-COVID-19) mortality, in people with cancer. Background mortality risks for 24 cancers with and without COVID-19-relevant comorbidities were obtained from population-based primary care cohort (Clinical Practice Research Datalink) on 3 862 012 adults in England.

Results

Declines in urgent referrals (median=-70.4%) and chemotherapy attendances (median=-41.5%) to a nadir (lowest point) in the pandemic were observed. By 31 May, these declines have only partially recovered; urgent referrals (median=-44.5%) and chemotherapy attendances (median=-31.2%). There were short-term excess death registrations for cancer (without COVID-19), with peak relative risk (RR) of 1.17 at week ending on 3 April. The peak RR for all-cause deaths was 2.1 from week ending on 17 April. Based on these findings and recent literature, we modelled 40% and 80% of cancer patients being affected by the pandemic in the long-term. At 40% affected, we estimated 1-year total (direct and indirect) excess deaths in people with cancer as between 7165 and 17 910, using RRs of 1.2 and 1.5, respectively, where 78% of excess deaths occured in patients with ≥1 comorbidity.

Conclusions

Dramatic reductions were detected in the demand for, and supply of, cancer services which have not fully recovered with lockdown easing. These may contribute, over a 1-year time horizon, to substantial excess mortality among people with cancer and multimorbidity. It is urgent to understand how the recovery of general practitioner, oncology and other hospital services might best mitigate these long-term excess mortality risks.",,pdf:https://bmjopen.bmj.com/content/bmjopen/10/11/e043828.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-043828; html:https://europepmc.org/articles/PMC7674020; pdf:https://europepmc.org/articles/PMC7674020?pdf=render -38336974,https://doi.org/10.1038/s41598-023-49923-3,VertXNet: an ensemble method for vertebral body segmentation and identification from cervical and lumbar spinal X-rays.,"Chen Y, Mo Y, Readie A, Ligozio G, Mandal I, Jabbar F, Coroller T, Papież BW.",,Scientific reports,2024,2024-02-09,Y,,,,"Accurate annotation of vertebral bodies is crucial for automating the analysis of spinal X-ray images. However, manual annotation of these structures is a laborious and costly process due to their complex nature, including small sizes and varying shapes. To address this challenge and expedite the annotation process, we propose an ensemble pipeline called VertXNet. This pipeline currently combines two segmentation mechanisms, semantic segmentation using U-Net, and instance segmentation using Mask R-CNN, to automatically segment and label vertebral bodies in lateral cervical and lumbar spinal X-ray images. VertXNet enhances its effectiveness by adopting a rule-based strategy (termed the ensemble rule) for effectively combining segmentation outcomes from U-Net and Mask R-CNN. It determines vertebral body labels by recognizing specific reference vertebral instances, such as cervical vertebra 2 ('C2') in cervical spine X-rays and sacral vertebra 1 ('S1') in lumbar spine X-rays. Those references are commonly relatively easy to identify at the edge of the spine. To assess the performance of our proposed pipeline, we conducted evaluations on three spinal X-ray datasets, including two in-house datasets and one publicly available dataset. The ground truth annotations were provided by radiologists for comparison. Our experimental results have shown that the proposed pipeline outperformed two state-of-the-art (SOTA) segmentation models on our test dataset with a mean Dice of 0.90, vs. a mean Dice of 0.73 for Mask R-CNN and 0.72 for U-Net. We also demonstrated that VertXNet is a modular pipeline that enables using other SOTA model, like nnU-Net to further improve its performance. Furthermore, to evaluate the generalization ability of VertXNet on spinal X-rays, we directly tested the pre-trained pipeline on two additional datasets. A consistently strong performance was observed, with mean Dice coefficients of 0.89 and 0.88, respectively. In summary, VertXNet demonstrated significantly improved performance in vertebral body segmentation and labeling for spinal X-ray imaging. Its robustness and generalization were presented through the evaluation of both in-house clinical trial data and publicly available datasets.",,pdf:https://www.nature.com/articles/s41598-023-49923-3.pdf; doi:https://doi.org/10.1038/s41598-023-49923-3; html:https://europepmc.org/articles/PMC10858234; pdf:https://europepmc.org/articles/PMC10858234?pdf=render 34249083,https://doi.org/10.3389/fgene.2021.652878,Polymorphism in INSR Locus Modifies Risk of Atrial Fibrillation in Patients on Thyroid Hormone Replacement Therapy.,"Soto-Pedre E, Siddiqui MK, Maroteau C, Dawed AY, Doney AS, Palmer CNA, Pearson ER, Leese GP.",,Frontiers in genetics,2021,2021-06-23,Y,Genetics; Insulin receptor; Hypothyroidism; Atrial fibrillation; Thyroid Hormone Replacement Therapy,,,"

Aims

Atrial fibrillation (AF) is a risk for patients receiving thyroid hormone replacement therapy. No published work has focused on pharmacogenetics relevant to thyroid dysfunction and AF risk. We aimed to assess the effect of L-thyroxine on AF risk stratified by a variation in a candidate gene.

Methods and results

A retrospective follow-up study was done among European Caucasian patients from the Genetics of Diabetes Audit and Research in Tayside Scotland cohort (Scotland, United Kingdom). Linked data on biochemistry, prescribing, hospital admissions, demographics, and genetic biobank were used to ascertain patients on L-thyroxine and diagnosis of AF. A GWAS-identified insulin receptor-INSR locus (rs4804416) was the candidate gene. Cox survival models and sensitivity analyses by taking competing risk of death into account were used. Replication was performed in additional sample (The Genetics of Scottish Health Research register, GoSHARE), and meta-analyses across the results of the study and replication cohorts were done. We analyzed 962 exposed to L-thyroxine and 5,840 unexposed patients who were rs4804416 genotyped. The rarer G/G genotype was present in 18% of the study population. The total follow-up was up to 20 years, and there was a significant increased AF risk for patients homozygous carriers of the G allele exposed to L-thyroxine (RHR = 2.35, P = 1.6e-02). The adjusted increased risk was highest within the first 3 years of exposure (RHR = 9.10, P = 8.5e-04). Sensitivity analysis yielded similar results. Effects were replicated in GoSHARE (n = 3,190).

Conclusion

Homozygous G/G genotype at the INSR locus (rs4804416) is associated with an increased risk of AF in patients on L-thyroxine, independent of serum of free thyroxine and thyroid-stimulating hormone serum concentrations.",,pdf:https://www.frontiersin.org/articles/10.3389/fgene.2021.652878/pdf; doi:https://doi.org/10.3389/fgene.2021.652878; html:https://europepmc.org/articles/PMC8260687; pdf:https://europepmc.org/articles/PMC8260687?pdf=render 37190903,https://doi.org/10.1002/ijc.34548,Cancer incidence and mortality in 23 000 patients with type 1 diabetes in the UK: Long-term follow-up.,"Swerdlow AJ, Jones ME, Slater SD, Burden ACF, Botha JL, Waugh NR, Morris AD, Gatling W, Gillespie KM, Patterson CC, Schoemaker MJ.",,International journal of cancer,2023,2023-05-15,Y,Cancer; type 1 diabetes; Cohort,,,"Type 2 diabetes is associated with raised risk of several cancers, but for type 1 diabetes risk data are fewer and inconsistent We assembled a cohort of 23 473 UK patients with insulin-treated diabetes diagnosed at ages <30, almost all of whom will have had type 1 diabetes, and for comparison 5058 diagnosed at ages 30 to 49, of whom we estimate two-thirds will have had type 2, and followed them for an average of 30 years for cancer incidence and mortality compared with general population rates. Patients aged <30 at diabetes diagnosis had significantly raised risks only for ovarian (standardised incidence ratio = 1.58; 95% confidence interval 1.16-2.11; P < .01) and vulval (3.55; 1.94-5.96; P < .001) cancers, with greatest risk when diabetes was diagnosed at ages 10-14. Risks of cancer overall (0.89; 0.84-0.95; P < .001) and sites including lung and larynx were significantly diminished. Patients diagnosed with diabetes at ages 30 to 49 had significantly raised risks of liver (1.76;1.08-2.72) and kidney (1.46;1.03-2.00) cancers, and reduced risk of cancer overall (0.89; 0.84-0.95). The raised ovarian and vulval cancer risks in patients with type 1 diabetes, especially with diabetes diagnosed around pubertal ages, suggest possible susceptibility of these organs at puberty to metabolic disruption at diabetes onset. Reduced risk of cancer overall, particularly smoking and alcohol-related sites, might reflect adoption of a healthy lifestyle.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ijc.34548; doi:https://doi.org/10.1002/ijc.34548; html:https://europepmc.org/articles/PMC10952206; pdf:https://europepmc.org/articles/PMC10952206?pdf=render +38336974,https://doi.org/10.1038/s41598-023-49923-3,VertXNet: an ensemble method for vertebral body segmentation and identification from cervical and lumbar spinal X-rays.,"Chen Y, Mo Y, Readie A, Ligozio G, Mandal I, Jabbar F, Coroller T, Papież BW.",,Scientific reports,2024,2024-02-09,Y,,,,"Accurate annotation of vertebral bodies is crucial for automating the analysis of spinal X-ray images. However, manual annotation of these structures is a laborious and costly process due to their complex nature, including small sizes and varying shapes. To address this challenge and expedite the annotation process, we propose an ensemble pipeline called VertXNet. This pipeline currently combines two segmentation mechanisms, semantic segmentation using U-Net, and instance segmentation using Mask R-CNN, to automatically segment and label vertebral bodies in lateral cervical and lumbar spinal X-ray images. VertXNet enhances its effectiveness by adopting a rule-based strategy (termed the ensemble rule) for effectively combining segmentation outcomes from U-Net and Mask R-CNN. It determines vertebral body labels by recognizing specific reference vertebral instances, such as cervical vertebra 2 ('C2') in cervical spine X-rays and sacral vertebra 1 ('S1') in lumbar spine X-rays. Those references are commonly relatively easy to identify at the edge of the spine. To assess the performance of our proposed pipeline, we conducted evaluations on three spinal X-ray datasets, including two in-house datasets and one publicly available dataset. The ground truth annotations were provided by radiologists for comparison. Our experimental results have shown that the proposed pipeline outperformed two state-of-the-art (SOTA) segmentation models on our test dataset with a mean Dice of 0.90, vs. a mean Dice of 0.73 for Mask R-CNN and 0.72 for U-Net. We also demonstrated that VertXNet is a modular pipeline that enables using other SOTA model, like nnU-Net to further improve its performance. Furthermore, to evaluate the generalization ability of VertXNet on spinal X-rays, we directly tested the pre-trained pipeline on two additional datasets. A consistently strong performance was observed, with mean Dice coefficients of 0.89 and 0.88, respectively. In summary, VertXNet demonstrated significantly improved performance in vertebral body segmentation and labeling for spinal X-ray imaging. Its robustness and generalization were presented through the evaluation of both in-house clinical trial data and publicly available datasets.",,pdf:https://www.nature.com/articles/s41598-023-49923-3.pdf; doi:https://doi.org/10.1038/s41598-023-49923-3; html:https://europepmc.org/articles/PMC10858234; pdf:https://europepmc.org/articles/PMC10858234?pdf=render 36933612,https://doi.org/10.1016/j.cct.2023.107162,Healthcare systems data in the context of clinical trials - A comparison of cardiovascular data from a clinical trial dataset with routinely collected data.,"Macnair A, Nankivell M, Murray ML, Rosen SD, Appleyard S, Sydes MR, Forcat S, Welland A, Clarke NW, Mangar S, Kynaston H, Kockelbergh R, Al-Hasso A, Deighan J, Marshall J, Parmar M, Langley RE, Gilbert DC.",,Contemporary clinical trials,2023,2023-03-16,N,Cardiovascular disease; prostate cancer; Clinical Trials; Healthcare Systems Data,,,"

Background

Routinely-collected healthcare systems data (HSD) are proposed to improve the efficiency of clinical trials. A comparison was undertaken between cardiovascular (CVS) data from a clinical trial database with two HSD resources.

Methods

Protocol-defined and clinically reviewed CVS events (heart failure (HF), acute coronary syndrome (ACS), thromboembolic stroke, venous and arterial thromboembolism) were identified within the trial data. Data (using pre-specified codes) was obtained from NHS Hospital Episode Statistics (HES) and National Institute for Cardiovascular Outcomes Research (NICOR) HF and myocardial ischaemia audits for trial participants recruited in England between 2010 and 2018 who had provided consent. The primary comparison was trial data versus HES inpatient (APC) main diagnosis (Box-1). Correlations are presented with descriptive statistics and Venn diagrams. Reasons for non-correlation were explored.

Results

From 1200 eligible participants, 71 protocol-defined clinically reviewed CVS events were recorded in the trial database. 45 resulted in a hospital admission and therefore could have been recorded by either HES APC/ NICOR. Of these, 27/45 (60%) were recorded by HES inpatient (Box-1) with an additional 30 potential events also identified. HF and ACS were potentially recorded in all 3 datasets; trial data recorded 18, HES APC 29 and NICOR 24 events respectively. 12/18 (67%) of the HF/ACS events in the trial dataset were recorded by NICOR.

Conclusion

Concordance between datasets was lower than anticipated and the HSD used could not straightforwardly replace current trial practices, nor directly identify protocol-defined CVS events. Further work is required to improve the quality of HSD and consider event definitions when designing clinical trials incorporating HSD.",,doi:https://doi.org/10.1016/j.cct.2023.107162; doi:https://doi.org/10.1016/j.cct.2023.107162 35932242,https://doi.org/10.1093/ageing/afac176,"Annual risk of falls resulting in emergency department and hospital attendances for older people: an observational study of 781,081 individuals living in Wales (United Kingdom) including deprivation, frailty and dementia diagnoses between 2010 and 2020.","Hollinghurst R, Williams N, Pedrick-Case R, North L, Long S, Fry R, Hollinghurst J.",,Age and ageing,2022,2022-08-01,Y,Frailty; Dementia; Falls; Older People; Covid-19,,,"

Background

falls are common in older people, but associations between falls, dementia and frailty are relatively unknown. The impact of the COVID-19 pandemic on falls admissions has not been studied.

Aim

to investigate the impact of dementia, frailty, deprivation, previous falls and the differences between years for falls resulting in an emergency department (ED) or hospital admission.

Study design

longitudinal cross-sectional observational study.

Setting

older people (aged 65+) resident in Wales between 1 January 2010 and 31 December 2020.

Methods

we created a binary (yes/no) indicator for a fall resulting in an attendance to an ED, hospital or both, per person, per year. We analysed the outcomes using multilevel logistic and multinomial models.

Results

we analysed a total of 5,141,244 person years of data from 781,081 individuals. Fall admission rates were highest in 2012 (4.27%) and lowest in 2020 (4.27%). We found an increased odds ratio (OR [95% confidence interval]) of a fall admission for age (1.05 [1.05, 1.05] per year of age), people with dementia (2.03 [2.00, 2.06]) and people who had a previous fall (2.55 [2.51, 2.60]). Compared with fit individuals, those with frailty had ORs of 1.60 [1.58, 1.62], 2.24 [2.21, 2.28] and 2.94 [2.89, 3.00] for mild, moderate and severe frailty respectively. Reduced odds were observed for males (0.73 [0.73, 0.74]) and less deprived areas; most deprived compared with least OR 0.75 [0.74, 0.76].

Conclusions

falls prevention should be targeted to those at highest risk, and investigations into the reduction in admissions in 2020 is warranted.",,doi:https://doi.org/10.1093/ageing/afac176; doi:https://doi.org/10.1093/ageing/afac176; html:https://europepmc.org/articles/PMC9356534; pdf:https://europepmc.org/articles/PMC9356534?pdf=render 35802764,https://doi.org/10.7189/jogh.12.05025,COVID-19 vaccine effectiveness against symptomatic SARS-CoV-2 infection and severe COVID-19 outcomes from Delta AY.4.2: Cohort and test-negative study of 5.4 million individuals in Scotland.,"Kerr S, Vasileiou E, Robertson C, Sheikh A.",,Journal of global health,2022,2022-07-09,Y,,,,"

Background

In July 2021, a new variant of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) in the Delta lineage was detected in the United Kingdom (UK), named AY.4.2 or ""Delta plus"". By October 2021, the AY.4.2 variant accounted for approximately 10-11% of cases in the UK. AY.4.2 was designated as a variant under investigation by the UK Health and Security Agency on 20 October 2021. This study aimed to investigate vaccine effectiveness (VE) against symptomatic COVID-19 (Coronavirus disease 2019) infection and COVID-19 hospitalisation/death for the AY.4.2 variant.

Methods

We used the Scotland-wide Early Pandemic Evaluation and Enhanced Surveillance (EAVE-II) platform to estimate the VE of the ChAdOx1, BNT162b2, and mRNA-1273 vaccines against symptomatic infection and severe COVID-19 outcomes in adults. The study was conducted from June 8 to October 25, 2021. We used a test-negative design (TND) to estimate VE against reverse transcriptase polymerase chain reaction (RT-PCR) confirmed symptomatic SARS-CoV-2 infection while adjusting for sex, socioeconomic status, number of coexisting conditions, and splines in time and age. We also performed a cohort study using a Cox proportional hazards model to estimate VE against a composite outcome of COVID-19 hospital admission or death, with the same adjustments.

Results

We found an overall VE against symptomatic SARS-CoV-2 infection due to AY.4.2 of 73% (95% confidence interval (CI) = 62-81) for >14 days post-second vaccine dose. Good protection against AY.4.2 symptomatic infection was observed for BNT162b2, ChAdOx1, and mRNA-1273. In unvaccinated individuals, the hazard ratio (HR) for COVID-19 hospital admission or death from AY.4.2 among community detected cases was 1.77 (95% CI = 1.02-3.07) relative to unvaccinated individuals who were infected with Delta, after adjusting for multiple potential confounders. VE against AY.4.2 COVID-19 admissions or deaths was 87% (95% CI = 74-93) >28 days post-second vaccination relative to unvaccinated.

Conclusions

We found that AY.4.2 was associated with an increased risk of COVID-19 hospitalisations or deaths in unvaccinated individuals compared with Delta and that vaccination provided substantial protection against symptomatic SARS-CoV-2 and severe COVID-19 outcomes following Delta AY.4.2 infection. High levels of vaccine uptake and protection offered by existing vaccines, as well as the rapid emergence of the Omicron variant may have contributed to the AY.4.2 variant never progressing to a variant of concern.",,pdf:https://jogh.org/wp-content/uploads/2022/07/jogh-12-05025.pdf; doi:https://doi.org/10.7189/jogh.12.05025; html:https://europepmc.org/articles/PMC9269984; pdf:https://europepmc.org/articles/PMC9269984?pdf=render -38528230,https://doi.org/10.1038/s43587-024-00590-7,Integration of polygenic and gut metagenomic risk prediction for common diseases.,"Liu Y, Ritchie SC, Teo SM, Ruuskanen MO, Kambur O, Zhu Q, Sanders J, Vázquez-Baeza Y, Verspoor K, Jousilahti P, Lahti L, Niiranen T, Salomaa V, Havulinna AS, Knight R, Méric G, Inouye M.",,Nature aging,2024,2024-03-25,Y,,,,"Multiomics has shown promise in noninvasive risk profiling and early detection of various common diseases. In the present study, in a prospective population-based cohort with ~18 years of e-health record follow-up, we investigated the incremental and combined value of genomic and gut metagenomic risk assessment compared with conventional risk factors for predicting incident coronary artery disease (CAD), type 2 diabetes (T2D), Alzheimer disease and prostate cancer. We found that polygenic risk scores (PRSs) improved prediction over conventional risk factors for all diseases. Gut microbiome scores improved predictive capacity over baseline age for CAD, T2D and prostate cancer. Integrated risk models of PRSs, gut microbiome scores and conventional risk factors achieved the highest predictive performance for all diseases studied compared with models based on conventional risk factors alone. The present study demonstrates that integrated PRSs and gut metagenomic risk models improve the predictive value over conventional risk factors for common chronic diseases.",,pdf:https://www.nature.com/articles/s43587-024-00590-7.pdf; doi:https://doi.org/10.1038/s43587-024-00590-7; html:https://europepmc.org/articles/PMC11031402; pdf:https://europepmc.org/articles/PMC11031402?pdf=render 35105585,https://doi.org/10.1136/bmjopen-2021-054376,Development of an algorithm to classify primary care electronic health records of alcohol consumption: experience using data linkage from UK Biobank and primary care electronic health data sources.,"Fraile-Navarro D, Azcoaga-Lorenzo A, Agrawal U, Jani B, Fagbamigbe A, Currie D, Baldacchino A, Sullivan F.",,BMJ open,2022,2022-02-01,Y,Public Health; Primary Care; Health Informatics,,,"

Objectives

Develop a novel algorithm to categorise alcohol consumption using primary care electronic health records (EHRs) and asses its reliability by comparing this classification with self-reported alcohol consumption data obtained from the UK Biobank (UKB) cohort.

Design

Cross-sectional study.

Setting

The UKB, a population-based cohort with participants aged between 40 and 69 years recruited across the UK between 2006 and 2010.

Participants

UKB participants from Scotland with linked primary care data.

Primary and secondary outcome measures

Create a rule-based multiclass algorithm to classify alcohol consumption reported by Scottish UKB participants and compare it with their classification using data present in primary care EHRs based on Read Codes. We evaluated agreement metrics (simple agreement and kappa statistic).

Results

Among the Scottish UKB participants, 18 838 (69%) had at least one Read Code related to alcohol consumption and were used in the classification. The agreement of alcohol consumption categories between UKB and primary care data, including assessments within 5 years was 59.6%, and kappa was 0.23 (95% CI 0.21 to 0.24). Differences in classification between the two sources were statistically significant (p<0.001); More individuals were classified as 'sensible drinkers' and in lower alcohol consumption levels in primary care records compared with the UKB. Agreement improved slightly when using only numerical values (k=0.29; 95% CI 0.27 to 0.31) and decreased when using qualitative descriptors only (k=0.18;95% CI 0.16 to 0.20).

Conclusion

Our algorithm classifies alcohol consumption recorded in Primary Care EHRs into discrete meaningful categories. These results suggest that alcohol consumption may be underestimated in primary care EHRs. Using numerical values (alcohol units) may improve classification when compared with qualitative descriptors.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/2/e054376.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-054376; html:https://europepmc.org/articles/PMC8808438; pdf:https://europepmc.org/articles/PMC8808438?pdf=render +38528230,https://doi.org/10.1038/s43587-024-00590-7,Integration of polygenic and gut metagenomic risk prediction for common diseases.,"Liu Y, Ritchie SC, Teo SM, Ruuskanen MO, Kambur O, Zhu Q, Sanders J, Vázquez-Baeza Y, Verspoor K, Jousilahti P, Lahti L, Niiranen T, Salomaa V, Havulinna AS, Knight R, Méric G, Inouye M.",,Nature aging,2024,2024-03-25,Y,,,,"Multiomics has shown promise in noninvasive risk profiling and early detection of various common diseases. In the present study, in a prospective population-based cohort with ~18 years of e-health record follow-up, we investigated the incremental and combined value of genomic and gut metagenomic risk assessment compared with conventional risk factors for predicting incident coronary artery disease (CAD), type 2 diabetes (T2D), Alzheimer disease and prostate cancer. We found that polygenic risk scores (PRSs) improved prediction over conventional risk factors for all diseases. Gut microbiome scores improved predictive capacity over baseline age for CAD, T2D and prostate cancer. Integrated risk models of PRSs, gut microbiome scores and conventional risk factors achieved the highest predictive performance for all diseases studied compared with models based on conventional risk factors alone. The present study demonstrates that integrated PRSs and gut metagenomic risk models improve the predictive value over conventional risk factors for common chronic diseases.",,pdf:https://www.nature.com/articles/s43587-024-00590-7.pdf; doi:https://doi.org/10.1038/s43587-024-00590-7; html:https://europepmc.org/articles/PMC11031402; pdf:https://europepmc.org/articles/PMC11031402?pdf=render 32206896,https://doi.org/10.1007/s00394-020-02220-5,Alcohol consumption in relation to carotid subclinical atherosclerosis and its progression: results from a European longitudinal multicentre study.,"Laguzzi F, Baldassarre D, Veglia F, Strawbridge RJ, Humphries SE, Rauramaa R, Smit AJ, Giral P, Silveira A, Tremoli E, Hamsten A, de Faire U, Frumento P, Leander K, IMPROVE Study group.",,European journal of nutrition,2021,2020-03-24,Y,Atherosclerosis; epidemiology; Carotid intima-media thickness; Alcohol drinking; Progression,,,"

Background/aim

The association between alcohol consumption and subclinical atherosclerosis is still unclear. Using data from a European multicentre study, we assess subclinical atherosclerosis and its 30-month progression by carotid intima-media thickness (C-IMT) measurements, and correlate this information with self-reported data on alcohol consumption.

Methods

Between 2002-2004, 1772 men and 1931 women aged 54-79 years with at least three risk factors for cardiovascular disease (CVD) were recruited in Italy, France, Netherlands, Sweden, and Finland. Self-reported alcohol consumption, assessed at baseline, was categorized as follows: none (0 g/d), very-low (0 - 5 g/d), low (> 5 to  ≤ 10 g/d), moderate (> 10 to ≤ 20 g/d for women,  > 10 to ≤ 30 g/d for men) and high (> 20 g/d for women, > 30 g/d for men). C-IMT was measured in millimeters at baseline and after 30 months. Measurements consisted of the mean and maximum values of the common carotids (CC), internal carotid artery (ICA), and bifurcations (Bif) and whole carotid tree. We used quantile regression to describe the associations between C-IMT measures and alcohol consumption categories, adjusting for sex, age, physical activity, education, smoking, diet, and latitude.

Results

Adjusted differences between median C-IMT values in different levels of alcohol consumption (vs. very-low) showed that moderate alcohol consumption was associated with lower C-IMTmax[- 0.17(95%CI - 0.32; - 0.02)], and Bif-IMTmean[- 0.07(95%CI - 0.13; - 0.01)] at baseline and decreasing C-IMTmean[- 0.006 (95%CI - 0.011; - 0.000)], Bif-IMTmean[- 0.016(95%CI - 0.027; - 0.005)], ICA-IMTmean[- 0.009(95% - 0.016; - 0.002)] and ICA-IMTmax[- 0.016(95%: - 0.032; - 0.000)] after 30 months. There was no evidence of departure from linearity in the association between alcohol consumption and C-IMT.

Conclusion

In this European population at high risk of CVD, findings show an inverse relation between moderate alcohol consumption and carotid subclinical atherosclerosis and its 30-month progression, independently of several potential confounders.",,pdf:https://link.springer.com/content/pdf/10.1007/s00394-020-02220-5.pdf; doi:https://doi.org/10.1007/s00394-020-02220-5; html:https://europepmc.org/articles/PMC7867553; pdf:https://europepmc.org/articles/PMC7867553?pdf=render 38589621,https://doi.org/10.1038/s41590-024-01778-0,Large-scale phenotyping of patients with long COVID post-hospitalization reveals mechanistic subtypes of disease.,"Liew F, Efstathiou C, Fontanella S, Richardson M, Saunders R, Swieboda D, Sidhu JK, Ascough S, Moore SC, Mohamed N, Nunag J, King C, Leavy OC, Elneima O, McAuley HJC, Shikotra A, Singapuri A, Sereno M, Harris VC, Houchen-Wolloff L, Greening NJ, Lone NI, Thorpe M, Thompson AAR, Rowland-Jones SL, Docherty AB, Chalmers JD, Ho LP, Horsley A, Raman B, Poinasamy K, Marks M, Kon OM, Howard LS, Wootton DG, Quint JK, de Silva TI, Ho A, Chiu C, Harrison EM, Greenhalf W, Baillie JK, Semple MG, Turtle L, Evans RA, Wain LV, Brightling C, Thwaites RS, Openshaw PJM, PHOSP-COVID collaborative group, ISARIC investigators.",,Nature immunology,2024,2024-04-08,Y,,,,"One in ten severe acute respiratory syndrome coronavirus 2 infections result in prolonged symptoms termed long coronavirus disease (COVID), yet disease phenotypes and mechanisms are poorly understood1. Here we profiled 368 plasma proteins in 657 participants ≥3 months following hospitalization. Of these, 426 had at least one long COVID symptom and 233 had fully recovered. Elevated markers of myeloid inflammation and complement activation were associated with long COVID. IL-1R2, MATN2 and COLEC12 were associated with cardiorespiratory symptoms, fatigue and anxiety/depression; MATN2, CSF3 and C1QA were elevated in gastrointestinal symptoms and C1QA was elevated in cognitive impairment. Additional markers of alterations in nerve tissue repair (SPON-1 and NFASC) were elevated in those with cognitive impairment and SCG3, suggestive of brain-gut axis disturbance, was elevated in gastrointestinal symptoms. Severe acute respiratory syndrome coronavirus 2-specific immunoglobulin G (IgG) was persistently elevated in some individuals with long COVID, but virus was not detected in sputum. Analysis of inflammatory markers in nasal fluids showed no association with symptoms. Our study aimed to understand inflammatory processes that underlie long COVID and was not designed for biomarker discovery. Our findings suggest that specific inflammatory pathways related to tissue damage are implicated in subtypes of long COVID, which might be targeted in future therapeutic trials.",,doi:https://doi.org/10.1038/s41590-024-01778-0; html:https://europepmc.org/articles/PMC11003868; pdf:https://europepmc.org/articles/PMC11003868?pdf=render 35813280,https://doi.org/10.1016/s2666-7568(22)00118-0,Antibody and cellular immune responses following dual COVID-19 vaccination within infection-naive residents of long-term care facilities: an observational cohort study.,"Tut G, Lancaster T, Sylla P, Butler MS, Kaur N, Spalkova E, Bentley C, Amin U, Jadir A, Hulme S, Ayodele M, Bone D, Tut E, Bruton R, Krutikov M, Giddings R, Shrotri M, Azmi B, Fuller C, Baynton V, Irwin-Singer A, Hayward A, Copas A, Shallcross L, Moss P.",,The lancet. Healthy longevity,2022,2022-07-04,Y,,,,"

Background

Older age and frailty are risk factors for poor clinical outcomes following SARS-CoV-2 infection. As such, COVID-19 vaccination has been prioritised for individuals with these factors, but there is concern that immune responses might be impaired due to age-related immune dysregulation and comorbidity. We aimed to study humoral and cellular responses to COVID-19 vaccines in residents of long-term care facilities (LTCFs).

Methods

In this observational cohort study, we assessed antibody and cellular immune responses following COVID-19 vaccination in members of staff and residents at 74 LTCFs across the UK. Staff and residents were eligible for inclusion if it was possible to link them to a pseudo-identifier in the COVID-19 datastore, if they had received two vaccine doses, and if they had given a blood sample 6 days after vaccination at the earliest. There were no comorbidity exclusion criteria. Participants were stratified by age (<65 years or ≥65 years) and infection status (previous SARS-CoV-2 infection [infection-primed group] or SARS-CoV-2 naive [infection-naive group]). Anticoagulated edetic acid (EDTA) blood samples were assessed and humoral and cellular responses were quantified.

Findings

Between Dec 11, 2020, and June 27, 2021, blood samples were taken from 220 people younger than 65 years (median age 51 years [IQR 39-61]; 103 [47%] had previously had a SARS-CoV-2 infection) and 268 people aged 65 years or older of LTCFs (median age 87 years [80-92]; 144 [43%] had a previous SARS-CoV-2 infection). Samples were taken a median of 82 days (IQR 72-100) after the second vaccination. Antibody responses following dual vaccination were strong and equivalent between participants younger then 65 years and those aged 65 years and older in the infection-primed group (median 125 285 Au/mL [1128 BAU/mL] for <65 year olds vs 157 979 Au/mL [1423 BAU/mL] for ≥65 year olds; p=0·47). The antibody response was reduced by 2·4-times (467 BAU/mL; p≤0·0001) in infection-naive people younger than 65 years and 8·1-times (174 BAU/mL; p≤0·0001) in infection-naive residents compared with their infection-primed counterparts. Antibody response was 2·6-times lower in infection-naive residents than in infection-naive people younger than 65 years (p=0·0006). Impaired neutralisation of delta (1.617.2) variant spike binding was also apparent in infection-naive people younger than 65 years and in those aged 65 years and older. Spike-specific T-cell responses were also significantly enhanced in the infection-primed group. Infection-naive people aged 65 years and older (203 SFU per million [IQR 89-374]) had a 52% lower T-cell response compared with infection-naive people younger than 65 years (85 SFU per million [30-206]; p≤0·0001). Post-vaccine spike-specific CD4 T-cell responses displayed single or dual production of IFN-γ and IL-2 were similar across infection status groups, whereas the infection-primed group had an extended functional profile with TNFα and CXCL10 production.

Interpretation

These data reveal suboptimal post-vaccine immune responses within infection-naive residents of LTCFs, and they suggest the need for optimisation of immune protection through the use of booster vaccination.

Funding

UK Government Department of Health and Social Care.",,pdf:http://pure-oai.bham.ac.uk/ws/files/173553190/1_s2.0_S2666756822001180_main.pdf; doi:https://doi.org/10.1016/S2666-7568(22)00118-0; html:https://europepmc.org/articles/PMC9252532; pdf:https://europepmc.org/articles/PMC9252532?pdf=render @@ -791,11 +791,11 @@ PMC9645061,https://doi.org/,Using population-scale medication data to evaluate t 37577380,https://doi.org/10.1093/braincomms/fcad211,Primary care blood tests show lipid profile changes in pre-symptomatic amyotrophic lateral sclerosis.,"Thompson AG, Marsden R, Talbot K, Turner MR.",,Brain communications,2023,2023-07-28,Y,Cholesterol; Biomarker; Amyotrophic Lateral Sclerosis; Motor Neurone Disease; Pre-symptomatic,,,"Multiple sources of evidence suggest that changes in metabolism may precede the onset of motor symptoms in amyotrophic lateral sclerosis. This study aimed to seek evidence for alterations in the levels of blood indices collected routinely in the primary care setting prior to the onset of motor symptoms in amyotrophic lateral sclerosis. Premorbid data, measured as part of routine health screening, for total cholesterol, high-density and low-density lipoprotein cholesterol, triglyceride, glycated haemoglobin A1c and creatinine were collected retrospectively from (i) a cohort of amyotrophic lateral sclerosis patients attending a specialist clinic (n = 143) and (ii) from primary care-linked data within UK Biobank. Data were fitted using linear mixed effects models with linear b-splines to identify inflection points, controlling for age and sex. In specialist amyotrophic lateral sclerosis clinic cases, models indicated decreasing levels of total and low-density lipoprotein cholesterol prior to an inflection point in the years before symptom onset (total cholesterol 3.25 years, low-density lipoprotein cholesterol 1.25 years), after which they stabilized or rose. A similar pattern was observed in amyotrophic lateral sclerosis cases within UK Biobank, occurring several years prior to diagnosis (total cholesterol 7 years, low-density lipoprotein cholesterol 7.25 years), differing significantly from matched controls. High-density lipoprotein cholesterol followed a similar pattern but was less robust to sensitivity analyses. Levels of triglyceride remained stable throughout. Glycated haemoglobin temporal profiles were not consistent between the clinic and biobank cohorts. Creatinine level trajectories prior to amyotrophic lateral sclerosis did not differ significantly from controls but decreased significantly in the symptomatic period after an inflection point of 0.25 years after symptom onset (clinic cohort) or 0.5 years before diagnosis (UK Biobank). These data provide further evidence for a pre-symptomatic period of dynamic metabolic change in amyotrophic lateral sclerosis, consistently associated with alterations in blood cholesterols. Such changes may ultimately contribute to biomarkers applicable to population screening and for pathways guiding the targeting of preventative therapy.",,pdf:https://academic.oup.com/braincomms/advance-article-pdf/doi/10.1093/braincomms/fcad211/51001698/fcad211.pdf; doi:https://doi.org/10.1093/braincomms/fcad211; html:https://europepmc.org/articles/PMC10412752; pdf:https://europepmc.org/articles/PMC10412752?pdf=render 32516805,https://doi.org/10.1093/eurheartj/ehaa375,Performance of the GRACE 2.0 score in patients with type 1 and type 2 myocardial infarction.,"Hung J, Roos A, Kadesjö E, McAllister DA, Kimenai DM, Shah ASV, Anand A, Strachan FE, Fox KAA, Mills NL, Chapman AR, Holzmann MJ.",,European heart journal,2021,2021-07-01,Y,Troponin; Grace; Type 2 Myocardial Infarction; High-sensitivity; Universal Definition; Type 1 Myocardial Infarction,,,"

Aims

The Global Registry of Acute Coronary Events (GRACE) score was developed to evaluate risk in patients with myocardial infarction. However, its performance in type 2 myocardial infarction is uncertain.

Methods and results

In two cohorts of consecutive patients with suspected acute coronary syndrome from 10 hospitals in Scotland (n = 48 282) and a tertiary care hospital in Sweden (n = 22 589), we calculated the GRACE 2.0 score to estimate death at 1 year. Discrimination was evaluated by the area under the receiver operating curve (AUC), and compared for those with an adjudicated diagnosis of type 1 and type 2 myocardial infarction using DeLong's test. Type 1 myocardial infarction was diagnosed in 4981 (10%) and 1080 (5%) patients in Scotland and Sweden, respectively. At 1 year, 720 (15%) and 112 (10%) patients died with an AUC for the GRACE 2.0 score of 0.83 [95% confidence interval (CI) 0.82-0.85] and 0.85 (95% CI 0.81-0.89). Type 2 myocardial infarction occurred in 1121 (2%) and 247 (1%) patients in Scotland and Sweden, respectively, with 258 (23%) and 57 (23%) deaths at 1 year. The AUC was 0.73 (95% CI 0.70-0.77) and 0.73 (95% CI 0.66-0.81) in type 2 myocardial infarction, which was lower than for type 1 myocardial infarction in both cohorts (P < 0.001 and P = 0.008, respectively).

Conclusion

The GRACE 2.0 score provided good discrimination for all-cause death at 1 year in patients with type 1 myocardial infarction, and moderate discrimination for those with type 2 myocardial infarction.

Trial registration

ClinicalTrials.gov number, NCT01852123.",,doi:https://doi.org/10.1093/eurheartj/ehaa375; doi:https://doi.org/10.1093/eurheartj/ehaa375; html:https://europepmc.org/articles/PMC8266602; pdf:https://europepmc.org/articles/PMC8266602?pdf=render 34353320,https://doi.org/10.1186/s12916-021-02045-x,Adverse childhood experiences and child mental health: an electronic birth cohort study.,"Lowthian E, Anthony R, Evans A, Daniel R, Long S, Bandyopadhyay A, John A, Bellis MA, Paranjothy S.",,BMC medicine,2021,2021-08-06,Y,Survival analysis; Cohort; Mental health; Wales; Administrative Data; Adverse Childhood Experiences,,,"

Background

Adverse childhood experiences (ACEs) are negatively associated with a range of child health outcomes. In this study, we explored associations between five individual ACEs and child mental health diagnoses or symptoms. ACEs included living with someone who had an alcohol-related problem, common mental health disorder or serious mental illness, or experienced victimisation or death of a household member.

Methods

We analysed data from a population-level electronic cohort of children in Wales, UK, (N = 191,035) between the years of 1998 and 2012. We used Cox regression with discrete time-varying exposure variables to model time to child mental health diagnosis during the first 15 years of life. Child mental health diagnoses include five categories: (i) externalising symptoms (anti-social behaviour), (ii) internalising symptoms (stress, anxiety, depression), (iii) developmental delay (e.g. learning disability), (iv) other (e.g. eating disorder, personality disorders), and (v) any mental health diagnosis, which was created by combining externalising symptoms, internalising symptoms and other. Our analyses were adjusted for social deprivation and perinatal risk factors.

Results

There were strong univariable associations between the five individual ACEs, sociodemographic and perinatal factors (e.g. gestational weight at birth) and an increased risk of child mental health diagnoses. After adjusting for sociodemographic and perinatal aspects, there was a remaining conditional increased risk of any child mental health diagnosis, associated with victimisation (conditional hazard ratio (cHR) 1.90, CI 95% 1.34-2.69), and living with an adult with a common mental health diagnosis (cHR 1.63, CI 95% 1.52-1.75). Coefficients of product terms between ACEs and deprivation were not statistically significant.

Conclusion

The increased risk of child mental health diagnosis associated with victimisation, or exposure to common mental health diagnoses, and alcohol problems in the household supports the need for policy measures and intervention strategies for children and their families.",,pdf:https://bmcmedicine.biomedcentral.com/track/pdf/10.1186/s12916-021-02045-x; doi:https://doi.org/10.1186/s12916-021-02045-x; html:https://europepmc.org/articles/PMC8344166; pdf:https://europepmc.org/articles/PMC8344166?pdf=render -37000839,https://doi.org/10.1371/journal.pone.0279076,Predicting a diagnosis of ankylosing spondylitis using primary care health records-A machine learning approach.,"Kennedy J, Kennedy N, Cooksey R, Choy E, Siebert S, Rahman M, Brophy S.",,PloS one,2023,2023-03-31,Y,,,,"Ankylosing spondylitis is the second most common cause of inflammatory arthritis. However, a successful diagnosis can take a decade to confirm from symptom onset (via x-rays). The aim of this study was to use machine learning methods to develop a profile of the characteristics of people who are likely to be given a diagnosis of AS in future. The Secure Anonymised Information Linkage databank was used. Patients with ankylosing spondylitis were identified using their routine data and matched with controls who had no record of a diagnosis of ankylosing spondylitis or axial spondyloarthritis. Data was analysed separately for men and women. The model was developed using feature/variable selection and principal component analysis to develop decision trees. The decision tree with the highest average F value was selected and validated with a test dataset. The model for men indicated that lower back pain, uveitis, and NSAID use under age 20 is associated with AS development. The model for women showed an older age of symptom presentation compared to men with back pain and multiple pain relief medications. The models showed good prediction (positive predictive value 70%-80%) in test data but in the general population where prevalence is very low (0.09% of the population in this dataset) the positive predictive value would be very low (0.33%-0.25%). Machine learning can be used to help profile and understand the characteristics of people who will develop AS, and in test datasets with artificially high prevalence, will perform well. However, when applied to a general population with low prevalence rates, such as that in primary care, the positive predictive value for even the best model would be 1.4%. Multiple models may be needed to narrow down the population over time to improve the predictive value and therefore reduce the time to diagnosis of ankylosing spondylitis.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0279076&type=printable; doi:https://doi.org/10.1371/journal.pone.0279076; html:https://europepmc.org/articles/PMC10065228; pdf:https://europepmc.org/articles/PMC10065228?pdf=render 33446033,https://doi.org/10.1177/1460458220977579,Identifying strategies to overcome roadblocks to utilising near real-time healthcare and administrative data to create a Scotland-wide learning health system.,"Mukherjee M, Cresswell K, Sheikh A.",,Health informatics journal,2021,2021-01-01,N,Qualitative Research; Governance; Electronic Health Records; Health Data; Learning Health System,,,"Creating a learning health system could help reduce variations in quality of care. Success is dependent on timely access to health data. To explore the barriers and facilitators to timely access to patients' data, we conducted in-depth semi-structured interviews with 37 purposively sampled participants from government, the NHS and academia across Scotland. Interviews were analysed using the framework approach. Participants were of the view that Scotland could play a leading role in the exploitation of routine data to drive forward service improvements, but highlighted major impediments: (i) persistence of paper-based records and a variety of information systems; (ii) the need for a proportionate approach to managing information governance; and (iii) the need for support structures to facilitate accrual, processing, linking, analysis and timely use and reuse of data for patient benefit. There is a pressing need to digitise and integrate existing health information infrastructures, guided by a nationwide proportionate information governance approach and the need to enhance technological and human capabilities to support these efforts.",,pdf:https://journals.sagepub.com/doi/pdf/10.1177/1460458220977579; doi:https://doi.org/10.1177/1460458220977579 +37000839,https://doi.org/10.1371/journal.pone.0279076,Predicting a diagnosis of ankylosing spondylitis using primary care health records-A machine learning approach.,"Kennedy J, Kennedy N, Cooksey R, Choy E, Siebert S, Rahman M, Brophy S.",,PloS one,2023,2023-03-31,Y,,,,"Ankylosing spondylitis is the second most common cause of inflammatory arthritis. However, a successful diagnosis can take a decade to confirm from symptom onset (via x-rays). The aim of this study was to use machine learning methods to develop a profile of the characteristics of people who are likely to be given a diagnosis of AS in future. The Secure Anonymised Information Linkage databank was used. Patients with ankylosing spondylitis were identified using their routine data and matched with controls who had no record of a diagnosis of ankylosing spondylitis or axial spondyloarthritis. Data was analysed separately for men and women. The model was developed using feature/variable selection and principal component analysis to develop decision trees. The decision tree with the highest average F value was selected and validated with a test dataset. The model for men indicated that lower back pain, uveitis, and NSAID use under age 20 is associated with AS development. The model for women showed an older age of symptom presentation compared to men with back pain and multiple pain relief medications. The models showed good prediction (positive predictive value 70%-80%) in test data but in the general population where prevalence is very low (0.09% of the population in this dataset) the positive predictive value would be very low (0.33%-0.25%). Machine learning can be used to help profile and understand the characteristics of people who will develop AS, and in test datasets with artificially high prevalence, will perform well. However, when applied to a general population with low prevalence rates, such as that in primary care, the positive predictive value for even the best model would be 1.4%. Multiple models may be needed to narrow down the population over time to improve the predictive value and therefore reduce the time to diagnosis of ankylosing spondylitis.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0279076&type=printable; doi:https://doi.org/10.1371/journal.pone.0279076; html:https://europepmc.org/articles/PMC10065228; pdf:https://europepmc.org/articles/PMC10065228?pdf=render 33469151,https://doi.org/10.1038/s42003-020-01613-w,LRIG proteins regulate lipid metabolism via BMP signaling and affect the risk of type 2 diabetes.,"Herdenberg C, Mutie PM, Billing O, Abdullah A, Strawbridge RJ, Dahlman I, Tuck S, Holmlund C, Arner P, Henriksson R, Franks PW, Hedman H.",,Communications biology,2021,2021-01-19,Y,,,,"Leucine-rich repeats and immunoglobulin-like domains (LRIG) proteins have been implicated as regulators of growth factor signaling; however, the possible redundancy among mammalian LRIG1, LRIG2, and LRIG3 has hindered detailed elucidation of their physiological functions. Here, we show that Lrig-null mouse embryonic fibroblasts (MEFs) are deficient in adipogenesis and bone morphogenetic protein (BMP) signaling. In contrast, transforming growth factor-beta (TGF-β) and receptor tyrosine kinase (RTK) signaling appeared unaltered in Lrig-null cells. The BMP signaling defect was rescued by ectopic expression of LRIG1 or LRIG3 but not by expression of LRIG2. Caenorhabditis elegans with mutant LRIG/sma-10 variants also exhibited a lipid storage defect. Human LRIG1 variants were strongly associated with increased body mass index (BMI) yet protected against type 2 diabetes; these effects were likely mediated by altered adipocyte morphology. These results demonstrate that LRIG proteins function as evolutionarily conserved regulators of lipid metabolism and BMP signaling and have implications for human disease.",,pdf:https://www.nature.com/articles/s42003-020-01613-w.pdf; doi:https://doi.org/10.1038/s42003-020-01613-w; html:https://europepmc.org/articles/PMC7815736; pdf:https://europepmc.org/articles/PMC7815736?pdf=render -38304287,https://doi.org/10.3389/fpsyt.2024.1347358,How will AI make sense of our messy lives and improve our mental health?,"Speechley J, McTernan M.",,Frontiers in psychiatry,2024,2024-01-18,Y,Artificial intelligence; Data; Mental health; TRUST; Patient And Public Engagement,,,,,doi:https://doi.org/10.3389/fpsyt.2024.1347358; html:https://europepmc.org/articles/PMC10832992; pdf:https://europepmc.org/articles/PMC10832992?pdf=render 36377225,https://doi.org/10.1177/18333583221135710,Concordance between coding sources of burn size and depth across Australian and New Zealand specialist burn services.,"Perkins M, Cleland H, Gabbe BJ, Tracy LM.",,Health information management : journal of the Health Information Management Association of Australia,2024,2022-11-14,N,Burns; Australia; New Zealand; Registries; Health Information Management; International Classification Of Diseases; Clinical Coding,,,"

Background

The percentage of total body surface area (%TBSA) burned and burn depth provide valuable information on burn injury severity.

Objective

This study investigated the concordance between The International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, Australian Modification (ICD-10-AM) codes and expert burn clinicians in assessing burn injury severity.

Method

We conducted a retrospective population-based review of all patients who sustained a burn injury between July 1, 2009, and June 30, 2019, requiring admission into a specialist burn service across Australia and New Zealand. The %TBSA burned (including the percentage of full thickness burns) recorded by expert burn clinicians within the Burns Registry of Australia and New Zealand (BRANZ) were compared to ICD-10-AM coding.

Results

20,642 cases (71.5%) with ICD-10-AM code data were recorded. Overall, kappa scores (95% confidence interval [CI]) for burn size ranged from 0.64 (95% CI 0.63-0.66) to 0.86 (95% CI 0.78-0.94) indicating substantial to almost perfect agreement across all %TBSA groups. When stratified by depth, the lowest agreement was observed for < 10% TBSA and < 10% full thickness (kappa 0.03; 95% CI 0.02-0.04) and the highest agreement was observed for burns of ≥ 90% TBSA and ≥ 90% full thickness (kappa 0.72; 95% CI 0.58-0.85).

Conclusion

Overall, there was substantial agreement between the BRANZ and ICD-10-AM coded data for %TBSA classification. When %TBSA classification was stratified by burn depth, greater agreement was observed for larger and deeper burns compared with smaller and superficial burns.

Implications

Greater consistency in the classification of burns is needed.",,doi:https://doi.org/10.1177/18333583221135710 +38304287,https://doi.org/10.3389/fpsyt.2024.1347358,How will AI make sense of our messy lives and improve our mental health?,"Speechley J, McTernan M.",,Frontiers in psychiatry,2024,2024-01-18,Y,Artificial intelligence; Data; Mental health; TRUST; Patient And Public Engagement,,,,,doi:https://doi.org/10.3389/fpsyt.2024.1347358; html:https://europepmc.org/articles/PMC10832992; pdf:https://europepmc.org/articles/PMC10832992?pdf=render 30727941,https://doi.org/10.1186/s12859-019-2633-8,DeepPVP: phenotype-based prioritization of causative variants using deep learning.,"Boudellioua I, Kulmanov M, Schofield PN, Gkoutos GV, Hoehndorf R.",,BMC bioinformatics,2019,2019-02-06,Y,Phenotype; Ontology; Machine Learning; Variant Prioritization,Applied Analytics,,"

Background

Prioritization of variants in personal genomic data is a major challenge. Recently, computational methods that rely on comparing phenotype similarity have shown to be useful to identify causative variants. In these methods, pathogenicity prediction is combined with a semantic similarity measure to prioritize not only variants that are likely to be dysfunctional but those that are likely involved in the pathogenesis of a patient's phenotype.

Results

We have developed DeepPVP, a variant prioritization method that combined automated inference with deep neural networks to identify the likely causative variants in whole exome or whole genome sequence data. We demonstrate that DeepPVP performs significantly better than existing methods, including phenotype-based methods that use similar features. DeepPVP is freely available at https://github.com/bio-ontology-research-group/phenomenet-vp .

Conclusions

DeepPVP further improves on existing variant prioritization methods both in terms of speed as well as accuracy.",,pdf:https://bmcbioinformatics.biomedcentral.com/track/pdf/10.1186/s12859-019-2633-8; doi:https://doi.org/10.1186/s12859-019-2633-8; html:https://europepmc.org/articles/PMC6364462; pdf:https://europepmc.org/articles/PMC6364462?pdf=render 35079022,https://doi.org/10.1038/s41467-022-28157-3,Regional excess mortality during the 2020 COVID-19 pandemic in five European countries.,"Konstantinoudis G, Cameletti M, Gómez-Rubio V, Gómez IL, Pirani M, Baio G, Larrauri A, Riou J, Egger M, Vineis P, Blangiardo M.",,Nature communications,2022,2022-01-25,Y,,,,"The impact of the COVID-19 pandemic on excess mortality from all causes in 2020 varied across and within European countries. Using data for 2015-2019, we applied Bayesian spatio-temporal models to quantify the expected weekly deaths at the regional level had the pandemic not occurred in England, Greece, Italy, Spain, and Switzerland. With around 30%, Madrid, Castile-La Mancha, Castile-Leon (Spain) and Lombardia (Italy) were the regions with the highest excess mortality. In England, Greece and Switzerland, the regions most affected were Outer London and the West Midlands (England), Eastern, Western and Central Macedonia (Greece), and Ticino (Switzerland), with 15-20% excess mortality in 2020. Our study highlights the importance of the large transportation hubs for establishing community transmission in the first stages of the pandemic. Here, we show that acting promptly to limit transmission around these hubs is essential to prevent spread to other regions and countries.",,pdf:https://www.nature.com/articles/s41467-022-28157-3.pdf; doi:https://doi.org/10.1038/s41467-022-28157-3; html:https://europepmc.org/articles/PMC8789777; pdf:https://europepmc.org/articles/PMC8789777?pdf=render 31971603,https://doi.org/10.2340/00015555-3384,Psoriasis and Genetics.,"Dand N, Mahil SK, Capon F, Smith CH, Simpson MA, Barker JN.",,Acta dermato-venereologica,2020,2020-01-30,Y,Genetics; Psoriasis; Treatment outcome; Disease Progression; Precision Medicine,,,"Psoriasis is a common inflammatory skin disease caused by the interplay between multiple genetic and environmental risk factors. This review summarises recent progress in elucidating the genetic basis of psoriasis, particularly through large genome-wide association studies. We illustrate the power of genetic analyses for disease stratification. Psoriasis can be stratified by phenotype (common plaque versus rare pustular variants), or by outcome (prognosis, comorbidities, response to treatment); recent progress has been made in delineating the genetic contribution in each of these areas. We also highlight how genetic data can directly inform the development of effective psoriasis treatments.",,doi:https://doi.org/10.2340/00015555-3384; doi:https://doi.org/10.2340/00015555-3384; html:https://europepmc.org/articles/PMC9128944; pdf:https://europepmc.org/articles/PMC9128944?pdf=render @@ -814,8 +814,8 @@ PMC9645061,https://doi.org/,Using population-scale medication data to evaluate t 36567336,https://doi.org/10.1186/s12872-022-03005-w,Diagnostic signature for heart failure with preserved ejection fraction (HFpEF): a machine learning approach using multi-modality electronic health record data.,"Farajidavar N, O'Gallagher K, Bean D, Nabeebaccus A, Zakeri R, Bromage D, Kraljevic Z, Teo JTH, Dobson RJ, Shah AM.",,BMC cardiovascular disorders,2022,2022-12-26,Y,Dyspnea; Machine Learning; Hfpef,,,"

Background

Heart failure with preserved ejection fraction (HFpEF) is thought to be highly prevalent yet remains underdiagnosed. Evidence-based treatments are available that increase quality of life and decrease hospitalization. We sought to develop a data-driven diagnostic model to predict from electronic health records (EHR) the likelihood of HFpEF among patients with unexplained dyspnea and preserved left ventricular EF.

Methods and results

The derivation cohort comprised patients with dyspnea and echocardiography results. Structured and unstructured data were extracted using an automated informatics pipeline. Patients were retrospectively diagnosed as HFpEF (cases), non-HF (control cohort I), or HF with reduced EF (HFrEF; control cohort II). The ability of clinical parameters and investigations to discriminate cases from controls was evaluated by extreme gradient boosting. A likelihood scoring system was developed and validated in a separate test cohort. The derivation cohort included 1585 consecutive patients: 133 cases of HFpEF (9%), 194 non-HF cases (Control cohort I) and 1258 HFrEF cases (Control cohort II). Two HFpEF diagnostic signatures were derived, comprising symptoms, diagnoses and investigation results. A final prediction model was generated based on the averaged likelihood scores from these two models. In a validation cohort consisting of 269 consecutive patients [with 66 HFpEF cases (24.5%)], the diagnostic power of detecting HFpEF had an AUROC of 90% (P < 0.001) and average precision of 74%.

Conclusion

This diagnostic signature enables discrimination of HFpEF from non-cardiac dyspnea or HFrEF from EHR and can assist in the diagnostic evaluation in patients with unexplained dyspnea. This approach will enable identification of HFpEF patients who may then benefit from new evidence-based therapies.",,pdf:https://bmccardiovascdisord.biomedcentral.com/counter/pdf/10.1186/s12872-022-03005-w; doi:https://doi.org/10.1186/s12872-022-03005-w; html:https://europepmc.org/articles/PMC9791783; pdf:https://europepmc.org/articles/PMC9791783?pdf=render 36808078,https://doi.org/10.1136/pn-2021-003286,Outpatient neurology diagnostic coding: a proposed scheme for standardised implementation.,"Biggin F, Knight J, Dayanandan R, Marson A, Wilson M, Nitkunan A, Rog D, Kipps C, Mummery C, Williams A, Emsley HCA.",,Practical neurology,2023,2023-02-20,Y,Clinical Neurology,,,"Clinical coding uses a classification system to assign standard codes to clinical terms and so facilitates good clinical practice through audit, service design and research. However, despite clinical coding being mandatory for inpatient activity, this is often not so for outpatient services, where most neurological care is delivered. Recent reports by the UK National Neurosciences Advisory Group and NHS England's 'Getting It Right First Time' initiative recommend implementing outpatient coding. The UK currently has no standardised system for outpatient neurology diagnostic coding. However, most new attendances at general neurology clinics appear to be classifiable with a limited number of diagnostic terms. We present the rationale for diagnostic coding and its benefits, and the need for clinical engagement to develop a system that is pragmatic, quick and easy to use. We outline a scheme developed in the UK that could be used elsewhere.",,pdf:https://pn.bmj.com/content/practneurol/early/2023/02/19/pn-2021-003286.full.pdf; doi:https://doi.org/10.1136/pn-2021-003286; html:https://europepmc.org/articles/PMC10423506; pdf:https://europepmc.org/articles/PMC10423506?pdf=render 34649997,https://doi.org/10.2337/dc21-0437,"Polycystic Ovary Syndrome, Combined Oral Contraceptives, and the Risk of Dysglycemia: A Population-Based Cohort Study With a Nested Pharmacoepidemiological Case-Control Study.","Kumarendran B, O'Reilly MW, Subramanian A, Šumilo D, Toulis K, Gokhale KM, Wijeratne CN, Coomarasamy A, Tahrani AA, Azoulay L, Arlt W, Nirantharakumar K.",,Diabetes care,2021,2021-10-14,Y,,,,"

Objective

Irregular menstrual cycles are associated with increased cardiovascular mortality. Polycystic ovary syndrome (PCOS) is characterized by androgen excess and irregular menses; androgens are drivers of increased metabolic risk in women with PCOS. Combined oral contraceptive pills (COCPs) are used in PCOS both for cycle regulation and to reduce the biologically active androgen fraction. We examined COCP use and risk of dysglycemia (prediabetes and type 2 diabetes) in women with PCOS.

Research design and methods

Using a large U.K. primary care database (The Health Improvement Network [THIN]; 3.7 million patients from 787 practices), we carried out a retrospective population-based cohort study to determine dysglycemia risk (64,051 women with PCOS and 123,545 matched control subjects), as well as a nested pharmacoepidemiological case-control study to investigate COCP use in relation to dysglycemia risk (2,407 women with PCOS with [case subjects] and without [control subjects] a diagnosis of dysglycemia during follow-up). Cox models were used to estimate the unadjusted and adjusted hazard ratio, and conditional logistic regression was used to obtain adjusted odds ratios (aORs).

Results

The adjusted hazard ratio for dysglycemia in women with PCOS was 1.87 (95% CI 1.78-1.97, P < 0.001; adjustment for age, social deprivation, BMI, ethnicity, and smoking), with increased rates of dysglycemia in all BMI subgroups. Women with PCOS and COCP use had a reduced dysglycemia risk (aOR 0.72, 95% CI 0.59-0.87).

Conclusions

In this study, limited by its retrospective nature and the use of routinely collected electronic general practice record data, which does not allow for exclusion of the impact of prescription-by-indication bias, women with PCOS exposed to COCPs had a reduced risk of dysglycemia across all BMI subgroups. Future prospective studies should be considered for further understanding of these observations and potential causality.",,pdf:https://diabetesjournals.org/care/article-pdf/44/12/2758/631597/dc210437.pdf; doi:https://doi.org/10.2337/dc21-0437; html:https://europepmc.org/articles/PMC8669537; pdf:https://europepmc.org/articles/PMC8669537?pdf=render -36895179,https://doi.org/10.1093/eurjpc/zwad055,Determining cardiovascular risk in patients with unattributed chest pain in UK primary care: an electronic health record study.,"Jordan KP, Rathod-Mistry T, van der Windt DA, Bailey J, Chen Y, Clarson L, Denaxas S, Hayward RA, Hemingway H, Kyriacou T, Mamas MA.",,European journal of preventive cardiology,2023,2023-08-01,Y,Cardiovascular disease; Chest pain; epidemiology; Primary Health Care; risk; Electronic Health Records,,,"

Aims

Most adults presenting in primary care with chest pain symptoms will not receive a diagnosis ('unattributed' chest pain) but are at increased risk of cardiovascular events. To assess within patients with unattributed chest pain, risk factors for cardiovascular events and whether those at greatest risk of cardiovascular disease can be ascertained by an existing general population risk prediction model or by development of a new model.

Methods and results

The study used UK primary care electronic health records from the Clinical Practice Research Datalink linked to admitted hospitalizations. Study population was patients aged 18 plus with recorded unattributed chest pain 2002-2018. Cardiovascular risk prediction models were developed with external validation and comparison of performance to QRISK3, a general population risk prediction model. There were 374 917 patients with unattributed chest pain in the development data set. The strongest risk factors for cardiovascular disease included diabetes, atrial fibrillation, and hypertension. Risk was increased in males, patients of Asian ethnicity, those in more deprived areas, obese patients, and smokers. The final developed model had good predictive performance (external validation c-statistic 0.81, calibration slope 1.02). A model using a subset of key risk factors for cardiovascular disease gave nearly identical performance. QRISK3 underestimated cardiovascular risk.

Conclusion

Patients presenting with unattributed chest pain are at increased risk of cardiovascular events. It is feasible to accurately estimate individual risk using routinely recorded information in the primary care record, focusing on a small number of risk factors. Patients at highest risk could be targeted for preventative measures.",,pdf:https://academic.oup.com/eurjpc/advance-article-pdf/doi/10.1093/eurjpc/zwad055/49604587/zwad055.pdf; doi:https://doi.org/10.1093/eurjpc/zwad055; html:https://europepmc.org/articles/PMC10442054; pdf:https://europepmc.org/articles/PMC10442054?pdf=render 33123364,https://doi.org/10.1093/ckj/sfaa192,Temporal changes in complement activation in haemodialysis patients with COVID-19 as a predictor of disease progression.,"Prendecki M, Clarke C, Medjeral-Thomas N, McAdoo SP, Sandhu E, Peters JE, Thomas DC, Willicombe M, Botto M, Pickering MC.",,Clinical kidney journal,2020,2020-10-02,Y,Complement; Haemodialysis; Covid-19,,,"

Background

Complement activation may play a pathogenic role in patients with severe coronavirus disease 2019 (COVID-19) by contributing to tissue inflammation and microvascular thrombosis.

Methods

Serial samples were collected from patients receiving maintenance haemodialysis (HD). Thirty-nine patients had confirmed COVID-19 and 10 patients had no evidence of COVID-19. Plasma C5a and C3a levels were measured using enzyme-linked immunosorbent assay.

Results

We identified elevated levels of plasma C3a and C5a in HD patients with severe COVID-19 compared with controls. Serial sampling identified that C5a levels were elevated prior to clinical deterioration in patients who developed severe disease. C3a more closely mirrored both clinical and biochemical disease severity.

Conclusions

Our findings suggest that activation of complement plays a role in the pathogenesis of COVID-19, leading to endothelial injury and lung damage. C5a may be an earlier biomarker of disease severity than conventional parameters such as C-reactive protein and this warrants further investigation in dedicated biomarker studies. Our data support the testing of complement inhibition as a therapeutic strategy for patients with severe COVID-19.",,pdf:https://academic.oup.com/ckj/article-pdf/13/5/889/33980535/sfaa192.pdf; doi:https://doi.org/10.1093/ckj/sfaa192; html:https://europepmc.org/articles/PMC7577776; pdf:https://europepmc.org/articles/PMC7577776?pdf=render +36895179,https://doi.org/10.1093/eurjpc/zwad055,Determining cardiovascular risk in patients with unattributed chest pain in UK primary care: an electronic health record study.,"Jordan KP, Rathod-Mistry T, van der Windt DA, Bailey J, Chen Y, Clarson L, Denaxas S, Hayward RA, Hemingway H, Kyriacou T, Mamas MA.",,European journal of preventive cardiology,2023,2023-08-01,Y,Cardiovascular disease; Chest pain; epidemiology; Primary Health Care; risk; Electronic Health Records,,,"

Aims

Most adults presenting in primary care with chest pain symptoms will not receive a diagnosis ('unattributed' chest pain) but are at increased risk of cardiovascular events. To assess within patients with unattributed chest pain, risk factors for cardiovascular events and whether those at greatest risk of cardiovascular disease can be ascertained by an existing general population risk prediction model or by development of a new model.

Methods and results

The study used UK primary care electronic health records from the Clinical Practice Research Datalink linked to admitted hospitalizations. Study population was patients aged 18 plus with recorded unattributed chest pain 2002-2018. Cardiovascular risk prediction models were developed with external validation and comparison of performance to QRISK3, a general population risk prediction model. There were 374 917 patients with unattributed chest pain in the development data set. The strongest risk factors for cardiovascular disease included diabetes, atrial fibrillation, and hypertension. Risk was increased in males, patients of Asian ethnicity, those in more deprived areas, obese patients, and smokers. The final developed model had good predictive performance (external validation c-statistic 0.81, calibration slope 1.02). A model using a subset of key risk factors for cardiovascular disease gave nearly identical performance. QRISK3 underestimated cardiovascular risk.

Conclusion

Patients presenting with unattributed chest pain are at increased risk of cardiovascular events. It is feasible to accurately estimate individual risk using routinely recorded information in the primary care record, focusing on a small number of risk factors. Patients at highest risk could be targeted for preventative measures.",,pdf:https://academic.oup.com/eurjpc/advance-article-pdf/doi/10.1093/eurjpc/zwad055/49604587/zwad055.pdf; doi:https://doi.org/10.1093/eurjpc/zwad055; html:https://europepmc.org/articles/PMC10442054; pdf:https://europepmc.org/articles/PMC10442054?pdf=render 36447757,https://doi.org/10.1136/gpsych-2022-100819,Body mass index and mortality in patients with schizophrenia spectrum disorders: a cohort study in a South London catchment area.,"Chen J, Perera G, Shetty H, Broadbent M, Xu Y, Stewart R.",,General psychiatry,2022,2022-11-04,Y,Schizophrenia; Life style; Mental Health Services,,,"

Background

People with schizophrenia have a high premature mortality risk. Obesity is a key potential underlying risk factor that is relatively unevaluated to date.

Aims

In this study, we investigated the associations of routinely recorded body size with all-cause mortality and deaths from common causes in a large cohort of people with schizophrenia spectrum disorders.

Methods

We assembled a retrospective observational cohort using data from a large mental health service in South London. We followed all patients over the age of 18 years with a clinical diagnosis of schizophrenia spectrum disorders from the date of their first recorded body mass index (BMI) between 1 January 2007 and 31 March 2018.

Results

Of 11 900 patients with a BMI recording, 1566 died. The Cox proportional hazards regression models, after adjusting for sociodemographic, socioeconomic variables and comorbidities, indicated that all-cause mortality was only associated with underweight status compared with healthy weight status (hazard ratio (HR): 1.33, 95% confidence interval (CI): 1.01 to 1.76). Obesity (HR: 1.24, 95% CI: 1.01 to 1.52) and morbid obesity (HR: 1.54, 95% CI: 1.03 to 2.42) were associated with all-cause mortality in the 18-45 years age range, and obesity was associated with lower risk (HR: 0.66, 95% CI: 0.50 to 0.87) in those aged 65+ years. Cancer mortality was raised in underweight individuals (HR: 1.93, 95% CI: 1.03 to 4.10) and respiratory disease mortality raised in those with morbid obesity (HR: 2.17, 95% CI: 1.02 to 5.22).

Conclusions

Overall, being underweight was associated with higher mortality in this disorder group; however, this was potentially accounted for by frailty in older age groups, and obesity was a risk factor for premature mortality in younger ages. The impact of obesity on life expectancy for people with schizophrenia spectrum disorders is clear from our findings. A deeper biological understanding of the relationship between these diseases and schizophrenia will help improve clinical practice.",,pdf:https://gpsych.bmj.com/content/gpsych/35/5/e100819.full.pdf; doi:https://doi.org/10.1136/gpsych-2022-100819; html:https://europepmc.org/articles/PMC9639123; pdf:https://europepmc.org/articles/PMC9639123?pdf=render 38036971,https://doi.org/10.1186/s12859-023-05576-7,Completing a genomic characterisation of microscopic tumour samples with copy number.,"Nulsen J, Hussain N, Al-Deka A, Yap J, Uddin K, Yau C, Ahmed AA.",,BMC bioinformatics,2023,2023-11-30,Y,Copy number; Microscopic Samples; Cancer Genomics,,,"

Background

Genomic insights in settings where tumour sample sizes are limited to just hundreds or even tens of cells hold great clinical potential, but also present significant technical challenges. We previously developed the DigiPico sequencing platform to accurately identify somatic mutations from such samples.

Results

Here, we complete this genomic characterisation with copy number. We present a novel protocol, PicoCNV, to call allele-specific somatic copy number alterations from picogram quantities of tumour DNA. We find that PicoCNV provides exactly accurate copy number in 84% of the genome for even the smallest samples, and demonstrate its clinical potential in maintenance therapy.

Conclusions

PicoCNV complements our existing platform, allowing for accurate and comprehensive genomic characterisations of cancers in settings where only microscopic samples are available.",,pdf:https://bmcbioinformatics.biomedcentral.com/counter/pdf/10.1186/s12859-023-05576-7; doi:https://doi.org/10.1186/s12859-023-05576-7; html:https://europepmc.org/articles/PMC10688092; pdf:https://europepmc.org/articles/PMC10688092?pdf=render 38018286,https://doi.org/10.1111/vox.13564,"The value of genetic data from 665,460 individuals in managing iron deficiency anaemia and suitability to donate blood.","Toivonen J, Allara E, FinnGen, Castrén J, di Angelantonio E, Arvas M.",,Vox sanguinis,2024,2023-11-28,N,statistical inference; Gwas; Iron Deficiency Anaemia; Genetic Risk; Prs; Hb-deferral,,,"

Background and objectives

Although the genetic determinants of haemoglobin and ferritin have been widely studied, those of the clinically and globally relevant iron deficiency anaemia (IDA) and deferral due to hypohaemoglobinemia (Hb-deferral) are unclear. In this investigation, we aimed to quantify the value of genetic information in predicting IDA and Hb-deferral.

Materials and methods

We analysed genetic data from up to 665,460 participants of the FinnGen, Blood Service Biobank and UK Biobank, and used INTERVAL (N = 39,979) for validation. We performed genome-wide association studies (GWASs) of IDA and Hb-deferral and utilized publicly available genetic associations to compute polygenic scores for IDA, ferritin and Hb. We fitted models to estimate the effect sizes of these polygenic risk scores (PRSs) on IDA and Hb-deferral risk while accounting for the individual's age, sex, weight, height, smoking status and blood donation history.

Results

Significant variants in GWASs of IDA and Hb-deferral appear to be a small subset of variants associated with ferritin and Hb. Effect sizes of genetic predictors of IDA and Hb-deferral are similar to those of age and weight which are typically used in blood donor management. A total genetic score for Hb-deferral was estimated for each individual. The odds ratio estimate between first decile against that at ninth decile of total genetic score distribution ranged from 1.4 to 2.2.

Conclusion

The value of genetic data in predicting IDA or suitability to donate blood appears to be on a practically useful level.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/vox.13564; doi:https://doi.org/10.1111/vox.13564 @@ -840,11 +840,11 @@ PMC10686417,https://doi.org/,The impact of restricted provision of publicly fund 37699069,https://doi.org/10.1093/ehjci/jead218,Phenotyping left ventricular systolic dysfunction in asymptomatic individuals for improved risk stratification.,"Rauseo E, Abdulkareem M, Khan A, Cooper J, Lee AM, Aung N, Slabaugh GG, Petersen SE.",,European heart journal. Cardiovascular Imaging,2023,2023-09-01,Y,Prognosis; Cardiovascular events; Risk stratification; Heart Failure; Cardiovascular Magnetic Resonance; Left Ventricular Systolic Dysfunction,,,"

Aims

Left ventricular systolic dysfunction (LSVD) is a heterogeneous condition with several factors influencing prognosis. Better phenotyping of asymptomatic individuals can inform preventative strategies. This study aims to explore the clinical phenotypes of LVSD in initially asymptomatic subjects and their association with clinical outcomes and cardiovascular abnormalities through multi-dimensional data clustering.

Methods and results

Clustering analysis was performed on 60 clinically available variables from 1563 UK Biobank participants without pre-existing heart failure (HF) and with left ventricular ejection fraction (LVEF) < 50% on cardiovascular magnetic resonance (CMR) assessment. Risks of developing HF, other cardiovascular events, death, and a composite of major adverse cardiovascular events (MACE) associated with clusters were investigated. Cardiovascular imaging characteristics, not included in the clustering analysis, were also evaluated. Three distinct clusters were identified, differing considerably in lifestyle habits, cardiovascular risk factors, electrocardiographic parameters, and cardiometabolic profiles. A stepwise increase in risk profile was observed from Cluster 1 to Cluster 3, independent of traditional risk factors and LVEF. Compared with Cluster 1, the lowest risk subset, the risk of MACE ranged from 1.42 [95% confidence interval (CI): 1.03-1.96; P < 0.05] for Cluster 2 to 1.72 (95% CI: 1.36-2.35; P < 0.001) for Cluster 3. Cluster 3, the highest risk profile, had features of adverse cardiovascular imaging with the greatest LV re-modelling, myocardial dysfunction, and decrease in arterial compliance.

Conclusions

Clustering of clinical variables identified three distinct risk profiles and clinical trajectories of LVSD amongst initially asymptomatic subjects. Improved characterization may facilitate tailored interventions based on the LVSD sub-type and improve clinical outcomes.",,doi:https://doi.org/10.1093/ehjci/jead218; html:https://europepmc.org/articles/PMC10531121; pdf:https://europepmc.org/articles/PMC10531121?pdf=render 36134690,https://doi.org/10.1242/dev.200654,Coupled myovascular expansion directs cardiac growth and regeneration.,"DeBenedittis P, Karpurapu A, Henry A, Thomas MC, McCord TJ, Brezitski K, Prasad A, Baker CE, Kobayashi Y, Shah SH, Kontos CD, Tata PR, Lumbers RT, Karra R.",,"Development (Cambridge, England)",2022,2022-09-22,N,Mouse; Cardiomyocyte proliferation; Heart regeneration; Myovascular,,,"Heart regeneration requires multiple cell types to enable cardiomyocyte (CM) proliferation. How these cells interact to create growth niches is unclear. Here, we profile proliferation kinetics of cardiac endothelial cells (CECs) and CMs in the neonatal mouse heart and find that they are spatiotemporally coupled. We show that coupled myovascular expansion during cardiac growth or regeneration is dependent upon VEGF-VEGFR2 signaling, as genetic deletion of Vegfr2 from CECs or inhibition of VEGFA abrogates both CEC and CM proliferation. Repair of cryoinjury displays poor spatial coupling of CEC and CM proliferation. Boosting CEC density after cryoinjury with virus encoding Vegfa enhances regeneration. Using Mendelian randomization, we demonstrate that circulating VEGFA levels are positively linked with human myocardial mass, suggesting that Vegfa can stimulate human cardiac growth. Our work demonstrates the importance of coupled CEC and CM expansion and reveals a myovascular niche that may be therapeutically targeted for heart regeneration.",,pdf:https://journals.biologists.com/dev/article-pdf/149/18/dev200654/2167548/dev200654.pdf; doi:https://doi.org/10.1242/dev.200654; html:https://europepmc.org/articles/PMC10692274; doi:https://doi.org/10.1242/dev.200654 37381004,https://doi.org/10.1186/s12913-023-09545-x,A qualitative descriptive study exploring clinicians' perspectives of the management of older trauma care in rural Australia.,"Ferrah N, Parker C, Ibrahim J, Gabbe B, Cameron P.",,BMC health services research,2023,2023-06-28,Y,Trauma; Rural; Interview; Older Adults,,,"

Background

For older trauma patients who sustain trauma in rural areas, the risk of adverse outcomes associated with advancing age, is compounded by the challenges encountered in rural healthcare such as geographic isolation, lack of resources, and accessibility. Little is known of the experience and challenges faced by rural clinicians who manage trauma in older adults. An understanding of stakeholders' views is paramount to the effective development and implementation of a trauma system inclusive of rural communities. The aim of this descriptive qualitative study was to explore the perspectives of clinicians who provide care to older trauma patients in rural settings.

Method

We conducted semi-structured interviews of health professionals (medical doctors, nurses, paramedics, and allied health professionals) who provide care to older trauma patients in rural Queensland, Australia. A thematic analysis consisting of both inductive and deductive coding approaches, was used to identify and develop themes from interviews.

Results

Fifteen participants took part in the interviews. Three key themes were identified: enablers of trauma care, barriers, and changes to improve trauma care of older people. The resilience of rural residents, and breadth of experience of rural clinicians were strengths identified by participants. The perceived systemic lack of resources, both material and in the workforce, and fragmentation of the health system across the state were barriers to the provision of trauma care to older rural patients. Some changes proposed by participants included tailored education programs that would be taught in rural centres, a dedicated case coordinator for older trauma patients from rural areas, and a centralised system designed to streamline the management of older trauma patients coming from rural regions.

Conclusions

Rural clinicians are important stakeholders who should be included in discussions on adapting trauma guidelines to the rural setting. In this study, participants formulated pertinent and concrete recommendations that should be weighed against the current evidence, and tested in rural centres.",,pdf:https://bmchealthservres.biomedcentral.com/counter/pdf/10.1186/s12913-023-09545-x; doi:https://doi.org/10.1186/s12913-023-09545-x; html:https://europepmc.org/articles/PMC10308762; pdf:https://europepmc.org/articles/PMC10308762?pdf=render -36879385,https://doi.org/10.1097/ta.0000000000003950,Cost-effectiveness of a purpose-built ward environment and new allied health model of care for major trauma.,"Gabbe BJ, Reeder S, Ekegren CL, Mather A, Kimmel L, Cameron PA, Higgins AM.",,The journal of trauma and acute care surgery,2023,2023-03-07,N,,,,"

Background

Targeted rehabilitation within the acute inpatient setting could have a substantial impact on improving outcomes for major trauma patients. The aim of this study was to investigate the cost-effectiveness of the introduction of a purpose-built ward environment, and a new allied health model of care (AHMOC) delivered in the acute inpatient setting, in a major trauma population.

Methods

The statewide trauma registry, the trauma center's data warehouse, and electronic medical record data were used for this observational study. There were three phases: baseline, new ward, and new AHMOC. Cost-effectiveness was measured as cost per quality-adjusted life year using preinjury, hospital discharge, 1-month and 6-month 5-level, EQ-5D utility scores. Total costs included initial acute and inpatient rehabilitation care, as well as outpatient, readmission and ED presentations to 6-months.

Results

Four hundred eleven patients were included. Case-mix was stable between phases. The median (IQR) number of allied health services received by patients was 8 (5-17) at baseline, 10 (5-19) in the new ward phase, and 17 (9-23) in the AHMOC phase. The proportion discharged to rehabilitation was 37% at baseline, 45% with the new ward and 28% with the new AHMOC. Mean (SD) total Australian dollar costs were $69,335 ($141,175) at baseline, $55,943 ($82,706) with the new ward and $37,833 ($49,004) with the AHMOC. The probability of the AHMOC being cost-effective at a willingness-to-pay threshold of $50,000 per quality-adjusted life year was 99.4% compared with baseline and 98% compared with the new ward.

Conclusion

The new allied health model of care was found to be a cost-effective intervention. Uptake of this model of allied health care at other trauma centers has the potential to reduce the cost and burden of major trauma.

Level of evidence

Economic and Value-based Evaluations; Level III.",,doi:https://doi.org/10.1097/TA.0000000000003950 31797917,https://doi.org/10.1038/s41398-019-0635-y,"Novel genome-wide associations for anhedonia, genetic correlation with psychiatric disorders, and polygenic association with brain structure.","Ward J, Lyall LM, Bethlehem RAI, Ferguson A, Strawbridge RJ, Lyall DM, Cullen B, Graham N, Johnston KJA, Bailey MES, Murray GK, Smith DJ.",,Translational psychiatry,2019,2019-12-04,Y,,,,"Anhedonia is a core symptom of several psychiatric disorders but its biological underpinnings are poorly understood. We performed a genome-wide association study of state anhedonia in 375,275 UK Biobank participants and assessed for genetic correlation between anhedonia and neuropsychiatric conditions (major depressive disorder, schizophrenia, bipolar disorder, obsessive compulsive disorder and Parkinson's Disease). We then used a polygenic risk score approach to test for association between genetic loading for anhedonia and both brain structure and brain function. This included: magnetic resonance imaging (MRI) assessments of total grey matter volume, white matter volume, cerebrospinal fluid volume, and 15 cortical/subcortical regions of interest; diffusion tensor imaging (DTI) measures of white matter tract integrity; and functional MRI activity during an emotion processing task. We identified 11 novel loci associated at genome-wide significance with anhedonia, with a SNP heritability estimate (h2SNP) of 5.6%. Strong positive genetic correlations were found between anhedonia and major depressive disorder, schizophrenia and bipolar disorder; but not with obsessive compulsive disorder or Parkinson's Disease. Polygenic risk for anhedonia was associated with poorer brain white matter integrity, smaller total grey matter volume, and smaller volumes of brain regions linked to reward and pleasure processing, including orbito-frontal cortex. In summary, the identification of novel anhedonia-associated loci substantially expands our current understanding of the biological basis of state anhedonia and genetic correlations with several psychiatric disorders confirm the utility of this phenotype as a transdiagnostic marker of vulnerability to mental illness. We also provide the first evidence that genetic risk for state anhedonia influences brain structure, including in regions associated with reward and pleasure processing.",This study assessed for genetic correlation between anhedonia and neuropsychiatric conditions. A polygenic risk score approach was applied to test for association between anhedonia and brain structure and brain function. Findings confirm that using anhedonia as a marker of vulnerability to mental illness. Findings also suggest that genetic risk for state anhedonia influences brain structure,pdf:https://www.nature.com/articles/s41398-019-0635-y.pdf; doi:https://doi.org/10.1038/s41398-019-0635-y; html:https://europepmc.org/articles/PMC6892870; pdf:https://europepmc.org/articles/PMC6892870?pdf=render +36879385,https://doi.org/10.1097/ta.0000000000003950,Cost-effectiveness of a purpose-built ward environment and new allied health model of care for major trauma.,"Gabbe BJ, Reeder S, Ekegren CL, Mather A, Kimmel L, Cameron PA, Higgins AM.",,The journal of trauma and acute care surgery,2023,2023-03-07,N,,,,"

Background

Targeted rehabilitation within the acute inpatient setting could have a substantial impact on improving outcomes for major trauma patients. The aim of this study was to investigate the cost-effectiveness of the introduction of a purpose-built ward environment, and a new allied health model of care (AHMOC) delivered in the acute inpatient setting, in a major trauma population.

Methods

The statewide trauma registry, the trauma center's data warehouse, and electronic medical record data were used for this observational study. There were three phases: baseline, new ward, and new AHMOC. Cost-effectiveness was measured as cost per quality-adjusted life year using preinjury, hospital discharge, 1-month and 6-month 5-level, EQ-5D utility scores. Total costs included initial acute and inpatient rehabilitation care, as well as outpatient, readmission and ED presentations to 6-months.

Results

Four hundred eleven patients were included. Case-mix was stable between phases. The median (IQR) number of allied health services received by patients was 8 (5-17) at baseline, 10 (5-19) in the new ward phase, and 17 (9-23) in the AHMOC phase. The proportion discharged to rehabilitation was 37% at baseline, 45% with the new ward and 28% with the new AHMOC. Mean (SD) total Australian dollar costs were $69,335 ($141,175) at baseline, $55,943 ($82,706) with the new ward and $37,833 ($49,004) with the AHMOC. The probability of the AHMOC being cost-effective at a willingness-to-pay threshold of $50,000 per quality-adjusted life year was 99.4% compared with baseline and 98% compared with the new ward.

Conclusion

The new allied health model of care was found to be a cost-effective intervention. Uptake of this model of allied health care at other trauma centers has the potential to reduce the cost and burden of major trauma.

Level of evidence

Economic and Value-based Evaluations; Level III.",,doi:https://doi.org/10.1097/TA.0000000000003950 35945198,https://doi.org/10.1038/s41467-022-32095-5,Transferability of genetic loci and polygenic scores for cardiometabolic traits in British Pakistani and Bangladeshi individuals.,"Huang QQ, Sallah N, Dunca D, Trivedi B, Hunt KA, Hodgson S, Lambert SA, Arciero E, Wright J, Griffiths C, Trembath RC, Hemingway H, Inouye M, Finer S, van Heel DA, Lumbers RT, Martin HC, Kuchenbaecker K.",,Nature communications,2022,2022-08-09,Y,,,,"Individuals with South Asian ancestry have a higher risk of heart disease than other groups but have been largely excluded from genetic research. Using data from 22,000 British Pakistani and Bangladeshi individuals with linked electronic health records from the Genes & Health cohort, we conducted genome-wide association studies of coronary artery disease and its key risk factors. Using power-adjusted transferability ratios, we found evidence for transferability for the majority of cardiometabolic loci powered to replicate. The performance of polygenic scores was high for lipids and blood pressure, but lower for BMI and coronary artery disease. Adding a polygenic score for coronary artery disease to clinical risk factors showed significant improvement in reclassification. In Mendelian randomisation using transferable loci as instruments, our findings were consistent with results in European-ancestry individuals. Taken together, trait-specific transferability of trait loci between populations is an important consideration with implications for risk prediction and causal inference.",,pdf:https://www.nature.com/articles/s41467-022-32095-5.pdf; doi:https://doi.org/10.1038/s41467-022-32095-5; html:https://europepmc.org/articles/PMC9363492; pdf:https://europepmc.org/articles/PMC9363492?pdf=render -37526977,https://doi.org/10.5830/cvja-2023-037,Yield of family screening in dilated cardiomyopathy within low-income setting: Tanzanian experience.,"Fundikira LS, Julius J, Chillo P, Mayala H, Kifai E, van Laake LW, Kamuhabwa A, Kwesigabo G, Asselbergs FW.",,Cardiovascular journal of Africa,2023,2023-07-25,N,Screening; Dilated cardiomyopathy; First‐degree Relatives,,,"

Background

Dilated cardiomyopathy (DCM) is often familial and screening of relatives is recommended. However, studies on the yield of screening are scarce in developing countries.

Aim

The aim of the study was to identify and characterise First-degree relatives of patients with DCM in Tanzania.

Methods

We recruited first-degree relatives of 57 DCM patients. DCM in the relatives was diagnosed using the 2016 revised definition by the European Society of Cardiology working group on myocardial and pericardial diseases.

Results

We screened 120 first-degree relatives. All were asymptomatic (100%) with a median age of 39.0 years (29.5-49.0), slightly over a half (53.3%) were females and 17 (14.1%) were found to have previously unknown DCM. The mean (± SD) indexed left ventricular end-diastolic volume was significantly higher in relatives with DCM (71 ± 11.5 ml) compared to relatives without DCM (50 ± 11.5) (p = 0.001).

Conclusion

First-degree relatives of patients with DCM are at risk of developing asymptomatic DCM at a young age.",,doi:https://doi.org/10.5830/CVJA-2023-037 29938349,https://doi.org/10.1007/s11892-018-1021-5,Shared Genetic Contribution of Type 2 Diabetes and Cardiovascular Disease: Implications for Prognosis and Treatment.,"Strawbridge RJ, van Zuydam NR.",,Current diabetes reports,2018,2018-06-25,Y,Type 2 diabetes; Ischemic stroke; coronary artery disease; risk factors; Peripheral Artery Disease; Genetics; Mendelian Randomisation,,,"

Purpose of review

The increased cardiovascular disease (CVD) risk in subjects with type 2 diabetes (T2D) is well established. This review collates the available evidence and assesses the shared genetic background between T2D and CVD: the causal contribution of common risk factors to T2D and CVD and how genetics can be used to improve drug development and clinical outcomes.

Recent findings

Large-scale genome-wide association studies (GWAS) of T2D and CVD support a shared genetic background but minimal individual locus overlap. Mendelian randomisation (MR) analyses show that T2D is causal for CVD, but GWAS of CVD, T2D and their common risk factors provided limited evidence for individual locus overlap. Distinct but functionally related pathways were enriched for CVD and T2D genetic associations reflecting the lack of locus overlap and providing some explanation for the variable associations of common risk factors with CVD and T2D from MR analyses.",,pdf:https://link.springer.com/content/pdf/10.1007/s11892-018-1021-5.pdf; doi:https://doi.org/10.1007/s11892-018-1021-5; html:https://europepmc.org/articles/PMC6015804; pdf:https://europepmc.org/articles/PMC6015804?pdf=render +37526977,https://doi.org/10.5830/cvja-2023-037,Yield of family screening in dilated cardiomyopathy within low-income setting: Tanzanian experience.,"Fundikira LS, Julius J, Chillo P, Mayala H, Kifai E, van Laake LW, Kamuhabwa A, Kwesigabo G, Asselbergs FW.",,Cardiovascular journal of Africa,2023,2023-07-25,N,Screening; Dilated cardiomyopathy; First‐degree Relatives,,,"

Background

Dilated cardiomyopathy (DCM) is often familial and screening of relatives is recommended. However, studies on the yield of screening are scarce in developing countries.

Aim

The aim of the study was to identify and characterise First-degree relatives of patients with DCM in Tanzania.

Methods

We recruited first-degree relatives of 57 DCM patients. DCM in the relatives was diagnosed using the 2016 revised definition by the European Society of Cardiology working group on myocardial and pericardial diseases.

Results

We screened 120 first-degree relatives. All were asymptomatic (100%) with a median age of 39.0 years (29.5-49.0), slightly over a half (53.3%) were females and 17 (14.1%) were found to have previously unknown DCM. The mean (± SD) indexed left ventricular end-diastolic volume was significantly higher in relatives with DCM (71 ± 11.5 ml) compared to relatives without DCM (50 ± 11.5) (p = 0.001).

Conclusion

First-degree relatives of patients with DCM are at risk of developing asymptomatic DCM at a young age.",,doi:https://doi.org/10.5830/CVJA-2023-037 36805366,https://doi.org/10.2196/43419,Prediction of Suicidal Behaviors in the Middle-aged Population: Machine Learning Analyses of UK Biobank.,"Wang J, Qiu J, Zhu T, Zeng Y, Yang H, Shang Y, Yin J, Sun Y, Qu Y, Valdimarsdóttir UA, Song H.",,JMIR public health and surveillance,2023,2023-02-20,Y,Sex; Model; Behavior; Genetic susceptibility; Data; Suicide; risk; Machine Learning; Risk Prediction; Cost-effective; Machine Learning Approach; Suicidal Behaviors,,,"

Background

Suicidal behaviors, including suicide deaths and attempts, are major public health concerns. However, previous suicide models required a huge amount of input features, resulting in limited applicability in clinical practice.

Objective

We aimed to construct applicable models (ie, with limited features) for short- and long-term suicidal behavior prediction. We further validated these models among individuals with different genetic risks of suicide.

Methods

Based on the prospective cohort of UK Biobank, we included 223 (0.06%) eligible cases of suicide attempts or deaths, according to hospital inpatient or death register data within 1 year from baseline and randomly selected 4460 (1.18%) controls (1:20) without such records. We similarly identified 833 (0.22%) cases of suicidal behaviors 1 to 6 years from baseline and 16,660 (4.42%) corresponding controls. Based on 143 input features, mainly including sociodemographic, environmental, and psychosocial factors; medical history; and polygenic risk scores (PRS) for suicidality, we applied a bagged balanced light gradient-boosting machine (LightGBM) with stratified 10-fold cross-validation and grid-search to construct the full prediction models for suicide attempts or deaths within 1 year or between 1 and 6 years. The Shapley Additive Explanations (SHAP) approach was used to quantify the importance of input features, and the top 20 features with the highest SHAP values were selected to train the applicable models. The external validity of the established models was assessed among 50,310 individuals who participated in UK Biobank repeated assessments both overall and by the level of PRS for suicidality.

Results

Individuals with suicidal behaviors were on average 56 years old, with equal sex distribution. The application of these full models in the external validation data set demonstrated good model performance, with the area under the receiver operating characteristic (AUROC) curves of 0.919 and 0.892 within 1 year and between 1 and 6 years, respectively. Importantly, the applicable models with the top 20 most important features showed comparable external-validated performance (AUROC curves of 0.901 and 0.885) as the full models, based on which we found that individuals in the top quintile of predicted risk accounted for 91.7% (n=11) and 80.7% (n=25) of all suicidality cases within 1 year and during 1 to 6 years, respectively. We further obtained comparable prediction accuracy when applying these models to subpopulations with different genetic susceptibilities to suicidality. For example, for the 1-year risk prediction, the AUROC curves were 0.907 and 0.885 for the high (>2nd tertile of PRS) and low (<1st) genetic susceptibilities groups, respectively.

Conclusions

We established applicable machine learning-based models for predicting both the short- and long-term risk of suicidality with high accuracy across populations of varying genetic risk for suicide, highlighting a cost-effective method of identifying individuals with a high risk of suicidality.",,pdf:https://publichealth.jmir.org/2023/1/e43419/PDF; doi:https://doi.org/10.2196/43419; html:https://europepmc.org/articles/PMC9989910 36773891,https://doi.org/10.1016/j.jinf.2023.02.012,"Real-world effectiveness of molnupiravir, nirmatrelvir-ritonavir, and sotrovimab on preventing hospital admission among higher-risk patients with COVID-19 in Wales: A retrospective cohort study.","Evans A, Qi C, Adebayo JO, Underwood J, Coulson J, Bailey R, Lyons R, Edwards A, Cooper A, John G, Akbari A.",,The Journal of infection,2023,2023-02-10,Y,Health protection; Public Health; Covid-19,,,"

Objective

To compare the effectiveness of molnupiravir, nirmatrelvir-ritonavir, and sotrovimab with no treatment in preventing hospital admission or death in higher-risk patients infected with SARS-CoV-2 in the community.

Design

Retrospective cohort study of non-hospitalized adult patients with COVID-19 using the Secure Anonymised Information Linkage (SAIL) Databank.

Setting

A real-world cohort study was conducted within the SAIL Databank (a secure trusted research environment containing anonymised, individual, population-scale electronic health record (EHR) data) for the population of Wales, UK.

Participants

Adult patients with COVID-19 in the community, at higher risk of hospitalization and death, testing positive for SARS-CoV-2 between 16th December 2021 and 22nd April 2022.

Interventions

Molnupiravir, nirmatrelvir-ritonavir, and sotrovimab given in the community by local health boards and the National Antiviral Service in Wales.

Main outcome measures

All-cause admission to hospital or death within 28 days of a positive test for SARS-CoV-2.

Statistical analysis

Cox proportional hazard model with treatment status (treated/untreated) as a time-dependent covariate and adjusted for age, sex, number of comorbidities, Welsh Index of Multiple Deprivation, and vaccination status. Secondary subgroup analyses were by treatment type, number of comorbidities, and before and on or after 20th February 2022, when omicron BA.1 and omicron BA.2 were the dominant subvariants in Wales.

Results

Between 16th December 2021 and 22nd April 2022, 7013 higher-risk patients were eligible for inclusion in the study. Of these, 2040 received treatment with molnupiravir (359, 17.6%), nirmatrelvir-ritonavir (602, 29.5%), or sotrovimab (1079, 52.9%). Patients in the treatment group were younger (mean age 53 vs 57 years), had fewer comorbidities, and a higher proportion had received four or more doses of the COVID-19 vaccine (36.3% vs 17.6%). Within 28 days of a positive test, 628 (9.0%) patients were admitted to hospital or died (84 treated and 544 untreated). The primary analysis indicated a lower risk of hospitalization or death at any point within 28 days in treated participants compared to those not receiving treatment. The adjusted hazard rate was 35% (95% CI: 18-49%) lower in treated than untreated participants. There was no indication of the superiority of one treatment over another and no evidence of a reduction in risk of hospitalization or death within 28 days for patients with no or only one comorbidity. In patients treated with sotrovimab, the event rates before and on or after 20th February 2022 were similar (5.0% vs 4.9%) with no significant difference in the hazard ratios for sotrovimab between the time periods.

Conclusions

In higher-risk adult patients in the community with COVID-19, those who received treatment with molnupiravir, nirmatrelvir-ritonavir, or sotrovimab were at lower risk of hospitalization or death than those not receiving treatment.",,pdf:http://www.journalofinfection.com/article/S0163445323000828/pdf; doi:https://doi.org/10.1016/j.jinf.2023.02.012; html:https://europepmc.org/articles/PMC9911979; pdf:https://europepmc.org/articles/PMC9911979?pdf=render 36112916,https://doi.org/10.1177/09622802211055853,Inferring risks of coronavirus transmission from community household data.,"House T, Riley H, Pellis L, Pouwels KB, Bacon S, Eidukas A, Jahanshahi K, Eggo RM, Sarah Walker A.",,Statistical methods in medical research,2022,2022-09-01,Y,Infection; Model; epidemic; risk factors; Covid-19,,,"The response of many governments to the COVID-19 pandemic has involved measures to control within- and between-household transmission, providing motivation to improve understanding of the absolute and relative risks in these contexts. Here, we perform exploratory, residual-based, and transmission-dynamic household analysis of the Office for National Statistics COVID-19 Infection Survey data from 26 April 2020 to 15 July 2021 in England. This provides evidence for: (i) temporally varying rates of introduction of infection into households broadly following the trajectory of the overall epidemic and vaccination programme; (ii) susceptible-Infectious transmission probabilities of within-household transmission in the 15-35% range; (iii) the emergence of the Alpha and Delta variants, with the former being around 50% more infectious than wildtype and 35% less infectious than Delta within households; (iv) significantly (in the range of 25-300%) more risk of bringing infection into the household for workers in patient-facing roles pre-vaccine; (v) increased risk for secondary school-age children of bringing the infection into the household when schools are open; (vi) increased risk for primary school-age children of bringing the infection into the household when schools were open since the emergence of new variants.",,doi:https://doi.org/10.1177/09622802211055853; doi:https://doi.org/10.1177/09622802211055853; html:https://europepmc.org/articles/PMC9465559; pdf:https://europepmc.org/articles/PMC9465559?pdf=render @@ -870,25 +870,25 @@ PMC10686417,https://doi.org/,The impact of restricted provision of publicly fund 33619467,https://doi.org/10.1093/jamiaopen/ooaa047,A semi-supervised approach for rapidly creating clinical biomarker phenotypes in the UK Biobank using different primary care EHR and clinical terminology systems.,"Denaxas S, Shah AD, Mateen BA, Kuan V, Quint JK, Fitzpatrick N, Torralbo A, Fatemifar G, Hemingway H.",,JAMIA open,2020,2020-12-05,Y,Phenotyping; Medical Informatics; Electronic Health Records; Uk Biobank,,,"

Objectives

The UK Biobank (UKB) is making primary care electronic health records (EHRs) for 500 000 participants available for COVID-19-related research. Data are extracted from four sources, recorded using five clinical terminologies and stored in different schemas. The aims of our research were to: (a) develop a semi-supervised approach for bootstrapping EHR phenotyping algorithms in UKB EHR, and (b) to evaluate our approach by implementing and evaluating phenotypes for 31 common biomarkers.

Materials and methods

We describe an algorithmic approach to phenotyping biomarkers in primary care EHR involving (a) bootstrapping definitions using existing phenotypes, (b) excluding generic, rare, or semantically distant terms, (c) forward-mapping terminology terms, (d) expert review, and (e) data extraction. We evaluated the phenotypes by assessing the ability to reproduce known epidemiological associations with all-cause mortality using Cox proportional hazards models.

Results

We created and evaluated phenotyping algorithms for 31 biomarkers many of which are directly related to COVID-19 complications, for example diabetes, cardiovascular disease, respiratory disease. Our algorithm identified 1651 Read v2 and Clinical Terms Version 3 terms and automatically excluded 1228 terms. Clinical review excluded 103 terms and included 44 terms, resulting in 364 terms for data extraction (sensitivity 0.89, specificity 0.92). We extracted 38 190 682 events and identified 220 978 participants with at least one biomarker measured.

Discussion and conclusion

Bootstrapping phenotyping algorithms from similar EHR can potentially address pre-existing methodological concerns that undermine the outputs of biomarker discovery pipelines and provide research-quality phenotyping algorithms.",,pdf:https://academic.oup.com/jamiaopen/article-pdf/3/4/545/36625793/ooaa047.pdf; doi:https://doi.org/10.1093/jamiaopen/ooaa047; html:https://europepmc.org/articles/PMC7717266; pdf:https://europepmc.org/articles/PMC7717266?pdf=render 33262478,https://doi.org/10.1038/s41433-020-01326-8,Risk factors for having diabetic retinopathy at first screening in persons with type 1 diabetes diagnosed under 18 years of age.,"Rafferty J, Owens DR, Luzio SD, Watts P, Akbari A, Thomas RL.",,"Eye (London, England)",2021,2020-12-01,N,,,,"

Objective

To determine the risk factors for having diabetic retinopathy (DR) in children and young people (CYP) with type 1 diabetes (T1DM) at first screening.

Methods

Records from the Diabetes Eye Screening Wales (DESW) service for people in Wales, UK, with T1DM diagnosed under age 18 years were combined with other electronic health record (EHR) data in the Secure Anonymised Information Linkage (SAIL) Databank. Data close to the screening date were collected, and risk factors derived from multivariate, multinomial logistic regression modelling.

Results

Data from 4172 persons, with median (lower quartile, upper quartile) age 16.3 (13.0, 22.3) years and duration of diabetes 6.6 (2.3, 12.3) years were analysed. 62.6% (n = 2613) had no DR, 26.7% (n = 1112) background DR, and 10.7% (n = 447) had referable DR (RDR). No RDR was observed under 19 years of age. Factors associated with an increased risk of DR were diabetes duration, elevated HbA1c, and diastolic blood pressure. People diagnosed with T1DM at 12 years or older had an additional risk for each year they had diabetes compared to those diagnosed before age 12 controlling for the diabetes duration (odds ratios 1.23 and 1.34, respectively).

Conclusions

This study found that 37.4% of the study cohort had DR at first screening, the risk being greater the longer the duration of diabetes or higher the HbA1c and diastolic blood pressure. In addition, people diagnosed at 12 years of age or over were more likely to have DR with each additional year with diabetes.",,pdf:https://www.nature.com/articles/s41433-020-01326-8.pdf; doi:https://doi.org/10.1038/s41433-020-01326-8; html:https://europepmc.org/articles/PMC8452782; pdf:https://europepmc.org/articles/PMC8452782?pdf=render; doi:https://doi.org/10.1038/s41433-020-01326-8 30423068,https://doi.org/10.1093/bioinformatics/bty605,Ontology-based validation and identification of regulatory phenotypes.,"Kulmanov M, Schofield PN, Gkoutos GV, Hoehndorf R.",,"Bioinformatics (Oxford, England)",2018,2018-09-01,Y,,"Applied Analytics, The Human Phenome",,"

Motivation

Function annotations of gene products, and phenotype annotations of genotypes, provide valuable information about molecular mechanisms that can be utilized by computational methods to identify functional and phenotypic relatedness, improve our understanding of disease and pathobiology, and lead to discovery of drug targets. Identifying functions and phenotypes commonly requires experiments which are time-consuming and expensive to carry out; creating the annotations additionally requires a curator to make an assertion based on reported evidence. Support to validate the mutual consistency of functional and phenotype annotations as well as a computational method to predict phenotypes from function annotations, would greatly improve the utility of function annotations.

Results

We developed a novel ontology-based method to validate the mutual consistency of function and phenotype annotations. We apply our method to mouse and human annotations, and identify several inconsistencies that can be resolved to improve overall annotation quality. We also apply our method to the rule-based prediction of regulatory phenotypes from functions and demonstrate that we can predict these phenotypes with Fmax of up to 0.647.

Availability and implementation

https://github.com/bio-ontology-research-group/phenogocon.",,pdf:https://academic.oup.com/bioinformatics/article-pdf/34/17/i857/25702307/bty605.pdf; doi:https://doi.org/10.1093/bioinformatics/bty605; html:https://europepmc.org/articles/PMC6129279; pdf:https://europepmc.org/articles/PMC6129279?pdf=render -37907891,https://doi.org/10.1186/s12888-023-05217-6,"Association between 5-min Apgar score and attention deficit hyperactivity disorder: a Scotland-wide record linkage study of 758,423 school children.","Bala JJ, Bala JD, Pell JP, Fleming M.",,BMC psychiatry,2023,2023-10-31,Y,attention deficit disorder with hyperactivity; Cohort studies; Education; Medical Record Linkage; Apgar Score,,,"

Background

Attention-deficit hyperactivity disorder (ADHD) affects around 1 in 20 children and is associated with life-long sequelae. Previous studies of the association between Apgar score and ADHD have reported inconsistent findings.

Methods

Record linkage of maternity, prescribing and school pupil census databases was used to conduct a population e-cohort study of singleton children born in Scotland and attending school in Scotland at any point between 2009 and 2013. Binary logistic regression analysis was used to investigate the association between 5-min Apgar score and treated ADHD adjusting for sociodemographic and maternity confounders.

Results

Of the 758,423 children, 7,292 (0.96%) received ADHD medication. The results suggested a potential dose-response relationship between Apgar score and treated ADHD independent of confounders. Referent to an Apgar score of 10, risk of treated ADHD was higher for scores of 0-3 (adjusted OR 1.76, 95% CI 1.32-2.34), 4-6 (adjusted OR 1.50, 95% CI 1.21-1.86) and even 7-9 (adjusted OR 1.26, 95% CI 1.18-1.36) which are traditionally considered within the normal range.

Conclusions

In addition to reinforcing the need to maximise Apgar score through good obstetric practice, the findings suggest that Apgar score may be useful in predicting future risk of ADHD and therefore facilitating early diagnosis and treatment.",,doi:https://doi.org/10.1186/s12888-023-05217-6; html:https://europepmc.org/articles/PMC10619264; pdf:https://europepmc.org/articles/PMC10619264?pdf=render 34135032,https://doi.org/10.1136/bmjopen-2020-043906,Realising the full potential of data-enabled trials in the UK: a call for action.,"Sydes MR, Barbachano Y, Bowman L, Denwood T, Farmer A, Garfield-Birkbeck S, Gibson M, Gulliford MC, Harrison DA, Hewitt C, Logue J, Navaie W, Norrie J, O'Kane M, Quint JK, Rycroft-Malone J, Sheffield J, Smeeth L, Sullivan F, Tizzard J, Walker P, Wilding J, Williamson PR, Landray M, Morris A, Walker RR, Williams HC, Valentine J, Data Enabled Trials Group Workshop Group members.",,BMJ open,2021,2021-06-16,Y,Clinical Trials; Health Informatics; Statistics & Research Methods,,,"

Rationale

Clinical trials are the gold standard for testing interventions. COVID-19 has further raised their public profile and emphasised the need to deliver better, faster, more efficient trials for patient benefit. Considerable overlap exists between data required for trials and data already collected routinely in electronic healthcare records (EHRs). Opportunities exist to use these in innovative ways to decrease duplication of effort and speed trial recruitment, conduct and follow-up.

Approach

The National Institute of Health Research (NIHR), Health Data Research UK and Clinical Practice Research Datalink co-organised a national workshop to accelerate the agenda for 'data-enabled clinical trials'. Showcasing successful examples and imagining future possibilities, the plenary talks, panel discussions, group discussions and case studies covered: design/feasibility; recruitment; conduct/follow-up; collecting benefits/harms; and analysis/interpretation.

Reflection

Some notable studies have successfully accessed and used EHR to identify potential recruits, support randomised trials, deliver interventions and supplement/replace trial-specific follow-up. Some outcome measures are already reliably collected; others, like safety, need detailed work to meet regulatory reporting requirements. There is a clear need for system interoperability and a 'route map' to identify and access the necessary datasets. Researchers running regulatory-facing trials must carefully consider how data quality and integrity would be assessed. An experience-sharing forum could stimulate wider adoption of EHR-based methods in trial design and execution.

Discussion

EHR offer opportunities to better plan clinical trials, assess patients and capture data more efficiently, reducing research waste and increasing focus on each trial's specific challenges. The short-term emphasis should be on facilitating patient recruitment and for postmarketing authorisation trials where research-relevant outcome measures are readily collectable. Sharing of case studies is encouraged. The workshop directly informed NIHR's funding call for ambitious data-enabled trials at scale. There is the opportunity for the UK to build upon existing data science capabilities to identify, recruit and monitor patients in trials at scale.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/6/e043906.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-043906; html:https://europepmc.org/articles/PMC8211043; pdf:https://europepmc.org/articles/PMC8211043?pdf=render -37657941,https://doi.org/10.1212/wnl.0000000000207777,Exploring the Role of Plasma Lipids and Statin Interventions on Multiple Sclerosis Risk and Severity: A Mendelian Randomization Study.,"Almramhi MM, Finan C, Storm CS, Schmidt AF, Kia DA, Coneys R, Chopade S, Hingorani AD, Wood NW.",,Neurology,2023,2023-09-01,Y,,,,"

Background and objectives

There has been considerable interest in statins because of their pleiotropic effects beyond their lipid-lowering properties. Many of these pleiotropic effects are predominantly ascribed to Rho small guanosine triphosphatases (Rho GTPases) proteins. We aimed to genetically investigate the role of lipids and statin interventions on multiple sclerosis (MS) risk and severity.

Method

We used two-sample Mendelian randomization (MR) to investigate (1) the causal role of genetically mimic both cholesterol-dependent (through low-density lipoprotein cholesterol (LDL-C) and cholesterol biosynthesis pathway) and cholesterol-independent (through Rho GTPases) effects of statins on MS risk and MS severity, (2) the causal link between lipids (high-density lipoprotein cholesterol [HDL-C] and triglycerides [TG]) levels and MS risk and severity, and (3) the reverse causation between lipid fractions and MS risk. We used summary statistics from the Global Lipids Genetics Consortium (GLGC), eQTLGen Consortium, and the International MS Genetics Consortium (IMSGC) for lipids, expression quantitative trait loci, and MS, respectively (GLGC: n = 188,577; eQTLGen: n = 31,684; IMSGC (MS risk): n = 41,505; IMSGC (MS severity): n = 7,069).

Results

The results of MR using the inverse-variance weighted method show that genetically predicted RAC2, a member of cholesterol-independent pathway (OR 0.86 [95% CI 0.78-0.95], p-value 3.80E-03), is implicated causally in reducing MS risk. We found no evidence for the causal role of LDL-C and the member of cholesterol biosynthesis pathway on MS risk. The MR results also show that lifelong higher HDL-C (OR 1.14 [95% CI 1.04-1.26], p-value 7.94E-03) increases MS risk but TG was not. Furthermore, we found no evidence for the causal role of lipids and genetically mimicked statins on MS severity. There is no evidence of reverse causation between MS risk and lipids.

Discussion

Evidence from this study suggests that RAC2 is a genetic modifier of MS risk. Because RAC2 has been reported to mediate some of the pleiotropic effects of statins, we suggest that statins may reduce MS risk through a cholesterol-independent pathway (that is, RAC2-related mechanism(s)). MR analyses also support a causal effect of HDL-C on MS risk.",,pdf:https://n.neurology.org/content/neurology/early/2023/09/01/WNL.0000000000207777.full.pdf; doi:https://doi.org/10.1212/WNL.0000000000207777; html:https://europepmc.org/articles/PMC10624499; pdf:https://europepmc.org/articles/PMC10624499?pdf=render +37907891,https://doi.org/10.1186/s12888-023-05217-6,"Association between 5-min Apgar score and attention deficit hyperactivity disorder: a Scotland-wide record linkage study of 758,423 school children.","Bala JJ, Bala JD, Pell JP, Fleming M.",,BMC psychiatry,2023,2023-10-31,Y,attention deficit disorder with hyperactivity; Cohort studies; Education; Medical Record Linkage; Apgar Score,,,"

Background

Attention-deficit hyperactivity disorder (ADHD) affects around 1 in 20 children and is associated with life-long sequelae. Previous studies of the association between Apgar score and ADHD have reported inconsistent findings.

Methods

Record linkage of maternity, prescribing and school pupil census databases was used to conduct a population e-cohort study of singleton children born in Scotland and attending school in Scotland at any point between 2009 and 2013. Binary logistic regression analysis was used to investigate the association between 5-min Apgar score and treated ADHD adjusting for sociodemographic and maternity confounders.

Results

Of the 758,423 children, 7,292 (0.96%) received ADHD medication. The results suggested a potential dose-response relationship between Apgar score and treated ADHD independent of confounders. Referent to an Apgar score of 10, risk of treated ADHD was higher for scores of 0-3 (adjusted OR 1.76, 95% CI 1.32-2.34), 4-6 (adjusted OR 1.50, 95% CI 1.21-1.86) and even 7-9 (adjusted OR 1.26, 95% CI 1.18-1.36) which are traditionally considered within the normal range.

Conclusions

In addition to reinforcing the need to maximise Apgar score through good obstetric practice, the findings suggest that Apgar score may be useful in predicting future risk of ADHD and therefore facilitating early diagnosis and treatment.",,doi:https://doi.org/10.1186/s12888-023-05217-6; html:https://europepmc.org/articles/PMC10619264; pdf:https://europepmc.org/articles/PMC10619264?pdf=render 37042240,https://doi.org/10.1161/circimaging.122.014519,Explainable Artificial Intelligence and Cardiac Imaging: Toward More Interpretable Models.,"Salih A, Boscolo Galazzo I, Gkontra P, Lee AM, Lekadir K, Raisi-Estabragh Z, Petersen SE.",,Circulation. Cardiovascular imaging,2023,2023-04-12,N,Artificial intelligence; Diagnostic Imaging; Machine Learning; Cardiac Imaging Techniques,,,"Artificial intelligence applications have shown success in different medical and health care domains, and cardiac imaging is no exception. However, some machine learning models, especially deep learning, are considered black box as they do not provide an explanation or rationale for model outcomes. Complexity and vagueness in these models necessitate a transition to explainable artificial intelligence (XAI) methods to ensure that model results are both transparent and understandable to end users. In cardiac imaging studies, there are a limited number of papers that use XAI methodologies. This article provides a comprehensive literature review of state-of-the-art works using XAI methods for cardiac imaging. Moreover, it provides simple and comprehensive guidelines on XAI. Finally, open issues and directions for XAI in cardiac imaging are discussed.",,doi:https://doi.org/10.1161/CIRCIMAGING.122.014519 29925668,https://doi.org/10.1136/jech-2017-210370,Emergency hospital admissions associated with a non-randomised housing intervention meeting national housing quality standards: a longitudinal data linkage study.,"Rodgers SE, Bailey R, Johnson R, Berridge D, Poortinga W, Lannon S, Smith R, Lyons RA.",,Journal of epidemiology and community health,2018,2018-06-20,Y,Morbidity; Health Services; Public Health; Housing; Longitudinal Studies,Improving Public Health,,"

Background

We investigated tenant healthcare utilisation associated with upgrading 8558 council houses to a national quality standard. Homes received multiple internal and external improvements and were analysed using repeated measures of healthcare utilisation.

Methods

The primary outcome was emergency hospital admissions for cardiorespiratory conditions and injuries for residents aged 60 years and over. Secondary outcomes included each of the separate conditions, for tenants aged 60 and over, and for all ages. Council home address and intervention records for eight housing cointerventions were anonymously linked to demographic data, hospital admissions and deaths for individuals in a dynamic cohort. Counts of health events were analysed using multilevel regression models to investigate associations between receipt of each housing improvement, adjusting for potential confounding factors and regional trends.

Results

Residents aged 60 years and over living in homes when improvements were made were associated with up to 39% fewer admissions compared with those living in homes that were not upgraded (incidence rate ratio=0.61, 95% CI 0.53 to 0.72). Reduced admissions were associated with electrical systems, windows and doors, wall insulation, and garden paths. There were small non-significant reductions for the primary outcome associated with upgrading heating, adequate loft insulation, new kitchens and new bathrooms.

Conclusion

Results suggest that hospital admissions can be avoided through improving whole home quality standards. This is the first large-scale longitudinal evaluation of a whole home intervention that has evaluated multiple improvement elements using individual-level objective routine health data.",,pdf:https://jech.bmj.com/content/jech/72/10/896.full.pdf; doi:https://doi.org/10.1136/jech-2017-210370; html:https://europepmc.org/articles/PMC6161658; pdf:https://europepmc.org/articles/PMC6161658?pdf=render +37657941,https://doi.org/10.1212/wnl.0000000000207777,Exploring the Role of Plasma Lipids and Statin Interventions on Multiple Sclerosis Risk and Severity: A Mendelian Randomization Study.,"Almramhi MM, Finan C, Storm CS, Schmidt AF, Kia DA, Coneys R, Chopade S, Hingorani AD, Wood NW.",,Neurology,2023,2023-09-01,Y,,,,"

Background and objectives

There has been considerable interest in statins because of their pleiotropic effects beyond their lipid-lowering properties. Many of these pleiotropic effects are predominantly ascribed to Rho small guanosine triphosphatases (Rho GTPases) proteins. We aimed to genetically investigate the role of lipids and statin interventions on multiple sclerosis (MS) risk and severity.

Method

We used two-sample Mendelian randomization (MR) to investigate (1) the causal role of genetically mimic both cholesterol-dependent (through low-density lipoprotein cholesterol (LDL-C) and cholesterol biosynthesis pathway) and cholesterol-independent (through Rho GTPases) effects of statins on MS risk and MS severity, (2) the causal link between lipids (high-density lipoprotein cholesterol [HDL-C] and triglycerides [TG]) levels and MS risk and severity, and (3) the reverse causation between lipid fractions and MS risk. We used summary statistics from the Global Lipids Genetics Consortium (GLGC), eQTLGen Consortium, and the International MS Genetics Consortium (IMSGC) for lipids, expression quantitative trait loci, and MS, respectively (GLGC: n = 188,577; eQTLGen: n = 31,684; IMSGC (MS risk): n = 41,505; IMSGC (MS severity): n = 7,069).

Results

The results of MR using the inverse-variance weighted method show that genetically predicted RAC2, a member of cholesterol-independent pathway (OR 0.86 [95% CI 0.78-0.95], p-value 3.80E-03), is implicated causally in reducing MS risk. We found no evidence for the causal role of LDL-C and the member of cholesterol biosynthesis pathway on MS risk. The MR results also show that lifelong higher HDL-C (OR 1.14 [95% CI 1.04-1.26], p-value 7.94E-03) increases MS risk but TG was not. Furthermore, we found no evidence for the causal role of lipids and genetically mimicked statins on MS severity. There is no evidence of reverse causation between MS risk and lipids.

Discussion

Evidence from this study suggests that RAC2 is a genetic modifier of MS risk. Because RAC2 has been reported to mediate some of the pleiotropic effects of statins, we suggest that statins may reduce MS risk through a cholesterol-independent pathway (that is, RAC2-related mechanism(s)). MR analyses also support a causal effect of HDL-C on MS risk.",,pdf:https://n.neurology.org/content/neurology/early/2023/09/01/WNL.0000000000207777.full.pdf; doi:https://doi.org/10.1212/WNL.0000000000207777; html:https://europepmc.org/articles/PMC10624499; pdf:https://europepmc.org/articles/PMC10624499?pdf=render 36620207,https://doi.org/10.3389/fphys.2022.1089343,Incorporating structural abnormalities in equivalent dipole layer based ECG simulations.,"Boonstra MJ, Oostendorp TF, Roudijk RW, Kloosterman M, Asselbergs FW, Loh P, Van Dam PM.",,Frontiers in physiology,2022,2022-12-22,Y,Simulation; Myocardial Disease; Electrocardiogram (Ecg); Cardiac Activation; Ecgsim; Equivalent Dipole Layer,,,"Introduction: Electrical activity of the myocardium is recorded with the 12-lead ECG. ECG simulations can improve our understanding of the relation between abnormal ventricular activation in diseased myocardium and body surface potentials (BSP). However, in equivalent dipole layer (EDL)-based ECG simulations, the presence of diseased myocardium breaks the equivalence of the dipole layer. To simulate diseased myocardium, patches with altered electrophysiological characteristics were incorporated within the model. The relation between diseased myocardium and corresponding BSP was investigated in a simulation study. Methods: Activation sequences in normal and diseased myocardium were simulated and corresponding 64-lead BSP were computed in four models with distinct patch locations. QRS-complexes were compared using correlation coefficient (CC). The effect of different types of patch activation was assessed. Of one patient, simulated electrograms were compared to electrograms recorded during invasive electro-anatomical mapping. Results: Hundred-fifty-three abnormal activation sequences were simulated. Median QRS-CC of delayed versus dyssynchronous were significantly different (1.00 vs. 0.97, p < 0.001). Depending on the location of the patch, BSP leads were affected differently. Within diseased regions, fragmentation, low bipolar voltages and late potentials were observed in both recorded and simulated electrograms. Discussion: A novel method to simulate cardiomyopathy in EDL-based ECG simulations was established and evaluated. The new patch-based approach created a realistic relation between ECG waveforms and underlying activation sequences. Findings in the simulated cases were in agreement with clinical observations. With this method, our understanding of disease progression in cardiomyopathies may be further improved and used in advanced inverse ECG procedures.",,pdf:https://www.frontiersin.org/articles/10.3389/fphys.2022.1089343/pdf; doi:https://doi.org/10.3389/fphys.2022.1089343; html:https://europepmc.org/articles/PMC9814485; pdf:https://europepmc.org/articles/PMC9814485?pdf=render 36475361,https://doi.org/10.1302/2633-1462.312.bjo-2022-0130.r1,Variation in timely surgery for severe open tibial fractures by time and place of presentation in England from 2012 to 2019 : a cohort study using data collected nationally by the Trauma Audit and Research Network.,"Shah A, Judge A, Griffin XL.",,Bone & joint open,2022,2022-12-01,Y,Trauma; Sensitivity analysis; Debridement; Logistic regression; Cohort study; Orthopaedics; Injury Severity Score; Health Care Quality; Soft-tissue; Open Fracture; Tarn; Regression Analyses; Open Fractures Of The Tibia,,,"

Aims

Several studies have reported that patients presenting during the evening or weekend have poorer quality healthcare. Our objective was to examine how timely surgery for patients with severe open tibial fracture varies by day and time of presentation and by type of hospital. This cohort study included patients with severe open tibial fractures from the Trauma Audit and Research Network (TARN).

Methods

Provision of prompt surgery (debridement within 12 hours and soft-tissue coverage in 72 hours) was examined, using multivariate logistic regression to derive adjusted risk ratios (RRs). Time was categorized into three eight-hour intervals for each day of the week. The models were adjusted for treatment in a major trauma centre (MTC), sex, age, year of presentation, injury severity score, injury mechanism, and number of operations each patient received.

Results

We studied 8,258 patients from 175 hospitals. Patients presenting during the day (08:00 to 15:59; risk ratio (RR) 1.11, 95% confidence interval (CI) 1.02 to 1.20) were more likely to receive debridement within 12 hours, and patients presenting at night (16:00 to 23:59; RR 0.56, 95% CI 0.51 to 0.62) were less likely to achieve the target; triage to a MTC had no effect. Day of presentation was associated with soft-tissue coverage within 72 hours; patients presenting on a Thursday or Friday being less likely to receive this surgery within 72 hours (Thursday RR 0.88, 95% CI 0.81 to 0.97; Friday RR 0.89, 95% CI 0.81 to 0.98), and the standard less likely to be achieved for those treated in 'non-MTC' hospitals (RR 0.76, 95% CI 0.70 to 0.82).

Conclusion

Variations in care were observed for timely surgery for severe open tibial fractures with debridement surgery affected by time of presentation and soft-tissue coverage affected by day of presentation and type of hospital. The variation is unwarranted and highlights that there are opportunities to substantially improve the delivery and quality of care for patients with severe open tibial fracture.Cite this article: Bone Jt Open 2022;3(12):941-952.",,pdf:https://boneandjoint.org.uk/article/10.1302/2633-1462.312.BJO-2022-0130.R1/pdf; doi:https://doi.org/10.1302/2633-1462.312.BJO-2022-0130.R1; html:https://europepmc.org/articles/PMC9783273; pdf:https://europepmc.org/articles/PMC9783273?pdf=render 37105743,https://doi.org/10.3399/bjgp.2022.0353,Impact of COVID-19 pandemic on incidence of long-term conditions in Wales: a population data linkage study using primary and secondary care health records.,"Qi C, Osborne T, Bailey R, Cooper A, Hollinghurst JP, Akbari A, Crowder R, Peters H, Law RJ, Lewis R, Smith D, Edwards A, Lyons RA.",,The British journal of general practice : the journal of the Royal College of General Practitioners,2023,2023-04-27,Y,Diagnosis; Chronic disease; Anxiety; Primary Health Care; Covid-19,,,"

Background

The COVID-19 pandemic has directly and indirectly had an impact on health service provision owing to surges and sustained pressures on the system. The effects of these pressures on the management of long-term or chronic conditions are not fully understood.

Aim

To explore the effects of COVID-19 on the recorded incidence of 17 long-term conditions.

Design and setting

This was an observational retrospective population data linkage study on the population of Wales using primary and secondary care data within the Secure Anonymised Information Linkage (SAIL) Databank.

Method

Monthly rates of new diagnosis between 2000 and 2021 are presented for each long-term condition. Incidence rates post-2020 were compared with expected rates predicted using time series modelling of pre-2020 trends. The proportion of annual incidence is presented by sociodemographic factors: age, sex, social deprivation, ethnicity, frailty, and learning disability.

Results

A total of 5 476 012 diagnoses from 2 257 992 individuals are included. Incidence rates from 2020 to 2021 were lower than mean expected rates across all conditions. The largest relative deficit in incidence was in chronic obstructive pulmonary disease corresponding to 343 (95% confidence interval = 230 to 456) undiagnosed patients per 100 000 population, followed by depression, type 2 diabetes, hypertension, anxiety disorders, and asthma. A GP practice of 10 000 patients might have over 400 undiagnosed long-term conditions. No notable differences between sociodemographic profiles of post- and pre-2020 incidences were observed.

Conclusion

There is a potential backlog of undiagnosed patients with multiple long-term conditions. Resources are required to tackle anticipated workload as part of COVID-19 recovery, particularly in primary care.",,pdf:https://bjgp.org/content/bjgp/early/2023/03/06/BJGP.2022.0353.full.pdf; doi:https://doi.org/10.3399/BJGP.2022.0353; html:https://europepmc.org/articles/PMC9997656; pdf:https://europepmc.org/articles/PMC9997656?pdf=render 32310142,https://doi.org/10.2196/14306,"Objective Characterization of Activity, Sleep, and Circadian Rhythm Patterns Using a Wrist-Worn Actigraphy Sensor: Insights Into Posttraumatic Stress Disorder.","Tsanas A, Woodward E, Ehlers A.",,JMIR mHealth and uHealth,2020,2020-04-20,Y,Sleep; Posttraumatic Stress Disorder; actigraphy; Wearable Technology; Geneactiv,,,"

Background

Wearables have been gaining increasing momentum and have enormous potential to provide insights into daily life behaviors and longitudinal health monitoring. However, to date, there is still a lack of principled algorithmic framework to facilitate the analysis of actigraphy and objectively characterize day-by-day data patterns, particularly in cohorts with sleep problems.

Objective

This study aimed to propose a principled algorithmic framework for the assessment of activity, sleep, and circadian rhythm patterns in people with posttraumatic stress disorder (PTSD), a mental disorder with long-lasting distressing symptoms such as intrusive memories, avoidance behaviors, and sleep disturbance. In clinical practice, these symptoms are typically assessed using retrospective self-reports that are prone to recall bias. The aim of this study was to develop objective measures from patients' everyday lives, which could potentially considerably enhance the understanding of symptoms, behaviors, and treatment effects.

Methods

Using a wrist-worn sensor, we recorded actigraphy, light, and temperature data over 7 consecutive days from three groups: 42 people diagnosed with PTSD, 43 traumatized controls, and 30 nontraumatized controls. The participants also completed a daily sleep diary over 7 days and the standardized Pittsburgh Sleep Quality Index questionnaire. We developed a novel approach to automatically determine sleep onset and offset, which can also capture awakenings that are crucial for assessing sleep quality. Moreover, we introduced a new intuitive methodology facilitating actigraphy exploration and characterize day-by-day data across 49 activity, sleep, and circadian rhythm patterns.

Results

We demonstrate that the new sleep detection algorithm closely matches the sleep onset and offset against the participants' sleep diaries consistently outperforming an existing open-access widely used approach. Participants with PTSD exhibited considerably more fragmented sleep patterns (as indicated by greater nocturnal activity, including awakenings) and greater intraday variability compared with traumatized and nontraumatized control groups, showing statistically significant (P<.05) and strong associations (|R|>0.3).

Conclusions

This study lays the foundation for objective assessment of activity, sleep, and circadian rhythm patterns using passively collected data from a wrist-worn sensor, facilitating large community studies to monitor longitudinally healthy and pathological cohorts under free-living conditions. These findings may be useful in clinical PTSD assessment and could inform therapy and monitoring of treatment effects.",,doi:https://doi.org/10.2196/14306; doi:https://doi.org/10.2196/14306; html:https://europepmc.org/articles/PMC7199134 -37859783,https://doi.org/10.1136/bmjmed-2023-000554,"Performance of polygenic risk scores in screening, prediction, and risk stratification: secondary analysis of data in the Polygenic Score Catalog.","Hingorani AD, Gratton J, Finan C, Schmidt AF, Patel R, Sofat R, Kuan V, Langenberg C, Hemingway H, Morris JK, Wald NJ.",,BMJ medicine,2023,2023-10-17,Y,Public Health; Preventive Medicine,,,"

Objective

To clarify the performance of polygenic risk scores in population screening, individual risk prediction, and population risk stratification.

Design

Secondary analysis of data in the Polygenic Score Catalog.

Setting

Polygenic Score Catalog, April 2022. Secondary analysis of 3915 performance metric estimates for 926 polygenic risk scores for 310 diseases to generate estimates of performance in population screening, individual risk, and population risk stratification.

Participants

Individuals contributing to the published studies in the Polygenic Score Catalog.

Main outcome measures

Detection rate for a 5% false positive rate (DR5) and the population odds of becoming affected given a positive result; individual odds of becoming affected for a person with a particular polygenic score; and odds of becoming affected for groups of individuals in different portions of a polygenic risk score distribution. Coronary artery disease and breast cancer were used as illustrative examples.

Results

For performance in population screening, median DR5 for all polygenic risk scores and all diseases studied was 11% (interquartile range 8-18%). Median DR5 was 12% (9-19%) for polygenic risk scores for coronary artery disease and 10% (9-12%) for breast cancer. The population odds of becoming affected given a positive results were 1:8 for coronary artery disease and 1:21 for breast cancer, with background 10 year odds of 1:19 and 1:41, respectively, which are typical for these diseases at age 50. For individual risk prediction, the corresponding 10 year odds of becoming affected for individuals aged 50 with a polygenic risk score at the 2.5th, 25th, 75th, and 97.5th centiles were 1:54, 1:29, 1:15, and 1:8 for coronary artery disease and 1:91, 1:56, 1:34, and 1:21 for breast cancer. In terms of population risk stratification, at age 50, the risk of coronary artery disease was divided into five groups, with 10 year odds of 1:41 and 1:11 for the lowest and highest quintile groups, respectively. The 10 year odds was 1:7 for the upper 2.5% of the polygenic risk score distribution for coronary artery disease, a group that contributed 7% of cases. The corresponding estimates for breast cancer were 1:72 and 1:26 for the lowest and highest quintile groups, and 1:19 for the upper 2.5% of the distribution, which contributed 6% of cases.

Conclusion

Polygenic risk scores performed poorly in population screening, individual risk prediction, and population risk stratification. Strong claims about the effect of polygenic risk scores on healthcare seem to be disproportionate to their performance.",,doi:https://doi.org/10.1136/bmjmed-2023-000554; html:https://europepmc.org/articles/PMC10582890; pdf:https://europepmc.org/articles/PMC10582890?pdf=render 33780550,https://doi.org/10.1111/anae.15457,Impact of a physician - critical care practitioner pre-hospital service in Wales on trauma survival: a retrospective analysis of linked registry data.,"Lyons J, Gabbe BJ, Rawlinson D, Lockey D, Fry RJ, Akbari A, Lyons RA.",,Anaesthesia,2021,2021-03-29,N,Trauma; Survival; Critical Care; Pre-hospital Care,,,"The Emergency Medical Retrieval and Transfer Service for Wales launched in 2015. This service delivers senior pre-hospital doctors and advanced critical care practitioners to the scene of time-critical life- and limb-threatening incidents to provide advanced decision-making and pre-hospital clinical care. The impact of the service on 30-day mortality was evaluated retrospectively using a data linkage system. The study included patients who sustained moderate-to-severe blunt traumatic injuries (injury severity score ≥ 9) between 27 April 2015 and 30 November 2018. The association between pre-hospital management by the Emergency Medical Retrieval and Transfer Service and 30-day mortality was assessed using multivariable logistic regression. In total, data from 4035 patients were analysed, of which 412 (10%) were treated by the Emergency Medical Retrieval and Transfer Service. A greater proportion of patients treated by the Emergency Medical Retrieval and Transfer Service had an injury severity score ≥ 16 and Glasgow coma scale ≤ 12 (288 (70%) vs. 1435 (40%) and 126 (31%) vs. 325 (9%), respectively). The unadjusted 30-day mortality rate was 11.7% for patients managed by the Emergency Medical Retrieval and Transfer Service compared with 9.6% for patients managed by standard pre-hospital care services. However, after adjustment for differences in case-mix, the 30-day mortality rate for patients treated by the Emergency Medical Retrieval and Transfer Service was 37% lower (adjusted odds ratio 0.63 (95%CI 0.41-0.97); p = 0.037). The introduction of an emergency medical retrieval service was associated with a reduction in 30-day mortality for patients with blunt traumatic injury.",,pdf:https://cronfa.swan.ac.uk/Record/cronfa56616/Download/56616__19761__8c6edaf906b846a69c8b19bdb94d015d.pdf; doi:https://doi.org/10.1111/anae.15457 +37859783,https://doi.org/10.1136/bmjmed-2023-000554,"Performance of polygenic risk scores in screening, prediction, and risk stratification: secondary analysis of data in the Polygenic Score Catalog.","Hingorani AD, Gratton J, Finan C, Schmidt AF, Patel R, Sofat R, Kuan V, Langenberg C, Hemingway H, Morris JK, Wald NJ.",,BMJ medicine,2023,2023-10-17,Y,Public Health; Preventive Medicine,,,"

Objective

To clarify the performance of polygenic risk scores in population screening, individual risk prediction, and population risk stratification.

Design

Secondary analysis of data in the Polygenic Score Catalog.

Setting

Polygenic Score Catalog, April 2022. Secondary analysis of 3915 performance metric estimates for 926 polygenic risk scores for 310 diseases to generate estimates of performance in population screening, individual risk, and population risk stratification.

Participants

Individuals contributing to the published studies in the Polygenic Score Catalog.

Main outcome measures

Detection rate for a 5% false positive rate (DR5) and the population odds of becoming affected given a positive result; individual odds of becoming affected for a person with a particular polygenic score; and odds of becoming affected for groups of individuals in different portions of a polygenic risk score distribution. Coronary artery disease and breast cancer were used as illustrative examples.

Results

For performance in population screening, median DR5 for all polygenic risk scores and all diseases studied was 11% (interquartile range 8-18%). Median DR5 was 12% (9-19%) for polygenic risk scores for coronary artery disease and 10% (9-12%) for breast cancer. The population odds of becoming affected given a positive results were 1:8 for coronary artery disease and 1:21 for breast cancer, with background 10 year odds of 1:19 and 1:41, respectively, which are typical for these diseases at age 50. For individual risk prediction, the corresponding 10 year odds of becoming affected for individuals aged 50 with a polygenic risk score at the 2.5th, 25th, 75th, and 97.5th centiles were 1:54, 1:29, 1:15, and 1:8 for coronary artery disease and 1:91, 1:56, 1:34, and 1:21 for breast cancer. In terms of population risk stratification, at age 50, the risk of coronary artery disease was divided into five groups, with 10 year odds of 1:41 and 1:11 for the lowest and highest quintile groups, respectively. The 10 year odds was 1:7 for the upper 2.5% of the polygenic risk score distribution for coronary artery disease, a group that contributed 7% of cases. The corresponding estimates for breast cancer were 1:72 and 1:26 for the lowest and highest quintile groups, and 1:19 for the upper 2.5% of the distribution, which contributed 6% of cases.

Conclusion

Polygenic risk scores performed poorly in population screening, individual risk prediction, and population risk stratification. Strong claims about the effect of polygenic risk scores on healthcare seem to be disproportionate to their performance.",,doi:https://doi.org/10.1136/bmjmed-2023-000554; html:https://europepmc.org/articles/PMC10582890; pdf:https://europepmc.org/articles/PMC10582890?pdf=render 35985824,https://doi.org/10.1212/wnl.0000000000201064,"Headache, Opiate Use, and Prescribing Trends in Women With Idiopathic Intracranial Hypertension: A Population-Based Matched Cohort Study.","Adderley NJ, Subramanian A, Perrins M, Nirantharakumar K, Mollan SP, Sinclair AJ.",,Neurology,2022,2022-10-31,Y,,,,"

Background and objectives

Physician prescribing habits for opiates and headache therapies have not been previously evaluated in a large, matched cohort study in idiopathic intracranial hypertension (IIH). Our objective was to evaluate opiate and headache medication prescribing habits in women with IIH compared with matched women with migraine and population controls. We also investigated the occurrence of new onset headache in IIH compared with population controls.

Methods

We performed a population-based matched, retrospective cohort study to explore headache outcomes. Cross-sectional analyses were used to describe medication prescribing patterns. We used data from IQVIA Medical Research Data, an anonymized, nationally representative primary care electronic medical record database in the United Kingdom, from January 1, 1995, to September 25, 2019. Women aged 16 years and older were eligible for inclusion. Women with IIH (exposure) were matched by age and body mass index with up to 10 control women without IIH but with migraine (migraine controls), and without IIH or migraine (population controls).

Results

A total of 3,411 women with IIH, 13,966 migraine controls, and 33,495 population controls were included. The adjusted hazard ratio for new onset headache in IIH compared with population controls was 3.09 (95% CI 2.78-3.43). In the first year after diagnosis, 58% of women with IIH were prescribed acetazolamide and 20% topiramate. In total, 20% of women with IIH were prescribed opiates within the first year of their diagnosis, reducing to 17% after 6 years, compared with 8% and 11% among those with migraine, respectively. Twice as many women with IIH were prescribed opiates compared with migraine controls, and 3 times as many women with IIH were prescribed opiates compared with population controls. Women with IIH were also prescribed more headache preventative medications compared with migraine controls.

Discussion

Women with IIH were more likely to be prescribed opiate and simple analgesics compared with both migraine and population controls. Women with IIH trialed more preventative medications over their disease course suggesting that headaches in IIH may be more refractory to treatment.",,pdf:https://n.neurology.org/content/neurology/99/18/e1968.full.pdf; doi:https://doi.org/10.1212/WNL.0000000000201064; html:https://europepmc.org/articles/PMC9651462; pdf:https://europepmc.org/articles/PMC9651462?pdf=render 35032176,https://doi.org/10.1007/s00125-021-05640-y,Cardiovascular risk prediction in type 2 diabetes: a comparison of 22 risk scores in primary care settings.,"Dziopa K, Asselbergs FW, Gratton J, Chaturvedi N, Schmidt AF.",,Diabetologia,2022,2022-01-15,Y,Prediction; Diabetes; Cardiovascular disease; Risk Score,,,"

Aims/hypothesis

We aimed to compare the performance of risk prediction scores for CVD (i.e., coronary heart disease and stroke), and a broader definition of CVD including atrial fibrillation and heart failure (CVD+), in individuals with type 2 diabetes.

Methods

Scores were identified through a literature review and were included irrespective of the type of predicted cardiovascular outcome or the inclusion of individuals with type 2 diabetes. Performance was assessed in a contemporary, representative sample of 168,871 UK-based individuals with type 2 diabetes (age ≥18 years without pre-existing CVD+). Missing observations were addressed using multiple imputation.

Results

We evaluated 22 scores: 13 derived in the general population and nine in individuals with type 2 diabetes. The Systemic Coronary Risk Evaluation (SCORE) CVD rule derived in the general population performed best for both CVD (C statistic 0.67 [95% CI 0.67, 0.67]) and CVD+ (C statistic 0.69 [95% CI 0.69, 0.70]). The C statistic of the remaining scores ranged from 0.62 to 0.67 for CVD, and from 0.64 to 0.69 for CVD+. Calibration slopes (1 indicates perfect calibration) ranged from 0.38 (95% CI 0.37, 0.39) to 0.74 (95% CI 0.72, 0.76) for CVD, and from 0.41 (95% CI 0.40, 0.42) to 0.88 (95% CI 0.86, 0.90) for CVD+. A simple recalibration process considerably improved the performance of the scores, with calibration slopes now ranging between 0.96 and 1.04 for CVD. Scores with more predictors did not outperform scores with fewer predictors: for CVD+, QRISK3 (19 variables) had a C statistic of 0.68 (95% CI 0.68, 0.69), compared with SCORE CVD (six variables) which had a C statistic of 0.69 (95% CI 0.69, 0.70). Scores specific to individuals with diabetes did not discriminate better than scores derived in the general population: the UK Prospective Diabetes Study (UKPDS) scores performed significantly worse than SCORE CVD (p value <0.001).

Conclusions/interpretation

CVD risk prediction scores could not accurately identify individuals with type 2 diabetes who experienced a CVD event in the 10 years of follow-up. All 22 evaluated models had a comparable and modest discriminative ability.",,pdf:https://link.springer.com/content/pdf/10.1007/s00125-021-05640-y.pdf; doi:https://doi.org/10.1007/s00125-021-05640-y; html:https://europepmc.org/articles/PMC8894164; pdf:https://europepmc.org/articles/PMC8894164?pdf=render 34641870,https://doi.org/10.1186/s12911-021-01638-z,An informatics consult approach for generating clinical evidence for treatment decisions.,"Lai AG, Chang WH, Parisinos CA, Katsoulis M, Blackburn RM, Shah AD, Nguyen V, Denaxas S, Davey Smith G, Gaunt TR, Nirantharakumar K, Cox MP, Forde D, Asselbergs FW, Harris S, Richardson S, Sofat R, Dobson RJB, Hingorani A, Patel R, Sterne J, Banerjee A, Denniston AK, Ball S, Sebire NJ, Shah NH, Foster GR, Williams B, Hemingway H.",,BMC medical informatics and decision making,2021,2021-10-12,Y,,,,"

Background

An Informatics Consult has been proposed in which clinicians request novel evidence from large scale health data resources, tailored to the treatment of a specific patient. However, the availability of such consultations is lacking. We seek to provide an Informatics Consult for a situation where a treatment indication and contraindication coexist in the same patient, i.e., anti-coagulation use for stroke prevention in a patient with both atrial fibrillation (AF) and liver cirrhosis.

Methods

We examined four sources of evidence for the effect of warfarin on stroke risk or all-cause mortality from: (1) randomised controlled trials (RCTs), (2) meta-analysis of prior observational studies, (3) trial emulation (using population electronic health records (N = 3,854,710) and (4) genetic evidence (Mendelian randomisation). We developed prototype forms to request an Informatics Consult and return of results in electronic health record systems.

Results

We found 0 RCT reports and 0 trials recruiting for patients with AF and cirrhosis. We found broad concordance across the three new sources of evidence we generated. Meta-analysis of prior observational studies showed that warfarin use was associated with lower stroke risk (hazard ratio [HR] = 0.71, CI 0.39-1.29). In a target trial emulation, warfarin was associated with lower all-cause mortality (HR = 0.61, CI 0.49-0.76) and ischaemic stroke (HR = 0.27, CI 0.08-0.91). Mendelian randomisation served as a drug target validation where we found that lower levels of vitamin K1 (warfarin is a vitamin K1 antagonist) are associated with lower stroke risk. A pilot survey with an independent sample of 34 clinicians revealed that 85% of clinicians found information on prognosis useful and that 79% thought that they should have access to the Informatics Consult as a service within their healthcare systems. We identified candidate steps for automation to scale evidence generation and to accelerate the return of results.

Conclusion

We performed a proof-of-concept Informatics Consult for evidence generation, which may inform treatment decisions in situations where there is dearth of randomised trials. Patients are surprised to know that their clinicians are currently not able to learn in clinic from data on 'patients like me'. We identify the key challenges in offering such an Informatics Consult as a service.",,doi:https://doi.org/10.1186/s12911-021-01638-z; doi:https://doi.org/10.1186/s12911-021-01638-z; html:https://europepmc.org/articles/PMC8506488; pdf:https://europepmc.org/articles/PMC8506488?pdf=render 33320878,https://doi.org/10.1371/journal.pone.0243843,Developing a national birth cohort for child health research using a hospital admissions database in England: The impact of changes to data collection practices.,"Zylbersztejn A, Gilbert R, Hardelid P.",,PloS one,2020,2020-12-15,Y,,,,"

Background

National birth cohorts derived from administrative health databases constitute unique resources for child health research due to whole country coverage, ongoing follow-up and linkage to other data sources. In England, a national birth cohort can be developed using Hospital Episode Statistics (HES), an administrative database covering details of all publicly funded hospital activity, including 97% of births, with longitudinal follow-up via linkage to hospital and mortality records. We present methods for developing a national birth cohort using HES and assess the impact of changes to data collection over time on coverage and completeness of linked follow-up records for children.

Methods

We developed a national cohort of singleton live births in 1998-2015, with information on key risk factors at birth (birth weight, gestational age, maternal age, ethnicity, area-level deprivation). We identified three changes to data collection, which could affect linkage of births to follow-up records: (1) the introduction of the ""NHS Numbers for Babies (NN4B)"", an on-line system which enabled maternity staff to request a unique healthcare patient identifier (NHS number) immediately at birth rather than at civil registration, in Q4 2002; (2) the introduction of additional data quality checks at civil registration in Q3 2009; and (3) correcting a postcode extraction error for births by the data provider in Q2 2013. We evaluated the impact of these changes on trends in two outcomes in infancy: hospital readmissions after birth (using interrupted time series analyses) and mortality rates (compared to published national statistics).

Results

The cohort covered 10,653,998 babies, accounting for 96% of singleton live births in England in 1998-2015. Overall, 2,077,929 infants (19.5%) had at least one hospital readmission after birth. Readmission rates declined by 0.2% percentage points per annual quarter in Q1 1998 to Q3 2002, shifted up by 6.1% percentage points (compared to the expected value based on the trend before Q4 2002) to 17.7% in Q4 2002 when NN4B was introduced, and increased by 0.1% percentage points per annual quarter thereafter. Infant mortality rates were under-reported by 16% for births in 1998-2002 and similar to published national mortality statistics for births in 2003-2015. The trends in infant readmission were not affected by changes to data collection practices in Q3 2009 and Q2 2013, but the proportion of unlinked mortality records in HES and in ONS further declined after 2009.

Discussion

HES can be used to develop a national birth cohort for child health research with follow-up via linkage to hospital and mortality records for children born from 2003 onwards. Re-linking births before 2003 to their follow-up records would maximise potential benefits of this rich resource, enabling studies of outcomes in adolescents with over 20 years of follow-up.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0243843&type=printable; doi:https://doi.org/10.1371/journal.pone.0243843; html:https://europepmc.org/articles/PMC7737962; pdf:https://europepmc.org/articles/PMC7737962?pdf=render 34174193,https://doi.org/10.1016/s1473-3099(21)00289-9,Vaccine effectiveness of the first dose of ChAdOx1 nCoV-19 and BNT162b2 against SARS-CoV-2 infection in residents of long-term care facilities in England (VIVALDI): a prospective cohort study.,"Shrotri M, Krutikov M, Palmer T, Giddings R, Azmi B, Subbarao S, Fuller C, Irwin-Singer A, Davies D, Tut G, Lopez Bernal J, Moss P, Hayward A, Copas A, Shallcross L.",,The Lancet. Infectious diseases,2021,2021-06-23,Y,,,,"

Background

The effectiveness of SARS-CoV-2 vaccines in older adults living in long-term care facilities is uncertain. We investigated the protective effect of the first dose of the Oxford-AstraZeneca non-replicating viral-vectored vaccine (ChAdOx1 nCoV-19; AZD1222) and the Pfizer-BioNTech mRNA-based vaccine (BNT162b2) in residents of long-term care facilities in terms of PCR-confirmed SARS-CoV-2 infection over time since vaccination.

Methods

The VIVALDI study is a prospective cohort study that commenced recruitment on June 11, 2020, to investigate SARS-CoV-2 transmission, infection outcomes, and immunity in residents and staff in long-term care facilities in England that provide residential or nursing care for adults aged 65 years and older. In this cohort study, we included long-term care facility residents undergoing routine asymptomatic SARS-CoV-2 testing between Dec 8, 2020 (the date the vaccine was first deployed in a long-term care facility), and March 15, 2021, using national testing data linked within the COVID-19 Datastore. Using Cox proportional hazards regression, we estimated the relative hazard of PCR-positive infection at 0-6 days, 7-13 days, 14-20 days, 21-27 days, 28-34 days, 35-48 days, and 49 days and beyond after vaccination, comparing unvaccinated and vaccinated person-time from the same cohort of residents, adjusting for age, sex, previous infection, local SARS-CoV-2 incidence, long-term care facility bed capacity, and clustering by long-term care facility. We also compared mean PCR cycle threshold (Ct) values for positive swabs obtained before and after vaccination. The study is registered with ISRCTN, number 14447421.

Findings

10 412 care home residents aged 65 years and older from 310 LTCFs were included in this analysis. The median participant age was 86 years (IQR 80-91), 7247 (69·6%) of 10 412 residents were female, and 1155 residents (11·1%) had evidence of previous SARS-CoV-2 infection. 9160 (88·0%) residents received at least one vaccine dose, of whom 6138 (67·0%) received ChAdOx1 and 3022 (33·0%) received BNT162b2. Between Dec 8, 2020, and March 15, 2021, there were 36 352 PCR results in 670 628 person-days, and 1335 PCR-positive infections (713 in unvaccinated residents and 612 in vaccinated residents) were included. Adjusted hazard ratios (HRs) for PCR-positive infection relative to unvaccinated residents declined from 28 days after the first vaccine dose to 0·44 (95% CI 0·24-0·81) at 28-34 days and 0·38 (0·19-0·77) at 35-48 days. Similar effect sizes were seen for ChAdOx1 (adjusted HR 0·32, 95% CI 0·15-0·66) and BNT162b2 (0·35, 0·17-0·71) vaccines at 35-48 days. Mean PCR Ct values were higher for infections that occurred at least 28 days after vaccination than for those occurring before vaccination (31·3 [SD 8·7] in 107 PCR-positive tests vs 26·6 [6·6] in 552 PCR-positive tests; p<0·0001).

Interpretation

Single-dose vaccination with BNT162b2 and ChAdOx1 vaccines provides substantial protection against infection in older adults from 4-7 weeks after vaccination and might reduce SARS-CoV-2 transmission. However, the risk of infection is not eliminated, highlighting the ongoing need for non-pharmaceutical interventions to prevent transmission in long-term care facilities.

Funding

UK Government Department of Health and Social Care.",,pdf:http://www.thelancet.com/article/S1473309921002899/pdf; doi:https://doi.org/10.1016/S1473-3099(21)00289-9; html:https://europepmc.org/articles/PMC8221738 35429382,https://doi.org/10.1093/infdis/jiac146,Severe Acute Respiratory Syndrome Coronavirus 2 Anti-Spike Antibody Levels Following Second Dose of ChAdOx1 nCov-19 or BNT162b2 Vaccine in Residents of Long-term Care Facilities in England (VIVALDI).,"Stirrup O, Krutikov M, Tut G, Palmer T, Bone D, Bruton R, Fuller C, Azmi B, Lancaster T, Sylla P, Kaur N, Spalkova E, Bentley C, Amin U, Jadir A, Hulme S, Giddings R, Nacer-Laidi H, Baynton V, Irwin-Singer A, Hayward A, Moss P, Copas A, Shallcross L.",,The Journal of infectious diseases,2022,2022-11-01,Y,Antibodies; Vaccination; Waning; Long-term Care Facilities; Covid-19,,,"General population studies have shown strong humoral response following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination with subsequent waning of anti-spike antibody levels. Vaccine-induced immune responses are often attenuated in frail and older populations, but published data are scarce. We measured SARS-CoV-2 anti-spike antibody levels in long-term care facility residents and staff following a second vaccination dose with Oxford-AstraZeneca or Pfizer-BioNTech. Vaccination elicited robust antibody responses in older residents, suggesting comparable levels of vaccine-induced immunity to that in the general population. Antibody levels are higher after Pfizer-BioNTech vaccination but fall more rapidly compared to Oxford-AstraZeneca recipients and are enhanced by prior infection in both groups.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9047242; doi:https://doi.org/10.1093/infdis/jiac146; html:https://europepmc.org/articles/PMC9047242; pdf:https://europepmc.org/articles/PMC9047242?pdf=render -38740716,https://doi.org/10.1007/s40266-024-01116-x,Associations Between Midlife Anticholinergic Medication Use and Subsequent Cognitive Decline: A British Birth Cohort Study.,"Rawle MJ, Lau WCY, Gonzalez-Izquierdo A, Patalay P, Richards M, Davis D.",,Drugs & aging,2024,2024-05-13,N,,,,"

Background

Anticholinergic medication use is associated with cognitive decline and incident dementia. Our study, a prospective birth cohort analysis, aimed to determine if repeated exposure to anticholinergic medications was associated with greater decline, and whether decline was reversed with medication reduction.

Methods

From the Medical Research Council (MRC) National Survey of Health and Development, a British birth cohort with all participants born in a single week of March 1946, we quantified anticholinergic exposure between ages 53 and 69 years using the Anticholinergic Cognitive Burden Scale (ACBS). We used multinomial regression to estimate associations with global cognition, quantified by the Addenbrooke's Cognitive Examination, 3rd Edition (ACE-III). Longitudinal associations between ACBS and cognitive test results (Verbal memory quantified by the Word Learning Test [WLT], and processing speed quantified by the Timed Letter Search Task [TLST]) at three time points (age 53, 60-64 and 69) were assessed using mixed and fixed effects linear regression models. Analyses were adjusted for sex, childhood cognition, education, chronic disease count and severity, and mental health symptoms.

Results

Anticholinergic exposure was associated cross-sectionally with lower ACE-III scores at age 69, with the greatest effects in those with high exposure at ages 60-64 (mean difference - 2.34, 95% confidence interval [CI] - 3.51 to - 1.17). Longitudinally, both mild-moderate and high ACBS scores were linked to lower WLT scores, again with high exposure showing larger effects (mean difference with contemporaneous exposure - 0.90, 95% CI - 1.63 to - 0.17; mean difference with lagged exposure - 1.53, 95% CI - 2.43 to - 0.64). Associations remained in fixed effects models (mean difference with contemporaneous exposure -1.78, 95% CI -2.85 to - 0.71; mean difference with lagged exposure - 2.23, 95% CI - 3.33 to - 1.13). Associations with TLST were noted only in isolated contemporaneous exposure (mean difference - 13.14, 95% CI - 19.04 to - 7.23; p < 0.01).

Conclusions

Anticholinergic exposure throughout mid and later life was associated with lower cognitive function. Reduced processing speed was associated only with contemporaneous anticholinergic medication use, and not historical use. Associations with lower verbal recall were evident with both historical and contemporaneous use of anticholinergic medication, and associations with historical use persisted in individuals even when their anticholinergic medication use decreased over the course of the study.",,doi:https://doi.org/10.1007/s40266-024-01116-x 36763324,https://doi.org/10.1007/s12687-023-00635-1,What makes a good life: using theatrical performance to enhance communication about polygenic risk scores research in patient and public involvement.,"Mason AM, Obi I, Ayodele O, Lambert SA, Fahle S.",,Journal of community genetics,2023,2023-02-10,Y,,,,"The aim of this patient and public involvement and engagement (PPIE) work was to explore improvised theatre as a tool for facilitating bi-directional dialogue between researchers and patients/members of the public on the topic of polygenic risk scores (PRS) use within primary or secondary care. PRS are a tool to quantify genetic risk for a heritable disease or trait and may be used to predict future health outcomes. In the United Kingdom (UK), they are often cited as a next-in-line public health tool to be implemented, and their use in consumer genetic testing as well as patient-facing settings is increasing. Despite their potential clinical utility, broader themes about how they might influence an individual's perception of disease risk and decision-making are an active area of research; however, this has mostly been in the setting of return of results to patients. We worked with a youth theatre group and patients involved in a PPIE group to develop two short plays about public perceptions of genetic risk information that could be captured by PRS. These plays were shared in a workshop with patients/members of the public to facilitate discussions about PRS and their perceived benefits, concerns and emotional reactions. Discussions with both performers and patients/public raised three key questions: (1) can the data be trusted?; (2) does knowing genetic risk actually help the patient?; and (3) what makes a life worthwhile? Creating and watching fictional narratives helped all participants explore the potential use of PRS in a clinical setting, informing future research considerations and improving communication between the researchers and lay members of the PPIE group.",,pdf:https://link.springer.com/content/pdf/10.1007/s12687-023-00635-1.pdf; doi:https://doi.org/10.1007/s12687-023-00635-1; html:https://europepmc.org/articles/PMC10576689; pdf:https://europepmc.org/articles/PMC10576689?pdf=render +38740716,https://doi.org/10.1007/s40266-024-01116-x,Associations Between Midlife Anticholinergic Medication Use and Subsequent Cognitive Decline: A British Birth Cohort Study.,"Rawle MJ, Lau WCY, Gonzalez-Izquierdo A, Patalay P, Richards M, Davis D.",,Drugs & aging,2024,2024-05-13,N,,,,"

Background

Anticholinergic medication use is associated with cognitive decline and incident dementia. Our study, a prospective birth cohort analysis, aimed to determine if repeated exposure to anticholinergic medications was associated with greater decline, and whether decline was reversed with medication reduction.

Methods

From the Medical Research Council (MRC) National Survey of Health and Development, a British birth cohort with all participants born in a single week of March 1946, we quantified anticholinergic exposure between ages 53 and 69 years using the Anticholinergic Cognitive Burden Scale (ACBS). We used multinomial regression to estimate associations with global cognition, quantified by the Addenbrooke's Cognitive Examination, 3rd Edition (ACE-III). Longitudinal associations between ACBS and cognitive test results (Verbal memory quantified by the Word Learning Test [WLT], and processing speed quantified by the Timed Letter Search Task [TLST]) at three time points (age 53, 60-64 and 69) were assessed using mixed and fixed effects linear regression models. Analyses were adjusted for sex, childhood cognition, education, chronic disease count and severity, and mental health symptoms.

Results

Anticholinergic exposure was associated cross-sectionally with lower ACE-III scores at age 69, with the greatest effects in those with high exposure at ages 60-64 (mean difference - 2.34, 95% confidence interval [CI] - 3.51 to - 1.17). Longitudinally, both mild-moderate and high ACBS scores were linked to lower WLT scores, again with high exposure showing larger effects (mean difference with contemporaneous exposure - 0.90, 95% CI - 1.63 to - 0.17; mean difference with lagged exposure - 1.53, 95% CI - 2.43 to - 0.64). Associations remained in fixed effects models (mean difference with contemporaneous exposure -1.78, 95% CI -2.85 to - 0.71; mean difference with lagged exposure - 2.23, 95% CI - 3.33 to - 1.13). Associations with TLST were noted only in isolated contemporaneous exposure (mean difference - 13.14, 95% CI - 19.04 to - 7.23; p < 0.01).

Conclusions

Anticholinergic exposure throughout mid and later life was associated with lower cognitive function. Reduced processing speed was associated only with contemporaneous anticholinergic medication use, and not historical use. Associations with lower verbal recall were evident with both historical and contemporaneous use of anticholinergic medication, and associations with historical use persisted in individuals even when their anticholinergic medication use decreased over the course of the study.",,doi:https://doi.org/10.1007/s40266-024-01116-x 34716166,https://doi.org/10.1136/bmjopen-2021-053268,Electronic reminders and rewards to improve adherence to inhaled asthma treatment in adolescents: a non-randomised feasibility study in tertiary care.,"De Simoni A, Fleming L, Holliday L, Horne R, Priebe S, Bush A, Sheikh A, Griffiths C.",,BMJ open,2021,2021-10-29,Y,Asthma; Respiratory Medicine (See Thoracic Medicine); Paediatric Thoracic Medicine,,,"

Objective

To test the feasibility and acceptability of a short-term reminder and incentives intervention in adolescents with low adherence to asthma medications.

Methods

Mixed-methods feasibility study in a tertiary care clinic. Adolescents recruited to a 24-week programme with three 8-weekly visits, receiving electronic reminders to prompt inhaled corticosteroid (ICS) inhalation through a mobile app coupled with electronic monitoring devices (EMD). From the second visit, monetary incentives based on adherence of ICS inhalation: £1 per dose, maximum £2 /day, up to £112/study, collected as gift cards at the third visit. End of study interviews and questionnaires assessing perceptions of asthma and ICS, analysed using the Perceptions and Practicalities Framework.

Participants

Adolescents (11-18 years) with documented low ICS adherence (<80% by EMD), and poor asthma control at the first clinic visit.

Results

10 out of 12 adolescents approached were recruited (7 males, 3 females, 12-16 years). Eight participants provided adherence measures up to the fourth visits and received rewards. Mean study duration was 281 days, with 7/10 participants unable to attend their fourth visit due to COVID-19 lockdown. Only 3/10 participants managed to pair the app/EMD up to the fourth visit, which was associated with improved ICS adherence (from 0.51, SD 0.07 to 0.86, SD 0.05). Adherence did not change in adolescents unable to pair the app/EMD. The intervention was acceptable to participants and parents/guardians. Exit interviews showed that participants welcomed reminders and incentives, though expressed frustration with app/EMD technological difficulties. Participants stated the intervention helped through reminding ICS doses, promoting self-monitoring and increasing motivation to take inhalers.

Conclusions

An intervention using electronic reminders and incentives through an app coupled with an EMD was feasible and acceptable to adolescents with asthma. A pilot randomised controlled trial is warranted to better estimate the effect size on adherence, with improved technical support for the EMD.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/10/e053268.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-053268; html:https://europepmc.org/articles/PMC8559117; pdf:https://europepmc.org/articles/PMC8559117?pdf=render 36382153,https://doi.org/10.5334/gh.1166,Risk Factors and Prevalence of Dilated Cardiomyopathy in Sub-Saharan Africa: A Systematic Review.,"Fundikira LS, Chillo P, Mutagaywa R, Kamuhabwa A, Kwesigabo G, Asselbergs FW, van Laake LW.",,Global heart,2022,2022-10-21,Y,Dilated cardiomyopathy; Sub-Saharan Africa; Cardiovascular risk factors,,,Highlights  Prevalence of DCM varies widely in SSA.Cardiovascular risk factors are important in patients with DCM.The role of genetics in idiopathic DCM is not studied in major part of SSA.,,pdf:http://globalheartjournal.com/articles/10.5334/gh.1166/galley/1329/download/; doi:https://doi.org/10.5334/gh.1166; html:https://europepmc.org/articles/PMC9585983; pdf:https://europepmc.org/articles/PMC9585983?pdf=render 31616478,https://doi.org/10.3389/fgene.2019.00922,Machine Learning Predicts Accurately Mycobacterium tuberculosis Drug Resistance From Whole Genome Sequencing Data.,"Deelder W, Christakoudi S, Phelan J, Benavente ED, Campino S, McNerney R, Palla L, Clark TG.",,Frontiers in genetics,2019,2019-09-26,Y,Mycobacterium tuberculosis; Drug resistance; Mdr-tb; Xdr-tb; Machine Learning,Applied Analytics,,"Background: Tuberculosis disease, caused by Mycobacterium tuberculosis, is a major public health problem. The emergence of M. tuberculosis strains resistant to existing treatments threatens to derail control efforts. Resistance is mainly conferred by mutations in genes coding for drug targets or converting enzymes, but our knowledge of these mutations is incomplete. Whole genome sequencing (WGS) is an increasingly common approach to rapidly characterize isolates and identify mutations predicting antimicrobial resistance and thereby providing a diagnostic tool to assist clinical decision making. Methods: We applied machine learning approaches to 16,688 M. tuberculosis isolates that have undergone WGS and laboratory drug-susceptibility testing (DST) across 14 antituberculosis drugs, with 22.5% of samples being multidrug resistant and 2.1% being extensively drug resistant. We used non-parametric classification-tree and gradient-boosted-tree models to predict drug resistance and uncover any associated novel putative mutations. We fitted separate models for each drug, with and without ""co-occurrent resistance"" markers known to be causing resistance to drugs other than the one of interest. Predictive performance was measured using sensitivity, specificity, and the area under the receiver operating characteristic curve, assuming DST results as the gold standard. Results: The predictive performance was highest for resistance to first-line drugs, amikacin, kanamycin, ciprofloxacin, moxifloxacin, and multidrug-resistant tuberculosis (area under the receiver operating characteristic curve above 96%), and lowest for third-line drugs such as D-cycloserine and Para-aminosalisylic acid (area under the curve below 85%). The inclusion of co-occurrent resistance markers led to improved performance for some drugs and superior results when compared to similar models in other large-scale studies, which had smaller sample sizes. Overall, the gradient-boosted-tree models performed better than the classification-tree models. The mutation-rank analysis detected no new single nucleotide polymorphisms linked to drug resistance. Discordance between DST and genotypically inferred resistance may be explained by DST errors, novel rare mutations, hetero-resistance, and nongenomic drivers such as efflux-pump upregulation. Conclusion: Our work demonstrates the utility of machine learning as a flexible approach to drug resistance prediction that is able to accommodate a much larger number of predictors and to summarize their predictive ability, thus assisting clinical decision making and single nucleotide polymorphism detection in an era of increasing WGS data generation.",,pdf:https://www.frontiersin.org/articles/10.3389/fgene.2019.00922/pdf; doi:https://doi.org/10.3389/fgene.2019.00922; html:https://europepmc.org/articles/PMC6775242; pdf:https://europepmc.org/articles/PMC6775242?pdf=render @@ -900,21 +900,21 @@ PMC10686417,https://doi.org/,The impact of restricted provision of publicly fund 38358949,https://doi.org/10.1371/journal.pmed.1004343,Health outcomes after myocardial infarction: A population study of 56 million people in England.,"Hall M, Smith L, Wu J, Hayward C, Batty JA, Lambert PC, Hemingway H, Gale CP.",,PLoS medicine,2024,2024-02-15,Y,,,,"

Background

The occurrence of a range of health outcomes following myocardial infarction (MI) is unknown. Therefore, this study aimed to determine the long-term risk of major health outcomes following MI and generate sociodemographic stratified risk charts in order to inform care recommendations in the post-MI period and underpin shared decision making.

Methods and findings

This nationwide cohort study includes all individuals aged ≥18 years admitted to one of 229 National Health Service (NHS) Trusts in England between 1 January 2008 and 31 January 2017 (final follow-up 27 March 2017). We analysed 11 non-fatal health outcomes (subsequent MI and first hospitalisation for heart failure, atrial fibrillation, cerebrovascular disease, peripheral arterial disease, severe bleeding, renal failure, diabetes mellitus, dementia, depression, and cancer) and all-cause mortality. Of the 55,619,430 population of England, 34,116,257 individuals contributing to 145,912,852 hospitalisations were included (mean age 41.7 years (standard deviation [SD 26.1]); n = 14,747,198 (44.2%) male). There were 433,361 individuals with MI (mean age 67.4 years [SD 14.4)]; n = 283,742 (65.5%) male). Following MI, all-cause mortality was the most frequent event (adjusted cumulative incidence at 9 years 37.8% (95% confidence interval [CI] [37.6,37.9]), followed by heart failure (29.6%; 95% CI [29.4,29.7]), renal failure (27.2%; 95% CI [27.0,27.4]), atrial fibrillation (22.3%; 95% CI [22.2,22.5]), severe bleeding (19.0%; 95% CI [18.8,19.1]), diabetes (17.0%; 95% CI [16.9,17.1]), cancer (13.5%; 95% CI [13.3,13.6]), cerebrovascular disease (12.5%; 95% CI [12.4,12.7]), depression (8.9%; 95% CI [8.7,9.0]), dementia (7.8%; 95% CI [7.7,7.9]), subsequent MI (7.1%; 95% CI [7.0,7.2]), and peripheral arterial disease (6.5%; 95% CI [6.4,6.6]). Compared with a risk-set matched population of 2,001,310 individuals, first hospitalisation of all non-fatal health outcomes were increased after MI, except for dementia (adjusted hazard ratio [aHR] 1.01; 95% CI [0.99,1.02];p = 0.468) and cancer (aHR 0.56; 95% CI [0.56,0.57];p < 0.001). The study includes data from secondary care only-as such diagnoses made outside of secondary care may have been missed leading to the potential underestimation of the total burden of disease following MI.

Conclusions

In this study, up to a third of patients with MI developed heart failure or renal failure, 7% had another MI, and 38% died within 9 years (compared with 35% deaths among matched individuals). The incidence of all health outcomes, except dementia and cancer, was higher than expected during the normal life course without MI following adjustment for age, sex, year, and socioeconomic deprivation. Efforts targeted to prevent or limit the accrual of chronic, multisystem disease states following MI are needed and should be guided by the demographic-specific risk charts derived in this study.",,pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1004343&type=printable; doi:https://doi.org/10.1371/journal.pmed.1004343; html:https://europepmc.org/articles/PMC10868847; pdf:https://europepmc.org/articles/PMC10868847?pdf=render 38176879,https://doi.org/10.1136/bmjopen-2023-078021,"RELEASE-HF study: a protocol for an observational, registry-based study on the effectiveness of telemedicine in heart failure in the Netherlands.","van Eijk J, Luijken K, Jaarsma T, Reitsma JB, Schuit E, Frederix GWJ, Derks L, Schaap J, Rutten FH, Brugts J, de Boer RA, Asselbergs FW, Trappenburg JCA, RELEASE-HF Investigators.",,BMJ open,2024,2024-01-04,Y,Heart Failure; Health Economics; Registries; Telemedicine; Clinical Decision-making; Protocols & Guidelines,,,"

Introduction

Meta-analyses show postive effects of telemedicine in heart failure (HF) management on hospitalisation, mortality and costs. However, these effects are heterogeneous due to variation in the included HF population, the telemedicine components and the quality of the comparator usual care. Still, telemedicine is gaining acceptance in HF management. The current nationwide study aims to identify (1) in which subgroup(s) of patients with HF telemedicine is (cost-)effective and (2) which components of telemedicine are most (cost-)effective.

Methods and analysis

The RELEASE-HF ('REsponsible roLl-out of E-heAlth through Systematic Evaluation - Heart Failure') study is a multicentre, observational, registry-based cohort study that plans to enrol 6480 patients with HF using data from the HF registry facilitated by the Netherlands Heart Registration. Collected data include patient characteristics, treatment information and clinical outcomes, and are measured at HF diagnosis and at 6 and 12 months afterwards. The components of telemedicine are described at the hospital level based on closed-ended interviews with clinicians and at the patient level based on additional data extracted from electronic health records and telemedicine-generated data. The costs of telemedicine are calculated using registration data and interviews with clinicians and finance department staff. To overcome missing data, additional national databases will be linked to the HF registry if feasible. Heterogeneity of the effects of offering telemedicine compared with not offering on days alive without unplanned hospitalisations in 1 year is assessed across predefined patient characteristics using exploratory stratified analyses. The effects of telemedicine components are assessed by fitting separate models for component contrasts.

Ethics and dissemination

The study has been approved by the Medical Ethics Committee 2021 of the University Medical Center Utrecht (the Netherlands). Results will be published in peer-reviewed journals and presented at (inter)national conferences. Effective telemedicine scenarios will be proposed among hospitals throughout the country and abroad, if applicable and feasible.

Trial registration number

NCT05654961.",,pdf:https://bmjopen.bmj.com/content/bmjopen/14/1/e078021.full.pdf; doi:https://doi.org/10.1136/bmjopen-2023-078021; html:https://europepmc.org/articles/PMC10773380; pdf:https://europepmc.org/articles/PMC10773380?pdf=render 36098502,https://doi.org/10.7554/elife.78427,"Effectiveness of rapid SARS-CoV-2 genome sequencing in supporting infection control for hospital-onset COVID-19 infection: Multicentre, prospective study.","Stirrup O, Blackstone J, Mapp F, MacNeil A, Panca M, Holmes A, Machin N, Shin GY, Mahungu T, Saeed K, Saluja T, Taha Y, Mahida N, Pope C, Chawla A, Cutino-Moguel MT, Tamuri A, Williams R, Darby A, Robertson DL, Flaviani F, Nastouli E, Robson S, Smith D, Loose M, Laing K, Monahan I, Kele B, Haldenby S, George R, Bashton M, Witney AA, Byott M, Coll F, Chapman M, Peacock SJ, COG-UK HOCI Investigators, COVID-19 Genomics UK (COG-UK) consortium, Hughes J, Nebbia G, Partridge DG, Parker M, Price JR, Peters C, Roy S, Snell LB, de Silva TI, Thomson E, Flowers P, Copas A, Breuer J.",,eLife,2022,2022-09-13,Y,Human; Microbiology; Infectious disease; Molecular epidemiology; Infection control; epidemiology; Global Health; Hospital-acquired Infection; Infection Prevention; Viral Genomics; Healthcare-associated Infection; Covid-19,,,"

Background

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

Methods

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

Results

A total of 2170 HOCI cases were recorded from October 2020 to April 2021, corresponding to a period of extreme strain on the health service, with sequence reports returned for 650/1320 (49.2%) during intervention phases. We did not detect a statistically significant change in weekly incidence of HAIs in longer-turnaround (incidence rate ratio 1.60, 95% CI 0.85-3.01; p=0.14) or rapid (0.85, 0.48-1.50; p=0.54) intervention phases compared to baseline phase. However, IPC practice was changed in 7.8 and 7.4% of all HOCI cases in rapid and longer-turnaround phases, respectively, and 17.2 and 11.6% of cases where the report was returned. In a 'per-protocol' sensitivity analysis, there was an impact on IPC actions in 20.7% of HOCI cases when the SRT report was returned within 5 days. Capacity to respond effectively to insights from sequencing was breached in most sites by the volume of cases and limited resources.

Conclusions

While we did not demonstrate a direct impact of sequencing on the incidence of nosocomial transmission, our results suggest that sequencing can inform IPC response to HOCIs, particularly when returned within 5 days.

Funding

COG-UK is supported by funding from the Medical Research Council (MRC) part of UK Research & Innovation (UKRI), the National Institute of Health Research (NIHR) (grant code: MC_PC_19027), and Genome Research Limited, operating as the Wellcome Sanger Institute.

Clinical trial number

NCT04405934.",,doi:https://doi.org/10.7554/elife.78427; doi:https://doi.org/10.7554/eLife.78427; html:https://europepmc.org/articles/PMC9596156; pdf:https://europepmc.org/articles/PMC9596156?pdf=render -35776101,https://doi.org/10.1093/ije/dyac140,Incremental value of risk factor variability for cardiovascular risk prediction in individuals with type 2 diabetes: results from UK primary care electronic health records.,"Xu Z, Arnold M, Sun L, Stevens D, Chung R, Ip S, Barrett J, Kaptoge S, Pennells L, Di Angelantonio E, Wood AM.",,International journal of epidemiology,2022,2022-12-01,Y,Variability; Cardiovascular disease; Type 2 diabetes; Risk Prediction; Repeated Measurements; Electronic Health Records,,,"

Background

Cardiovascular disease (CVD) risk prediction models for individuals with type 2 diabetes are important tools to guide intensification of interventions for CVD prevention. We aimed to assess the added value of incorporating risk factors variability in CVD risk prediction for people with type 2 diabetes.

Methods

We used electronic health records (EHRs) data from 83 910 adults with type 2 diabetes but without pre-existing CVD from the UK Clinical Practice Research Datalink for 2004-2017. Using a landmark-modelling approach, we developed and validated sex-specific Cox models, incorporating conventional predictors and trajectories plus variability of systolic blood pressure (SBP), total and high-density lipoprotein (HDL) cholesterol, and glycated haemoglobin (HbA1c). Such models were compared against simpler models using single last observed values or means.

Results

The standard deviations (SDs) of SBP, HDL cholesterol and HbA1c were associated with higher CVD risk (P < 0.05). Models incorporating trajectories and variability of continuous predictors demonstrated improvement in risk discrimination (C-index = 0.659, 95% CI: 0.654-0.663) as compared with using last observed values (C-index = 0.651, 95% CI: 0.646-0.656) or means (C-index = 0.650, 95% CI: 0.645-0.655). Inclusion of SDs of SBP yielded the greatest improvement in discrimination (C-index increase = 0.005, 95% CI: 0.004-0.007) in comparison to incorporating SDs of total cholesterol (C-index increase = 0.002, 95% CI: 0.000-0.003), HbA1c (C-index increase = 0.002, 95% CI: 0.000-0.003) or HDL cholesterol (C-index increase= 0.003, 95% CI: 0.002-0.005).

Conclusion

Incorporating variability of predictors from EHRs provides a modest improvement in CVD risk discrimination for individuals with type 2 diabetes. Given that repeat measures are readily available in EHRs especially for regularly monitored patients with diabetes, this improvement could easily be achieved.",,pdf:https://academic.oup.com/ije/advance-article-pdf/doi/10.1093/ije/dyac140/45030523/dyac140.pdf; doi:https://doi.org/10.1093/ije/dyac140; html:https://europepmc.org/articles/PMC9749723; pdf:https://europepmc.org/articles/PMC9749723?pdf=render -38563665,https://doi.org/10.1148/radiol.232455,Left Ventricular Trabeculations at Cardiac MRI: Reference Ranges and Association with Cardiovascular Risk Factors in UK Biobank.,"Aung N, Bartoli A, Rauseo E, Cortaredona S, Sanghvi MM, Fournel J, Ghattas B, Khanji MY, Petersen SE, Jacquier A.",,Radiology,2024,2024-04-01,N,,,,"Background The extent of left ventricular (LV) trabeculation and its relationship with cardiovascular (CV) risk factors is unclear. Purpose To apply automated segmentation to UK Biobank cardiac MRI scans to (a) assess the association between individual characteristics and CV risk factors and trabeculated LV mass (LVM) and (b) establish normal reference ranges in a selected group of healthy UK Biobank participants. Materials and Methods In this cross-sectional secondary analysis, prospectively collected data from the UK Biobank (2006 to 2010) were retrospectively analyzed. Automated segmentation of trabeculations was performed using a deep learning algorithm. After excluding individuals with known CV diseases, White adults without CV risk factors (reference group) and those with preexisting CV risk factors (hypertension, hyperlipidemia, diabetes mellitus, or smoking) (exposed group) were compared. Multivariable regression models, adjusted for potential confounders (age, sex, and height), were fitted to evaluate the associations between individual characteristics and CV risk factors and trabeculated LVM. Results Of 43 038 participants (mean age, 64 years ± 8 [SD]; 22 360 women), 28 672 individuals (mean age, 66 years ± 7; 14 918 men) were included in the exposed group, and 7384 individuals (mean age, 60 years ± 7; 4729 women) were included in the reference group. Higher body mass index (BMI) (β = 0.66 [95% CI: 0.63, 0.68]; P < .001), hypertension (β = 0.42 [95% CI: 0.36, 0.48]; P < .001), and higher physical activity level (β = 0.15 [95% CI: 0.12, 0.17]; P < .001) were associated with higher trabeculated LVM. In the reference group, the median trabeculated LVM was 6.3 g (IQR, 4.7-8.5 g) for men and 4.6 g (IQR, 3.4-6.0 g) for women. Median trabeculated LVM decreased with age for men from 6.5 g (IQR, 4.8-8.7 g) at age 45-50 years to 5.9 g (IQR, 4.3-7.8 g) at age 71-80 years (P = .03). Conclusion Higher trabeculated LVM was observed with hypertension, higher BMI, and higher physical activity level. Age- and sex-specific reference ranges of trabeculated LVM in a healthy middle-aged White population were established. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Kawel-Boehm in this issue.",,doi:https://doi.org/10.1148/radiol.232455 34161326,https://doi.org/10.1371/journal.pcbi.1009121,Contrasting factors associated with COVID-19-related ICU admission and death outcomes in hospitalised patients by means of Shapley values.,"Cavallaro M, Moiz H, Keeling MJ, McCarthy ND.",,PLoS computational biology,2021,2021-06-23,Y,,,,"Identification of those at greatest risk of death due to the substantial threat of COVID-19 can benefit from novel approaches to epidemiology that leverage large datasets and complex machine-learning models, provide data-driven intelligence, and guide decisions such as intensive-care unit admission (ICUA). The objective of this study is two-fold, one substantive and one methodological: substantively to evaluate the association of demographic and health records with two related, yet different, outcomes of severe COVID-19 (viz., death and ICUA); methodologically to compare interpretations based on logistic regression and on gradient-boosted decision tree (GBDT) predictions interpreted by means of the Shapley impacts of covariates. Very different association of some factors, e.g., obesity and chronic respiratory diseases, with death and ICUA may guide review of practice. Shapley explanation of GBDTs identified varying effects of some factors among patients, thus emphasising the importance of individual patient assessment. The results of this study are also relevant for the evaluation of complex automated clinical decision systems, which should optimise prediction scores whilst remaining interpretable to clinicians and mitigating potential biases.",,pdf:https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1009121&type=printable; doi:https://doi.org/10.1371/journal.pcbi.1009121; html:https://europepmc.org/articles/PMC8259985; pdf:https://europepmc.org/articles/PMC8259985?pdf=render +35776101,https://doi.org/10.1093/ije/dyac140,Incremental value of risk factor variability for cardiovascular risk prediction in individuals with type 2 diabetes: results from UK primary care electronic health records.,"Xu Z, Arnold M, Sun L, Stevens D, Chung R, Ip S, Barrett J, Kaptoge S, Pennells L, Di Angelantonio E, Wood AM.",,International journal of epidemiology,2022,2022-12-01,Y,Variability; Cardiovascular disease; Type 2 diabetes; Risk Prediction; Repeated Measurements; Electronic Health Records,,,"

Background

Cardiovascular disease (CVD) risk prediction models for individuals with type 2 diabetes are important tools to guide intensification of interventions for CVD prevention. We aimed to assess the added value of incorporating risk factors variability in CVD risk prediction for people with type 2 diabetes.

Methods

We used electronic health records (EHRs) data from 83 910 adults with type 2 diabetes but without pre-existing CVD from the UK Clinical Practice Research Datalink for 2004-2017. Using a landmark-modelling approach, we developed and validated sex-specific Cox models, incorporating conventional predictors and trajectories plus variability of systolic blood pressure (SBP), total and high-density lipoprotein (HDL) cholesterol, and glycated haemoglobin (HbA1c). Such models were compared against simpler models using single last observed values or means.

Results

The standard deviations (SDs) of SBP, HDL cholesterol and HbA1c were associated with higher CVD risk (P < 0.05). Models incorporating trajectories and variability of continuous predictors demonstrated improvement in risk discrimination (C-index = 0.659, 95% CI: 0.654-0.663) as compared with using last observed values (C-index = 0.651, 95% CI: 0.646-0.656) or means (C-index = 0.650, 95% CI: 0.645-0.655). Inclusion of SDs of SBP yielded the greatest improvement in discrimination (C-index increase = 0.005, 95% CI: 0.004-0.007) in comparison to incorporating SDs of total cholesterol (C-index increase = 0.002, 95% CI: 0.000-0.003), HbA1c (C-index increase = 0.002, 95% CI: 0.000-0.003) or HDL cholesterol (C-index increase= 0.003, 95% CI: 0.002-0.005).

Conclusion

Incorporating variability of predictors from EHRs provides a modest improvement in CVD risk discrimination for individuals with type 2 diabetes. Given that repeat measures are readily available in EHRs especially for regularly monitored patients with diabetes, this improvement could easily be achieved.",,pdf:https://academic.oup.com/ije/advance-article-pdf/doi/10.1093/ije/dyac140/45030523/dyac140.pdf; doi:https://doi.org/10.1093/ije/dyac140; html:https://europepmc.org/articles/PMC9749723; pdf:https://europepmc.org/articles/PMC9749723?pdf=render 36715329,https://doi.org/10.1093/bjd/ljac090,"The epidemiology, healthcare and societal burden of basal cell carcinoma in Wales 2000-2018: a retrospective nationwide analysis.","Ibrahim N, Jovic M, Ali S, Williams N, Gibson JAG, Griffiths R, Dobbs TD, Akbari A, Lyons RA, Hutchings HA, Whitaker IS.",,The British journal of dermatology,2023,2023-02-01,N,,,,"

Background

Basal cell carcinoma (BCC) represents the most commonly occurring cancer worldwide within the white population. Reports predict 298 308 cases of BCC in the UK by 2025, at a cost of £265-366 million to the National Health Service (NHS). Despite the morbidity, societal and healthcare pressures brought about by BCC, routinely collected healthcare data and global registration remain limited.

Objectives

To calculate the incidence of BCC in Wales between 2000 and 2018 and to establish the related healthcare utilization and estimated cost of care.

Methods

The Secure Anonymised Information Linkage (SAIL) databank is one of the largest and most robust health and social care data repositories in the UK. Cancer registry data were linked to routinely collected healthcare databases between 2000 and 2018. Pathological data from Swansea Bay University Health Board (SBUHB) were used for internal validation.

Results

A total of 61 404 histologically proven BCCs were identified within the SAIL Databank during the study period. The European age-standardized incidence for BCC in 2018 was 224.6 per 100 000 person-years. Based on validated regional data, a 45% greater incidence was noted within SBUHB pathology vs. matched regions within SAIL between 2016 and 2018. A negative association between deprivation and incidence was noted with a higher incidence in the least socially deprived and rural dwellers. Approximately 2% travelled 25-50 miles for dermatological services compared with 37% for plastic surgery. Estimated NHS costs of surgically managed lesions for 2002-2019 equated to £119.2-164.4 million.

Conclusions

Robust epidemiological data that are internationally comparable and representative are scarce for nonmelanoma skin cancer. The rising global incidence coupled with struggling healthcare systems in the post-COVID-19 recovery period serve to intensify the societal and healthcare impact. This study is the first to demonstrate the incidence of BCC in Wales and is one of a small number in the UK using internally validated large cohort datasets. Furthermore, our findings demonstrate one of the highest published incidences within the UK and Europe.",,pdf:https://cronfa.swan.ac.uk/Record/cronfa62055/Download/62055__26915__ae11794993454389b6ceddbb7f50caaa.pdf; doi:https://doi.org/10.1093/bjd/ljac090 +38563665,https://doi.org/10.1148/radiol.232455,Left Ventricular Trabeculations at Cardiac MRI: Reference Ranges and Association with Cardiovascular Risk Factors in UK Biobank.,"Aung N, Bartoli A, Rauseo E, Cortaredona S, Sanghvi MM, Fournel J, Ghattas B, Khanji MY, Petersen SE, Jacquier A.",,Radiology,2024,2024-04-01,N,,,,"Background The extent of left ventricular (LV) trabeculation and its relationship with cardiovascular (CV) risk factors is unclear. Purpose To apply automated segmentation to UK Biobank cardiac MRI scans to (a) assess the association between individual characteristics and CV risk factors and trabeculated LV mass (LVM) and (b) establish normal reference ranges in a selected group of healthy UK Biobank participants. Materials and Methods In this cross-sectional secondary analysis, prospectively collected data from the UK Biobank (2006 to 2010) were retrospectively analyzed. Automated segmentation of trabeculations was performed using a deep learning algorithm. After excluding individuals with known CV diseases, White adults without CV risk factors (reference group) and those with preexisting CV risk factors (hypertension, hyperlipidemia, diabetes mellitus, or smoking) (exposed group) were compared. Multivariable regression models, adjusted for potential confounders (age, sex, and height), were fitted to evaluate the associations between individual characteristics and CV risk factors and trabeculated LVM. Results Of 43 038 participants (mean age, 64 years ± 8 [SD]; 22 360 women), 28 672 individuals (mean age, 66 years ± 7; 14 918 men) were included in the exposed group, and 7384 individuals (mean age, 60 years ± 7; 4729 women) were included in the reference group. Higher body mass index (BMI) (β = 0.66 [95% CI: 0.63, 0.68]; P < .001), hypertension (β = 0.42 [95% CI: 0.36, 0.48]; P < .001), and higher physical activity level (β = 0.15 [95% CI: 0.12, 0.17]; P < .001) were associated with higher trabeculated LVM. In the reference group, the median trabeculated LVM was 6.3 g (IQR, 4.7-8.5 g) for men and 4.6 g (IQR, 3.4-6.0 g) for women. Median trabeculated LVM decreased with age for men from 6.5 g (IQR, 4.8-8.7 g) at age 45-50 years to 5.9 g (IQR, 4.3-7.8 g) at age 71-80 years (P = .03). Conclusion Higher trabeculated LVM was observed with hypertension, higher BMI, and higher physical activity level. Age- and sex-specific reference ranges of trabeculated LVM in a healthy middle-aged White population were established. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Kawel-Boehm in this issue.",,doi:https://doi.org/10.1148/radiol.232455 37777816,https://doi.org/10.1186/s13643-023-02337-8,Patient-reported outcome (PRO) instruments used in patients undergoing adoptive cell therapy (ACT) for the treatment of cancer: a systematic review.,"Taylor S, Law K, Coomber-Moore J, Davies M, Thistlethwaite F, Calvert M, Aiyegbusi O, Yorke J.",,Systematic reviews,2023,2023-09-30,Y,Cancer; Systematic; Review; Quality of life; Patient-reported Outcomes (Pros); Adoptive Cell Therapy (Act),,,"

Introduction

Adoptive cell therapy (ACT) is a rapidly evolving field. Patient-reported outcomes (PROs) allow patients to report the impact of treatment on their quality of life during and after treatment. The systematic review aims to characterise the breadth of PROs utilised in ACT cancer care and provide guidance for the use of PROs in this patient population in the future.

Methods

A systematic search was conducted (MEDLINE, PsycINFO, Embase and CINAHL) in August 2021 by two reviewers. Search terms covered the following: ""adoptive cell therapy"", ""patient-reported outcomes"" and ""cancer"". Studies were included if they used a PRO measure to report the impact of ACT. The methodological quality of PROs was assessed. Forward and backward reference searching was conducted of any relevant papers. A quality grading scale was applied based on Cochrane and Revenson criteria for classification of high-quality studies. Key data from the studies and the included PROs was extracted by two researchers and tabulated.

Results

One-hundred nine papers were identified; 11 papers were included. The majority of studies were single-arm trials or observational studies. Twenty-two different PROs were identified; none was ACT specific. The PROMIS-29 and EQ-5D were most commonly used. Few studies collected PRO data in the first 1-2 weeks. Four studies followed patients up for over a year, and a further four studies followed patients for approximately 3 months.

Discussion

None of the PROs identified have been designed specifically for ACT. Appropriateness of existing instruments should be considered. It should be considered whether it is appropriate to collect data more frequently in the acute stage and then less frequently during follow-up. It should be considered if one tool is suitable at all time points or if the tool should be adapted depending on time since treatment. More research is needed to identify the exact timings of PRO assessments, and qualitative work with patients is needed to determine the most important issues for them throughout the treatment and follow-up.",,pdf:https://systematicreviewsjournal.biomedcentral.com/counter/pdf/10.1186/s13643-023-02337-8; doi:https://doi.org/10.1186/s13643-023-02337-8; html:https://europepmc.org/articles/PMC10541698; pdf:https://europepmc.org/articles/PMC10541698?pdf=render 35039282,https://doi.org/10.1136/bmjopen-2021-049506,Development and external validation of prognostic models for COVID-19 to support risk stratification in secondary care.,"Adderley NJ, Taverner T, Price MJ, Sainsbury C, Greenwood D, Chandan JS, Takwoingi Y, Haniffa R, Hosier I, Welch C, Parekh D, Gallier S, Gokhale K, Denniston AK, Sapey E, Nirantharakumar K.",,BMJ open,2022,2022-01-17,Y,Public Health; Covid-19,,,"

Objectives

Existing UK prognostic models for patients admitted to the hospital with COVID-19 are limited by reliance on comorbidities, which are under-recorded in secondary care, and lack of imaging data among the candidate predictors. Our aims were to develop and externally validate novel prognostic models for adverse outcomes (death and intensive therapy unit (ITU) admission) in UK secondary care and externally validate the existing 4C score.

Design

Candidate predictors included demographic variables, symptoms, physiological measures, imaging and laboratory tests. Final models used logistic regression with stepwise selection.

Setting

Model development was performed in data from University Hospitals Birmingham (UHB). External validation was performed in the CovidCollab dataset.

Participants

Patients with COVID-19 admitted to UHB January-August 2020 were included.

Main outcome measures

Death and ITU admission within 28 days of admission.

Results

1040 patients with COVID-19 were included in the derivation cohort; 288 (28%) died and 183 (18%) were admitted to ITU within 28 days of admission. Area under the receiver operating characteristic curve (AUROC) for mortality was 0.791 (95% CI 0.761 to 0.822) in UHB and 0.767 (95% CI 0.754 to 0.780) in CovidCollab; AUROC for ITU admission was 0.906 (95% CI 0.883 to 0.929) in UHB and 0.811 (95% CI 0.795 to 0.828) in CovidCollab. Models showed good calibration. Addition of comorbidities to candidate predictors did not improve model performance. AUROC for the International Severe Acute Respiratory and Emerging Infection Consortium 4C score in the UHB dataset was 0.753 (95% CI 0.720 to 0.785).

Conclusions

The novel prognostic models showed good discrimination and calibration in derivation and external validation datasets, and performed at least as well as the existing 4C score using only routinely collected patient information. The models can be integrated into electronic medical records systems to calculate each individual patient's probability of death or ITU admission at the time of hospital admission. Implementation of the models and clinical utility should be evaluated.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/1/e049506.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-049506; html:https://europepmc.org/articles/PMC8764710; pdf:https://europepmc.org/articles/PMC8764710?pdf=render -37840686,https://doi.org/10.3389/fdgth.2023.1184919,Understanding the performance and reliability of NLP tools: a comparison of four NLP tools predicting stroke phenotypes in radiology reports.,"Casey A, Davidson E, Grover C, Tobin R, Grivas A, Zhang H, Schrempf P, O'Neil AQ, Lee L, Walsh M, Pellie F, Ferguson K, Cvoro V, Wu H, Whalley H, Mair G, Whiteley W, Alex B.",,Frontiers in digital health,2023,2023-09-28,Y,Electronic Health Records; Natural Language Processing; Stroke Phenotype; Brain Radiology,,,"

Background

Natural language processing (NLP) has the potential to automate the reading of radiology reports, but there is a need to demonstrate that NLP methods are adaptable and reliable for use in real-world clinical applications.

Methods

We tested the F1 score, precision, and recall to compare NLP tools on a cohort from a study on delirium using images and radiology reports from NHS Fife and a population-based cohort (Generation Scotland) that spans multiple National Health Service health boards. We compared four off-the-shelf rule-based and neural NLP tools (namely, EdIE-R, ALARM+, ESPRESSO, and Sem-EHR) and reported on their performance for three cerebrovascular phenotypes, namely, ischaemic stroke, small vessel disease (SVD), and atrophy. Clinical experts from the EdIE-R team defined phenotypes using labelling techniques developed in the development of EdIE-R, in conjunction with an expert researcher who read underlying images.

Results

EdIE-R obtained the highest F1 score in both cohorts for ischaemic stroke, ≥93%, followed by ALARM+, ≥87%. The F1 score of ESPRESSO was ≥74%, whilst that of Sem-EHR is ≥66%, although ESPRESSO had the highest precision in both cohorts, 90% and 98%. For F1 scores for SVD, EdIE-R scored ≥98% and ALARM+ ≥90%. ESPRESSO scored lowest with ≥77% and Sem-EHR ≥81%. In NHS Fife, F1 scores for atrophy by EdIE-R and ALARM+ were 99%, dropping in Generation Scotland to 96% for EdIE-R and 91% for ALARM+. Sem-EHR performed lowest for atrophy at 89% in NHS Fife and 73% in Generation Scotland. When comparing NLP tool output with brain image reads using F1 scores, ALARM+ scored 80%, outperforming EdIE-R at 66% in ischaemic stroke. For SVD, EdIE-R performed best, scoring 84%, with Sem-EHR 82%. For atrophy, EdIE-R and both ALARM+ versions were comparable at 80%.

Conclusions

The four NLP tools show varying F1 (and precision/recall) scores across all three phenotypes, although more apparent for ischaemic stroke. If NLP tools are to be used in clinical settings, this cannot be performed ""out of the box."" It is essential to understand the context of their development to assess whether they are suitable for the task at hand or whether further training, re-training, or modification is required to adapt tools to the target task.",,pdf:https://www.frontiersin.org/articles/10.3389/fdgth.2023.1184919/pdf?isPublishedV2=False; doi:https://doi.org/10.3389/fdgth.2023.1184919; html:https://europepmc.org/articles/PMC10569314; pdf:https://europepmc.org/articles/PMC10569314?pdf=render 31960476,https://doi.org/10.1111/ppe.12627,Phenotyping congenital anomalies in administrative hospital records.,"Zylbersztejn A, Verfürden M, Hardelid P, Gilbert R, Wijlaars L.",,Paediatric and perinatal epidemiology,2020,2020-01-01,Y,Phenotyping; Congenital Anomalies; International Comparison; Administrative Data,Improving Public Health,,"

Background

Congenital anomalies are a major cause of co-morbidity in children. Diagnostic code lists are increasingly used to identify congenital anomalies in administrative health records. Evidence is lacking on comparability of these code lists.

Objectives

To compare prevalence of congenital anomalies and prognostic outcomes for children with congenital anomalies identified in administrative health records using three different code lists.

Methods

We developed national cohorts of singleton livebirths in England (n = 7 354 363, 2003-2014) and Scotland (n = 493 556, 2003-2011). Children with congenital anomalies were identified if congenital anomaly diagnosis was recorded at birth, during subsequent hospital admission or as cause of death before 2 years old. We used three code lists: the EUROCAT list for congenital anomaly surveillance in Europe; the Hardelid list developed to identify children with chronic conditions (including congenital anomalies) admitted to hospital in England; and the Feudtner list developed to indicate children with complex chronic conditions (including congenital anomalies) admitted to hospitals in the United States. We compared prevalence, and risks of postnatal hospital readmission and death according to each code list in England and Scotland.

Results

Prevalence of congenital anomalies was highest using the EUROCAT list (4.1% of livebirths in England, 3.7% in Scotland), followed by Hardelid (3.1% and 3.0% of livebirths, respectively) and Feudtner (1.8% and 1.5% of livebirths, respectively). 67.2%-73.3% of children with congenital anomalies in England and 65.2%-77.0% in Scotland had at least one postnatal hospital admission across the three code lists; mortality ranged between 42.6-75.4 and 41.5-88.7 deaths per 1000 births in England Scotland, respectively. The risk of these adverse outcomes was highest using Feudtner and lowest using EUROCAT code lists.

Conclusions

The prevalence of congenital anomalies varied by congenital anomaly code list, over time and between countries, reflecting in part differences in hospital coding practices and admission thresholds. As a minimum, researchers using administrative health data to study congenital anomalies should report sensitivity analyses using different code lists.","This study identifies children born with congenital anomalies from administrative health data. The the prevalence of congenital anomalies and prognostic outcomes for children with congenital anomalies are compared using three different code lists. The study found that the prevalence of congenital anomalies varied by code list, over time and between countries. This reflects differences in hospital coding practices and admission thresholds.",pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/ppe.12627; doi:https://doi.org/10.1111/ppe.12627; html:https://europepmc.org/articles/PMC7003968; pdf:https://europepmc.org/articles/PMC7003968?pdf=render +37840686,https://doi.org/10.3389/fdgth.2023.1184919,Understanding the performance and reliability of NLP tools: a comparison of four NLP tools predicting stroke phenotypes in radiology reports.,"Casey A, Davidson E, Grover C, Tobin R, Grivas A, Zhang H, Schrempf P, O'Neil AQ, Lee L, Walsh M, Pellie F, Ferguson K, Cvoro V, Wu H, Whalley H, Mair G, Whiteley W, Alex B.",,Frontiers in digital health,2023,2023-09-28,Y,Electronic Health Records; Natural Language Processing; Stroke Phenotype; Brain Radiology,,,"

Background

Natural language processing (NLP) has the potential to automate the reading of radiology reports, but there is a need to demonstrate that NLP methods are adaptable and reliable for use in real-world clinical applications.

Methods

We tested the F1 score, precision, and recall to compare NLP tools on a cohort from a study on delirium using images and radiology reports from NHS Fife and a population-based cohort (Generation Scotland) that spans multiple National Health Service health boards. We compared four off-the-shelf rule-based and neural NLP tools (namely, EdIE-R, ALARM+, ESPRESSO, and Sem-EHR) and reported on their performance for three cerebrovascular phenotypes, namely, ischaemic stroke, small vessel disease (SVD), and atrophy. Clinical experts from the EdIE-R team defined phenotypes using labelling techniques developed in the development of EdIE-R, in conjunction with an expert researcher who read underlying images.

Results

EdIE-R obtained the highest F1 score in both cohorts for ischaemic stroke, ≥93%, followed by ALARM+, ≥87%. The F1 score of ESPRESSO was ≥74%, whilst that of Sem-EHR is ≥66%, although ESPRESSO had the highest precision in both cohorts, 90% and 98%. For F1 scores for SVD, EdIE-R scored ≥98% and ALARM+ ≥90%. ESPRESSO scored lowest with ≥77% and Sem-EHR ≥81%. In NHS Fife, F1 scores for atrophy by EdIE-R and ALARM+ were 99%, dropping in Generation Scotland to 96% for EdIE-R and 91% for ALARM+. Sem-EHR performed lowest for atrophy at 89% in NHS Fife and 73% in Generation Scotland. When comparing NLP tool output with brain image reads using F1 scores, ALARM+ scored 80%, outperforming EdIE-R at 66% in ischaemic stroke. For SVD, EdIE-R performed best, scoring 84%, with Sem-EHR 82%. For atrophy, EdIE-R and both ALARM+ versions were comparable at 80%.

Conclusions

The four NLP tools show varying F1 (and precision/recall) scores across all three phenotypes, although more apparent for ischaemic stroke. If NLP tools are to be used in clinical settings, this cannot be performed ""out of the box."" It is essential to understand the context of their development to assess whether they are suitable for the task at hand or whether further training, re-training, or modification is required to adapt tools to the target task.",,pdf:https://www.frontiersin.org/articles/10.3389/fdgth.2023.1184919/pdf?isPublishedV2=False; doi:https://doi.org/10.3389/fdgth.2023.1184919; html:https://europepmc.org/articles/PMC10569314; pdf:https://europepmc.org/articles/PMC10569314?pdf=render 35139069,https://doi.org/10.1371/journal.pcbi.1009806,Known allosteric proteins have central roles in genetic disease.,"Abrusán G, Ascher DB, Inouye M.",,PLoS computational biology,2022,2022-02-09,Y,,,,"Allostery is a form of protein regulation, where ligands that bind sites located apart from the active site can modify the activity of the protein. The molecular mechanisms of allostery have been extensively studied, because allosteric sites are less conserved than active sites, and drugs targeting them are more specific than drugs binding the active sites. Here we quantify the importance of allostery in genetic disease. We show that 1) known allosteric proteins are central in disease networks, contribute to genetic disease and comorbidities much more than non-allosteric proteins, and there is an association between being allosteric and involvement in disease; 2) they are enriched in many major disease types like hematopoietic diseases, cardiovascular diseases, cancers, diabetes, or diseases of the central nervous system; 3) variants from cancer genome-wide association studies are enriched near allosteric proteins, indicating their importance to polygenic traits; and 4) the importance of allosteric proteins in disease is due, at least partly, to their central positions in protein-protein interaction networks, and less due to their dynamical properties.",,doi:https://doi.org/10.1371/journal.pcbi.1009806; doi:https://doi.org/10.1371/journal.pcbi.1009806; html:https://europepmc.org/articles/PMC10138267; pdf:https://europepmc.org/articles/PMC10138267?pdf=render 34626176,https://doi.org/10.1093/brain/awab253,Whole-exome sequencing reveals a role of HTRA1 and EGFL8 in brain white matter hyperintensities.,"Malik R, Beaufort N, Frerich S, Gesierich B, Georgakis MK, Rannikmäe K, Ferguson AC, Haffner C, Traylor M, Ehrmann M, Sudlow CLM, Dichgans M.",,Brain : a journal of neurology,2021,2021-10-01,N,Whole-exome Sequencing; White Matter Hyperintensities; Uk Biobank; Htra1; Burden Test,,,"White matter hyperintensities (WMH) are among the most common radiological abnormalities in the ageing population and an established risk factor for stroke and dementia. While common variant association studies have revealed multiple genetic loci with an influence on their volume, the contribution of rare variants to the WMH burden in the general population remains largely unexplored. We conducted a comprehensive analysis of this burden in the UK Biobank using publicly available whole-exome sequencing data (n up to 17 830) and found a splice-site variant in GBE1, encoding 1,4-alpha-glucan branching enzyme 1, to be associated with lower white matter burden on an exome-wide level [c.691+2T>C, β = -0.74, standard error (SE) = 0.13, P = 9.7 × 10-9]. Applying whole-exome gene-based burden tests, we found damaging missense and loss-of-function variants in HTRA1 (frequency of 1 in 275 in the UK Biobank population) to associate with an increased WMH volume (P = 5.5 × 10-6, false discovery rate = 0.04). HTRA1 encodes a secreted serine protease implicated in familial forms of small vessel disease. Domain-specific burden tests revealed that the association with WMH volume was restricted to rare variants in the protease domain (amino acids 204-364; β = 0.79, SE = 0.14, P = 9.4 × 10-8). The frequency of such variants in the UK Biobank population was 1 in 450. The WMH volume was brought forward by ∼11 years in carriers of a rare protease domain variant. A comparison with the effect size of established risk factors for WMH burden revealed that the presence of a rare variant in the HTRA1 protease domain corresponded to a larger effect than meeting the criteria for hypertension (β = 0.26, SE = 0.02, P = 2.9 × 10-59) or being in the upper 99.8% percentile of the distribution of a polygenic risk score based on common genetic variants (β = 0.44, SE = 0.14, P = 0.002). In biochemical experiments, most (6/9) of the identified protease domain variants resulted in markedly reduced protease activity. We further found EGFL8, which showed suggestive evidence for association with WMH volume (P = 1.5 × 10-4, false discovery rate = 0.22) in gene burden tests, to be a direct substrate of HTRA1 and to be preferentially expressed in cerebral arterioles and arteries. In a phenome-wide association study mapping ICD-10 diagnoses to 741 standardized Phecodes, rare variants in the HTRA1 protease domain were associated with multiple neurological and non-neurological conditions including migraine with aura (odds ratio = 12.24, 95%CI: 2.54-35.25; P = 8.3 × 10-5]. Collectively, these findings highlight an important role of rare genetic variation and the HTRA1 protease in determining WMH burden in the general population.",,pdf:https://academic.oup.com/brain/article-pdf/144/9/2670/40880367/awab253.pdf; doi:https://doi.org/10.1093/brain/awab253; html:https://europepmc.org/articles/PMC8557338; pdf:https://europepmc.org/articles/PMC8557338?pdf=render; doi:https://doi.org/10.1093/brain/awab253 36881701,https://doi.org/10.1097/jtn.0000000000000708,Perceptions of an Interactive Trauma Recovery Information Booklet.,"Reeder SC, Ekegren CL, Mather AM, Kimmel LA, Webb MJ, Pellegrini M, Cameron PA, Cameron PA, Gabbe BJ.",,Journal of trauma nursing : the official journal of the Society of Trauma Nurses,2023,2023-03-01,N,,,,"

Background

Previous research has shown that people with traumatic injuries have unmet information needs with respect to their injuries, management, and recovery. An interactive trauma recovery information booklet was developed and implemented to address these information needs at a major trauma center in Victoria, Australia.

Objective

The aim of this quality improvement project was to explore patient and clinician perceptions of a recovery information booklet introduced into a trauma ward.

Methods

Semistructured interviews with trauma patients, family members, and health professionals were undertaken and thematically analyzed using a framework approach. In total, 34 patients, 10 family members, and 26 health professionals were interviewed.

Results

Overall, the booklet was well accepted by most participants and was perceived to contain useful information. The design, content, pictures, and readability were all positively appraised. Many participants used the booklet to record personalized information and to ask health professionals questions about their injuries and management.

Conclusion

Our findings highlight the usefulness and acceptability of a low-cost interactive booklet intervention to facilitate the provision of quality of information and patient-health professional interactions on a trauma ward.",,doi:https://doi.org/10.1097/JTN.0000000000000708 37350492,https://doi.org/10.1093/eurheartj/ehad376,Troponin in early presenters to rule out myocardial infarction.,"Lowry MTH, Doudesis D, Boeddinghaus J, Kimenai DM, Bularga A, Taggart C, Wereski R, Ferry AV, Stewart SD, Tuck C, Koechlin L, Nestelberger T, Lopez-Ayala P, Huré G, Lee KK, Chapman AR, Newby DE, Anand A, Collinson PO, Mueller C, Mills NL, High-STEACS Investigators.",,European heart journal,2023,2023-08-01,Y,Myocardial infarction; cardiac troponin; Symptoms,,,"

Aims

Whether a single cardiac troponin measurement can safely rule out myocardial infarction in patients presenting within a few hours of symptom onset is uncertain. The study aim was to assess the performance of troponin in early presenters.

Methods and results

In patients with possible myocardial infarction, the diagnostic performance of a single measurement of high-sensitivity cardiac troponin I at presentation was evaluated and externally validated in those tested ≤3, 4-12, and >12 h from symptom onset. The limit-of-detection (2 ng/L), rule-out (5 ng/L), and sex-specific 99th centile (16 ng/L in women; 34 ng/L in men) thresholds were compared. In 41 103 consecutive patients [60 (17) years, 46% women], 12 595 (31%) presented within 3 h, and 3728 (9%) had myocardial infarction. In those presenting ≤3 h, a threshold of 2 ng/L had greater sensitivity and negative predictive value [99.4% (95% confidence interval 99.2%-99.5%) and 99.7% (99.6%-99.8%)] compared with 5 ng/L [96.5% (96.2%-96.8%) and 99.3% (99.1%-99.4%)]. In those presenting ≥3 h, the sensitivity and negative predictive value were similar for both thresholds. The sensitivity of the 99th centile was low in early and late presenters at 71.4% (70.6%-72.2%) and 92.5% (92.0%-93.0%), respectively. Findings were consistent in an external validation cohort of 7088 patients.

Conclusion

In early presenters, a single measurement of high-sensitivity cardiac troponin I below the limit of detection may facilitate the safe rule out of myocardial infarction. The 99th centile should not be used to rule out myocardial infarction at presentation even in those presenting later following symptom onset.",,pdf:https://academic.oup.com/eurheartj/advance-article-pdf/doi/10.1093/eurheartj/ehad376/50684614/ehad376.pdf; doi:https://doi.org/10.1093/eurheartj/ehad376; html:https://europepmc.org/articles/PMC10406338; pdf:https://europepmc.org/articles/PMC10406338?pdf=render 33413610,https://doi.org/10.1186/s13073-020-00822-6,An integrated in silico immuno-genetic analytical platform provides insights into COVID-19 serological and vaccine targets.,"Ward D, Higgins M, Phelan JE, Hibberd ML, Campino S, Clark TG.",,Genome medicine,2021,2021-01-07,Y,Mutation; Epitopes; Surveillance; cross-reactivity; Immuno-informatics; Sars-cov-2; Covid; Human-coronavirus,,,"During COVID-19, diagnostic serological tools and vaccines have been developed. To inform control activities in a post-vaccine surveillance setting, we have developed an online ""immuno-analytics"" resource that combines epitope, sequence, protein and SARS-CoV-2 mutation analysis. SARS-CoV-2 spike and nucleocapsid proteins are both vaccine and serological diagnostic targets. Using the tool, the nucleocapsid protein appears to be a sub-optimal target for use in serological platforms. Spike D614G (and nsp12 L314P) mutations were most frequent (> 86%), whilst spike A222V/L18F have recently increased. Also, Orf3a proteins may be a suitable target for serology. The tool can accessed from: http://genomics.lshtm.ac.uk/immuno (online); https://github.com/dan-ward-bio/COVID-immunoanalytics (source code).",,pdf:https://genomemedicine.biomedcentral.com/counter/pdf/10.1186/s13073-020-00822-6; doi:https://doi.org/10.1186/s13073-020-00822-6; html:https://europepmc.org/articles/PMC7790334; pdf:https://europepmc.org/articles/PMC7790334?pdf=render -37294923,https://doi.org/10.1093/eurjpc/zwad192,Incidence of 12 common cardiovascular diseases and subsequent mortality risk in the general population.,"Prugger C, Perier MC, Gonzalez-Izquierdo A, Hemingway H, Denaxas S, Empana JP.",,European journal of preventive cardiology,2023,2023-10-01,N,Prevention; Survival analysis; Stroke; epidemiology; Coronary Heart Disease; incidence,,,"

Background

Incident events of cardiovascular diseases (CVDs) are heterogenous and may result in different mortality risks. Such evidence may help inform patient and physician decisions in CVD prevention and risk factor management.

Aims

This study aimed to determine the extent to which incident events of common CVD show heterogeneous associations with subsequent mortality risk in the general population.

Methods and results

Based on England-wide linked electronic health records, we established a cohort of 1 310 518 people ≥30 years of age initially free of CVD and followed up for non-fatal events of 12 common CVD and cause-specific mortality. The 12 CVDs were considered as time-varying exposures in Cox's proportional hazards models to estimate hazard rate ratios (HRRs) with 95% confidence intervals (CIs). Over the median follow-up of 4.2 years (2010-16), 81 516 non-fatal CVD, 10 906 cardiovascular deaths, and 40 843 non-cardiovascular deaths occurred. All 12 CVDs were associated with increased risk of cardiovascular mortality, with HRR (95% CI) ranging from 1.67 (1.47-1.89) for stable angina to 7.85 (6.62-9.31) for haemorrhagic stroke. All 12 CVDs were also associated with increased non-cardiovascular and all-cause mortality risk but to a lesser extent: HRR (95% CI) ranged from 1.10 (1.00-1.22) to 4.55 (4.03-5.13) and from 1.24 (1.13-1.35) to 4.92 (4.44-5.46) for transient ischaemic attack and sudden cardiac arrest, respectively.

Conclusion

Incident events of 12 common CVD show significant adverse and markedly differential associations with subsequent cardiovascular, non-cardiovascular, and all-cause mortality risk in the general population.",,doi:https://doi.org/10.1093/eurjpc/zwad192 37156273,https://doi.org/10.1016/j.jad.2023.04.138,Subjective and objective sleep and circadian parameters as predictors of depression-related outcomes: A machine learning approach in UK Biobank.,"Lyall LM, Sangha N, Zhu X, Lyall DM, Ward J, Strawbridge RJ, Cullen B, Smith DJ.",,Journal of affective disorders,2023,2023-05-06,N,Sleep; Depression; Circadian rhythms; Postnatal Depression; Inactivity; Rest-activity,,,"

Background

Sleep and circadian disruption are associated with depression onset and severity, but it is unclear which features (e.g., sleep duration, chronotype) are important and whether they can identify individuals showing poorer outcomes.

Methods

Within a subset of the UK Biobank with actigraphy and mental health data (n = 64,353), penalised regression identified the most useful of 51 sleep/rest-activity predictors of depression-related outcomes; including case-control (Major Depression (MD) vs. controls; postnatal depression vs. controls) and within-case comparisons (severe vs. moderate MD; early vs. later onset, atypical vs. typical symptoms; comorbid anxiety; suicidality). Best models (of lasso, ridge, and elastic net) were selected based on Area Under the Curve (AUC).

Results

For MD vs. controls (n(MD) = 24,229; n(control) = 40,124), lasso AUC was 0.68, 95 % confidence interval (CI) 0.67-0.69. Discrimination was reasonable for atypical vs. typical symptoms (n(atypical) = 958; n(typical) = 18,722; ridge: AUC 0.74, 95 % CI 0.71-0.77) but poor for remaining models (AUCs 0.59-0.67). Key predictors across most models included: difficulty getting up, insomnia symptoms, snoring, actigraphy-measured daytime inactivity and lower morning activity (~8 am). In a distinct subset (n = 310,718), the number of these factors shown was associated with all depression outcomes.

Limitations

Analyses were cross-sectional and in middle-/older aged adults: comparison with longitudinal investigations and younger cohorts is necessary.

Discussion

Sleep and circadian measures alone provided poor to moderate discrimination of depression outcomes, but several characteristics were identified that may be clinically useful. Future work should assess these features alongside broader sociodemographic, lifestyle and genetic features.",,doi:https://doi.org/10.1016/j.jad.2023.04.138; doi:https://doi.org/10.1016/j.jad.2023.04.138 +37294923,https://doi.org/10.1093/eurjpc/zwad192,Incidence of 12 common cardiovascular diseases and subsequent mortality risk in the general population.,"Prugger C, Perier MC, Gonzalez-Izquierdo A, Hemingway H, Denaxas S, Empana JP.",,European journal of preventive cardiology,2023,2023-10-01,N,Prevention; Survival analysis; Stroke; epidemiology; Coronary Heart Disease; incidence,,,"

Background

Incident events of cardiovascular diseases (CVDs) are heterogenous and may result in different mortality risks. Such evidence may help inform patient and physician decisions in CVD prevention and risk factor management.

Aims

This study aimed to determine the extent to which incident events of common CVD show heterogeneous associations with subsequent mortality risk in the general population.

Methods and results

Based on England-wide linked electronic health records, we established a cohort of 1 310 518 people ≥30 years of age initially free of CVD and followed up for non-fatal events of 12 common CVD and cause-specific mortality. The 12 CVDs were considered as time-varying exposures in Cox's proportional hazards models to estimate hazard rate ratios (HRRs) with 95% confidence intervals (CIs). Over the median follow-up of 4.2 years (2010-16), 81 516 non-fatal CVD, 10 906 cardiovascular deaths, and 40 843 non-cardiovascular deaths occurred. All 12 CVDs were associated with increased risk of cardiovascular mortality, with HRR (95% CI) ranging from 1.67 (1.47-1.89) for stable angina to 7.85 (6.62-9.31) for haemorrhagic stroke. All 12 CVDs were also associated with increased non-cardiovascular and all-cause mortality risk but to a lesser extent: HRR (95% CI) ranged from 1.10 (1.00-1.22) to 4.55 (4.03-5.13) and from 1.24 (1.13-1.35) to 4.92 (4.44-5.46) for transient ischaemic attack and sudden cardiac arrest, respectively.

Conclusion

Incident events of 12 common CVD show significant adverse and markedly differential associations with subsequent cardiovascular, non-cardiovascular, and all-cause mortality risk in the general population.",,doi:https://doi.org/10.1093/eurjpc/zwad192 36654802,https://doi.org/10.1002/lrh2.10315,"A framework for understanding, designing, developing and evaluating learning health systems.","Foley T, Vale L.",,Learning health systems,2023,2022-05-20,Y,Quality improvement; Informatics; Implementation Science; Learning Health Systems; Learning Healthcare Systems,,,"

Introduction

A Learning Health System is not a technical project. It is the evolution of an existing health system into one capable of learning from every patient. This paper outlines a recently published framework intended to aid the understanding, design, development and evaluation of Learning Health Systems.

Methods

This work extended an existing repository of Learning Health System evidence, adding five more workshops. The total was subjected to thematic analysis, yielding a framework of elements important to understanding, designing, developing and evaluating Learning Health Systems. Purposeful literature reviews were conducted on each element. The findings were revised following a review by a group of international experts.

Results

The resulting framework was arranged around four questions:What is our rationale for developing a Learning Health System?There can be many reasons for developing a Learning Health System. Understanding these will guide its development.What sources of complexity exist at the system and the intervention level?An understanding of complexity is central to making Learning Health Systems work. The non-adoption, abandonment, scale-up, spread and sustainability framework was utilised to help understand and manage it.What strategic approaches to change do we need to consider?A range of strategic issues must be addressed to enable successful change in a Learning Health System. These include, strategy, organisational structure, culture, workforce, implementation science, behaviour change, co-design and evaluation.What technical building blocks will we need?A Learning Health System must capture data from practice, turn it into knowledge and apply it back into practice. There are many methods to achieve this and a range of platforms to help.

Discussion

The results form a framework for understanding, designing, developing and evaluating Learning Health Systems at any scale.

Conclusion

It is hoped that this framework will evolve with use and feedback.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9835047; doi:https://doi.org/10.1002/lrh2.10315; html:https://europepmc.org/articles/PMC9835047; pdf:https://europepmc.org/articles/PMC9835047?pdf=render 33112263,https://doi.org/10.1530/eje-20-0296,Pubertal timing in boys and girls born to mothers with gestational diabetes mellitus: a systematic review.,"Subramanian A, Idkowiak J, Toulis KA, Thangaratinam S, Arlt W, Nirantharakumar K.",,European journal of endocrinology,2021,2021-01-01,Y,,,,"

Context

The incidence of gestational diabetes mellitus (GDM) has been on the rise, driven by maternal obesity. In parallel, pubertal tempo has increased in the general population, driven by childhood obesity.

Objective

To evaluate the available evidence on pubertal timing of boys and girls born to mothers with GDM.

Data sources

We searched MEDLINE, EMBASE, CINAHL Plus, Cochrane library and grey literature for observational studies up to October 2019.

Study selection and extraction

Two reviewers independently selected studies, collected data and appraised the studies for risk of bias. Results were tabulated and narratively described as reported in the primary studies.

Results

Seven articles (six for girls and four for boys) were included. Study quality score was mostly moderate (ranging from 4 to 10 out of 11). In girls born to mothers with GDM, estimates suggest earlier timing of pubarche, thelarche and menarche although for each of these outcomes only one study each showed a statistically significant association. In boys, there was some association between maternal GDM and earlier pubarche, but inconsistency in the direction of shift of age at onset of genital and testicular development and first ejaculation. Only a single study analysed growth patterns in children of mothers with GDM, describing a 3-month advancement in the age of attainment of peak height velocity and a slight increase in pubertal tempo.

Conclusions

Pubertal timing may be influenced by the presence of maternal GDM, though current evidence is sparse and of limited quality. Prospective cohort studies should be conducted, ideally coupled with objective biochemical tests.",,pdf:https://eje.bioscientifica.com/downloadpdf/journals/eje/184/1/EJE-20-0296.pdf; doi:https://doi.org/10.1530/EJE-20-0296; html:https://europepmc.org/articles/PMC7707806; pdf:https://europepmc.org/articles/PMC7707806?pdf=render 32226230,https://doi.org/10.1016/j.neucom.2018.04.087,Covariate shift estimation based adaptive ensemble learning for handling non-stationarity in motor imagery related EEG-based brain-computer interface.,"Raza H, Rathee D, Zhou SM, Cecotti H, Prasad G.",,Neurocomputing,2019,2019-05-01,Y,"Electroencephalogram (Eeg); Pca, Principal Component Analysis; Brain-computer Interface (Bci); Ensemble Learning; Lda, Linear Discriminant Analysis; Eeg, Electroencephalography; Ssl, Semi-supervised Learning; Mi, Motor Imagery; Covariate Shift; Non-stationary Learning; Bci, Brain-computer-interface; Cs, Covariate Shift; Csa, Covariate Shift Adaptation; Cse, Covariate Shift Estimation; Cse-uael, Cse-based Unsupervised Adaptive Ensemble Learning; Csp, Common Spatial Pattern; Csv, Covariate Shift Validation; Csw, Covariate Shift Warning; Dwec, Dynamically Weighted Ensemble Classification; Erd, Synchronization; Ers, Desynchronization; Ewma, Exponential Weighted Moving Average; Fb, Frequency Band; Fbcsp, Filter Bank Common Spatial Pattern; Knn, K-nearest-neighbors; Nsl, Non-stationary Learning; Pwknn, Probabilistic Weighted K-nearest Neighbour; Rsm, Random Subspace Method",Applied Analytics,neurological,"The non-stationary nature of electroencephalography (EEG) signals makes an EEG-based brain-computer interface (BCI) a dynamic system, thus improving its performance is a challenging task. In addition, it is well-known that due to non-stationarity based covariate shifts, the input data distributions of EEG-based BCI systems change during inter- and intra-session transitions, which poses great difficulty for developments of online adaptive data-driven systems. Ensemble learning approaches have been used previously to tackle this challenge. However, passive scheme based implementation leads to poor efficiency while increasing high computational cost. This paper presents a novel integration of covariate shift estimation and unsupervised adaptive ensemble learning (CSE-UAEL) to tackle non-stationarity in motor-imagery (MI) related EEG classification. The proposed method first employs an exponentially weighted moving average model to detect the covariate shifts in the common spatial pattern features extracted from MI related brain responses. Then, a classifier ensemble was created and updated over time to account for changes in streaming input data distribution wherein new classifiers are added to the ensemble in accordance with estimated shifts. Furthermore, using two publicly available BCI-related EEG datasets, the proposed method was extensively compared with the state-of-the-art single-classifier based passive scheme, single-classifier based active scheme and ensemble based passive schemes. The experimental results show that the proposed active scheme based ensemble learning algorithm significantly enhances the BCI performance in MI classifications.",,doi:https://doi.org/10.1016/j.neucom.2018.04.087; doi:https://doi.org/10.1016/j.neucom.2018.04.087; html:https://europepmc.org/articles/PMC7086459 @@ -944,8 +944,8 @@ PMC10686417,https://doi.org/,The impact of restricted provision of publicly fund 37367415,https://doi.org/10.3390/jcdd10060250,Risk Factors of Secondary Cardiovascular Events in a Multi-Ethnic Asian Population with Acute Myocardial Infarction: A Retrospective Cohort Study from Malaysia.,"Ismail SR, Mohammad MSF, Butterworth AS, Chowdhury R, Danesh J, Di Angelantonio E, Griffin SJ, Pennells L, Wood AM, Md Noh MF, Shah SA.",,Journal of cardiovascular development and disease,2023,2023-06-09,Y,Myocardial infarction; risk factors; Asian; Cardiovascular Mortality; Major Adverse Cardiovascular Events,,,"This retrospective cohort study investigated the incidence and risk factors of major adverse cardiovascular events (MACE) after 1 year of first-documented myocardial infarctions (MIs) in a multi-ethnic Asian population. Secondary MACE were observed in 231 (14.3%) individuals, including 92 (5.7%) cardiovascular-related deaths. Both histories of hypertension and diabetes were associated with secondary MACE after adjustment for age, sex, and ethnicity (HR 1.60 [95%CI 1.22-2.12] and 1.46 [95%CI 1.09-1.97], respectively). With further adjustments for traditional risk factors, individuals with conduction disturbances demonstrated higher risks of MACE: new left-bundle branch block (HR 2.86 [95%CI 1.15-6.55]), right-bundle branch block (HR 2.09 [95%CI 1.02-4.29]), and second-degree heart block (HR 2.45 [95%CI 0.59-10.16]). These associations were broadly similar across different age, sex, and ethnicity groups, although somewhat greater for history of hypertension and BMI among women versus men, for HbA1c control in individuals aged >50 years, and for LVEF ≤ 40% in those with Indian versus Chinese or Bumiputera ethnicities. Several traditional and cardiac risk factors are associated with a higher risk of secondary major adverse cardiovascular events. In addition to hypertension and diabetes, the identification of conduction disturbances in individuals with first-onset MI may be useful for the risk stratification of high-risk individuals.",,pdf:https://www.mdpi.com/2308-3425/10/6/250/pdf?version=1686288586; doi:https://doi.org/10.3390/jcdd10060250; html:https://europepmc.org/articles/PMC10299045; pdf:https://europepmc.org/articles/PMC10299045?pdf=render 38274035,https://doi.org/10.1136/bmjmed-2023-000738,Availability of results of clinical trials registered on EU Clinical Trials Register: cross sectional audit study.,"DeVito NJ, Morley J, Smith JA, Drysdale H, Goldacre B, Heneghan C.",,BMJ medicine,2024,2024-01-12,Y,"Ethics, Medical; Clinical Governance; Clinical Trial; Health Policy",,,"

Objective

To identify the availability of results for trials registered on the European Union Clinical Trials Register (EUCTR) compared with other dissemination routes to understand its value as a results repository.

Design

Cross sectional audit study.

Setting

EUCTR protocols and results sections, data extracted 1-3 December 2020.

Population

Random sample of 500 trials registered on EUCTR with a completion date of more than two years from the beginning of searches (ie, 1 December 2018).

Main outcome measures

Proportion of trials with results across the examined dissemination routes (EUCTR, ClinicalTrials.gov, ISRCTN registry, and journal publications), and for each dissemination route individually. Prespecified secondary outcomes were number and proportion of unique results, and the timing of results, for each dissemination route.

Results

In the sample of 500 trials, availability of results on EUCTR (53.2%, 95% confidence interval 48.8% to 57.6%) was similar to the peer reviewed literature (58.6%, 54.3% to 62.9%) and exceeded the proportion of results available on other registries with matched records. Among the 383 trials with any results, 55 (14.4%, 10.9% to 17.9%) were only available on EUCTR. Also, after the launch of the EUCTR results database, median time to results was fastest on EUCTR (1142 days, 95% confidence interval 812 to 1492), comparable with journal publications (1226 days, 1074 to 1551), and exceeding ClinicalTrials.gov (3321 days, 1653 to undefined). For 117 trials (23.4%, 19.7% to 27.1%), however, results were published elsewhere but not submitted to the EUCTR registry, and no results were located in any dissemination route for 117 trials (23.4%, 19.7% to 27.1).

Conclusions

EUCTR should be considered in results searches for systematic reviews and can help researchers and the public to access the results of clinical trials, unavailable elsewhere, in a timely way. Reporting requirements, such as the EU's, can help in avoiding research waste by ensuring results are reported. The registry's true value, however, is unrealised because of inadequate compliance with EU guidelines, and problems with data quality that complicate the routine use of the registry. As the EU transitions to a new registry, continuing to emphasise the importance of EUCTR and the provision of timely and complete data is critical. For the future, EUCTR will still hold important information from the past two decades of clinical research in Europe. With increased efforts from sponsors and regulators, the registry can continue to grow as a source of results of clinical trials, many of which might be unavailable from other dissemination routes.",,doi:https://doi.org/10.1136/bmjmed-2023-000738; html:https://europepmc.org/articles/PMC10806997; pdf:https://europepmc.org/articles/PMC10806997?pdf=render 37679419,https://doi.org/10.1038/s41588-023-01462-3,"GWAS of random glucose in 476,326 individuals provide insights into diabetes pathophysiology, complications and treatment stratification.","Lagou V, Jiang L, Ulrich A, Zudina L, González KSG, Balkhiyarova Z, Faggian A, Maina JG, Chen S, Todorov PV, Sharapov S, David A, Marullo L, Mägi R, Rujan RM, Ahlqvist E, Thorleifsson G, Gao Η, Εvangelou Ε, Benyamin B, Scott RA, Isaacs A, Zhao JH, Willems SM, Johnson T, Gieger C, Grallert H, Meisinger C, Müller-Nurasyid M, Strawbridge RJ, Goel A, Rybin D, Albrecht E, Jackson AU, Stringham HM, Corrêa IR, Farber-Eger E, Steinthorsdottir V, Uitterlinden AG, Munroe PB, Brown MJ, Schmidberger J, Holmen O, Thorand B, Hveem K, Wilsgaard T, Mohlke KL, Wang Z, GWA-PA Consortium, Shmeliov A, den Hoed M, Loos RJF, Kratzer W, Haenle M, Koenig W, Boehm BO, Tan TM, Tomas A, Salem V, Barroso I, Tuomilehto J, Boehnke M, Florez JC, Hamsten A, Watkins H, Njølstad I, Wichmann HE, Caulfield MJ, Khaw KT, van Duijn CM, Hofman A, Wareham NJ, Langenberg C, Whitfield JB, Martin NG, Montgomery G, Scapoli C, Tzoulaki I, Elliott P, Thorsteinsdottir U, Stefansson K, Brittain EL, McCarthy MI, Froguel P, Sexton PM, Wootten D, Groop L, Dupuis J, Meigs JB, Deganutti G, Demirkan A, Pers TH, Reynolds CA, Aulchenko YS, Kaakinen MA, Jones B, Prokopenko I, Meta-Analysis of Glucose and Insulin-Related Traits Consortium (MAGIC).",,Nature genetics,2023,2023-09-07,Y,,,,"Conventional measurements of fasting and postprandial blood glucose levels investigated in genome-wide association studies (GWAS) cannot capture the effects of DNA variability on 'around the clock' glucoregulatory processes. Here we show that GWAS meta-analysis of glucose measurements under nonstandardized conditions (random glucose (RG)) in 476,326 individuals of diverse ancestries and without diabetes enables locus discovery and innovative pathophysiological observations. We discovered 120 RG loci represented by 150 distinct signals, including 13 with sex-dimorphic effects, two cross-ancestry and seven rare frequency signals. Of these, 44 loci are new for glycemic traits. Regulatory, glycosylation and metagenomic annotations highlight ileum and colon tissues, indicating an underappreciated role of the gastrointestinal tract in controlling blood glucose. Functional follow-up and molecular dynamics simulations of lower frequency coding variants in glucagon-like peptide-1 receptor (GLP1R), a type 2 diabetes treatment target, reveal that optimal selection of GLP-1R agonist therapy will benefit from tailored genetic stratification. We also provide evidence from Mendelian randomization that lung function is modulated by blood glucose and that pulmonary dysfunction is a diabetes complication. Our investigation yields new insights into the biology of glucose regulation, diabetes complications and pathways for treatment stratification.",,pdf:https://www.nature.com/articles/s41588-023-01462-3.pdf; doi:https://doi.org/10.1038/s41588-023-01462-3; html:https://europepmc.org/articles/PMC10484788; pdf:https://europepmc.org/articles/PMC10484788?pdf=render -34481555,https://doi.org/10.1016/s2213-8587(21)00207-2,"Identifying adults at high-risk for change in weight and BMI in England: a longitudinal, large-scale, population-based cohort study using electronic health records.","Katsoulis M, Lai AG, Diaz-Ordaz K, Gomes M, Pasea L, Banerjee A, Denaxas S, Tsilidis K, Lagiou P, Misirli G, Bhaskaran K, Wannamethee G, Dobson R, Batterham RL, Kipourou DK, Lumbers RT, Wen L, Wareham N, Langenberg C, Hemingway H.",,The lancet. Diabetes & endocrinology,2021,2021-09-02,Y,,,,"

Background

Targeted obesity prevention policies would benefit from the identification of population groups with the highest risk of weight gain. The relative importance of adult age, sex, ethnicity, geographical region, and degree of social deprivation on weight gain is not known. We aimed to identify high-risk groups for changes in weight and BMI using electronic health records (EHR).

Methods

In this longitudinal, population-based cohort study we used linked EHR data from 400 primary care practices (via the Clinical Practice Research Datalink) in England, accessed via the CALIBER programme. Eligible participants were aged 18-74 years, were registered at a general practice clinic, and had BMI and weight measurements recorded between Jan 1, 1998, and June 30, 2016, during the period when they had eligible linked data with at least 1 year of follow-up time. We calculated longitudinal changes in BMI over 1, 5, and 10 years, and investigated the absolute risk and odds ratios (ORs) of transitioning between BMI categories (underweight, normal weight, overweight, obesity class 1 and 2, and severe obesity [class 3]), as defined by WHO. The associations of demographic factors with BMI transitions were estimated by use of logistic regression analysis, adjusting for baseline BMI, family history of cardiovascular disease, use of diuretics, and prevalent chronic conditions.

Findings

We included 2 092 260 eligible individuals with more than 9 million BMI measurements in our study. Young adult age was the strongest risk factor for weight gain at 1, 5, and 10 years of follow-up. Compared with the oldest age group (65-74 years), adults in the youngest age group (18-24 years) had the highest OR (4·22 [95% CI 3·86-4·62]) and greatest absolute risk (37% vs 24%) of transitioning from normal weight to overweight or obesity at 10 years. Likewise, adults in the youngest age group with overweight or obesity at baseline were also at highest risk to transition to a higher BMI category; OR 4·60 (4·06-5·22) and absolute risk (42% vs 18%) of transitioning from overweight to class 1 and 2 obesity, and OR 5·87 (5·23-6·59) and absolute risk (22% vs 5%) of transitioning from class 1 and 2 obesity to class 3 obesity. Other demographic factors were consistently less strongly associated with these transitions; for example, the OR of transitioning from normal weight to overweight or obesity in people living in the most socially deprived versus least deprived areas was 1·23 (1·18-1·27), for men versus women was 1·12 (1·08-1·16), and for Black individuals versus White individuals was 1·13 (1·04-1·24). We provide an open access online risk calculator, and present high-resolution obesity risk charts over a 1-year, 5-year, and 10-year follow-up period.

Interpretation

A radical shift in policy is required to focus on individuals at the highest risk of weight gain (ie, young adults aged 18-24 years) for individual-level and population-level prevention of obesity and its long-term consequences for health and health care.

Funding

The British Hearth Foundation, Health Data Research UK, the UK Medical Research Council, and the National Institute for Health Research.",,pdf:http://www.thelancet.com/article/S2213858721002072/pdf; doi:https://doi.org/10.1016/S2213-8587(21)00207-2; html:https://europepmc.org/articles/PMC8440227; pdf:https://europepmc.org/articles/PMC8440227?pdf=render 32626822,https://doi.org/10.1007/s41109-020-00273-3,Normalised degree variance.,"Smith KM, Escudero J.",,Applied network science,2020,2020-06-22,Y,,,,"Finding graph indices which are unbiased to network size and density is of high importance both within a given field and across fields for enhancing comparability of modern network science studies. The degree variance is an important metric for characterising network degree heterogeneity. Here, we provide an analytically valid normalisation of degree variance to replace previous normalisations which are either invalid or not applicable to all networks. It is shown that this normalisation provides equal values for graphs and their complements; it is maximal in the star graph (and its complement); and its expected value is constant with respect to density for Erdös-Rényi (ER) random graphs of the same size. We strengthen these results with model observations in ER random graphs, random geometric graphs, scale-free networks, random hierarchy networks and resting-state brain networks, showing that the proposed normalisation is generally less affected by both network size and density than previous normalisation attempts. The closed form expression proposed also benefits from high computational efficiency and straightforward mathematical analysis. Analysis of 184 real-world binary networks across different disciplines shows that normalised degree variance is not correlated with average degree and is robust to node and edge subsampling. Comparisons across subdomains of biological networks reveals greater degree heterogeneity among brain connectomes and food webs than in protein interaction networks.",,pdf:https://appliednetsci.springeropen.com/track/pdf/10.1007/s41109-020-00273-3; doi:https://doi.org/10.1007/s41109-020-00273-3; html:https://europepmc.org/articles/PMC7319291; pdf:https://europepmc.org/articles/PMC7319291?pdf=render +34481555,https://doi.org/10.1016/s2213-8587(21)00207-2,"Identifying adults at high-risk for change in weight and BMI in England: a longitudinal, large-scale, population-based cohort study using electronic health records.","Katsoulis M, Lai AG, Diaz-Ordaz K, Gomes M, Pasea L, Banerjee A, Denaxas S, Tsilidis K, Lagiou P, Misirli G, Bhaskaran K, Wannamethee G, Dobson R, Batterham RL, Kipourou DK, Lumbers RT, Wen L, Wareham N, Langenberg C, Hemingway H.",,The lancet. Diabetes & endocrinology,2021,2021-09-02,Y,,,,"

Background

Targeted obesity prevention policies would benefit from the identification of population groups with the highest risk of weight gain. The relative importance of adult age, sex, ethnicity, geographical region, and degree of social deprivation on weight gain is not known. We aimed to identify high-risk groups for changes in weight and BMI using electronic health records (EHR).

Methods

In this longitudinal, population-based cohort study we used linked EHR data from 400 primary care practices (via the Clinical Practice Research Datalink) in England, accessed via the CALIBER programme. Eligible participants were aged 18-74 years, were registered at a general practice clinic, and had BMI and weight measurements recorded between Jan 1, 1998, and June 30, 2016, during the period when they had eligible linked data with at least 1 year of follow-up time. We calculated longitudinal changes in BMI over 1, 5, and 10 years, and investigated the absolute risk and odds ratios (ORs) of transitioning between BMI categories (underweight, normal weight, overweight, obesity class 1 and 2, and severe obesity [class 3]), as defined by WHO. The associations of demographic factors with BMI transitions were estimated by use of logistic regression analysis, adjusting for baseline BMI, family history of cardiovascular disease, use of diuretics, and prevalent chronic conditions.

Findings

We included 2 092 260 eligible individuals with more than 9 million BMI measurements in our study. Young adult age was the strongest risk factor for weight gain at 1, 5, and 10 years of follow-up. Compared with the oldest age group (65-74 years), adults in the youngest age group (18-24 years) had the highest OR (4·22 [95% CI 3·86-4·62]) and greatest absolute risk (37% vs 24%) of transitioning from normal weight to overweight or obesity at 10 years. Likewise, adults in the youngest age group with overweight or obesity at baseline were also at highest risk to transition to a higher BMI category; OR 4·60 (4·06-5·22) and absolute risk (42% vs 18%) of transitioning from overweight to class 1 and 2 obesity, and OR 5·87 (5·23-6·59) and absolute risk (22% vs 5%) of transitioning from class 1 and 2 obesity to class 3 obesity. Other demographic factors were consistently less strongly associated with these transitions; for example, the OR of transitioning from normal weight to overweight or obesity in people living in the most socially deprived versus least deprived areas was 1·23 (1·18-1·27), for men versus women was 1·12 (1·08-1·16), and for Black individuals versus White individuals was 1·13 (1·04-1·24). We provide an open access online risk calculator, and present high-resolution obesity risk charts over a 1-year, 5-year, and 10-year follow-up period.

Interpretation

A radical shift in policy is required to focus on individuals at the highest risk of weight gain (ie, young adults aged 18-24 years) for individual-level and population-level prevention of obesity and its long-term consequences for health and health care.

Funding

The British Hearth Foundation, Health Data Research UK, the UK Medical Research Council, and the National Institute for Health Research.",,pdf:http://www.thelancet.com/article/S2213858721002072/pdf; doi:https://doi.org/10.1016/S2213-8587(21)00207-2; html:https://europepmc.org/articles/PMC8440227; pdf:https://europepmc.org/articles/PMC8440227?pdf=render 34870259,https://doi.org/10.1016/j.xgen.2021.100005,Sequencing-based genome-wide association studies reporting standards.,"McMahon A, Lewis E, Buniello A, Cerezo M, Hall P, Sollis E, Parkinson H, Hindorff LA, Harris LW, MacArthur JAL.",,Cell genomics,2021,2021-10-01,Y,,,,"Genome sequencing has recently become a viable genotyping technology for use in genome-wide association studies (GWASs), offering the potential to analyze a broader range of genome-wide variation, including rare variants. To survey current standards, we assessed the content and quality of reporting of statistical methods, analyses, results, and datasets in 167 exome- or genome-wide-sequencing-based GWAS publications published from 2014 to 2020; 81% of publications included tests of aggregate association across multiple variants, with multiple test models frequently used. We observed a lack of standardized terms and incomplete reporting of datasets, particularly for variants analyzed in aggregate tests. We also find a lower frequency of sharing of summary statistics compared with array-based GWASs. Reporting standards and increased data sharing are required to ensure sequencing-based association study data are findable, interoperable, accessible, and reusable (FAIR). To support that, we recommend adopting the standard terminology of sequencing-based GWAS (seqGWAS). Further, we recommend that single-variant analyses be reported following the same standards and conventions as standard array-based GWASs and be shared in the GWAS Catalog. We also provide initial recommended standards for aggregate analyses metadata and summary statistics.",,doi:https://doi.org/10.1016/j.xgen.2021.100005; doi:https://doi.org/10.1016/j.xgen.2021.100005; html:https://europepmc.org/articles/PMC8637874; pdf:https://europepmc.org/articles/PMC8637874?pdf=render 37578823,https://doi.org/10.2196/45233,Challenges in Using mHealth Data From Smartphones and Wearable Devices to Predict Depression Symptom Severity: Retrospective Analysis.,"Sun S, Folarin AA, Zhang Y, Cummins N, Garcia-Dias R, Stewart C, Ranjan Y, Rashid Z, Conde P, Laiou P, Sankesara H, Matcham F, Leightley D, White KM, Oetzmann C, Ivan A, Lamers F, Siddi S, Simblett S, Nica R, Rintala A, Mohr DC, Myin-Germeys I, Wykes T, Haro JM, Penninx BWJH, Vairavan S, Narayan VA, Annas P, Hotopf M, Dobson RJB, RADAR-CNS Consortium.",,Journal of medical Internet research,2023,2023-08-14,Y,Depression; Mobile phone; Missing Data; Smartphones; Behavioral Patterns; Digital Phenotypes; Mobile Health; Wearable Devices,,,"

Background

Major depressive disorder (MDD) affects millions of people worldwide, but timely treatment is not often received owing in part to inaccurate subjective recall and variability in the symptom course. Objective and frequent MDD monitoring can improve subjective recall and help to guide treatment selection. Attempts have been made, with varying degrees of success, to explore the relationship between the measures of depression and passive digital phenotypes (features) extracted from smartphones and wearables devices to remotely and continuously monitor changes in symptomatology. However, a number of challenges exist for the analysis of these data. These include maintaining participant engagement over extended time periods and therefore understanding what constitutes an acceptable threshold of missing data; distinguishing between the cross-sectional and longitudinal relationships for different features to determine their utility in tracking within-individual longitudinal variation or screening individuals at high risk; and understanding the heterogeneity with which depression manifests itself in behavioral patterns quantified by the passive features.

Objective

We aimed to address these 3 challenges to inform future work in stratified analyses.

Methods

Using smartphone and wearable data collected from 479 participants with MDD, we extracted 21 features capturing mobility, sleep, and smartphone use. We investigated the impact of the number of days of available data on feature quality using the intraclass correlation coefficient and Bland-Altman analysis. We then examined the nature of the correlation between the 8-item Patient Health Questionnaire (PHQ-8) depression scale (measured every 14 days) and the features using the individual-mean correlation, repeated measures correlation, and linear mixed effects model. Furthermore, we stratified the participants based on their behavioral difference, quantified by the features, between periods of high (depression) and low (no depression) PHQ-8 scores using the Gaussian mixture model.

Results

We demonstrated that at least 8 (range 2-12) days were needed for reliable calculation of most of the features in the 14-day time window. We observed that features such as sleep onset time correlated better with PHQ-8 scores cross-sectionally than longitudinally, whereas features such as wakefulness after sleep onset correlated well with PHQ-8 longitudinally but worse cross-sectionally. Finally, we found that participants could be separated into 3 distinct clusters according to their behavioral difference between periods of depression and periods of no depression.

Conclusions

This work contributes to our understanding of how these mobile health-derived features are associated with depression symptom severity to inform future work in stratified analyses.",,pdf:https://www.jmir.org/2023/1/e45233/PDF; doi:https://doi.org/10.2196/45233; html:https://europepmc.org/articles/PMC10463088 38811438,https://doi.org/10.1007/s00586-024-08315-5,Early evaluation of a natural language processing tool to improve access to educational resources for surgical patients.,"Booker J, Penn J, Noor K, Dobson RJB, Funnell JP, Koh CH, Khan DZ, Newall N, Rowland D, Sinha S, Williams SC, Sayal P, Marcus HJ.",,"European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society",2024,2024-05-30,N,Spine; Education; Machine Learning; Natural Language Processing; automation,,,"

Purpose

Accessible patient information sources are vital in educating patients about the benefits and risks of spinal surgery, which is crucial for obtaining informed consent. We aim to assess the effectiveness of a natural language processing (NLP) pipeline in recognizing surgical procedures from clinic letters and linking this with educational resources.

Methods

Retrospective examination of letters from patients seeking surgery for degenerative spinal disease at a single neurosurgical center. We utilized MedCAT, a named entity recognition and linking NLP, integrated into the electronic health record (EHR), which extracts concepts and links them to systematized nomenclature of medicine-clinical terms (SNOMED-CT). Investigators reviewed clinic letters, identifying words or phrases that described or identified operations and recording the SNOMED-CT terms as ground truth. This was compared to SNOMED-CT terms identified by the model, untrained on our dataset. A pipeline linking clinic letters to patient-specific educational resources was established, and precision, recall, and F1 scores were calculated.

Results

Across 199 letters the model identified 582 surgical procedures, and the overall pipeline after adding rules a total of 784 procedures (precision = 0.94, recall = 0.86, F1 = 0.91). Across 187 letters with identified SNOMED-CT terms the integrated pipeline linking education resources directly to the EHR was successful in 157 (78%) patients (precision = 0.99, recall = 0.87, F1 = 0.92).

Conclusions

NLP accurately identifies surgical procedures in pre-operative clinic letters within an untrained subspecialty. Performance varies among letter authors and depends on the language used by clinicians. The identified procedures can be linked to patient education resources, potentially improving patients' understanding of surgical procedures.",,doi:https://doi.org/10.1007/s00586-024-08315-5; doi:https://doi.org/10.1007/s00586-024-08315-5 @@ -970,23 +970,23 @@ PMC10686417,https://doi.org/,The impact of restricted provision of publicly fund 35055401,https://doi.org/10.3390/jpm12010086,Predicting Hospital Readmission for Campylobacteriosis from Electronic Health Records: A Machine Learning and Text Mining Perspective.,"Zhou SM, Lyons RA, Rahman MA, Holborow A, Brophy S.",,Journal of personalized medicine,2022,2022-01-10,Y,Hospitalisation; Feature Selection; Machine Learning; Readmission; Electronic Health Records; Text Mining; Campylobacter Infections,,,"(1) Background: This study investigates influential risk factors for predicting 30-day readmission to hospital for Campylobacter infections (CI). (2) Methods: We linked general practitioner and hospital admission records of 13,006 patients with CI in Wales (1990-2015). An approach called TF-zR (term frequency-zRelevance) technique was presented to evaluates how relevant a clinical term is to a patient in a cohort characterized by coded health records. The zR is a supervised term-weighting metric to assign weight to a term based on relative frequencies of the term across different classes. Cost-sensitive classifier with swarm optimization and weighted subset learning was integrated to identify influential clinical signals as predictors and optimal model for readmission prediction. (3) Results: From a pool of up to 17,506 variables, 33 most predictive factors were identified, including age, gender, Townsend deprivation quintiles, comorbidities, medications, and procedures. The predictive model predicted readmission with 73% sensitivity and 54% specificity. Variables associated with readmission included male gender, recurrent tonsillitis, non-healing open wounds, operation for in-gown toenails. Cystitis, paracetamol/codeine use, age (21-25), and heliclear triple pack use, were associated with a lower risk of readmission. (4) Conclusions: This study gives a profile of clustered variables that are predictive of readmission associated with campylobacteriosis.",,pdf:https://www.mdpi.com/2075-4426/12/1/86/pdf?version=1641832520; doi:https://doi.org/10.3390/jpm12010086; html:https://europepmc.org/articles/PMC8779953; pdf:https://europepmc.org/articles/PMC8779953?pdf=render 36525457,https://doi.org/10.1371/journal.pone.0279250,Undergoing radical treatment for prostate cancer and its impact on wellbeing: A qualitative study exploring men's experiences.,"Vyas N, Brunckhorst O, Fox L, Van Hemelrijck M, Muir G, Stewart R, Dasgupta P, Ahmed K.",,PloS one,2022,2022-12-16,Y,,,,"

Introduction

Quality of life in prostate cancer survivorship is becoming increasingly important, with mental and social wellbeing recognised as key components. However, limited global evaluation of psychosocial challenges experienced after treatment exists. Therefore, we aimed to explore the lived experiences of men who underwent radical treatment, and its psychosocial impact.

Material and methods

This qualitative study was conducted using 19 men who had undergone radical treatment (prostatectomy or radiotherapy) for their cancer. Semi-structured interviews were conducted exploring lived experiences of men after treatment. A Structured thematic analysis of collected data was undertaken, with an inductive co-construction of themes through the lens of the biopsychosocial model. Themes generated were considered within a psychological, social, and physical wellbeing framework.

Results

An initial knowledge gap meant mental wellbeing was strongly impacted initially leading to a 'Diagnostic Blow and the Search for Clarity'. Doubt over individuals' future resulted in 'An Uncertain Future' in many men. Once treatment was completed a 'Reflective journey' began, with men considering their outcomes and decisions made. Social wellbeing was also impacted with many identifying the 'Emotional Repercussions' on their relationships and the impact their diagnosis had on their partner and family. Many subsequently sought to increase their support through 'The Social Network and Advocacy', while physical changes led to an increased need for 'Social Planning'. Finally, physical wellbeing was highlighted by a continual acknowledgement of the 'Natural process of ageing' leading to a reluctancy to seek help, whilst simultaneously attempting to improve existing health via 'The Health Kick'.

Conclusions

Radical treatments have a considerable impact on mental and social wellbeing of individuals. Anxiety after diagnosis and significant uncertainty over individual futures exist, with physical complications of treatment leading to social repercussions. Future research should aim to identify forms of support to improve quality of life of these men.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0279250&type=printable; doi:https://doi.org/10.1371/journal.pone.0279250; html:https://europepmc.org/articles/PMC9757548; pdf:https://europepmc.org/articles/PMC9757548?pdf=render 37953241,https://doi.org/10.1186/s12916-023-03153-6,Cardiovascular events and venous thromboembolism after primary malignant or non-malignant brain tumour diagnosis: a population matched cohort study in Wales (United Kingdom).,"Poon MTC, Brennan PM, Jin K, Sudlow CLM, Figueroa JD.",,BMC medicine,2023,2023-11-13,Y,Brain cancer; Cerebrovascular disease; Neuro-oncology; Population-based,,,"

Background

Elevated standardised mortality ratio of cardiovascular diseases (CVD) in patients with brain tumours may result from differences in the CVD incidences and cardiovascular risk factors. We compared the risk of CVD among patients with a primary malignant or non-malignant brain tumour to a matched general population cohort, accounting for other co-morbidities.

Methods

Using data from the Secured Anonymised Information Linkage (SAIL) Databank in Wales (United Kingdom), we identified all adults aged ≥ 18 years in the primary care database with first diagnosis of malignant or non-malignant brain tumour identified in the cancer registry in 2000-2014 and a matched cohort (case-to-control ratio 1:5) by age, sex and primary care provider from the general population without any cancer diagnosis. Outcomes included fatal and non-fatal major vascular events (stroke, ischaemic heart disease, aortic and peripheral vascular diseases) and venous thromboembolism (VTE). We used multivariable Cox models adjusted for clinical risk factors to compare risks, stratified by tumour behaviour (malignant or non-malignant) and follow-up period.

Results

There were 2869 and 3931 people diagnosed with malignant or non-malignant brain tumours, respectively, between 2000 and 2014 in Wales. They were matched to 33,785 controls. Within the first year of tumour diagnosis, malignant tumour was associated with a higher risk of VTE (hazard ratio [HR] 21.58, 95% confidence interval 16.12-28.88) and stroke (HR 3.32, 2.44-4.53). After the first year, the risks of VTE (HR 2.20, 1.52-3.18) and stroke (HR 1.45, 1.00-2.10) remained higher than controls. Patients with non-malignant tumours had higher risks of VTE (HR 3.72, 2.73-5.06), stroke (HR 4.06, 3.35-4.93) and aortic and peripheral arterial disease (HR 2.09, 1.26-3.48) within the first year of diagnosis compared with their controls.

Conclusions

The elevated CVD and VTE risks suggested risk reduction may be a strategy to improve life quality and survival in people with a brain tumour.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-023-03153-6; doi:https://doi.org/10.1186/s12916-023-03153-6; html:https://europepmc.org/articles/PMC10641987; pdf:https://europepmc.org/articles/PMC10641987?pdf=render -38660461,https://doi.org/10.1089/neur.2023.0116,The Australian Traumatic Brain Injury Initiative: Statement of Working Principles and Rapid Review of Methods to Define Data Dictionaries for Neurological Conditions.,"Bagg MK, Hicks AJ, Hellewell SC, Ponsford JL, Lannin NA, O'Brien TJ, Cameron PA, Cooper DJ, Rushworth N, Gabbe BJ, Fitzgerald M.",,Neurotrauma reports,2024,2024-04-11,Y,Brain injuries; Traumatic; Neurology; Common Data Elements; Systematic Review [Publication Type],,,"The Australian Traumatic Brain Injury Initiative (AUS-TBI) aims to develop a health informatics approach to collect data predictive of outcomes for persons with moderate-severe TBI across Australia. Central to this approach is a data dictionary; however, no systematic reviews of methods to define and develop data dictionaries exist to-date. This rapid systematic review aimed to identify and characterize methods for designing data dictionaries to collect outcomes or variables in persons with neurological conditions. Database searches were conducted from inception through October 2021. Records were screened in two stages against set criteria to identify methods to define data dictionaries for neurological conditions (International Classification of Diseases, 11th Revision: 08, 22, and 23). Standardized data were extracted. Processes were checked at each stage by independent review of a random 25% of records. Consensus was reached through discussion where necessary. Thirty-nine initiatives were identified across 29 neurological conditions. No single established or recommended method for defining a data dictionary was identified. Nine initiatives conducted systematic reviews to collate information before implementing a consensus process. Thirty-seven initiatives consulted with end-users. Methods of consultation were ""roundtable"" discussion (n = 30); with facilitation (n = 16); that was iterative (n = 27); and frequently conducted in-person (n = 27). Researcher stakeholders were involved in all initiatives and clinicians in 25. Importantly, only six initiatives involved persons with lived experience of TBI and four involved carers. Methods for defining data dictionaries were variable and reporting is sparse. Our findings are instructive for AUS-TBI and can be used to further development of methods for defining data dictionaries.",,doi:https://doi.org/10.1089/neur.2023.0116; html:https://europepmc.org/articles/PMC11040195; pdf:https://europepmc.org/articles/PMC11040195?pdf=render 37812323,https://doi.org/10.1186/s41687-023-00634-3,Development and usability testing of an electronic patient-reported outcome (ePRO) solution for patients with inflammatory diseases in an Advanced Therapy Medicinal Product (ATMP) basket trial.,"McMullan C, Retzer A, Hughes SE, Aiyegbusi OL, Bathurst C, Boyd A, Coleman J, Davies EH, Denniston AK, Dunster H, Frost C, Harding R, Hunn A, Kyte D, Malpass R, McNamara G, Mitchell S, Mittal S, Newsome PN, Price G, Rowe A, van Reil W, Walker A, Wilson R, Calvert M.",,Journal of patient-reported outcomes,2023,2023-10-09,Y,Inflammatory Conditions; Usability Testing; Cognitive Interviews; Electronic Patient Reported Outcomes; Early Phase Advanced Therapy Trial,,,"

Background

Electronic patient-reported outcome (ePRO) systems are increasingly used in clinical trials to provide evidence of efficacy and tolerability of treatment from the patient perspective. The aim of this study is twofold: (1) to describe how we developed an electronic platform for patients to report their symptoms, and (2) to develop and undertake usability testing of an ePRO solution for use in a study of cell therapy seeking to provide early evidence of efficacy and tolerability of treatment and test the feasibility of the system for use in later phase studies.

Methods

An ePRO system was designed to be used in a single arm, multi-centre, phase II basket trial investigating the safety and activity of the use of ORBCEL-C™ in the treatment of patients with inflammatory conditions. ORBCEL-C™ is an enriched Mesenchymal Stromal Cells product isolated from human umbilical cord tissue using CD362+ cell selection. Usability testing sessions were conducted using cognitive interviews and the 'Think Aloud' method with patient advisory group members and Research Nurses to assess the usability of the system.

Results

Nine patient partners and seven research nurses took part in one usability testing session. Measures of fatigue and health-related quality of life, the PRO-CTCAE™ and FACT-GP5 global tolerability question were included in the ePRO system. Alert notifications to the clinical team were triggered by PRO-CTCAE™ and FACT-GP5 scores. Patient participants liked the simplicity and responsiveness of the patient-facing app. Two patients were unable to complete the testing session, due to technical issues. Research Nurses suggested minor modifications to improve functionality and the layout of the clinician dashboard and the training materials.

Conclusion

By testing the effectiveness, efficiency, and satisfaction of our novel ePRO system (PROmicsR), we learnt that most people with an inflammatory condition found it easy to report their symptoms using an app on their own device. Their experiences using the PROmicsR ePRO system within a trial environment will be further explored in our upcoming feasibility testing. Research nurses were also positive and found the clinical dashboard easy-to-use. Using ePROs in early phase trials is important in order to provide evidence of therapeutic responses and tolerability, increase the evidence based, and inform methodology development.

Trial registration

ISRCTN, ISRCTN80103507. Registered 01 April 2022, https://www.isrctn.com/ISRCTN80103507.",,pdf:https://jpro.springeropen.com/counter/pdf/10.1186/s41687-023-00634-3; doi:https://doi.org/10.1186/s41687-023-00634-3; html:https://europepmc.org/articles/PMC10562321; pdf:https://europepmc.org/articles/PMC10562321?pdf=render +38660461,https://doi.org/10.1089/neur.2023.0116,The Australian Traumatic Brain Injury Initiative: Statement of Working Principles and Rapid Review of Methods to Define Data Dictionaries for Neurological Conditions.,"Bagg MK, Hicks AJ, Hellewell SC, Ponsford JL, Lannin NA, O'Brien TJ, Cameron PA, Cooper DJ, Rushworth N, Gabbe BJ, Fitzgerald M.",,Neurotrauma reports,2024,2024-04-11,Y,Brain injuries; Traumatic; Neurology; Common Data Elements; Systematic Review [Publication Type],,,"The Australian Traumatic Brain Injury Initiative (AUS-TBI) aims to develop a health informatics approach to collect data predictive of outcomes for persons with moderate-severe TBI across Australia. Central to this approach is a data dictionary; however, no systematic reviews of methods to define and develop data dictionaries exist to-date. This rapid systematic review aimed to identify and characterize methods for designing data dictionaries to collect outcomes or variables in persons with neurological conditions. Database searches were conducted from inception through October 2021. Records were screened in two stages against set criteria to identify methods to define data dictionaries for neurological conditions (International Classification of Diseases, 11th Revision: 08, 22, and 23). Standardized data were extracted. Processes were checked at each stage by independent review of a random 25% of records. Consensus was reached through discussion where necessary. Thirty-nine initiatives were identified across 29 neurological conditions. No single established or recommended method for defining a data dictionary was identified. Nine initiatives conducted systematic reviews to collate information before implementing a consensus process. Thirty-seven initiatives consulted with end-users. Methods of consultation were ""roundtable"" discussion (n = 30); with facilitation (n = 16); that was iterative (n = 27); and frequently conducted in-person (n = 27). Researcher stakeholders were involved in all initiatives and clinicians in 25. Importantly, only six initiatives involved persons with lived experience of TBI and four involved carers. Methods for defining data dictionaries were variable and reporting is sparse. Our findings are instructive for AUS-TBI and can be used to further development of methods for defining data dictionaries.",,doi:https://doi.org/10.1089/neur.2023.0116; html:https://europepmc.org/articles/PMC11040195; pdf:https://europepmc.org/articles/PMC11040195?pdf=render 35964473,https://doi.org/10.1016/j.socscimed.2022.115237,"""We've all got the virus inside us now"": Disaggregating public health relations and responsibilities for health protection in pandemic London.","Kasstan B, Mounier-Jack S, Gaskell KM, Eggo RM, Marks M, Chantler T.",,Social science & medicine (1982),2022,2022-08-07,Y,Pandemic; Public Health; Judaism; Responsibility; London; Covid-19,,,"The COVID-19 pandemic has disproportionately impacted ethnic minorities in the global north, evidenced by higher rates of transmission, morbidity, and mortality relative to population sizes. Orthodox Jewish neighbourhoods in London had extremely high SARS-CoV-2 seroprevalence rates, reflecting patterns in Israel and the US. The aim of this paper is to examine how responsibilities over health protection are conveyed, and to what extent responsibility is sought by, and shared between, state services, and 'community' stakeholders or representative groups, and families in public health emergencies. The study investigates how public health and statutory services stakeholders, Orthodox Jewish communal custodians and households sought to enact health protection in London during the first year of the pandemic (March 2020-March 2021). Twenty-eight semi-structured interviews were conducted across these cohorts. Findings demonstrate that institutional relations - both their formation and at times fragmentation - were directly shaped by issues surrounding COVID-19 control measures. Exchanges around protective interventions (whether control measures, contact tracing technologies, or vaccines) reveal diverse and diverging attributions of responsibility and authority. The paper develops a framework of public health relations to understand negotiations between statutory services and minority groups over responsiveness and accountability in health protection. Disaggregating public health relations can help social scientists to critique who and what characterises institutional relationships with minority groups, and what ideas of responsibility and responsiveness are projected by differently-positioned stakeholders in health protection.",,doi:https://doi.org/10.1016/j.socscimed.2022.115237; doi:https://doi.org/10.1016/j.socscimed.2022.115237; html:https://europepmc.org/articles/PMC9357441; pdf:https://europepmc.org/articles/PMC9357441?pdf=render 36745557,https://doi.org/10.1093/bjd/ljac132,"Factors associated with depression, anxiety and severe mental illness among adults with atopic eczema or psoriasis: a systematic review and meta-analysis.","Adesanya EI, Matthewman J, Schonmann Y, Hayes JF, Henderson A, Mathur R, Mulick AR, Smith CH, Langan SM, Mansfield KE.",,The British journal of dermatology,2023,2023-03-01,N,,,,"

Background

Evidence suggests an association between atopic eczema (AE) or psoriasis and mental illness; however, the factors associated with mental illness are unclear.

Objectives

To synthesize and evaluate all available evidence on factors associated with depression, anxiety and severe mental illness (SMI) among adults with AE or psoriasis.

Methods

We searched electronic databases, grey literature databases and clinical trial registries from inception to February 2022 for studies of adults with AE or psoriasis. Eligible studies included randomized controlled trials (RCTs), cohort, cross-sectional or case-control studies where effect estimates of factors associated with depression, anxiety or SMI were reported. We did not apply language or geographical restrictions. We assessed risk of bias using the Quality in Prognosis Studies tool. We synthesized results narratively, and if at least two studies were sufficiently homogeneous, we pooled effect estimates in a random effects meta-analysis.

Results

We included 21 studies (11 observational, 10 RCTs). No observational studies in AE fulfilled our eligibility criteria. Observational studies in people with psoriasis mostly investigated factors associated with depression or anxiety - one cross-sectional study investigated factors associated with schizophrenia. Pooled effect estimates suggest that female sex and psoriatic arthritis were associated with depression [female sex: odds ratio (OR) 1.62, 95% confidence interval (CI) 1.09-2.40, 95% prediction intervals (PIs) 0.62-4.23, I2 = 24.90%, τ2 = 0.05; psoriatic arthritis: OR 2.26, 95% CI 1.56-3.25, 95% PI 0.21-24.23, I2 = 0.00%, τ2 = 0.00] and anxiety (female sex: OR 2.59, 95% CI 1.32-5.07, 95% PI 0.00-3956.27, I2 = 61.90%, τ2 = 0.22; psoriatic arthritis: OR 1.98, 95% CI 1.33-2.94, I2 = 0.00%, τ2 = 0.00). Moderate/severe psoriasis was associated with anxiety (OR 1.14, 95% CI 1.05-1.25, I2 0.00%, τ2 = 0.00), but not depression. Evidence from RCTs suggested that adults with AE or psoriasis given placebo had higher depression and anxiety scores compared with comparators given targeted treatment (e.g. biologic agents).

Conclusions

Our review highlights limited existing research on factors associated with depression, anxiety and SMI in adults with AE or psoriasis. Observational evidence on factors associated with depression or anxiety in people with psoriasis was conflicting or from single studies, but some identified factors were consistent with those in the general population. Evidence on factors associated with SMIs in people with AE or psoriasis was particularly limited. Evidence from RCTs suggested that AE and psoriasis treated with placebo was associated with higher depression and anxiety scores compared with skin disease treated with targeted therapy; however, follow-up was limited. Therefore, long-term effects on mental health are unclear.",,pdf:https://academic.oup.com/bjd/article-pdf/188/4/460/51790111/ljac132.pdf; doi:https://doi.org/10.1093/bjd/ljac132 -36962513,https://doi.org/10.1371/journal.pgph.0000502,"Association between mobility, non-pharmaceutical interventions, and COVID-19 transmission in Ghana: A modelling study using mobile phone data.","Gibbs H, Liu Y, Abbott S, Baffoe-Nyarko I, Laryea DO, Akyereko E, Kuma-Aboagye P, Asante IA, Mitjà O, LSHTM CMMID COVID-19 Working Group, Ampofo W, Asiedu-Bekoe F, Marks M, Eggo RM.",,PLOS global public health,2022,2022-09-13,Y,,,,"Governments around the world have implemented non-pharmaceutical interventions to limit the transmission of COVID-19. Here we assess if increasing NPI stringency was associated with a reduction in COVID-19 cases in Ghana. While lockdowns and physical distancing have proven effective for reducing COVID-19 transmission, there is still limited understanding of how NPI measures are reflected in indicators of human mobility. Further, there is a lack of understanding about how findings from high-income settings correspond to low and middle-income contexts. In this study, we assess the relationship between indicators of human mobility, NPIs, and estimates of Rt, a real-time measure of the intensity of COVID-19 transmission. We construct a multilevel generalised linear mixed model, combining local disease surveillance data from subnational districts of Ghana with the timing of NPIs and indicators of human mobility from Google and Vodafone Ghana. We observe a relationship between reductions in human mobility and decreases in Rt during the early stages of the COVID-19 epidemic in Ghana. We find that the strength of this relationship varies through time, decreasing after the most stringent period of interventions in the early epidemic. Our findings demonstrate how the association of NPI and mobility indicators with COVID-19 transmission may vary through time. Further, we demonstrate the utility of combining local disease surveillance data with large scale human mobility data to augment existing surveillance capacity to monitor the impact of NPI policies.",,pdf:https://journals.plos.org/globalpublichealth/article/file?id=10.1371/journal.pgph.0000502&type=printable; doi:https://doi.org/10.1371/journal.pgph.0000502; html:https://europepmc.org/articles/PMC10021296; pdf:https://europepmc.org/articles/PMC10021296?pdf=render 30240446,https://doi.org/10.1371/journal.pone.0203896,Polygenic risk scores for major depressive disorder and neuroticism as predictors of antidepressant response: Meta-analysis of three treatment cohorts.,"Ward J, Graham N, Strawbridge RJ, Ferguson A, Jenkins G, Chen W, Hodgson K, Frye M, Weinshilboum R, Uher R, Lewis CM, Biernacka J, Smith DJ.",,PloS one,2018,2018-09-21,Y,,Better Care,,"There are currently no reliable approaches for correctly identifying which patients with major depressive disorder (MDD) will respond well to antidepressant therapy. However, recent genetic advances suggest that Polygenic Risk Scores (PRS) could allow MDD patients to be stratified for antidepressant response. We used PRS for MDD and PRS for neuroticism as putative predictors of antidepressant response within three treatment cohorts: The Genome-based Therapeutic Drugs for Depression (GENDEP) cohort, and 2 sub-cohorts from the Pharmacogenomics Research Network Antidepressant Medication Pharmacogenomics Study PRGN-AMPS (total patient number = 760). Results across cohorts were combined via meta-analysis within a random effects model. Overall, PRS for MDD and neuroticism did not significantly predict antidepressant response but there was a consistent direction of effect, whereby greater genetic loading for both MDD (best MDD result, p < 5*10-5 MDD-PRS at 4 weeks, β = -0.019, S.E = 0.008, p = 0.01) and neuroticism (best neuroticism result, p < 0.1 neuroticism-PRS at 8 weeks, β = -0.017, S.E = 0.008, p = 0.03) were associated with less favourable response. We conclude that the PRS approach may offer some promise for treatment stratification in MDD and should now be assessed within larger clinical cohorts.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0203896&type=printable; doi:https://doi.org/10.1371/journal.pone.0203896; html:https://europepmc.org/articles/PMC6150505; pdf:https://europepmc.org/articles/PMC6150505?pdf=render +36962513,https://doi.org/10.1371/journal.pgph.0000502,"Association between mobility, non-pharmaceutical interventions, and COVID-19 transmission in Ghana: A modelling study using mobile phone data.","Gibbs H, Liu Y, Abbott S, Baffoe-Nyarko I, Laryea DO, Akyereko E, Kuma-Aboagye P, Asante IA, Mitjà O, LSHTM CMMID COVID-19 Working Group, Ampofo W, Asiedu-Bekoe F, Marks M, Eggo RM.",,PLOS global public health,2022,2022-09-13,Y,,,,"Governments around the world have implemented non-pharmaceutical interventions to limit the transmission of COVID-19. Here we assess if increasing NPI stringency was associated with a reduction in COVID-19 cases in Ghana. While lockdowns and physical distancing have proven effective for reducing COVID-19 transmission, there is still limited understanding of how NPI measures are reflected in indicators of human mobility. Further, there is a lack of understanding about how findings from high-income settings correspond to low and middle-income contexts. In this study, we assess the relationship between indicators of human mobility, NPIs, and estimates of Rt, a real-time measure of the intensity of COVID-19 transmission. We construct a multilevel generalised linear mixed model, combining local disease surveillance data from subnational districts of Ghana with the timing of NPIs and indicators of human mobility from Google and Vodafone Ghana. We observe a relationship between reductions in human mobility and decreases in Rt during the early stages of the COVID-19 epidemic in Ghana. We find that the strength of this relationship varies through time, decreasing after the most stringent period of interventions in the early epidemic. Our findings demonstrate how the association of NPI and mobility indicators with COVID-19 transmission may vary through time. Further, we demonstrate the utility of combining local disease surveillance data with large scale human mobility data to augment existing surveillance capacity to monitor the impact of NPI policies.",,pdf:https://journals.plos.org/globalpublichealth/article/file?id=10.1371/journal.pgph.0000502&type=printable; doi:https://doi.org/10.1371/journal.pgph.0000502; html:https://europepmc.org/articles/PMC10021296; pdf:https://europepmc.org/articles/PMC10021296?pdf=render 35781133,https://doi.org/10.3310/zyzc8514,Long-term impact of pre-incision antibiotics on children born by caesarean section: a longitudinal study based on UK electronic health records.,"Šumilo D, Nirantharakumar K, Willis BH, Rudge GM, Martin J, Gokhale K, Thayakaran R, Adderley NJ, Chandan JS, Okoth K, Harris IM, Hewston R, Skrybant M, Deeks JJ, Brocklehurst P.",,"Health technology assessment (Winchester, England)",2022,2022-06-01,N,Asthma; Caesarean section; Eczema; Child Health; Anti-bacterial Agents; Microbiome; Electronic Health Records; Interrupted Time Series Analysis,,,"

Background

Since changes in the national guidance in 2011, prophylactic antibiotics for women undergoing caesarean section are recommended prior to skin incision, rather than after the baby's umbilical cord has been clamped. Evidence from randomised controlled trials conducted outside the UK has shown that this reduces maternal infectious morbidity; however, the prophylactic antibiotics also cross the placenta, meaning that babies are exposed to them around the time of birth. Antibiotics are known to affect the gut microbiota of the babies, but the long-term effects of exposure to high-dose broad-spectrum antibiotics around the time of birth on allergy and immune-related diseases are unknown.

Objectives

We aimed to examine whether or not in-utero exposure to antibiotics immediately prior to birth compared with no pre-incisional antibiotic exposure increases the risk of (1) asthma and (2) eczema in children born by caesarean section.

Design

This was a controlled interrupted time series study.

Setting

The study took place in primary and secondary care.

Participants

Children born in the UK during 2006-18 delivered by caesarean section were compared with a control cohort delivered vaginally.

Interventions

In-utero exposure to antibiotics immediately prior to birth.

Main outcome measures

Asthma and eczema in children in the first 5 years of life. Additional secondary outcomes, including other allergy-related conditions, autoimmune diseases, infections, other immune system-related diseases and neurodevelopmental conditions, were also assessed.

Data sources

The Health Improvement Network (THIN) and the Clinical Practice Research Datalink (CPRD) primary care databases and the Hospital Episode Statistics (HES) database. Previously published linkage strategies were adapted to link anonymised data on mothers and babies in these databases. Duplicate practices contributing to both THIN and the CPRD databases were removed to create a THIN-CPRD data set.

Results

In the THIN-CPRD and HES data sets, records of 515,945 and 3,945,351 mother-baby pairs were analysed, respectively. The risk of asthma was not significantly higher in children born by caesarean section exposed to pre-incision antibiotics than in children whose mothers received post-cord clamping antibiotics, with an incidence rate ratio of 0.91 (95% confidence interval 0.78 to 1.05) for diagnosis of asthma in primary care and an incidence rate ratio of 1.05 (95% confidence interval 0.99 to 1.11) for asthma resulting in a hospital admission. We also did not find an increased risk of eczema, with an incidence rate ratio of 0.98 (95% confidence interval 0.94 to1.03) and an incidence rate ratio of 0.96 (95% confidence interval 0.71 to 1.29) for diagnosis in primary care and hospital admissions, respectively.

Limitations

It was not possible to ascertain the exposure to pre-incision antibiotics at an individual level. The maximum follow-up of children was 5 years.

Conclusions

There was no evidence that the policy change from post-cord clamping to pre-incision prophylactic antibiotics for caesarean sections during 2006-18 had an impact on the incidence of asthma and eczema in early childhood in the UK.

Future work

There is a need for further research to investigate if pre-incision antibiotics have any impact on developing asthma and other allergy and immune-related conditions in older children.

Study registration

This study is registered as researchregistry3736.

Funding

This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 30. See the NIHR Journals Library website for further project information.",,pdf:https://njl-admin.nihr.ac.uk/document/download/2039937; doi:https://doi.org/10.3310/ZYZC8514 36446449,https://doi.org/10.1136/bmjopen-2022-061849,Effect of lifting COVID-19 restrictions on utilisation of primary care services in Nepal: a difference-in-differences analysis.,"Kapoor NR, Aryal A, Mehata S, Dulal M, Kruk ME, Bauhoff S, Arsenault C.",,BMJ open,2022,2022-11-29,Y,Primary Care; Health Policy; Covid-19,,,"

Introduction

An increasing number of studies have reported disruptions in health service utilisation due to the COVID-19 pandemic and its associated restrictions. However, little is known about the effect of lifting COVID-19 restrictions on health service utilisation. The objective of this study was to estimate the effect of lifting COVID-19 restrictions on primary care service utilisation in Nepal.

Methods

Data on utilisation of 10 primary care services were extracted from the Health Management Information System across all health facilities in Nepal. We used a difference-in-differences design and linear fixed effects regressions to estimate the effect of lifting COVID-19 restrictions. The treatment group included palikas that had lifted restrictions in place from 17 August 2020 to 16 September 2020 (Bhadra 2077) and the control group included palikas that had maintained restrictions during that period. The pre-period included the 4 months of national lockdown from 24 March 2020 to 22 July 2020 (Chaitra 2076 to Ashar 2077). Models included month and palika fixed effects and controlled for COVID-19 incidence.

Results

We found that lifting COVID-19 restrictions was associated with an average increase per palika of 57.5 contraceptive users (95% CI 14.6 to 100.5), 15.6 antenatal care visits (95% CI 5.3 to 25.9) and 1.6 child pneumonia visits (95% CI 0.2 to 2.9). This corresponded to a 9.4% increase in contraceptive users, 34.2% increase in antenatal care visits and 15.6% increase in child pneumonia visits. Utilisation of most other primary care services also increased after lifting restrictions, but coefficients were not statistically significant.

Conclusions

Despite the ongoing pandemic, lifting restrictions can lead to an increase in some primary care services. Our results point to a causal link between restrictions and health service utilisation and call for policy makers in low- and middle-income countries to carefully consider the trade-offs of strict lockdowns during future COVID-19 waves or future pandemics.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/11/e061849.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-061849; html:https://europepmc.org/articles/PMC9709811; pdf:https://europepmc.org/articles/PMC9709811?pdf=render 32398093,https://doi.org/10.1186/s13063-020-04329-8,Access to routinely collected health data for clinical trials - review of successful data requests to UK registries.,"Lensen S, Macnair A, Love SB, Yorke-Edwards V, Noor NM, Martyn M, Blenkinsop A, Diaz-Montana C, Powell G, Williamson E, Carpenter J, Sydes MR.",,Trials,2020,2020-05-12,Y,Systematic review; Rct; Registry; Routinely Collected Health Data,,,"

Background

Clinical trials generally each collect their own data despite routinely collected health data (RCHD) increasing in quality and breadth. Our aim is to quantify UK-based randomised controlled trials (RCTs) accessing RCHD for participant data, characterise how these data are used and thereby recommend how more trials could use RCHD.

Methods

We conducted a systematic review of RCTs accessing RCHD from at least one registry in the UK between 2013 and 2018 for the purposes of informing or supplementing participant data. A list of all registries holding RCHD in the UK was compiled. In cases where registries published release registers, these were searched for RCTs accessing RCHD. Where no release register was available, registries were contacted to request a list of RCTs. For each identified RCT, information was collected from all publicly available sources (release registers, websites, protocol etc.). The search and data extraction were undertaken between January and May 2019.

Results

We identified 160 RCTs accessing RCHD between 2013 and 2018 from a total of 22 registries; this corresponds to only a very small proportion of all UK RCTs (about 3%). RCTs accessing RCHD were generally large (median sample size 1590), commonly evaluating treatments for cancer or cardiovascular disease. Most of the included RCTs accessed RCHD from NHS Digital (68%), and the most frequently accessed datasets were mortality (76%) and hospital visits (55%). RCHD was used to inform the primary trial (82%) and long-term follow-up (57%). There was substantial variation in how RCTs used RCHD to inform participant outcome measures. A limitation was the lack of information and transparency from registries and RCTs with respect to which datasets have been accessed and for what purposes.

Conclusions

In the last five years, only a small minority of UK-based RCTs have accessed RCHD to inform participant data. We ask for improved accessibility, confirmed data quality and joined-up thinking between the registries and the regulatory authorities.

Trial registration

PROSPERO CRD42019123088.",,pdf:https://trialsjournal.biomedcentral.com/track/pdf/10.1186/s13063-020-04329-8; doi:https://doi.org/10.1186/s13063-020-04329-8; html:https://europepmc.org/articles/PMC7218527; pdf:https://europepmc.org/articles/PMC7218527?pdf=render 33262239,https://doi.org/10.1128/msystems.00677-20,Investigating the Role of Diet and Exercise in Gut Microbe-Host Cometabolism.,"Penney N, Barton W, Posma JM, Darzi A, Frost G, Cotter PD, Holmes E, Shanahan F, O'Sullivan O, Garcia-Perez I.",,mSystems,2020,2020-12-01,Y,Metabolism; Diet; Exercise; Microbiome,,,"We investigated the individual and combined effects of diet and physical exercise on metabolism and the gut microbiome to establish how these lifestyle factors influence host-microbiome cometabolism. Urinary and fecal samples were collected from athletes and less active controls. Individuals were further classified according to an objective dietary assessment score of adherence to healthy dietary habits according to WHO guidelines, calculated from their proton nuclear magnetic resonance (1H-NMR) urinary profiles. Subsequent models were generated comparing extremes of dietary habits, exercise, and the combined effect of both. Differences in metabolic phenotypes and gut microbiome profiles between the two groups were assessed. Each of the models pertaining to diet healthiness, physical exercise, or a combination of both displayed a metabolic and functional microbial signature, with a significant proportion of the metabolites identified as discriminating between the various pairwise comparisons resulting from gut microbe-host cometabolism. Microbial diversity was associated with a combination of high adherence to healthy dietary habits and exercise and was correlated with a distinct array of microbially derived metabolites, including markers of proteolytic activity. Improved control of dietary confounders, through the use of an objective dietary assessment score, has uncovered further insights into the complex, multifactorial relationship between diet, exercise, the gut microbiome, and metabolism. Furthermore, the observation of higher proteolytic activity associated with higher microbial diversity indicates that increased microbial diversity may confer deleterious as well as beneficial effects on the host.IMPORTANCE Improved control of dietary confounders, through the use of an objective dietary assessment score, has uncovered further insights into the complex, multifactorial relationship between diet, exercise, the gut microbiome, and metabolism. Each of the models pertaining to diet healthiness, physical exercise, or a combination of both, displayed a distinct metabolic and functional microbial signature. A significant proportion of the metabolites identified as discriminating between the various pairwise comparisons result from gut microbe-host cometabolism, and the identified interactions have expanded current knowledge in this area. Furthermore, although increased microbial diversity has previously been linked with health, our observation of higher microbial diversity being associated with increased proteolytic activity indicates that it may confer deleterious as well as beneficial effects on the host.",,pdf:http://spiral.imperial.ac.uk/bitstream/10044/1/85021/8/mSystems-2020-Penney-e00677-20.full.pdf; doi:https://doi.org/10.1128/mSystems.00677-20; html:https://europepmc.org/articles/PMC7716389; pdf:https://europepmc.org/articles/PMC7716389?pdf=render 37717234,https://doi.org/10.1111/1742-6723.14312,Prevalence of alcohol and other drug detections in non-transport injury events.,"Lau G, Mitra B, Gabbe BJ, Dietze PM, Reeder S, Cameron PA, Smit V, Schneider HG, Symons E, Koolstra C, Stewart C, Beck B.",,Emergency medicine Australasia : EMA,2024,2023-09-17,Y,Alcoholic Intoxication; Illicit Drug; Blood Alcohol Content; Wounds And Injury; Substance-related Disorder; Substance Use Detection,,,"

Objective

To measure the prevalence of alcohol and/or other drug (AOD) detections in suspected major trauma patients with non-transport injuries who presented to an adult major trauma centre.

Methods

This registry-based cohort study examined the prevalence of AOD detections in patients aged ≥18 years who: (i) sustained non-transport injuries; and (ii) met predefined trauma call-out criteria and were therefore managed by an interdisciplinary trauma team between 1 July 2021 and 31 December 2022. Prevalence was measured using routine in-hospital blood alcohol and urine drug screens.

Results

A total of 1469 cases met the inclusion criteria. Of cases with a valid blood test (n = 1248, 85.0%), alcohol was detected in 313 (25.1%) patients. Of the 733 (49.9%) cases with urine drug screen results, cannabinoids were most commonly detected (n = 103, 14.1%), followed by benzodiazepines (n = 98, 13.4%), amphetamine-type substances (n = 80, 10.9%), opioids (n = 28, 3.8%) and cocaine (n = 17, 2.3%). Alcohol and/or at least one other drug was detected in 37.4% (n = 472) of cases with either a blood alcohol or urine drug test completed (n = 1263, 86.0%). Multiple substances were detected in 16.6% (n = 119) of cases with both blood alcohol and urine drug screens (n = 718, 48.9%). Detections were prevalent in cases of interpersonal violence (n = 123/179, 68.7%) and intentional self-harm (n = 50/106, 47.2%), and in those occurring on Friday and Saturday nights (n = 118/191, 61.8%).

Conclusion

AOD detections were common in trauma patients with non-transport injury causes. Population-level surveillance is needed to inform prevention strategies that address AOD use as a significant risk factor for serious injury.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/1742-6723.14312; doi:https://doi.org/10.1111/1742-6723.14312; html:https://europepmc.org/articles/PMC10952644; pdf:https://europepmc.org/articles/PMC10952644?pdf=render -38581198,https://doi.org/10.1001/jama.2024.4011,Prostate-Specific Antigen Screening and 15-Year Prostate Cancer Mortality: A Secondary Analysis of the CAP Randomized Clinical Trial.,"Martin RM, Turner EL, Young GJ, Metcalfe C, Walsh EI, Lane JA, Sterne JAC, Noble S, Holding P, Ben-Shlomo Y, Williams NJ, Pashayan N, Bui MN, Albertsen PC, Seibert TM, Zietman AL, Oxley J, Adolfsson J, Mason MD, Davey Smith G, Neal DE, Hamdy FC, Donovan JL, CAP Trial Group.",,JAMA,2024,2024-05-01,N,,,,"

Importance

The Cluster Randomized Trial of PSA Testing for Prostate Cancer (CAP) reported no effect of prostate-specific antigen (PSA) screening on prostate cancer mortality at a median 10-year follow-up (primary outcome), but the long-term effects of PSA screening on prostate cancer mortality remain unclear.

Objective

To evaluate the effect of a single invitation for PSA screening on prostate cancer-specific mortality at a median 15-year follow-up compared with no invitation for screening.

Design, setting, and participants

This secondary analysis of the CAP randomized clinical trial included men aged 50 to 69 years identified at 573 primary care practices in England and Wales. Primary care practices were randomized between September 25, 2001, and August 24, 2007, and men were enrolled between January 8, 2002, and January 20, 2009. Follow-up was completed on March 31, 2021.

Intervention

Men received a single invitation for a PSA screening test with subsequent diagnostic tests if the PSA level was 3.0 ng/mL or higher. The control group received standard practice (no invitation).

Main outcomes and measures

The primary outcome was reported previously. Of 8 prespecified secondary outcomes, results of 4 were reported previously. The 4 remaining prespecified secondary outcomes at 15-year follow-up were prostate cancer-specific mortality, all-cause mortality, and prostate cancer stage and Gleason grade at diagnosis.

Results

Of 415 357 eligible men (mean [SD] age, 59.0 [5.6] years), 98% were included in these analyses. Overall, 12 013 and 12 958 men with a prostate cancer diagnosis were in the intervention and control groups, respectively (15-year cumulative risk, 7.08% [95% CI, 6.95%-7.21%] and 6.94% [95% CI, 6.82%-7.06%], respectively). At a median 15-year follow-up, 1199 men in the intervention group (0.69% [95% CI, 0.65%-0.73%]) and 1451 men in the control group (0.78% [95% CI, 0.73%-0.82%]) died of prostate cancer (rate ratio [RR], 0.92 [95% CI, 0.85-0.99]; P = .03). Compared with the control, the PSA screening intervention increased detection of low-grade (Gleason score [GS] ≤6: 2.2% vs 1.6%; P < .001) and localized (T1/T2: 3.6% vs 3.1%; P < .001) disease but not intermediate (GS of 7), high-grade (GS ≥8), locally advanced (T3), or distally advanced (T4/N1/M1) tumors. There were 45 084 all-cause deaths in the intervention group (23.2% [95% CI, 23.0%-23.4%]) and 50 336 deaths in the control group (23.3% [95% CI, 23.1%-23.5%]) (RR, 0.97 [95% CI, 0.94-1.01]; P = .11). Eight of the prostate cancer deaths in the intervention group (0.7%) and 7 deaths in the control group (0.5%) were related to a diagnostic biopsy or prostate cancer treatment.

Conclusions and relevance

In this secondary analysis of a randomized clinical trial, a single invitation for PSA screening compared with standard practice without routine screening reduced prostate cancer deaths at a median follow-up of 15 years. However, the absolute reduction in deaths was small.

Trial registration

isrctn.org Identifier: ISRCTN92187251.",,doi:https://doi.org/10.1001/jama.2024.4011 32460529,https://doi.org/10.1161/circimaging.119.010389,Novel Approach to Imaging Active Takayasu Arteritis Using Somatostatin Receptor Positron Emission Tomography/Magnetic Resonance Imaging.,"Tarkin JM, Wall C, Gopalan D, Aloj L, Manavaki R, Fryer TD, Aboagye EO, Bennett MR, Peters JE, Rudd JHF, Mason JC.",,Circulation. Cardiovascular imaging,2020,2020-05-28,N,Positron emission tomography; Vasculitis; Aortic Diseases; Molecular Imaging; Takayasu Arteritis,,,,,pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCIMAGING.119.010389; doi:https://doi.org/10.1161/CIRCIMAGING.119.010389; html:https://europepmc.org/articles/PMC7610536; pdf:https://europepmc.org/articles/PMC7610536?pdf=render; doi:https://doi.org/10.1161/circimaging.119.010389 -36617894,https://doi.org/10.1080/1354750x.2022.2162966,Longitudinal profile of circulating endothelial cells in post-acute coronary syndrome patients.,"de Bakker M, Kraan J, Akkerhuis KM, Oemrawsingh R, Asselbergs FW, Hoefer I, Kardys I, Boersma E.",,"Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals",2023,2023-01-08,N,Atherosclerosis; Cardiovascular disease; Circulating endothelial cells; acute coronary syndrome; Vascular Injury; Repeated Measurements,,,"IntroductionPatients who have experienced an acute coronary syndrome (ACS) are at risk of a recurrent event, but their level of risk varies. Because of their close temporal relationship with vascular injury, longitudinal measurements of circulating endothelial cells (CECs) carry potential to improve individual risk assessment.MethodsWe conducted an explorative nested case-control study within our multicenter, prospective, observational biomarker study (BIOMArCS) of 844 ACS patients. Following an index ACS, high-frequency blood sampling was performed during 1-year follow-up. CECs were identified using flow cytometric analyses in 15 cases with recurrent event, and 30 matched controls.ResultsCases and controls had a median (25th-75thpercentile) age of 64.1 (58.1-75.1) years and 80% were men. During the months preceding the endpoint, the mean (95%CI) CEC concentration in cases was persistently higher than in controls (12.8 [8.2-20.0] versus 10.0 [7.0-14.4] cells/ml), although this difference was non-significant (P = 0.339). In controls, the mean cell concentration was significantly (P = 0.030) lower in post 30-day samples compared to samples collected within one day after index ACS: 10.1 (7.5-13.6) versus 17.0 (10.8-26.6) cells/ml. Similar results were observed for CEC subsets co-expressing CD133 and CD309 (VEGFR-2) or CD106 (VCAM-1).ConclusionDespite their close relation to vascular damage, no increase in cell concentrations were found prior to the occurrence of a secondary adverse cardiac event.",,doi:https://doi.org/10.1080/1354750x.2022.2162966; doi:https://doi.org/10.1080/1354750X.2022.2162966 31912053,https://doi.org/,Described Practices for Assessing Fluid Resuscitation in Acute Hospital Care: A Qualitative Study.,"Lloyd E, Ignatowicz A, Sapey E, Lasserson D, Seccombe A.",,Acute medicine,2019,2019-01-01,N,,,,"Fluid resuscitation is a widely-used treatment in acute and emergency medicine, however, the process used to perform a fluid assessment has never been studied. This qualitative study explored how acute physicians describe their approach to assessing for fluid resuscitation. 18 clinicians of varying grades consented to a semi-structured interview. Transcripts were coded and analysed using thematic analysis. Participants described three subtypes of assessment; screening assessment, emergency assessment and formal assessment. Whether a patient was 'sick' was key to determining which assessment they would receive. Marked heterogeneity was noted in the assessment processes, particularly regarding the use of history-taking. Further research is required to determine how the information gathered in these assessments is used to decide when fluid resuscitation is indicated.",, -36769754,https://doi.org/10.3390/jcm12031106,The Causal Association of Irritable Bowel Syndrome with Multiple Disease Outcomes: A Phenome-Wide Mendelian Randomization Study.,"Li C, Chen Y, Chen Y, Ying Z, Hu Y, Kuang Y, Yang H, Song H, Zeng X.",,Journal of clinical medicine,2023,2023-01-31,Y,irritable bowel syndrome; Phenome-wide Association Study; Individual-level Mendelian Randomization; Summary-level Mendelian Randomization,,,"

Background

This study aimed to identify novel associations between irritable bowel syndrome (IBS) and a broad range of outcomes.

Methods

In total, 346,352 white participants in the U.K. Biobank were randomly divided into two halves, in which a genome-wide association study (GWAS) of IBS and a polygenic risk score (PRS) analysis of IBS using GWAS summary statistics were conducted, respectively. A phenome-wide association study (PheWAS) based on the PRS of IBS was performed to identify disease outcomes associated with IBS. Then, the causalities of these associations were tested by both one-sample (individual-level data in U.K. Biobank) and two-sample (publicly available summary statistics) Mendelian randomization (MR). Sex-stratified PheWAS-MR analyses were performed in male and female, separately.

Results

Our PheWAS identified five diseases associated with genetically predicted IBS. Conventional MR confirmed these causal associations between IBS and depression (OR: 1.07, 95%CI: 1.01-1.14, p = 0.02), diverticular diseases of the intestine (OR: 1.13, 95%CI: 1.08-1.19, p = 3.00 × 10-6), gastro-esophageal reflux disease (OR: 1.09, 95%CI: 1.05-1.13, p = 3.72 × 10-5), dyspepsia (OR: 1.21, 95%CI: 1.13-1.30, p = 9.28 × 10-8), and diaphragmatic hernia (OR: 1.10, 95%CI: 1.05-1.15, p = 2.75 × 10-5). The causality of these associations was observed in female only, but not men.

Conclusions

Increased risks of IBS is found to cause a series of disease outcomes. Our findings support further investigation on the clinical relevance of increased IBS risks with mental and digestive disorders.",,doi:https://doi.org/10.3390/jcm12031106; doi:https://doi.org/10.3390/jcm12031106; html:https://europepmc.org/articles/PMC9918111; pdf:https://europepmc.org/articles/PMC9918111?pdf=render +38581198,https://doi.org/10.1001/jama.2024.4011,Prostate-Specific Antigen Screening and 15-Year Prostate Cancer Mortality: A Secondary Analysis of the CAP Randomized Clinical Trial.,"Martin RM, Turner EL, Young GJ, Metcalfe C, Walsh EI, Lane JA, Sterne JAC, Noble S, Holding P, Ben-Shlomo Y, Williams NJ, Pashayan N, Bui MN, Albertsen PC, Seibert TM, Zietman AL, Oxley J, Adolfsson J, Mason MD, Davey Smith G, Neal DE, Hamdy FC, Donovan JL, CAP Trial Group.",,JAMA,2024,2024-05-01,N,,,,"

Importance

The Cluster Randomized Trial of PSA Testing for Prostate Cancer (CAP) reported no effect of prostate-specific antigen (PSA) screening on prostate cancer mortality at a median 10-year follow-up (primary outcome), but the long-term effects of PSA screening on prostate cancer mortality remain unclear.

Objective

To evaluate the effect of a single invitation for PSA screening on prostate cancer-specific mortality at a median 15-year follow-up compared with no invitation for screening.

Design, setting, and participants

This secondary analysis of the CAP randomized clinical trial included men aged 50 to 69 years identified at 573 primary care practices in England and Wales. Primary care practices were randomized between September 25, 2001, and August 24, 2007, and men were enrolled between January 8, 2002, and January 20, 2009. Follow-up was completed on March 31, 2021.

Intervention

Men received a single invitation for a PSA screening test with subsequent diagnostic tests if the PSA level was 3.0 ng/mL or higher. The control group received standard practice (no invitation).

Main outcomes and measures

The primary outcome was reported previously. Of 8 prespecified secondary outcomes, results of 4 were reported previously. The 4 remaining prespecified secondary outcomes at 15-year follow-up were prostate cancer-specific mortality, all-cause mortality, and prostate cancer stage and Gleason grade at diagnosis.

Results

Of 415 357 eligible men (mean [SD] age, 59.0 [5.6] years), 98% were included in these analyses. Overall, 12 013 and 12 958 men with a prostate cancer diagnosis were in the intervention and control groups, respectively (15-year cumulative risk, 7.08% [95% CI, 6.95%-7.21%] and 6.94% [95% CI, 6.82%-7.06%], respectively). At a median 15-year follow-up, 1199 men in the intervention group (0.69% [95% CI, 0.65%-0.73%]) and 1451 men in the control group (0.78% [95% CI, 0.73%-0.82%]) died of prostate cancer (rate ratio [RR], 0.92 [95% CI, 0.85-0.99]; P = .03). Compared with the control, the PSA screening intervention increased detection of low-grade (Gleason score [GS] ≤6: 2.2% vs 1.6%; P < .001) and localized (T1/T2: 3.6% vs 3.1%; P < .001) disease but not intermediate (GS of 7), high-grade (GS ≥8), locally advanced (T3), or distally advanced (T4/N1/M1) tumors. There were 45 084 all-cause deaths in the intervention group (23.2% [95% CI, 23.0%-23.4%]) and 50 336 deaths in the control group (23.3% [95% CI, 23.1%-23.5%]) (RR, 0.97 [95% CI, 0.94-1.01]; P = .11). Eight of the prostate cancer deaths in the intervention group (0.7%) and 7 deaths in the control group (0.5%) were related to a diagnostic biopsy or prostate cancer treatment.

Conclusions and relevance

In this secondary analysis of a randomized clinical trial, a single invitation for PSA screening compared with standard practice without routine screening reduced prostate cancer deaths at a median follow-up of 15 years. However, the absolute reduction in deaths was small.

Trial registration

isrctn.org Identifier: ISRCTN92187251.",,doi:https://doi.org/10.1001/jama.2024.4011 +36617894,https://doi.org/10.1080/1354750x.2022.2162966,Longitudinal profile of circulating endothelial cells in post-acute coronary syndrome patients.,"de Bakker M, Kraan J, Akkerhuis KM, Oemrawsingh R, Asselbergs FW, Hoefer I, Kardys I, Boersma E.",,"Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals",2023,2023-01-08,N,Atherosclerosis; Cardiovascular disease; Circulating endothelial cells; acute coronary syndrome; Vascular Injury; Repeated Measurements,,,"IntroductionPatients who have experienced an acute coronary syndrome (ACS) are at risk of a recurrent event, but their level of risk varies. Because of their close temporal relationship with vascular injury, longitudinal measurements of circulating endothelial cells (CECs) carry potential to improve individual risk assessment.MethodsWe conducted an explorative nested case-control study within our multicenter, prospective, observational biomarker study (BIOMArCS) of 844 ACS patients. Following an index ACS, high-frequency blood sampling was performed during 1-year follow-up. CECs were identified using flow cytometric analyses in 15 cases with recurrent event, and 30 matched controls.ResultsCases and controls had a median (25th-75thpercentile) age of 64.1 (58.1-75.1) years and 80% were men. During the months preceding the endpoint, the mean (95%CI) CEC concentration in cases was persistently higher than in controls (12.8 [8.2-20.0] versus 10.0 [7.0-14.4] cells/ml), although this difference was non-significant (P = 0.339). In controls, the mean cell concentration was significantly (P = 0.030) lower in post 30-day samples compared to samples collected within one day after index ACS: 10.1 (7.5-13.6) versus 17.0 (10.8-26.6) cells/ml. Similar results were observed for CEC subsets co-expressing CD133 and CD309 (VEGFR-2) or CD106 (VCAM-1).ConclusionDespite their close relation to vascular damage, no increase in cell concentrations were found prior to the occurrence of a secondary adverse cardiac event.",,doi:https://doi.org/10.1080/1354750x.2022.2162966; doi:https://doi.org/10.1080/1354750X.2022.2162966 35297226,https://doi.org/10.1002/jcsm.12971,Association of shorter leucocyte telomere length with risk of frailty.,"Bountziouka V, Nelson CP, Codd V, Wang Q, Musicha C, Allara E, Kaptoge S, Di Angelantonio E, Butterworth AS, Thompson JR, Curtis EM, Wood AM, Danesh JN, Harvey NC, Cooper C, Samani NJ.",,"Journal of cachexia, sarcopenia and muscle",2022,2022-03-17,Y,Frailty; Biological Age; Uk Biobank; Leucocyte Telomere Length,,,"

Background

Frailty is a multidimensional syndrome of decline that affects multiple systems and predisposes to adverse health outcomes. Although chronological age is the major risk factor, inter-individual variation in risk is not fully understood. Leucocyte telomere length (LTL), a proposed marker of biological age, has been associated with risk of many diseases. We sought to determine whether LTL is associated with risk of frailty.

Methods

We utilized cross-sectional data from 441 781 UK Biobank participants (aged 40-69 years), with complete data on frailty indicators and LTL. Frailty was defined as the presence of at least three of five indicators: weaker grip strength, slower walking pace, weight loss in the past year, lower physical activity, and exhaustion in the past 2 weeks. LTL was measured using a validated qPCR method and reported as a ratio of the telomere repeat number (T) to a single-copy gene (S) (T/S ratio). Association of LTL with frailty was evaluated using adjusted (chronological age, sex, deprivation, smoking, alcohol intake, body mass index, and multimorbidity) multinomial and ordinal regression models, and results are presented as relative risk (RRR) or odds ratios (OR), respectively, alongside the 95% confidence interval (CI). Mendelian randomization (MR), using 131 genetic variants associated with LTL, was used to assess if the association of LTL with frailty was causal.

Results

Frail participants (4.6%) were older (median age difference (95% CI): 3 (2.5; 3.5) years, P = 2.73 × 10-33 ), more likely to be female (61%, P = 1.97 × 10-129 ), and had shorter LTL (-0.13SD vs. 0.03SD, P = 5.43 × 10-111 ) than non-frail. In adjusted analyses, both age and LTL were associated with frailty (RRR = 1.03 (95% CI: 1.02; 1.04) per year of older chronological age, P = 3.99 × 10-12 ; 1.10 (1.08; 1.11) per SD shorter LTL, P = 1.46 × 10-30 ). Within each age group (40-49, 50-59, 60-69 years), the prevalence of frailty was about 33% higher in participants with shorter (-2SD) versus longer telomeres (+2SD). MR analysis showed an association of LTL with frailty that was directionally consistent with the observational association, but not statistically significant (MR-Median: OR (95% CI): 1.08 (0.98; 1.19) per SD shorter LTL, P = 0.13).

Conclusions

Inter-individual variation in LTL is associated with the risk of frailty independently of chronological age and other risk factors. Our findings provide evidence for an additional biological determinant of frailty.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/jcsm.12971; doi:https://doi.org/10.1002/jcsm.12971; html:https://europepmc.org/articles/PMC9178164; pdf:https://europepmc.org/articles/PMC9178164?pdf=render +36769754,https://doi.org/10.3390/jcm12031106,The Causal Association of Irritable Bowel Syndrome with Multiple Disease Outcomes: A Phenome-Wide Mendelian Randomization Study.,"Li C, Chen Y, Chen Y, Ying Z, Hu Y, Kuang Y, Yang H, Song H, Zeng X.",,Journal of clinical medicine,2023,2023-01-31,Y,irritable bowel syndrome; Phenome-wide Association Study; Individual-level Mendelian Randomization; Summary-level Mendelian Randomization,,,"

Background

This study aimed to identify novel associations between irritable bowel syndrome (IBS) and a broad range of outcomes.

Methods

In total, 346,352 white participants in the U.K. Biobank were randomly divided into two halves, in which a genome-wide association study (GWAS) of IBS and a polygenic risk score (PRS) analysis of IBS using GWAS summary statistics were conducted, respectively. A phenome-wide association study (PheWAS) based on the PRS of IBS was performed to identify disease outcomes associated with IBS. Then, the causalities of these associations were tested by both one-sample (individual-level data in U.K. Biobank) and two-sample (publicly available summary statistics) Mendelian randomization (MR). Sex-stratified PheWAS-MR analyses were performed in male and female, separately.

Results

Our PheWAS identified five diseases associated with genetically predicted IBS. Conventional MR confirmed these causal associations between IBS and depression (OR: 1.07, 95%CI: 1.01-1.14, p = 0.02), diverticular diseases of the intestine (OR: 1.13, 95%CI: 1.08-1.19, p = 3.00 × 10-6), gastro-esophageal reflux disease (OR: 1.09, 95%CI: 1.05-1.13, p = 3.72 × 10-5), dyspepsia (OR: 1.21, 95%CI: 1.13-1.30, p = 9.28 × 10-8), and diaphragmatic hernia (OR: 1.10, 95%CI: 1.05-1.15, p = 2.75 × 10-5). The causality of these associations was observed in female only, but not men.

Conclusions

Increased risks of IBS is found to cause a series of disease outcomes. Our findings support further investigation on the clinical relevance of increased IBS risks with mental and digestive disorders.",,doi:https://doi.org/10.3390/jcm12031106; doi:https://doi.org/10.3390/jcm12031106; html:https://europepmc.org/articles/PMC9918111; pdf:https://europepmc.org/articles/PMC9918111?pdf=render 34227657,https://doi.org/10.1093/bjs/znab183,Machine learning risk prediction of mortality for patients undergoing surgery with perioperative SARS-CoV-2: the COVIDSurg mortality score.,"COVIDSurg Collaborative .",,The British journal of surgery,2021,2021-11-01,Y,,,,,,pdf:https://academic.oup.com/bjs/article-pdf/108/11/1274/47371055/znab183.pdf; doi:https://doi.org/10.1093/bjs/znab183; html:https://europepmc.org/articles/PMC8344569; pdf:https://europepmc.org/articles/PMC8344569?pdf=render 36529816,https://doi.org/10.1038/s41598-022-26357-x,Novel multimorbidity clusters in people with eczema and asthma: a population-based cluster analysis.,"Mulick AR, Henderson AD, Prieto-Merino D, Mansfield KE, Matthewman J, Quint JK, Lyons RA, Sheikh A, McAllister DA, Nitsch D, Langan SM.",,Scientific reports,2022,2022-12-18,Y,,,,"Eczema and asthma are allergic diseases and two of the commonest chronic conditions in high-income countries. Their co-existence with other allergic conditions is common, but little research exists on wider multimorbidity with these conditions. We set out to identify and compare clusters of multimorbidity in people with eczema or asthma and people without. Using routinely-collected primary care data from the U.K. Clinical Research Practice Datalink GOLD, we identified adults ever having eczema (or asthma), and comparison groups never having eczema (or asthma). We derived clusters of multimorbidity from hierarchical cluster analysis of Jaccard distances between pairs of diagnostic categories estimated from mixed-effects logistic regressions. We analysed 434,422 individuals with eczema (58% female, median age 47 years) and 1,333,281 individuals without (55% female, 47 years), and 517,712 individuals with asthma (53% female, 44 years) and 1,601,210 individuals without (53% female, 45 years). Age at first morbidity, sex and having eczema/asthma affected the scope of multimorbidity, with women, older age and eczema/asthma being associated with larger morbidity clusters. Injuries, digestive, nervous system and mental health disorders were more commonly seen in eczema and asthma than control clusters. People with eczema and asthma of all ages and both sexes may experience greater multimorbidity than people without eczema and asthma, including conditions not previously recognised as contributing to their disease burden. This work highlights areas where there is a critical need for research addressing the burden and drivers of multimorbidity in order to inform strategies to reduce poor health outcomes.",,pdf:https://www.nature.com/articles/s41598-022-26357-x.pdf; doi:https://doi.org/10.1038/s41598-022-26357-x; html:https://europepmc.org/articles/PMC9760185; pdf:https://europepmc.org/articles/PMC9760185?pdf=render @@ -994,15 +994,15 @@ PMC10686417,https://doi.org/,The impact of restricted provision of publicly fund 34571200,https://doi.org/10.1016/j.jaip.2021.09.026,Atopic Eczema-Associated Fracture Risk and Oral Corticosteroids: A Population-Based Cohort Study.,"Matthewman J, Mansfield KE, Prieto-Alhambra D, Mulick AR, Smeeth L, Lowe KE, Silverwood RJ, Langan SM.",,The journal of allergy and clinical immunology. In practice,2022,2021-09-24,Y,Fracture; Atopic Eczema; Atopic Dermatitis; osteoporotic fracture; Oral Corticosteroids,,,"

Background

Evidence suggests adults with atopic eczema have increased fracture risk. However, it is unclear whether oral corticosteroids explain the association.

Objective

To assess to what extent oral corticosteroids mediate the relationship between atopic eczema and fractures.

Methods

We conducted a cohort study using English primary care (Clinical Practice Research Datalink) and hospital admissions (Hospital Episode Statistics) records (1998-2016) including adults (18 years old and older) with atopic eczema matched (age, sex, and general practice) with up to 5 adults without atopic eczema. We used Cox regression to estimate hazard ratios (HRs) for specific major osteoporotic fractures (hip, spine, pelvis, or wrist) and for any-site fracture comparing individuals with atopic eczema with those without, adjusting for 6 different definitions of time-updated oral corticosteroid use (ever any prescription, ever high-dose, and recent, cumulative, current, or peak dose).

Results

We identified 526,808 individuals with atopic eczema and 2,569,030 without. We saw evidence of an association between atopic eczema and major osteoporotic fractures (eg, spine HR 1.15, 99% CI 1.08-1.22; hip HR 1.11, 99% CI 1.08-1.15) that remained after additionally adjusting for oral corticosteroids (eg, cumulative corticosteroid dose: spine HR 1.09, 99% CI 1.03-1.16; hip HR 1.09, 99% CI 1.06-1.12). Fracture rates were higher in people with severe atopic eczema than in people without even after adjusting for oral corticosteroids (eg, spine HR [99% CI]: confounder-adjusted 2.31 [1.91-2.81]; additionally adjusted for cumulative dose 1.71 [1.40-2.09]).

Conclusions

Our findings suggest that little of the association between atopic eczema and major osteoporotic fractures is explained by oral corticosteroid use.",,pdf:http://www.jaci-inpractice.org/article/S2213219821010187/pdf; doi:https://doi.org/10.1016/j.jaip.2021.09.026; html:https://europepmc.org/articles/PMC7612204; pdf:https://europepmc.org/articles/PMC7612204?pdf=render 35143670,https://doi.org/10.1093/molbev/msac034,The Carbon Footprint of Bioinformatics.,"Grealey J, Lannelongue L, Saw WY, Marten J, Méric G, Ruiz-Carmona S, Inouye M.",,Molecular biology and evolution,2022,2022-03-01,Y,Bioinformatics; Genomics; Carbon Footprint; Green Algorithms,,,"Bioinformatic research relies on large-scale computational infrastructures which have a nonzero carbon footprint but so far, no study has quantified the environmental costs of bioinformatic tools and commonly run analyses. In this work, we estimate the carbon footprint of bioinformatics (in kilograms of CO2 equivalent units, kgCO2e) using the freely available Green Algorithms calculator (www.green-algorithms.org, last accessed 2022). We assessed 1) bioinformatic approaches in genome-wide association studies (GWAS), RNA sequencing, genome assembly, metagenomics, phylogenetics, and molecular simulations, as well as 2) computation strategies, such as parallelization, CPU (central processing unit) versus GPU (graphics processing unit), cloud versus local computing infrastructure, and geography. In particular, we found that biobank-scale GWAS emitted substantial kgCO2e and simple software upgrades could make it greener, for example, upgrading from BOLT-LMM v1 to v2.3 reduced carbon footprint by 73%. Moreover, switching from the average data center to a more efficient one can reduce carbon footprint by approximately 34%. Memory over-allocation can also be a substantial contributor to an algorithm's greenhouse gas emissions. The use of faster processors or greater parallelization reduces running time but can lead to greater carbon footprint. Finally, we provide guidance on how researchers can reduce power consumption and minimize kgCO2e. Overall, this work elucidates the carbon footprint of common analyses in bioinformatics and provides solutions which empower a move toward greener research.",,pdf:https://academic.oup.com/mbe/article-pdf/39/3/msac034/42692776/msac034.pdf; doi:https://doi.org/10.1093/molbev/msac034; html:https://europepmc.org/articles/PMC8892942; pdf:https://europepmc.org/articles/PMC8892942?pdf=render 37327673,https://doi.org/10.1016/j.ebiom.2023.104655,HFrEF subphenotypes based on 4210 repeatedly measured circulating proteins are driven by different biological mechanisms.,"Petersen TB, de Bakker M, Asselbergs FW, Harakalova M, Akkerhuis KM, Brugts JJ, van Ramshorst J, Lumbers RT, Ostroff RM, Katsikis PD, van der Spek PJ, Umans VA, Boersma E, Rizopoulos D, Kardys I.",,EBioMedicine,2023,2023-06-14,Y,Proteomics; Phenotypes; Biomarkers; Heart Failure; Unsupervised Machine Learning,,,"

Background

HFrEF is a heterogenous condition with high mortality. We used serial assessments of 4210 circulating proteins to identify distinct novel protein-based HFrEF subphenotypes and to investigate underlying dynamic biological mechanisms. Herewith we aimed to gain pathophysiological insights and fuel opportunities for personalised treatment.

Methods

In 382 patients, we performed trimonthly blood sampling during a median follow-up of 2.1 [IQR:1.1-2.6] years. We selected all baseline samples and two samples closest to the primary endpoint (PEP; composite of cardiovascular mortality, HF hospitalization, LVAD implantation, and heart transplantation) or censoring, and applied an aptamer-based multiplex proteomic approach. Using unsupervised machine learning methods, we derived clusters from 4210 repeatedly measured proteomic biomarkers. Sets of proteins that drove cluster allocation were analysed via an enrichment analysis. Differences in clinical characteristics and PEP occurrence were evaluated.

Findings

We identified four subphenotypes with different protein profiles, prognosis and clinical characteristics, including age (median [IQR] for subphenotypes 1-4, respectively:70 [64, 76], 68 [60, 79], 57 [47, 65], 59 [56, 66]years), EF (30 [26, 36], 26 [20, 38], 26 [22, 32], 33 [28, 37]%), and chronic renal failure (45%, 65%, 36%, 37%). Subphenotype allocation was driven by subsets of proteins associated with various biological functions, such as oxidative stress, inflammation and extracellular matrix organisation. Clinical characteristics of the subphenotypes were aligned with these associations. Subphenotypes 2 and 3 had the worst prognosis compared to subphenotype 1 (adjHR (95%CI):3.43 (1.76-6.69), and 2.88 (1.37-6.03), respectively).

Interpretation

Four circulating-protein based subphenotypes are present in HFrEF, which are driven by varying combinations of protein subsets, and have different clinical characteristics and prognosis.

Clinical trial registration

ClinicalTrials.gov Identifier: NCT01851538https://clinicaltrials.gov/ct2/show/NCT01851538.

Funding

EU/EFPIA IMI2JU BigData@Heart grant n°116074, Jaap Schouten Foundation and Noordwest Academie.",,pdf:http://www.thelancet.com/article/S2352396423002207/pdf; doi:https://doi.org/10.1016/j.ebiom.2023.104655; html:https://europepmc.org/articles/PMC10279550; pdf:https://europepmc.org/articles/PMC10279550?pdf=render -38040454,https://doi.org/10.1101/cshperspect.a041473,Environmental Impacts of Machine Learning Applications in Protein Science.,"Lannelongue L, Inouye M.",,Cold Spring Harbor perspectives in biology,2023,2023-12-01,N,,,,"Computing tools and machine learning models play an increasingly important role in biology and are now an essential part of discoveries in protein science. The growing energy needs of modern algorithms have raised concerns in the computational science community in light of the climate emergency. In this work, we summarize the different ways in which protein science can negatively impact the environment and we present the carbon footprint of some popular protein algorithms: molecular simulations, inference of protein-protein interactions, and protein structure prediction. We show that large deep learning models such as AlphaFold and ESMFold can have carbon footprints reaching over 100 tonnes of CO2e in some cases. The magnitude of these impacts highlights the importance of monitoring and mitigating them, and we list actions scientists can take to achieve more sustainable protein computational science.",,pdf:http://cshperspectives.cshlp.org/content/15/12/a041473.full.pdf; doi:https://doi.org/10.1101/cshperspect.a041473 32616677,https://doi.org/10.1212/wnl.0000000000009924,Accuracy of identifying incident stroke cases from linked health care data in UK Biobank.,"Rannikmäe K, Ngoh K, Bush K, Al-Shahi Salman R, Doubal F, Flaig R, Henshall DE, Hutchison A, Nolan J, Osborne S, Samarasekera N, Schnier C, Whiteley W, Wilkinson T, Wilson K, Woodfield R, Zhang Q, Allen N, Sudlow CLM.",,Neurology,2020,2020-07-02,Y,,,,"

Objective

In UK Biobank (UKB), a large population-based prospective study, cases of many diseases are ascertained through linkage to routinely collected, coded national health datasets. We assessed the accuracy of these for identifying incident strokes.

Methods

In a regional UKB subpopulation (n = 17,249), we identified all participants with ≥1 code signifying a first stroke after recruitment (incident stroke-coded cases) in linked hospital admission, primary care, or death record data. Stroke physicians reviewed their full electronic patient records (EPRs) and generated reference standard diagnoses. We evaluated the number and proportion of cases that were true-positives (i.e., positive predictive value [PPV]) for all codes combined and by code source and type.

Results

Of 232 incident stroke-coded cases, 97% had EPR information available. Data sources were 30% hospital admission only, 39% primary care only, 28% hospital and primary care, and 3% death records only. While 42% of cases were coded as unspecified stroke type, review of EPRs enabled a pathologic type to be assigned in >99%. PPVs (95% confidence intervals) were 79% (73%-84%) for any stroke (89% for hospital admission codes, 80% for primary care codes) and 83% (74%-90%) for ischemic stroke. PPVs for small numbers of death record and hemorrhagic stroke codes were low but imprecise.

Conclusions

Stroke and ischemic stroke cases in UKB can be ascertained through linked health datasets with sufficient accuracy for many research studies. Further work is needed to understand the accuracy of death record and hemorrhagic stroke codes and to develop scalable approaches for better identifying stroke types.",,pdf:https://n.neurology.org/content/neurology/95/6/e697.full.pdf; doi:https://doi.org/10.1212/WNL.0000000000009924; html:https://europepmc.org/articles/PMC7455356; pdf:https://europepmc.org/articles/PMC7455356?pdf=render +38040454,https://doi.org/10.1101/cshperspect.a041473,Environmental Impacts of Machine Learning Applications in Protein Science.,"Lannelongue L, Inouye M.",,Cold Spring Harbor perspectives in biology,2023,2023-12-01,N,,,,"Computing tools and machine learning models play an increasingly important role in biology and are now an essential part of discoveries in protein science. The growing energy needs of modern algorithms have raised concerns in the computational science community in light of the climate emergency. In this work, we summarize the different ways in which protein science can negatively impact the environment and we present the carbon footprint of some popular protein algorithms: molecular simulations, inference of protein-protein interactions, and protein structure prediction. We show that large deep learning models such as AlphaFold and ESMFold can have carbon footprints reaching over 100 tonnes of CO2e in some cases. The magnitude of these impacts highlights the importance of monitoring and mitigating them, and we list actions scientists can take to achieve more sustainable protein computational science.",,pdf:http://cshperspectives.cshlp.org/content/15/12/a041473.full.pdf; doi:https://doi.org/10.1101/cshperspect.a041473 34819519,https://doi.org/10.1038/s41467-021-27164-0,Synergistic insights into human health from aptamer- and antibody-based proteomic profiling.,"Pietzner M, Wheeler E, Carrasco-Zanini J, Kerrison ND, Oerton E, Koprulu M, Luan J, Hingorani AD, Williams SA, Wareham NJ, Langenberg C.",,Nature communications,2021,2021-11-24,Y,,,,"Affinity-based proteomics has enabled scalable quantification of thousands of protein targets in blood enhancing biomarker discovery, understanding of disease mechanisms, and genetic evaluation of drug targets in humans through protein quantitative trait loci (pQTLs). Here, we integrate two partly complementary techniques-the aptamer-based SomaScan® v4 assay and the antibody-based Olink assays-to systematically assess phenotypic consequences of hundreds of pQTLs discovered for 871 protein targets across both platforms. We create a genetically anchored cross-platform proteome-phenome network comprising 547 protein-phenotype connections, 36.3% of which were only seen with one of the two platforms suggesting that both techniques capture distinct aspects of protein biology. We further highlight discordance of genetically predicted effect directions between assays, such as for PILRA and Alzheimer's disease. Our results showcase the synergistic nature of these technologies to better understand and identify disease mechanisms and provide a benchmark for future cross-platform discoveries.",,pdf:https://www.nature.com/articles/s41467-021-27164-0.pdf; doi:https://doi.org/10.1038/s41467-021-27164-0; html:https://europepmc.org/articles/PMC8613205; pdf:https://europepmc.org/articles/PMC8613205?pdf=render 32926504,https://doi.org/10.1002/pds.5121,Implementing high-dimensional propensity score principles to improve confounder adjustment in UK electronic health records.,"Tazare J, Smeeth L, Evans SJW, Williamson E, Douglas IJ.",,Pharmacoepidemiology and drug safety,2020,2020-09-14,N,Pharmacoepidemiology; Electronic Health Records; Electronic Medical Records; High-dimensional Propensity Score; Database Research; Confounder Adjustment,,,"

Purpose

Recent evidence from US claims data suggests use of high-dimensional propensity score (hd-PS) methods improve adjustment for confounding in non-randomised studies of interventions. However, it is unclear how best to apply hd-PS principles outside their original setting, given important differences between claims data and electronic health records (EHRs). We aimed to implement the hd-PS in the setting of United Kingdom (UK) EHRs.

Methods

We studied the interaction between clopidogrel and proton pump inhibitors (PPIs). Whilst previous observational studies suggested an interaction (with reduced effect of clopidogrel), case-only, genetic and randomised trial approaches showed no interaction, strongly suggesting the original observational findings were subject to confounding. We derived a cohort of clopidogrel users from the UK Clinical Practice Research Datalink linked with the Myocardial Ischaemia National Audit Project. Analyses estimated the hazard ratio (HR) for myocardial infarction (MI) comparing PPI users with non-users using a Cox model adjusting for confounders. To reflect unique characteristics of UK EHRs, we varied the application of hd-PS principles including the level of grouping within coding systems and adapting the assessment of code recurrence. Results were compared with traditional analyses.

Results

Twenty-four thousand four hundred and seventy-one patients took clopidogrel, of whom 9111 were prescribed a PPI. Traditional PS approaches obtained a HR for the association between PPI use and MI of 1.17 (95% CI: 1.00-1.35). Applying hd-PS modifications resulted in estimates closer to the expected null (HR 1.00; 95% CI: 0.78-1.28).

Conclusions

hd-PS provided improved adjustment for confounding compared with other approaches, suggesting hd-PS can be usefully applied in UK EHRs.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/pds.5121; doi:https://doi.org/10.1002/pds.5121 36082449,https://doi.org/10.1002/ijc.34279,"Global colorectal cancer research, 2007-2021: Outputs and funding.","Begum M, Lewison G, Wang X, Dunne PD, Maughan T, Sullivan R, Lawler M.",,International journal of cancer,2023,2022-09-28,Y,Funding; Colorectal Cancer; disease burden; Research Outputs; Research Domains,,,"The purpose of this study was to provide an evidence base for colorectal cancer research activity that might influence policy, mainly at the national level. Improvements in healthcare delivery have lengthened life expectancy, but within a situation of increased cancer incidence. The disease burden of CRC has risen significantly, particularly in Africa, Asia and Latin America. Research is key to its control and reduction, but few studies have delineated the volume and funding of global research on CRC. We identified research papers in the Web of Science (WoS) from 2007 to 2021, and determined the contributions of the leading countries, the research domains studied, and their sources of funding. We identified 62 716 papers, representing 5.7% of all cancer papers. This percentage was somewhat disproportionate to the disease burden (7.7% in 2015), especially in Eastern Europe. International collaboration increased over the time period in almost all countries except in China. Genetics, surgery and prognosis were the leading research domains. However, research on palliative care and quality-of-life in CRC was lacking. In Western Europe, the main funding source was the charity sector, particularly in the UK, but in most other countries government played the leading role, especially in China and the USA. There was little support from industry. Several Asian countries provided minimal contestable funding, which may have reduced the impact of their CRC research. Certain countries must perform more CRC research overall, especially in domains such as screening, palliative care and quality-of-life. The private-non-profit sector should be an alternative source of support.",,doi:https://doi.org/10.1002/ijc.34279; doi:https://doi.org/10.1002/ijc.34279; html:https://europepmc.org/articles/PMC10086800; pdf:https://europepmc.org/articles/PMC10086800?pdf=render -35459950,https://doi.org/10.1093/intqhc/mzac031,Modelling the effect of COVID-19 mass vaccination on acute hospital admissions.,"Booton RD, Powell AL, Turner KME, Wood RM.",,International journal for quality in health care : journal of the International Society for Quality in Health Care,2022,2022-05-01,N,Vaccination; Coronavirus; Mathematical Modelling; Bed Management; Hospital Capacity; Covid-19,,,"

Background

Managing high levels of acute COVID-19 bed occupancy can affect the quality of care provided to both affected patients and those requiring other hospital services. Mass vaccination has offered a route to reduce societal restrictions while protecting hospitals from being overwhelmed. Yet, early in the mass vaccination effort, the possible impact on future bed pressures remained subject to considerable uncertainty.

Objective

The aim of this study was to model the effect of vaccination on projections of acute and intensive care bed demand within a 1 million resident healthcare system located in South West England.

Methods

An age-structured epidemiological model of the susceptible-exposed-infectious-recovered type was fitted to local data up to the time of the study, in early March 2021. Model parameters and vaccination scenarios were calibrated through a system-wide multidisciplinary working group, comprising public health intelligence specialists, healthcare planners, epidemiologists and academics. Scenarios assumed incremental relaxations to societal restrictions according to the envisaged UK Government timeline, with all restrictions to be removed by 21 June 2021.

Results

Achieving 95% vaccine uptake in adults by 31 July 2021 would not avert the third wave in autumn 2021 but would produce a median peak bed requirement ∼6% (IQR: 1-24%) of that experienced during the second wave (January 2021). A 2-month delay in vaccine rollout would lead to significantly higher peak bed occupancy, at 66% (11-146%) of that of the second wave. If only 75% uptake was achieved (the amount typically associated with vaccination campaigns), then the second wave peak for acute and intensive care beds would be exceeded by 4% and 19%, respectively, an amount which would seriously pressure hospital capacity.

Conclusion

Modelling influenced decision-making among senior managers in setting COVID-19 bed capacity levels, as well as highlighting the importance of public health in promoting high vaccine uptake among the population. Forecast accuracy has since been supported by actual data collected following the analysis, with observed peak bed occupancy falling comfortably within the inter-quartile range of modelled projections.",,pdf:https://academic.oup.com/intqhc/article-pdf/34/2/mzac031/43704475/mzac031.pdf; doi:https://doi.org/10.1093/intqhc/mzac031 33306026,https://doi.org/10.2196/23369,Engagement With a Behavior Change App for Alcohol Reduction: Data Visualization for Longitudinal Observational Study.,"Bell L, Garnett C, Qian T, Perski O, Williamson E, Potts HW.",,Journal of medical Internet research,2020,2020-12-11,Y,Engagement; Behavior Change; Apps; Mobile Health; Digital Health; Just-in-time Adaptive Interventions; Push Notifications; Micro-randomized Trial; Data Visualizations,,,"

Background

Behavior change apps can develop iteratively, where the app evolves into a complex, dynamic, or personalized intervention through cycles of research, development, and implementation. Understanding how existing users engage with an app (eg, frequency, amount, depth, and duration of use) can help guide further incremental improvements. We aim to explore how simple visualizations can provide a good understanding of temporal patterns of engagement, as usage data are often longitudinal and rich.

Objective

This study aims to visualize behavioral engagement with Drink Less, a behavior change app to help reduce hazardous and harmful alcohol consumption in the general adult population of the United Kingdom.

Methods

We explored behavioral engagement among 19,233 existing users of Drink Less. Users were included in the sample if they were from the United Kingdom; were 18 years or older; were interested in reducing their alcohol consumption; had a baseline Alcohol Use Disorders Identification Test score of 8 or above, indicative of excessive drinking; and had downloaded the app between May 17, 2017, and January 22, 2019 (615 days). Measures of when sessions begin, length of sessions, time to disengagement, and patterns of use were visualized with heat maps, timeline plots, k-modes clustering analyses, and Kaplan-Meier plots.

Results

The daily 11 AM notification is strongly associated with a change in engagement in the following hour; reduction in behavioral engagement over time, with 50.00% (9617/19,233) of users disengaging (defined as no use for 7 or more consecutive days) 22 days after download; identification of 3 distinct trajectories of use, namely engagers (4651/19,233, 24.18% of users), slow disengagers (3679/19,233, 19.13% of users), and fast disengagers (10,903/19,233, 56.68% of users); and limited depth of engagement with 85.076% (7,095,348/8,340,005) of screen views occurring within the Self-monitoring and Feedback module. In addition, a peak of both frequency and amount of time spent per session was observed in the evenings.

Conclusions

Visualizations play an important role in understanding engagement with behavior change apps. Here, we discuss how simple visualizations helped identify important patterns of engagement with Drink Less. Our visualizations of behavioral engagement suggest that the daily notification substantially impacts engagement. Furthermore, the visualizations suggest that a fixed notification policy can be effective for maintaining engagement for some users but ineffective for others. We conclude that optimizing the notification policy to target both effectiveness and engagement is a worthwhile investment. Our future goal is to both understand the causal effect of the notification on engagement and further optimize the notification policy within Drink Less by tailoring to contextual circumstances of individuals over time. Such tailoring will be informed from the findings of our micro-randomized trial (MRT), and these visualizations were useful in both gaining a better understanding of engagement and designing the MRT.",,pdf:https://www.jmir.org/2020/12/e23369/PDF; doi:https://doi.org/10.2196/23369; html:https://europepmc.org/articles/PMC7762688 -34543272,https://doi.org/10.1371/journal.pcbi.1009324,Ten simple rules to make your computing more environmentally sustainable.,"Lannelongue L, Grealey J, Bateman A, Inouye M.",,PLoS computational biology,2021,2021-09-20,Y,,,,,,pdf:https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1009324&type=printable; doi:https://doi.org/10.1371/journal.pcbi.1009324; html:https://europepmc.org/articles/PMC8452068; pdf:https://europepmc.org/articles/PMC8452068?pdf=render +35459950,https://doi.org/10.1093/intqhc/mzac031,Modelling the effect of COVID-19 mass vaccination on acute hospital admissions.,"Booton RD, Powell AL, Turner KME, Wood RM.",,International journal for quality in health care : journal of the International Society for Quality in Health Care,2022,2022-05-01,N,Vaccination; Coronavirus; Mathematical Modelling; Bed Management; Hospital Capacity; Covid-19,,,"

Background

Managing high levels of acute COVID-19 bed occupancy can affect the quality of care provided to both affected patients and those requiring other hospital services. Mass vaccination has offered a route to reduce societal restrictions while protecting hospitals from being overwhelmed. Yet, early in the mass vaccination effort, the possible impact on future bed pressures remained subject to considerable uncertainty.

Objective

The aim of this study was to model the effect of vaccination on projections of acute and intensive care bed demand within a 1 million resident healthcare system located in South West England.

Methods

An age-structured epidemiological model of the susceptible-exposed-infectious-recovered type was fitted to local data up to the time of the study, in early March 2021. Model parameters and vaccination scenarios were calibrated through a system-wide multidisciplinary working group, comprising public health intelligence specialists, healthcare planners, epidemiologists and academics. Scenarios assumed incremental relaxations to societal restrictions according to the envisaged UK Government timeline, with all restrictions to be removed by 21 June 2021.

Results

Achieving 95% vaccine uptake in adults by 31 July 2021 would not avert the third wave in autumn 2021 but would produce a median peak bed requirement ∼6% (IQR: 1-24%) of that experienced during the second wave (January 2021). A 2-month delay in vaccine rollout would lead to significantly higher peak bed occupancy, at 66% (11-146%) of that of the second wave. If only 75% uptake was achieved (the amount typically associated with vaccination campaigns), then the second wave peak for acute and intensive care beds would be exceeded by 4% and 19%, respectively, an amount which would seriously pressure hospital capacity.

Conclusion

Modelling influenced decision-making among senior managers in setting COVID-19 bed capacity levels, as well as highlighting the importance of public health in promoting high vaccine uptake among the population. Forecast accuracy has since been supported by actual data collected following the analysis, with observed peak bed occupancy falling comfortably within the inter-quartile range of modelled projections.",,pdf:https://academic.oup.com/intqhc/article-pdf/34/2/mzac031/43704475/mzac031.pdf; doi:https://doi.org/10.1093/intqhc/mzac031 32103533,https://doi.org/10.1002/sim.8503,Propensity scores using missingness pattern information: a practical guide.,"Blake HA, Leyrat C, Mansfield KE, Seaman S, Tomlinson LA, Carpenter J, Williamson EJ.",,Statistics in medicine,2020,2020-02-27,N,Electronic Health Records; Propensity Score Analysis; Missingness Pattern; Missing Indicator; Missing Confounder Data,,,"Electronic health records are a valuable data source for investigating health-related questions, and propensity score analysis has become an increasingly popular approach to address confounding bias in such investigations. However, because electronic health records are typically routinely recorded as part of standard clinical care, there are often missing values, particularly for potential confounders. In our motivating study-using electronic health records to investigate the effect of renin-angiotensin system blockers on the risk of acute kidney injury-two key confounders, ethnicity and chronic kidney disease stage, have 59% and 53% missing data, respectively. The missingness pattern approach (MPA), a variant of the missing indicator approach, has been proposed as a method for handling partially observed confounders in propensity score analysis. In the MPA, propensity scores are estimated separately for each missingness pattern present in the data. Although the assumptions underlying the validity of the MPA are stated in the literature, it can be difficult in practice to assess their plausibility. In this article, we explore the MPA's underlying assumptions by using causal diagrams to assess their plausibility in a range of simple scenarios, drawing general conclusions about situations in which they are likely to be violated. We present a framework providing practical guidance for assessing whether the MPA's assumptions are plausible in a particular setting and thus deciding when the MPA is appropriate. We apply our framework to our motivating study, showing that the MPA's underlying assumptions appear reasonable, and we demonstrate the application of MPA to this study.",,pdf:https://researchonline.lshtm.ac.uk/id/eprint/4656008/1/manuscript.pdf; doi:https://doi.org/10.1002/sim.8503; html:https://europepmc.org/articles/PMC7612316; pdf:https://europepmc.org/articles/PMC7612316?pdf=render; doi:https://doi.org/10.1002/sim.8503 +34543272,https://doi.org/10.1371/journal.pcbi.1009324,Ten simple rules to make your computing more environmentally sustainable.,"Lannelongue L, Grealey J, Bateman A, Inouye M.",,PLoS computational biology,2021,2021-09-20,Y,,,,,,pdf:https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1009324&type=printable; doi:https://doi.org/10.1371/journal.pcbi.1009324; html:https://europepmc.org/articles/PMC8452068; pdf:https://europepmc.org/articles/PMC8452068?pdf=render 32788201,https://doi.org/10.1136/archdischild-2020-319027,Predictive value of indicators for identifying child maltreatment and intimate partner violence in coded electronic health records: a systematic review and meta-analysis.,"Syed S, Ashwick R, Schlosser M, Gonzalez-Izquierdo A, Li L, Gilbert R.",,Archives of disease in childhood,2021,2020-08-11,Y,Data collection; epidemiology; Child Abuse; Health Services Research; Drug Withdrawal,,,"

Objective

Electronic health records (EHRs) are routinely used to identify family violence, yet reliable evidence of their validity remains limited. We conducted a systematic review and meta-analysis to evaluate the positive predictive values (PPVs) of coded indicators in EHRs for identifying intimate partner violence (IPV) and child maltreatment (CM), including prenatal neglect.

Methods

We searched 18 electronic databases between January 1980 and May 2020 for studies comparing any coded indicator of IPV or CM including prenatal neglect defined as neonatal abstinence syndrome (NAS) or fetal alcohol syndrome (FAS), against an independent reference standard. We pooled PPVs for each indicator using random effects meta-analyses.

Results

We included 88 studies (3 875 183 individuals) involving 15 indicators for identifying CM in the prenatal period and childhood (0-18 years) and five indicators for IPV among women of reproductive age (12-50 years). Based on the International Classification of Disease system, the pooled PPV was over 80% for NAS (16 studies) but lower for FAS (<40%; seven studies). For young children, primary diagnoses of CM, specific injury presentations (eg, rib fractures and retinal haemorrhages) and assaults showed a high PPV for CM (pooled PPVs: 55.9%-87.8%). Indicators of IPV in women had a high PPV, with primary diagnoses correctly identifying IPV in >85% of cases.

Conclusions

Coded indicators in EHRs have a high likelihood of correctly classifying types of CM and IPV across the life course, providing a useful tool for assessment, support and monitoring of high-risk groups in health services and research.",,pdf:https://adc.bmj.com/content/archdischild/106/1/44.full.pdf; doi:https://doi.org/10.1136/archdischild-2020-319027; html:https://europepmc.org/articles/PMC7788194; pdf:https://europepmc.org/articles/PMC7788194?pdf=render 35898465,https://doi.org/10.3389/fendo.2022.888924,Diabetic Foot Risk Classification at the Time of Type 2 Diabetes Diagnosis and Subsequent Risk of Mortality: A Population-Based Cohort Study.,"Wang Z, Hazlehurst J, Subramanian A, Tahrani AA, Hanif W, Thomas N, Singh P, Wang J, Sainsbury C, Nirantharakumar K, Crowe FL.",,Frontiers in endocrinology,2022,2022-07-11,Y,Mortality; Type 2 diabetes; Diabetic Foot Disease; Diabetic Foot Risk; Foot Risk Examination,,,"

Aim

We aimed to compare the mortality of individuals at low, moderate, and high risk of diabetic foot disease (DFD) in the context of newly diagnosed type 2 diabetes, before developing active diabetic foot problem.

Methods

This was a population-based cohort study of adults with newly diagnosed type 2 diabetes utilizing IQVIA Medical Research Data. The outcome was all-cause mortality among individuals with low, moderate, and high risk of DFD, and also in those with no record of foot assessment and those who declined foot examination.

Results

Of 225,787 individuals with newly diagnosed type 2 diabetes, 34,061 (15.1%) died during the study period from January 1, 2000 to December 31, 2019. Moderate risk and high risk of DFD were associated with increased mortality risk compared to low risk of DFD (adjusted hazard ratio [aHR] 1.50, 95% CI 1.42, 1.58; aHR 2.01, 95% CI 1.84, 2.20, respectively). Individuals who declined foot examination or who had no record also had increased mortality risk of 75% and 25% vs. those at low risk of DFD, respectively (aHR 1.75, 95% CI 1.51, 2.04; aHR 1.25, 95% CI 1.20, 1.30).

Conclusion

Individuals with new-onset type 2 diabetes who had moderate to high risk of DFD were more likely to die compared to those at low risk of DFD. The associations between declined foot examination and absence of foot examinations, and increased risk of mortality further highlight the importance of assessing foot risk as it identifies not only patients at risk of diabetic foot ulceration but also mortality.",,pdf:https://www.frontiersin.org/articles/10.3389/fendo.2022.888924/pdf; doi:https://doi.org/10.3389/fendo.2022.888924; html:https://europepmc.org/articles/PMC9309507; pdf:https://europepmc.org/articles/PMC9309507?pdf=render 36812613,https://doi.org/10.1371/journal.pdig.0000190,Optimizing cardiovascular risk assessment and registration in a developing cardiovascular learning health care system: Women benefit most.,"Groenhof TKJ, Haitjema S, Lely AT, Grobbee DE, Asselbergs FW, Bots ML, UCC-CVRM and UPOD Study groups.",,PLOS digital health,2023,2023-02-08,Y,,,,"Since 2015 we organized a uniform, structured collection of a fixed set of cardiovascular risk factors according the (inter)national guidelines on cardiovascular risk management. We evaluated the current state of a developing cardiovascular towards learning healthcare system-the Utrecht Cardiovascular Cohort Cardiovascular Risk Management (UCC-CVRM)-and its potential effect on guideline adherence in cardiovascular risk management. We conducted a before-after study comparing data from patients included in UCC-CVRM (2015-2018) and patients treated in our center before UCC-CVRM (2013-2015) who would have been eligible for UCC-CVRM using the Utrecht Patient Oriented Database (UPOD). Proportions of cardiovascular risk factor measurement before and after UCC-CVRM initiation were compared, as were proportions of patients that required (change of) blood pressure, lipid, or blood glucose lowering treatment. We estimated the likelihood to miss patients with hypertension, dyslipidemia, and elevated HbA1c before UCC-CVRM for the whole cohort and stratified for sex. In the present study, patients included up to October 2018 (n = 1904) were matched with 7195 UPOD patients with similar age, sex, department of referral and diagnose description. Completeness of risk factor measurement increased, ranging from 0% -77% before to 82%-94% after UCC-CVRM initiation. Before UCC-CVRM, we found more unmeasured risk factors in women compared to men. This sex-gap resolved in UCC-CVRM. The likelihood to miss hypertension, dyslipidemia, and elevated HbA1c was reduced by 67%, 75% and 90%, respectively, after UCC-CVRM initiation. A finding more pronounced in women compared to men. In conclusion, a systematic registration of the cardiovascular risk profile substantially improves guideline adherent assessment and decreases the risk of missing patients with elevated levels with an indication for treatment. The sex-gap disappeared after UCC-CVRM initiation. Thus, an LHS approach contributes to a more inclusive insight into quality of care and prevention of cardiovascular disease (progression).",,pdf:https://journals.plos.org/digitalhealth/article/file?id=10.1371/journal.pdig.0000190&type=printable; doi:https://doi.org/10.1371/journal.pdig.0000190; html:https://europepmc.org/articles/PMC9931327; pdf:https://europepmc.org/articles/PMC9931327?pdf=render @@ -1033,22 +1033,22 @@ PMC10686417,https://doi.org/,The impact of restricted provision of publicly fund 37963560,https://doi.org/10.1098/rsif.2023.0410,Spatio-temporal surveillance and early detection of SARS-CoV-2 variants of concern: a retrospective analysis.,"Cavallaro M, Dyson L, Tildesley MJ, Todkill D, Keeling MJ.",,"Journal of the Royal Society, Interface",2023,2023-11-15,Y,Disease Emergence; Anomaly Detection; Early Warning Signals; Sars-cov-2,,,"The SARS-CoV-2 pandemic has been characterized by the repeated emergence of genetically distinct virus variants of increased transmissibility and immune evasion compared to pre-existing lineages. In many countries, their containment required the intervention of public health authorities and the imposition of control measures. While the primary role of testing is to identify infection, target treatment, and limit spread (through isolation and contact tracing), a secondary benefit is in terms of surveillance and the early detection of new variants. Here we study the spatial invasion and early spread of the Alpha, Delta and Omicron (BA.1 and BA.2) variants in England from September 2020 to February 2022 using the random neighbourhood covering (RaNCover) method. This is a statistical technique for the detection of aberrations in spatial point processes, which we tailored here to community PCR (polymerase-chain-reaction) test data where the TaqPath kit provides a proxy measure of the switch between variants. Retrospectively, RaNCover detected the earliest signals associated with the four novel variants that led to large infection waves in England. With suitable data our method therefore has the potential to rapidly detect outbreaks of future SARS-CoV-2 variants, thus helping to inform targeted public health interventions.",,doi:https://doi.org/10.1098/rsif.2023.0410; html:https://europepmc.org/articles/PMC10645511; pdf:https://europepmc.org/articles/PMC10645511?pdf=render 31765395,https://doi.org/10.1371/journal.pone.0225625,Semantic computational analysis of anticoagulation use in atrial fibrillation from real world data.,"Bean DM, Teo J, Wu H, Oliveira R, Patel R, Bendayan R, Shah AM, Dobson RJB, Scott PA.",,PloS one,2019,2019-11-25,Y,,,,"Atrial fibrillation (AF) is the most common arrhythmia and significantly increases stroke risk. This risk is effectively managed by oral anticoagulation. Recent studies using national registry data indicate increased use of anticoagulation resulting from changes in guidelines and the availability of newer drugs. The aim of this study is to develop and validate an open source risk scoring pipeline for free-text electronic health record data using natural language processing. AF patients discharged from 1st January 2011 to 1st October 2017 were identified from discharge summaries (N = 10,030, 64.6% male, average age 75.3 ± 12.3 years). A natural language processing pipeline was developed to identify risk factors in clinical text and calculate risk for ischaemic stroke (CHA2DS2-VASc) and bleeding (HAS-BLED). Scores were validated vs two independent experts for 40 patients. Automatic risk scores were in strong agreement with the two independent experts for CHA2DS2-VASc (average kappa 0.78 vs experts, compared to 0.85 between experts). Agreement was lower for HAS-BLED (average kappa 0.54 vs experts, compared to 0.74 between experts). In high-risk patients (CHA2DS2-VASc ≥2) OAC use has increased significantly over the last 7 years, driven by the availability of DOACs and the transitioning of patients from AP medication alone to OAC. Factors independently associated with OAC use included components of the CHA2DS2-VASc and HAS-BLED scores as well as discharging specialty and frailty. OAC use was highest in patients discharged under cardiology (69%). Electronic health record text can be used for automatic calculation of clinical risk scores at scale. Open source tools are available today for this task but require further validation. Analysis of routinely collected EHR data can replicate findings from large-scale curated registries.","Bean et al. looked at using clinical notes to calculate risk scores: CHADSVASC and HASBLED for 10,030 AF patients from 2011 to October 2017), they’ve validated their natural language processing algorithm with getting clinicians to calculate the risk in conventional manner for 40 of cases, the two scores were in higher agreement for stroke risk compared to HAS-BLED They’ve concluded on usefulness of NLP method in risk calculation at the large scale.",pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0225625&type=printable; doi:https://doi.org/10.1371/journal.pone.0225625; html:https://europepmc.org/articles/PMC6876873; pdf:https://europepmc.org/articles/PMC6876873?pdf=render 37194197,https://doi.org/10.1111/acps.13566,Low risk of some common cancers in women with anorexia nervosa: Evidence from a national record-linkage study.,"Seminog O, Thakrar DB, James AC, Goldacre MJ.",,Acta psychiatrica Scandinavica,2023,2023-05-16,Y,Cancer; Caloric restriction; epidemiology; Anorexia Nervosa; risk,,,"

Background

Some studies report that women with anorexia nervosa (AN) have lower risk than others of breast cancer, but increased risk of cancers of other sites. No work has been done to quantify the risk in the English population.

Methods

Retrospective cohort study using a national linked dataset of Hospital Episode Statistics for 1999-2021. We selected individuals with a hospital admission for AN, and compared their relative risk (RR) of developing site-specific cancers, with that in a reference cohort.

Results

We identified 75 cancers in 15,029 women hospitalised with AN. There was a low RR of all cancers combined at 0.75 (95%CI 0.59-0.94), and, notably, low RR for breast cancer 0.43 (0.20-0.81), cancers of secondary and ill-defined sites 0.52 (0.26-0.93). The RR for parotid gland cancer was 4.4 (1.4-10.6) within a year of first recorded diagnosis of AN. In men, we found 12 cancers in 1413 individuals hospitalised with AN, but no increased risks beyond the first year of diagnosis of AN.

Conclusions

This is the first report on the association between AN and cancers in the all-England population. The study showed low rates of breast cancer, and of all cancers combined, in women hospitalised with AN. It is possible that some of the metabolic or hormonal changes observed in AN could work as a protective factor for breast cancer. More experimental work is needed to identify and explain these factors. The new finding on the higher risk of salivary gland tumours could inform clinicians caring for patients with AN.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/acps.13566; doi:https://doi.org/10.1111/acps.13566; html:https://europepmc.org/articles/PMC10953461; pdf:https://europepmc.org/articles/PMC10953461?pdf=render -37717030,https://doi.org/10.1186/s13756-023-01280-6,The impact of the COVID-19 pandemic on the treatment of common infections in primary care and the change to antibiotic prescribing in England.,"Yang YT, Zhong X, Fahmi A, Watts S, Ashcroft DM, Massey J, Fisher L, MacKenna B, Mehrkar A, Bacon SCJ, Goldacre B, Hand K, van Staa T, Palin V.",,Antimicrobial resistance and infection control,2023,2023-09-16,Y,Infection; Antibiotics; Primary Care; Antibiotic Stewardship; Covid-19 Pandemic,,,"

Background

There is concern that the COVID-19 pandemic altered the management of common infections in primary care. This study aimed to evaluate infection-coded consultation rates and antibiotic use during the pandemic and how any change may have affected clinical outcomes.

Methods

With the approval of NHS England, a retrospective cohort study using the OpenSAFELY platform analysed routinely collected electronic health data from GP practices in England between January 2019 and December 2021. Infection coded consultations and antibiotic prescriptions were used estimate multiple measures over calendar months, including age-sex adjusted prescribing rates, prescribing by infection and antibiotic type, infection consultation rates, coding quality and rate of same-day antibiotic prescribing for COVID-19 infections. Interrupted time series (ITS) estimated the effect of COVID-19 pandemic on infection-coded consultation rates. The impact of the pandemic on non- COVID-19 infection-related hospitalisations was also estimated.

Results

Records from 24 million patients were included. The rate of infection-related consultations fell for all infections (mean reduction of 39% in 2020 compared to 2019 mean rate), except for UTI which remained stable. Modelling infection-related consultation rates highlighted this with an incidence rate ratio of 0.44 (95% CI 0.36-0.53) for incident consultations and 0.43 (95% CI 0.33-0.54) for prevalent consultations. Lower respiratory tract infections (LRTI) saw the largest reduction of 0.11 (95% CI 0.07-0.17). Antibiotic prescribing rates fell with a mean reduction of 118.4 items per 1000 patients in 2020, returning to pre-pandemic rates by summer 2021. Prescribing for LRTI decreased 20% and URTI increased 15.9%. Over 60% of antibiotics were issued without an associated same-day infection code, which increased during the pandemic. Infection-related hospitalisations reduced (by 62%), with the largest reduction observed for pneumonia infections (72.9%). Same-day antibiotic prescribing for COVID-19 infection increased from 1 to 10.5% between the second and third national lockdowns and rose again during 2022.

Conclusions

Changes to consultations and hospital admissions may be driven by reduced transmission of non-COVID-19 infections due to reduced social mixing and lockdowns. Inconsistencies in coding practice emphasises the need for improvement to inform new antibiotic stewardship policies and prevent resistance to novel infections.",,pdf:https://aricjournal.biomedcentral.com/counter/pdf/10.1186/s13756-023-01280-6; doi:https://doi.org/10.1186/s13756-023-01280-6; html:https://europepmc.org/articles/PMC10504725; pdf:https://europepmc.org/articles/PMC10504725?pdf=render 32790708,https://doi.org/10.1371/journal.pone.0237298,Clinical academic research in the time of Corona: A simulation study in England and a call for action.,"Banerjee A, Katsoulis M, Lai AG, Pasea L, Treibel TA, Manisty C, Denaxas S, Quarta G, Hemingway H, Cavalcante JL, Noursadeghi M, Moon JC.",,PloS one,2020,2020-08-13,Y,,,,"

Objectives

We aimed to model the impact of coronavirus (COVID-19) on the clinical academic response in England, and to provide recommendations for COVID-related research.

Design

A stochastic model to determine clinical academic capacity in England, incorporating the following key factors which affect the ability to conduct research in the COVID-19 climate: (i) infection growth rate and population infection rate (from UK COVID-19 statistics and WHO); (ii) strain on the healthcare system (from published model); and (iii) availability of clinical academic staff with appropriate skillsets affected by frontline clinical activity and sickness (from UK statistics).

Setting

Clinical academics in primary and secondary care in England.

Participants

Equivalent of 3200 full-time clinical academics in England.

Interventions

Four policy approaches to COVID-19 with differing population infection rates: ""Italy model"" (6%), ""mitigation"" (10%), ""relaxed mitigation"" (40%) and ""do-nothing"" (80%) scenarios. Low and high strain on the health system (no clinical academics able to do research at 10% and 5% infection rate, respectively.

Main outcome measures

Number of full-time clinical academics available to conduct clinical research during the pandemic in England.

Results

In the ""Italy model"", ""mitigation"", ""relaxed mitigation"" and ""do-nothing"" scenarios, from 5 March 2020 the duration (days) and peak infection rates (%) are 95(2.4%), 115(2.5%), 240(5.3%) and 240(16.7%) respectively. Near complete attrition of academia (87% reduction, <400 clinical academics) occurs 35 days after pandemic start for 11, 34, 62, 76 days respectively-with no clinical academics at all for 37 days in the ""do-nothing"" scenario. Restoration of normal academic workforce (80% of normal capacity) takes 11, 12, 30 and 26 weeks respectively.

Conclusions

Pandemic COVID-19 crushes the science needed at system level. National policies mitigate, but the academic community needs to adapt. We highlight six key strategies: radical prioritisation (eg 3-4 research ideas per institution), deep resourcing, non-standard leadership (repurposing of key non-frontline teams), rationalisation (profoundly simple approaches), careful site selection (eg protected sites with large academic backup) and complete suspension of academic competition with collaborative approaches.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0237298&type=printable; doi:https://doi.org/10.1371/journal.pone.0237298; html:https://europepmc.org/articles/PMC7425844; pdf:https://europepmc.org/articles/PMC7425844?pdf=render +37717030,https://doi.org/10.1186/s13756-023-01280-6,The impact of the COVID-19 pandemic on the treatment of common infections in primary care and the change to antibiotic prescribing in England.,"Yang YT, Zhong X, Fahmi A, Watts S, Ashcroft DM, Massey J, Fisher L, MacKenna B, Mehrkar A, Bacon SCJ, Goldacre B, Hand K, van Staa T, Palin V.",,Antimicrobial resistance and infection control,2023,2023-09-16,Y,Infection; Antibiotics; Primary Care; Antibiotic Stewardship; Covid-19 Pandemic,,,"

Background

There is concern that the COVID-19 pandemic altered the management of common infections in primary care. This study aimed to evaluate infection-coded consultation rates and antibiotic use during the pandemic and how any change may have affected clinical outcomes.

Methods

With the approval of NHS England, a retrospective cohort study using the OpenSAFELY platform analysed routinely collected electronic health data from GP practices in England between January 2019 and December 2021. Infection coded consultations and antibiotic prescriptions were used estimate multiple measures over calendar months, including age-sex adjusted prescribing rates, prescribing by infection and antibiotic type, infection consultation rates, coding quality and rate of same-day antibiotic prescribing for COVID-19 infections. Interrupted time series (ITS) estimated the effect of COVID-19 pandemic on infection-coded consultation rates. The impact of the pandemic on non- COVID-19 infection-related hospitalisations was also estimated.

Results

Records from 24 million patients were included. The rate of infection-related consultations fell for all infections (mean reduction of 39% in 2020 compared to 2019 mean rate), except for UTI which remained stable. Modelling infection-related consultation rates highlighted this with an incidence rate ratio of 0.44 (95% CI 0.36-0.53) for incident consultations and 0.43 (95% CI 0.33-0.54) for prevalent consultations. Lower respiratory tract infections (LRTI) saw the largest reduction of 0.11 (95% CI 0.07-0.17). Antibiotic prescribing rates fell with a mean reduction of 118.4 items per 1000 patients in 2020, returning to pre-pandemic rates by summer 2021. Prescribing for LRTI decreased 20% and URTI increased 15.9%. Over 60% of antibiotics were issued without an associated same-day infection code, which increased during the pandemic. Infection-related hospitalisations reduced (by 62%), with the largest reduction observed for pneumonia infections (72.9%). Same-day antibiotic prescribing for COVID-19 infection increased from 1 to 10.5% between the second and third national lockdowns and rose again during 2022.

Conclusions

Changes to consultations and hospital admissions may be driven by reduced transmission of non-COVID-19 infections due to reduced social mixing and lockdowns. Inconsistencies in coding practice emphasises the need for improvement to inform new antibiotic stewardship policies and prevent resistance to novel infections.",,pdf:https://aricjournal.biomedcentral.com/counter/pdf/10.1186/s13756-023-01280-6; doi:https://doi.org/10.1186/s13756-023-01280-6; html:https://europepmc.org/articles/PMC10504725; pdf:https://europepmc.org/articles/PMC10504725?pdf=render 32864476,https://doi.org/10.23889/ijpds.v5i1.1157,"Prevalence of Down's Syndrome in England, 1998-2013: Comparison of linked surveillance data and electronic health records.","Doidge JC, Morris JK, Harron KL, Stevens S, Gilbert R.",,International journal of population data science,2020,2020-01-01,Y,Prevalence; Data Linkage; Disease Surveillance; Down’s Syndrome; Electronic Health Records; Linkage Error,,,"

Introduction

Disease registers and electronic health records are valuable resources for disease surveillance and research but can be limited by variation in data quality over time. Quality may be limited in terms of the accuracy of clinical information, of the internal linkage that supports person-based analysis of most administrative datasets, or by errors in linkage between multiple datasets.

Objectives

By linking the National Down Syndrome Cytogenetic Register (NDSCR) to Hospital Episode Statistics for England (HES), we aimed to assess the quality of each and establish a consistent approach for analysis of trends in prevalence of Down's syndrome among live births in England.

Methods

Probabilistic record linkage of NDSCR to HES for the period 1998-2013 was supported by linkage of babies to mothers within HES. Comparison of prevalence estimates in England were made using NDSCR only, HES data only, and linked data. Capture-recapture analysis and quantitative bias analysis were used to account for potential errors, including false positive diagnostic codes, unrecorded diagnoses, and linkage error.

Results

Analyses of single-source data indicated increasing live birth prevalence of Down's Syndrome, particularly in the analysis of HES. Linked data indicated a contrastingly stable prevalence of 12.3 (plausible range: 11.6-12.7) cases per 10 000 live births.

Conclusion

Case ascertainment in NDSCR improved slightly over time, creating a picture of slowly increasing prevalence. The emerging epidemic suggested by HES primarily reflects improving linkage within HES (assignment of unique patient identifiers to hospital episodes). Administrative data are valuable but trends should be interpreted with caution, and with assessment of data quality over time. Data linkage with quantitative bias analysis can provide more robust estimation and, in this case, stronger evidence that prevalence is not increasing. Routine linkage of administrative and register data can enhance the value of each.",,pdf:https://ijpds.org/article/download/1157/2531; doi:https://doi.org/10.23889/ijpds.v5i1.1157; html:https://europepmc.org/articles/PMC7115985; pdf:https://europepmc.org/articles/PMC7115985?pdf=render 35317796,https://doi.org/10.1186/s12916-022-02308-1,"Correction to: Lifetime risk of cardiovascular-renal disease in type 2 diabetes: a population-based study in 473,399 individuals.","Zhang R, Mamza JB, Morris T, Godfrey G, Asselbergs FW, Denaxas S, Hemingway H, Banerjee A.",,BMC medicine,2022,2022-03-23,Y,,,,,,pdf:https://bmcmedicine.biomedcentral.com/track/pdf/10.1186/s12916-022-02308-1; doi:https://doi.org/10.1186/s12916-022-02308-1; html:https://europepmc.org/articles/PMC8941726; pdf:https://europepmc.org/articles/PMC8941726?pdf=render 35640889,https://doi.org/10.1093/ehjci/jeac101,Pericardial adiposity is independently linked to adverse cardiovascular phenotypes: a CMR study of 42 598 UK Biobank participants.,"Ardissino M, McCracken C, Bard A, Antoniades C, Neubauer S, Harvey NC, Petersen SE, Raisi-Estabragh Z.",,European heart journal. Cardiovascular Imaging,2022,2022-10-01,Y,Arterial stiffness; Cardiovascular Magnetic Resonance; Left ventricle; Pericardial Fat; Left Atrium; Cardiometabolic Disease,,,"

Aims

We evaluated independent associations of cardiovascular magnetic resonance (CMR)-measured pericardial adipose tissue (PAT) with cardiovascular structure and function and considered underlying mechanism in 42 598 UK Biobank participants.

Methods and results

We extracted PAT and selected CMR metrics using automated pipelines. We estimated associations of PAT with each CMR metric using linear regression adjusting for age, sex, ethnicity, deprivation, smoking, exercise, processed food intake, body mass index, diabetes, hypertension, height cholesterol, waist-to-hip ratio, impedance fat measures, and magnetic resonance imaging abdominal visceral adiposity measures. Higher PAT was independently associated with unhealthy left ventricular (LV) structure (greater wall thickness, higher LV mass, more concentric pattern of LV hypertrophy), poorer LV function (lower LV global function index, lower LV stroke volume), lower left atrial ejection fraction, and lower aortic distensibility. We used multiple mediation analysis to examine the potential mediating effect of cardiometabolic diseases and blood biomarkers (lipid profile, glycaemic control, inflammation) in the PAT-CMR relationships. Higher PAT was associated with cardiometabolic disease (hypertension, diabetes, high cholesterol), adverse serum lipids, poorer glycaemic control, and greater systemic inflammation. We identified potential mediation pathways via hypertension, adverse lipids, and inflammation markers, which overall only partially explained the PAT-CMR relationships.

Conclusion

We demonstrate association of PAT with unhealthy cardiovascular structure and function, independent of baseline comorbidities, vascular risk factors, inflammatory markers, and multiple non-invasive and imaging measures of obesity. Our findings support an independent role of PAT in adversely impacting cardiovascular health and highlight CMR-measured PAT as a potential novel imaging biomarker of cardiovascular risk.",,pdf:https://academic.oup.com/ehjcimaging/article-pdf/23/11/1471/46583486/jeac101.pdf; doi:https://doi.org/10.1093/ehjci/jeac101; html:https://europepmc.org/articles/PMC9584621; pdf:https://europepmc.org/articles/PMC9584621?pdf=render 31951005,https://doi.org/10.1093/jamia/ocz211,On classifying sepsis heterogeneity in the ICU: insight using machine learning.,"Ibrahim ZM, Wu H, Hamoud A, Stappen L, Dobson RJB, Agarossi A.",,Journal of the American Medical Informatics Association : JAMIA,2020,2020-03-01,Y,Sepsis; Machine Learning; Artificial Intelligence In Medicine; Sepsis Prediction; Sepsis Subtypes,Applied Analytics,,"

Objectives

Current machine learning models aiming to predict sepsis from electronic health records (EHR) do not account 20 for the heterogeneity of the condition despite its emerging importance in prognosis and treatment. This work demonstrates the added value of stratifying the types of organ dysfunction observed in patients who develop sepsis in the intensive care unit (ICU) in improving the ability to recognize patients at risk of sepsis from their EHR data.

Materials and methods

Using an ICU dataset of 13 728 records, we identify clinically significant sepsis subpopulations with distinct organ dysfunction patterns. We perform classification experiments with random forest, gradient boost trees, and support vector machines, using the identified subpopulations to distinguish patients who develop sepsis in the ICU from those who do not.

Results

The classification results show that features selected using sepsis subpopulations as background knowledge yield a superior performance in distinguishing septic from non-septic patients regardless of the classification model used. The improved performance is especially pronounced in specificity, which is a current bottleneck in sepsis prediction machine learning models.

Conclusion

Our findings can steer machine learning efforts toward more personalized models for complex conditions including sepsis.",Ibrahim et al. categorized patients in groups based on the type of organ failure. This categorization helped machine based algorithms to correctly identify those at high risk of sepsis.,pdf:https://academic.oup.com/jamia/article-pdf/27/3/437/34153319/ocz211.pdf; doi:https://doi.org/10.1093/jamia/ocz211; html:https://europepmc.org/articles/PMC7025363; pdf:https://europepmc.org/articles/PMC7025363?pdf=render 31628383,https://doi.org/10.1038/s41598-019-51562-6,Whole genome sequencing of drug resistant Mycobacterium tuberculosis isolates from a high burden tuberculosis region of North West Pakistan.,"Jabbar A, Phelan JE, de Sessions PF, Khan TA, Rahman H, Khan SN, Cantillon DM, Wildner LM, Ali S, Campino S, Waddell SJ, Clark TG.",,Scientific reports,2019,2019-10-18,Y,,,,"Tuberculosis (TB), caused by Mycobacterium tuberculosis bacteria, is a leading infectious cause of mortality worldwide, including in Pakistan. Drug resistant M. tuberculosis is an emerging threat for TB control, making it important to detect the underlying genetic mutations, and thereby inform treatment decision making and prevent transmission. Whole genome sequencing has emerged as the new diagnostic to reliably predict drug resistance within a clinically relevant time frame, and its deployment will have the greatest impact on TB control in highly endemic regions. To evaluate the mutations leading to drug resistance and to assess for evidence of the transmission of resistant strains, 81 M. tuberculosis samples from Khyber Pakhtunkhwa province (North West Pakistan) were subjected to whole genome sequencing and standard drug susceptibility testing for eleven anti-TB drugs. We found the majority of M. tuberculosis isolates were the CAS/Delhi strain-type (lineage 3; n = 57; 70.4%) and multi-drug resistant (MDR; n = 62; 76.5%). The most frequent resistance mutations were observed in the katG and rpoB genes, conferring resistance to isoniazid and rifampicin respectively. Mutations were also observed in genes conferring resistance to other first and second-line drugs, including in pncA (pyrazinamide), embB (ethambutol), gyrA (fluoroquinolones), rrs (aminoglycosides), rpsL, rrs and giB (streptomycin) loci. Whilst the majority of mutations have been reported in global datasets, we describe unreported putative resistance markers in katG, ethA (ethionamide), gyrA and gyrB (fluoroquinolones), and pncA. Analysis of the mutations revealed that acquisition of rifampicin resistance often preceded isoniazid in our isolates. We also observed a high proportion (17.6%) of pre-MDR isolates with fluoroquinolone resistance markers, potentially due to unregulated anti-TB drug use. Our isolates were compared to previously sequenced strains from Pakistan in a combined phylogenetic tree analysis. The presence of lineage 2 was only observed in our isolates. Using a cut-off of less than ten genome-wide mutation differences between isolates, a transmission analysis revealed 18 M. tuberculosis isolates clustering within eight networks, thereby providing evidence of drug-resistant TB transmission in the Khyber Pakhtunkhwa province. Overall, we have demonstrated that drug-resistant TB isolates are circulating and transmitted in North West Pakistan. Further, we have shown the usefulness of whole genome sequencing as a diagnostic tool for characterizing M. tuberculosis isolates, which will assist future epidemiological studies and disease control activities in Pakistan.",,pdf:https://www.nature.com/articles/s41598-019-51562-6.pdf; doi:https://doi.org/10.1038/s41598-019-51562-6; html:https://europepmc.org/articles/PMC6802378; pdf:https://europepmc.org/articles/PMC6802378?pdf=render 33851963,https://doi.org/10.1001/jamadermatol.2021.0009,Association Between Atopic Dermatitis and Educational Attainment in Denmark.,"Schmidt SAJ, Mailhac A, Darvalics B, Mulick A, Deleuran MS, Sørensen HT, Riis JL, Langan SM.",,JAMA dermatology,2021,2021-04-14,Y,,,,"

Importance

Atopic dermatitis (AD) may affect academic performance through multiple pathways, including poor concentration associated with itching, sleep deprivation, or adverse effects of medications. Because educational attainment is associated with health and well-being, any association with a prevalent condition such as AD is of major importance.

Objective

To examine whether a childhood diagnosis of AD is associated with lower educational attainment.

Design, setting, and participants

This population-based cohort study used linked routine health care data from January 1, 1977, to June 30, 2017 (end of registry follow-up), in Denmark. The study population included all children born in Denmark on June 30, 1987, or earlier with an inpatient or outpatient hospital clinic diagnosis of AD recorded before their 13th birthday (baseline) and a comparison cohort of children from the general population matched by birth year and sex. A secondary analysis included exposure-discordant full siblings as a comparison cohort to account for familial factors. Data were analyzed from September 11, 2019, to January 21, 2021.

Exposures

Hospital-diagnosed AD.

Main outcomes and measures

Estimated probability or risk of not attaining specific educational levels (lower secondary, upper secondary, and higher) by 30 years of age among children with AD compared with children in the matched general population cohort. Corresponding risk ratios (RRs) were computed using Poisson regression that was conditioned on matched sets and adjusted for age. The sibling analysis was conditioned on family and adjusted for sex and age.

Results

The study included a total of 61 153 children, 5927 in the AD cohort (3341 male [56.4%]) and 55 226 from the general population (31 182 male [56.5%]). Compared with matched children from the general population, children with AD were at increased risk of not attaining lower secondary education (150 of 5927 [2.5%] vs 924 of 55 226 [1.7%]; adjusted RR, 1.50; 95% CI, 1.26-1.78) and upper secondary education (1141 of 5777 [19.8%] vs 8690 of 52 899 [16.4%]; RR, 1.16; 95% CI, 1.09-1.24), but not higher education (2406 of 4636 [51.9%] vs 18 785 of 35 408 [53.1%]; RR, 0.95; 95% CI, 0.91-1.00). The absolute differences in probability were less than 3.5%. The comparison of 3259 children with AD and 4046 of their full siblings yielded estimates that were less pronounced than those in the main analysis (adjusted RR for lower secondary education, 1.29 [95% CI, 0.92-1.82]; adjusted RR for upper secondary education, 1.05 [95% CI, 0.93-1.18]; adjusted RR for higher education, 0.94 [95% CI, 0.87-1.02]).

Conclusions and relevance

This population-based cohort study found that hospital-diagnosed AD was associated with reduced educational attainment, but the clinical importance was uncertain owing to small absolute differences and possible confounding by familial factors in this study. Future studies should examine for replicability in other populations and variation by AD phenotype.",,pdf:https://jamanetwork.com/journals/jamadermatology/articlepdf/2778389/jamadermatology_schmidt_2021_oi_210002_1623774349.64965.pdf; doi:https://doi.org/10.1001/jamadermatol.2021.0009; html:https://europepmc.org/articles/PMC8047754 -37705832,https://doi.org/10.5837/bjc.2023.003,SGLT2 inhibitors in CKD and HFpEF: two new large trials and two new meta-analyses.,"Mayne KJ, Preiss D, Herrington WG.",,The British journal of cardiology,2023,2023-02-21,N,Cardiovascular disease; Heart Failure; Chronic Kidney Disease; Sodium-Glucose Co-Transporter 2 (Sglt2) Inhibitor,,,,,doi:https://doi.org/10.5837/bjc.2023.003; html:https://europepmc.org/articles/PMC10495762; pdf:https://europepmc.org/articles/PMC10495762?pdf=render; doi:https://doi.org/10.5837/bjc.2023.003 35463778,https://doi.org/10.3389/fcvm.2022.859310,Fairness in Cardiac Magnetic Resonance Imaging: Assessing Sex and Racial Bias in Deep Learning-Based Segmentation.,"Puyol-Antón E, Ruijsink B, Mariscal Harana J, Piechnik SK, Neubauer S, Petersen SE, Razavi R, Chowienczyk P, King AP.",,Frontiers in cardiovascular medicine,2022,2022-04-07,Y,Segmentation; Cardiac Magnetic Resonance; Deep Learning; Fair Ai; Inequality Fairness In Deep Learning-Based Cmr Segmentation,,,"

Background

Artificial intelligence (AI) techniques have been proposed for automation of cine CMR segmentation for functional quantification. However, in other applications AI models have been shown to have potential for sex and/or racial bias. The objective of this paper is to perform the first analysis of sex/racial bias in AI-based cine CMR segmentation using a large-scale database.

Methods

A state-of-the-art deep learning (DL) model was used for automatic segmentation of both ventricles and the myocardium from cine short-axis CMR. The dataset consisted of end-diastole and end-systole short-axis cine CMR images of 5,903 subjects from the UK Biobank database (61.5 ± 7.1 years, 52% male, 81% white). To assess sex and racial bias, we compared Dice scores and errors in measurements of biventricular volumes and function between patients grouped by race and sex. To investigate whether segmentation bias could be explained by potential confounders, a multivariate linear regression and ANCOVA were performed.

Results

Results on the overall population showed an excellent agreement between the manual and automatic segmentations. We found statistically significant differences in Dice scores between races (white ∼94% vs. minority ethnic groups 86-89%) as well as in absolute/relative errors in volumetric and functional measures, showing that the AI model was biased against minority racial groups, even after correction for possible confounders. The results of a multivariate linear regression analysis showed that no covariate could explain the Dice score bias between racial groups. However, for the Mixed and Black race groups, sex showed a weak positive association with the Dice score. The results of an ANCOVA analysis showed that race was the main factor that can explain the overall difference in Dice scores between racial groups.

Conclusion

We have shown that racial bias can exist in DL-based cine CMR segmentation models when training with a database that is sex-balanced but not race-balanced such as the UK Biobank.",,pdf:https://www.frontiersin.org/articles/10.3389/fcvm.2022.859310/pdf; doi:https://doi.org/10.3389/fcvm.2022.859310; html:https://europepmc.org/articles/PMC9021445; pdf:https://europepmc.org/articles/PMC9021445?pdf=render +37705832,https://doi.org/10.5837/bjc.2023.003,SGLT2 inhibitors in CKD and HFpEF: two new large trials and two new meta-analyses.,"Mayne KJ, Preiss D, Herrington WG.",,The British journal of cardiology,2023,2023-02-21,N,Cardiovascular disease; Heart Failure; Chronic Kidney Disease; Sodium-Glucose Co-Transporter 2 (Sglt2) Inhibitor,,,,,doi:https://doi.org/10.5837/bjc.2023.003; html:https://europepmc.org/articles/PMC10495762; pdf:https://europepmc.org/articles/PMC10495762?pdf=render; doi:https://doi.org/10.5837/bjc.2023.003 36834176,https://doi.org/10.3390/ijerph20043477,"Non-Pharmacological Therapies for Post-Viral Syndromes, Including Long COVID: A Systematic Review.","Chandan JS, Brown KR, Simms-Williams N, Bashir NZ, Camaradou J, Heining D, Turner GM, Rivera SC, Hotham R, Minhas S, Nirantharakumar K, Sivan M, Khunti K, Raindi D, Marwaha S, Hughes SE, McMullan C, Marshall T, Calvert MJ, Haroon S, Aiyegbusi OL, TLC Study.",,International journal of environmental research and public health,2023,2023-02-16,Y,Rehabilitation; Systematic review; Pvs; Non-pharmacological Intervention; Covid-19; Long Covid; Post-covid-19 Condition; Post-acute Sequelae Of Sars-cov-2 Infection (Pasc); Post-Viral Syndromes,,,"

Background

Post-viral syndromes (PVS), including Long COVID, are symptoms sustained from weeks to years following an acute viral infection. Non-pharmacological treatments for these symptoms are poorly understood. This review summarises the evidence for the effectiveness of non-pharmacological treatments for PVS.

Methods

We conducted a systematic review to evaluate the effectiveness of non-pharmacological interventions for PVS, as compared to either standard care, alternative non-pharmacological therapy, or placebo. The outcomes of interest were changes in symptoms, exercise capacity, quality of life (including mental health and wellbeing), and work capability. We searched five databases (Embase, MEDLINE, PsycINFO, CINAHL, MedRxiv) for randomised controlled trials (RCTs) published between 1 January 2001 to 29 October 2021. The relevant outcome data were extracted, the study quality was appraised using the Cochrane risk-of-bias tool, and the findings were synthesised narratively.

Findings

Overall, five studies of five different interventions (Pilates, music therapy, telerehabilitation, resistance exercise, neuromodulation) met the inclusion criteria. Aside from music-based intervention, all other selected interventions demonstrated some support in the management of PVS in some patients.

Interpretation

In this study, we observed a lack of robust evidence evaluating the non-pharmacological treatments for PVS, including Long COVID. Considering the prevalence of prolonged symptoms following acute viral infections, there is an urgent need for clinical trials evaluating the effectiveness and cost-effectiveness of non-pharmacological treatments for patients with PVS.

Registration

The study protocol was registered with PROSPERO [CRD42021282074] in October 2021 and published in BMJ Open in 2022.",,pdf:https://www.mdpi.com/1660-4601/20/4/3477/pdf?version=1677135187; doi:https://doi.org/10.3390/ijerph20043477; html:https://europepmc.org/articles/PMC9967466; pdf:https://europepmc.org/articles/PMC9967466?pdf=render -37897346,https://doi.org/10.1093/eurheartj/ehad727,Five critical quality criteria for artificial intelligence-based prediction models.,"van Royen FS, Asselbergs FW, Alfonso F, Vardas P, van Smeden M.",,European heart journal,2023,2023-12-01,Y,Prediction; Artificial intelligence; Diagnosis; Prognosis; Digital Health,,,"To raise the quality of clinical artificial intelligence (AI) prediction modelling studies in the cardiovascular health domain and thereby improve their impact and relevancy, the editors for digital health, innovation, and quality standards of the European Heart Journal propose five minimal quality criteria for AI-based prediction model development and validation studies: complete reporting, carefully defined intended use of the model, rigorous validation, large enough sample size, and openness of code and software.",,doi:https://doi.org/10.1093/eurheartj/ehad727; html:https://europepmc.org/articles/PMC10702458; pdf:https://europepmc.org/articles/PMC10702458?pdf=render 33497994,https://doi.org/10.1016/j.puhe.2020.12.003,Obesity during the COVID-19 pandemic: both cause of high risk and potential effect of lockdown? A population-based electronic health record study.,"Katsoulis M, Pasea L, Lai AG, Dobson RJB, Denaxas S, Hemingway H, Banerjee A.",,Public health,2021,2020-12-14,Y,Obesity; Diabetes; Coronavirus; Physical Activity; cardiovascular,,,"

Objectives

Obesity is a modifiable risk factor for coronavirus disease 2019 (COVID-19)-related mortality. We estimated excess mortality in obesity, both 'direct', through infection, and 'indirect', through changes in health care, and also due to potential increasing obesity during lockdown.

Study design

The study design of this study is a retrospective cohort study and causal inference methods.

Methods

In population-based electronic health records for 1,958,638 individuals in England, we estimated 1-year mortality risk ('direct' and 'indirect' effects) for obese individuals, incorporating (i) pre-COVID-19 risk by age, sex and comorbidities, (ii) population infection rate and (iii) relative impact on mortality (relative risk [RR]: 1.2, 1.5, 2.0 and 3.0). Using causal inference models, we estimated impact of change in body mass index (BMI) and physical activity during 3-month lockdown on 1-year incidence for high-risk conditions (cardiovascular diseases, diabetes, chronic obstructive pulmonary disease and chronic kidney disease), accounting for confounders.

Results

For severely obese individuals (3.5% at baseline), at 10% population infection rate, we estimated direct impact of 240 and 479 excess deaths in England at RR 1.5 and 2.0, respectively, and indirect effect of 383-767 excess deaths, assuming 40% and 80% will be affected at RR = 1.2. Owing to BMI change during the lockdown, we estimated that 97,755 (5.4%: normal weight to overweight, 5.0%: overweight to obese and 1.3%: obese to severely obese) to 434,104 individuals (15%: normal weight to overweight, 15%: overweight to obese and 6%: obese to severely obese) would be at higher risk for COVID-19 over one year.

Conclusions

Prevention of obesity and promotion of physical activity are at least as important as physical isolation of severely obese individuals during the pandemic.",,doi:https://doi.org/10.1016/j.puhe.2020.12.003; doi:https://doi.org/10.1016/j.puhe.2020.12.003; html:https://europepmc.org/articles/PMC7832229; pdf:https://europepmc.org/articles/PMC7832229?pdf=render 33516523,https://doi.org/10.1016/j.jaci.2020.12.001,"Atopic eczema in adulthood and mortality: UK population-based cohort study, 1998-2016.","Silverwood RJ, Mansfield KE, Mulick A, Wong AYS, Schmidt SAJ, Roberts A, Smeeth L, Abuabara K, Langan SM.",,The Journal of allergy and clinical immunology,2021,2021-01-27,Y,Activity; Mortality; Cohort study; United Kingdom; Primary Care; Atopic Eczema; Severity; Population-based; Electronic Health Care Records,,,"

Background

Atopic eczema affects up to 10% of adults and is becoming more common globally. Few studies have assessed whether atopic eczema increases the risk of death.

Objective

We aimed to determine whether adults with atopic eczema were at increased risk of death overall and by specific causes and to assess whether the risk varied by atopic eczema severity and activity.

Methods

The study was a population-based matched cohort study using UK primary care electronic health care records from the Clinical Practice Research Datalink with linked hospitalization data from Hospital Episode Statistics and mortality data from the Office for National Statistics from 1998 to 2016.

Results

A total of 526,736 patients with atopic eczema were matched to 2,567,872 individuals without atopic eczema. The median age at entry was 41.8 years, and the median follow-up time was 4.5 years. There was limited evidence of increased hazard for all-cause mortality in those with atopic eczema (hazard ratio = 1.04; 99% CI = 1.03-1.06), but there were somewhat stronger associations (8%-14% increased hazard) for deaths due to infectious, digestive, and genitourinary causes. Differences on the absolute scale were modest owing to low overall mortality rates. Mortality risk increased markedly with eczema severity and activity. For example, patients with severe atopic eczema had a 62% increased hazard (hazard ratio = 1.62; 99% CI = 1.54-1.71) for mortality compared with those without eczema, with the strongest associations for infectious, respiratory, and genitourinary causes.

Conclusion

The increased hazards for all-cause and cause-specific mortality were largely restricted to those with the most severe or predominantly active atopic eczema. Understanding the reasons for these increased hazards for mortality is an urgent priority.",,pdf:http://www.jacionline.org/article/S0091674920317127/pdf; doi:https://doi.org/10.1016/j.jaci.2020.12.001; html:https://europepmc.org/articles/PMC8098860; pdf:https://europepmc.org/articles/PMC8098860?pdf=render -37814053,https://doi.org/10.1038/s41588-023-01522-8,Age-dependent topic modeling of comorbidities in UK Biobank identifies disease subtypes with differential genetic risk.,"Jiang X, Zhang MJ, Zhang Y, Durvasula A, Inouye M, Holmes C, Price AL, McVean G.",,Nature genetics,2023,2023-10-09,Y,,,,"The analysis of longitudinal data from electronic health records (EHRs) has the potential to improve clinical diagnoses and enable personalized medicine, motivating efforts to identify disease subtypes from patient comorbidity information. Here we introduce an age-dependent topic modeling (ATM) method that provides a low-rank representation of longitudinal records of hundreds of distinct diseases in large EHR datasets. We applied ATM to 282,957 UK Biobank samples, identifying 52 diseases with heterogeneous comorbidity profiles; analyses of 211,908 All of Us samples produced concordant results. We defined subtypes of the 52 heterogeneous diseases based on their comorbidity profiles and compared genetic risk across disease subtypes using polygenic risk scores (PRSs), identifying 18 disease subtypes whose PRS differed significantly from other subtypes of the same disease. We further identified specific genetic variants with subtype-dependent effects on disease risk. In conclusion, ATM identifies disease subtypes with differential genome-wide and locus-specific genetic risk profiles.",,pdf:https://www.nature.com/articles/s41588-023-01522-8.pdf; doi:https://doi.org/10.1038/s41588-023-01522-8; html:https://europepmc.org/articles/PMC10632146; pdf:https://europepmc.org/articles/PMC10632146?pdf=render +37897346,https://doi.org/10.1093/eurheartj/ehad727,Five critical quality criteria for artificial intelligence-based prediction models.,"van Royen FS, Asselbergs FW, Alfonso F, Vardas P, van Smeden M.",,European heart journal,2023,2023-12-01,Y,Prediction; Artificial intelligence; Diagnosis; Prognosis; Digital Health,,,"To raise the quality of clinical artificial intelligence (AI) prediction modelling studies in the cardiovascular health domain and thereby improve their impact and relevancy, the editors for digital health, innovation, and quality standards of the European Heart Journal propose five minimal quality criteria for AI-based prediction model development and validation studies: complete reporting, carefully defined intended use of the model, rigorous validation, large enough sample size, and openness of code and software.",,doi:https://doi.org/10.1093/eurheartj/ehad727; html:https://europepmc.org/articles/PMC10702458; pdf:https://europepmc.org/articles/PMC10702458?pdf=render 37008054,https://doi.org/10.14336/ad.2022.0829,Identifying Dynamic Patterns of Polypharmacy for Patients with Dementia from Primary Care Electronic Health Records: A Machine Learning Driven Longitudinal Study.,"Longo E, Burnett B, Bauermeister S, Zhou SM.",,Aging and disease,2023,2023-04-01,Y,Diagnosis; Dementia; Patient Safety; Machine Learning; Polypharmacy; Electronic Health Records; Exploratory Factor Analysis,,,"It is unclear how medication use evolved before diagnosis of dementia (DoD). This study aims to identify varied patterns of polypharmacy before DoD, their prevalence and possible complications. We collected primary care e-health records for 33,451 dementia patients in Wales from 1990 to 2015. The medication uses in every 5-year period along with 20-years prior to dementia diagnosis were considered. Exploratory factor analysis was used to identify clusters of medicines for every 5-year period. The prevalence of patients taking three or more medications was 82.16%, 69.7%, 41.1% and 5.5% in the Period 1 (0-5 years before DoD) ~ Period 4 (16-20 years before DoD) respectively. The Period 1 showed 3 clusters of polypharmacy - medicines for respiratory/urinary infections, arthropathies and rheumatism, and cardio-vascular disease (CVD) (66.55%); medicines for infections, arthropathies and rheumatism (AR), cardio-metabolic disease (CMD) and depression (22.02%); and medicines for arthropathies, rheumatism and osteoarthritis (2.6%). The Period 2 showed 4 clusters of polypharmacy - medicines for infections, arthropathies, and CVD (69.7%); medicines for CVD and depression (3%); medicines for CMD and arthropathies (0.3%); and medicines for AR, and CVD (2,5%). The Period 3 showed 6 clusters of polypharmacy - medicines for infections, arthropathies, and CVD (41.1%); medicines for CVD, acute-respiratory-infection (ARI), and arthropathies (1.25%); medicines for AR (1.16%); medicines for depression, anxiety (0.06%); medicines for CMD (1.4%); and medicines for dermatologic disorders (0.9%). The Period 4 showed 3 main clusters of polypharmacy - medicines for infections, arthropathy, and CVD (5.5%); medicines for anxiety, ARI (2.4%); and medicines for ARI and CVD (2.1%). As the development towards dementia progressed, the associative diseases tended to cluster with a larger prevalence in each cluster. Farther away before DoD, the clusters of polypharmacy tended to be clearly distinct between each other, resulting in an increasing number of patterns, but in a smaller prevalence.",,doi:https://doi.org/10.14336/ad.2022.0829; doi:https://doi.org/10.14336/AD.2022.0829; html:https://europepmc.org/articles/PMC10017143; pdf:https://europepmc.org/articles/PMC10017143?pdf=render +37814053,https://doi.org/10.1038/s41588-023-01522-8,Age-dependent topic modeling of comorbidities in UK Biobank identifies disease subtypes with differential genetic risk.,"Jiang X, Zhang MJ, Zhang Y, Durvasula A, Inouye M, Holmes C, Price AL, McVean G.",,Nature genetics,2023,2023-10-09,Y,,,,"The analysis of longitudinal data from electronic health records (EHRs) has the potential to improve clinical diagnoses and enable personalized medicine, motivating efforts to identify disease subtypes from patient comorbidity information. Here we introduce an age-dependent topic modeling (ATM) method that provides a low-rank representation of longitudinal records of hundreds of distinct diseases in large EHR datasets. We applied ATM to 282,957 UK Biobank samples, identifying 52 diseases with heterogeneous comorbidity profiles; analyses of 211,908 All of Us samples produced concordant results. We defined subtypes of the 52 heterogeneous diseases based on their comorbidity profiles and compared genetic risk across disease subtypes using polygenic risk scores (PRSs), identifying 18 disease subtypes whose PRS differed significantly from other subtypes of the same disease. We further identified specific genetic variants with subtype-dependent effects on disease risk. In conclusion, ATM identifies disease subtypes with differential genome-wide and locus-specific genetic risk profiles.",,pdf:https://www.nature.com/articles/s41588-023-01522-8.pdf; doi:https://doi.org/10.1038/s41588-023-01522-8; html:https://europepmc.org/articles/PMC10632146; pdf:https://europepmc.org/articles/PMC10632146?pdf=render 38374065,https://doi.org/10.1038/s41467-024-45779-x,Genetic influences on circulating retinol and its relationship to human health.,"Reay WR, Kiltschewskij DJ, Di Biase MA, Gerring ZF, Kundu K, Surendran P, Greco LA, Clarke ED, Collins CE, Mondul AM, Albanes D, Cairns MJ.",,Nature communications,2024,2024-02-19,Y,,,,"Retinol is a fat-soluble vitamin that plays an essential role in many biological processes throughout the human lifespan. Here, we perform the largest genome-wide association study (GWAS) of retinol to date in up to 22,274 participants. We identify eight common variant loci associated with retinol, as well as a rare-variant signal. An integrative gene prioritisation pipeline supports novel retinol-associated genes outside of the main retinol transport complex (RBP4:TTR) related to lipid biology, energy homoeostasis, and endocrine signalling. Genetic proxies of circulating retinol were then used to estimate causal relationships with almost 20,000 clinical phenotypes via a phenome-wide Mendelian randomisation study (MR-pheWAS). The MR-pheWAS suggests that retinol may exert causal effects on inflammation, adiposity, ocular measures, the microbiome, and MRI-derived brain phenotypes, amongst several others. Conversely, circulating retinol may be causally influenced by factors including lipids and serum creatinine. Finally, we demonstrate how a retinol polygenic score could identify individuals more likely to fall outside of the normative range of circulating retinol for a given age. In summary, this study provides a comprehensive evaluation of the genetics of circulating retinol, as well as revealing traits which should be prioritised for further investigation with respect to retinol related therapies or nutritional intervention.",,pdf:https://www.nature.com/articles/s41467-024-45779-x.pdf; doi:https://doi.org/10.1038/s41467-024-45779-x; html:https://europepmc.org/articles/PMC10876955; pdf:https://europepmc.org/articles/PMC10876955?pdf=render 38400634,https://doi.org/10.1093/ageing/afae021,Adherence to the Atrial fibrillation Better Care pathway and the risk of adverse health outcomes in older care home residents with atrial fibrillation: a retrospective data linkage study 2003-18.,"Ritchie LA, Harrison SL, Penson PE, Akbari A, Torabi F, Hollinghurst J, Harris D, Oke OB, Akpan A, Halcox JP, Rodgers SE, Lip GYH, Lane DA.",,Age and ageing,2024,2024-02-01,Y,Atrial fibrillation; Older People; Care Homes; Integrated Care; Health Outcomes,,,"

Background

The Atrial fibrillation Better Care (ABC) pathway is the gold-standard approach to atrial fibrillation (AF) management, but the effect of implementation on health outcomes in care home residents is unknown.

Objective

To examine associations between ABC pathway adherence and stroke, transient ischaemic attack, cardiovascular hospitalisation, major bleeding, mortality and a composite of all these outcomes in care home residents.

Methods

A retrospective cohort study of older care home residents (≥65 years) in Wales with AF was conducted between 1 January 2003 and 31 December 2018 using the Secure Anonymised Information Linkage Databank. Adherence to the ABC pathway was assessed at care home entry using pre-specified definitions. Cox proportional hazard and competing risk models were used to estimate the risk of health outcomes according to ABC adherence.

Results

From 14,493 residents (median [interquartile range] age 87.0 [82.6-91.2] years, 35.2% male) with AF, 5,531 (38.2%) were ABC pathway adherent. Pathway adherence was not significantly associated with risk of the composite outcome (adjusted hazard ratio, 95% confidence interval [CI]: 1.01 [0.97-1.05]). There was a significant independent association observed between ABC pathway adherence and a reduced risk of myocardial infarction (0.70 [0.50-0.98]), but a higher risk of haemorrhagic stroke (1.59 [1.06-2.39]). ABC pathway adherence was not significantly associated with any other individual health outcomes examined.

Conclusion

An ABC adherent approach in care home residents was not consistently associated with improved health outcomes. Findings should be interpreted with caution owing to difficulties in defining pathway adherence using routinely collected data and an individualised approach is recommended.",,doi:https://doi.org/10.1093/ageing/afae021; html:https://europepmc.org/articles/PMC10891424; pdf:https://europepmc.org/articles/PMC10891424?pdf=render 32444447,https://doi.org/10.1136/archdischild-2019-317902,Emergency paediatric critical care in England: describing trends using routine hospital data.,"Lewis KM, Parekh SM, Ramnarayan P, Gilbert R, Hardelid P, Wijlaars L.",,Archives of disease in childhood,2020,2020-05-22,Y,epidemiology; Intensive Care,,,"

Objective

To determine trends in emergency admission rates requiring different levels of critical care in hospitals with and without a paediatric intensive care unit (PICU).

Design

Birth cohort study created from Hospital Episode Statistics.

Setting

National Health Service funded hospitals in England.

Patients

8 577 680 singleton children born between 1 May 2003 and 31 April 2017.

Outcome measures

Using procedure and diagnostic codes, we assigned indicators of high dependency care (eg, non-invasive ventilation) or intensive care (eg, invasive ventilation) to emergency admissions.

Interventions

Children were followed up until their fifth birthday to estimate high dependency and intensive care admission rates in hospitals with and without a PICU. We tested the yearly trend of high dependency and intensive care admissions to hospitals without a PICU using logistic regression models.

Results

Emergency admissions requiring high dependency care in hospitals without a PICU increased from 3.30 (95% CI 3.09 to 3.51) per 10 000 child-years in 2008/2009 to 7.58 (95% CI 7.28 to 7.89) in 2016/2017 and overtook hospitals with a PICU in 2015/2016. The odds of an admission requiring high dependency care to a hospital without a PICU compared with a hospital with a PICU increased by 9% per study year (OR 1.09, 95% CI 1.08 to 1.10). The same trend was not present for admissions requiring intensive care (OR 1.01, 95% CI 0.99 to 1.03).

Conclusions

Between 2008/2009 and 2016/2017, an increasing proportion of admissions with indicators of high dependency care took place in hospitals without a PICU.",,pdf:https://adc.bmj.com/content/archdischild/105/11/1061.full.pdf; doi:https://doi.org/10.1136/archdischild-2019-317902; html:https://europepmc.org/articles/PMC7588403; pdf:https://europepmc.org/articles/PMC7588403?pdf=render @@ -1059,15 +1059,15 @@ PMC10686417,https://doi.org/,The impact of restricted provision of publicly fund 35870544,https://doi.org/10.1016/j.cpcardiol.2022.101330,Artificial Intelligence and Cardiovascular Magnetic Resonance Imaging in Myocardial Infarction Patients.,"Chong JH, Abdulkareem M, Petersen SE, Khanji MY.",,Current problems in cardiology,2022,2022-07-21,N,,,,"Cardiovascular magnetic resonance (CMR) is an important cardiac imaging tool for assessing the prognostic extent of myocardial injury after myocardial infarction (MI). Within the context of clinical trials, CMR is also useful for assessing the efficacy of potential cardioprotective therapies in reducing MI size and preventing adverse left ventricular (LV) remodelling in reperfused MI. However, manual contouring and analysis can be time-consuming with interobserver and intra-observer variability, which can in turn lead to reduction in accuracy and precision of analysis. There is thus a need to automate CMR scan analysis in MI patients to save time, increase accuracy, increase reproducibility and increase precision. In this regard, automated imaging analysis techniques based on artificial intelligence (AI) that are developed with machine learning (ML), and more specifically deep learning (DL) strategies, can enable efficient, robust, accurate and clinician-friendly tools to be built so as to try and improve both clinician productivity and quality of patient care. In this review, we discuss basic concepts of ML in CMR, important prognostic CMR imaging biomarkers in MI and the utility of current ML applications in their analysis as assessed in research studies. We highlight potential barriers to the mainstream implementation of these automated strategies and discuss related governance and quality control issues. Lastly, we discuss the future role of ML applications in clinical trials and the need for global collaboration in growing this field.",,pdf:https://qmro.qmul.ac.uk/xmlui/bitstream/123456789/79542/2/Petersen%20Artificial%20intelligence%20and%20cardiovascular%202022%20Accepted.pdf; doi:https://doi.org/10.1016/j.cpcardiol.2022.101330 35322592,https://doi.org/10.1002/ehf2.13910,Cardiovascular outcomes associated with treatment of type 2 diabetes in patients with ischaemic heart failure.,"Godec TR, Bromage DI, Pujades-Rodriguez M, Cannatà A, Gonzalez-Izquierdo A, Denaxas S, Hemingway H, Shah AM, Yellon DM, McDonagh TA.",,ESC heart failure,2022,2022-03-23,Y,Type 2 diabetes; Metformin; Heart Failure; Outcomes; Ischaemic Cardiomyopathy; Antidiabetic Agents,,,"

Aim

The optimal strategy for diabetes control in patients with heart failure (HF) following myocardial infarction (MI) remains unknown. Metformin, a guideline-recommended therapy for patients with chronic HF and type 2 diabetes mellitus (T2DM), is associated with reduced mortality and HF hospitalizations. However, worse outcomes have been reported when used at the time of MI. We compared outcomes of patients with T2DM and HF of ischaemic aetiology according to antidiabetic treatment.

Methods and results

This study used linked data from primary care, hospital admissions, and death registries for 4.7 million inhabitants in England, as part of the CALIBER resource. The primary endpoint was a composite of cardiovascular mortality and HF hospitalization. The secondary endpoints were the individual components of the primary endpoint and all-cause mortality. To evaluate the effect of temporal changes in diabetes treatment, antidiabetic medication was included as time-dependent covariates in survival analyses. The study included 1172 patients with T2DM and prior MI and incident HF between 3 January 1998 and 26 February 2010. Five hundred and ninety-six patients had the primary outcome over median follow-up of 2.53 (IQR: 0.98-4.92) years. Adjusted analyses showed a reduced hazard of the composite endpoint for exposure to all antidiabetic medication with hazard ratios (HRs) of 0.50 [95% confidence interval (CI): 0.42-0.59], 0.66 (95% CI: 0.55-0.80), and 0.53 (95% CI: 0.43-0.65), respectively. A similar effect was seen for all-cause mortality [HRs of 0.43 (95% CI: 0.35-0.52), 0.57 (95% CI: 0.46-0.70), and 0.34 (95% CI: 0.27-0.43), respectively].

Conclusions

When considering changes in antidiabetic treatment over time, all drug classes were associated with reduced risk of cardiovascular mortality and HF hospitalization.",,pdf:https://kclpure.kcl.ac.uk/ws/files/173598342/ESC_Heart_Failure_2022_Godec_Cardiovascular_outcomes_associated_with_treatment_of_type_2_diabetes_in_patients_with.pdf; doi:https://doi.org/10.1002/ehf2.13910; html:https://europepmc.org/articles/PMC9065866; pdf:https://europepmc.org/articles/PMC9065866?pdf=render 34564897,https://doi.org/10.1002/gps.5627,Living well with dementia: What is possible and how to promote it.,"Quinn C, Pickett JA, Litherland R, Morris RG, Martyr A, Clare L, On behalf of the IDEAL Programme Team.",,International journal of geriatric psychiatry,2022,2021-10-13,Y,Quality of life; Alzheimer's; Well-being; Carer; Post-diagnostic Support,,,,,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/gps.5627; doi:https://doi.org/10.1002/gps.5627; html:https://europepmc.org/articles/PMC9292841; pdf:https://europepmc.org/articles/PMC9292841?pdf=render -37850214,https://doi.org/10.1183/23120541.00110-2023,Mapping inpatient care pathways for patients with COPD: an observational study using routinely collected electronic hospital record data.,"Evison F, Cooper R, Gallier S, Missier P, Sayer AA, Sapey E, Witham MD.",,ERJ open research,2023,2023-09-01,Y,,,,"

Introduction

Respiratory specialist ward care is associated with better outcomes for patients with COPD exacerbations. We assessed patient pathways and associated factors for people admitted to hospital with COPD exacerbations.

Methods

We analysed routinely collected electronic health data for patients admitted with COPD exacerbation in 2018 to Queen Elizabeth Hospital, Birmingham, UK. We extracted data on demographics, deprivation index, Elixhauser comorbidities, ward moves, length of stay, and in-hospital and 1-year mortality. We compared care pathways with recommended care pathways (transition from initial assessment area to respiratory wards or discharge). We used Markov state transition models to derive probabilities of following recommended pathways for patient subgroups.

Results

Of 42 555 patients with unplanned admissions during 2018, 571 patients were admitted at least once with an exacerbation of COPD. The mean±sd age was 51±11 years; 313 (55%) were women, 337 (59%) lived in the most deprived neighbourhoods and 45 (9%) were from non-white ethnic backgrounds. 428 (75.0%) had ≥4 comorbidities. Age >70 years was associated with higher in-hospital and 1-year mortality, more places of care (wards) and longer length of stay; having ≥4 comorbidities was associated with higher mortality and longer length of stay. Older age was associated with a significantly lower probability of following a recommended pathway (>70 years: 0.514, 95% CI 0.458-0.571; ≤70 years: 0.636, 95% CI 0.572-0.696; p=0.004).

Conclusions

Only older age was associated with a lower chance of following recommended hospital pathways of care. Such analyses could help refine appropriate care pathways for patients with COPD exacerbations.",,pdf:https://openres.ersjournals.com/content/erjor/early/2023/08/24/23120541.00110-2023.full.pdf; doi:https://doi.org/10.1183/23120541.00110-2023; html:https://europepmc.org/articles/PMC10577591; pdf:https://europepmc.org/articles/PMC10577591?pdf=render 32954362,https://doi.org/10.1038/s43016-020-0093-y,Nutriome-metabolome relationships provide insights into dietary intake and metabolism.,"Posma JM, Garcia-Perez I, Frost G, Aljuraiban GS, Chan Q, Van Horn L, Daviglus M, Stamler J, Holmes E, Elliott P, Nicholson JK.",,Nature food,2020,2020-06-22,N,,,,"Dietary assessment traditionally relies on self-reported data which are often inaccurate and may result in erroneous diet-disease risk associations. We illustrate how urinary metabolic phenotyping can be used as alternative approach for obtaining information on dietary patterns. We used two multi-pass 24-hr dietary recalls, obtained on two occasions on average three weeks apart, paired with two 24-hr urine collections from 1,848 U.S. individuals; 67 nutrients influenced the urinary metabotype measured with 1H-NMR spectroscopy characterized by 46 structurally identified metabolites. We investigated the stability of each metabolite over time and showed that the urinary metabolic profile is more stable within individuals than reported dietary patterns. The 46 metabolites accurately predicted healthy and unhealthy dietary patterns in a free-living U.S. cohort and replicated in an independent U.K. cohort. We mapped these metabolites into a host-microbial metabolic network to identify key pathways and functions. These data can be used in future studies to evaluate how this set of diet-derived, stable, measurable bioanalytical markers are associated with disease risk. This knowledge may give new insights into biological pathways that characterize the shift from a healthy to unhealthy metabolic phenotype and hence give entry points for prevention and intervention strategies.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7497842; doi:https://doi.org/10.1038/s43016-020-0093-y; html:https://europepmc.org/articles/PMC7497842; pdf:https://europepmc.org/articles/PMC7497842?pdf=render; doi:https://doi.org/10.1038/s43016-020-0093-y +37850214,https://doi.org/10.1183/23120541.00110-2023,Mapping inpatient care pathways for patients with COPD: an observational study using routinely collected electronic hospital record data.,"Evison F, Cooper R, Gallier S, Missier P, Sayer AA, Sapey E, Witham MD.",,ERJ open research,2023,2023-09-01,Y,,,,"

Introduction

Respiratory specialist ward care is associated with better outcomes for patients with COPD exacerbations. We assessed patient pathways and associated factors for people admitted to hospital with COPD exacerbations.

Methods

We analysed routinely collected electronic health data for patients admitted with COPD exacerbation in 2018 to Queen Elizabeth Hospital, Birmingham, UK. We extracted data on demographics, deprivation index, Elixhauser comorbidities, ward moves, length of stay, and in-hospital and 1-year mortality. We compared care pathways with recommended care pathways (transition from initial assessment area to respiratory wards or discharge). We used Markov state transition models to derive probabilities of following recommended pathways for patient subgroups.

Results

Of 42 555 patients with unplanned admissions during 2018, 571 patients were admitted at least once with an exacerbation of COPD. The mean±sd age was 51±11 years; 313 (55%) were women, 337 (59%) lived in the most deprived neighbourhoods and 45 (9%) were from non-white ethnic backgrounds. 428 (75.0%) had ≥4 comorbidities. Age >70 years was associated with higher in-hospital and 1-year mortality, more places of care (wards) and longer length of stay; having ≥4 comorbidities was associated with higher mortality and longer length of stay. Older age was associated with a significantly lower probability of following a recommended pathway (>70 years: 0.514, 95% CI 0.458-0.571; ≤70 years: 0.636, 95% CI 0.572-0.696; p=0.004).

Conclusions

Only older age was associated with a lower chance of following recommended hospital pathways of care. Such analyses could help refine appropriate care pathways for patients with COPD exacerbations.",,pdf:https://openres.ersjournals.com/content/erjor/early/2023/08/24/23120541.00110-2023.full.pdf; doi:https://doi.org/10.1183/23120541.00110-2023; html:https://europepmc.org/articles/PMC10577591; pdf:https://europepmc.org/articles/PMC10577591?pdf=render 35130878,https://doi.org/10.1186/s12916-022-02234-2,"Lifetime risk of cardiovascular-renal disease in type 2 diabetes: a population-based study in 473,399 individuals.","Zhang R, Mamza JB, Morris T, Godfrey G, Asselbergs FW, Denaxas S, Hemingway H, Banerjee A.",,BMC medicine,2022,2022-02-07,Y,Kidney; Type 2 diabetes; lifetime; Attributable Risk; Population Health; cardiovascular,,,"

Background

Cardiovascular and renal diseases (CVRD) are major causes of mortality in individuals with type 2 diabetes (T2D). Studies of lifetime risk have neither considered all CVRD together nor the relative contribution of major risk factors to combined disease burden.

Methods

In a population-based cohort study using national electronic health records, we studied 473,399 individuals with T2D in England 2007-2018. Lifetime risk of individual and combined major adverse renal cardiovascular events, MARCE (including CV death and CVRD: heart failure; chronic kidney disease; myocardial infarction; stroke or peripheral artery disease), were estimated, accounting for baseline CVRD status and competing risk of death. We calculated population attributable risk for individual CVRD components. Ideal cardiovascular health was defined by blood pressure, cholesterol, glucose, smoking, physical activity, diet, and body mass index (i.e. modifiable risk factors).

Results

In individuals with T2D, lifetime risk of MARCE was 80% in those free from CVRD and was 97%, 93%, 98%, 89% and 91% in individuals with heart failure, chronic kidney disease, myocardial infarction, stroke and peripheral arterial disease, respectively at baseline. Among CVRD-free individuals, lifetime risk of chronic kidney disease was highest (54%), followed by CV death (41%), heart failure (29%), stroke (20%), myocardial infarction (19%) and peripheral arterial disease (9%). In those with HF only, 75% of MARCE after index T2D can be attributed to HF after adjusting for age, gender, and comorbidities. Compared with those with > 1, < 3 and ≥3 modifiable health risk behaviours, achieving ideal cardiovascular health could reduce MARCE by approximately 41.5%, 23.6% and 17.2%, respectively, in the T2D population.

Conclusions

Four out of five individuals with T2D free from CVRD, and nearly all those with history of CVRD, will develop MARCE over their lifetime. Early preventive measures in T2D patients are clinical, public health and policy priorities.",,pdf:https://bmcmedicine.biomedcentral.com/track/pdf/10.1186/s12916-022-02234-2; doi:https://doi.org/10.1186/s12916-022-02234-2; html:https://europepmc.org/articles/PMC8822817; pdf:https://europepmc.org/articles/PMC8822817?pdf=render 34969173,https://doi.org/10.1002/ejhf.2417,"A population-based study of 92 clinically recognized risk factors for heart failure: co-occurrence, prognosis and preventive potential.","Banerjee A, Pasea L, Chung SC, Direk K, Asselbergs FW, Grobbee DE, Kotecha D, Anker SD, Dyszynski T, Tyl B, Denaxas S, Lumbers RT, Hemingway H.",,European journal of heart failure,2022,2022-01-26,Y,Risk factor; epidemiology; Heart Failure; Primary Prevention,,,"

Aims

Primary prevention strategies for heart failure (HF) have had limited success, possibly due to a wide range of underlying risk factors (RFs). Systematic evaluations of the prognostic burden and preventive potential across this wide range of risk factors are lacking. We aimed at estimating evidence, prevalence and co-occurrence for primary prevention and impact on prognosis of RFs for incident HF.

Methods and results

We systematically reviewed trials and observational evidence of primary HF prevention across 92 putative aetiologic RFs for HF identified from US and European clinical practice guidelines. We identified 170 885 individuals aged ≥30 years with incident HF from 1997 to 2017, using linked primary and secondary care UK electronic health records (EHR) and rule-based phenotypes (ICD-10, Read Version 2, OPCS-4 procedure and medication codes) for each of 92 RFs. Only 10/92 factors had high quality observational evidence for association with incident HF; 7 had effective randomized controlled trial (RCT)-based interventions for HF prevention (RCT-HF), and 6 for cardiovascular disease prevention, but not HF (RCT-CVD), and the remainder had no RCT-based preventive interventions (RCT-0). We were able to map 91/92 risk factors to EHR using 5961 terms, and 88/91 factors were represented by at least one patient. In the 5 years prior to HF diagnosis, 44.3% had ≥4 RFs. By RCT evidence, the most common RCT-HF RFs were hypertension (48.5%), stable angina (34.9%), unstable angina (16.8%), myocardial infarction (15.8%), and diabetes (15.1%); RCT-CVD RFs were smoking (46.4%) and obesity (29.9%); and RCT-0 RFs were atrial arrhythmias (17.2%), cancer (16.5%), heavy alcohol intake (14.9%). Mortality at 1 year varied across all 91 factors (lowest: pregnancy-related hormonal disorder 4.2%; highest: phaeochromocytoma 73.7%). Among new HF cases, 28.5% had no RCT-HF RFs and 38.6% had no RCT-CVD RFs. 15.6% had either no RF or only RCT-0 RFs.

Conclusion

One in six individuals with HF have no recorded RFs or RFs without trials. We provide a systematic map of primary preventive opportunities across a wide range of RFs for HF, demonstrating a high burden of co-occurrence and the need for trials tackling multiple RFs.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ejhf.2417; doi:https://doi.org/10.1002/ejhf.2417; html:https://europepmc.org/articles/PMC9305958; pdf:https://europepmc.org/articles/PMC9305958?pdf=render 33890864,https://doi.org/10.2196/24728,The Value of Routinely Collected Data in Evaluating Home Assessment and Modification Interventions to Prevent Falls in Older People: Systematic Literature Review.,"Daniels H, Hollinghurst J, Fry R, Clegg A, Hillcoat-Nallétamby S, Nikolova S, Rodgers SE, Williams N, Akbari A.",,JMIR aging,2021,2021-04-23,Y,Aged; Evaluation research; Systematic review; Falls; Routinely Collected Data,,,"

Background

Falls in older people commonly occur at home. Home assessment and modification (HAM) interventions can be effective in reducing falls; however, there are some concerns over the validity of evaluation findings. Routinely collected data could improve the quality of HAM evaluations and strengthen their evidence base.

Objective

The aim of this study is to conduct a systematic review of the evidence of the use of routinely collected data in the evaluations of HAM interventions.

Methods

We searched the following databases from inception until January 31, 2020: PubMed, Ovid, CINAHL, OpenGrey, CENTRAL, LILACS, and Web of Knowledge. Eligible studies were those evaluating HAMs designed to reduce falls involving participants aged 60 years or more. We included study protocols and full reports. Bias was assessed using the Risk Of Bias In Non-Randomized Studies of Interventions (ROBINS-I) tool.

Results

A total of 7 eligible studies were identified in 8 papers. Government organizations provided the majority of data across studies, with health care providers and third-sector organizations also providing data. Studies used a range of demographic, clinical and health, and administrative data. The purpose of using routinely collected data spanned recruiting and creating a sample, stratification, generating independent variables or covariates, and measuring key study-related outcomes. Nonhome-based modification interventions (eg, in nursing homes) using routinely collected data were not included in this study. We included two protocols, which meant that the results of those studies were not available. MeSH headings were excluded from the PubMed search because of a reduction in specificity. This means that some studies that met the inclusion criteria may not have been identified.

Conclusions

Routine data can be used successfully in many aspects of HAM evaluations and can reduce biases and improve other important design considerations. However, the use of these data in these studies is currently not widespread. There are a number of governance barriers to be overcome to allow these types of linkage and to ensure that the use of routinely collected data in evaluations of HAM interventions is exploited to its full potential.",,pdf:https://aging.jmir.org/2021/2/e24728/PDF; doi:https://doi.org/10.2196/24728; html:https://europepmc.org/articles/PMC8105762; pdf:https://europepmc.org/articles/PMC8105762?pdf=render 36439548,https://doi.org/10.3389/fsurg.2022.870494,Development and validation of an automated basal cell carcinoma histopathology information extraction system using natural language processing.,"Ali SR, Strafford H, Dobbs TD, Fonferko-Shadrach B, Lacey AS, Pickrell WO, Hutchings HA, Whitaker IS.",,Frontiers in surgery,2022,2022-08-24,Y,Electronic Health Records (Ehrs); Natural Language Processing (Nlp); Basal Cell Carcinoma (Bcc); Non-melanoma Skin Cancer (Nmsc); Information Extraction (Ie),,,"

Introduction

Routinely collected healthcare data are a powerful research resource, but often lack detailed disease-specific information that is collected in clinical free text such as histopathology reports. We aim to use natural Language Processing (NLP) techniques to extract detailed clinical and pathological information from histopathology reports to enrich routinely collected data.

Methods

We used the general architecture for text engineering (GATE) framework to build an NLP information extraction system using rule-based techniques. During validation, we deployed our rule-based NLP pipeline on 200 previously unseen, de-identified and pseudonymised basal cell carcinoma (BCC) histopathological reports from Swansea Bay University Health Board, Wales, UK. The results of our algorithm were compared with gold standard human annotation by two independent and blinded expert clinicians involved in skin cancer care.

Results

We identified 11,224 items of information with a mean precision, recall, and F1 score of 86.0% (95% CI: 75.1-96.9), 84.2% (95% CI: 72.8-96.1), and 84.5% (95% CI: 73.0-95.1), respectively. The difference between clinician annotator F1 scores was 7.9% in comparison with 15.5% between the NLP pipeline and the gold standard corpus. Cohen's Kappa score on annotated tokens was 0.85.

Conclusion

Using an NLP rule-based approach for named entity recognition in BCC, we have been able to develop and validate a pipeline with a potential application in improving the quality of cancer registry data, supporting service planning, and enhancing the quality of routinely collected data for research.",,pdf:https://www.frontiersin.org/articles/10.3389/fsurg.2022.870494/pdf; doi:https://doi.org/10.3389/fsurg.2022.870494; html:https://europepmc.org/articles/PMC9683031; pdf:https://europepmc.org/articles/PMC9683031?pdf=render +33414147,https://doi.org/10.1136/bmjopen-2020-041536,Estimating the COVID-19 epidemic trajectory and hospital capacity requirements in South West England: a mathematical modelling framework.,"Booton RD, MacGregor L, Vass L, Looker KJ, Hyams C, Bright PD, Harding I, Lazarus R, Hamilton F, Lawson D, Danon L, Pratt A, Wood R, Brooks-Pollock E, Turner KME.",,BMJ open,2021,2021-01-07,Y,Infection control; epidemiology; Public Health,,,"

Objectives

To develop a regional model of COVID-19 dynamics for use in estimating the number of infections, deaths and required acute and intensive care (IC) beds using the South West England (SW) as an example case.

Design

Open-source age-structured variant of a susceptible-exposed-infectious-recovered compartmental mathematical model. Latin hypercube sampling and maximum likelihood estimation were used to calibrate to cumulative cases and cumulative deaths.

Setting

SW at a time considered early in the pandemic, where National Health Service authorities required evidence to guide localised planning and support decision-making.

Participants

Publicly available data on patients with COVID-19.

Primary and secondary outcome measures

The expected numbers of infected cases, deaths due to COVID-19 infection, patient occupancy of acute and IC beds and the reproduction ('R') number over time.

Results

SW model projections indicate that, as of 11 May 2020 (when 'lockdown' measures were eased), 5793 (95% credible interval (CrI) 2003 to 12 051) individuals were still infectious (0.10% of the total SW population, 95% CrI 0.04% to 0.22%), and a total of 189 048 (95% CrI 141 580 to 277 955) had been infected with the virus (either asymptomatically or symptomatically), but recovered, which is 3.4% (95% CrI 2.5% to 5.0%) of the SW population. The total number of patients in acute and IC beds in the SW on 11 May 2020 was predicted to be 701 (95% CrI 169 to 1543) and 110 (95% CrI 8 to 464), respectively. The R value in SW was predicted to be 2.6 (95% CrI 2.0 to 3.2) prior to any interventions, with social distancing reducing this to 2.3 (95% CrI 1.8 to 2.9) and lockdown/school closures further reducing the R value to 0.6 (95% CrI 0.5 to 0.7).

Conclusions

The developed model has proved a valuable asset for regional healthcare services. The model will be used further in the SW as the pandemic evolves, and-as open-source software-is portable to healthcare systems in other geographies.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/1/e041536.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-041536; html:https://europepmc.org/articles/PMC7797241; pdf:https://europepmc.org/articles/PMC7797241?pdf=render 38124256,https://doi.org/10.1093/ageing/afad219,New Horizons in artificial intelligence in the healthcare of older people.,"Shiwani T, Relton S, Evans R, Kale A, Heaven A, Clegg A, Ageing Data Research Collaborative (Geridata) AI group , Todd O.",,Age and ageing,2023,2023-12-01,Y,Artificial intelligence; Technology; Ageing; Health; Older People,,,"Artificial intelligence (AI) in healthcare describes algorithm-based computational techniques which manage and analyse large datasets to make inferences and predictions. There are many potential applications of AI in the care of older people, from clinical decision support systems that can support identification of delirium from clinical records to wearable devices that can predict the risk of a fall. We held four meetings of older people, clinicians and AI researchers. Three priority areas were identified for AI application in the care of older people. These included: monitoring and early diagnosis of disease, stratified care and care coordination between healthcare providers. However, the meetings also highlighted concerns that AI may exacerbate health inequity for older people through bias within AI models, lack of external validation amongst older people, infringements on privacy and autonomy, insufficient transparency of AI models and lack of safeguarding for errors. Creating effective interventions for older people requires a person-centred approach to account for the needs of older people, as well as sufficient clinical and technological governance to meet standards of generalisability, transparency and effectiveness. Education of clinicians and patients is also needed to ensure appropriate use of AI technologies, with investment in technological infrastructure required to ensure equity of access.",,doi:https://doi.org/10.1093/ageing/afad219; html:https://europepmc.org/articles/PMC10733173; pdf:https://europepmc.org/articles/PMC10733173?pdf=render -33414147,https://doi.org/10.1136/bmjopen-2020-041536,Estimating the COVID-19 epidemic trajectory and hospital capacity requirements in South West England: a mathematical modelling framework.,"Booton RD, MacGregor L, Vass L, Looker KJ, Hyams C, Bright PD, Harding I, Lazarus R, Hamilton F, Lawson D, Danon L, Pratt A, Wood R, Brooks-Pollock E, Turner KME.",,BMJ open,2021,2021-01-07,Y,Infection control; epidemiology; Public Health,,,"

Objectives

To develop a regional model of COVID-19 dynamics for use in estimating the number of infections, deaths and required acute and intensive care (IC) beds using the South West England (SW) as an example case.

Design

Open-source age-structured variant of a susceptible-exposed-infectious-recovered compartmental mathematical model. Latin hypercube sampling and maximum likelihood estimation were used to calibrate to cumulative cases and cumulative deaths.

Setting

SW at a time considered early in the pandemic, where National Health Service authorities required evidence to guide localised planning and support decision-making.

Participants

Publicly available data on patients with COVID-19.

Primary and secondary outcome measures

The expected numbers of infected cases, deaths due to COVID-19 infection, patient occupancy of acute and IC beds and the reproduction ('R') number over time.

Results

SW model projections indicate that, as of 11 May 2020 (when 'lockdown' measures were eased), 5793 (95% credible interval (CrI) 2003 to 12 051) individuals were still infectious (0.10% of the total SW population, 95% CrI 0.04% to 0.22%), and a total of 189 048 (95% CrI 141 580 to 277 955) had been infected with the virus (either asymptomatically or symptomatically), but recovered, which is 3.4% (95% CrI 2.5% to 5.0%) of the SW population. The total number of patients in acute and IC beds in the SW on 11 May 2020 was predicted to be 701 (95% CrI 169 to 1543) and 110 (95% CrI 8 to 464), respectively. The R value in SW was predicted to be 2.6 (95% CrI 2.0 to 3.2) prior to any interventions, with social distancing reducing this to 2.3 (95% CrI 1.8 to 2.9) and lockdown/school closures further reducing the R value to 0.6 (95% CrI 0.5 to 0.7).

Conclusions

The developed model has proved a valuable asset for regional healthcare services. The model will be used further in the SW as the pandemic evolves, and-as open-source software-is portable to healthcare systems in other geographies.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/1/e041536.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-041536; html:https://europepmc.org/articles/PMC7797241; pdf:https://europepmc.org/articles/PMC7797241?pdf=render 34286192,https://doi.org/10.7861/fhj.2021-0083,Making trials part of good clinical care: lessons from the RECOVERY trial.,"Pessoa-Amorim G, Campbell M, Fletcher L, Horby P, Landray M, Mafham M, Haynes R.",,Future healthcare journal,2021,2021-07-01,N,Recovery; RANDOMISED CONTROLLED TRIALS; evidence-based medicine; Quality-by-design; Covid-19,,,"When COVID-19 hit the UK in early 2020, there were no known treatments for a condition that results in the death of around one in four patients hospitalised with this disease. Around the world, possible treatments were administered to huge numbers of patients, without any reliable assessments of safety and efficacy. The rapid generation of high-quality evidence was vital. RECOVERY is a streamlined, pragmatic, randomised controlled trial, which was set up in response to this challenge. As of April 2021, over 39,000 patients have been enrolled from 178 hospital sites in the UK. Within 100 days of its initiation, RECOVERY demonstrated that dexamethasone improves survival for patients with severe disease; a result that was rapidly implemented in the UK and internationally saving hundreds of thousands of lives. Importantly, it also showed that other widely used treatments (such as hydroxychloroquine and azithromycin) have no meaningful benefit for hospitalised patients. This was only possible through randomisation of large numbers of patients and the adoption of streamlined and pragmatic procedures focused on quality, together with widespread collaboration focused on a single goal. RECOVERY illustrates how clinical trials and healthcare can be integrated, even in a pandemic. This approach provides new opportunities to generate the evidence needed for high-quality healthcare not only for a pandemic but for the many other conditions that place a burden on patients and the healthcare system.",,pdf:https://www.rcpjournals.org/content/futurehosp/8/2/e243.full.pdf; doi:https://doi.org/10.7861/fhj.2021-0083; html:https://europepmc.org/articles/PMC8285150; pdf:https://europepmc.org/articles/PMC8285150?pdf=render; doi:https://doi.org/10.7861/fhj.2021-0083 32060159,https://doi.org/10.1136/bmjopen-2019-034396,Data-driven discovery of changes in clinical code usage over time: a case-study on changes in cardiovascular disease recording in two English electronic health records databases (2001-2015).,"Rockenschaub P, Nguyen V, Aldridge RW, Acosta D, García-Gómez JM, Sáez C.",,BMJ open,2020,2020-02-13,Y,Cardiovascular disease; Data Quality; Electronic Health Records; Clinical Coding; Statistics & Research Methods,The Human Phenome,,"

Objectives

To demonstrate how data-driven variability methods can be used to identify changes in disease recording in two English electronic health records databases between 2001 and 2015.

Design

Repeated cross-sectional analysis that applied data-driven temporal variability methods to assess month-by-month changes in routinely collected medical data. A measure of difference between months was calculated based on joint distributions of age, gender, socioeconomic status and recorded cardiovascular diseases. Distances between months were used to identify temporal trends in data recording.

Setting

400 English primary care practices from the Clinical Practice Research Datalink (CPRD GOLD) and 451 hospital providers from the Hospital Episode Statistics (HES).

Main outcomes

The proportion of patients (CPRD GOLD) and hospital admissions (HES) with a recorded cardiovascular disease (CPRD GOLD: coronary heart disease, heart failure, peripheral arterial disease, stroke; HES: International Classification of Disease codes I20-I69/G45).

Results

Both databases showed gradual changes in cardiovascular disease recording between 2001 and 2008. The recorded prevalence of included cardiovascular diseases in CPRD GOLD increased by 47%-62%, which partially reversed after 2008. For hospital records in HES, there was a relative decrease in angina pectoris (-34.4%) and unspecified stroke (-42.3%) over the same time period, with a concomitant increase in chronic coronary heart disease (+14.3%). Multiple abrupt changes in the use of myocardial infarction codes in hospital were found in March/April 2010, 2012 and 2014, possibly linked to updates of clinical coding guidelines.

Conclusions

Identified temporal variability could be related to potentially non-medical causes such as updated coding guidelines. These artificial changes may introduce temporal correlation among diagnoses inferred from routine data, violating the assumptions of frequently used statistical methods. Temporal variability measures provide an objective and robust technique to identify, and subsequently account for, those changes in electronic health records studies without any prior knowledge of the data collection process.",,pdf:https://bmjopen.bmj.com/content/bmjopen/10/2/e034396.full.pdf; doi:https://doi.org/10.1136/bmjopen-2019-034396; html:https://europepmc.org/articles/PMC7045100; pdf:https://europepmc.org/articles/PMC7045100?pdf=render 33612430,https://doi.org/10.1016/s2589-7500(21)00017-0,Indirect acute effects of the COVID-19 pandemic on physical and mental health in the UK: a population-based study.,"Mansfield KE, Mathur R, Tazare J, Henderson AD, Mulick AR, Carreira H, Matthews AA, Bidulka P, Gayle A, Forbes H, Cook S, Wong AYS, Strongman H, Wing K, Warren-Gash C, Cadogan SL, Smeeth L, Hayes JF, Quint JK, McKee M, Langan SM.",,The Lancet. Digital health,2021,2021-02-18,Y,,,,"

Background

There are concerns that the response to the COVID-19 pandemic in the UK might have worsened physical and mental health, and reduced use of health services. However, the scale of the problem is unquantified, impeding development of effective mitigations. We aimed to ascertain what has happened to general practice contacts for acute physical and mental health outcomes during the pandemic.

Methods

Using de-identified electronic health records from the Clinical Research Practice Datalink (CPRD) Aurum (covering 13% of the UK population), between 2017 and 2020, we calculated weekly primary care contacts for selected acute physical and mental health conditions: anxiety, depression, self-harm (fatal and non-fatal), severe mental illness, eating disorder, obsessive-compulsive disorder, acute alcohol-related events, asthma exacerbation, chronic obstructive pulmonary disease exacerbation, acute cardiovascular events (cerebrovascular accident, heart failure, myocardial infarction, transient ischaemic attacks, unstable angina, and venous thromboembolism), and diabetic emergency. Primary care contacts included remote and face-to-face consultations, diagnoses from hospital discharge letters, and secondary care referrals, and conditions were identified through primary care records for diagnoses, symptoms, and prescribing. Our overall study population included individuals aged 11 years or older who had at least 1 year of registration with practices contributing to CPRD Aurum in the specified period, but denominator populations varied depending on the condition being analysed. We used an interrupted time-series analysis to formally quantify changes in conditions after the introduction of population-wide restrictions (defined as March 29, 2020) compared with the period before their introduction (defined as Jan 1, 2017 to March 7, 2020), with data excluded for an adjustment-to-restrictions period (March 8-28).

Findings

The overall population included 9 863 903 individuals on Jan 1, 2017, and increased to 10 226 939 by Jan 1, 2020. Primary care contacts for almost all conditions dropped considerably after the introduction of population-wide restrictions. The largest reductions were observed for contacts for diabetic emergencies (odds ratio 0·35 [95% CI 0·25-0·50]), depression (0·53 [0·52-0·53]), and self-harm (0·56 [0·54-0·58]). In the interrupted time-series analysis, with the exception of acute alcohol-related events (0·98 [0·89-1·10]), there was evidence of a reduction in contacts for all conditions (anxiety 0·67 [0·66-0·67], eating disorders 0·62 [0·59-0·66], obsessive-compulsive disorder [0·69 [0·64-0·74]], self-harm 0·56 [0·54-0·58], severe mental illness 0·80 [0·78-0·83], stroke 0·59 [0·56-0·62], transient ischaemic attack 0·63 [0·58-0·67], heart failure 0·62 [0·60-0·64], myocardial infarction 0·72 [0·68-0·77], unstable angina 0·72 [0·60-0·87], venous thromboembolism 0·94 [0·90-0·99], and asthma exacerbation 0·88 [0·86-0·90]). By July, 2020, except for unstable angina and acute alcohol-related events, contacts for all conditions had not recovered to pre-lockdown levels.

Interpretation

There were substantial reductions in primary care contacts for acute physical and mental conditions following the introduction of restrictions, with limited recovery by July, 2020. Further research is needed to ascertain whether these reductions reflect changes in disease frequency or missed opportunities for care. Maintaining health-care access should be a key priority in future public health planning, including further restrictions. The conditions we studied are sufficiently severe that any unmet need will have substantial ramifications for the people with the conditions as well as health-care provision.

Funding

Wellcome Trust Senior Fellowship, Health Data Research UK.",,pdf:http://www.thelancet.com/article/S2589750021000170/pdf; doi:https://doi.org/10.1016/S2589-7500(21)00017-0; html:https://europepmc.org/articles/PMC7985613; pdf:https://europepmc.org/articles/PMC7985613?pdf=render @@ -1078,18 +1078,18 @@ PMC10686417,https://doi.org/,The impact of restricted provision of publicly fund 34169636,https://doi.org/10.1002/pst.2148,Assessing safety at the end of clinical trials using system organ classes: A case and comparative study.,"Carragher R, Robertson C.",,Pharmaceutical statistics,2021,2021-06-24,N,Safety; False Discovery Rate; Adverse Events; System Organ Class; Bayesian Hierarchy,,,"Recent approaches to the statistical analysis of adverse event (AE) data in clinical trials have proposed the use of groupings of related AEs, such as by system organ class (SOC). These methods have opened up the possibility of scanning large numbers of AEs while controlling for multiple comparisons, making the comparative performance of the different methods in terms of AE detection and error rates of interest to investigators. We apply two Bayesian models and two procedures for controlling the false discovery rate (FDR), which use groupings of AEs, to real clinical trial safety data. We find that while the Bayesian models are appropriate for the full data set, the error controlling methods only give similar results to the Bayesian methods when low incidence AEs are removed. A simulation study is used to compare the relative performances of the methods. We investigate the differences between the methods over full trial data sets, and over data sets with low incidence AEs and SOCs removed. We find that while the removal of low incidence AEs increases the power of the error controlling procedures, the estimated power of the Bayesian methods remains relatively constant over all data sizes. Automatic removal of low-incidence AEs however does have an effect on the error rates of all the methods, and a clinically guided approach to their removal is needed. Overall we found that the Bayesian approaches are particularly useful for scanning the large amounts of AE data gathered.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/pst.2148; doi:https://doi.org/10.1002/pst.2148 32908801,https://doi.org/10.1167/tvst.9.9.38,Merging Information From Infrared and Autofluorescence Fundus Images for Monitoring of Chorioretinal Atrophic Lesions.,"Ometto G, Montesano G, Sadeghi Afgeh S, Lazaridis G, Liu X, Keane PA, Crabb DP, Denniston AK.",,Translational vision science & technology,2020,2020-08-25,Y,Autofluorescence; Segmentation; infrared; Uveitis; Multimodal,,,"

Purpose

To develop a method for automated detection and progression analysis of chorioretinal atrophic lesions using the combined information of standard infrared (IR) and autofluorescence (AF) fundus images.

Methods

Eighteen eyes (from 16 subjects) with punctate inner choroidopathy were analyzed. Macular IR and blue AF images were acquired in all eyes with a Spectralis HRA+OCT device (Heidelberg Engineering, Heidelberg, Germany). Two clinical experts manually segmented chorioretinal lesions on the AF image. AF images were aligned to the corresponding IR. Two random forest models were trained to classify pixels of lesions, one based on the AF image only, the other based on the aligned IR-AF. The models were validated using a leave-one-out cross-validation and were tested against the manual segmentation to compare their performance. A time series from one eye was identified and used to evaluate the method based on the IR-AF in a case study.

Results

The method based on the AF images correctly classified 95% of the pixels (i.e., in vs. out of the lesion) with a Dice's coefficient of 0.80. The method based on the combined IR-AF correctly classified 96% of the pixels with a Dice's coefficient of 0.84.

Conclusions

The automated segmentation of chorioretinal lesions using IR and AF shows closer alignment to manual segmentation than the same method based on AF only. Merging information from multimodal images improves the automatic and objective segmentation of chorioretinal lesions even when based on a small dataset.

Translational relevance

Merged information from multimodal images improves segmentation performance of chorioretinal lesions.",,doi:https://doi.org/10.1167/tvst.9.9.38; doi:https://doi.org/10.1167/tvst.9.9.38; html:https://europepmc.org/articles/PMC7453042; pdf:https://europepmc.org/articles/PMC7453042?pdf=render 33704068,https://doi.org/10.7554/elife.64827,Longitudinal proteomic profiling of dialysis patients with COVID-19 reveals markers of severity and predictors of death.,"Gisby J, Clarke CL, Medjeral-Thomas N, Malik TH, Papadaki A, Mortimer PM, Buang NB, Lewis S, Pereira M, Toulza F, Fagnano E, Mawhin MA, Dutton EE, Tapeng L, Richard AC, Kirk PD, Behmoaras J, Sandhu E, McAdoo SP, Prendecki MF, Pickering MC, Botto M, Willicombe M, Thomas DC, Peters JE.",,eLife,2021,2021-03-11,Y,Human; Cytokines; Proteomics; Inflammation; Medicine; Biomarkers; immunology; Longitudinal; End-stage Kidney Disease; Covid-19,,,"End-stage kidney disease (ESKD) patients are at high risk of severe COVID-19. We measured 436 circulating proteins in serial blood samples from hospitalised and non-hospitalised ESKD patients with COVID-19 (n = 256 samples from 55 patients). Comparison to 51 non-infected patients revealed 221 differentially expressed proteins, with consistent results in a separate subcohort of 46 COVID-19 patients. Two hundred and three proteins were associated with clinical severity, including IL6, markers of monocyte recruitment (e.g. CCL2, CCL7), neutrophil activation (e.g. proteinase-3), and epithelial injury (e.g. KRT19). Machine-learning identified predictors of severity including IL18BP, CTSD, GDF15, and KRT19. Survival analysis with joint models revealed 69 predictors of death. Longitudinal modelling with linear mixed models uncovered 32 proteins displaying different temporal profiles in severe versus non-severe disease, including integrins and adhesion molecules. These data implicate epithelial damage, innate immune activation, and leucocyte-endothelial interactions in the pathology of severe COVID-19 and provide a resource for identifying drug targets.",,doi:https://doi.org/10.7554/elife.64827; doi:https://doi.org/10.7554/eLife.64827; html:https://europepmc.org/articles/PMC8064756; pdf:https://europepmc.org/articles/PMC8064756?pdf=render -37140153,https://doi.org/10.1093/ehjci/jead093,Determinants of post-operative left ventricular dysfunction in degenerative mitral regurgitation.,"Althunayyan AM, Alborikan S, Badiani S, Wong K, Uppal R, Patel N, Petersen SE, Lloyd G, Bhattacharyya S.",,European heart journal. Cardiovascular Imaging,2023,2023-08-01,N,Surgery; Mitral regurgitation; Mitral Valve Prolapse; Global Longitudinal Strain; Lv Volumes,,,"

Aims

Chronic degenerative mitral regurgitation leads to volume overload causing left ventricular (LV) enlargement and eventually LV impairment. Current guidelines determining thresholds for intervention are based on LV diameters and ejection fraction (LVEF). There are sparse data examining the value of LV volumes and newer markers of LV performance on outcomes of surgery in mitral valve prolapse. The aim of this study is to identify the best marker of LV impairment after mitral valve surgery.

Methods and results

Prospective, observational study of patients with mitral valve prolapse undergoing mitral valve surgery. Pre-operative LV diameters, volumes, LVEF, global longitudinal strain (GLS), and myocardial work measured. Post-operative LV impairment defined as LVEF < 50% at 1 year post-surgery. Eighty-seven patients included. Thirteen percent developed post-operative LV impairment. Patients with post-operative LV dysfunction showed significantly larger indexed LV end-systolic diameters, indexed LV end-systolic volumes (LVESVi), lower LVEF, and more abnormal GLS than patients without post-operative LV dysfunction. In multivariate analysis, LVESVi [odds ratio 1.11 (95% CI 1.01-1.23), P = 0.039] and GLS [odds ratio 1.46 (95% CI 1.00-2.14), P = 0.054] were the only independent predictors of post-operative LV dysfunction. The optimal cut-off of 36.3 mL/m2 for LVESVi had a sensitivity of 82% and specificity of 78% for detection of post-operative LV impairment.

Conclusion

Post-operative LV impairment is common. Indexed LV volumes (36.3 mL/m2) provided the best marker of post-operative LV impairment.",,pdf:https://academic.oup.com/ehjcimaging/advance-article-pdf/doi/10.1093/ehjci/jead093/50200028/jead093.pdf; doi:https://doi.org/10.1093/ehjci/jead093 35667411,https://doi.org/10.1016/j.jamda.2022.05.003,Stroke in Older Adults Living in Care Homes: Results From a National Data Linkage Study in Wales.,"Harrison SL, Lip GYH, Akbari A, Torabi F, Ritchie LA, Akpan A, Halcox J, Rodgers S, Hollinghurst J, Harris D, Lane DA.",,Journal of the American Medical Directors Association,2022,2022-06-03,N,Anticoagulants; Cerebrovascular disease; Nursing Homes; Antiplatelets,,,"

Objectives

To determine the proportion of older people moving to care homes with a recent stroke, incidence of stroke after moving to a care home, mortality following stroke, and secondary stroke prevention management in older care home residents.

Design

Retrospective cohort study using population-scale individual-level linked data sources between 2003 and 2018 in the Secure Anonymized Information Linkage (SAIL) Databank.

Setting and participants

People aged ≥65 years residing in long-term care homes in Wales.

Methods

Competing risk models and logistic regression models were used to examine the association between prior stroke, incident stroke, and mortality following stroke.

Results

Of 86,602 individuals, 7.0% (n = 6055) experienced a stroke in the 12 months prior to care home entry. The incidence of stroke within 12 months after entry to a care home was 26.2 per 1000 person-years [95% confidence interval (CI) 25.0, 27.5]. Previous stroke was associated with higher risk of incident stroke after moving to a care home (subdistribution hazard ratio 1.83, 95% CI 1.57, 2.13) and 30-day mortality following stroke (odds ratio 2.18, 95% CI 1.59, 2.98). Severe frailty was not significantly associated with risk of stroke or 30-day mortality following stroke. Secondary stroke prevention included statins (51.0%), antiplatelets (61.2%), anticoagulants (52.4% of those with atrial fibrillation), and antihypertensives (92.1% of those with hypertension).

Conclusions and implications

At the time of care home entry, individuals with history of stroke in the previous 12 months are at a higher risk of incident stroke and mortality following an incident stroke. These individuals are frequently not prescribed medications for secondary stroke prevention. Further evidence is needed to determine the optimal care pathways for older people living in long-term care homes with history of stroke.",,pdf:https://cronfa.swan.ac.uk/Record/cronfa60151/Download/60151__25104__e0e71818d5bd49acba048a3d98682425.pdf; doi:https://doi.org/10.1016/j.jamda.2022.05.003 +37140153,https://doi.org/10.1093/ehjci/jead093,Determinants of post-operative left ventricular dysfunction in degenerative mitral regurgitation.,"Althunayyan AM, Alborikan S, Badiani S, Wong K, Uppal R, Patel N, Petersen SE, Lloyd G, Bhattacharyya S.",,European heart journal. Cardiovascular Imaging,2023,2023-08-01,N,Surgery; Mitral regurgitation; Mitral Valve Prolapse; Global Longitudinal Strain; Lv Volumes,,,"

Aims

Chronic degenerative mitral regurgitation leads to volume overload causing left ventricular (LV) enlargement and eventually LV impairment. Current guidelines determining thresholds for intervention are based on LV diameters and ejection fraction (LVEF). There are sparse data examining the value of LV volumes and newer markers of LV performance on outcomes of surgery in mitral valve prolapse. The aim of this study is to identify the best marker of LV impairment after mitral valve surgery.

Methods and results

Prospective, observational study of patients with mitral valve prolapse undergoing mitral valve surgery. Pre-operative LV diameters, volumes, LVEF, global longitudinal strain (GLS), and myocardial work measured. Post-operative LV impairment defined as LVEF < 50% at 1 year post-surgery. Eighty-seven patients included. Thirteen percent developed post-operative LV impairment. Patients with post-operative LV dysfunction showed significantly larger indexed LV end-systolic diameters, indexed LV end-systolic volumes (LVESVi), lower LVEF, and more abnormal GLS than patients without post-operative LV dysfunction. In multivariate analysis, LVESVi [odds ratio 1.11 (95% CI 1.01-1.23), P = 0.039] and GLS [odds ratio 1.46 (95% CI 1.00-2.14), P = 0.054] were the only independent predictors of post-operative LV dysfunction. The optimal cut-off of 36.3 mL/m2 for LVESVi had a sensitivity of 82% and specificity of 78% for detection of post-operative LV impairment.

Conclusion

Post-operative LV impairment is common. Indexed LV volumes (36.3 mL/m2) provided the best marker of post-operative LV impairment.",,pdf:https://academic.oup.com/ehjcimaging/advance-article-pdf/doi/10.1093/ehjci/jead093/50200028/jead093.pdf; doi:https://doi.org/10.1093/ehjci/jead093 34673925,https://doi.org/10.1093/ageing/afab201,"Do home adaptation interventions help to reduce emergency fall admissions? A national longitudinal data-linkage study of 657,536 older adults living in Wales (UK) between 2010 and 2017.","Hollinghurst J, Daniels H, Fry R, Akbari A, Rodgers S, Watkins A, Hillcoat-Nallétamby S, Williams N, Nikolova S, Meads D, Clegg A.",,Age and ageing,2022,2022-01-01,Y,Frailty; Falls; Older People; Falls Prevention,,,"

Background

falls are common in older people, but evidence for the effectiveness of preventative home adaptations is limited.

Aim

determine whether a national home adaptation service, Care&Repair Cymru (C&RC), identified individuals at risk of falls occurring at home and reduced the likelihood of falls.

Study design

retrospective longitudinal controlled non-randomised intervention cohort study.

Setting

our cohort consisted of 657,536 individuals aged 60+ living in Wales (UK) between 1 January 2010 and 31 December 2017. About 123,729 individuals received a home adaptation service.

Methods

we created a dataset with up to 41 quarterly observations per person. For each quarter, we observed if a fall occurred at home that resulted in either an emergency department or an emergency hospital admission. We analysed the data using multilevel logistic regression.

Results

compared to the control group, C&RC clients had higher odds of falling, with an odds ratio (OR [95% confidence interval]) of 1.93 [1.87, 2.00]. Falls odds was higher for females (1.44 [1.42, 1.46]), older age (1.07 [1.07, 1.07]), increased frailty (mild 1.57 [1.55, 1.60], moderate 2.31 [2.26, 2.35], severe 3.05 [2.96, 3.13]), and deprivation (most deprived compared to least: 1.16 [1.13, 1.19]). Client fall odds decreased post-intervention; OR 0.97 [0.96, 0.97] per quarter. Regional variation existed for falls (5.8%), with most variation at the individual level (31.3%).

Conclusions

C&RC identified people more likely to have an emergency fall admission occurring at home, and their service reduced the odds of falling post-intervention. Service provisioning should meet the needs of an individual and need varies by personal and regional circumstance.",,pdf:https://academic.oup.com/ageing/article-pdf/51/1/afab201/42083711/afab201.pdf; doi:https://doi.org/10.1093/ageing/afab201; html:https://europepmc.org/articles/PMC8753038; pdf:https://europepmc.org/articles/PMC8753038?pdf=render -38450564,https://doi.org/10.1089/neu.2023.0462,The Australian Traumatic Brain Injury Initiative: Systematic Review and Consensus Process to Determine the Predictive Value of Pre-existing Health Conditions for People with Moderate-Severe Traumatic Brain Injury.,"Antonic-Baker A, Auvrez C, Tao G, Bagg MK, Gadowski A, McKimmie A, Hicks AJ, Hill R, Romero L, Ponsford JL, Lannin NA, Gabbe BJ, Cameron PA, Cooper DJ, Rushworth N, Fitzgerald M, O'Brien TJ.",,Journal of neurotrauma,2024,2024-04-15,N,"Health care; Mental health; Comorbidity; Common Data Elements; Multiple Chronic Conditions; Brain Injuries, Traumatic; Outcome Assessment, Systematic Review [Publication Type]",,,"The first aim of the Australian Traumatic Brain Injury Initiative (AUS-TBI) encompasses development of a set of measures that comprehensively predict outcomes for people with moderate-severe TBI across Australia. This process engaged diverse stakeholders and information sources across six areas: social, health, and clinical factors; biological markers; treatments; and longer-term outcomes. Here, we report the systematic review of pre-existing health conditions as predictors of outcome for people with moderate-severe TBI. Standardized searches were implemented across databases until March 31, 2022. English-language reports of studies evaluating association between pre-existing health conditions and clinical outcome in at least 10 patients with moderate-severe TBI were included. A predefined algorithm was used to assign a judgement of predictive value to each observed association. The list of identified pre-existing health conditions was then discussed with key stakeholders during a consensus meeting to determine the feasibility of incorporating them into standard care. The searches retrieved 22,217 records, of which 47 articles were included. The process led to identification of 88 unique health predictors (homologized to 21 predictor categories) of 55 outcomes (homologized to 19 outcome categories). Only pre-existing health conditions with high and moderate predictive values were discussed during the consensus meeting. Following the consensus meeting, 5 out of 11 were included (migraine, mental health conditions, ≥4 pre-existing health conditions, osteoporosis, and body mass index [BMI]) as common data elements in the AUS-TBI data dictionary. Upon further discussion, 3 additional pre-existing health conditions were included. These are pre-existing heart disease, frailty score, and previous incidence of TBI.",,doi:https://doi.org/10.1089/neu.2023.0462 34026049,https://doi.org/10.12688/f1000research.25484.2,PUblications Metadata Augmentation (PUMA) pipeline.,"Butters OW, Wilson RC, Garner H, Burton TWY.",,F1000Research,2020,2020-09-04,Y,bibliometrics; Bibliography; Alspac; Longitudinal Birth Cohort,,,"Cohort studies collect, generate and distribute data over long periods of time - often over the lifecourse of their participants. It is common for these studies to host a list of publications (which can number many thousands) on their website to demonstrate the impact of the study and facilitate the search of existing research to which the study data has contributed. The ability to search and explore these publication lists varies greatly between studies. We believe a lack of rich search and exploration functionality of study publications is a barrier to entry for new or prospective users of a study's data, since it may be difficult to find and evaluate previous work in a given area. These lists of publications are also typically manually curated, resulting in a lack of rich metadata to analyse, making bibliometric analysis difficult. We present here a software pipeline that aggregates metadata from a variety of third-party providers to power a web based search and exploration tool for lists of publications. Alongside core publication metadata (i.e. author lists, keywords etc.), we include geocoding of first authors and citation counts in our pipeline. This allows a characterisation of a study as a whole based on common locations of authors, frequency of keywords, citation profile etc. This enriched publications metadata can be useful for generating study impact metrics and web-based graphics for public dissemination. In addition, the pipeline produces a research data set for bibliometric analysis or social studies of science. We use a previously published list of publications from a cohort study as an exemplar input data set to show the output and utility of the pipeline here.",,pdf:https://f1000research.com/articles/9-1095/v2/pdf; doi:https://doi.org/10.12688/f1000research.25484.2; html:https://europepmc.org/articles/PMC8108552; pdf:https://europepmc.org/articles/PMC8108552?pdf=render +38450564,https://doi.org/10.1089/neu.2023.0462,The Australian Traumatic Brain Injury Initiative: Systematic Review and Consensus Process to Determine the Predictive Value of Pre-existing Health Conditions for People with Moderate-Severe Traumatic Brain Injury.,"Antonic-Baker A, Auvrez C, Tao G, Bagg MK, Gadowski A, McKimmie A, Hicks AJ, Hill R, Romero L, Ponsford JL, Lannin NA, Gabbe BJ, Cameron PA, Cooper DJ, Rushworth N, Fitzgerald M, O'Brien TJ.",,Journal of neurotrauma,2024,2024-04-15,N,"Health care; Mental health; Comorbidity; Common Data Elements; Multiple Chronic Conditions; Brain Injuries, Traumatic; Outcome Assessment, Systematic Review [Publication Type]",,,"The first aim of the Australian Traumatic Brain Injury Initiative (AUS-TBI) encompasses development of a set of measures that comprehensively predict outcomes for people with moderate-severe TBI across Australia. This process engaged diverse stakeholders and information sources across six areas: social, health, and clinical factors; biological markers; treatments; and longer-term outcomes. Here, we report the systematic review of pre-existing health conditions as predictors of outcome for people with moderate-severe TBI. Standardized searches were implemented across databases until March 31, 2022. English-language reports of studies evaluating association between pre-existing health conditions and clinical outcome in at least 10 patients with moderate-severe TBI were included. A predefined algorithm was used to assign a judgement of predictive value to each observed association. The list of identified pre-existing health conditions was then discussed with key stakeholders during a consensus meeting to determine the feasibility of incorporating them into standard care. The searches retrieved 22,217 records, of which 47 articles were included. The process led to identification of 88 unique health predictors (homologized to 21 predictor categories) of 55 outcomes (homologized to 19 outcome categories). Only pre-existing health conditions with high and moderate predictive values were discussed during the consensus meeting. Following the consensus meeting, 5 out of 11 were included (migraine, mental health conditions, ≥4 pre-existing health conditions, osteoporosis, and body mass index [BMI]) as common data elements in the AUS-TBI data dictionary. Upon further discussion, 3 additional pre-existing health conditions were included. These are pre-existing heart disease, frailty score, and previous incidence of TBI.",,doi:https://doi.org/10.1089/neu.2023.0462 33653161,https://doi.org/10.1177/1740774520976617,Making a distinction between data cleaning and central monitoring in clinical trials.,"Love SB, Yorke-Edwards V, Diaz-Montana C, Murray ML, Masters L, Gabriel M, Joffe N, Sydes MR.",,"Clinical trials (London, England)",2021,2021-03-02,Y,,,,,,pdf:https://journals.sagepub.com/doi/pdf/10.1177/1740774520976617; doi:https://doi.org/10.1177/1740774520976617; html:https://europepmc.org/articles/PMC8174009; pdf:https://europepmc.org/articles/PMC8174009?pdf=render -35634533,https://doi.org/10.12688/wellcomeopenres.17360.1,A comprehensive high cost drugs dataset from the NHS in England - An OpenSAFELY-TPP Short Data Report.,"Rowan A, Bates C, Hulme W, Evans D, Davy S, A Kennedy N, Galloway J, E Mansfield K, Bechman K, Matthewman J, Yates M, Brown J, Schultze A, Norton S, J Walker A, E Morton C, Bhaskaran K, T Rentsch C, Williamson E, Croker R, Bacon S, Hickman G, Ward T, Green A, Fisher L, J Curtis H, Tazare J, M Eggo R, Inglesby P, Cockburn J, I McDonald H, Mathur R, Ys Wong A, Forbes H, Parry J, Hester F, Harper S, J Douglas I, Smeeth L, A Tomlinson L, W Lees C, Evans S, Smith C, M Langan S, Mehkar A, MacKenna B, Goldacre B.",,Wellcome open research,2021,2021-12-22,Y,Medications; Biosimilars; Healthcare Administration; Opensafely,,,"Background: At the outset of the COVID-19 pandemic, there was no routine comprehensive hospital medicines data from the UK available to researchers. These records can be important for many analyses including the effect of certain medicines on the risk of severe COVID-19 outcomes. With the approval of NHS England, we set out to obtain data on one specific group of medicines, ""high-cost drugs"" (HCD) which are typically specialist medicines for the management of long-term conditions, prescribed by hospitals to patients. Additionally, we aimed to make these data available to all approved researchers in OpenSAFELY-TPP. This report is intended to support all studies carried out in OpenSAFELY-TPP, and those elsewhere, working with this dataset or similar data. Methods: Working with the North East Commissioning Support Unit and NHS Digital, we arranged for collation of a single national HCD dataset to help inform responses to the COVID-19 pandemic. The dataset was developed from payment submissions from hospitals to commissioners. Results: In the financial year (FY) 2018/19 there were 2.8 million submissions for 1.1 million unique patient IDs recorded in the HCD. The average number of submissions per patient over the year was 2.6. In FY 2019/20 there were 4.0 million submissions for 1.3 million unique patient IDs. The average number of submissions per patient over the year was 3.1. Of the 21 variables in the dataset, three are now available for analysis in OpenSafely-TPP: Financial year and month of drug being dispensed; drug name; and a description of the drug dispensed. Conclusions: We have described the process for sourcing a national HCD dataset, making these data available for COVID-19-related analysis through OpenSAFELY-TPP and provided information on the variables included in the dataset, data coverage and an initial descriptive analysis.",,doi:https://doi.org/10.12688/wellcomeopenres.17360.1; html:https://europepmc.org/articles/PMC9120928; pdf:https://europepmc.org/articles/PMC9120928?pdf=render 32665523,https://doi.org/10.1097/hjh.0000000000002579,Association of SBP and BMI with cognitive and structural brain phenotypes in UK Biobank.,"Ferguson AC, Tank R, Lyall LM, Ward J, Welsh P, Celis-Morales C, McQueenie R, Strawbridge RJ, Mackay DF, Pell JP, Smith DJ, Sattar N, Cavanagh J, Lyall DM.",,Journal of hypertension,2020,2020-12-01,N,,,,"

Objective

To test for associations between SBP and BMI, with domain-specific cognitive abilities and examine which brain structural phenotypes mediate those associations.

Methods

Using cross-sectional UK Biobank data (final N = 28 412), we examined SBP/BMI vs. cognitive test scores of pairs-matching, matrix completion, trail making test A/B, digit symbol substitution, verbal-numerical reasoning, tower rearranging and simple reaction time. We adjusted for potential confounders of age, sex, deprivation, medication, apolipoprotein e4 genotype, smoking, population stratification and genotypic array. We tested for mediation via multiple structural brain imaging phenotypes and corrected for multiple testing with false discovery rate.

Results

We found positive associations for higher BMI with worse reaction time, reasoning, tower rearranging and matrix completion tasks by 0.024-0.067 SDs per BMI SD (all P < 0.001). Higher SBP was associated with worse reasoning (0.034 SDs) and matrix completion scores (-0.024 SDs; both P < 0.001). Both BMI and SBP were associated with multiple brain structural metrics including total grey/white matter volumes, frontal lobe volumes, white matter tract integrity and white matter hyperintensity volumes: specific metrics mediated around one-third of the associations with cognition.

Conclusion

Our findings add to the body of evidence that addressing cardiovascular risk factors may also preserve cognitive function, via specific aspects of brain structure.",,html:https://journals.lww.com/jhypertension/Fulltext/2020/12000/Association_of_SBP_and_BMI_with_cognitive_and.22.aspx; doi:https://doi.org/10.1097/HJH.0000000000002579 +35634533,https://doi.org/10.12688/wellcomeopenres.17360.1,A comprehensive high cost drugs dataset from the NHS in England - An OpenSAFELY-TPP Short Data Report.,"Rowan A, Bates C, Hulme W, Evans D, Davy S, A Kennedy N, Galloway J, E Mansfield K, Bechman K, Matthewman J, Yates M, Brown J, Schultze A, Norton S, J Walker A, E Morton C, Bhaskaran K, T Rentsch C, Williamson E, Croker R, Bacon S, Hickman G, Ward T, Green A, Fisher L, J Curtis H, Tazare J, M Eggo R, Inglesby P, Cockburn J, I McDonald H, Mathur R, Ys Wong A, Forbes H, Parry J, Hester F, Harper S, J Douglas I, Smeeth L, A Tomlinson L, W Lees C, Evans S, Smith C, M Langan S, Mehkar A, MacKenna B, Goldacre B.",,Wellcome open research,2021,2021-12-22,Y,Medications; Biosimilars; Healthcare Administration; Opensafely,,,"Background: At the outset of the COVID-19 pandemic, there was no routine comprehensive hospital medicines data from the UK available to researchers. These records can be important for many analyses including the effect of certain medicines on the risk of severe COVID-19 outcomes. With the approval of NHS England, we set out to obtain data on one specific group of medicines, ""high-cost drugs"" (HCD) which are typically specialist medicines for the management of long-term conditions, prescribed by hospitals to patients. Additionally, we aimed to make these data available to all approved researchers in OpenSAFELY-TPP. This report is intended to support all studies carried out in OpenSAFELY-TPP, and those elsewhere, working with this dataset or similar data. Methods: Working with the North East Commissioning Support Unit and NHS Digital, we arranged for collation of a single national HCD dataset to help inform responses to the COVID-19 pandemic. The dataset was developed from payment submissions from hospitals to commissioners. Results: In the financial year (FY) 2018/19 there were 2.8 million submissions for 1.1 million unique patient IDs recorded in the HCD. The average number of submissions per patient over the year was 2.6. In FY 2019/20 there were 4.0 million submissions for 1.3 million unique patient IDs. The average number of submissions per patient over the year was 3.1. Of the 21 variables in the dataset, three are now available for analysis in OpenSafely-TPP: Financial year and month of drug being dispensed; drug name; and a description of the drug dispensed. Conclusions: We have described the process for sourcing a national HCD dataset, making these data available for COVID-19-related analysis through OpenSAFELY-TPP and provided information on the variables included in the dataset, data coverage and an initial descriptive analysis.",,doi:https://doi.org/10.12688/wellcomeopenres.17360.1; html:https://europepmc.org/articles/PMC9120928; pdf:https://europepmc.org/articles/PMC9120928?pdf=render 33692093,https://doi.org/10.1136/heartjnl-2020-318557,Improving the diagnosis of heart failure in patients with atrial fibrillation.,"Bunting KV, Gill SK, Sitch A, Mehta S, O'Connor K, Lip GY, Kirchhof P, Strauss VY, Rahimi K, Camm AJ, Stanbury M, Griffith M, Townend JN, Gkoutos GV, Karwath A, Steeds RP, Kotecha D, RAte control Therapy Evaluation in permanent Atrial Fibrillation (RATE-AF) trial group.",,Heart (British Cardiac Society),2021,2021-03-10,Y,Atrial fibrillation; Echocardiography; Heart Failure; Systolic; Diastolic,,,"

Objective

To improve the echocardiographic assessment of heart failure in patients with atrial fibrillation (AF) by comparing conventional averaging of consecutive beats with an index-beat approach, whereby measurements are taken after two cycles with similar R-R interval.

Methods

Transthoracic echocardiography was performed using a standardised and blinded protocol in patients enrolled in the RATE-AF (RAte control Therapy Evaluation in permanent Atrial Fibrillation) randomised trial. We compared reproducibility of the index-beat and conventional consecutive-beat methods to calculate left ventricular ejection fraction (LVEF), global longitudinal strain (GLS) and E/e' (mitral E wave max/average diastolic tissue Doppler velocity), and assessed intraoperator/interoperator variability, time efficiency and validity against natriuretic peptides.

Results

160 patients were included, 46% of whom were women, with a median age of 75 years (IQR 69-82) and a median heart rate of 100 beats per minute (IQR 86-112). The index-beat had the lowest within-beat coefficient of variation for LVEF (32%, vs 51% for 5 consecutive beats and 53% for 10 consecutive beats), GLS (26%, vs 43% and 42%) and E/e' (25%, vs 41% and 41%). Intraoperator (n=50) and interoperator (n=18) reproducibility were both superior for index-beats and this method was quicker to perform (p<0.001): 35.4 s to measure E/e' (95% CI 33.1 to 37.8) compared with 44.7 s for 5-beat (95% CI 41.8 to 47.5) and 98.1 s for 10-beat (95% CI 91.7 to 104.4) analyses. Using a single index-beat did not compromise the association of LVEF, GLS or E/e' with natriuretic peptide levels.

Conclusions

Compared with averaging of multiple beats in patients with AF, the index-beat approach improves reproducibility and saves time without a negative impact on validity, potentially improving the diagnosis and classification of heart failure in patients with AF.",,pdf:https://heart.bmj.com/content/heartjnl/107/11/902.full.pdf; doi:https://doi.org/10.1136/heartjnl-2020-318557; html:https://europepmc.org/articles/PMC8142420; pdf:https://europepmc.org/articles/PMC8142420?pdf=render 32462176,https://doi.org/10.1093/ehjci/jeaa088,A head-to-head comparison of speckle tracking echocardiography and feature tracking cardiovascular magnetic resonance imaging in right ventricular deformation.,"Taha K, Bourfiss M, Te Riele ASJM, Cramer MM, van der Heijden JF, Asselbergs FW, Velthuis BK, Teske AJ.",,European heart journal. Cardiovascular Imaging,2021,2021-07-01,Y,Right Ventricle; Strain Imaging; Speckle Tracking; Arvc; Feature Tracking; Deformation Imaging,,,"

Aims

Speckle tracking echocardiography (STE) and feature tracking cardiovascular magnetic resonance imaging (FT-CMR) are advanced imaging techniques which are both used for quantification of global and regional myocardial strain. Direct comparisons of STE and FT-CMR regarding right ventricular (RV) strain analysis are limited. We aimed to study clinical performance, correlation and agreement of RV strain by these techniques, using arrhythmogenic right ventricular cardiomyopathy (ARVC) as a model for RV disease.

Methods and results

We enrolled 110 subjects, including 34 patients with definite ARVC, 30 preclinical relatives of ARVC patients, and 46 healthy control subjects. Global and regional RV longitudinal peak strain (PS) were measured by STE and FT-CMR. Both modalities showed reduced strain values in ARVC patients compared to ARVC relatives (STE global PS: P < 0.001; FT-CMR global PS: P < 0.001) and reduced strain values in ARVC relatives compared to healthy control subjects (STE global PS: P = 0.042; FT-CMR global PS: P = 0.084). There was a moderate, albeit significant correlation between RV strain values obtained by STE and FT-CMR [global PS r = 0.578 (95% confidence interval 0.427-0.697), P < 0.001]. Agreement between the techniques was weak (limits of agreement for global PS: ±11.8%). Correlation and agreement both deteriorated when regional strain was studied.

Conclusion

RV STE and FT-CMR show a similar trend within the spectrum of ARVC and have significant correlation, but inter-modality agreement is weak. STE and FT-CMR may therefore both individually have added value for assessment of RV function, but RV PS values obtained by these techniques currently cannot be used interchangeably in clinical practice.",,pdf:https://academic.oup.com/ehjcimaging/article-pdf/22/8/950/39199744/jeaa088.pdf; doi:https://doi.org/10.1093/ehjci/jeaa088; html:https://europepmc.org/articles/PMC8291671; pdf:https://europepmc.org/articles/PMC8291671?pdf=render -37662524,https://doi.org/10.1016/j.eclinm.2023.102172,Tafamidis treatment in patients with transthyretin amyloid cardiomyopathy: a systematic review and meta-analysis.,"Wang J, Chen H, Tang Z, Zhang J, Xu Y, Wan K, Hussain K, Gkoutos GV, Han Y, Chen Y.",,EClinicalMedicine,2023,2023-08-24,Y,Prognosis; Tafamidis; Attr; Transthyretin Amyloid Cardiomyopathy,,,"

Background

Previous studies have reported that tafamidis treatment was associated with better outcomes in patients with transthyretin amyloid cardiomyopathy (ATTR-CM) compared with those without tafamidis treatment. Therefore, we aimed to systematically assess the association of tafamidis treatment with outcomes in patients with ATTR-CM.

Methods

The protocol for this systematic review and meta-analysis was registered in the PROSPERO (CRD42022381985). Pubmed, Ovid Embase, Scopus, Cochrane Library, and Web of Science were interrogated to identify studies that evaluated the impact of tafamidis on prognosis in ATTR-CM, from January 1, 2000 to June 1, 2023. A random-effects model was used to determine the pooled risk ratio (RR) for the adverse endpoints. In addition, the main outcomes included all-cause death or heart transplantation, the composite endpoints included all-cause death, heart transplantation, cardiac-assist device implantation, heart failure exacerbations, and hospitalization.

Findings

Fifteen studies comprising 2765 patients (mean age 75.9 ± 9.3 years; 83.7% male) with a mean follow-up duration of 18.7 ± 17.1 months were included in the meta-analysis. There was a decrease in left ventricular ejection fraction (LVEF) (standard mean differences (SMD: -0.17; 95% confidence interval (CI), -0.31 to -0.03; P = 0.02) but were no significant differences in intraventricular septum (IVS) thickness or global longitudinal strain (GLS) after tafamidis treatment. However, subgroup analysis showed no significant deterioration in LVEF in the patients with wild-type ATTR after tafamidis treatment (SMD: -0.11; 95% CI, -0.34 to 0.12, P = 0.34). In addition, the group with tafamidis treatment had a decreased risk for all-cause death or heart transplantation compared to patients without treatment (the pooled RR, 0.44; 95% CI, 0.31-0.65; P < 0.01). Subgroup analysis showed that there was no significant difference of tafamidis on the outcomes in patients with wild-type or hereditary ATTR (RR, 0.44; 95% CI, 0.27-0.73 versus 0.21, 95% CI, 0.11-0.40, P = 0.08). Furthermore, tafamidis treatment was associated with a lower risk of the composite endpoint (RR, 0.57; 95% CI, 0.42-0.77; P < 0.01).

Interpretation

Our findings suggested that there was no significant deterioration in LVEF in the patients with wild-type ATTR after tafamidis treatment. In addition, tafamidis treatment was associated with a low risk of all-cause death and adverse cardiovascular events.

Funding

This work was supported by grants from the Natural Science Foundation of Sichuan Province [Grant Number: 23NSFSC4589] and the National Natural Science Foundation of China [Grant Number: 82202248].",,doi:https://doi.org/10.1016/j.eclinm.2023.102172; html:https://europepmc.org/articles/PMC10474377; pdf:https://europepmc.org/articles/PMC10474377?pdf=render 36682888,https://doi.org/10.1111/cch.13097,Adversity profiles of children receiving care and support from social services: A latent-class analysis of school-aged children in Wales.,"Anthony R, Scourfield J, Moore G, Paranjothy S, Evans A, Brophy S, Daniel R, Long S.",,"Child: care, health and development",2023,2023-01-31,Y,Care; Child Welfare; Social Services; Latent Class Analysis; Adverse Childhood Experiences,,,"

Background

Children receive care and support from social services due to the risk of harm or impeded development or because of disability. This study aimed to identify typologies of adversity experienced by children receiving care and support from social services and to explore how typologies differ by sociodemographic characteristics.

Methods

This is a cross-sectional study of 'Children Receiving Care and Support' (N = 12 792) during 2017/2018 in Wales, UK. We sought to (1) examine the prevalence of household adversities experienced by children in receipt of care and support from social services; (2) identify typologies of household adversities; and (3) explore how typologies of household adversities differ by family characteristics (demographics, measures of social disadvantage, perinatal and care factors).

Results

We found evidence for multiple risk factor constellations. The four-class solution suggested four distinct classes of adversities: child disability (50.0%), low adversities (20.3%), family poor health (6.7%) and multiple risks (23.0%). Children in the 'multiple risk' class were significantly more likely to be younger, more deprived and 'looked after' by the local authority compared with those in the 'low adversities' class.

Conclusions

Given the presence of different constellations of household adversities, policies and interventions that address multiple risk factors simultaneously may be more effective and have longer-lasting benefits.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/cch.13097; doi:https://doi.org/10.1111/cch.13097; html:https://europepmc.org/articles/PMC10946723; pdf:https://europepmc.org/articles/PMC10946723?pdf=render +37662524,https://doi.org/10.1016/j.eclinm.2023.102172,Tafamidis treatment in patients with transthyretin amyloid cardiomyopathy: a systematic review and meta-analysis.,"Wang J, Chen H, Tang Z, Zhang J, Xu Y, Wan K, Hussain K, Gkoutos GV, Han Y, Chen Y.",,EClinicalMedicine,2023,2023-08-24,Y,Prognosis; Tafamidis; Attr; Transthyretin Amyloid Cardiomyopathy,,,"

Background

Previous studies have reported that tafamidis treatment was associated with better outcomes in patients with transthyretin amyloid cardiomyopathy (ATTR-CM) compared with those without tafamidis treatment. Therefore, we aimed to systematically assess the association of tafamidis treatment with outcomes in patients with ATTR-CM.

Methods

The protocol for this systematic review and meta-analysis was registered in the PROSPERO (CRD42022381985). Pubmed, Ovid Embase, Scopus, Cochrane Library, and Web of Science were interrogated to identify studies that evaluated the impact of tafamidis on prognosis in ATTR-CM, from January 1, 2000 to June 1, 2023. A random-effects model was used to determine the pooled risk ratio (RR) for the adverse endpoints. In addition, the main outcomes included all-cause death or heart transplantation, the composite endpoints included all-cause death, heart transplantation, cardiac-assist device implantation, heart failure exacerbations, and hospitalization.

Findings

Fifteen studies comprising 2765 patients (mean age 75.9 ± 9.3 years; 83.7% male) with a mean follow-up duration of 18.7 ± 17.1 months were included in the meta-analysis. There was a decrease in left ventricular ejection fraction (LVEF) (standard mean differences (SMD: -0.17; 95% confidence interval (CI), -0.31 to -0.03; P = 0.02) but were no significant differences in intraventricular septum (IVS) thickness or global longitudinal strain (GLS) after tafamidis treatment. However, subgroup analysis showed no significant deterioration in LVEF in the patients with wild-type ATTR after tafamidis treatment (SMD: -0.11; 95% CI, -0.34 to 0.12, P = 0.34). In addition, the group with tafamidis treatment had a decreased risk for all-cause death or heart transplantation compared to patients without treatment (the pooled RR, 0.44; 95% CI, 0.31-0.65; P < 0.01). Subgroup analysis showed that there was no significant difference of tafamidis on the outcomes in patients with wild-type or hereditary ATTR (RR, 0.44; 95% CI, 0.27-0.73 versus 0.21, 95% CI, 0.11-0.40, P = 0.08). Furthermore, tafamidis treatment was associated with a lower risk of the composite endpoint (RR, 0.57; 95% CI, 0.42-0.77; P < 0.01).

Interpretation

Our findings suggested that there was no significant deterioration in LVEF in the patients with wild-type ATTR after tafamidis treatment. In addition, tafamidis treatment was associated with a low risk of all-cause death and adverse cardiovascular events.

Funding

This work was supported by grants from the Natural Science Foundation of Sichuan Province [Grant Number: 23NSFSC4589] and the National Natural Science Foundation of China [Grant Number: 82202248].",,doi:https://doi.org/10.1016/j.eclinm.2023.102172; html:https://europepmc.org/articles/PMC10474377; pdf:https://europepmc.org/articles/PMC10474377?pdf=render 32763878,https://doi.org/10.2196/18690,Notifications to Improve Engagement With an Alcohol Reduction App: Protocol for a Micro-Randomized Trial.,"Bell L, Garnett C, Qian T, Perski O, Potts HWW, Williamson E.",,JMIR research protocols,2020,2020-08-07,Y,Alcohol; Engagement; Mhealth; Mobile Health; Excessive Alcohol Consumption; Smartphone App; Push Notifications; Digital Behavior Change; Micro-randomized Trial,,,"

Background

Drink Less is a behavior change app that aims to help users in the general adult population reduce hazardous and harmful alcohol consumption. The app includes a daily push notification, delivered at 11 am, asking users to ""Please complete your mood and drinking diaries."" Previous analysis of Drink Less engagement data suggests the current notification strongly influences how users engage with the app in the subsequent hour. To exploit a potential increase of vulnerability of excess drinking and opportunity to engage with the app in the evenings, we changed the delivery time from 11 am to 8 pm. We now aim to further optimise the content and sequence of notifications, testing 30 new evidence-informed notifications targeting the user's perceived usefulness of the app.

Objective

The primary objective is to assess whether sending a notification at 8 pm increases behavioral engagement (opening the app) in the subsequent hour. Secondary objectives include comparing the effect of the new bank of messages with the standard message and effect moderation over time. We also aim to more generally understand the role notifications have on the overall duration, depth, and frequency of engagement with Drink Less over the first 30 days after download.

Methods

This is a protocol for a micro-randomized trial with two additional parallel arms. Inclusion criteria are Drink Less users who (1) consent to participate in the trial; (2) self-report a baseline Alcohol Use Disorders Identification Test score of 8 or above; (3) reside in the United Kingdom; (4) age ≥18 years and; (5) report interest in drinking less alcohol. In the micro-randomized trial, participants will be randomized daily at 8 pm to receive no notification, a notification with text from the new message bank, or the standard message. The primary outcome is the time-varying, binary outcome of ""Did the user open the app in the hour from 8 pm to 9 pm?"". The primary analysis will estimate the marginal relative risk for the notifications using an estimator developed for micro-randomized trials with binary outcomes. Participants randomized to the parallel arms will receive no notifications (Secondary Arm A), or the standard notification delivered daily at 11 am (Secondary Arm B) over 30 days, allowing the comparison of overall engagement between different notification delivery strategies.

Results

Approval was granted by the University College of London's Departmental Research Ethics Committee (CEHP/2016/556) on October 11, 2019, and The London School of Hygiene and Tropical Medicine Interventions Research Ethics Committee (17929) on November 27, 2019. Recruitment began on January 2, 2020, and is ongoing.

Conclusions

Understanding how push notifications may impact engagement with a behavior change app can lead to further improvements in engagement, and ultimately help users reduce their alcohol consumption. This understanding may also be generalizable to other apps that target a variety of behavior changes.

International registered report identifier (irrid)

DERR1-10.2196/18690.",,pdf:https://www.researchprotocols.org/2020/8/e18690/PDF; doi:https://doi.org/10.2196/18690; html:https://europepmc.org/articles/PMC7442945 31711534,https://doi.org/10.1186/s13326-019-0216-2,Combining string and phonetic similarity matching to identify misspelt names of drugs in medical records written in Portuguese.,"Tissot H, Dobson R.",,Journal of biomedical semantics,2019,2019-11-12,Y,Similarity Search; Phonetic Similarity; Misspelt Names Of Drugs,,,"

Background

There is an increasing amount of unstructured medical data that can be analysed for different purposes. However, information extraction from free text data may be particularly inefficient in the presence of spelling errors. Existing approaches use string similarity methods to search for valid words within a text, coupled with a supporting dictionary. However, they are not rich enough to encode both typing and phonetic misspellings.

Results

Experimental results showed a joint string and language-dependent phonetic similarity is more accurate than traditional string distance metrics when identifying misspelt names of drugs in a set of medical records written in Portuguese.

Conclusion

We present a hybrid approach to efficiently perform similarity match that overcomes the loss of information inherit from using either exact match search or string based similarity search methods.",,pdf:https://jbiomedsem.biomedcentral.com/track/pdf/10.1186/s13326-019-0216-2; doi:https://doi.org/10.1186/s13326-019-0216-2; html:https://europepmc.org/articles/PMC6849162; pdf:https://europepmc.org/articles/PMC6849162?pdf=render 38115960,https://doi.org/10.1016/j.lanepe.2023.100763,"Prevalence of chronic pain or analgesic use in children and young people and its long-term impact on substance misuse, mental illness, and prescription opioid use: a retrospective longitudinal cohort study.","Lambarth A, Katsoulis M, Ju C, Warwick A, Takhar R, Dale C, Prieto-Merino D, Morris A, Sen D, Wei L, Sofat R.",,The Lancet regional health. Europe,2023,2023-11-15,Y,Chronic pain; Mental health; Substance Misuse; Prescription Opioids; Analgesic Medicines; Paediatric And Adolescent Health,,,"

Background

Epidemiological studies suggest chronic and recurrent pain affects around a quarter of children, while 8% report intense and frequent pain. The long-term implications of chronic pain in childhood are uncertain. Using electronic health records (EHRs) we used both disease codes and medicines prescription records to investigate the scale of chronic pain and long-term analgesic use in children and young people (CYP), and if chronic pain and/or use of analgesic medicines at an early age is associated with substance misuse, use of prescription opioids, and poor mental health in adulthood.

Methods

We conducted a cohort study using data from IQVIA Medical Research Data UK. We identified individuals aged 2-24 with exposure to either a diagnostic code indicating chronic pain (diagnosis-exposed), repeat prescription for medicines commonly used to treat pain (prescription-exposed), or both. Follow-up began at 25, and the unexposed population acted as comparators. We calculated hazard ratios (HR) for mental health and substance misuse outcomes, and rate ratios (RR) for opioid prescriptions in adulthood. Additionally, we investigated which diagnoses, if any, were over-represented in the prescription-exposed subgroup.

Findings

The cohort constituted 853,625 individuals; 146,431 had one or more of the exposures of interest (diagnosis-exposed = 115,101, prescription-exposed = 20,298, both-exposed = 11,032), leaving 707,194 as comparators. Median age at index exposure was 18.7 years (IQR 14.7-22.3). On average during follow-up, the pooled exposed group had, respectively, a 31% and 17% higher risk of adverse mental health and substance misuse outcomes (adjusted HR [95% CI] of 1.31 [1.29-1.32] and 1.17 [1.11-1.24]). Exposed individuals also received prescription opioids at double the rate of unexposed individuals on average during follow-up (adjusted RR 2.01 [95% CI 1.95-2.10]). Outcomes varied between exposure subgroups, with prescription- and both-exposure tending to have worse outcomes. Unlike these two subgroups, in the diagnosis-exposed subgroup we did not detect a greater risk of substance misuse.

Interpretation

Chronic pain in CYP is associated with increased prescription opioid use and adverse mental health outcomes in adulthood, as is repeat prescription for analgesic medicines, but only the latter is also associated with substance misuse in adulthood. It is essential to avoid the harms of under-treating pain in CYP while giving due consideration to the risks posed by analgesic medicines. Early recognition of chronic pain in CYP and utilising non-pharmacological management options may help minimise overprescribing, and long-term reliance on dependence-forming-drugs.

Funding

AL is an NIHR funded academic clinical fellow, and was supported by funding from UCLH Charities while carrying out this work. RS and DS are part of the Advanced Pain Discovery Platform and were supported by a UKRI and Versus Arthritis grant (MR/W002566/1) as part of the Consortium Against Pain Inequality. AW was supported by the Wellcome Trust (220558/Z/20/Z).",,doi:https://doi.org/10.1016/j.lanepe.2023.100763; doi:https://doi.org/10.1016/j.lanepe.2023.100763; html:https://europepmc.org/articles/PMC10730316; pdf:https://europepmc.org/articles/PMC10730316?pdf=render @@ -1097,23 +1097,23 @@ PMC10686417,https://doi.org/,The impact of restricted provision of publicly fund 36197964,https://doi.org/10.1126/scitranslmed.abq4810,"Comment on ""A proteomic surrogate for cardiovascular outcomes that is sensitive to multiple mechanisms of change in risk"".","Kivimäki M, Hingorani AD, Lindbohm JV.",,Science translational medicine,2022,2022-10-05,N,,,,"A 27-protein signature has been proposed to predict cardiovascular disease, but its applicability in clinical decision-making remains unclear.",,pdf:https://www.science.org/doi/pdf/10.1126/scitranslmed.abq4810?download=true; doi:https://doi.org/10.1126/scitranslmed.abq4810 34890511,https://doi.org/10.1080/09638288.2021.1992517,"""It's been a long hard road"": challenges faced in the first three years following traumatic brain injury.","Downing MG, Hicks AJ, Braaf S, Myles DB, Gabbe BJ, Ponsford J.",,Disability and rehabilitation,2022,2021-12-10,N,Recovery; Challenges; Traumatic brain injury; Outcome; Qualitative Study,,,"

Purpose

There is limited qualitative research exploring challenges experienced following severe traumatic brain injury (TBI). We investigated challenges to recovery identified by individuals who sustained severe TBI three years earlier or their close others (COs), as well as suggestions for managing these challenges.

Materials and methods

Nine participants with TBI and 16 COs completed semi-structured interviews. Using reflexive thematic analysis, challenges were identified across several timeframes (i.e., at the injury, acute care, inpatient rehabilitation, outpatient rehabilitation, and at home/other location).

Results

Challenges experienced across all timeframes included: lack of information and poor communication, pre-existing conditions, missed injuries, and issues with medical staff, and continuity of care. From acute care onwards, there were TBI-related consequences, issues with coping and emotional adjustment, negative outlook, insufficient treatment, lack of support for COs, and issues with compensation and funding for rehabilitation needs. Some challenges were unique to a specific timeframe (e.g., over-stimulating ward setting during acute care, and limited or unsupportive families once injured individuals went home). Suggestions for managing some of the challenges were provided (e.g., information provision, having peer supports).

Conclusion

Suggestions should be considered to promote successful outcomes following severe TBI.IMPLICATIONS FOR REHABILITATIONRecovery following a severe traumatic brain injury can be hindered by challenges, such as poor communication, limited information provision, injury-related consequences, limited services and emotional support for the injured individual and their Close Others, and a need for education of the broader community about traumatic brain injury.Suggestions for managing these challenges (e.g., peer supports; services closer to home) could be used to inform clinical guidelines that could be used in a rehabilitation context.These suggestions ultimately aim to improve the post-injury experience and outcomes of individuals with traumatic brain injury and their Close Others.",,doi:https://doi.org/10.1080/09638288.2021.1992517 31329239,https://doi.org/10.1093/jamia/ocz105,UK phenomics platform for developing and validating electronic health record phenotypes: CALIBER.,"Denaxas S, Gonzalez-Izquierdo A, Direk K, Fitzpatrick NK, Fatemifar G, Banerjee A, Dobson RJB, Howe LJ, Kuan V, Lumbers RT, Pasea L, Patel RS, Shah AD, Hingorani AD, Sudlow C, Hemingway H.",,Journal of the American Medical Informatics Association : JAMIA,2019,2019-12-01,Y,Phenotyping; Medical Informatics; Personalized Medicine; Electronic Health Records,The Human Phenome,,"

Objective

Electronic health records (EHRs) are a rich source of information on human diseases, but the information is variably structured, fragmented, curated using different coding systems, and collected for purposes other than medical research. We describe an approach for developing, validating, and sharing reproducible phenotypes from national structured EHR in the United Kingdom with applications for translational research.

Materials and methods

We implemented a rule-based phenotyping framework, with up to 6 approaches of validation. We applied our framework to a sample of 15 million individuals in a national EHR data source (population-based primary care, all ages) linked to hospitalization and death records in England. Data comprised continuous measurements (for example, blood pressure; medication information; coded diagnoses, symptoms, procedures, and referrals), recorded using 5 controlled clinical terminologies: (1) read (primary care, subset of SNOMED-CT [Systematized Nomenclature of Medicine Clinical Terms]), (2) International Classification of Diseases-Ninth Revision and Tenth Revision (secondary care diagnoses and cause of mortality), (3) Office of Population Censuses and Surveys Classification of Surgical Operations and Procedures, Fourth Revision (hospital surgical procedures), and (4) DM+D prescription codes.

Results

Using the CALIBER phenotyping framework, we created algorithms for 51 diseases, syndromes, biomarkers, and lifestyle risk factors and provide up to 6 validation approaches. The EHR phenotypes are curated in the open-access CALIBER Portal (https://www.caliberresearch.org/portal) and have been used by 40 national and international research groups in 60 peer-reviewed publications.

Conclusions

We describe a UK EHR phenomics approach within the CALIBER EHR data platform with initial evidence of validity and use, as an important step toward international use of UK EHR data for health research.",,doi:https://doi.org/10.1093/jamia/ocz105; doi:https://doi.org/10.1093/jamia/ocz105; html:https://europepmc.org/articles/PMC6857510; pdf:https://europepmc.org/articles/PMC6857510?pdf=render -36538350,https://doi.org/10.2196/41200,Identifying Patterns of Clinical Interest in Clinicians' Treatment Preferences: Hypothesis-free Data Science Approach to Prioritizing Prescribing Outliers for Clinical Review.,"MacKenna B, Curtis HJ, Hopcroft LEM, Walker AJ, Croker R, Macdonald O, Evans SJW, Inglesby P, Evans D, Morley J, Bacon SCJ, Goldacre B.",,JMIR medical informatics,2022,2022-12-20,Y,Prescribing; Clinical Audit; Antipsychotics; Pericyazine; Data Science; Nhs England; Promazine Hydrochloride,,,"

Background

Data analysis is used to identify signals suggestive of variation in treatment choice or clinical outcome. Analyses to date have generally focused on a hypothesis-driven approach.

Objective

This study aimed to develop a hypothesis-free approach to identify unusual prescribing behavior in primary care data. We aimed to apply this methodology to a national data set in a cross-sectional study to identify chemicals with significant variation in use across Clinical Commissioning Groups (CCGs) for further clinical review, thereby demonstrating proof of concept for prioritization approaches.

Methods

Here we report a new data-driven approach to identify unusual prescribing behaviour in primary care data. This approach first applies a set of filtering steps to identify chemicals with prescribing rate distributions likely to contain outliers, then applies two ranking approaches to identify the most extreme outliers amongst those candidates. This methodology has been applied to three months of national prescribing data (June-August 2017).

Results

Our methodology provides rankings for all chemicals by administrative region. We provide illustrative results for 2 antipsychotic drugs of particular clinical interest: promazine hydrochloride and pericyazine, which rank highly by outlier metrics. Specifically, our method identifies that, while promazine hydrochloride and pericyazine are barely used by most clinicians (with national prescribing rates of 11.1 and 6.2 per 1000 antipsychotic prescriptions, respectively), they make up a substantial proportion of antipsychotic prescribing in 2 small geographic regions in England during the study period (with maximum regional prescribing rates of 298.7 and 241.1 per 1000 antipsychotic prescriptions, respectively).

Conclusions

Our hypothesis-free approach is able to identify candidates for audit and review in clinical practice. To illustrate this, we provide 2 examples of 2 very unusual antipsychotics used disproportionately in 2 small geographic areas of England.",,pdf:https://medinform.jmir.org/2022/12/e41200/PDF; doi:https://doi.org/10.2196/41200; html:https://europepmc.org/articles/PMC9812268 32946551,https://doi.org/10.1093/ageing/afaa158,Do home modifications reduce care home admissions for older people? A matched control evaluation of the Care & Repair Cymru service in Wales.,"Hollinghurst J, Fry R, Akbari A, Watkins A, Williams N, Hillcoat-Nallétamby S, Lyons RA, Clegg A, Rodgers SE.",,Age and ageing,2020,2020-10-01,Y,Frailty; Interventions; Older People; Care Homes; Administrative Data,,,"

Background

home advice and modification interventions aim to promote independent living for those living in the community, but quantitative evidence of their effectiveness is limited.

Aim

assess the risk of care home admissions for people with different frailty levels receiving home advice and modification interventions against a control group who do not.

Study design and setting

matched control evaluation using linked longitudinal data from the Secure Anonymised Information Linkage (SAIL) Databank, comprising people aged 60-95, registered with a SAIL contributing general practice. The intervention group received the Care & Repair Cymru (C & RC) service, a home advice and modification service available to residents in Wales.

Methods

frailty, age and gender were used in propensity score matching to assess the Hazard Ratio (HR) of care home admissions within a 1-, 3- and 5-year period for the intervention group (N = 93,863) compared to a matched control group (N = 93,863). Kaplan-Meier curves were used to investigate time to a care home admission.

Results

the intervention group had an increased risk of a care home admission at 1-, 3- and 5-years [HR (95%CI)] for those classified as fit [1-year: 2.02 (1.73, 2.36), 3-years: 1.87 (1.72, 2.04), 5-years: 1.99 (1.86, 2.13)] and mildly frail [1-year: 1.25 (1.09, 1.42), 3-years: 1.25 (1.17, 1.34), 5-years: 1.30 (1.23, 1.38)], but a reduced risk of care home admission for moderately [1-year: 0.66 (0.58, 0.75), 3-years: 0.75 (0.70, 0.80), 5-years: 0.83 (0.78, 0.88)] and severely frail individuals [1-year: 0.44 (0.37, 0.54), 3-years: 0.54 (0.49, 0.60), 5-years: 0.60(0.55, 0.66)].

Conclusions

HRs indicated that the C & RC service helped to prevent care home admissions for moderately and severely frail individuals. The HRs generally increased with follow-up duration.",,pdf:https://academic.oup.com/ageing/article-pdf/49/6/1056/33993322/afaa158.pdf; doi:https://doi.org/10.1093/ageing/afaa158; html:https://europepmc.org/articles/PMC7583515; pdf:https://europepmc.org/articles/PMC7583515?pdf=render +36538350,https://doi.org/10.2196/41200,Identifying Patterns of Clinical Interest in Clinicians' Treatment Preferences: Hypothesis-free Data Science Approach to Prioritizing Prescribing Outliers for Clinical Review.,"MacKenna B, Curtis HJ, Hopcroft LEM, Walker AJ, Croker R, Macdonald O, Evans SJW, Inglesby P, Evans D, Morley J, Bacon SCJ, Goldacre B.",,JMIR medical informatics,2022,2022-12-20,Y,Prescribing; Clinical Audit; Antipsychotics; Pericyazine; Data Science; Nhs England; Promazine Hydrochloride,,,"

Background

Data analysis is used to identify signals suggestive of variation in treatment choice or clinical outcome. Analyses to date have generally focused on a hypothesis-driven approach.

Objective

This study aimed to develop a hypothesis-free approach to identify unusual prescribing behavior in primary care data. We aimed to apply this methodology to a national data set in a cross-sectional study to identify chemicals with significant variation in use across Clinical Commissioning Groups (CCGs) for further clinical review, thereby demonstrating proof of concept for prioritization approaches.

Methods

Here we report a new data-driven approach to identify unusual prescribing behaviour in primary care data. This approach first applies a set of filtering steps to identify chemicals with prescribing rate distributions likely to contain outliers, then applies two ranking approaches to identify the most extreme outliers amongst those candidates. This methodology has been applied to three months of national prescribing data (June-August 2017).

Results

Our methodology provides rankings for all chemicals by administrative region. We provide illustrative results for 2 antipsychotic drugs of particular clinical interest: promazine hydrochloride and pericyazine, which rank highly by outlier metrics. Specifically, our method identifies that, while promazine hydrochloride and pericyazine are barely used by most clinicians (with national prescribing rates of 11.1 and 6.2 per 1000 antipsychotic prescriptions, respectively), they make up a substantial proportion of antipsychotic prescribing in 2 small geographic regions in England during the study period (with maximum regional prescribing rates of 298.7 and 241.1 per 1000 antipsychotic prescriptions, respectively).

Conclusions

Our hypothesis-free approach is able to identify candidates for audit and review in clinical practice. To illustrate this, we provide 2 examples of 2 very unusual antipsychotics used disproportionately in 2 small geographic areas of England.",,pdf:https://medinform.jmir.org/2022/12/e41200/PDF; doi:https://doi.org/10.2196/41200; html:https://europepmc.org/articles/PMC9812268 36942567,https://doi.org/10.1161/circep.122.011585,Outcomes of Early Rhythm Control Therapy in Patients With Atrial Fibrillation and a High Comorbidity Burden in Large Real-World Cohorts.,"Dickow J, Kany S, Roth Cardoso V, Ellinor PT, Gkoutos GV, Van Houten HK, Kirchhof P, Metzner A, Noseworthy PA, Yao X, Rillig A.",,Circulation. Arrhythmia and electrophysiology,2023,2023-03-21,N,Atrial fibrillation; Stroke; Catheter ablation; Heart Failure; Comorbidity,,,"

Background

A recent subanalysis of the EAST-AFNET 4 (Early Treatment of Atrial Fibrillation for Stroke Prevention Trial) suggests a stronger benefit of early rhythm control (ERC) in patients with atrial fibrillation and a high comorbidity burden when compared to patients with a lower comorbidity burden.

Methods

We identified 109 739 patients with newly diagnosed atrial fibrillation in a large United States deidentified administrative claims database (OptumLabs) and 11 625 patients in the population-based UKB (UK Biobank). ERC was defined as atrial fibrillation ablation or antiarrhythmic drug therapy within the first year after atrial fibrillation diagnosis. Patients were classified as (1) ERC and high comorbidity burden (CHA2DS2-VASc score ≥4); (2) ERC and lower comorbidity burden (CHA2DS2-VASc score 2-3); (3) no ERC and high comorbidity burden; and (4) no ERC and lower comorbidity burden. Patients without an elevated comorbidity burden (CHA2DS2-VASc score 0-1) were excluded. Propensity score overlap weighting and cox proportional hazards regression were used to balance patients and compare groups for the primary composite outcome of all-cause mortality, stroke, or hospitalization with the diagnoses heart failure or myocardial infarction as well as for a primary composite safety outcome of death, stroke, and serious adverse events related to ERC.

Results

In both cohorts, ERC was associated with a reduced risk for the primary composite outcome in patients with a high comorbidity burden (OptumLabs: hazard ratio, 0.83 [95% CI 0.72-0.95]; P=0.006; UKB: hazard ratio, 0.77 [95% CI, 0.63-0.94]; P=0.009). In patients with a lower comorbidity burden, the difference in outcomes was not significant (OptumLabs: hazard ratio, 0.92 [95% CI, 0.54-1.57]; P=0.767; UKB: hazard ratio, 0.94 [95% CI, 0.83-1.06]; P=0.310). The comorbidity burden interacted with ERC in the UKB (interaction- P=0.027) but not in OptumLabs (interaction-P=0.720). ERC was not associated with an increased risk for the primary safety outcome.

Conclusions

ERC is safe and may be more favorable in a population-based sample of patients with high a comorbidity burden (CHA2DS2-VASc score ≥4).",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCEP.122.011585; doi:https://doi.org/10.1161/CIRCEP.122.011585; html:https://europepmc.org/articles/PMC10205477; pdf:https://europepmc.org/articles/PMC10205477?pdf=render; doi:https://doi.org/10.1161/circep.122.011585 36134546,https://doi.org/10.7189/jogh.12.05044,Risk of COVID-19 hospitalizations among school-aged children in Scotland: A national incident cohort study.,"Shi T, Pan J, Moore E, Katikireddi SV, Docherty AB, Fenton L, McCowan C, Agrawal U, Kerr S, Shah SA, Stock SJ, Simpson CR, Robertson C, Sheikh A, Public Health Scotland and the EAVE II Collaborators.",,Journal of global health,2022,2022-09-23,Y,,,,"

Background

There is considerable policy, clinical and public interest about whether children should be vaccinated against SARS-CoV-2 and, if so, which children should be prioritised (particularly if vaccine resources are limited). To inform such deliberations, we sought to identify children and young people at highest risk of hospitalization from COVID-19.

Methods

We used the Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II) platform to undertake a national incident cohort analysis to investigate the risk of hospitalization among 5-17 years old living in Scotland in risk groups defined by the living risk prediction algorithm (QCOVID). A Cox proportional hazard model was used to derive hazard ratios (HR) and 95% confidence intervals (CIs) for the association between risk groups and COVID-19 hospital admission. Adjustments were made for age, sex, socioeconomic status, co-morbidity, and prior hospitalization.

Results

Between March 1, 2020 and November 22, 2021, there were 146 183 (19.4% of all 752 867 children in Scotland) polymerase chain reaction (PCR) confirmed SARS-CoV-2 infections among 5-17 years old. Of those with confirmed infection, 973 (0.7%) were admitted to hospital with COVID-19. The rate of COVID-19 hospitalization was higher in those within each QCOVID risk group compared to those without the condition. Similar results were found in age stratified analyses (5-11 and 12-17 years old). Risk groups associated with an increased risk of COVID-19 hospital admission, included (adjusted HR, 95% CIs): sickle cell disease 14.35 (8.48-24.28), chronic kidney disease 11.34 (4.61-27.87), blood cancer 6.32 (3.24-12.35), rare pulmonary diseases 5.04 (2.58-9.86), type 2 diabetes 3.04 (1.34-6.92), epilepsy 2.54 (1.69-3.81), type 1 diabetes 2.48 (1.47-4.16), Down syndrome 2.45 (0.96-6.25), cerebral palsy 2.37 (1.26-4.47), severe mental illness 1.43 (0.63-3.24), fracture 1.41 (1.02-1.95), congenital heart disease 1.35 (0.82-2.23), asthma 1.28 (1.06-1.55), and learning disability (excluding Down syndrome) 1.08 (0.82-1.42), when compared to those without these conditions. Although our Cox models were adjusted for a number of potential confounders, residual confounding remains a possibility.

Conclusions

In this national study, we observed an increased risk of COVID-19 hospital admissions among school-aged children with specific underlying long-term health conditions compared with children without these conditions.",,pdf:https://jogh.org/wp-content/uploads/2022/10/jogh-12-05044.pdf; doi:https://doi.org/10.7189/jogh.12.05044; html:https://europepmc.org/articles/PMC9494196; pdf:https://europepmc.org/articles/PMC9494196?pdf=render 36276403,https://doi.org/10.3389/fpubh.2022.875198,The mental health experiences of ethnic minorities in the UK during the Coronavirus pandemic: A qualitative exploration.,"Van Bortel T, Lombardo C, Guo L, Solomon S, Martin S, Hughes K, Weeks L, Crepaz-Keay D, McDaid S, Chantler O, Thorpe L, Morton A, Davidson G, John A, Kousoulis AA.",,Frontiers in public health,2022,2022-10-06,Y,Mental health; United Kingdom; Inequalities; Ethnic Minorities; Covid-19; Coronavirus Pandemic; Bame Ethnicity,,,"

Background

Worldwide, the Coronavirus pandemic has had a major impact on people's health, lives, and livelihoods. However, this impact has not been felt equally across various population groups. People from ethnic minority backgrounds in the UK have been more adversely affected by the pandemic, especially in terms of their physical health. Their mental health, on the other hand, has received less attention. This study aimed to explore the mental health experiences of UK adults from ethnic minorities during the Coronavirus pandemic. This work forms part of our wider long-term UK population study ""Mental Health in the Pandemic.""

Methods

We conducted an exploratory qualitative study with people from ethnic minority communities across the UK. A series of in-depth interviews were conducted with 15 women, 14 men and 1 non-binary person from ethnic minority backgrounds, aged between 18 and 65 years old (mean age = 40). We utilized purposefully selected maximum variation sampling in order to capture as wide a variety of views, perceptions and experiences as possible. Inclusion criteria: adults (18+) from ethnic minorities across the UK; able to provide full consent to participate; able to participate in a video- or phone-call interview. All interviews took place via MS Teams or Zoom. The gathered data were transcribed verbatim and underwent thematic analysis following Braun and Clarke carried out using NVivo 12 software.

Results

The qualitative data analysis yielded seven overarching themes: (1) pandemic-specific mental health and wellbeing experiences; (2) issues relating to the media; (3) coping mechanisms; (4) worries around and attitudes toward vaccination; (5) suggestions for support in moving forward; (6) best and worst experiences during pandemic and lockdowns; (7) biggest areas of change in personal life. Generally, participants' mental health experiences varied with some not being affected by the pandemic in a way related to their ethnicity, some sharing positive experiences and coping strategies (exercising more, spending more time with family, community cohesion), and some expressing negative experiences (eating or drinking more, feeling more isolated, or even racism and abuse, especially toward Asian communities). Concerns were raised around trust issues in relation to the media, the inadequate representation of ethnic minorities, and the spread of fake news especially on social media. Attitudes toward vaccinations varied too, with some people more willing to have the vaccine than others.

Conclusion

This study's findings highlight the diversity in the pandemic mental health experiences of ethnic minorities in the UK and has implications for policy, practice and further research. To enable moving forward beyond the pandemic, our study surfaced the need for culturally appropriate mental health support, financial support (as a key mental health determinant), accurate media representation, and clear communication messaging from the Governments of the UK.",,pdf:https://www.frontiersin.org/articles/10.3389/fpubh.2022.875198/pdf; doi:https://doi.org/10.3389/fpubh.2022.875198; html:https://europepmc.org/articles/PMC9582845; pdf:https://europepmc.org/articles/PMC9582845?pdf=render 38113090,https://doi.org/10.2196/41540,Association Between Household Online Grocery Delivery Service Use and Food and Drink Purchase Behavior in England: Cross-Sectional Analysis.,"Yau A, Law C, Cornelsen L, Adams J, Boyland E, Burgoine T, de Vocht F, White M, Cummins S.",,JMIR public health and surveillance,2023,2023-12-19,Y,Delivery; Diet; Internet; Public Health; Lifestyle; Consumer Behavior; Inequality; Sociodemographic Factors; Online; Food Preferences; Food Purchase; Supermarkets; Food And Beverages; Online Purchase; Grocery Purchase; Grocery; Online Grocery,,,"

Background

Online grocery delivery services (OGDSs) are a popular way of acquiring food. However, it is unclear whether OGDS use is associated with the healthiness of purchases and whether there are sociodemographic differences in OGDS use. If so, the increased prevalence of OGDS use may have implications for population diet, and differential OGDS use could contribute to diet inequalities.

Objective

This study aimed to examine whether OGDS use varies by sociodemographic characteristics and is associated with the amount and types of groceries purchased.

Methods

Item-level take-home food and drink purchase data (n=3,233,920 items) from households in London and the North of England were available from the 2019 UK Kantar fast-moving consumer goods panel (N=1911). Purchases were categorized as being bought online or in-store. We used logistic regression to estimate the likelihood of an above-median frequency of OGDS use by sociodemographic characteristics. We used Poisson regression to estimate the differences in energy and nutrients purchased by households that had above- and below-median OGDS use and the proportion of energy purchased from products high in fat, salt, and sugar (HFSS) online versus in-store among households that used both shopping methods (n=665).

Results

In total, 668 (35%) households used OGDSs at least once in 2019. Of the households that used OGDSs, the median use was 5 occasions in 2019. Households were more likely to have above-median use in London versus in the North of England (odds ratio 1.29, 95% CI 1.01-1.65) and if they had a higher annual household income (odds ratio 1.56, 95% CI 1.02-2.38 for ≥£50,000 [US $64,000] vs <£20,000 [$25,600]). Households with above-median OGDS use had a higher weekly mean purchase of energy by 1461 (95% CI 1448-1474) kcal per person compared with households with below-median OGDS use. For households that used a combination of in-store and online shopping, HFSS products made up a lower proportion (-10.1%, 95% CI -12% to -8.1%) of energy purchased online compared to in-store.

Conclusions

Differences in grocery purchases between households with above- and below-median OGDS use could have positive or negative consequences. The extra energy purchased among households with above-median OGDS use could lead to overconsumption or food waste, which has negative consequences for population and environmental health. Alternatively, this extra energy may be replacing out-of-home purchasing, which tends to be less healthy, and may be beneficial for the population diet. Households made fewer HFSS purchases when shopping online compared to in-store, which may be due to differences in the shopping environment or experience, such as fewer promotions and advertisements when shopping online or not having to transport and carry purchases home. As higher-income households used OGDS more frequently, the implications of this sociodemographic pattern on dietary inequalities must be explored.",,doi:https://doi.org/10.2196/41540; html:https://europepmc.org/articles/PMC10762614 32896935,https://doi.org/10.1002/cbm.2166,Are Liaison and Diversion interventions in policing delivering the planned impact: A longitudinal evaluation in two constabularies?,"Kane E, Evans E, Mitsch J, Jilani T.",,Criminal behaviour and mental health : CBMH,2020,2020-09-08,N,Mental health; Outcomes; Offending; Policing; Liaison & Diversion,,,"Liaison and Diversion (L&D) has twin objectives: improving mental health outcomes and reducing re-offending. Early diversion from police custody seems promising, but evidence of benefit is required to sustain such programmes. To test the hypothesis that contact with L&D services while in police custody would lead to improved mental health outcomes and a reduction in type and level of offending, we used a pre-post service use design. National Health Service (NHS) records in two counties were searched for evidence that patients had been involved with L&D services while in police custody during the period July 2009-December 2017. We defined January 2009-July 2014 as the pre-intervention period and any time after contact as the post-intervention period. Data from the Police National Computer were gathered for each period for these individuals, to assess their pre-post L&D contact offending histories. NHS Trust data were similarly gathered to assess their pre-post use of mental health legislation. 4,462 individuals were identified who had used L&D services in police custody. There were statistically significant reductions in the amount of offending following contact with the L&D service (whether one or two contacts), regardless of offence type. Statistically significant reductions were also observed in use of the four most commonly used legislative powers for detaining patients in hospital on mental disorder grounds, regardless of offending status (prolific/non-prolific). Our results indicate positive associations between the L&D interventions and change in offending and use of compulsory hospital detention. Whilst our research does not allow a direct causal relationship to be established in either area, the findings go beyond other impact assessments of L&D which have either been with small samples or relied only on qualitative data or expert opinion.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/cbm.2166; doi:https://doi.org/10.1002/cbm.2166 38045433,https://doi.org/10.1093/ehjdh/ztad049,Developing a personalized remote patient monitoring algorithm: a proof-of-concept in heart failure.,"Moazeni M, Numan L, Brons M, Houtgraaf J, Rutten FH, Oberski DL, van Laake LW, Asselbergs FW, Aarts E.",,European heart journal. Digital health,2023,2023-08-23,Y,Heart Failure; dynamic monitoring; Process Monitoring; Intensive Longitudinal Data; Statistical Process Control Chart; Remote Patient Monitoring,,,"

Aims

Non-invasive remote patient monitoring is an increasingly popular technique to aid clinicians in the early detection of worsening heart failure (HF) alongside regular follow-ups. However, previous studies have shown mixed results in the performance of such systems. Therefore, we developed and evaluated a personalized monitoring algorithm aimed at increasing positive-predictive-value (PPV) (i.e. alarm quality) and compared performance with simple rule-of-thumb and moving average convergence-divergence algorithms (MACD).

Methods and results

In this proof-of-concept study, the developed algorithm was applied to retrospective data of daily bodyweight, heart rate, and systolic blood pressure of 74 HF-patients with a median observation period of 327 days (IQR: 183 days), during which 31 patients experienced 64 clinical worsening HF episodes. The algorithm combined information on both the monitored patients and a group of stable HF patients, and is increasingly personalized over time, using linear mixed-effect modelling and statistical process control charts. Optimized on alarm quality, heart rate showed the highest PPV (Personalized: 92%, MACD: 2%, Rule-of-thumb: 7%) with an F1 score of (Personalized: 28%, MACD: 6%, Rule-of-thumb: 8%). Bodyweight demonstrated the lowest PPV (Personalized: 16%, MACD: 0%, Rule-of-thumb: 6%) and F1 score (Personalized: 10%, MACD: 3%, Rule-of-thumb: 7%) overall compared methods.

Conclusion

The personalized algorithm with flexible patient-tailored thresholds led to higher PPV, and performance was more sensitive compared to common simple monitoring methods (rule-of-thumb and MACD). However, many episodes of worsening HF remained undetected. Heart rate and systolic blood pressure monitoring outperformed bodyweight in predicting worsening HF. The algorithm source code is publicly available for future validation and improvement.",,doi:https://doi.org/10.1093/ehjdh/ztad049; html:https://europepmc.org/articles/PMC10689918; pdf:https://europepmc.org/articles/PMC10689918?pdf=render -33468531,https://doi.org/10.1136/bmjopen-2020-047101,Protocol for the development of the Wales Multimorbidity e-Cohort (WMC): data sources and methods to construct a population-based research platform to investigate multimorbidity.,"Lyons J, Akbari A, Agrawal U, Harper G, Azcoaga-Lorenzo A, Bailey R, Rafferty J, Watkins A, Fry R, McCowan C, Dezateux C, Robson JP, Peek N, Holmes C, Denaxas S, Owen R, Abrams KR, John A, O'Reilly D, Richardson S, Hall M, Gale CP, Davies J, Davies C, Cross L, Gallacher J, Chess J, Brookes AJ, Lyons RA.",,BMJ open,2021,2021-01-19,Y,epidemiology; Public Health; Primary Care; Geriatric Medicine; Health Policy,,,"

Introduction

Multimorbidity is widely recognised as the presence of two or more concurrent long-term conditions, yet remains a poorly understood global issue despite increasing in prevalence.We have created the Wales Multimorbidity e-Cohort (WMC) to provide an accessible research ready data asset to further the understanding of multimorbidity. Our objectives are to create a platform to support research which would help to understand prevalence, trajectories and determinants in multimorbidity, characterise clusters that lead to highest burden on individuals and healthcare services, and evaluate and provide new multimorbidity phenotypes and algorithms to the National Health Service and research communities to support prevention, healthcare planning and the management of individuals with multimorbidity.

Methods and analysis

The WMC has been created and derived from multisourced demographic, administrative and electronic health record data relating to the Welsh population in the Secure Anonymised Information Linkage (SAIL) Databank. The WMC consists of 2.9 million people alive and living in Wales on the 1 January 2000 with follow-up until 31 December 2019, Welsh residency break or death. Published comorbidity indices and phenotype code lists will be used to measure and conceptualise multimorbidity.Study outcomes will include: (1) a description of multimorbidity using published data phenotype algorithms/ontologies, (2) investigation of the associations between baseline demographic factors and multimorbidity, (3) identification of temporal trajectories of clusters of conditions and multimorbidity and (4) investigation of multimorbidity clusters with poor outcomes such as mortality and high healthcare service utilisation.

Ethics and dissemination

The SAIL Databank independent Information Governance Review Panel has approved this study (SAIL Project: 0911). Study findings will be presented to policy groups, public meetings, national and international conferences, and published in peer-reviewed journals.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/1/e047101.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-047101; html:https://europepmc.org/articles/PMC7817800; pdf:https://europepmc.org/articles/PMC7817800?pdf=render 31398202,https://doi.org/10.1371/journal.pone.0220771,The role of health and social factors in education outcome: A record-linked electronic birth cohort analysis.,"Evans A, Dunstan F, Fone DL, Bandyopadhyay A, Schofield B, Demmler JC, Rahman MA, Lyons RA, Paranjothy S.",,PloS one,2019,2019-08-09,Y,,Improving Public Health,,"

Background and objective

Health status in childhood is correlated with educational outcomes. Emergency hospital admissions during childhood are common but it is not known how these unplanned breaks from schooling impact on education outcomes. We hypothesised that children who had emergency hospital admissions had an increased risk of lower educational attainment, in addition to the increased risks associated with other health, social and school factors.

Methods

This record-linked electronic birth cohort, included children born in Wales between 1 January 1998 and 31 August 2001. We fitted multilevel logistic regression models grouped by schools, to determine whether emergency hospital inpatient admission before age 7 years was associated with the educational outcome of not attaining the expected level in a teacher-based assessment at age 7 years (KS1). We adjusted for pregnancy, perinatal, socio-economic, neighbourhood, pupil mobility and school-level factors.

Results

The cohort comprised 64 934 children. Overall, 4680 (7.2%) did not attain the expected educational level. Emergency admission to hospital was associated with poor educational attainment (OR 1.12 95% Credible Interval (CI) 1.05, 1.20 for all causes during childhood, OR 1.19 95%CI 1.07, 1.32 for injuries and external causes and OR 1.31 95%CI 1.04, 1.22 for admissions during infancy), after adjusting for known determinants of education outcomes such as extreme prematurity, being small for gestational age and socio-economic indicators, such as eligibility for free school meals.

Conclusion

Emergency inpatient hospital admission during childhood, particularly during infancy or for injuries and external causes was associated with an increased risk of lower education attainment at age 7 years, in addition to the effects of pregnancy factors (gestational age, birthweight) and social deprivation. These findings support the need for injury prevention measures and additional support in school for affected children to help them to achieve their potential.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0220771&type=printable; doi:https://doi.org/10.1371/journal.pone.0220771; html:https://europepmc.org/articles/PMC6688802; pdf:https://europepmc.org/articles/PMC6688802?pdf=render +33468531,https://doi.org/10.1136/bmjopen-2020-047101,Protocol for the development of the Wales Multimorbidity e-Cohort (WMC): data sources and methods to construct a population-based research platform to investigate multimorbidity.,"Lyons J, Akbari A, Agrawal U, Harper G, Azcoaga-Lorenzo A, Bailey R, Rafferty J, Watkins A, Fry R, McCowan C, Dezateux C, Robson JP, Peek N, Holmes C, Denaxas S, Owen R, Abrams KR, John A, O'Reilly D, Richardson S, Hall M, Gale CP, Davies J, Davies C, Cross L, Gallacher J, Chess J, Brookes AJ, Lyons RA.",,BMJ open,2021,2021-01-19,Y,epidemiology; Public Health; Primary Care; Geriatric Medicine; Health Policy,,,"

Introduction

Multimorbidity is widely recognised as the presence of two or more concurrent long-term conditions, yet remains a poorly understood global issue despite increasing in prevalence.We have created the Wales Multimorbidity e-Cohort (WMC) to provide an accessible research ready data asset to further the understanding of multimorbidity. Our objectives are to create a platform to support research which would help to understand prevalence, trajectories and determinants in multimorbidity, characterise clusters that lead to highest burden on individuals and healthcare services, and evaluate and provide new multimorbidity phenotypes and algorithms to the National Health Service and research communities to support prevention, healthcare planning and the management of individuals with multimorbidity.

Methods and analysis

The WMC has been created and derived from multisourced demographic, administrative and electronic health record data relating to the Welsh population in the Secure Anonymised Information Linkage (SAIL) Databank. The WMC consists of 2.9 million people alive and living in Wales on the 1 January 2000 with follow-up until 31 December 2019, Welsh residency break or death. Published comorbidity indices and phenotype code lists will be used to measure and conceptualise multimorbidity.Study outcomes will include: (1) a description of multimorbidity using published data phenotype algorithms/ontologies, (2) investigation of the associations between baseline demographic factors and multimorbidity, (3) identification of temporal trajectories of clusters of conditions and multimorbidity and (4) investigation of multimorbidity clusters with poor outcomes such as mortality and high healthcare service utilisation.

Ethics and dissemination

The SAIL Databank independent Information Governance Review Panel has approved this study (SAIL Project: 0911). Study findings will be presented to policy groups, public meetings, national and international conferences, and published in peer-reviewed journals.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/1/e047101.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-047101; html:https://europepmc.org/articles/PMC7817800; pdf:https://europepmc.org/articles/PMC7817800?pdf=render 33503030,https://doi.org/10.1371/journal.pone.0245636,Classification of road traffic injury collision characteristics using text mining analysis: Implications for road injury prevention.,"Giummarra MJ, Beck B, Gabbe BJ.",,PloS one,2021,2021-01-27,Y,,,,"Road traffic injuries are a leading cause of morbidity and mortality globally. Understanding circumstances leading to road traffic injury is crucial to improve road safety, and implement countermeasures to reduce the incidence and severity of road trauma. We aimed to characterise crash characteristics of road traffic collisions in Victoria, Australia, and to examine the relationship between crash characteristics and fault attribution. Data were extracted from the Victorian State Trauma Registry for motor vehicle drivers, motorcyclists, pedal cyclists and pedestrians with a no-fault compensation claim, aged > = 16 years and injured 2010-2016. People with intentional injury, serious head injury, no compensation claim/missing injury event description or who died < = 12-months post-injury were excluded, resulting in a sample of 2,486. Text mining of the injury event using QDA Miner and Wordstat was used to classify crash circumstances for each road user group. Crashes in which no other was at fault included circumstances involving lost control or avoiding a hazard, mechanical failure or medical conditions. Collisions in which another was predominantly at fault occurred at intersections with another vehicle entering from an adjacent direction, and head-on collisions. Crashes with higher prevalence of unknown fault included multi-vehicle collisions, pedal cyclists injured in rear-end collisions, and pedestrians hit while crossing the road or navigating slow traffic areas. We discuss several methods to promote road safety and to reduce the incidence and severity of road traffic injuries. Our recommendations take into consideration the incidence and impact of road trauma for different types of road users, and include engineering and infrastructure controls through to interventions targeting or accommodating human behaviour.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0245636&type=printable; doi:https://doi.org/10.1371/journal.pone.0245636; html:https://europepmc.org/articles/PMC7840051; pdf:https://europepmc.org/articles/PMC7840051?pdf=render 36050271,https://doi.org/10.1016/s2589-7500(22)00151-0,CODE-EHR best-practice framework for the use of structured electronic health-care records in clinical research.,"Kotecha D, Asselbergs FW, Achenbach S, Anker SD, Atar D, Baigent C, Banerjee A, Beger B, Brobert G, Casadei B, Ceccarelli C, Cowie MR, Crea F, Cronin M, Denaxas S, Derix A, Fitzsimons D, Fredriksson M, Gale CP, Gkoutos GV, Goettsch W, Hemingway H, Ingvar M, Jonas A, Kazmierski R, Løgstrup S, Lumbers RT, Lüscher TF, McGreavy P, Piña IL, Roessig L, Steinbeisser C, Sundgren M, Tyl B, Thiel GV, Bochove KV, Vardas PE, Villanueva T, Vrana M, Weber W, Weidinger F, Windecker S, Wood A, Grobbee DE, Innovative Medicines Initiative BigData@Heart Consortium, European Society of Cardiology, and CODE-EHR International Consensus Group.",,The Lancet. Digital health,2022,2022-08-29,N,,,,"Big data is important to new developments in global clinical science that aim to improve the lives of patients. Technological advances have led to the regular use of structured electronic health-care records with the potential to address key deficits in clinical evidence that could improve patient care. The COVID-19 pandemic has shown this potential in big data and related analytics but has also revealed important limitations. Data verification, data validation, data privacy, and a mandate from the public to conduct research are important challenges to effective use of routine health-care data. The European Society of Cardiology and the BigData@Heart consortium have brought together a range of international stakeholders, including representation from patients, clinicians, scientists, regulators, journal editors, and industry members. In this Review, we propose the CODE-EHR minimum standards framework to be used by researchers and clinicians to improve the design of studies and enhance transparency of study methods. The CODE-EHR framework aims to develop robust and effective utilisation of health-care data for research purposes.",,doi:https://doi.org/10.1016/s2589-7500(22)00151-0; doi:https://doi.org/10.1016/S2589-7500(22)00151-0 +34088700,https://doi.org/10.2337/dc20-2518,"Type 2 Diabetes, Metabolic Traits, and Risk of Heart Failure: A Mendelian Randomization Study.","Mordi IR, Lumbers RT, Palmer CNA, Pearson ER, Sattar N, Holmes MV, Lang CC, HERMES Consortium.",,Diabetes care,2021,2021-06-04,Y,,,,"

Objective

The aim of this study was to use Mendelian randomization (MR) techniques to estimate the causal relationships between genetic liability to type 2 diabetes (T2D), glycemic traits, and risk of heart failure (HF).

Research design and methods

Summary-level data were obtained from genome-wide association studies of T2D, insulin resistance (IR), glycated hemoglobin, fasting insulin and glucose, and HF. MR was conducted using the inverse-variance weighted method. Sensitivity analyses included the MR-Egger method, weighted median and mode methods, and multivariable MR conditioning on potential mediators.

Results

Genetic liability to T2D was causally related to higher risk of HF (odds ratio [OR] 1.13 per 1-log unit higher risk of T2D; 95% CI 1.11-1.14; P < 0.001); however, sensitivity analysis revealed evidence of directional pleiotropy. The relationship between T2D and HF was attenuated when adjusted for coronary disease, BMI, LDL cholesterol, and blood pressure in multivariable MR. Genetically instrumented higher IR was associated with higher risk of HF (OR 1.19 per 1-log unit higher risk of IR; 95% CI 1.00-1.41; P = 0.041). There were no notable associations identified between fasting insulin, glucose, or glycated hemoglobin and risk of HF. Genetic liability to HF was causally linked to higher risk of T2D (OR 1.49; 95% CI 1.01-2.19; P = 0.042), although again with evidence of pleiotropy.

Conclusions

These findings suggest a possible causal role of T2D and IR in HF etiology, although the presence of both bidirectional effects and directional pleiotropy highlights potential sources of bias that must be considered.",,pdf:https://diabetesjournals.org/care/article-pdf/44/7/1699/632992/dc202518.pdf; doi:https://doi.org/10.2337/dc20-2518; html:https://europepmc.org/articles/PMC8323186; pdf:https://europepmc.org/articles/PMC8323186?pdf=render 38672093,https://doi.org/10.3390/biomedicines12040737,Determinants of Carotid Wall Echolucency in a Cohort of European High Cardiovascular Risk Subjects: A Cross-Sectional Analysis of IMPROVE Baseline Data.,"Frigerio B, Coggi D, Bonomi A, Amato M, Capra N, Colombo GI, Sansaro D, Ravani A, Savonen K, Giral P, Gallo A, Pirro M, Gigante B, Eriksson P, Strawbridge RJ, Mulder DJ, Tremoli E, Veglia F, Baldassarre D, IMPROVE Study Group.",,Biomedicines,2024,2024-03-26,N,Atherosclerosis; Carotid plaque; risk factors; cardiovascular; Intima–media Thickness; Gray-scale Median; Echolucency,,,"Echolucency, a measure of plaque instability associated with increased cardiovascular risk, can be assessed in both the carotid plaque and the plaque-free common carotid intima-media (IM) complex as a gray-scale median (plaque-GSM and IM-GSM, respectively). The impact of specific vascular risk factors on these two phenotypes remains uncertain, including the nature and extent of their influence. This study aims to seek the determinants of plaque-GSM and IM-GSM. Plaque-GSM and IM-GSM were measured in subjects from the IMPROVE study cohort (aged 54-79, 46% men) recruited in five European countries. Plaque-GSM was measured in subjects who had at least one IMTmax ≥ 1.5 mm (n = 2138), whereas IM-GSM was measured in all subjects included in the study (n = 3188). Multiple regression with internal cross-validation was used to find independent predictors of plaque-GSM and IM-GSM. Plaque-GSM determinants were plaque-size (IMTmax), and diastolic blood pressure. IM-GSM determinants were the thickness of plaque-free common carotid intima-media complex (PF CC-IMTmean), height, systolic blood pressure, waist/hip ratio, treatment with fibrates, mean corpuscular volume, treatment with alpha-2 inhibitors (sartans), educational level, and creatinine. Latitude, and pack-yearscode were determinants of both plaque-GSM and IM-GSM. The overall models explain 12.0% of plaque-GSM variability and 19.7% of IM-GSM variability. A significant correlation (r = 0.51) was found between plaque-GSM and IM-GSM. Our results indicate that IM-GSM is a weighty risk marker alternative to plaque-GSM, offering the advantage of being readily measurable in all subjects, including those in the early phases of atherosclerosis where plaque occurrence is relatively infrequent.",,doi:https://doi.org/10.3390/biomedicines12040737 37739596,https://doi.org/10.1016/j.jtha.2023.07.008,"""C1-inhibitor levels and venous thromboembolism: results from a Mendelian randomization study"": reply.","Cupido AJ, Petersen RS, Schmidt AF, Levi M, Cohn DM, Fijen LM.",,Journal of thrombosis and haemostasis : JTH,2023,2023-10-01,N,,,,,,doi:https://doi.org/10.1016/j.jtha.2023.07.008 -34088700,https://doi.org/10.2337/dc20-2518,"Type 2 Diabetes, Metabolic Traits, and Risk of Heart Failure: A Mendelian Randomization Study.","Mordi IR, Lumbers RT, Palmer CNA, Pearson ER, Sattar N, Holmes MV, Lang CC, HERMES Consortium.",,Diabetes care,2021,2021-06-04,Y,,,,"

Objective

The aim of this study was to use Mendelian randomization (MR) techniques to estimate the causal relationships between genetic liability to type 2 diabetes (T2D), glycemic traits, and risk of heart failure (HF).

Research design and methods

Summary-level data were obtained from genome-wide association studies of T2D, insulin resistance (IR), glycated hemoglobin, fasting insulin and glucose, and HF. MR was conducted using the inverse-variance weighted method. Sensitivity analyses included the MR-Egger method, weighted median and mode methods, and multivariable MR conditioning on potential mediators.

Results

Genetic liability to T2D was causally related to higher risk of HF (odds ratio [OR] 1.13 per 1-log unit higher risk of T2D; 95% CI 1.11-1.14; P < 0.001); however, sensitivity analysis revealed evidence of directional pleiotropy. The relationship between T2D and HF was attenuated when adjusted for coronary disease, BMI, LDL cholesterol, and blood pressure in multivariable MR. Genetically instrumented higher IR was associated with higher risk of HF (OR 1.19 per 1-log unit higher risk of IR; 95% CI 1.00-1.41; P = 0.041). There were no notable associations identified between fasting insulin, glucose, or glycated hemoglobin and risk of HF. Genetic liability to HF was causally linked to higher risk of T2D (OR 1.49; 95% CI 1.01-2.19; P = 0.042), although again with evidence of pleiotropy.

Conclusions

These findings suggest a possible causal role of T2D and IR in HF etiology, although the presence of both bidirectional effects and directional pleiotropy highlights potential sources of bias that must be considered.",,pdf:https://diabetesjournals.org/care/article-pdf/44/7/1699/632992/dc202518.pdf; doi:https://doi.org/10.2337/dc20-2518; html:https://europepmc.org/articles/PMC8323186; pdf:https://europepmc.org/articles/PMC8323186?pdf=render -37440761,https://doi.org/10.1093/ehjci/jead166,Neuroticism personality traits are linked to adverse cardiovascular phenotypes in the UK Biobank.,"Mahmood A, Simon J, Cooper J, Murphy T, McCracken C, Quiroz J, Laranjo L, Aung N, Lee AM, Khanji MY, Neubauer S, Raisi-Estabragh Z, Maurovich-Horvat P, Petersen SE.",,European heart journal. Cardiovascular Imaging,2023,2023-10-01,Y,Cardiac function; Cardiac morphology; Mental health; Cardiovascular Magnetic Resonance; Neuroticism; Cardiovascular Remodelling,,,"

Aims

To evaluate the relationship between neuroticism personality traits and cardiovascular magnetic resonance (CMR) measures of cardiac morphology and function, considering potential differential associations in men and women.

Methods and results

The analysis includes 36 309 UK Biobank participants (average age = 63.9 ± 7.7 years; 47.8% men) with CMR available and neuroticism score assessed by the 12-item Eysenck Personality Questionnaire-Revised Short Form. CMR scans were performed on 1.5 Tesla scanners (MAGNETOM Aera, Siemens Healthcare, Erlangen, Germany) according to pre-defined protocols and analysed using automated pipelines. We considered measures of left ventricular (LV) and right ventricular (RV) structure and function, and indicators of arterial compliance. Multivariable linear regression was used to estimate association of neuroticism score with individual CMR metrics, with adjustment for age, sex, obesity, deprivation, smoking, diabetes, hypertension, hypercholesterolaemia, alcohol use, exercise, and education. Higher neuroticism scores were associated with smaller LV and RV end-diastolic volumes, lower LV mass, greater concentricity (higher LV mass to volume ratio), and higher native T1. Greater neuroticism was also linked to poorer LV and RV function (lower stroke volumes) and greater arterial stiffness. In sex-stratified analyses, the relationships between neuroticism and LV stroke volume, concentricity, and arterial stiffness were attenuated in women. In men, association (with exception of native T1) remained robust.

Conclusion

Greater tendency towards neuroticism personality traits is linked to smaller, poorer functioning ventricles with lower LV mass, higher myocardial fibrosis, and higher arterial stiffness. These relationships are independent of traditional vascular risk factors and are more robust in men than women.",,pdf:https://academic.oup.com/ehjcimaging/advance-article-pdf/doi/10.1093/ehjci/jead166/50880139/jead166.pdf; doi:https://doi.org/10.1093/ehjci/jead166; html:https://europepmc.org/articles/PMC10610755; pdf:https://europepmc.org/articles/PMC10610755?pdf=render 37649471,https://doi.org/10.23889/ijpds.v6i3.1705,Data linkage can reduce the burden and increase the opportunities in the implementation of Value-Based Health Care policy: a study in patients with ulcerative colitis (PROUD-UC Study).,"Walshe J, Akbari A, Hawthorne AB, Laing H.",,International journal of population data science,2021,2021-01-01,Y,"Colitis, ulcerative; Health Policy; Patient Reported Outcome Measure; Routinely Collected Health Data; Data Science; Value-based Health Care",,,"

Introduction

Healthcare systems face rising demand and unsustainable cost pressures. In response, health policymakers are adopting Value-Based Health Care (VBHC), targeting available resources to achieve the best possible patient outcomes at the lowest possible cost and actively disinvesting in care of low-value. This requires the evaluation of longitudinal clinical and patient reported outcome measures (PROMs) at an individual-level and population-scale, which can create significant data challenges. Achieving this through routinely collected electronic health record (EHR) data-linkage could facilitate the implementation of VBHC without an unacceptable data burden on patients or health systems and release time for higher-value activities.

Objectives

Our study tested the ability to report an international, patient-centred outcome dataset (ICHOM-IBD) using only anonymised individual-level population-scale linked electronic health record (EHR) data sources, including clinical and patient-reported outcomes, in a cohort of patients with moderate-to-severe ulcerative colitis (UC), receiving biopharmaceutical therapies (""biologics"") in a single, publicly funded, healthcare system.

Results

We identified a cohort of 17,632 patients with UC in Wales and a cohort from two Health Boards of 447 patients with UC receiving biologics. 112 of these patients had completed 866 condition-specific PROMs during their biologics treatment. 44 out of 59 (74.6%) items in the ICHOM-IBD could be derived from routinely collected data of which a primary care source was essential for eight items and desirable for 21.

Conclusions

We demonstrated that it is possible to report most but not all the ICHOM-IBD outcomes using routinely collected data from multiple sources without additional system burden, potentially supporting Value-Based Health Care implementation with population data science. As digital collection of PROMs and use of condition-specific registries grow, greater utility of this approach can be anticipated. We have identified that the availability of longitudinal primary and secondary care data linked with PROMs is essential for this to be possible.",,pdf:https://ijpds.org/article/download/1705/4121; doi:https://doi.org/10.23889/ijpds.v6i3.1705; html:https://europepmc.org/articles/PMC10464864; pdf:https://europepmc.org/articles/PMC10464864?pdf=render +37440761,https://doi.org/10.1093/ehjci/jead166,Neuroticism personality traits are linked to adverse cardiovascular phenotypes in the UK Biobank.,"Mahmood A, Simon J, Cooper J, Murphy T, McCracken C, Quiroz J, Laranjo L, Aung N, Lee AM, Khanji MY, Neubauer S, Raisi-Estabragh Z, Maurovich-Horvat P, Petersen SE.",,European heart journal. Cardiovascular Imaging,2023,2023-10-01,Y,Cardiac function; Cardiac morphology; Mental health; Cardiovascular Magnetic Resonance; Neuroticism; Cardiovascular Remodelling,,,"

Aims

To evaluate the relationship between neuroticism personality traits and cardiovascular magnetic resonance (CMR) measures of cardiac morphology and function, considering potential differential associations in men and women.

Methods and results

The analysis includes 36 309 UK Biobank participants (average age = 63.9 ± 7.7 years; 47.8% men) with CMR available and neuroticism score assessed by the 12-item Eysenck Personality Questionnaire-Revised Short Form. CMR scans were performed on 1.5 Tesla scanners (MAGNETOM Aera, Siemens Healthcare, Erlangen, Germany) according to pre-defined protocols and analysed using automated pipelines. We considered measures of left ventricular (LV) and right ventricular (RV) structure and function, and indicators of arterial compliance. Multivariable linear regression was used to estimate association of neuroticism score with individual CMR metrics, with adjustment for age, sex, obesity, deprivation, smoking, diabetes, hypertension, hypercholesterolaemia, alcohol use, exercise, and education. Higher neuroticism scores were associated with smaller LV and RV end-diastolic volumes, lower LV mass, greater concentricity (higher LV mass to volume ratio), and higher native T1. Greater neuroticism was also linked to poorer LV and RV function (lower stroke volumes) and greater arterial stiffness. In sex-stratified analyses, the relationships between neuroticism and LV stroke volume, concentricity, and arterial stiffness were attenuated in women. In men, association (with exception of native T1) remained robust.

Conclusion

Greater tendency towards neuroticism personality traits is linked to smaller, poorer functioning ventricles with lower LV mass, higher myocardial fibrosis, and higher arterial stiffness. These relationships are independent of traditional vascular risk factors and are more robust in men than women.",,pdf:https://academic.oup.com/ehjcimaging/advance-article-pdf/doi/10.1093/ehjci/jead166/50880139/jead166.pdf; doi:https://doi.org/10.1093/ehjci/jead166; html:https://europepmc.org/articles/PMC10610755; pdf:https://europepmc.org/articles/PMC10610755?pdf=render 34671274,https://doi.org/10.3389/fphys.2021.730736,Comparing Non-invasive Inverse Electrocardiography With Invasive Endocardial and Epicardial Electroanatomical Mapping During Sinus Rhythm.,"Roudijk RW, Boonstra MJ, Brummel R, Kassenberg W, Blom LJ, Oostendorp TF, Te Riele ASJM, van der Heijden JF, Asselbergs FW, van Dam PM, Loh P.",,Frontiers in physiology,2021,2021-10-04,Y,Cardiac Arrhythmia; Sudden Cardiac Death; Electroanatomical Mapping; Electrocardiographic Imaging (Ecgi); Non-invasive Mapping; Equivalent Dipole Layer; Inverse Problem Of Electrocardiography,,,"This study presents a novel non-invasive equivalent dipole layer (EDL) based inverse electrocardiography (iECG) technique which estimates both endocardial and epicardial ventricular activation sequences. We aimed to quantitatively compare our iECG approach with invasive electro-anatomical mapping (EAM) during sinus rhythm with the objective of enabling functional substrate imaging and sudden cardiac death risk stratification in patients with cardiomyopathy. Thirteen patients (77% males, 48 ± 20 years old) referred for endocardial and epicardial EAM underwent 67-electrode body surface potential mapping and CT imaging. The EDL-based iECG approach was improved by mimicking the effects of the His-Purkinje system on ventricular activation. EAM local activation timing (LAT) maps were compared with iECG-LAT maps using absolute differences and Pearson's correlation coefficient, reported as mean ± standard deviation [95% confidence interval]. The correlation coefficient between iECG-LAT maps and EAM was 0.54 ± 0.19 [0.49-0.59] for epicardial activation, 0.50 ± 0.27 [0.41-0.58] for right ventricular endocardial activation and 0.44 ± 0.29 [0.32-0.56] for left ventricular endocardial activation. The absolute difference in timing between iECG maps and EAM was 17.4 ± 7.2 ms for epicardial maps, 19.5 ± 7.7 ms for right ventricular endocardial maps, 27.9 ± 8.7 ms for left ventricular endocardial maps. The absolute distance between right ventricular endocardial breakthrough sites was 30 ± 16 mm and 31 ± 17 mm for the left ventricle. The absolute distance for latest epicardial activation was median 12.8 [IQR: 2.9-29.3] mm. This first in-human quantitative comparison of iECG and invasive LAT-maps on both the endocardial and epicardial surface during sinus rhythm showed improved agreement, although with considerable absolute difference and moderate correlation coefficient. Non-invasive iECG requires further refinements to facilitate clinical implementation and risk stratification.",,pdf:https://www.frontiersin.org/articles/10.3389/fphys.2021.730736/pdf; doi:https://doi.org/10.3389/fphys.2021.730736; html:https://europepmc.org/articles/PMC8521153; pdf:https://europepmc.org/articles/PMC8521153?pdf=render 35673545,https://doi.org/10.12688/wellcomeopenres.17231.2,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody lateral flow assay for antibody prevalence studies following vaccination: a diagnostic accuracy study.,"Cann A, Clarke C, Brown J, Thomson T, Prendecki M, Moshe M, Badhan A, Simmons B, Klaber B, Elliott P, Darzi A, Riley S, Ashby D, Martin P, Gleeson S, Willicombe M, Kelleher P, Ward H, Barclay WS, Cooke GS.",,Wellcome open research,2021,2021-01-01,Y,Antibodies; Seroprevalence; Lateral Flow; Neutralisation; Lfia; Covid-19; Sars-cov-2,,,"Background: Lateral flow immunoassays (LFIAs) are able to achieve affordable, large scale antibody testing and provide rapid results without the support of central laboratories. As part of the development of the REACT programme extensive evaluation of LFIA performance was undertaken with individuals following natural infection. Here we assess the performance of the selected LFIA to detect antibody responses in individuals who have received at least one dose of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. Methods: This was a prospective diagnostic accuracy study. Sampling was carried out at renal outpatient clinic and healthcare worker testing sites at Imperial College London NHS Trust. Two cohorts of patients were recruited; the first was a cohort of 108 renal transplant patients attending clinic following two doses of SARS-CoV-2 vaccine, the second cohort comprised 40 healthcare workers attending for first SARS-CoV-2 vaccination and subsequent follow up. During the participants visit, finger-prick blood samples were analysed on LFIA device, while paired venous sampling was sent for serological assessment of antibodies to the spike protein (anti-S) antibodies. Anti-S IgG was detected using the Abbott Architect SARS-CoV-2 IgG Quant II CMIA. A total of 186 paired samples were collected. The accuracy of Fortress LFIA in detecting IgG antibodies to SARS-CoV-2 compared to anti-spike protein detection on Abbott Assay Results: The LFIA had an estimated sensitivity of 92.0% (114/124; 95% confidence interval [CI] 85.7% to 96.1%) and specificity of 93.6% (58/62; 95% CI 84.3% to 98.2%) using the Abbott assay as reference standard (using the threshold for positivity of 7.10 BAU/ml) Conclusions: Fortress LFIA performs well in the detection of antibody responses for intended purpose of population level surveillance but does not meet criteria for individual testing.",,doi:https://doi.org/10.12688/wellcomeopenres.17231.2; html:https://europepmc.org/articles/PMC9152464; pdf:https://europepmc.org/articles/PMC9152464?pdf=render 35132056,https://doi.org/10.1038/s41467-022-28252-5,Genome-wide association meta-analysis identifies 29 new acne susceptibility loci.,"Mitchell BL, Saklatvala JR, Dand N, Hagenbeek FA, Li X, Min JL, Thomas L, Bartels M, Jan Hottenga J, Lupton MK, Boomsma DI, Dong X, Hveem K, Løset M, Martin NG, Barker JN, Han J, Smith CH, Rentería ME, Simpson MA.",,Nature communications,2022,2022-02-07,Y,,,,"Acne vulgaris is a highly heritable skin disorder that primarily impacts facial skin. Severely inflamed lesions may leave permanent scars that have been associated with long-term psychosocial consequences. Here, we perform a GWAS meta-analysis comprising 20,165 individuals with acne from nine independent European ancestry cohorts. We identify 29 novel genome-wide significant loci and replicate 14 of the 17 previously identified risk loci, bringing the total number of reported acne risk loci to 46. Using fine-mapping and eQTL colocalisation approaches, we identify putative causal genes at several acne susceptibility loci that have previously been implicated in Mendelian hair and skin disorders, including pustular psoriasis. We identify shared genetic aetiology between acne, hormone levels, hormone-sensitive cancers and psychiatric traits. Finally, we show that a polygenic risk score calculated from our results explains up to 5.6% of the variance in acne liability in an independent cohort.",,pdf:https://www.nature.com/articles/s41467-022-28252-5.pdf; doi:https://doi.org/10.1038/s41467-022-28252-5; html:https://europepmc.org/articles/PMC8821634; pdf:https://europepmc.org/articles/PMC8821634?pdf=render @@ -1121,39 +1121,39 @@ PMC10686417,https://doi.org/,The impact of restricted provision of publicly fund 38633019,https://doi.org/10.1002/lrh2.10391,ROAD2H: Development and evaluation of an open-source explainable artificial intelligence approach for managing co-morbidity and clinical guidelines.,"Domínguez J, Prociuk D, Marović B, Čyras K, Cocarascu O, Ruiz F, Mi E, Mi E, Ramtale C, Rago A, Darzi A, Toni F, Curcin V, Delaney B.",,Learning health systems,2024,2023-09-12,Y,Clinical Decision Support Systems; Argumentation; Fhir; Cds Hooks; Co‐morbidity; Transition‐based Medical Recommendation Model,,,"

Introduction

Clinical decision support (CDS) systems (CDSSs) that integrate clinical guidelines need to reflect real-world co-morbidity. In patient-specific clinical contexts, transparent recommendations that allow for contraindications and other conflicts arising from co-morbidity are a requirement. In this work, we develop and evaluate a non-proprietary, standards-based approach to the deployment of computable guidelines with explainable argumentation, integrated with a commercial electronic health record (EHR) system in Serbia, a middle-income country in West Balkans.

Methods

We used an ontological framework, the Transition-based Medical Recommendation (TMR) model, to represent, and reason about, guideline concepts, and chose the 2017 International global initiative for chronic obstructive lung disease (GOLD) guideline and a Serbian hospital as the deployment and evaluation site, respectively. To mitigate potential guideline conflicts, we used a TMR-based implementation of the Assumptions-Based Argumentation framework extended with preferences and Goals (ABA+G). Remote EHR integration of computable guidelines was via a microservice architecture based on HL7 FHIR and CDS Hooks. A prototype integration was developed to manage chronic obstructive pulmonary disease (COPD) with comorbid cardiovascular or chronic kidney diseases, and a mixed-methods evaluation was conducted with 20 simulated cases and five pulmonologists.

Results

Pulmonologists agreed 97% of the time with the GOLD-based COPD symptom severity assessment assigned to each patient by the CDSS, and 98% of the time with one of the proposed COPD care plans. Comments were favourable on the principles of explainable argumentation; inclusion of additional co-morbidities was suggested in the future along with customisation of the level of explanation with expertise.

Conclusion

An ontological model provided a flexible means of providing argumentation and explainable artificial intelligence for a long-term condition. Extension to other guidelines and multiple co-morbidities is needed to test the approach further.",,doi:https://doi.org/10.1002/lrh2.10391; html:https://europepmc.org/articles/PMC11019374; pdf:https://europepmc.org/articles/PMC11019374?pdf=render 38304411,https://doi.org/10.26633/rpsp.2024.12,[Guidelines for clinical trial protocols for interventions involving artificial intelligence: the SPIRIT-AI extensionDiretrizes para protocolos de ensaios clínicos com intervenções que utilizam inteligência artificial: a extensão SPIRIT-AI].,"Cruz Rivera S, Liu X, Chan AW, Denniston AK, Calvert MJ, Grupo de Trabajo SPIRIT-AI y CONSORT-AI, Grupo Directivo SPIRIT-AI y CONSORT-AI , Grupo de Consenso SPIRIT-AI y CONSORT-AI .",,Revista panamericana de salud publica = Pan American journal of public health,2024,2023-02-01,Y,,,,"The SPIRIT 2013 statement aims to improve the completeness of clinical trial protocol reporting by providing evidence-based recommendations for the minimum set of items to be addressed. This guidance has been instrumental in promoting transparent evaluation of new interventions. More recently, there has been a growing recognition that interventions involving artificial intelligence (AI) need to undergo rigorous, prospective evaluation to demonstrate their impact on health outcomes. The SPIRIT-AI (Standard Protocol Items: Recommendations for Interventional Trials-Artificial Intelligence) extension is a new reporting guideline for clinical trial protocols evaluating interventions with an AI component. It was developed in parallel with its companion statement for trial reports: CONSORT-AI (Consolidated Standards of Reporting Trials-Artificial Intelligence). Both guidelines were developed through a staged consensus process involving literature review and expert consultation to generate 26 candidate items, which were consulted upon by an international multi-stakeholder group in a two-stage Delphi survey (103 stakeholders), agreed upon in a consensus meeting (31 stakeholders) and refined through a checklist pilot (34 participants). The SPIRIT-AI extension includes 15 new items that were considered sufficiently important for clinical trial protocols of AI interventions. These new items should be routinely reported in addition to the core SPIRIT 2013 items. SPIRIT-AI recommends that investigators provide clear descriptions of the AI intervention, including instructions and skills required for use, the setting in which the AI intervention will be integrated, considerations for the handling of input and output data, the human-AI interaction and analysis of error cases. SPIRIT-AI will help promote transparency and completeness for clinical trial protocols for AI interventions. Its use will assist editors and peer reviewers, as well as the general readership, to understand, interpret and critically appraise the design and risk of bias for a planned clinical trial.",,pdf:https://iris.paho.org/bitstream/10665.2/59241/1/v48e122024.pdf; doi:https://doi.org/10.26633/RPSP.2024.12; html:https://europepmc.org/articles/PMC10832304; pdf:https://europepmc.org/articles/PMC10832304?pdf=render 36333542,https://doi.org/10.1007/s10654-022-00934-w,Biases arising from linked administrative data for epidemiological research: a conceptual framework from registration to analyses.,"Shaw RJ, Harron KL, Pescarini JM, Pinto Junior EP, Allik M, Siroky AN, Campbell D, Dundas R, Ichihara MY, Leyland AH, Barreto ML, Katikireddi SV.",,European journal of epidemiology,2022,2022-11-05,Y,Data Linkage; Record Linkage; Administrative Data; Epidemiological Biases; Linkage Error,,,"Linked administrative data offer a rich source of information that can be harnessed to describe patterns of disease, understand their causes and evaluate interventions. However, administrative data are primarily collected for operational reasons such as recording vital events for legal purposes, and planning, provision and monitoring of services. The processes involved in generating and linking administrative datasets may generate sources of bias that are often not adequately considered by researchers. We provide a framework describing these biases, drawing on our experiences of using the 100 Million Brazilian Cohort (100MCohort) which contains records of more than 131 million people whose families applied for social assistance between 2001 and 2018. Datasets for epidemiological research were derived by linking the 100MCohort to health-related databases such as the Mortality Information System and the Hospital Information System. Using the framework, we demonstrate how selection and misclassification biases may be introduced in three different stages: registering and recording of people's life events and use of services, linkage across administrative databases, and cleaning and coding of variables from derived datasets. Finally, we suggest eight recommendations which may reduce biases when analysing data from administrative sources.",,pdf:https://link.springer.com/content/pdf/10.1007/s10654-022-00934-w.pdf; doi:https://doi.org/10.1007/s10654-022-00934-w; html:https://europepmc.org/articles/PMC9792414; pdf:https://europepmc.org/articles/PMC9792414?pdf=render -36864090,https://doi.org/10.1038/s41598-023-30369-6,Effect of tissue-grouped regulatory variants associated to type 2 diabetes in related secondary outcomes.,"Hemerich D, Smit RAJ, Preuss M, Stalbow L, van der Laan SW, Asselbergs FW, van Setten J, Tragante V.",,Scientific reports,2023,2023-03-02,Y,,,,"Genome-wide association studies have identified over five hundred loci that contribute to variation in type 2 diabetes (T2D), an established risk factor for many diseases. However, the mechanisms and extent through which these loci contribute to subsequent outcomes remain elusive. We hypothesized that combinations of T2D-associated variants acting on tissue-specific regulatory elements might account for greater risk for tissue-specific outcomes, leading to diversity in T2D disease progression. We searched for T2D-associated variants acting on regulatory elements and expression quantitative trait loci (eQTLs) in nine tissues. We used T2D tissue-grouped variant sets as genetic instruments to conduct 2-Sample Mendelian Randomization (MR) in ten related outcomes whose risk is increased by T2D using the FinnGen cohort. We performed PheWAS analysis to investigate whether the T2D tissue-grouped variant sets had specific predicted disease signatures. We identified an average of 176 variants acting in nine tissues implicated in T2D, and an average of 30 variants acting on regulatory elements that are unique to the nine tissues of interest. In 2-Sample MR analyses, all subsets of regulatory variants acting in different tissues were associated with increased risk of the ten secondary outcomes studied on similar levels. No tissue-grouped variant set was associated with an outcome significantly more than other tissue-grouped variant sets. We did not identify different disease progression profiles based on tissue-specific regulatory and transcriptome information. Bigger sample sizes and other layers of regulatory information in critical tissues may help identify subsets of T2D variants that are implicated in certain secondary outcomes, uncovering system-specific disease progression.",,pdf:https://www.nature.com/articles/s41598-023-30369-6.pdf; doi:https://doi.org/10.1038/s41598-023-30369-6; html:https://europepmc.org/articles/PMC9981672; pdf:https://europepmc.org/articles/PMC9981672?pdf=render 35135774,https://doi.org/10.1136/bmjopen-2021-055603,"Observational retrospective study calculating health service costs of patients receiving surgery for chronic rhinosinusitis in England, using linked patient-level primary and secondary care electronic data.","Clarke CS, Williamson E, Denaxas S, Carpenter JR, Thomas M, Blackshaw H, Schilder AGM, Philpott CM, Hopkins C, Morris S, MACRO programme team.",,BMJ open,2022,2022-02-08,Y,Otolaryngology; Clinical Trials; Health Economics,,,"

Objectives

Chronic rhinosinusitis (CRS) symptoms are experienced by an estimated 11% of UK adults, and symptoms have major impacts on quality of life. Data from UK and elsewhere suggest high economic burden of CRS, but detailed cost information and economic analyses regarding surgical pathway are lacking. This paper estimates healthcare costs for patients receiving surgery for CRS in England.

Design

Observational retrospective study examining cost of healthcare of patients receiving CRS surgery.

Setting

Linked electronic health records from the Clinical Practice Research Datalink, Hospital Episode Statistics and Office for National Statistics databases in England.

Participants

A phenotyping algorithm using medical ontology terms identified 'definite' CRS cases who received CRS surgery. Patients were registered with a general practice in England. Data covered the period 1997-2016. A cohort of 13 462 patients had received surgery for CRS, with 9056 (67%) having confirmed nasal polyps.

Outcome measures

Information was extracted on numbers and types of primary care prescriptions and consultations, and inpatient and outpatient hospital investigations and procedures. Resource use was costed using published sources.

Results

Total National Health Service costs in CRS surgery patients were £2173 over 1 year including surgery. Total costs per person-quarter were £1983 in the quarter containing surgery, mostly comprising surgical inpatient care costs (£1902), and around £60 per person-quarter in the 2 years before and after surgery, of which half were outpatient costs. Outpatient and primary care costs were low compared with the peak in inpatient costs at surgery. The highest outpatient expenditure was on CT scans, peaking in the quarter preceding surgery.

Conclusions

We present the first study of costs to the English healthcare system for patients receiving surgery for CRS. The total aggregate costs provide a further impetus for trials to evaluate the relative benefit of surgical intervention.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/2/e055603.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-055603; html:https://europepmc.org/articles/PMC8830221; pdf:https://europepmc.org/articles/PMC8830221?pdf=render +36864090,https://doi.org/10.1038/s41598-023-30369-6,Effect of tissue-grouped regulatory variants associated to type 2 diabetes in related secondary outcomes.,"Hemerich D, Smit RAJ, Preuss M, Stalbow L, van der Laan SW, Asselbergs FW, van Setten J, Tragante V.",,Scientific reports,2023,2023-03-02,Y,,,,"Genome-wide association studies have identified over five hundred loci that contribute to variation in type 2 diabetes (T2D), an established risk factor for many diseases. However, the mechanisms and extent through which these loci contribute to subsequent outcomes remain elusive. We hypothesized that combinations of T2D-associated variants acting on tissue-specific regulatory elements might account for greater risk for tissue-specific outcomes, leading to diversity in T2D disease progression. We searched for T2D-associated variants acting on regulatory elements and expression quantitative trait loci (eQTLs) in nine tissues. We used T2D tissue-grouped variant sets as genetic instruments to conduct 2-Sample Mendelian Randomization (MR) in ten related outcomes whose risk is increased by T2D using the FinnGen cohort. We performed PheWAS analysis to investigate whether the T2D tissue-grouped variant sets had specific predicted disease signatures. We identified an average of 176 variants acting in nine tissues implicated in T2D, and an average of 30 variants acting on regulatory elements that are unique to the nine tissues of interest. In 2-Sample MR analyses, all subsets of regulatory variants acting in different tissues were associated with increased risk of the ten secondary outcomes studied on similar levels. No tissue-grouped variant set was associated with an outcome significantly more than other tissue-grouped variant sets. We did not identify different disease progression profiles based on tissue-specific regulatory and transcriptome information. Bigger sample sizes and other layers of regulatory information in critical tissues may help identify subsets of T2D variants that are implicated in certain secondary outcomes, uncovering system-specific disease progression.",,pdf:https://www.nature.com/articles/s41598-023-30369-6.pdf; doi:https://doi.org/10.1038/s41598-023-30369-6; html:https://europepmc.org/articles/PMC9981672; pdf:https://europepmc.org/articles/PMC9981672?pdf=render 34985035,https://doi.org/10.1097/htr.0000000000000741,Epidemiology and 6- and 12-Month Outcomes of Intimate Partner Violence and Other Violence-Related Traumatic Brain Injury in Major Trauma: A Population-Based Trauma Registry Study.,"Gabbe BJ, Braaf S, Cameron PA, Berecki-Gisolf J.",,The Journal of head trauma rehabilitation,2022,2022-01-01,N,,,,"

Objective

To compare the epidemiology, in-hospital outcomes, and 6-month and 12-month patient-reported, outcomes of major trauma patients with intimate partner violence (IPV)-related traumatic brain injury (TBI) with other interpersonal violence (OV)-related TBI.

Setting

Victoria, Australia.

Participants

Adult (≥18 years) major trauma cases with TBI (concussion, skull fracture, or intracranial injury), injured through IPV or OV, between July 2010 and June 2020, and included on the population-based Victorian State Trauma Registry. There were 133 adult major trauma cases due to IPV and 1796 due to OV. The prevalence of TBI was 39% (n = 52) in the IPV group and 56% (n = 1010) in the OV group.

Design

Registry-based cohort study.

Main measures

Trauma care indicators and 6- and 12-month patient-reported outcomes (self-reported disability, Glasgow Outcome Scale-Extended, EQ-5D-3L, and return to work).

Results

The annual incidence (95% CI) of major trauma involving TBI was 0.11 (0.08-0.14) per 100 000 population for IPV and 2.11 (1.98-2.24) per 100 000 for OV. A higher proportion of IPV-related cases were women (73% vs 5%), had sustained a severe TBI (Glasgow Coma Scale score 3-8; 27% vs 15%), were admitted to intensive care (56% vs 37%), and died in hospital (14% vs 5%). The median (interquartile range) time to definitive care (4.7 hours vs 3.3 hours) and head computed tomographic scan (5.0 hours vs 3.1 hours) was longer in the IPV group. Follow-up rates at 6 and 12 months were 71% and 69%, respectively. The 6- and 12-month outcomes were generally poorer in the IPV-related group.

Conclusion

The incidence of IPV-related major trauma with TBI was low. However, the prevalence of severe TBI, the time to key aspects of clinical care, in-hospital mortality, and longer-term work-related disability were higher. However, power to detect differences was low due to the small number of IPV-related cases compared with the OV group.",,doi:https://doi.org/10.1097/HTR.0000000000000741 34847088,https://doi.org/10.1097/ede.0000000000001429,The Authors Respond.,"Katsoulis M, De Stavola B, Lai AG, Gomes M, Diaz-Ordaz K.",,"Epidemiology (Cambridge, Mass.)",2022,2022-01-01,N,,,,,,html:https://journals.lww.com/epidem/Fulltext/2022/01000/The_Authors_Respond.22.aspx; doi:https://doi.org/10.1097/EDE.0000000000001429 37456658,https://doi.org/10.12688/hrbopenres.13667.1,Qualitative data sharing practices in clinical trials in the UK and Ireland: towards the production of good practice guidance.,"McCarthy M, Gillies K, Rousseau N, Wade J, Gamble C, Toomey E, Matvienko-Sikar K, Sydes M, Dowling M, Bryant V, Biesty L, Houghton C.",,HRB open research,2023,2023-02-06,Y,data sharing; Qualitative; trials; Focus Groups,,,"Background: Data sharing enables researchers to conduct novel research with previously collected datasets, thus maximising scientific findings and cost effectiveness, and reducing research waste. The value of sharing, even de-identified, quantitative data from clinical trials is well recognised with a moderated access approach recommended. While substantial challenges to sharing quantitative data remain, there are additional challenges for sharing qualitative data in trials. Incorporating the necessary information about how qualitative data will be shared into already complex trial recruitment and consent processes proves challenging. The aim of this study was to explore whether and how trial teams share qualitative data collected as part of the design, conduct, analysis, or delivery of clinical trials. Methods: Phase 1 involved semi-structured, in-depth qualitative interviews and focus groups with key trial stakeholder groups including trial managers and clinical trialists (n=3), qualitative researchers in trials (n=9), members of research funding bodies (n=2) and trial participants (n=1). Data were analysed using thematic analysis. In Phase 2, we conducted a content analysis of 16 participant information leaflets (PIL) and consent forms (CF) for trials that collected qualitative data. Results: Three key themes were identified from our Phase 1 findings: ' Understanding and experiences of the potential benefits of sharing qualitative data from trials', 'Concerns about qualitative data sharing', and ' Future guidance and funding'. In phase 2, the PILs and CFs received revealed that the benefits of data sharing for participants were only explained in two of the study documents. Conclusions: The value of sharing qualitative data was acknowledged, but there are many uncertainties as to how, when, and where to share this data. In addition, there were ethical concerns in relation to the consent process required for qualitative data sharing in trials. This study provides insight into the existing practice of qualitative data sharing in trials.",,pdf:https://hrbopenresearch.org/articles/6-10/pdf; doi:https://doi.org/10.12688/hrbopenres.13667.1; html:https://europepmc.org/articles/PMC10345597; pdf:https://europepmc.org/articles/PMC10345597?pdf=render -37293269,https://doi.org/10.1140/epjds/s13688-023-00394-6,Do poverty and wealth look the same the world over? A comparative study of 12 cities from five high-income countries using street images.,"Suel E, Muller E, Bennett JE, Blakely T, Doyle Y, Lynch J, Mackenbach JD, Middel A, Mizdrak A, Nathvani R, Brauer M, Ezzati M.",,EPJ data science,2023,2023-06-07,Y,Computer vision; Visual Similarity; Urban Inequalities; Street Images,,,"Urbanization and inequalities are two of the major policy themes of our time, intersecting in large cities where social and economic inequalities are particularly pronounced. Large scale street-level images are a source of city-wide visual information and allow for comparative analyses of multiple cities. Computer vision methods based on deep learning applied to street images have been shown to successfully measure inequalities in socioeconomic and environmental features, yet existing work has been within specific geographies and have not looked at how visual environments compare across different cities and countries. In this study, we aim to apply existing methods to understand whether, and to what extent, poor and wealthy groups live in visually similar neighborhoods across cities and countries. We present novel insights on similarity of neighborhoods using street-level images and deep learning methods. We analyzed 7.2 million images from 12 cities in five high-income countries, home to more than 85 million people: Auckland (New Zealand), Sydney (Australia), Toronto and Vancouver (Canada), Atlanta, Boston, Chicago, Los Angeles, New York, San Francisco, and Washington D.C. (United States of America), and London (United Kingdom). Visual features associated with neighborhood disadvantage are more distinct and unique to each city than those associated with affluence. For example, from what is visible from street images, high density poor neighborhoods located near the city center (e.g., in London) are visually distinct from poor suburban neighborhoods characterized by lower density and lower accessibility (e.g., in Atlanta). This suggests that differences between two cities is also driven by historical factors, policies, and local geography. Our results also have implications for image-based measures of inequality in cities especially when trained on data from cities that are visually distinct from target cities. We showed that these are more prone to errors for disadvantaged areas especially when transferring across cities, suggesting more attention needs to be paid to improving methods for capturing heterogeneity in poor environment across cities around the world.

Supplementary information

The online version contains supplementary material available at 10.1140/epjds/s13688-023-00394-6.",,pdf:https://epjdatascience.springeropen.com/counter/pdf/10.1140/epjds/s13688-023-00394-6; doi:https://doi.org/10.1140/epjds/s13688-023-00394-6; html:https://europepmc.org/articles/PMC10245348; pdf:https://europepmc.org/articles/PMC10245348?pdf=render 32728709,https://doi.org/10.1093/pubmed/fdaa115,Are children who are home from school at an increased risk of child maltreatment?,"Syed S, Gilbert R.",,"Journal of public health (Oxford, England)",2021,2021-04-01,N,,,,,,pdf:https://discovery.ucl.ac.uk/10110375/1/Syed%20and%20Gilbert%20%282020%29.%20Are%20children%20who%20are%20home%20from%20school%20at%20an%20increased%20risk%20of%20child%20maltreatment.pdf; doi:https://doi.org/10.1093/pubmed/fdaa115 -37920183,https://doi.org/10.3389/fcvm.2023.1148931,Unraveling the relationships between alpha- and beta-adrenergic modulation and the risk of heart failure.,"Baudier C, Fougerousse F, Asselbergs FW, Guedj M, Komajda M, Kotecha D, Thomas Lumbers R, Schmidt AF, Tyl B.",,Frontiers in cardiovascular medicine,2023,2023-10-18,Y,"adrenergic receptors; Beta-blockers; Mendelian Randomization; Alpha-blockers; Target Validation, Drug",,,"

Background

The effects of α and ß adrenergic receptor modulation on the risk of developing heart failure (HF) remains uncertain due to a lack of randomized controlled trials. This study aimed to estimate the effects of α and ß adrenergic receptors modulation on the risk of HF and to provide proof of principle for genetic target validation studies in HF.

Methods

Genetic variants within the cis regions encoding the adrenergic receptors α1A, α2B, ß1, and ß2 associated with blood pressure in a 757,601-participant genome-wide association study (GWAS) were selected as instruments to perform a drug target Mendelian randomization study. Effects of these variants on HF risk were derived from the HERMES GWAS (542,362 controls; 40,805 HF cases).

Results

Lower α1A or ß1 activity was associated with reduced HF risk: odds ratio (OR) 0.83 (95% CI 0.74-0.93, P = 0.001) and 0.95 (95% CI 0.93-0.97, P = 8 × 10-6). Conversely, lower α2B activity was associated with increased HF risk: OR 1.09 (95% CI 1.05-1.12, P = 3 × 10-7). No evidence of an effect of lower ß2 activity on HF risk was found: OR 0.99 (95% CI 0.92-1.07, P = 0.95). Complementary analyses showed that these effects were consistent with those on left ventricular dimensions and acted independently of any potential effect on coronary artery disease.

Conclusions

This study provides genetic evidence that α1A or ß1 receptor inhibition will likely decrease HF risk, while lower α2B activity may increase this risk. Genetic variant analysis can assist with drug development for HF prevention.",,doi:https://doi.org/10.3389/fcvm.2023.1148931; html:https://europepmc.org/articles/PMC10619754; pdf:https://europepmc.org/articles/PMC10619754?pdf=render +37293269,https://doi.org/10.1140/epjds/s13688-023-00394-6,Do poverty and wealth look the same the world over? A comparative study of 12 cities from five high-income countries using street images.,"Suel E, Muller E, Bennett JE, Blakely T, Doyle Y, Lynch J, Mackenbach JD, Middel A, Mizdrak A, Nathvani R, Brauer M, Ezzati M.",,EPJ data science,2023,2023-06-07,Y,Computer vision; Visual Similarity; Urban Inequalities; Street Images,,,"Urbanization and inequalities are two of the major policy themes of our time, intersecting in large cities where social and economic inequalities are particularly pronounced. Large scale street-level images are a source of city-wide visual information and allow for comparative analyses of multiple cities. Computer vision methods based on deep learning applied to street images have been shown to successfully measure inequalities in socioeconomic and environmental features, yet existing work has been within specific geographies and have not looked at how visual environments compare across different cities and countries. In this study, we aim to apply existing methods to understand whether, and to what extent, poor and wealthy groups live in visually similar neighborhoods across cities and countries. We present novel insights on similarity of neighborhoods using street-level images and deep learning methods. We analyzed 7.2 million images from 12 cities in five high-income countries, home to more than 85 million people: Auckland (New Zealand), Sydney (Australia), Toronto and Vancouver (Canada), Atlanta, Boston, Chicago, Los Angeles, New York, San Francisco, and Washington D.C. (United States of America), and London (United Kingdom). Visual features associated with neighborhood disadvantage are more distinct and unique to each city than those associated with affluence. For example, from what is visible from street images, high density poor neighborhoods located near the city center (e.g., in London) are visually distinct from poor suburban neighborhoods characterized by lower density and lower accessibility (e.g., in Atlanta). This suggests that differences between two cities is also driven by historical factors, policies, and local geography. Our results also have implications for image-based measures of inequality in cities especially when trained on data from cities that are visually distinct from target cities. We showed that these are more prone to errors for disadvantaged areas especially when transferring across cities, suggesting more attention needs to be paid to improving methods for capturing heterogeneity in poor environment across cities around the world.

Supplementary information

The online version contains supplementary material available at 10.1140/epjds/s13688-023-00394-6.",,pdf:https://epjdatascience.springeropen.com/counter/pdf/10.1140/epjds/s13688-023-00394-6; doi:https://doi.org/10.1140/epjds/s13688-023-00394-6; html:https://europepmc.org/articles/PMC10245348; pdf:https://europepmc.org/articles/PMC10245348?pdf=render 34798287,https://doi.org/10.1016/j.jclinepi.2021.11.023,Missing data is poorly handled and reported in prediction model studies using machine learning: a literature review.,"Nijman S, Leeuwenberg AM, Beekers I, Verkouter I, Jacobs J, Bots ML, Asselbergs FW, Moons K, Debray T.",,Journal of clinical epidemiology,2022,2021-11-16,N,Prediction; Literature review; Reporting; Missing Data; Machine Learning,,,"

Objectives

Missing data is a common problem during the development, evaluation, and implementation of prediction models. Although machine learning (ML) methods are often said to be capable of circumventing missing data, it is unclear how these methods are used in medical research. We aim to find out if and how well prediction model studies using machine learning report on their handling of missing data.

Study design and setting

We systematically searched the literature on published papers between 2018 and 2019 about primary studies developing and/or validating clinical prediction models using any supervised ML methodology across medical fields. From the retrieved studies information about the amount and nature (e.g. missing completely at random, potential reasons for missingness) of missing data and the way they were handled were extracted.

Results

We identified 152 machine learning-based clinical prediction model studies. A substantial amount of these 152 papers did not report anything on missing data (n = 56/152). A majority (n = 96/152) reported details on the handling of missing data (e.g., methods used), though many of these (n = 46/96) did not report the amount of the missingness in the data. In these 96 papers the authors only sometimes reported possible reasons for missingness (n = 7/96) and information about missing data mechanisms (n = 8/96). The most common approach for handling missing data was deletion (n = 65/96), mostly via complete-case analysis (CCA) (n = 43/96). Very few studies used multiple imputation (n = 8/96) or built-in mechanisms such as surrogate splits (n = 7/96) that directly address missing data during the development, validation, or implementation of the prediction model.

Conclusion

Though missing values are highly common in any type of medical research and certainly in the research based on routine healthcare data, a majority of the prediction model studies using machine learning does not report sufficient information on the presence and handling of missing data. Strategies in which patient data are simply omitted are unfortunately the most often used methods, even though it is generally advised against and well known that it likely causes bias and loss of analytical power in prediction model development and in the predictive accuracy estimates. Prediction model researchers should be much more aware of alternative methodologies to address missing data.",,pdf:http://www.jclinepi.com/article/S0895435621003759/pdf; doi:https://doi.org/10.1016/j.jclinepi.2021.11.023 +37920183,https://doi.org/10.3389/fcvm.2023.1148931,Unraveling the relationships between alpha- and beta-adrenergic modulation and the risk of heart failure.,"Baudier C, Fougerousse F, Asselbergs FW, Guedj M, Komajda M, Kotecha D, Thomas Lumbers R, Schmidt AF, Tyl B.",,Frontiers in cardiovascular medicine,2023,2023-10-18,Y,"adrenergic receptors; Beta-blockers; Mendelian Randomization; Alpha-blockers; Target Validation, Drug",,,"

Background

The effects of α and ß adrenergic receptor modulation on the risk of developing heart failure (HF) remains uncertain due to a lack of randomized controlled trials. This study aimed to estimate the effects of α and ß adrenergic receptors modulation on the risk of HF and to provide proof of principle for genetic target validation studies in HF.

Methods

Genetic variants within the cis regions encoding the adrenergic receptors α1A, α2B, ß1, and ß2 associated with blood pressure in a 757,601-participant genome-wide association study (GWAS) were selected as instruments to perform a drug target Mendelian randomization study. Effects of these variants on HF risk were derived from the HERMES GWAS (542,362 controls; 40,805 HF cases).

Results

Lower α1A or ß1 activity was associated with reduced HF risk: odds ratio (OR) 0.83 (95% CI 0.74-0.93, P = 0.001) and 0.95 (95% CI 0.93-0.97, P = 8 × 10-6). Conversely, lower α2B activity was associated with increased HF risk: OR 1.09 (95% CI 1.05-1.12, P = 3 × 10-7). No evidence of an effect of lower ß2 activity on HF risk was found: OR 0.99 (95% CI 0.92-1.07, P = 0.95). Complementary analyses showed that these effects were consistent with those on left ventricular dimensions and acted independently of any potential effect on coronary artery disease.

Conclusions

This study provides genetic evidence that α1A or ß1 receptor inhibition will likely decrease HF risk, while lower α2B activity may increase this risk. Genetic variant analysis can assist with drug development for HF prevention.",,doi:https://doi.org/10.3389/fcvm.2023.1148931; html:https://europepmc.org/articles/PMC10619754; pdf:https://europepmc.org/articles/PMC10619754?pdf=render 36936265,https://doi.org/10.1136/bmjmed-2022-000276,"Trends, variation, and clinical characteristics of recipients of antiviral drugs and neutralising monoclonal antibodies for covid-19 in community settings: retrospective, descriptive cohort study of 23.4 million people in OpenSAFELY.","Green ACA, Curtis HJ, Higgins R, Nab L, Mahalingasivam V, Smith RM, Mehrkar A, Inglesby P, Drysdale H, DeVito NJ, Croker R, Rentsch CT, Bhaskaran K, Tazare J, Zheng B, Andrews CD, Bacon SCJ, Davy S, Dillingham I, Evans D, Fisher L, Hickman G, Hopcroft LEM, Hulme WJ, Massey J, MacDonald O, Morley J, Morton CE, Park RY, Walker AJ, Ward T, Wiedemann M, Bates C, Cockburn J, Parry J, Hester F, Harper S, Douglas IJ, Evans SJW, Goldacre B, Tomlinson LA, MacKenna B.",,BMJ medicine,2023,2023-01-13,Y,Therapeutics; Community health services; Public Health; Covid-19,,,"

Objective

To ascertain patient eligibility status and describe coverage of antiviral drugs and neutralising monoclonal antibodies (nMAB) as treatment for covid-19 in community settings in England.

Design

Retrospective, descriptive cohort study, approved by NHS England.

Setting

Routine clinical data from 23.4 million people linked to data on covid-19 infection and treatment, within the OpenSAFELY-TPP database.

Participants

Outpatients with covid-19 at high risk of severe outcomes.

Interventions

Nirmatrelvir/ritonavir (paxlovid), sotrovimab, molnupiravir, casirivimab/imdevimab, or remdesivir, used in the community by covid-19 medicine delivery units.

Results

93 870 outpatients with covid-19 were identified between 11 December 2021 and 28 April 2022 to be at high risk of severe outcomes and therefore potentially eligible for antiviral or nMAB treatment (or both). Of these patients, 19 040 (20%) received treatment (sotrovimab, 9660 (51%); molnupiravir, 4620 (24%); paxlovid, 4680 (25%); casirivimab/imdevimab, 50 (<1%); and remdesivir, 30 (<1%)). The proportion of patients treated increased from 9% (190/2220) in the first week of treatment availability to 29% (460/1600) in the latest week. The proportion treated varied by high risk group, being lowest in those with liver disease (16%; 95% confidence interval 15% to 17%); by treatment type, with sotrovimab favoured over molnupiravir and paxlovid in all but three high risk groups (Down's syndrome (35%; 30% to 39%), rare neurological conditions (45%; 43% to 47%), and immune deficiencies (48%; 47% to 50%)); by age, ranging from ≥80 years (13%; 12% to 14%) to 50-59 years (23%; 22% to 23%); by ethnic group, ranging from black (11%; 10% to 12%) to white (21%; 21% to 21%); by NHS region, ranging from 13% (12% to 14%) in Yorkshire and the Humber to 25% (24% to 25%) in the East of England); and by deprivation level, ranging from 15% (14% to 15%) in the most deprived areas to 23% (23% to 24%) in the least deprived areas. Groups that also had lower coverage included unvaccinated patients (7%; 6% to 9%), those with dementia (6%; 5% to 7%), and care home residents (6%; 6% to 7%).

Conclusions

Using the OpenSAFELY platform, we were able to identify patients with covid-19 at high risk of severe outcomes who were potentially eligible to receive treatment and assess the coverage of these new treatments among these patients. In the context of a rapid deployment of a new service, the NHS analytical code used to determine eligibility could have been over-inclusive and some of the eligibility criteria not fully captured in healthcare data. However targeted activity might be needed to resolve apparent lower treatment coverage observed among certain groups, in particular (at present): different NHS regions, ethnic groups, people aged ≥80 years, those living in socioeconomically deprived areas, and care home residents.",,pdf:https://bmjmedicine.bmj.com/content/bmjmed/2/1/e000276.full.pdf; doi:https://doi.org/10.1136/bmjmed-2022-000276; html:https://europepmc.org/articles/PMC9951378; pdf:https://europepmc.org/articles/PMC9951378?pdf=render 36719715,https://doi.org/10.2196/41248,Patterns in the Use of Heart Failure Telemonitoring: Post Hoc Analysis of the e-Vita Heart Failure Trial.,"Brons M, Ten Klooster I, van Gemert-Pijnen L, Jaarsma T, Asselbergs FW, Oerlemans MIFJ, Koudstaal S, Rutten FH.",,JMIR cardio,2023,2023-01-31,Y,Adherence; Heart Failure; Patient Monitoring; Remote Monitoring; Telemonitoring; Ehealth; Electronic Personal Health Record,,,"

Background

Research on the use of home telemonitoring data and adherence to it can provide new insights into telemonitoring for the daily management of patients with heart failure (HF).

Objective

We described the use of a telemonitoring platform-including remote patient monitoring of blood pressure, pulse, and weight-and the use of the electronic personal health record. Patient characteristics were assessed in both adherent and nonadherent patients to weight transmissions.

Methods

We used the data of the e-Vita HF study, a 3-arm parallel randomized trial performed in stable patients with HF managed in outpatient clinics in the Netherlands. In this study, data were analyzed from the participants in the intervention arm (ie, e-Vita HF platform). Adherence to weight transmissions was defined as transmitting weight ≥3 times per week for at least 42 weeks during a year.

Results

Data from 150 patients (mean age 67, SD 11 years; n=37, 25% female; n=123, 82% self-assessed New York Heart Association class I-II) were analyzed. One-year adherence to weight transmissions was 74% (n=111). Patients adherent to weight transmissions were less often hospitalized for HF in the 6 months before enrollment in the study compared to those who were nonadherent (n=9, 8% vs n=9, 23%; P=.02). The percentage of patients visiting the personal health record dropped steadily over time (n=140, 93% vs n=59, 39% at one year). With univariable analyses, there was no significant correlation between patient characteristics and adherence to weight transmissions.

Conclusions

Adherence to remote patient monitoring was high among stable patients with HF and best for weighing; however, adherence decreased over time. Clinical and demographic variables seem not related to adherence to transmitting weight.

Trial registration

ClinicalTrials.gov NCT01755988; https://clinicaltrials.gov/ct2/show/NCT01755988.",,pdf:https://cardio.jmir.org/2023/1/e41248/PDF; doi:https://doi.org/10.2196/41248; html:https://europepmc.org/articles/PMC9929726; pdf:https://europepmc.org/articles/PMC9929726?pdf=render 36013179,https://doi.org/10.3390/jpm12081230,Grip Strength Trajectories and Cognition in English and Chilean Older Adults: A Cross-Cohort Study.,"Angel B, Ajnakina O, Albala C, Lera L, Márquez C, Leipold L, Bilovich A, Dobson R, Bendayan R.",,Journal of personalized medicine,2022,2022-07-27,Y,Cognition; Longitudinal study; Older Adults; Grip Strength,,,"Growing evidence about the link between cognitive and physical decline suggests the early changes in physical functioning as a potential biomarker for cognitive impairment. Thus, we compared grip-strength trajectories over 12-16 years in three groups classified according to their cognitive status (two stable patterns, normal and impaired cognitive performance, and a declining pattern) in two representative UK and Chilean older adult samples. The samples consisted of 7069 UK (ELSA) and 1363 Chilean participants (ALEXANDROS). Linear Mixed models were performed. Adjustments included socio-demographics and health variables. The Declined and Impaired group had significantly lower grip-strength at baseline when compared to the Non-Impaired. In ELSA, the Declined and Impaired showed a faster decline in their grip strength compared to the Non-Impaired group but differences disappeared in the fully adjusted models. In ALEXANDROS, the differences were only found between the Declined and Non-Impaired and they were partially attenuated by covariates. Our study provides robust evidence of the association between grip strength and cognitive performance and how socio-economic factors might be key to understanding this association and their variability across countries. This has implications for future epidemiological research, as hand-grip strength measurements have the potential to be used as an indicator of cognitive performance.",,pdf:https://www.mdpi.com/2075-4426/12/8/1230/pdf?version=1659687887; doi:https://doi.org/10.3390/jpm12081230; html:https://europepmc.org/articles/PMC9410389; pdf:https://europepmc.org/articles/PMC9410389?pdf=render -35921096,https://doi.org/10.1001/jamacardio.2022.2333,Joint Genetic Inhibition of PCSK9 and CETP and the Association With Coronary Artery Disease: A Factorial Mendelian Randomization Study.,"Cupido AJ, Reeskamp LF, Hingorani AD, Finan C, Asselbergs FW, Hovingh GK, Schmidt AF.",,JAMA cardiology,2022,2022-09-01,N,,,,"

Importance

Cholesteryl ester transfer protein inhibition (CETP) has been shown to increase levels of high-density lipoprotein cholesterol (HDL-C) and reduce levels of low-density lipoprotein cholesterol (LDL-C). Current LDL-C target attainment is low, and novel phase 3 trials are underway to investigate whether CETP inhibitors result in reduction of cardiovascular disease risk in high-risk patients who may be treated with PCSK9-inhibiting agents.

Objective

To explore the associations of combined reduction of CETP and PCSK9 concentrations with risk of coronary artery disease (CAD) and other clinical and safety outcomes.

Design, setting, and participants

Two-sample 2 × 2 factorial Mendelian randomization study in a general population sample that includes data for UK Biobank participants of European ancestry.

Exposures

Separate genetic scores were constructed for CETP and PCSK9 plasma protein concentrations, which were combined to determine the associations of combined genetically reduced CETP and PCSK9 concentrations with disease.

Main outcomes and measures

Blood lipid and lipoprotein concentrations, blood pressure, CAD, age-related macular degeneration, type 2 diabetes, any stroke and ischemic stroke, Alzheimer disease, vascular dementia, heart failure, atrial fibrillation, chronic kidney disease, asthma, and multiple sclerosis.

Results

Data for 425 354 UKB participants were included; the median (IQR) age was 59 years (51-64), and 229 399 (53.9%) were female. The associations of lower CETP and lower PCSK9 concentrations with CAD are similar when scaled per 10-mg/dL reduction in LDL-C concentrations (CETP: odds ratio [OR], 0.74; 95% CI, 0.67 to 0.81; PCSK9: OR, 0.75; 95% CI, 0.71 to 0.79). Combined exposure to lower CETP and PCSK9 concentrations was associated with an additive magnitude with lipids and all outcomes, and we did not observe any nonadditive interactions, most notably for LDL-C (CETP: effect size, -1.11 mg/dL; 95% CI, -1.40 to -0.82; PCSK9: effect size, -2.13 mg/dL; 95% CI, -2.43 to -1.84; combined: effect size, -3.47 mg/dL; 95% CI, -3.76 to -3.18; P = .34 for interaction) and CAD (CETP: OR, 0.96; 95% CI, 0.94 to 1.00; PCSK9: OR, 0.94; 95% CI, 0.91 to 0.97; combined: OR, 0.90; 95% CI, 0.87 to 0.93; P = .83 for interaction). In addition, when corrected for multiple testing, lower CETP concentrations were associated with increased age-related macular degeneration (OR, 1.11; 95% CI, 1.04 to 1.19).

Conclusions and relevance

Our results suggest that joint inhibition of CETP and PCSK9 has additive effects on lipid traits and disease risk, including a lower risk of CAD. Further research may explore whether a combination of CETP- and PCSK9-related therapeutics can benefit high-risk patients who are unable to reach treatment targets with existing options.",,doi:https://doi.org/10.1001/jamacardio.2022.2333; html:https://europepmc.org/articles/PMC9350849; doi:https://doi.org/10.1001/jamacardio.2022.2333 -38528983,https://doi.org/10.3389/fpsyt.2024.1347100,Machine learning in mental health and its relationship with epidemiological practice.,"DelPozo-Banos M, Stewart R, John A.",,Frontiers in psychiatry,2024,2024-03-11,Y,Research methods; Mental health; epidemiology; Machine Learning; Challenges And Opportunities,,,,,pdf:https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2024.1347100/pdf; doi:https://doi.org/10.3389/fpsyt.2024.1347100; html:https://europepmc.org/articles/PMC10961376; pdf:https://europepmc.org/articles/PMC10961376?pdf=render 31477110,https://doi.org/10.1186/s12913-019-4286-8,Weekend admissions and mortality for major acute disorders across England and Wales: record linkage cohort studies.,"Roberts SE, John A, Lewis KE, Brown J, Lyons RA, Williams JG.",,BMC health services research,2019,2019-09-02,Y,Mortality; Weekend Admissions; Acute Disorders,Improving Public Health,,"

Background

To establish which major disorders are susceptible to increased mortality following acute admissions on weekends, compared with week days, and how this may be explained.

Methods

Cohorts based on national administrative inpatient and mortality data for 14,168,443 hospitalised patients in England and 913,068 in Wales who were admitted for 66 disorders that were associated with at least 200 deaths within 30 days of acute admission. The main outcome measure was the weekend mortality effect (defined as the conventional mortality odds ratio for admissions on weekends compared with week days).

Results

There were large, statistically significant weekend mortality effects (> 20%) in England for 22 of the 66 conditions and in both countries for 14. These 14 were 4 of 13 cancers (oesophageal, colorectal, lung and lymphomas); 4 of 13 circulatory disorders (angina, abdominal aortic aneurysm, peripheral vascular disease and arterial embolism & thrombosis); one of 8 respiratory disorders (pleural effusion); 2 of 12 gastrointestinal disorders (alcoholic and other liver disease); 2 of 3 ageing-related disorders (Alzheimer's disease and dementia); none of 7 trauma conditions; and one of 10 other disorders (acute renal failure). Across the disorders, 64% of the variation in weekend mortality effects in England and Wales was explained by reductions in admission rates at weekends and the medical disease category.

Conclusions

The effect of weekend admission on 30 day mortality is seen mainly for cancers, some circulatory disorders, liver disease and a few other conditions which are mainly ageing- or cancer-related. Most of the increased mortality is associated with reduced admission rates at weekends and the medical disease category.",,pdf:https://bmchealthservres.biomedcentral.com/counter/pdf/10.1186/s12913-019-4286-8; doi:https://doi.org/10.1186/s12913-019-4286-8; html:https://europepmc.org/articles/PMC6720086; pdf:https://europepmc.org/articles/PMC6720086?pdf=render +35921096,https://doi.org/10.1001/jamacardio.2022.2333,Joint Genetic Inhibition of PCSK9 and CETP and the Association With Coronary Artery Disease: A Factorial Mendelian Randomization Study.,"Cupido AJ, Reeskamp LF, Hingorani AD, Finan C, Asselbergs FW, Hovingh GK, Schmidt AF.",,JAMA cardiology,2022,2022-09-01,N,,,,"

Importance

Cholesteryl ester transfer protein inhibition (CETP) has been shown to increase levels of high-density lipoprotein cholesterol (HDL-C) and reduce levels of low-density lipoprotein cholesterol (LDL-C). Current LDL-C target attainment is low, and novel phase 3 trials are underway to investigate whether CETP inhibitors result in reduction of cardiovascular disease risk in high-risk patients who may be treated with PCSK9-inhibiting agents.

Objective

To explore the associations of combined reduction of CETP and PCSK9 concentrations with risk of coronary artery disease (CAD) and other clinical and safety outcomes.

Design, setting, and participants

Two-sample 2 × 2 factorial Mendelian randomization study in a general population sample that includes data for UK Biobank participants of European ancestry.

Exposures

Separate genetic scores were constructed for CETP and PCSK9 plasma protein concentrations, which were combined to determine the associations of combined genetically reduced CETP and PCSK9 concentrations with disease.

Main outcomes and measures

Blood lipid and lipoprotein concentrations, blood pressure, CAD, age-related macular degeneration, type 2 diabetes, any stroke and ischemic stroke, Alzheimer disease, vascular dementia, heart failure, atrial fibrillation, chronic kidney disease, asthma, and multiple sclerosis.

Results

Data for 425 354 UKB participants were included; the median (IQR) age was 59 years (51-64), and 229 399 (53.9%) were female. The associations of lower CETP and lower PCSK9 concentrations with CAD are similar when scaled per 10-mg/dL reduction in LDL-C concentrations (CETP: odds ratio [OR], 0.74; 95% CI, 0.67 to 0.81; PCSK9: OR, 0.75; 95% CI, 0.71 to 0.79). Combined exposure to lower CETP and PCSK9 concentrations was associated with an additive magnitude with lipids and all outcomes, and we did not observe any nonadditive interactions, most notably for LDL-C (CETP: effect size, -1.11 mg/dL; 95% CI, -1.40 to -0.82; PCSK9: effect size, -2.13 mg/dL; 95% CI, -2.43 to -1.84; combined: effect size, -3.47 mg/dL; 95% CI, -3.76 to -3.18; P = .34 for interaction) and CAD (CETP: OR, 0.96; 95% CI, 0.94 to 1.00; PCSK9: OR, 0.94; 95% CI, 0.91 to 0.97; combined: OR, 0.90; 95% CI, 0.87 to 0.93; P = .83 for interaction). In addition, when corrected for multiple testing, lower CETP concentrations were associated with increased age-related macular degeneration (OR, 1.11; 95% CI, 1.04 to 1.19).

Conclusions and relevance

Our results suggest that joint inhibition of CETP and PCSK9 has additive effects on lipid traits and disease risk, including a lower risk of CAD. Further research may explore whether a combination of CETP- and PCSK9-related therapeutics can benefit high-risk patients who are unable to reach treatment targets with existing options.",,doi:https://doi.org/10.1001/jamacardio.2022.2333; html:https://europepmc.org/articles/PMC9350849; doi:https://doi.org/10.1001/jamacardio.2022.2333 38206619,https://doi.org/10.1093/europace/euad368,Influence of stressful life events and personality traits on PLN cardiomyopathy severity: an exploratory study.,"van Drie E, Taal SEL, Schmidt AF, Verstraelen TE, de Brouwer R, Schoormans D, Mommersteeg PMC, de Boer RA, Wilde AAM, Asselbergs FW, Baas AF, van Tintelen JP, van den Heuvel LM.",,"Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology",2023,2023-12-01,Y,Personality Traits; Stressful Life Events; Phospholamban; Arrhythmogenic Cardiomyopathy; Distressed Personality,,,,,pdf:https://academic.oup.com/europace/article-pdf/26/1/euad368/55443084/euad368.pdf; doi:https://doi.org/10.1093/europace/euad368; html:https://europepmc.org/articles/PMC10783237; pdf:https://europepmc.org/articles/PMC10783237?pdf=render +38528983,https://doi.org/10.3389/fpsyt.2024.1347100,Machine learning in mental health and its relationship with epidemiological practice.,"DelPozo-Banos M, Stewart R, John A.",,Frontiers in psychiatry,2024,2024-03-11,Y,Research methods; Mental health; epidemiology; Machine Learning; Challenges And Opportunities,,,,,pdf:https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2024.1347100/pdf; doi:https://doi.org/10.3389/fpsyt.2024.1347100; html:https://europepmc.org/articles/PMC10961376; pdf:https://europepmc.org/articles/PMC10961376?pdf=render 34435642,https://doi.org/10.1093/eurheartj/ehab350,Evidence to support magnetic resonance conditional labelling of all pacemaker and defibrillator leads in patients with cardiac implantable electronic devices.,"Bhuva AN, Moralee R, Brunker T, Lascelles K, Cash L, Patel KP, Lowe M, Sekhri N, Alpendurada F, Pennell DJ, Schilling R, Lambiase PD, Chow A, Moon JC, Litt H, Baksi AJ, Manisty CH.",,European heart journal,2022,2022-07-01,Y,Pacemaker; Magnetic Resonance Imaging; Defibrillator,,,"

Aims

Many cardiac pacemakers and defibrillators are not approved by regulators for magnetic resonance imaging (MRI). Even following generator exchange to an approved magnetic resonance (MR)-conditional model, many systems remain classified 'non-MR conditional' due to the leads. This classification makes patient access to MRI challenging, but there is no evidence of increased clinical risk. We compared the effect of MRI on non-MR conditional and MR-conditional pacemaker and defibrillator leads.

Methods and results

Patients undergoing clinical 1.5T MRI with pacemakers and defibrillators in three centres over 5 years were included. Magnetic resonance imaging protocols were similar for MR-conditional and non-MR conditional systems. Devices were interrogated pre- and immediately post-scan, and at follow-up, and adverse clinical events recorded. Lead parameter changes peri-scan were stratified by MR-conditional labelling. A total of 1148 MRI examinations were performed in 970 patients (54% non-MR conditional systems, 39% defibrillators, 15% pacing-dependent) with 2268 leads. There were no lead-related adverse clinical events, and no clinically significant immediate or late lead parameter changes following MRI in either MR-conditional or non-MR conditional leads. Small reductions in atrial and right ventricular sensed amplitudes and impedances were similar between groups, with no difference in the proportion of leads with parameter changes greater than pre-defined thresholds (7.1%, 95% confidence interval: 6.1-8.3).

Conclusions

There was no increased risk of MRI in patients with non-MR conditional pacemaker or defibrillator leads when following recommended protocols. Standardizing MR conditions for all leads would significantly improve access to MRI by enabling patients to be scanned in non-specialist centres, with no discernible incremental risk.",,pdf:https://academic.oup.com/eurheartj/advance-article-pdf/doi/10.1093/eurheartj/ehab350/39932149/ehab350.pdf; doi:https://doi.org/10.1093/eurheartj/ehab350; html:https://europepmc.org/articles/PMC9259370; pdf:https://europepmc.org/articles/PMC9259370?pdf=render 34629034,https://doi.org/10.1080/02640414.2021.1928409,Are individual and social factors specific to the home associated with children's behaviour and physical environment at home.,"Sheldrick MPR, Maitland C, Mackintosh KA, Rosenberg M, Griffiths LJ, Fry R, Stratton G.",,Journal of sports sciences,2021,2021-10-09,N,Youth; Family; House; Sedentary Time; Moderate-vigorous Physical Activity,,,"This study used linear regression analyses to investigate the influence of parent-reported home-specific social and individual factors on: (i) 235 children's home-based objectively measured overall sitting time, breaks in sitting, and PA, and; (ii) the home physical environment via an audit. Parental importance assigned to active play for children was positively associated with PA equipment (accessibility and availability), as well as light physical activity (LPA) and sitting breaks on both weekdays and weekend days. Parental preference for being active at home and limits on screen-time were associated with less household media equipment and portable media equipment, respectively. Greater parental importance placed on playing electronic games/using computers for fun was associated with less LPA and more sitting on weekdays. Further, children who preferred being sedentary sat more and engaged in less moderate-vigorous physical activity (MVPA) on weekdays. Parental and child preferences and priorities, as well as parental rules for activity at home, were associated with children's home-based sitting and PA, especially on weekdays. Such factors were also associated with the physical environment in the expected directions. The findings suggest interventions need to target social and individual factors, alongside adapting the physical environment to create homes more promotive of physical activity.",,pdf:https://cronfa.swan.ac.uk/Record/cronfa56833/Download/56833__19829__9b0bb77f67e84342b525fbccaba98e67.pdf; doi:https://doi.org/10.1080/02640414.2021.1928409 34610958,https://doi.org/10.1136/emermed-2019-209368,Association between anticoagulants and mortality and functional outcomes in older patients with major trauma.,"Sato N, Cameron P, Mclellan S, Beck B, Gabbe B.",,Emergency medicine journal : EMJ,2021,2021-10-05,N,Research; Trauma; Geriatrics; Major Trauma Management; Death/mortality,,,"

Background

The number of trauma patients taking anticoagulants and antiplatelet agents is increasing as society ages. However, there have been limited and inconsistent reports of the association between anticoagulants and mortality and functional outcomes. This study aimed to quantify the association between anticoagulant/antiplatelet medication at the time of injury and both short-term and longer-term outcomes in older major trauma patients.

Methods

This was a population-based registry study using data from the Victorian State Trauma Registry from July 2017 to June 2018. We included patients with major trauma aged 65 years and older. The outcomes of interest were in-hospital mortality, hospital length of stay, intensive care unit length of stay and the Extended Glasgow Outcome Scale (GOS-E) at 6 months after injury. We examined the association between the outcomes and anticoagulants/antiplatelet agents at the time of injury and used multivariable logistic regression models to account for known confounders.

Results

There were 1323 older adults eligible for inclusion in the study, of which 249 (18.8%) were taking anticoagulants (n=8 were taking both anticoagulants and antiplatelet agents), 380 (28.7%) were taking antiplatelet agents and 694 (52.5%) were not using either. Any anticoagulant use was associated with higher odds of in-hospital mortality (adjusted OR (AOR), 2.38; 95% CI 1.58 to 3.59) compared with not using anticoagulants. No differences were observed in the GOS-E at 6 months after injury between any anticoagulants use, antiplatelet use and no anticoagulant use (anticoagulant AOR, 0.71; 95% CI 0.48 to 1.05, antiplatelet AOR, 1.02; 95% CI 0.73 to 1.42).

Conclusion

Anticoagulant use at the time of injury was associated with higher odds of in-hospital mortality but did not adversely impact functional outcomes at 6 months after injury. These findings demonstrate the importance of seeking an accurate history of anticoagulant use and its indication, as well as the immediate initiation of reversal therapies.",,doi:https://doi.org/10.1136/emermed-2019-209368 -35896705,https://doi.org/10.1038/s41598-022-16639-9,Estimation of biological heart age using cardiovascular magnetic resonance radiomics.,"Raisi-Estabragh Z, Salih A, Gkontra P, Atehortúa A, Radeva P, Boscolo Galazzo I, Menegaz G, Harvey NC, Lekadir K, Petersen SE.",,Scientific reports,2022,2022-07-27,Y,,,,"We developed a novel interpretable biological heart age estimation model using cardiovascular magnetic resonance radiomics measures of ventricular shape and myocardial character. We included 29,996 UK Biobank participants without cardiovascular disease. Images were segmented using an automated analysis pipeline. We extracted 254 radiomics features from the left ventricle, right ventricle, and myocardium of each study. We then used Bayesian ridge regression with tenfold cross-validation to develop a heart age estimation model using the radiomics features as the model input and chronological age as the model output. We examined associations of radiomics features with heart age in men and women, observing sex-differential patterns. We subtracted actual age from model estimated heart age to calculate a ""heart age delta"", which we considered as a measure of heart aging. We performed a phenome-wide association study of 701 exposures with heart age delta. The strongest correlates of heart aging were measures of obesity, adverse serum lipid markers, hypertension, diabetes, heart rate, income, multimorbidity, musculoskeletal health, and respiratory health. This technique provides a new method for phenotypic assessment relating to cardiovascular aging; further studies are required to assess whether it provides incremental risk information over current approaches.",,pdf:https://www.nature.com/articles/s41598-022-16639-9.pdf; doi:https://doi.org/10.1038/s41598-022-16639-9; html:https://europepmc.org/articles/PMC9329281; pdf:https://europepmc.org/articles/PMC9329281?pdf=render 34427560,https://doi.org/10.1684/ejd.2021.4108,"The association between immunosuppression and skin cancer in solid organ transplant recipients: a control-matched cohort study of 2,852 patients.","Gibson JAG, Cordaro A, Dobbs TD, Griffiths R, Akbari A, Whitaker S, Hutchings HA, Lyons RA, Whitaker IS.",,European journal of dermatology : EJD,2021,2021-12-01,N,Transplant; Oncology; immunosuppression; Skin Cancer,,,"Skin cancer is more common in transplant recipients, although the quoted incidence is variable. This study investigated the incidence of skin cancer in solid organ transplant recipients (OTRs) in a national cohort and the effect of pharmacotherapeutic agents Transplant patients were identified from Patient Episode Database for Wales (PEDW) using Office of Population Census and Surveys Classifications of Interventions and Procedures-4 (OPCS-4) codes. Controls were matched to cases according to age, sex and socioeconomic status. Skin cancer data were obtained from linkage with other national data sources. Incidence was calculated per 100,000 person-years at risk (PYAR). Negative binomial regression was used to calculate adjusted incidence rate ratios (IRRs) for each organ type. During 2000-2018, 2,852 Welsh patients underwent solid organ transplantation. A total of 13,527 controls were matched from the general population. The incidence of skin cancer within the OTR cohort was 1203.2 per 100,000 PYAR vs 133.9 in the matched control group. Age, male gender and azathioprine use were all associated with an increased risk of skin cancer. Contemporary immunomodulators such as tacrolimus and mycophenolate were associated with a reduction in skin cancer risk when compared to their predecessors, cyclosporin and azathioprine. The highest adjusted IRR was observed in heart transplant recipients (IRR: 10.82; 95% CI: 3.64-32.19) and the lowest in liver transplant recipients (IRR: 2.86; 95% CI: 1.15-7.13). This study highlights the need for long-term routine skin cancer surveillance for all OTRs and the importance of using contemporary immunomodulators, when possible, for risk reduction.",,doi:https://doi.org/10.1684/ejd.2021.4108 +35896705,https://doi.org/10.1038/s41598-022-16639-9,Estimation of biological heart age using cardiovascular magnetic resonance radiomics.,"Raisi-Estabragh Z, Salih A, Gkontra P, Atehortúa A, Radeva P, Boscolo Galazzo I, Menegaz G, Harvey NC, Lekadir K, Petersen SE.",,Scientific reports,2022,2022-07-27,Y,,,,"We developed a novel interpretable biological heart age estimation model using cardiovascular magnetic resonance radiomics measures of ventricular shape and myocardial character. We included 29,996 UK Biobank participants without cardiovascular disease. Images were segmented using an automated analysis pipeline. We extracted 254 radiomics features from the left ventricle, right ventricle, and myocardium of each study. We then used Bayesian ridge regression with tenfold cross-validation to develop a heart age estimation model using the radiomics features as the model input and chronological age as the model output. We examined associations of radiomics features with heart age in men and women, observing sex-differential patterns. We subtracted actual age from model estimated heart age to calculate a ""heart age delta"", which we considered as a measure of heart aging. We performed a phenome-wide association study of 701 exposures with heart age delta. The strongest correlates of heart aging were measures of obesity, adverse serum lipid markers, hypertension, diabetes, heart rate, income, multimorbidity, musculoskeletal health, and respiratory health. This technique provides a new method for phenotypic assessment relating to cardiovascular aging; further studies are required to assess whether it provides incremental risk information over current approaches.",,pdf:https://www.nature.com/articles/s41598-022-16639-9.pdf; doi:https://doi.org/10.1038/s41598-022-16639-9; html:https://europepmc.org/articles/PMC9329281; pdf:https://europepmc.org/articles/PMC9329281?pdf=render 34939031,https://doi.org/10.1093/braincomms/fcab241,Degeneration of basal and limbic networks is a core feature of behavioural variant frontotemporal dementia.,"Vuksanović V, Staff RT, Morson S, Ahearn T, Bracoud L, Murray AD, Bentham P, Kipps CM, Harrington CR, Wischik CM.",,Brain communications,2021,2021-10-21,Y,Neurodegeneration; Brain Networks; Behavioural Variant Frontotemporal Dementia; Rich Club; Anatomical Subtypes,,,"The behavioural variant of frontotemporal dementia is a clinical syndrome characterized by changes in behaviour, cognition and functional ability. Although atrophy in frontal and temporal regions would appear to be a defining feature, neuroimaging studies have identified volumetric differences distributed across large parts of the cortex, giving rise to a classification into distinct neuroanatomical subtypes. Here, we extended these neuroimaging studies to examine how distributed patterns of cortical atrophy map onto brain network hubs. We used baseline structural magnetic resonance imaging data collected from 213 behavioural variant of frontotemporal dementia patients meeting consensus diagnostic criteria and having definite evidence of frontal and/or temporal lobe atrophy from a global clinical trial conducted in 70 sites in Canada, United States of America, Australia, Asia and Europe. These were compared with data from 244 healthy elderly subjects from a well-characterized cohort study. We have used statistical methods of hierarchical agglomerative clustering of 68 regional cortical and subcortical volumes (34 in each hemisphere) to determine the reproducibility of previously described neuroanatomical subtypes in a global study. We have also attempted to link the structural findings to clinical features defined systematically using well-validated clinical scales (Addenbrooke's Cognitive Examination Revised, the Mini-Mental Status Examination, the Frontotemporal Dementia Rating Scale and the Functional Assessment Questionnaire) and subscales derived from them. Whilst we can confirm that the subtypes are robust, they have limited value in explaining the clinical heterogeneity of the syndrome. We have found that a common pattern of degeneration affecting a small number of subcortical, limbic and frontal nodes within highly connected networks (most previously identified as rich club members or functional binding nodes) is shared by all the anatomical subtypes. Degeneration in these core regions is correlated with cognitive and functional impairment, but less so with behavioural impairment. These findings suggest that degeneration in highly connected basal, limbic and frontal networks is a core feature of the behavioural variant of frontotemporal dementia phenotype irrespective of neuroanatomical and clinical heterogeneity, and may underly the impairment of integration in cognition, function and behaviour responsible for the loss of insight that characterizes the syndrome.",,pdf:https://academic.oup.com/braincomms/article-pdf/3/4/fcab241/41829863/fcab241.pdf; doi:https://doi.org/10.1093/braincomms/fcab241; html:https://europepmc.org/articles/PMC8688778; pdf:https://europepmc.org/articles/PMC8688778?pdf=render +31748543,https://doi.org/10.1038/s41398-019-0613-4,Identification of novel common variants associated with chronic pain using conditional false discovery rate analysis with major depressive disorder and assessment of pleiotropic effects of LRFN5.,"Johnston KJA, Adams MJ, Nicholl BI, Ward J, Strawbridge RJ, McIntosh AM, Smith DJ, Bailey MES.",,Translational psychiatry,2019,2019-11-20,Y,,Understanding the Causes of Disease,,"Chronic pain is a complex trait that is moderately heritable and genetically, as well as phenotypically, correlated with major depressive disorder (MDD). Use of the conditional false discovery rate (cFDR) approach, which leverages pleiotropy identified from existing GWAS outputs, has been successful in discovering novel associated variants in related phenotypes. Here, genome-wide association study outputs for both von Korff chronic pain grade and for MDD were used to identify variants meeting a cFDR threshold for each outcome phenotype separately, as well as a conjunctional cFDR (ccFDR) threshold for both phenotypes together. Using a moderately conservative threshold, we identified a total of 11 novel single nucleotide polymorphisms (SNPs), six of which were associated with chronic pain grade and nine of which were associated with MDD. Four SNPs on chromosome 14 were associated with both chronic pain grade and MDD. SNPs associated only with chronic pain grade were located within SLC16A7 on chromosome 12. SNPs associated only with MDD were located either in a gene-dense region on chromosome 1 harbouring LINC01360, LRRIQ3, FPGT and FPGT-TNNI3K, or within/close to LRFN5 on chromosome 14. The SNPs associated with both outcomes were also located within LRFN5. Several of the SNPs on chromosomes 1 and 14 were identified as being associated with expression levels of nearby genes in the brain and central nervous system. Overall, using the cFDR approach, we identified several novel genetic loci associated with chronic pain and we describe likely pleiotropic effects of a recently identified MDD locus on chronic pain.","This study aimed to identify parts of the genome that cause chronic pain (self-reported as lasting 3+ months), or major depressive disorder (MDD) and to investigate if these two conditions share common genetic causes. They identified 11 different parts of the genome where a specific change (SNP) was linked to chronic pain (6 parts of the genome), MDD (9 parts), or symptoms shared by both conditions (4 parts). The results also suggest that one of parts of the genome that causes chronic pain may influence the development of MDD (but not vice versa), including through lifestyle factors.",pdf:https://www.nature.com/articles/s41398-019-0613-4.pdf; doi:https://doi.org/10.1038/s41398-019-0613-4; html:https://europepmc.org/articles/PMC6868167; pdf:https://europepmc.org/articles/PMC6868167?pdf=render 38784722,https://doi.org/10.1093/jbmrpl/ziae058,"Bone health, cardiovascular disease, and imaging outcomes in UK Biobank: a causal analysis.","Condurache DG, D'Angelo S, Salih AM, Szabo L, McCracken C, Mahmood A, Curtis EM, Altmann A, Petersen SE, Harvey NC, Raisi-Estabragh Z.",,JBMR plus,2024,2024-04-25,Y,Cardiovascular diseases; Osteoporosis; BMD; Bone Health; Cardiovascular Magnetic Resonance; Mendelian Randomization; Cardiovascular Imaging; Heel Ultrasound,,,"This study examined the association of estimated heel bone mineral density (eBMD, derived from quantitative ultrasound) with: (1) prevalent and incident cardiovascular diseases (CVDs: ischemic heart disease (IHD), myocardial infarction (MI), heart failure (HF), non-ischemic cardiomyopathy (NICM), arrhythmia), (2) mortality (all-cause, CVD, IHD), and (3) cardiovascular magnetic resonance (CMR) measures of left ventricular and atrial structure and function and aortic distensibility, in the UK Biobank. Clinical outcomes were ascertained using health record linkage over 12.3 yr of prospective follow-up. Two-sample Mendelian randomization (MR) was conducted to assess causal associations between BMD and CMR metrics using genetic instrumental variables identified from published genome-wide association studies. The analysis included 485 257 participants (55% women, mean age 56.5 ± 8.1 yr). Higher heel eBMD was associated with lower odds of all prevalent CVDs considered. The greatest magnitude of effect was seen in association with HF and NICM, where 1-SD increase in eBMD was associated with 15% lower odds of HF and 16% lower odds of NICM. Association between eBMD and incident IHD and MI was non-significant; the strongest relationship was with incident HF (SHR: 0.90 [95% CI, 0.89-0.92]). Higher eBMD was associated with a decreased risk in all-cause, CVD, and IHD mortality, in the fully adjusted model. Higher eBMD was associated with greater aortic distensibility; associations with other CMR metrics were null. Higher heel eBMD is linked to reduced risk of a range of prevalent and incident CVD and mortality outcomes. Although observational analyses suggest associations between higher eBMD and greater aortic compliance, MR analysis did not support a causal relationship between genetically predicted BMD and CMR phenotypes. These findings support the notion that bone-cardiovascular associations reflect shared risk factors/mechanisms rather than direct causal pathways.",,doi:https://doi.org/10.1093/jbmrpl/ziae058; html:https://europepmc.org/articles/PMC11114472; pdf:https://europepmc.org/articles/PMC11114472?pdf=render 37218687,https://doi.org/10.1093/ehjqcco/qcad029,Sex-based differences in risk factors for incident myocardial infarction and stroke in the UK Biobank.,"Remfry E, Ardissino M, McCracken C, Szabo L, Neubauer S, Harvey NC, Mamas MA, Robson J, Petersen SE, Raisi-Estabragh Z.",,European heart journal. Quality of care & clinical outcomes,2024,2024-03-01,Y,Myocardial infarction; Stroke; Sex differences; risk factors,,,"

Aim

This study examined sex-based differences in associations of vascular risk factors with incident cardiovascular events in the UK Biobank.

Methods

Baseline participant demographic, clinical, laboratory, anthropometric, and imaging characteristics were collected. Multivariable Cox regression was used to estimate independent associations of vascular risk factors with incident myocardial infarction (MI) and ischaemic stroke for men and women. Women-to-men ratios of hazard ratios (RHRs), and related 95% confidence intervals, represent the relative effect-size magnitude by sex.

Results

Among the 363 313 participants (53.5% women), 8470 experienced MI (29.9% women) and 7705 experienced stroke (40.1% women) over 12.66 [11.93, 13.38] years of prospective follow-up. Men had greater risk factor burden and higher arterial stiffness index at baseline. Women had greater age-related decline in aortic distensibility. Older age [RHR: 1.02 (1.01-1.03)], greater deprivation [RHR: 1.02 (1.00-1.03)], hypertension [RHR: 1.14 (1.02-1.27)], and current smoking [RHR: 1.45 (1.27-1.66)] were associated with a greater excess risk of MI in women than men. Low-density lipoprotein cholesterol was associated with excess MI risk in men [RHR: 0.90 (0.84-0.95)] and apolipoprotein A (ApoA) was less protective for MI in women [RHR: 1.65 (1.01-2.71)]. Older age was associated with excess risk of stroke [RHR: 1.01 (1.00-1.02)] and ApoA was less protective for stroke in women [RHR: 2.55 (1.58-4.14)].

Conclusion

Older age, hypertension, and smoking appeared stronger drivers of cardiovascular disease in women, whereas lipid metrics appeared stronger risk determinants for men. These findings highlight the importance of sex-specific preventive strategies and suggest priority targets for intervention in men and women.",,pdf:https://academic.oup.com/ehjqcco/advance-article-pdf/doi/10.1093/ehjqcco/qcad029/50422842/qcad029.pdf; doi:https://doi.org/10.1093/ehjqcco/qcad029; html:https://europepmc.org/articles/PMC10904726; pdf:https://europepmc.org/articles/PMC10904726?pdf=render -31748543,https://doi.org/10.1038/s41398-019-0613-4,Identification of novel common variants associated with chronic pain using conditional false discovery rate analysis with major depressive disorder and assessment of pleiotropic effects of LRFN5.,"Johnston KJA, Adams MJ, Nicholl BI, Ward J, Strawbridge RJ, McIntosh AM, Smith DJ, Bailey MES.",,Translational psychiatry,2019,2019-11-20,Y,,Understanding the Causes of Disease,,"Chronic pain is a complex trait that is moderately heritable and genetically, as well as phenotypically, correlated with major depressive disorder (MDD). Use of the conditional false discovery rate (cFDR) approach, which leverages pleiotropy identified from existing GWAS outputs, has been successful in discovering novel associated variants in related phenotypes. Here, genome-wide association study outputs for both von Korff chronic pain grade and for MDD were used to identify variants meeting a cFDR threshold for each outcome phenotype separately, as well as a conjunctional cFDR (ccFDR) threshold for both phenotypes together. Using a moderately conservative threshold, we identified a total of 11 novel single nucleotide polymorphisms (SNPs), six of which were associated with chronic pain grade and nine of which were associated with MDD. Four SNPs on chromosome 14 were associated with both chronic pain grade and MDD. SNPs associated only with chronic pain grade were located within SLC16A7 on chromosome 12. SNPs associated only with MDD were located either in a gene-dense region on chromosome 1 harbouring LINC01360, LRRIQ3, FPGT and FPGT-TNNI3K, or within/close to LRFN5 on chromosome 14. The SNPs associated with both outcomes were also located within LRFN5. Several of the SNPs on chromosomes 1 and 14 were identified as being associated with expression levels of nearby genes in the brain and central nervous system. Overall, using the cFDR approach, we identified several novel genetic loci associated with chronic pain and we describe likely pleiotropic effects of a recently identified MDD locus on chronic pain.","This study aimed to identify parts of the genome that cause chronic pain (self-reported as lasting 3+ months), or major depressive disorder (MDD) and to investigate if these two conditions share common genetic causes. They identified 11 different parts of the genome where a specific change (SNP) was linked to chronic pain (6 parts of the genome), MDD (9 parts), or symptoms shared by both conditions (4 parts). The results also suggest that one of parts of the genome that causes chronic pain may influence the development of MDD (but not vice versa), including through lifestyle factors.",pdf:https://www.nature.com/articles/s41398-019-0613-4.pdf; doi:https://doi.org/10.1038/s41398-019-0613-4; html:https://europepmc.org/articles/PMC6868167; pdf:https://europepmc.org/articles/PMC6868167?pdf=render 37563310,https://doi.org/10.1038/s41590-023-01588-w,Genetics of circulating inflammatory proteins identifies drivers of immune-mediated disease risk and therapeutic targets.,"Zhao JH, Stacey D, Eriksson N, Macdonald-Dunlop E, Hedman ÅK, Kalnapenkis A, Enroth S, Cozzetto D, Digby-Bell J, Marten J, Folkersen L, Herder C, Jonsson L, Bergen SE, Gieger C, Needham EJ, Surendran P, Estonian Biobank Research Team, Paul DS, Polasek O, Thorand B, Grallert H, Roden M, Võsa U, Esko T, Hayward C, Johansson Å, Gyllensten U, Powell N, Hansson O, Mattsson-Carlgren N, Joshi PK, Danesh J, Padyukov L, Klareskog L, Landén M, Wilson JF, Siegbahn A, Wallentin L, Mälarstig A, Butterworth AS, Peters JE.",,Nature immunology,2023,2023-08-10,Y,,,,"Circulating proteins have important functions in inflammation and a broad range of diseases. To identify genetic influences on inflammation-related proteins, we conducted a genome-wide protein quantitative trait locus (pQTL) study of 91 plasma proteins measured using the Olink Target platform in 14,824 participants. We identified 180 pQTLs (59 cis, 121 trans). Integration of pQTL data with eQTL and disease genome-wide association studies provided insight into pathogenesis, implicating lymphotoxin-α in multiple sclerosis. Using Mendelian randomization (MR) to assess causality in disease etiology, we identified both shared and distinct effects of specific proteins across immune-mediated diseases, including directionally discordant effects of CD40 on risk of rheumatoid arthritis versus multiple sclerosis and inflammatory bowel disease. MR implicated CXCL5 in the etiology of ulcerative colitis (UC) and we show elevated gut CXCL5 transcript expression in patients with UC. These results identify targets of existing drugs and provide a powerful resource to facilitate future drug target prioritization.",,pdf:https://www.nature.com/articles/s41590-023-01588-w.pdf; doi:https://doi.org/10.1038/s41590-023-01588-w; html:https://europepmc.org/articles/PMC10457199; pdf:https://europepmc.org/articles/PMC10457199?pdf=render 33820530,https://doi.org/10.1186/s12916-021-01940-7,"Machine learning for subtype definition and risk prediction in heart failure, acute coronary syndromes and atrial fibrillation: systematic review of validity and clinical utility.","Banerjee A, Chen S, Fatemifar G, Zeina M, Lumbers RT, Mielke J, Gill S, Kotecha D, Freitag DF, Denaxas S, Hemingway H.",,BMC medicine,2021,2021-04-06,Y,Subtype; Cardiovascular disease; Systematic review; Machine Learning; Informatics; Risk Prediction,,,"

Background

Machine learning (ML) is increasingly used in research for subtype definition and risk prediction, particularly in cardiovascular diseases. No existing ML models are routinely used for cardiovascular disease management, and their phase of clinical utility is unknown, partly due to a lack of clear criteria. We evaluated ML for subtype definition and risk prediction in heart failure (HF), acute coronary syndromes (ACS) and atrial fibrillation (AF).

Methods

For ML studies of subtype definition and risk prediction, we conducted a systematic review in HF, ACS and AF, using PubMed, MEDLINE and Web of Science from January 2000 until December 2019. By adapting published criteria for diagnostic and prognostic studies, we developed a seven-domain, ML-specific checklist.

Results

Of 5918 studies identified, 97 were included. Across studies for subtype definition (n = 40) and risk prediction (n = 57), there was variation in data source, population size (median 606 and median 6769), clinical setting (outpatient, inpatient, different departments), number of covariates (median 19 and median 48) and ML methods. All studies were single disease, most were North American (n = 61/97) and only 14 studies combined definition and risk prediction. Subtype definition and risk prediction studies respectively had limitations in development (e.g. 15.0% and 78.9% of studies related to patient benefit; 15.0% and 15.8% had low patient selection bias), validation (12.5% and 5.3% externally validated) and impact (32.5% and 91.2% improved outcome prediction; no effectiveness or cost-effectiveness evaluations).

Conclusions

Studies of ML in HF, ACS and AF are limited by number and type of included covariates, ML methods, population size, country, clinical setting and focus on single diseases, not overlap or multimorbidity. Clinical utility and implementation rely on improvements in development, validation and impact, facilitated by simple checklists. We provide clear steps prior to safe implementation of machine learning in clinical practice for cardiovascular diseases and other disease areas.",,pdf:https://bmcmedicine.biomedcentral.com/track/pdf/10.1186/s12916-021-01940-7; doi:https://doi.org/10.1186/s12916-021-01940-7; html:https://europepmc.org/articles/PMC8022365; pdf:https://europepmc.org/articles/PMC8022365?pdf=render -37986130,https://doi.org/10.1186/s41512-023-00159-9,An external validation of the Kidney Donor Risk Index in the UK transplant population in the presence of semi-competing events.,"Riley S, Tam K, Tse WY, Connor A, Wei Y.",,Diagnostic and prognostic research,2023,2023-11-21,Y,Survival analysis; Kidney transplantation; Risk Prediction; External Validation; Time-to-event Model; Competing Events,,,"

Background

Transplantation represents the optimal treatment for many patients with end-stage kidney disease. When a donor kidney is available to a waitlisted patient, clinicians responsible for the care of the potential recipient must make the decision to accept or decline the offer based upon complex and variable information about the donor, the recipient and the transplant process. A clinical prediction model may be able to support clinicians in their decision-making. The Kidney Donor Risk Index (KDRI) was developed in the United States to predict graft failure following kidney transplantation. The survival process following transplantation consists of semi-competing events where death precludes graft failure, but not vice-versa.

Methods

We externally validated the KDRI in the UK kidney transplant population and assessed whether validation under a semi-competing risks framework impacted predictive performance. Additionally, we explored whether the KDRI requires updating. We included 20,035 adult recipients of first, deceased donor, single, kidney-only transplants between January 1, 2004, and December 31, 2018, collected by the UK Transplant Registry and held by NHS Blood and Transplant. The outcomes of interest were 1- and 5-year graft failure following transplantation. In light of the semi-competing events, recipient death was handled in two ways: censoring patients at the time of death and modelling death as a competing event. Cox proportional hazard models were used to validate the KDRI when censoring graft failure by death, and cause-specific Cox models were used to account for death as a competing event.

Results

The KDRI underestimated event probabilities for those at higher risk of graft failure. For 5-year graft failure, discrimination was poorer in the semi-competing risks model (0.625, 95% CI 0.611 to 0.640;0.611, 95% CI 0.597 to 0.625), but predictions were more accurate (Brier score 0.117, 95% CI 0.112 to 0.121; 0.114, 95% CI 0.109 to 0.118). Calibration plots were similar regardless of whether the death was modelled as a competing event or not. Updating the KDRI worsened calibration, but marginally improved discrimination.

Conclusions

Predictive performance for 1-year graft failure was similar between death-censored and competing event graft failure, but differences appeared when predicting 5-year graft failure. The updated index did not have superior performance and we conclude that updating the KDRI in the present form is not required.",,doi:https://doi.org/10.1186/s41512-023-00159-9; html:https://europepmc.org/articles/PMC10662562; pdf:https://europepmc.org/articles/PMC10662562?pdf=render 32908284,https://doi.org/10.1038/s41591-020-1037-7,Guidelines for clinical trial protocols for interventions involving artificial intelligence: the SPIRIT-AI extension.,"Cruz Rivera S, Liu X, Chan AW, Denniston AK, Calvert MJ, SPIRIT-AI and CONSORT-AI Working Group, SPIRIT-AI and CONSORT-AI Steering Group, SPIRIT-AI and CONSORT-AI Consensus Group.",,Nature medicine,2020,2020-09-09,Y,,,,"The SPIRIT 2013 statement aims to improve the completeness of clinical trial protocol reporting by providing evidence-based recommendations for the minimum set of items to be addressed. This guidance has been instrumental in promoting transparent evaluation of new interventions. More recently, there has been a growing recognition that interventions involving artificial intelligence (AI) need to undergo rigorous, prospective evaluation to demonstrate their impact on health outcomes. The SPIRIT-AI (Standard Protocol Items: Recommendations for Interventional Trials-Artificial Intelligence) extension is a new reporting guideline for clinical trial protocols evaluating interventions with an AI component. It was developed in parallel with its companion statement for trial reports: CONSORT-AI (Consolidated Standards of Reporting Trials-Artificial Intelligence). Both guidelines were developed through a staged consensus process involving literature review and expert consultation to generate 26 candidate items, which were consulted upon by an international multi-stakeholder group in a two-stage Delphi survey (103 stakeholders), agreed upon in a consensus meeting (31 stakeholders) and refined through a checklist pilot (34 participants). The SPIRIT-AI extension includes 15 new items that were considered sufficiently important for clinical trial protocols of AI interventions. These new items should be routinely reported in addition to the core SPIRIT 2013 items. SPIRIT-AI recommends that investigators provide clear descriptions of the AI intervention, including instructions and skills required for use, the setting in which the AI intervention will be integrated, considerations for the handling of input and output data, the human-AI interaction and analysis of error cases. SPIRIT-AI will help promote transparency and completeness for clinical trial protocols for AI interventions. Its use will assist editors and peer reviewers, as well as the general readership, to understand, interpret and critically appraise the design and risk of bias for a planned clinical trial.",,pdf:https://www.nature.com/articles/s41591-020-1037-7.pdf; doi:https://doi.org/10.1038/s41591-020-1037-7; html:https://europepmc.org/articles/PMC7598944; pdf:https://europepmc.org/articles/PMC7598944?pdf=render +37986130,https://doi.org/10.1186/s41512-023-00159-9,An external validation of the Kidney Donor Risk Index in the UK transplant population in the presence of semi-competing events.,"Riley S, Tam K, Tse WY, Connor A, Wei Y.",,Diagnostic and prognostic research,2023,2023-11-21,Y,Survival analysis; Kidney transplantation; Risk Prediction; External Validation; Time-to-event Model; Competing Events,,,"

Background

Transplantation represents the optimal treatment for many patients with end-stage kidney disease. When a donor kidney is available to a waitlisted patient, clinicians responsible for the care of the potential recipient must make the decision to accept or decline the offer based upon complex and variable information about the donor, the recipient and the transplant process. A clinical prediction model may be able to support clinicians in their decision-making. The Kidney Donor Risk Index (KDRI) was developed in the United States to predict graft failure following kidney transplantation. The survival process following transplantation consists of semi-competing events where death precludes graft failure, but not vice-versa.

Methods

We externally validated the KDRI in the UK kidney transplant population and assessed whether validation under a semi-competing risks framework impacted predictive performance. Additionally, we explored whether the KDRI requires updating. We included 20,035 adult recipients of first, deceased donor, single, kidney-only transplants between January 1, 2004, and December 31, 2018, collected by the UK Transplant Registry and held by NHS Blood and Transplant. The outcomes of interest were 1- and 5-year graft failure following transplantation. In light of the semi-competing events, recipient death was handled in two ways: censoring patients at the time of death and modelling death as a competing event. Cox proportional hazard models were used to validate the KDRI when censoring graft failure by death, and cause-specific Cox models were used to account for death as a competing event.

Results

The KDRI underestimated event probabilities for those at higher risk of graft failure. For 5-year graft failure, discrimination was poorer in the semi-competing risks model (0.625, 95% CI 0.611 to 0.640;0.611, 95% CI 0.597 to 0.625), but predictions were more accurate (Brier score 0.117, 95% CI 0.112 to 0.121; 0.114, 95% CI 0.109 to 0.118). Calibration plots were similar regardless of whether the death was modelled as a competing event or not. Updating the KDRI worsened calibration, but marginally improved discrimination.

Conclusions

Predictive performance for 1-year graft failure was similar between death-censored and competing event graft failure, but differences appeared when predicting 5-year graft failure. The updated index did not have superior performance and we conclude that updating the KDRI in the present form is not required.",,doi:https://doi.org/10.1186/s41512-023-00159-9; html:https://europepmc.org/articles/PMC10662562; pdf:https://europepmc.org/articles/PMC10662562?pdf=render 32908283,https://doi.org/10.1038/s41591-020-1034-x,Reporting guidelines for clinical trial reports for interventions involving artificial intelligence: the CONSORT-AI extension.,"Liu X, Cruz Rivera S, Moher D, Calvert MJ, Denniston AK, SPIRIT-AI and CONSORT-AI Working Group.",,Nature medicine,2020,2020-09-09,Y,,,,"The CONSORT 2010 statement provides minimum guidelines for reporting randomized trials. Its widespread use has been instrumental in ensuring transparency in the evaluation of new interventions. More recently, there has been a growing recognition that interventions involving artificial intelligence (AI) need to undergo rigorous, prospective evaluation to demonstrate impact on health outcomes. The CONSORT-AI (Consolidated Standards of Reporting Trials-Artificial Intelligence) extension is a new reporting guideline for clinical trials evaluating interventions with an AI component. It was developed in parallel with its companion statement for clinical trial protocols: SPIRIT-AI (Standard Protocol Items: Recommendations for Interventional Trials-Artificial Intelligence). Both guidelines were developed through a staged consensus process involving literature review and expert consultation to generate 29 candidate items, which were assessed by an international multi-stakeholder group in a two-stage Delphi survey (103 stakeholders), agreed upon in a two-day consensus meeting (31 stakeholders) and refined through a checklist pilot (34 participants). The CONSORT-AI extension includes 14 new items that were considered sufficiently important for AI interventions that they should be routinely reported in addition to the core CONSORT 2010 items. CONSORT-AI recommends that investigators provide clear descriptions of the AI intervention, including instructions and skills required for use, the setting in which the AI intervention is integrated, the handling of inputs and outputs of the AI intervention, the human-AI interaction and provision of an analysis of error cases. CONSORT-AI will help promote transparency and completeness in reporting clinical trials for AI interventions. It will assist editors and peer reviewers, as well as the general readership, to understand, interpret and critically appraise the quality of clinical trial design and risk of bias in the reported outcomes.",,pdf:https://www.nature.com/articles/s41591-020-1034-x.pdf; doi:https://doi.org/10.1038/s41591-020-1034-x; html:https://europepmc.org/articles/PMC7598943; pdf:https://europepmc.org/articles/PMC7598943?pdf=render 37143831,https://doi.org/10.1183/23120541.00591-2022,Ethnic variation in asthma healthcare utilisation and exacerbation: systematic review and meta-analysis.,"Akin-Imran A, Bajpai A, McCartan D, Heaney LG, Kee F, Redmond C, Busby J.",,ERJ open research,2023,2023-05-02,Y,,,,"

Background

Patients from ethnic minority groups (EMGs) frequently report poorer asthma outcomes; however, a broad synthesis summarising ethnic disparities is yet to be undertaken. What is the magnitude of ethnic disparities in asthma healthcare utilisation, exacerbations and mortality?

Methods

MEDLINE, Embase and Web of Science databases were searched for studies reporting ethnic variation in asthma healthcare outcomes (primary care attendance, exacerbation, emergency department (ED) visits, hospitalisation, hospital readmission, ventilation/intubation and mortality) between White patients and those from EMGs. Estimates were displayed using forest plots and random-effects models were used to calculate pooled estimates. We conducted subgroup analyses to explore heterogeneity, including by specific ethnicity (Black, Hispanic, Asian and other).

Results

65 studies, comprising 699 882 patients, were included. Most studies (92.3%) were conducted in the United States of America (USA). Patients from EMGs had evidence suggestive of lower levels of primary care attendance (OR 0.72, 95% CI 0.48-1.09), but substantially higher ED visits (OR 1.74, 95% CI 1.53-1.98), hospitalisations (OR 1.63, 95% CI 1.48-1.79) and ventilation/intubation (OR 2.67, 95% CI 1.65-4.31) when compared to White patients. In addition, we found evidence suggestive of increased hospital readmissions (OR 1.19, 95% CI 0.90-1.57) and exacerbation rates (OR 1.10, 95% CI 0.94-1.28) among EMGs. No eligible studies explored disparities in mortality. ED visits were much higher among Black and Hispanic patients, while Asian and other ethnicities had similar rates to White patients.

Conclusions

EMGs had higher secondary care utilisation and exacerbations. Despite the global importance of this issue, the majority of studies were performed in the USA. Further research into the causes of these disparities, including whether these vary by specific ethnicity, is required to aid the design of effective interventions.",,pdf:https://openres.ersjournals.com/content/erjor/early/2023/02/16/23120541.00591-2022.full.pdf; doi:https://doi.org/10.1183/23120541.00591-2022; html:https://europepmc.org/articles/PMC10152257; pdf:https://europepmc.org/articles/PMC10152257?pdf=render -37200150,https://doi.org/10.1210/clinem/dgad276,Preconception Management of Hyperthyroidism and Thyroid Status in Subsequent Pregnancy: A Population-Based Cohort Study.,"Minassian C, Allen LA, Okosieme O, Vaidya B, Taylor P.",,The Journal of clinical endocrinology and metabolism,2023,2023-10-01,Y,Pregnancy; Thyroxine; Hyperthyroidism; Thyroid stimulating hormone; TSH; Thyroid function; Ft3; Ft4; Carbimazole; Tri-iodothyronine; Ptu; Cprd,,,"

Context

Optimal thyroid status in pregnancy is essential in reducing the risk of adverse outcomes. The management of hyperthyroidism in women of reproductive age poses unique challenges and it is unclear how preconception treatment strategies impact on thyroid status in subsequent pregnancy.

Objective

We aimed to determine trends in the management of hyperthyroidism before and during pregnancy and to assess the impact of different preconception treatment strategies on maternal thyroid status.

Methods

We utilized the Clinical Practice Research Datalink database to evaluate all females aged 15-45 years with a clinical diagnosis of hyperthyroidism and a subsequent pregnancy (January 2000 to December 2017). We compared thyroid status in pregnancy according to preconception treatment, namely, (1) antithyroid drugs up to or beyond pregnancy onset, (2) definitive treatment with thyroidectomy or radioiodine before pregnancy, and (3) no treatment at pregnancy onset.

Results

Our study cohort comprised 4712 pregnancies. Thyrotropin (TSH) was measured in only 53.1% of pregnancies, of which 28.1% showed suboptimal thyroid status (TSH >4.0 mU/L or TSH <0.1 mU/L plus FT4 >reference range). Pregnancies with prior definitive treatment were more likely to have suboptimal thyroid status compared with pregnancies starting during antithyroid drug treatment (odds ratio 4.72, 95% CI 3.50-6.36). A steady decline in the use of definitive treatment before pregnancy was observed from 2000 to 2017. One-third (32.6%) of first trimester carbimazole-exposed pregnancies were switched to propylthiouracil while 6.0% of propylthiouracil-exposed pregnancies switched to carbimazole.

Conclusion

The management of women with hyperthyroidism who become pregnant is suboptimal, particularly in those with preconception definitive treatment, and needs urgent improvement. Better thyroid monitoring and prenatal counseling are needed to optimize thyroid status, reduce teratogenic drug exposure, and ultimately reduce the risk of adverse pregnancy outcomes.",,doi:https://doi.org/10.1210/clinem/dgad276; doi:https://doi.org/10.1210/clinem/dgad276; html:https://europepmc.org/articles/PMC10584009 35151869,https://doi.org/10.1016/j.jbi.2022.104010,Patient-centric characterization of multimorbidity trajectories in patients with severe mental illnesses: A temporal bipartite network modeling approach.,"Wang T, Bendayan R, Msosa Y, Pritchard M, Roberts A, Stewart R, Dobson R.",,Journal of biomedical informatics,2022,2022-02-11,Y,Network Evolution; Multimorbidity; Severe Mental Illnesses; Disease Trajectories; Ehr Data Linkage; Temporal Bipartite Network,,,"Multimorbidity is a major factor contributing to increased mortality among people with severe mental illnesses (SMI). Previous studies either focus on estimating prevalence of a disease in a population without considering relationships between diseases or ignore heterogeneity of individual patients in examining disease progression by looking merely at aggregates across a whole cohort. Here, we present a temporal bipartite network model to jointly represent detailed information on both individual patients and diseases, which allows us to systematically characterize disease trajectories from both patient and disease centric perspectives. We apply this approach to a large set of longitudinal diagnostic records for patients with SMI collected through a data linkage between electronic health records from a large UK mental health hospital and English national hospital administrative database. We find that the resulting diagnosis networks show disassortative mixing by degree, suggesting that patients affected by a small number of diseases tend to suffer from prevalent diseases. Factors that determine the network structures include an individual's age, gender and ethnicity. Our analysis on network evolution further shows that patients and diseases become more interconnected over the illness duration of SMI, which is largely driven by the process that patients with similar attributes tend to suffer from the same conditions. Our analytic approach provides a guide for future patient-centric research on multimorbidity trajectories and contributes to achieving precision medicine.",,doi:https://doi.org/10.1016/j.jbi.2022.104010; doi:https://doi.org/10.1016/j.jbi.2022.104010; html:https://europepmc.org/articles/PMC8894882 +37200150,https://doi.org/10.1210/clinem/dgad276,Preconception Management of Hyperthyroidism and Thyroid Status in Subsequent Pregnancy: A Population-Based Cohort Study.,"Minassian C, Allen LA, Okosieme O, Vaidya B, Taylor P.",,The Journal of clinical endocrinology and metabolism,2023,2023-10-01,Y,Pregnancy; Thyroxine; Hyperthyroidism; Thyroid stimulating hormone; TSH; Thyroid function; Ft3; Ft4; Carbimazole; Tri-iodothyronine; Ptu; Cprd,,,"

Context

Optimal thyroid status in pregnancy is essential in reducing the risk of adverse outcomes. The management of hyperthyroidism in women of reproductive age poses unique challenges and it is unclear how preconception treatment strategies impact on thyroid status in subsequent pregnancy.

Objective

We aimed to determine trends in the management of hyperthyroidism before and during pregnancy and to assess the impact of different preconception treatment strategies on maternal thyroid status.

Methods

We utilized the Clinical Practice Research Datalink database to evaluate all females aged 15-45 years with a clinical diagnosis of hyperthyroidism and a subsequent pregnancy (January 2000 to December 2017). We compared thyroid status in pregnancy according to preconception treatment, namely, (1) antithyroid drugs up to or beyond pregnancy onset, (2) definitive treatment with thyroidectomy or radioiodine before pregnancy, and (3) no treatment at pregnancy onset.

Results

Our study cohort comprised 4712 pregnancies. Thyrotropin (TSH) was measured in only 53.1% of pregnancies, of which 28.1% showed suboptimal thyroid status (TSH >4.0 mU/L or TSH <0.1 mU/L plus FT4 >reference range). Pregnancies with prior definitive treatment were more likely to have suboptimal thyroid status compared with pregnancies starting during antithyroid drug treatment (odds ratio 4.72, 95% CI 3.50-6.36). A steady decline in the use of definitive treatment before pregnancy was observed from 2000 to 2017. One-third (32.6%) of first trimester carbimazole-exposed pregnancies were switched to propylthiouracil while 6.0% of propylthiouracil-exposed pregnancies switched to carbimazole.

Conclusion

The management of women with hyperthyroidism who become pregnant is suboptimal, particularly in those with preconception definitive treatment, and needs urgent improvement. Better thyroid monitoring and prenatal counseling are needed to optimize thyroid status, reduce teratogenic drug exposure, and ultimately reduce the risk of adverse pregnancy outcomes.",,doi:https://doi.org/10.1210/clinem/dgad276; doi:https://doi.org/10.1210/clinem/dgad276; html:https://europepmc.org/articles/PMC10584009 37729117,https://doi.org/10.1371/journal.pdig.0000309,Training and testing of a gradient boosted machine learning model to predict adverse outcome in patients presenting to emergency departments with suspected covid-19 infection in a middle-income setting.,"Fuller GW, Hasan M, Hodkinson P, McAlpine D, Goodacre S, Bath PA, Sbaffi L, Omer Y, Wallis L, Marincowitz C.",,PLOS digital health,2023,2023-09-20,Y,,,,"COVID-19 infection rates remain high in South Africa. Clinical prediction models may be helpful for rapid triage, and supporting clinical decision making, for patients with suspected COVID-19 infection. The Western Cape, South Africa, has integrated electronic health care data facilitating large-scale linked routine datasets. The aim of this study was to develop a machine learning model to predict adverse outcome in patients presenting with suspected COVID-19 suitable for use in a middle-income setting. A retrospective cohort study was conducted using linked, routine data, from patients presenting with suspected COVID-19 infection to public-sector emergency departments (EDs) in the Western Cape, South Africa between 27th August 2020 and 31st October 2021. The primary outcome was death or critical care admission at 30 days. An XGBoost machine learning model was trained and internally tested using split-sample validation. External validation was performed in 3 test cohorts: Western Cape patients presenting during the Omicron COVID-19 wave, a UK cohort during the ancestral COVID-19 wave, and a Sudanese cohort during ancestral and Eta waves. A total of 282,051 cases were included in a complete case training dataset. The prevalence of 30-day adverse outcome was 4.0%. The most important features for predicting adverse outcome were the requirement for supplemental oxygen, peripheral oxygen saturations, level of consciousness and age. Internal validation using split-sample test data revealed excellent discrimination (C-statistic 0.91, 95% CI 0.90 to 0.91) and calibration (CITL of 1.05). The model achieved C-statistics of 0.84 (95% CI 0.84 to 0.85), 0.72 (95% CI 0.71 to 0.73), and 0.62, (95% CI 0.59 to 0.65) in the Omicron, UK, and Sudanese test cohorts. Results were materially unchanged in sensitivity analyses examining missing data. An XGBoost machine learning model achieved good discrimination and calibration in prediction of adverse outcome in patients presenting with suspected COVID19 to Western Cape EDs. Performance was reduced in temporal and geographical external validation.",,pdf:https://journals.plos.org/digitalhealth/article/file?id=10.1371/journal.pdig.0000309&type=printable; doi:https://doi.org/10.1371/journal.pdig.0000309; html:https://europepmc.org/articles/PMC10511129; pdf:https://europepmc.org/articles/PMC10511129?pdf=render 36644660,https://doi.org/10.1177/20552076221128677,Evaluation of prototype risk prediction tools for clinicians and people living with type 2 diabetes in North West London using the think aloud method.,"Gardner C, Wake D, Brodie D, Silverstein A, Young S, Cunningham S, Sainsbury C, Ilia M, Lucas A, Willis T, Halligan J.",,Digital health,2023,2023-01-08,Y,Artificial intelligence; Internet; Diabetes; Qualitative; risk factors; Machine Learning; Health Informatics; Behaviour Change; Personalised Medicine; Digital Health,,,"The prevalence of type 2 diabetes in North West London (NWL) is relatively high compared to other parts of the United Kingdom with outcomes suboptimal. This presents a need for more effective strategies to identify people living with type 2 diabetes who need additional support. An emerging subset of web-based interventions for diabetes self-management and population management has used artificial intelligence and machine learning models to stratify the risk of complications from diabetes and identify patients in need of immediate support. In this study, two prototype risk prediction tools on the MyWay Diabetes and MyWay Clinical platforms were evaluated with six clinicians and six people living with type 2 diabetes in NWL using the think aloud method. The results of the sessions with people living with type 2 diabetes showed that the concept of the tool was intuitive, however, more instruction on how to correctly use the risk prediction tool would be valuable. The feedback from the sessions with clinicians was that the data presented in the tool aligned with the key diabetes targets in NWL, and that this would be useful for identifying and inviting patients to the practice who are overdue for tests and at risk of complications. The findings of the evaluation have been used to support the development of the prototype risk predictions tools. This study demonstrates the value of conducting usability testing on web-based interventions designed to support the targeted management of type 2 diabetes in local communities.",,doi:https://doi.org/10.1177/20552076221128677; doi:https://doi.org/10.1177/20552076221128677; html:https://europepmc.org/articles/PMC9834412; pdf:https://europepmc.org/articles/PMC9834412?pdf=render 35792838,https://doi.org/10.1093/bioinformatics/btac453,Flashfm-ivis: interactive visualization for fine-mapping of multiple quantitative traits.,"Zhou F, Butterworth AS, Asimit JL.",,"Bioinformatics (Oxford, England)",2022,2022-09-01,Y,,,,"

Summary

flashfm-ivis provides a suite of interactive visualization plots to view potential causal genetic variants that underlie associations that are shared or distinct between multiple quantitative traits and compares results between single- and multi-trait fine-mapping. Unique features include network diagrams that show joint effects between variants for each trait and regional association plots that integrate fine-mapping results, all with user-controlled zoom features for an interactive exploration of potential causal variants across traits.

Availability and implementation

flashfm-ivis is an open-source software under the MIT license. It is available as an interactive web-based tool (http://shiny.mrc-bsu.cam.ac.uk/apps/flashfm-ivis/) and as an R package. Code and documentation are available at https://github.com/fz-cambridge/flashfm-ivis and https://zenodo.org/record/6376244#.YjnarC-l2X0. Additional features can be downloaded as standalone R libraries to encourage reuse.

Supplementary information

Supplementary information are available at Bioinformatics online.",,pdf:https://academic.oup.com/bioinformatics/article-pdf/38/17/4238/49889636/btac453.pdf; doi:https://doi.org/10.1093/bioinformatics/btac453; html:https://europepmc.org/articles/PMC9438951; pdf:https://europepmc.org/articles/PMC9438951?pdf=render @@ -1171,38 +1171,38 @@ PMC10686417,https://doi.org/,The impact of restricted provision of publicly fund 33085509,https://doi.org/10.7326/m20-4986,COVID-19 Mortality Risk in Down Syndrome: Results From a Cohort Study of 8 Million Adults.,"Clift AK, Coupland CAC, Keogh RH, Hemingway H, Hippisley-Cox J.",,Annals of internal medicine,2021,2020-10-21,Y,,,,,,pdf:https://europepmc.org/articles/pmc7592804?pdf=render; doi:https://doi.org/10.7326/M20-4986; html:https://europepmc.org/articles/PMC7592804; pdf:https://europepmc.org/articles/PMC7592804?pdf=render 34270458,https://doi.org/10.4269/ajtmh.21-0482,The Need for a Practical Approach to Evaluate the Effectiveness of COVID-19 Vaccines for Low- and Middle-Income Countries.,"Nsanzimana S, Gupta A, Uwizihiwe JP, Haggstrom J, Dron L, Arora P, Park JJH.",,The American journal of tropical medicine and hygiene,2021,2021-07-16,Y,,,,"The global demand for coronavirus disease 2019 (COVID-19) vaccines currently far outweighs the available global supply and manufacturing capacity. As a result, securing doses of vaccines for low- and middle-income countries has been challenging, particularly for African countries. Clinical trial investigation for COVID-19 vaccines has been rare in Africa, with the only randomized clinical trials (RCTs) for COVID-19 vaccines having been conducted in South Africa. In addition to addressing the current inequities in the vaccine roll-out for low- and middle-income countries, there is a need to monitor the real-world effectiveness of COVID-19 vaccines in these regions. Although RCTs are the superior method for evaluating vaccine efficacy, the feasibility of conducting RCTs to monitor COVID-19 vaccine effectiveness during mass vaccine campaigns will likely be low. There is still a need to evaluate the effectiveness of mass COVID-19 vaccine distribution in a practical manner. We discuss how target trial emulation, the application of trial design principles from RCTs to the analysis of observational data, can be used as a practical, cost-effective way to evaluate real-world effectiveness for COVID-19 vaccines. There are several study design considerations that need to be made in the analyses of observational data, such as uncontrolled confounders and selection biases. Target trial emulation accounts for these considerations to improve the analyses of observational data. The framework of target trial emulation provides a practical way to monitor the effectiveness of mass vaccine campaigns for COVID-19 using observational data.",,pdf:https://www.ajtmh.org/downloadpdf/journals/tpmd/105/3/article-p561.pdf; doi:https://doi.org/10.4269/ajtmh.21-0482; html:https://europepmc.org/articles/PMC8592367; pdf:https://europepmc.org/articles/PMC8592367?pdf=render 31442537,https://doi.org/10.1016/j.jaad.2019.08.039,Atopic dermatitis and risk of atrial fibrillation or flutter: A 35-year follow-up study.,"Schmidt SAJ, Olsen M, Schmidt M, Vestergaard C, Langan SM, Deleuran MS, Riis JL.",,Journal of the American Academy of Dermatology,2020,2019-08-20,Y,Validation; Atrial fibrillation; Atrial flutter; Cohort study; risk factors; Atopic Dermatitis,Understanding the Causes of Disease,,"

Background

Atopic dermatitis is characterized by chronic inflammation, which is a risk factor for atrial fibrillation.

Objective

To examine the association between hospital-diagnosed atopic dermatitis and atrial fibrillation.

Methods

Using linked population-based Danish registries, we identified persons with an inpatient or outpatient hospital diagnosis of atopic dermatitis during 1977-2013 and a comparison cohort individually matched to the atopic dermatitis cohort. We followed cohorts until death, emigration, atrial fibrillation diagnosis, or end of study (January 1, 2013). We compared 35-year risk of atrial fibrillation and estimated hazard ratios with 95% confidence intervals using Cox regression, adjusting for birth year and sex. We validated 100 atopic dermatitis diagnoses from a dermatologic department through medical record review.

Results

We included 13,126 persons with atopic dermatitis and 124,211 comparators and followed them for a median of 19.3 years. The 35-year risk of atrial fibrillation was 0.81% and 0.67%, respectively. The positive predictive value of atopic dermatitis diagnoses was 99%. The hazard ratio was 1.2 (95% confidence interval 1.0-1.6) and remained increased after adjusting for various atrial fibrillation risk factors.

Limitations

Analyses were limited to persons with moderate-to-severe atopic dermatitis, and we had no lifestyle data.

Conclusion

Patients with hospital-diagnosed atopic dermatitis have a 20% increased long-term risk of atrial fibrillation, but the absolute risk remains low.",,pdf:http://www.jaad.org/article/S0190962219326143/pdf; doi:https://doi.org/10.1016/j.jaad.2019.08.039; html:https://europepmc.org/articles/PMC7704103; pdf:https://europepmc.org/articles/PMC7704103?pdf=render -37703231,https://doi.org/10.1371/journal.pdig.0000334,A population-based study exploring phenotypic clusters and clinical outcomes in stroke using unsupervised machine learning approach.,"Akyea RK, Ntaios G, Kontopantelis E, Georgiopoulos G, Soria D, Asselbergs FW, Kai J, Weng SF, Qureshi N.",,PLOS digital health,2023,2023-09-13,Y,,,,"Individuals developing stroke have varying clinical characteristics, demographic, and biochemical profiles. This heterogeneity in phenotypic characteristics can impact on cardiovascular disease (CVD) morbidity and mortality outcomes. This study uses a novel clustering approach to stratify individuals with incident stroke into phenotypic clusters and evaluates the differential burden of recurrent stroke and other cardiovascular outcomes. We used linked clinical data from primary care, hospitalisations, and death records in the UK. A data-driven clustering analysis (kamila algorithm) was used in 48,114 patients aged ≥ 18 years with incident stroke, from 1-Jan-1998 to 31-Dec-2017 and no prior history of serious vascular events. Cox proportional hazards regression was used to estimate hazard ratios (HRs) for subsequent adverse outcomes, for each of the generated clusters. Adverse outcomes included coronary heart disease (CHD), recurrent stroke, peripheral vascular disease (PVD), heart failure, CVD-related and all-cause mortality. Four distinct phenotypes with varying underlying clinical characteristics were identified in patients with incident stroke. Compared with cluster 1 (n = 5,201, 10.8%), the risk of composite recurrent stroke and CVD-related mortality was higher in the other 3 clusters (cluster 2 [n = 18,655, 38.8%]: hazard ratio [HR], 1.07; 95% CI, 1.02-1.12; cluster 3 [n = 10,244, 21.3%]: HR, 1.20; 95% CI, 1.14-1.26; and cluster 4 [n = 14,014, 29.1%]: HR, 1.44; 95% CI: 1.37-1.50). Similar trends in risk were observed for composite recurrent stroke and all-cause mortality outcome, and subsequent recurrent stroke outcome. However, results were not consistent for subsequent risk in CHD, PVD, heart failure, CVD-related mortality, and all-cause mortality. In this proof of principle study, we demonstrated how a heterogenous population of patients with incident stroke can be stratified into four relatively homogenous phenotypes with differential risk of recurrent and major cardiovascular outcomes. This offers an opportunity to revisit the stratification of care for patients with incident stroke to improve patient outcomes.",,pdf:https://journals.plos.org/digitalhealth/article/file?id=10.1371/journal.pdig.0000334&type=printable; doi:https://doi.org/10.1371/journal.pdig.0000334; html:https://europepmc.org/articles/PMC10499205; pdf:https://europepmc.org/articles/PMC10499205?pdf=render 33655079,https://doi.org/10.12688/wellcomeopenres.16304.2,Impact of baseline cases of cough and fever on UK COVID-19 diagnostic testing rates: estimates from the Bug Watch community cohort study.,"Eyre MT, Burns R, Kirkby V, Smith C, Denaxas S, Nguyen V, Hayward A, Shallcross L, Fragaszy E, Aldridge RW.",,Wellcome open research,2020,2020-01-01,Y,Fever; Cough; United Kingdom; Diagnostic Testing Capacity; Covid-19; Swab Test,,,"Background: Diagnostic testing forms a major part of the UK's response to the current coronavirus disease 2019 (COVID-19) pandemic with tests offered to anyone with a continuous cough, high temperature or anosmia. Testing capacity must be sufficient during the winter respiratory season when levels of cough and fever are high due to non-COVID-19 causes. This study aims to make predictions about the contribution of baseline cough or fever to future testing demand in the UK. Methods: In this analysis of the Bug Watch community cohort study, we estimated the incidence of cough or fever in England in 2018-2019. We then estimated the COVID-19 diagnostic testing rates required in the UK for baseline cough or fever cases for the period July 2020-June 2021. This was explored for different rates of the population requesting tests, four COVID-19 second wave scenarios and high and low baseline cough or fever incidence scenarios. Results: Under the high baseline cough or fever scenario, incidence in the UK is expected to rise rapidly from 250,708 (95%CI 181,095 - 347,080) cases per day in September to a peak of 444,660 (95%CI 353,084 - 559,988) in December. If 80% of these cases request tests, testing demand would exceed 1.4 million tests per week for five consecutive months. Demand was significantly lower in the low cough or fever incidence scenario, with 129,115 (95%CI 111,596 - 151,679) tests per day in January 2021, compared to 340,921 (95%CI 276,039 - 424,491) tests per day in the higher incidence scenario. Conclusions: Our results show that national COVID-19 testing demand is highly dependent on background cough or fever incidence. This study highlights that the UK's response to the COVID-19 pandemic must ensure that a high proportion of people with symptoms request tests, and that testing capacity is sufficient to meet the high predicted demand.",,doi:https://doi.org/10.12688/wellcomeopenres.16304.2; html:https://europepmc.org/articles/PMC7890379; pdf:https://europepmc.org/articles/PMC7890379?pdf=render +37703231,https://doi.org/10.1371/journal.pdig.0000334,A population-based study exploring phenotypic clusters and clinical outcomes in stroke using unsupervised machine learning approach.,"Akyea RK, Ntaios G, Kontopantelis E, Georgiopoulos G, Soria D, Asselbergs FW, Kai J, Weng SF, Qureshi N.",,PLOS digital health,2023,2023-09-13,Y,,,,"Individuals developing stroke have varying clinical characteristics, demographic, and biochemical profiles. This heterogeneity in phenotypic characteristics can impact on cardiovascular disease (CVD) morbidity and mortality outcomes. This study uses a novel clustering approach to stratify individuals with incident stroke into phenotypic clusters and evaluates the differential burden of recurrent stroke and other cardiovascular outcomes. We used linked clinical data from primary care, hospitalisations, and death records in the UK. A data-driven clustering analysis (kamila algorithm) was used in 48,114 patients aged ≥ 18 years with incident stroke, from 1-Jan-1998 to 31-Dec-2017 and no prior history of serious vascular events. Cox proportional hazards regression was used to estimate hazard ratios (HRs) for subsequent adverse outcomes, for each of the generated clusters. Adverse outcomes included coronary heart disease (CHD), recurrent stroke, peripheral vascular disease (PVD), heart failure, CVD-related and all-cause mortality. Four distinct phenotypes with varying underlying clinical characteristics were identified in patients with incident stroke. Compared with cluster 1 (n = 5,201, 10.8%), the risk of composite recurrent stroke and CVD-related mortality was higher in the other 3 clusters (cluster 2 [n = 18,655, 38.8%]: hazard ratio [HR], 1.07; 95% CI, 1.02-1.12; cluster 3 [n = 10,244, 21.3%]: HR, 1.20; 95% CI, 1.14-1.26; and cluster 4 [n = 14,014, 29.1%]: HR, 1.44; 95% CI: 1.37-1.50). Similar trends in risk were observed for composite recurrent stroke and all-cause mortality outcome, and subsequent recurrent stroke outcome. However, results were not consistent for subsequent risk in CHD, PVD, heart failure, CVD-related mortality, and all-cause mortality. In this proof of principle study, we demonstrated how a heterogenous population of patients with incident stroke can be stratified into four relatively homogenous phenotypes with differential risk of recurrent and major cardiovascular outcomes. This offers an opportunity to revisit the stratification of care for patients with incident stroke to improve patient outcomes.",,pdf:https://journals.plos.org/digitalhealth/article/file?id=10.1371/journal.pdig.0000334&type=printable; doi:https://doi.org/10.1371/journal.pdig.0000334; html:https://europepmc.org/articles/PMC10499205; pdf:https://europepmc.org/articles/PMC10499205?pdf=render 35987738,https://doi.org/10.1016/j.jcmg.2022.06.017,Benefits of Machine Learning to Predict Survival Using Stress Perfusion CMR and Basic Clinical Information.,"Petersen SE, Aung N.",,JACC. Cardiovascular imaging,2022,2022-08-17,N,Machine Learning; Cardiovascular Magnetic Resonance; Vasodilator Stress Perfusion,,,,,doi:https://doi.org/10.1016/j.jcmg.2022.06.017; doi:https://doi.org/10.1016/j.jcmg.2022.06.017 37338108,https://doi.org/10.1093/eurjpc/zwad202,The relevance of competing risk adjustment in cardiovascular risk prediction models for clinical practice.,"Hageman SHJ, Dorresteijn JAN, Pennells L, van Smeden M, Bots ML, Di Angelantonio E, Visseren FLJ.",,European journal of preventive cardiology,2023,2023-11-01,N,Education; Personalized Medicine; Risk Prediction; Competing Risks; Score2,,,"

Background

Many models developed for predicting the risk of cardiovascular disease (CVD) are adjusted for the competing risk of non-CVD mortality, which has been suggested to reduce potential overestimation of cumulative incidence in populations where the risk of competing events is high. The objective was to evaluate and illustrate the clinical impact of competing risk adjustment when deriving a CVD prediction model in a high-risk population.

Methods and results

Individuals with established atherosclerotic CVD were included from the Utrecht Cardiovascular Cohort-Secondary Manifestations of ARTerial disease (UCC-SMART). In 8355 individuals, followed for a median of 8.2 years (IQR 4.2-12.5), two similar prediction models for the estimation of 10-year residual CVD risk were derived: with competing risk adjustment using a Fine and Gray model and without competing risk adjustment using a Cox proportional hazards model. On average, predictions were higher from the Cox model. The Cox model predictions overestimated the cumulative incidence [predicted-observed ratio 1.14 (95% CI 1.09-1.20)], which was most apparent in the highest risk quartiles and in older persons. Discrimination of both models was similar. When determining treatment eligibility on thresholds of predicted risks, more individuals would be treated based on the Cox model predictions. If, for example, individuals with a predicted risk > 20% were considered eligible for treatment, 34% of the population would be treated according to the Fine and Gray model predictions and 44% according to the Cox model predictions.

Interpretation

Individual predictions from the model unadjusted for competing risks were higher, reflecting the different interpretations of both models. For models aiming to accurately predict absolute risks, especially in high-risk populations, competing risk adjustment must be considered.",,doi:https://doi.org/10.1093/eurjpc/zwad202; doi:https://doi.org/10.1093/eurjpc/zwad202 36580444,https://doi.org/10.1371/journal.pmed.1004141,Associations of genetically predicted fatty acid levels across the phenome: A mendelian randomisation study.,"Zagkos L, Dib MJ, Pinto R, Gill D, Koskeridis F, Drenos F, Markozannes G, Elliott P, Zuber V, Tsilidis K, Dehghan A, Tzoulaki I.",,PLoS medicine,2022,2022-12-29,Y,,,,"

Background

Fatty acids are important dietary factors that have been extensively studied for their implication in health and disease. Evidence from epidemiological studies and randomised controlled trials on their role in cardiovascular, inflammatory, and other diseases remains inconsistent. The objective of this study was to assess whether genetically predicted fatty acid concentrations affect the risk of disease across a wide variety of clinical health outcomes.

Methods and findings

The UK Biobank (UKB) is a large study involving over 500,000 participants aged 40 to 69 years at recruitment from 2006 to 2010. We used summary-level data for 117,143 UKB samples (base dataset), to extract genetic associations of fatty acids, and individual-level data for 322,232 UKB participants (target dataset) to conduct our discovery analysis. We studied potentially causal relationships of circulating fatty acids with 845 clinical diagnoses, using mendelian randomisation (MR) approach, within a phenome-wide association study (PheWAS) framework. Regression models in PheWAS were adjusted for sex, age, and the first 10 genetic principal components. External summary statistics were used for replication. When several fatty acids were associated with a health outcome, multivariable MR and MR-Bayesian method averaging (MR-BMA) was applied to disentangle their causal role. Genetic predisposition to higher docosahexaenoic acid (DHA) was associated with cholelithiasis and cholecystitis (odds ratio per mmol/L: 0.76, 95% confidence interval: 0.66 to 0.87). This was supported in replication analysis (FinnGen study) and by the genetically predicted omega-3 fatty acids analyses. Genetically predicted linoleic acid (LA), omega-6, polyunsaturated fatty acids (PUFAs), and total fatty acids (total FAs) showed positive associations with cardiovascular outcomes with support from replication analysis. Finally, higher genetically predicted levels of DHA (0.83, 0.73 to 0.95) and omega-3 (0.83, 0.75 to 0.92) were found to have a protective effect on obesity, which was supported using body mass index (BMI) in the GIANT consortium as replication analysis. Multivariable MR analysis suggested a direct detrimental effect of LA (1.64, 1.07 to 2.50) and omega-6 fatty acids (1.81, 1.06 to 3.09) on coronary heart disease (CHD). MR-BMA prioritised LA and omega-6 fatty acids as the top risk factors for CHD. Although we present a range of sensitivity analyses to the address MR assumptions, horizontal pleiotropy may still bias the reported associations and further evaluation in clinical trials is needed.

Conclusions

Our study suggests potentially protective effects of circulating DHA and omega-3 concentrations on cholelithiasis and cholecystitis and on obesity, highlighting the need to further assess them as prevention treatments in clinical trials. Moreover, our findings do not support the supplementation of unsaturated fatty acids for cardiovascular disease prevention.",,pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1004141&type=printable; doi:https://doi.org/10.1371/journal.pmed.1004141; html:https://europepmc.org/articles/PMC9799317; pdf:https://europepmc.org/articles/PMC9799317?pdf=render 30532623,https://doi.org/10.3897/bdj.6.e29232,"Modifier Ontologies for frequency, certainty, degree, and coverage phenotype modifier.","Endara L, Thessen AE, Cole HA, Walls R, Gkoutos G, Cao Y, Chong SS, Cui H.",,Biodiversity data journal,2018,2018-11-28,Y,Phenotype Modifiers; Modifier Ontology; Certainty Modifiers; Coverage Modifiers; Degree Modifiers; Frequency Modifiers; Literary Warrant; User Consensus; User Warrant,The Human Phenome,,"Background: When phenotypic characters are described in the literature, they may be constrained or clarified with additional information such as the location or degree of expression, these terms are called ""modifiers"". With effort underway to convert narrative character descriptions to computable data, ontologies for such modifiers are needed. Such ontologies can also be used to guide term usage in future publications. Spatial and method modifiers are the subjects of ontologies that already have been developed or are under development. In this work, frequency (e.g., rarely, usually), certainty (e.g., probably, definitely), degree (e.g., slightly, extremely), and coverage modifiers (e.g., sparsely, entirely) are collected, reviewed, and used to create two modifier ontologies with different design considerations. The basic goal is to express the sequential relationships within a type of modifiers, for example, usually is more frequent than rarely, in order to allow data annotated with ontology terms to be classified accordingly. Method: Two designs are proposed for the ontology, both using the list pattern: a closed ordered list (i.e., five-bin design) and an open ordered list design. The five-bin design puts the modifier terms into a set of 5 fixed bins with interval object properties, for example, one_level_more/less_frequently_than, where new terms can only be added as synonyms to existing classes. The open list approach starts with 5 bins, but supports the extensibility of the list via ordinal properties, for example, more/less_frequently_than, allowing new terms to be inserted as a new class anywhere in the list. The consequences of the different design decisions are discussed in the paper. CharaParser was used to extract modifiers from plant, ant, and other taxonomic descriptions. After a manual screening, 130 modifier words were selected as the candidate terms for the modifier ontologies. Four curators/experts (three biologists and one information scientist specialized in biosemantics) reviewed and categorized the terms into 20 bins using the Ontology Term Organizer (OTO) (http://biosemantics.arizona.edu/OTO). Inter-curator variations were reviewed and expressed in the final ontologies. Results: Frequency, certainty, degree, and coverage terms with complete agreement among all curators were used as class labels or exact synonyms. Terms with different interpretations were either excluded or included using ""broader synonym"" or ""not recommended"" annotation properties. These annotations explicitly allow for the user to be aware of the semantic ambiguity associated with the terms and whether they should be used with caution or avoided. Expert categorization results showed that 16 out of 20 bins contained terms with full agreements, suggesting differentiating the modifiers into 5 levels/bins balances the need to differentiate modifiers and the need for the ontology to reflect user consensus. Two ontologies, developed using the Protege ontology editor, are made available as OWL files and can be downloaded from https://github.com/biosemantics/ontologies. Contribution: We built the first two modifier ontologies following a consensus-based approach with terms commonly used in taxonomic literature. The five-bin ontology has been used in the Explorer of Taxon Concepts web toolkit to compute the similarity between characters extracted from literature to facilitate taxon concepts alignments. The two ontologies will also be used in an ontology-informed authoring tool for taxonomists to facilitate consistency in modifier term usage.",,pdf:https://bdj.pensoft.net/article/29232/download/pdf/; doi:https://doi.org/10.3897/BDJ.6.e29232; html:https://europepmc.org/articles/PMC6281706; pdf:https://europepmc.org/articles/PMC6281706?pdf=render 35440465,https://doi.org/10.3399/bjgp.2021.0689,Association between oral anticoagulants and COVID-19-related outcomes: a population-based cohort study.,"Wong AY, Tomlinson L, Brown JP, Elson W, Walker AJ, Schultze A, Morton CE, Evans D, Inglesby P, MacKenna B, Bhaskaran K, Rentsch CT, Powell E, Williamson E, Croker R, Bacon S, Hulme W, Bates C, Curtis HJ, Mehrkar A, Cockburn J, McDonald HI, Mathur R, Wing K, Forbes H, Eggo RM, Evans SJ, Smeeth L, Goldacre B, Douglas IJ, (The OpenSAFELY Collaborative).",,The British journal of general practice : the journal of the Royal College of General Practitioners,2022,2022-06-30,Y,Warfarin; Factor Xa Inhibitors; Dabigatran; Covid-19,,,"

Background

Early evidence has shown that anticoagulant reduces the risk of thrombotic events in those infected with COVID-19. However, evidence of the role of routinely prescribed oral anticoagulants (OACs) in COVID-19 outcomes is limited.

Aim

To investigate the association between OACs and COVID-19 outcomes in those with atrial fibrillation and a CHA2DS2-VASc score of 2.

Design and setting

On behalf of NHS England, a population-based cohort study was conducted.

Method

The study used primary care data and pseudonymously-linked SARS-CoV-2 antigen testing data, hospital admissions, and death records from England. Cox regression was used to estimate hazard ratios (HRs) for COVID-19 outcomes comparing people with current OAC use versus non-use, accounting for age, sex, comorbidities, other medications, deprivation, and general practice.

Results

Of 71 103 people with atrial fibrillation and a CHA2DS2-VASc score of 2, there were 52 832 current OAC users and 18 271 non-users. No difference in risk of being tested for SARS-CoV-2 was associated with current use (adjusted HR [aHR] 0.99, 95% confidence interval [CI] = 0.95 to 1.04) versus non-use. A lower risk of testing positive for SARS-CoV-2 (aHR 0.77, 95% CI = 0.63 to 0.95) and a marginally lower risk of COVID-19-related death (aHR, 0.74, 95% CI = 0.53 to 1.04) were associated with current use versus non-use.

Conclusion

Among those at low baseline stroke risk, people receiving OACs had a lower risk of testing positive for SARS-CoV-2 and severe COVID-19 outcomes than non-users; this might be explained by a causal effect of OACs in preventing severe COVID-19 outcomes or unmeasured confounding, including more cautious behaviours leading to reduced infection risk.",,pdf:https://bjgp.org/content/bjgp/early/2022/04/19/BJGP.2021.0689.full.pdf; doi:https://doi.org/10.3399/BJGP.2021.0689; html:https://europepmc.org/articles/PMC9037187; pdf:https://europepmc.org/articles/PMC9037187?pdf=render 37067859,https://doi.org/10.1136/bmjmed-2022-000245,Sex differences in cardiovascular complications and mortality in hospital patients with covid-19: registry based observational study.,"Hockham C, Linschoten M, Asselbergs FW, Ghossein C, Woodward M, Peters SAE, CAPACITY-COVID Collaborative Consortium .",,BMJ medicine,2023,2023-02-14,Y,epidemiology; Heart Failure; Cardiology; Covid-19,,,"

Objective

To assess whether the risk of cardiovascular complications of covid-19 differ between the sexes and to determine whether any sex differences in risk are reduced in individuals with pre-existing cardiovascular disease.

Design

Registry based observational study.

Setting

74 hospitals across 13 countries (eight European) participating in CAPACITY-COVID (Cardiac complicAtions in Patients With SARS Corona vIrus 2 regisTrY), from March 2020 to May 2021.

Participants

All adults (aged ≥18 years), predominantly European, admitted to hospital with highly suspected covid-19 disease or covid-19 disease confirmed by positive laboratory test results (n=11 167 patients).

Main outcome measures

Any cardiovascular complication during admission to hospital. Secondary outcomes were in-hospital mortality and individual cardiovascular complications with ≥20 events for each sex. Logistic regression was used to examine sex differences in the risk of cardiovascular outcomes, overall and grouped by pre-existing cardiovascular disease.

Results

Of 11 167 adults (median age 68 years, 40% female participants) included, 3423 (36% of whom were female participants) had pre-existing cardiovascular disease. In both sexes, the most common cardiovascular complications were supraventricular tachycardias (4% of female participants, 6% of male participants), pulmonary embolism (3% and 5%), and heart failure (decompensated or de novo) (2% in both sexes). After adjusting for age, ethnic group, pre-existing cardiovascular disease, and risk factors for cardiovascular disease, female individuals were less likely than male individuals to have a cardiovascular complication (odds ratio 0.72, 95% confidence interval 0.64 to 0.80) or die (0.65, 0.59 to 0.72). Differences between the sexes were not modified by pre-existing cardiovascular disease; for the primary outcome, the female-to-male ratio of the odds ratio in those without, compared with those with, pre-existing cardiovascular disease was 0.84 (0.67 to 1.07).

Conclusions

In patients admitted to hospital for covid-19, female participants were less likely than male participants to have a cardiovascular complication. The differences between the sexes could not be attributed to the lower prevalence of pre-existing cardiovascular disease in female individuals. The reasons for this advantage in female individuals requires further research.",,pdf:https://bmjmedicine.bmj.com/content/bmjmed/2/1/e000245.full.pdf; doi:https://doi.org/10.1136/bmjmed-2022-000245; html:https://europepmc.org/articles/PMC10083523; pdf:https://europepmc.org/articles/PMC10083523?pdf=render -36369983,https://doi.org/10.1093/eurheartj/ehac650,Fit for the future: empowering clinical trials with digital technology.,"Kotecha D, DeVore AD, Asselbergs FW.",,European heart journal,2023,2023-01-01,N,,,,,,pdf:https://discovery.ucl.ac.uk/10159909/1/Asselbergs_EHJ%20digital%20viewpoint%202022_final%20accepted.pdf; doi:https://doi.org/10.1093/eurheartj/ehac650 35842339,https://doi.org/10.1016/j.vaccine.2022.06.080,Linking cohort data and Welsh routine health records to investigate children at risk of delayed primary vaccination.,"Walton S, Cortina-Borja M, Dezateux C, Griffiths LJ, Tingay K, Akbari A, Bandyopadhyay A, Lyons RA, Roberts R, Bedford H.",,Vaccine,2022,2022-07-13,Y,Child; Vaccination; Dtp Vaccine; Timeliness; Child Health Systems; Millennium Cohort Study (Mcs),,,"

Background

Delayed primary vaccination is one of the strongest predictors of subsequent incomplete immunisation. Identifying children at risk of such delay may enable targeting of interventions, thus decreasing vaccine-preventable illness.

Objectives

To explore socio-demographic factors associated with delayed receipt of the Diphtheria, Tetanus and Pertussis (DTP) vaccine.

Methods

We included 1,782 children, born between 2000 and 2001, participating in the Millennium Cohort Study (MCS) and resident in Wales, whose parents gave consent for linkage to National Community Child Health Database records at the age seven years contact. We examined child, maternal, family and area characteristics associated with delayed receipt of the first dose of the DTP vaccine.

Results

98.6% received the first dose of DTP. The majority, 79.6% (n = 1,429) received it on time (between 8 and 12 weeks of age), 14.2% (n = 251) received it early (prior to 8 weeks of age) and 4.8% (n = 79) were delayed (after 12 weeks of age); 1.4% (n = 23) never received it. Delayed primary vaccination was more likely among children with older natural siblings (risk ratio 3.82, 95% confidence interval (1.97, 7.38)), children admitted to special/intensive care (3.15, (1.65, 5.99)), those whose birth weight was > 4Kg (2.02, (1.09, 3.73)) and boys (1.53, (1.01, 2.31)). There was a reduced risk of delayed vaccination with increasing maternal age (0.73, (0.53, 1.00) per 5 year increase) and for babies born to graduate mothers (0.27, (0.08, 0.90)).

Conclusions

Although the majority of infants were vaccinated in a timely manner, identification of infants at increased risk of early or delayed vaccination will enable targeting of interventions to facilitate timely immunisation. This is to our knowledge the first study exploring individual level socio-demographic factors associated with delayed primary vaccination in the UK and demonstrates the benefits of linking cohort data to routinely-collected child health data.",,doi:https://doi.org/10.1016/j.vaccine.2022.06.080; doi:https://doi.org/10.1016/j.vaccine.2022.06.080; html:https://europepmc.org/articles/PMC10499753; pdf:https://europepmc.org/articles/PMC10499753?pdf=render -37740900,https://doi.org/10.1093/ageing/afad176,Interventions for reducing anticholinergic medication burden in older adults-a systematic review and meta-analysis.,"Braithwaite E, Todd OM, Atkin A, Hulatt R, Tadrous R, Alldred DP, Pirmohamed M, Walker L, Lawton R, Clegg A.",,Age and ageing,2023,2023-09-01,Y,Cognition; Meta-analysis; Systematic review; Falls; Older People; Older Adult; Anticholinergic Medication,,,"

Introduction

Anticholinergic medications block the neurotransmitter acetylcholine in the brain and peripheral nervous system. Many medications have anticholinergic properties, and the cumulative effect of these medications is termed anticholinergic burden. Increased anticholinergic burden can have short-term side effects such as dry mouth, blurred vision and urinary retention as well as long-term effects including dementia, worsening physical function and falls.

Methods

We carried out a systematic review (SR) with meta-analysis (MA) looking at randomised controlled trials addressing interventions to reduce anticholinergic burden in older adults.

Results

We identified seven papers suitable for inclusion in our SR and MA. Interventions included multi-disciplinary involvement in medication reviews and deprescribing of AC medications. Pooled data revealed no significant difference in outcomes between control and intervention group for falls (OR = 0.76, 95% CI: 0.52-1.11, n = 647), cognition (mean difference = 1.54, 95% CI: -0.04 to 3.13, n = 405), anticholinergic burden (mean difference = 0.04, 95% CI: -0.11 to 0.18, n = 710) or quality of life (mean difference = 0.04, 95% CI: -0.04 to 0.12, n = 461).

Discussion

Overall, there was no significant difference with interventions to reduce anticholinergic burden. As we did not see a significant change in anticholinergic burden scores following interventions, it is likely other outcomes would not change. Short follow-up time and lack of training and support surrounding successful deprescribing may have contributed.",,pdf:https://academic.oup.com/ageing/article-pdf/52/9/afad176/51729004/afad176.pdf; doi:https://doi.org/10.1093/ageing/afad176; html:https://europepmc.org/articles/PMC10517713; pdf:https://europepmc.org/articles/PMC10517713?pdf=render +36369983,https://doi.org/10.1093/eurheartj/ehac650,Fit for the future: empowering clinical trials with digital technology.,"Kotecha D, DeVore AD, Asselbergs FW.",,European heart journal,2023,2023-01-01,N,,,,,,pdf:https://discovery.ucl.ac.uk/10159909/1/Asselbergs_EHJ%20digital%20viewpoint%202022_final%20accepted.pdf; doi:https://doi.org/10.1093/eurheartj/ehac650 33328049,https://doi.org/10.1016/s2589-7500(20)30219-3,Guidelines for clinical trial protocols for interventions involving artificial intelligence: the SPIRIT-AI extension.,"Cruz Rivera S, Liu X, Chan AW, Denniston AK, Calvert MJ, SPIRIT-AI and CONSORT-AI Working Group.",,The Lancet. Digital health,2020,2020-09-09,Y,,,,"The SPIRIT 2013 statement aims to improve the completeness of clinical trial protocol reporting by providing evidence-based recommendations for the minimum set of items to be addressed. This guidance has been instrumental in promoting transparent evaluation of new interventions. More recently, there has been a growing recognition that interventions involving artificial intelligence (AI) need to undergo rigorous, prospective evaluation to demonstrate their impact on health outcomes. The SPIRIT-AI (Standard Protocol Items: Recommendations for Interventional Trials-Artificial Intelligence) extension is a new reporting guideline for clinical trial protocols evaluating interventions with an AI component. It was developed in parallel with its companion statement for trial reports: CONSORT-AI (Consolidated Standards of Reporting Trials-Artificial Intelligence). Both guidelines were developed through a staged consensus process involving literature review and expert consultation to generate 26 candidate items, which were consulted upon by an international multi-stakeholder group in a two-stage Delphi survey (103 stakeholders), agreed upon in a consensus meeting (31 stakeholders) and refined through a checklist pilot (34 participants). The SPIRIT-AI extension includes 15 new items that were considered sufficiently important for clinical trial protocols of AI interventions. These new items should be routinely reported in addition to the core SPIRIT 2013 items. SPIRIT-AI recommends that investigators provide clear descriptions of the AI intervention, including instructions and skills required for use, the setting in which the AI intervention will be integrated, considerations for the handling of input and output data, the human-AI interaction and analysis of error cases. SPIRIT-AI will help promote transparency and completeness for clinical trial protocols for AI interventions. Its use will assist editors and peer reviewers, as well as the general readership, to understand, interpret, and critically appraise the design and risk of bias for a planned clinical trial.",,pdf:http://www.thelancet.com/article/S2589750020302193/pdf; doi:https://doi.org/10.1016/S2589-7500(20)30219-3; html:https://europepmc.org/articles/PMC8212701; pdf:https://europepmc.org/articles/PMC8212701?pdf=render +37740900,https://doi.org/10.1093/ageing/afad176,Interventions for reducing anticholinergic medication burden in older adults-a systematic review and meta-analysis.,"Braithwaite E, Todd OM, Atkin A, Hulatt R, Tadrous R, Alldred DP, Pirmohamed M, Walker L, Lawton R, Clegg A.",,Age and ageing,2023,2023-09-01,Y,Cognition; Meta-analysis; Systematic review; Falls; Older People; Older Adult; Anticholinergic Medication,,,"

Introduction

Anticholinergic medications block the neurotransmitter acetylcholine in the brain and peripheral nervous system. Many medications have anticholinergic properties, and the cumulative effect of these medications is termed anticholinergic burden. Increased anticholinergic burden can have short-term side effects such as dry mouth, blurred vision and urinary retention as well as long-term effects including dementia, worsening physical function and falls.

Methods

We carried out a systematic review (SR) with meta-analysis (MA) looking at randomised controlled trials addressing interventions to reduce anticholinergic burden in older adults.

Results

We identified seven papers suitable for inclusion in our SR and MA. Interventions included multi-disciplinary involvement in medication reviews and deprescribing of AC medications. Pooled data revealed no significant difference in outcomes between control and intervention group for falls (OR = 0.76, 95% CI: 0.52-1.11, n = 647), cognition (mean difference = 1.54, 95% CI: -0.04 to 3.13, n = 405), anticholinergic burden (mean difference = 0.04, 95% CI: -0.11 to 0.18, n = 710) or quality of life (mean difference = 0.04, 95% CI: -0.04 to 0.12, n = 461).

Discussion

Overall, there was no significant difference with interventions to reduce anticholinergic burden. As we did not see a significant change in anticholinergic burden scores following interventions, it is likely other outcomes would not change. Short follow-up time and lack of training and support surrounding successful deprescribing may have contributed.",,pdf:https://academic.oup.com/ageing/article-pdf/52/9/afad176/51729004/afad176.pdf; doi:https://doi.org/10.1093/ageing/afad176; html:https://europepmc.org/articles/PMC10517713; pdf:https://europepmc.org/articles/PMC10517713?pdf=render 34871122,https://doi.org/10.1080/09638288.2021.2008526,Pain and mental health symptom patterns and treatment trajectories following road trauma: a registry-based cohort study.,"Huang S, Dipnall JF, Gabbe BJ, Giummarra MJ.",,Disability and rehabilitation,2022,2021-12-06,N,Injury; Recovery; Pain; Mental health; Healthcare Use,,,"

Purpose

This study aimed to characterise recovery from pain and mental health symptoms, and identify whether treatment use facilitates recovery.

Methods

Victorian State Trauma Registry and Victorian Orthopaedic Trauma Outcomes Registry participants without neurotrauma who had transport injury claims with the Transport Accident Commission from 2007 to 2014 were included (n = 5908). Latent transition analysis of pain Numeric Rating Scale, SF-12, and EQ-5D-3L pain and mental health items from 6 to 12 months, and 12 to 24 months post-injury were used to identify symptom transitions.

Results

Four transition groups were identified: transition to low problems by 12-months; transition to low problems at 24-months; stable low problems; and no transition from problems. Group-based trajectory modelling of pain and mental health treatments found three treatment trajectories: low/no treatment, a moderate treatment that declined to low treatment 3-12 months post-injury, and increasing treatment over time. Predictors of pain and mental health recovery transitions, identified using multinomial logistic regression, were primarily found to be non-modifiable socioeconomic and health-related characteristics (e.g., higher education, working pre-injury, and not having comorbidities), and low treatment trajectories.

Conclusions

Targeted and collaborative rehabilitation should be considered for people at risk of persistent pain or mental health symptoms to optimise their recovery, particularly patients with socioeconomic disadvantage.IMPLICATIONS FOR REHABILITATIONTwo-thirds of people experience pain and/or mental health within the first 24-months after hospitalization for road trauma, of whom only 6-7% recover by 12-months, and a further 6% recover by 24-months post-injury.There were three main trajectories of administrative records of treatments received in the first two years after injury: 76 and 83% had low treatment, 18 and 12% had moderate then declining treatment levels, and 6 and 5% had stable high treatment for pain or mental health, respectively.People who recovered from pain or mental health symptoms generally had lower treatment and higher socioeconomic position, highlighting that coordinated rehabilitation care should be prioritized for people living with socioeconomic disadvantage.",,doi:https://doi.org/10.1080/09638288.2021.2008526 34053271,https://doi.org/10.1098/rstb.2020.0266,Real-time monitoring of COVID-19 dynamics using automated trend fitting and anomaly detection.,"Jombart T, Ghozzi S, Schumacher D, Taylor TJ, Leclerc QJ, Jit M, Flasche S, Greaves F, Ward T, Eggo RM, Nightingale E, Meakin S, Brady OJ, Centre for Mathematical Modelling of Infectious Diseases COVID-19 Working Group, Medley GF, Höhle M, Edmunds WJ.",,"Philosophical transactions of the Royal Society of London. Series B, Biological sciences",2021,2021-05-31,Y,Algorithm; Surveillance; outbreak; Machine Learning; Asmodee; Trendbreaker,,,"As several countries gradually release social distancing measures, rapid detection of new localized COVID-19 hotspots and subsequent intervention will be key to avoiding large-scale resurgence of transmission. We introduce ASMODEE (automatic selection of models and outlier detection for epidemics), a new tool for detecting sudden changes in COVID-19 incidence. Our approach relies on automatically selecting the best (fitting or predicting) model from a range of user-defined time series models, excluding the most recent data points, to characterize the main trend in an incidence. We then derive prediction intervals and classify data points outside this interval as outliers, which provides an objective criterion for identifying departures from previous trends. We also provide a method for selecting the optimal breakpoints, used to define how many recent data points are to be excluded from the trend fitting procedure. The analysis of simulated COVID-19 outbreaks suggests ASMODEE compares favourably with a state-of-art outbreak-detection algorithm while being simpler and more flexible. As such, our method could be of wider use for infectious disease surveillance. We illustrate ASMODEE using publicly available data of National Health Service (NHS) Pathways reporting potential COVID-19 cases in England at a fine spatial scale, showing that the method would have enabled the early detection of the flare-ups in Leicester and Blackburn with Darwen, two to three weeks before their respective lockdown. ASMODEE is implemented in the free R package trendbreaker. This article is part of the theme issue 'Modelling that shaped the early COVID-19 pandemic response in the UK'.",,doi:https://doi.org/10.1098/rstb.2020.0266; doi:https://doi.org/10.1098/rstb.2020.0266; html:https://europepmc.org/articles/PMC8165581; pdf:https://europepmc.org/articles/PMC8165581?pdf=render 32065794,https://doi.org/10.3233/jad-191163,Working Towards a Blood-Derived Gene Expression Biomarker Specific for Alzheimer's Disease.,"Patel H, Iniesta R, Stahl D, Dobson RJB, Newhouse SJ.",,Journal of Alzheimer's disease : JAD,2020,2020-01-01,Y,Human; Biomarkers; Alzheimer’s disease; Dementia; Gene Expression; Neurodegenerative Disorders; Machine Learning; Microarray Analysis; Age-related Memory Disorders,,,"

Background

The typical approach to identify blood-derived gene expression signatures as a biomarker for Alzheimer's disease (AD) have relied on training classification models using AD and healthy controls only. This may inadvertently result in the identification of markers for general illness rather than being disease-specific.

Objective

Investigate whether incorporating additional related disorders in the classification model development process can lead to the discovery of an AD-specific gene expression signature.

Methods

Two types of XGBoost classification models were developed. The first used 160 AD and 127 healthy controls and the second used the same 160 AD with 6,318 upsampled mixed controls consisting of Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, bipolar disorder, schizophrenia, coronary artery disease, rheumatoid arthritis, chronic obstructive pulmonary disease, and cognitively healthy subjects. Both classification models were evaluated in an independent cohort consisting of 127 AD and 687 mixed controls.

Results

The AD versus healthy control models resulted in an average 48.7% sensitivity (95% CI = 34.7-64.6), 41.9% specificity (95% CI = 26.8-54.3), 13.6% PPV (95% CI = 9.9-18.5), and 81.1% NPV (95% CI = 73.3-87.7). In contrast, the mixed control models resulted in an average of 40.8% sensitivity (95% CI = 27.5-52.0), 95.3% specificity (95% CI = 93.3-97.1), 61.4% PPV (95% CI = 53.8-69.6), and 89.7% NPV (95% CI = 87.8-91.4).

Conclusions

This early work demonstrates the value of incorporating additional related disorders into the classification model developmental process, which can result in models with improved ability to distinguish AD from a heterogeneous aging population. However, further improvement to the sensitivity of the test is still required.",,pdf:https://content.iospress.com:443/download/journal-of-alzheimers-disease/jad191163?id=journal-of-alzheimers-disease%2Fjad191163; doi:https://doi.org/10.3233/JAD-191163; html:https://europepmc.org/articles/PMC7175937; pdf:https://europepmc.org/articles/PMC7175937?pdf=render 35188950,https://doi.org/10.1001/jamaneurol.2021.5420,Risk Factors and Prognosis of Early Posttraumatic Seizures in Moderate to Severe Traumatic Brain Injury.,"Laing J, Gabbe B, Chen Z, Perucca P, Kwan P, O'Brien TJ.",,JAMA neurology,2022,2022-04-01,N,,,,"

Importance

Early posttraumatic seizures (EPS) that may occur following a traumatic brain injury (TBI) are associated with poorer outcomes and development of posttraumatic epilepsy (PTE).

Objective

To evaluate risk factors for EPS, associated morbidity and mortality, and contribution to PTE.

Design, setting, and participants

Data were collected from an Australian registry-based cohort study of adults (age ≥18 years) with moderate to severe TBI from January 2005 to December 2019, with 2-year follow-up. The statewide trauma registry, conducted on an opt-out basis in Victoria (population 6.5 million), had 15 152 patients with moderate to severe TBI identified via Abbreviated Injury Scale (AIS) head severity score, with an opt-out rate less than 0.5% (opt-out n = 136).

Main outcomes and measures

EPS were identified via International Statistical Classification of Diseases, Tenth Revision, Australian Modification (ICD-10-AM) codes recorded after the acute admission. Outcome measures also included in-hospital metrics, 2-year outcomes including PTE, and post-discharge mortality. Adaptive least absolute shrinkage and selection operator (LASSO) regression was used to build a prediction model for risk factors of EPS.

Results

Among the 15 152 participants (10 457 [69%] male; median [IQR] age, 60 [35-79] y), 416 (2.7%) were identified with EPS, including 27 (0.2%) with status epilepticus. Significant risk factors on multivariable analysis for developing EPS were younger age, higher Charlson Comorbidity Index, TBI sustained from a low fall, subdural hemorrhage, subarachnoid hemorrhage, higher Injury Severity Score, and greater head injury severity, measured using the AIS and Glasgow Coma Score. After adjustment for confounders, EPS were associated with increased ICU admission and ICU length of stay, ventilation and duration, hospital length of stay, and discharge to inpatient rehabilitation rather than home, but not in-hospital mortality. Outcomes in TBI admission survivors at 24 months, including mortality (relative risk [RR] = 2.14; 95% CI, 1.32-3.46; P = .002), development of PTE (RR = 2.91; 95% CI, 2.22-3.81; P < .001), and use of antiseizure medications (RR = 2.44; 95% CI, 1.98-3.02; P < .001), were poorer for cases with EPS after adjustment for confounders. The prediction model for EPS had an area under the receiver operating characteristic curve of 0.72 (95% CI, 0.66-0.79), sensitivity of 66%, and specificity of 73% in the validation set.

Discussion

We identified important risk factors for EPS following moderate to severe TBI. Early posttraumatic seizures were associated with longer ICU and hospital admissions, ICU ventilation, and poorer 24-month outcomes including mortality and development of PTE.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8861899; doi:https://doi.org/10.1001/jamaneurol.2021.5420; html:https://europepmc.org/articles/PMC8861899; doi:https://doi.org/10.1001/jamaneurol.2021.5420 37505992,https://doi.org/10.1093/ageing/afad136,The extent of anticholinergic burden across an older Welsh population living with frailty: cross-sectional analysis of general practice records.,"Cheong VL, Mehdizadeh D, Todd OM, Gardner P, Zaman H, Clegg A, Alldred DP, Faisal M.",,Age and ageing,2023,2023-07-01,Y,Frailty; Older People; Older Adults; Routine Data; Anticholinergic Burden; Structured Medication Review,,,"

Background

Anticholinergic medicines are associated with adverse outcomes for older people. However, little is known about their use in frailty. The objectives were to (i) investigate the prevalence of anticholinergic prescribing for older patients, and (ii) examine anticholinergic burden according to frailty status.

Methods

Cross-sectional analysis of Welsh primary care data from the Secure Anonymised Information Linkage databank including patients aged ≥65 at their first GP consultation between 1 January and 31 December 2018. Frailty was identified using the electronic Frailty Index and anticholinergic burden using the Anticholinergic Cognitive Burden (ACB) scale. Descriptive analysis and logistic regression were conducted to (i) describe the type and frequency of anticholinergics prescribed; and (ii) to estimate the association between frailty and cumulative ACB score (ACB-Sum).

Results

In this study of 529,095 patients, 47.4% of patients receiving any prescription medications were prescribed at least one anticholinergic medicine. Adjusted regression analysis showed that patients with increasing frailty had higher odds of having an ACB-Sum of >3 compared with patients who were fit (mild frailty, adj OR 1.062 (95%CI 1.061-1.064), moderate frailty, adj OR 1.134 (95%CI 1.131-1.136), severe frailty, adj OR 1.208 (95%CI 1.203-1.213)).

Conclusions

Anticholinergic prescribing was high in this older population. Older people with advancing frailty are exposed to the highest anticholinergic burden despite being the most vulnerable to the associated adverse effects. Older people with advancing frailty should be considered for medicines review to prevent overaccumulation of anticholinergic medications, given the risks of functional and cognitive decline that frailty presents.",,pdf:https://academic.oup.com/ageing/article-pdf/52/7/afad136/50976589/afad136.pdf; doi:https://doi.org/10.1093/ageing/afad136; html:https://europepmc.org/articles/PMC10378723; pdf:https://europepmc.org/articles/PMC10378723?pdf=render 38091687,https://doi.org/10.1016/j.bjps.2023.10.106,Revisiting basal cell carcinoma clinical margins: Leveraging natural language processing and multivariate analysis with updated Royal College of Pathologists histological reporting standards.,"Ali SR, Dobbs TD, Jovic M, Strafford H, Lacey AS, Williams N, Pickrell WO, Hutchings HA, Whitaker IS.",,"Journal of plastic, reconstructive & aesthetic surgery : JPRAS",2024,2023-10-20,N,multivariate analysis; Royal College Of Pathologists; Basal Cell Carcinoma; Natural Language Processing; Clinical Margins; Histological Reporting Guidelines,,,"

Introduction

Data supporting the current British Association of Dermatologists guidelines for the management of basal cell carcinoma (BCC) are based on historic studies and do not consider the updated Royal College of Pathologists (RCPath) histological reporting standards. The aim of this study was to use natural language processing (NLP)-derived data and undertake a multivariate analysis with updated RCPath standards, providing a contemporary update on the excision margins required to achieve histological clearance in BCC.

Methods

A validated NLP information extraction model was used to perform a rapid multi-centre, pan-specialty, consecutive retrospective analysis of BCCs, managed with surgical excision using a pre-determined clinical margin, over a 17-year period (2004-2021) at Swansea Bay University Health Board. Logistic regression assessed the relationship between the peripheral and deep margins and histological clearance.

Results

We ran our NLP algorithm on 34,955 BCCs. Out of the 1447 BCCs that met the inclusion criteria, the peripheral margin clearance was not influenced by the BCC risk level (p = 0.670). A clinical peripheral margin of 6 mm achieved a 95% histological clearance rate (95% confidence interval [CI], 0.93-0.98). Tumour thickness inversely affected deep-margin histological clearance (OR 0.720, 95% CI, 0.525-0.991, p < 0.05). Depth level 2 had a 97% probability of achieving deep-margin histological clearance across all tumour thicknesses.

Conclusion

Updated RCPath reporting standards minimally impact the peripheral margin histological clearance in BCC. Larger clinical peripheral margins than those indicated by current guidelines may be necessary to achieve excision rates of ≥95%. These findings emphasise the need for continuous reassessment of clinical standards to enhance patient care.",,pdf:http://www.jprasurg.com/article/S1748681523006769/pdf; doi:https://doi.org/10.1016/j.bjps.2023.10.106 -36707908,https://doi.org/10.1186/s13643-023-02173-w,A comparison of international modelling methods to evaluate health economics of colorectal cancer screening: a systematic review protocol.,"Adair O, McFerran E, Owen T, McKee C, Lamrock F, Lawler M.",,Systematic reviews,2023,2023-01-27,Y,Screening; Economic evaluation; Colorectal Cancer; Health Economics; Cost-effectiveness Analysis; Quality-adjusted Life Years; Cost-utility; Incremental Cost-effectiveness Ratio; Cost–benefit; Life Years Gained,,,"

Background

Colorectal cancer (CRC) is becoming an increasing health problem worldwide. However, with the help of screening, early diagnosis can reduce incidence and mortality rates. To elevate the economic burden that CRC can cause, cost-effectiveness analysis (CEA) can assist healthcare systems to make screening programmes more cost-effective and prolong survival for early-stage CRC patients. This review aims to identify different CEA modelling methods used internationally to evaluate health economics of CRC screening.

Methods

This review will systematically search electronic databases which include MEDLINE, EMBASE, Web of Science and Scopus. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidance recommendations will design the review, and the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement will be used to extract relevant data from studies retrieved. Two reviewers will screen through the evidence using the PICOS (Participant, Intervention, Comparators, Outcomes, Study Design) framework, with a third reviewer to settle any disagreements. Once data extraction and quality assessment are complete, the results will be presented qualitatively and tabulated using the CHEERS checklist.

Discussion

The results obtained from the systematic review will highlight how different CRC screening programmes around the world utilise and incorporate health economic modelling methods to be more cost-effective. This information can help modellers develop CEA models which can be adapted to suit the specific screening programmes that they are evaluating.

Systematic review registration

PROSPERO CRD42022296113.",,pdf:https://systematicreviewsjournal.biomedcentral.com/counter/pdf/10.1186/s13643-023-02173-w; doi:https://doi.org/10.1186/s13643-023-02173-w; html:https://europepmc.org/articles/PMC9883863; pdf:https://europepmc.org/articles/PMC9883863?pdf=render 34912046,https://doi.org/10.1038/s41366-021-01048-1,"30-day morbidity and mortality of sleeve gastrectomy, Roux-en-Y gastric bypass and one anastomosis gastric bypass: a propensity score-matched analysis of the GENEVA data.","Singhal R, Cardoso VR, Wiggins T, Super J, Ludwig C, Gkoutos GV, Mahawar K, GENEVA Collaborators.",,International journal of obesity (2005),2022,2021-12-15,Y,,,,"

Background

There is a paucity of data comparing 30-day morbidity and mortality of sleeve gastrectomy (SG), Roux-en-Y gastric bypass (RYGB), and one anastomosis gastric bypass (OAGB). This study aimed to compare the 30-day safety of SG, RYGB, and OAGB in propensity score-matched cohorts.

Materials and methods

This analysis utilised data collected from the GENEVA study which was a multicentre observational cohort study of bariatric and metabolic surgery (BMS) in 185 centres across 42 countries between 01/05/2022 and 31/10/2020 during the Coronavirus Disease-2019 (COVID-19) pandemic. 30-day complications were categorised according to the Clavien-Dindo classification. Patients receiving SG, RYGB, or OAGB were propensity-matched according to baseline characteristics and 30-day complications were compared between groups.

Results

In total, 6770 patients (SG 3983; OAGB 702; RYGB 2085) were included in this analysis. Prior to matching, RYGB was associated with highest 30-day complication rate (SG 5.8%; OAGB 7.5%; RYGB 8.0% (p = 0.006)). On multivariate regression modelling, Insulin-dependent type 2 diabetes mellitus and hypercholesterolaemia were associated with increased 30-day complications. Being a non-smoker was associated with reduced complication rates. When compared to SG as a reference category, RYGB, but not OAGB, was associated with an increased rate of 30-day complications. A total of 702 pairs of SG and OAGB were propensity score-matched. The complication rate in the SG group was 7.3% (n = 51) as compared to 7.5% (n = 53) in the OAGB group (p = 0.68). Similarly, 2085 pairs of SG and RYGB were propensity score-matched. The complication rate in the SG group was 6.1% (n = 127) as compared to 7.9% (n = 166) in the RYGB group (p = 0.09). And, 702 pairs of OAGB and RYGB were matched. The complication rate in both groups was the same at 7.5 % (n = 53; p = 0.07).

Conclusions

This global study found no significant difference in the 30-day morbidity and mortality of SG, RYGB, and OAGB in propensity score-matched cohorts.",,pdf:https://www.nature.com/articles/s41366-021-01048-1.pdf; doi:https://doi.org/10.1038/s41366-021-01048-1; html:https://europepmc.org/articles/PMC8671878; pdf:https://europepmc.org/articles/PMC8671878?pdf=render +36707908,https://doi.org/10.1186/s13643-023-02173-w,A comparison of international modelling methods to evaluate health economics of colorectal cancer screening: a systematic review protocol.,"Adair O, McFerran E, Owen T, McKee C, Lamrock F, Lawler M.",,Systematic reviews,2023,2023-01-27,Y,Screening; Economic evaluation; Colorectal Cancer; Health Economics; Cost-effectiveness Analysis; Quality-adjusted Life Years; Cost-utility; Incremental Cost-effectiveness Ratio; Cost–benefit; Life Years Gained,,,"

Background

Colorectal cancer (CRC) is becoming an increasing health problem worldwide. However, with the help of screening, early diagnosis can reduce incidence and mortality rates. To elevate the economic burden that CRC can cause, cost-effectiveness analysis (CEA) can assist healthcare systems to make screening programmes more cost-effective and prolong survival for early-stage CRC patients. This review aims to identify different CEA modelling methods used internationally to evaluate health economics of CRC screening.

Methods

This review will systematically search electronic databases which include MEDLINE, EMBASE, Web of Science and Scopus. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidance recommendations will design the review, and the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement will be used to extract relevant data from studies retrieved. Two reviewers will screen through the evidence using the PICOS (Participant, Intervention, Comparators, Outcomes, Study Design) framework, with a third reviewer to settle any disagreements. Once data extraction and quality assessment are complete, the results will be presented qualitatively and tabulated using the CHEERS checklist.

Discussion

The results obtained from the systematic review will highlight how different CRC screening programmes around the world utilise and incorporate health economic modelling methods to be more cost-effective. This information can help modellers develop CEA models which can be adapted to suit the specific screening programmes that they are evaluating.

Systematic review registration

PROSPERO CRD42022296113.",,pdf:https://systematicreviewsjournal.biomedcentral.com/counter/pdf/10.1186/s13643-023-02173-w; doi:https://doi.org/10.1186/s13643-023-02173-w; html:https://europepmc.org/articles/PMC9883863; pdf:https://europepmc.org/articles/PMC9883863?pdf=render 37606853,https://doi.org/10.1007/s00520-023-07944-8,"The impact of the COVID-19 pandemic on community prescription of opioid and antineuropathic analgesics for cancer patients in Wales, UK.","Han J, Rolles M, Torabi F, Griffiths R, Bedston S, Akbari A, Burnett B, Lyons J, Greene G, Thomas R, Long T, Arnold C, Huws DW, Lawler M, Lyons RA.",,Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer,2023,2023-08-22,Y,Analgesia; Cancer; Pain; Primary Care; Prescription; Covid-19 Pandemic,,,"

Purpose

Public health measures instituted at the onset of the COVID-19 pandemic in the UK in 2020 had profound effects on the cancer patient pathway. We hypothesise that this may have affected analgesic prescriptions for cancer patients in primary care.

Methods

A whole-nation retrospective, observational study of opioid and antineuropathic analgesics prescribed in primary care for two cohorts of cancer patients in Wales, using linked anonymised data to evaluate the impact of the pandemic and variation between different demographic backgrounds.

Results

We found a significant increase in strong opioid prescriptions during the pandemic for patients within their first 12 months of diagnosis with a common cancer (incidence rate ratio (IRR) 1.15, 95% CI: 1.12-1.18, p < 0.001 for strong opioids) and significant increases in strong opioid and antineuropathic prescriptions for patients in the last 3 months prior to a cancer-related death (IRR = 1.06, 95% CI: 1.04-1.07, p < 0.001 for strong opioids; IRR = 1.11, 95% CI: 1.08-1.14, p < 0.001 for antineuropathics). A spike in opioid prescriptions for patients diagnosed in Q2 2020 and those who died in Q2 2020 was observed and interpreted as stockpiling. More analgesics were prescribed in more deprived quintiles. This differential was less pronounced in patients towards the end of life, which we attribute to closer professional supervision.

Conclusions

We demonstrate significant changes to community analgesic prescriptions for cancer patients related to the UK pandemic and illustrate prescription patterns linked to patients' demographic background.",,pdf:https://link.springer.com/content/pdf/10.1007/s00520-023-07944-8.pdf; doi:https://doi.org/10.1007/s00520-023-07944-8; html:https://europepmc.org/articles/PMC10444652; pdf:https://europepmc.org/articles/PMC10444652?pdf=render -38023948,https://doi.org/10.18332/ejm/171802,A qualitative study exploring healthcare workers' lived experiences of the impacts of COVID-19 policies and guidelines on maternal and reproductive healthcare services in the United Kingdom.,"Chaloner J, Qureshi I, Gogoi M, Ekezie WC, Al-Oraibi A, Wobi F, Agbonmwandolor JO, Nellums LB, Pareek M.",,European journal of midwifery,2023,2023-11-08,Y,Healthcare Workers; Vaccine Hesitancy; Redeployment; Infection Controls; Covid-19; Policies And Guidelines,,,"

Introduction

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

Methods

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

Results

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

Conclusions

COVID-19 demonstrated how a global health crisis can impact maternal and reproductive health services, leading to reduced service quality and surgical delays due to staff redeployment policies. Our findings underscore the implications of policy and future health crises preparedness. This includes tailored infection control policies, addressing elective surgery backlogs early and improved dissemination of relevant vaccine information.",,pdf:https://www.europeanjournalofmidwifery.eu/pdf-171802-96110?filename=A qualitative study.pdf; doi:https://doi.org/10.18332/ejm/171802; html:https://europepmc.org/articles/PMC10630987; pdf:https://europepmc.org/articles/PMC10630987?pdf=render 30659777,https://doi.org/10.1111/ijpo.12505,Are children with clinical obesity at increased risk of inpatient hospital admissions? An analysis using linked electronic health records in the UK millennium cohort study.,"Griffiths LJ, Cortina-Borja M, Bandyopadhyay A, Tingay K, De Stavola BL, Bedford H, Akbari A, Firman N, Lyons RA, Dezateux C.",,Pediatric obesity,2019,2019-01-18,Y,Obesity; Cohort study; Record Linkage; Health Service Utilization,Improving Public Health,,"

Background

Few studies have examined health service utilization of children with overweight or obesity by using linked electronic health records (EHRs).

Objective/methods

We analysed EHRs from 3269 children (1678 boys; 51.3% [weighted]) participating in the Millennium Cohort Study, living in Wales or Scotland at age seven whose parents consented to record linkage. We used height and weight measurements at age five to categorize children as obese (>98th centile) or overweight (>91st centile) (UK1990 clinical reference standards) and linked to hospital admissions, up to age 14 years, in the Patient Episode Database for Wales and Scottish Morbidity Records. Negative binomial regression models compared rates of inpatient admissions by weight status at age five.

Results

At age five, 11.5% and 6.7% of children were overweight or obese, respectively; 1221 (38%) children were subsequently admitted to hospital at least once. Admissions were not increased among children with overweight or obesity (adjusted rate ratio [RR], 95% confidence interval [CI]: 0.87, 0.68-1.10 and 1.16, 0.87-1.54, respectively).

Conclusions

In this nationally representative cohort of children in Wales and Scotland, those with overweight or obesity at entry to primary school did not have increased rates of hospital admissions in later childhood and early adolescence.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/ijpo.12505; doi:https://doi.org/10.1111/ijpo.12505; html:https://europepmc.org/articles/PMC6563186; pdf:https://europepmc.org/articles/PMC6563186?pdf=render +38023948,https://doi.org/10.18332/ejm/171802,A qualitative study exploring healthcare workers' lived experiences of the impacts of COVID-19 policies and guidelines on maternal and reproductive healthcare services in the United Kingdom.,"Chaloner J, Qureshi I, Gogoi M, Ekezie WC, Al-Oraibi A, Wobi F, Agbonmwandolor JO, Nellums LB, Pareek M.",,European journal of midwifery,2023,2023-11-08,Y,Healthcare Workers; Vaccine Hesitancy; Redeployment; Infection Controls; Covid-19; Policies And Guidelines,,,"

Introduction

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

Methods

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

Results

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

Conclusions

COVID-19 demonstrated how a global health crisis can impact maternal and reproductive health services, leading to reduced service quality and surgical delays due to staff redeployment policies. Our findings underscore the implications of policy and future health crises preparedness. This includes tailored infection control policies, addressing elective surgery backlogs early and improved dissemination of relevant vaccine information.",,pdf:https://www.europeanjournalofmidwifery.eu/pdf-171802-96110?filename=A qualitative study.pdf; doi:https://doi.org/10.18332/ejm/171802; html:https://europepmc.org/articles/PMC10630987; pdf:https://europepmc.org/articles/PMC10630987?pdf=render 32771960,https://doi.org/10.1016/j.ijmedinf.2020.104237,Core competencies for clinical informaticians: A systematic review.,"Davies A, Mueller J, Moulton G.",,International journal of medical informatics,2020,2020-07-24,N,Bioinformatics; Health; Clinical; Pharmacy; Skills; Informatics; Requirements; Core Competencies; Healthcare Data Science,,,"

Background

Building on initial work carried out by the Faculty of Clinical Informatics (FCI) in the UK, the creation of a national competency framework for Clinical Informatics is required for the definition of clinical informaticians' professional attributes and skills. We aimed to systematically review the academic literature relating to competencies, skills and existing course curricula in the clinical and health related informatics domains.

Methods

Two independent reviewers searched Web of Science, EMBASE, ERIC, PubMed and CINAHL. Publications were included if they reported details of relevant competencies, skills and existing course curricula. We report findings using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement.

Results

A total of 82 publications were included. The most frequently used method was surveys (30 %) followed by narrative descriptions (28 %). Most of the publications describe curriculum design (23 %) followed by competency definition (18 %) and skills, qualifications & training (18 %). Core skills surrounding data, information systems and information management appear to be cross-cutting across the various informatics disciplines with Bioinformatics and Pharmacy Informatics expressing the most unique competency requirements.

Conclusion

We identified eight key domains that cut across the different sub-disciplines of health informatics, including data, information management, human factors, project management, research skills/knowledge, leadership and management, systems development and evaluation, and health/healthcare. Some informatics disciplines such as Nursing Informatics appear to be further ahead at achieving widespread competency standardisation. Attempts at standardisation for competencies should be tempered with flexibility to allow for local variation and requirements.",,doi:https://doi.org/10.1016/j.ijmedinf.2020.104237 35642867,https://doi.org/10.1111/bjhp.12606,"Perceived threat of COVID-19, attitudes towards vaccination, and vaccine hesitancy: A prospective longitudinal study in the UK.","Phillips R, Gillespie D, Hallingberg B, Evans J, Taiyari K, Torrens-Burton A, Cannings-John R, Williams D, Sheils E, Ashfield-Watt P, Akbari A, Hughes K, Thomas-Jones E, James D, Wood F.",,British journal of health psychology,2022,2022-06-01,Y,Risk Perception; Behaviour Change; Vaccine Hesitancy; Covid-19; Sars Cov2,,,"

Objectives

Using the Health Belief Model as a conceptual framework, we investigated the association between attitudes towards COVID-19, COVID-19 vaccinations, and vaccine hesitancy and change in these variables over a 9-month period in a UK cohort.

Methods

The COPE study cohort (n = 11,113) was recruited via an online survey at enrolment in March/April 2020. The study was advertised via the HealthWise Wales research registry and social media. Follow-up data were available for 6942 people at 3 months (June/July 2020) and 5037 at 12 months (March/April 2021) post-enrolment. Measures included demographics, perceived threat of COVID-19, perceived control, intention to accept or decline a COVID-19 vaccination, and attitudes towards vaccination. Logistic regression models were fitted cross-sectionally at 3 and 12 months to assess the association between motivational factors and vaccine hesitancy. Longitudinal changes in motivational variables for vaccine-hesitant and non-hesitant groups were examined using mixed-effect analysis of variance models.

Results

Fear of COVID-19, perceived susceptibility to COVID-19, and perceived personal control over COVID-19 infection transmission decreased between the 3- and 12-month surveys. Vaccine hesitancy at 12 months was independently associated with low fear of the disease and more negative attitudes towards COVID-19 vaccination. Specific barriers to COVID-19 vaccine uptake included concerns about safety and efficacy in light of its rapid development, mistrust of government and pharmaceutical companies, dislike of coercive policies, and perceived lack of relaxation in COVID-19-related restrictions as the vaccination programme progressed.

Conclusions

Decreasing fear of COVID-19, perceived susceptibility to the disease, and perceptions of personal control over reducing infection-transmission may impact future COVID-19 vaccination uptake.",,pdf:https://cronfa.swan.ac.uk/Record/cronfa60128/Download/60128__24479__4d74009536e649b0b17180e2bfd80435.pdf; doi:https://doi.org/10.1111/bjhp.12606; html:https://europepmc.org/articles/PMC9347957; pdf:https://europepmc.org/articles/PMC9347957?pdf=render -36501061,https://doi.org/10.3390/nu14235031,Associations of Genetically Predicted Vitamin B12 Status across the Phenome.,"Dib MJ, Ahmadi KR, Zagkos L, Gill D, Morris B, Elliott P, Dehghan A, Tzoulaki I.",,Nutrients,2022,2022-11-26,Y,Vitamin B12; Deficiency; epidemiology; Mendelian Randomisation; Pernicious Anaemia,,,"Variation in vitamin B12 levels has been associated with a range of diseases across the life-course, the causal nature of which remains elusive. We aimed to interrogate genetically predicted vitamin B12 status in relation to a plethora of clinical outcomes available in the UK Biobank. Genome-wide association study (GWAS) summary data obtained from a Danish and Icelandic cohort of 45,576 individuals were used to identify 8 genetic variants associated with vitamin B12 levels, serving as genetic instruments for vitamin B12 status in subsequent analyses. We conducted a Mendelian randomisation (MR)-phenome-wide association study (PheWAS) of vitamin B12 status with 945 distinct phenotypes in 439,738 individuals from the UK Biobank using these 8 genetic instruments to proxy alterations in vitamin B12 status. We used external GWAS summary statistics for replication of significant findings. Correction for multiple testing was taken into consideration using a 5% false discovery rate (FDR) threshold. MR analysis identified an association between higher genetically predicted vitamin B12 status and lower risk of vitamin B deficiency (including all B vitamin deficiencies), serving as a positive control outcome. We further identified associations between higher genetically predicted vitamin B12 status and a reduced risk of megaloblastic anaemia (OR = 0.35, 95% CI: 0.20-0.50) and pernicious anaemia (0.29, 0.19-0.45), which was supported in replication analyses. Our study highlights that higher genetically predicted vitamin B12 status is potentially protective of risk of vitamin B12 deficiency associated with pernicious anaemia diagnosis, and reduces risk of megaloblastic anaemia. The potential use of genetically predicted vitamin B12 status in disease diagnosis, progression and management remains to be investigated.",,pdf:https://www.mdpi.com/2072-6643/14/23/5031/pdf?version=1669449806; doi:https://doi.org/10.3390/nu14235031; html:https://europepmc.org/articles/PMC9740080; pdf:https://europepmc.org/articles/PMC9740080?pdf=render 32046816,https://doi.org/10.2807/1560-7917.es.2020.25.5.2000080,Effectiveness of airport screening at detecting travellers infected with novel coronavirus (2019-nCoV).,"Quilty BJ, Clifford S, CMMID nCoV working group2, Flasche S, Eggo RM.",,Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin,2020,2020-02-01,Y,Surveillance; Effectiveness; Interventions; Emerging Infections; 2019-Ncov; Thermal Scanning; Airport Screening,,,"We evaluated effectiveness of thermal passenger screening for 2019-nCoV infection at airport exit and entry to inform public health decision-making. In our baseline scenario, we estimated that 46% (95% confidence interval: 36 to 58) of infected travellers would not be detected, depending on incubation period, sensitivity of exit and entry screening, and proportion of asymptomatic cases. Airport screening is unlikely to detect a sufficient proportion of 2019-nCoV infected travellers to avoid entry of infected travellers.",,pdf:https://www.eurosurveillance.org/deliver/fulltext/eurosurveillance/25/5/eurosurv-25-5-2.pdf?itemId=%2Fcontent%2F10.2807%2F1560-7917.ES.2020.25.5.2000080&mimeType=pdf&containerItemId=content/eurosurveillance; doi:https://doi.org/10.2807/1560-7917.ES.2020.25.5.2000080; html:https://europepmc.org/articles/PMC7014668; pdf:https://europepmc.org/articles/PMC7014668?pdf=render -38660106,https://doi.org/10.1016/j.jacasi.2024.02.003,Depression and Incident Cardiovascular Disease.,"Pennells L, Mascie-Taylor CGN.",,JACC. Asia,2024,2024-04-03,Y,Sex difference; Depression; Cardiovascular disease; epidemiology,,,,,doi:https://doi.org/10.1016/j.jacasi.2024.02.003; html:https://europepmc.org/articles/PMC11035929; pdf:https://europepmc.org/articles/PMC11035929?pdf=render +36501061,https://doi.org/10.3390/nu14235031,Associations of Genetically Predicted Vitamin B12 Status across the Phenome.,"Dib MJ, Ahmadi KR, Zagkos L, Gill D, Morris B, Elliott P, Dehghan A, Tzoulaki I.",,Nutrients,2022,2022-11-26,Y,Vitamin B12; Deficiency; epidemiology; Mendelian Randomisation; Pernicious Anaemia,,,"Variation in vitamin B12 levels has been associated with a range of diseases across the life-course, the causal nature of which remains elusive. We aimed to interrogate genetically predicted vitamin B12 status in relation to a plethora of clinical outcomes available in the UK Biobank. Genome-wide association study (GWAS) summary data obtained from a Danish and Icelandic cohort of 45,576 individuals were used to identify 8 genetic variants associated with vitamin B12 levels, serving as genetic instruments for vitamin B12 status in subsequent analyses. We conducted a Mendelian randomisation (MR)-phenome-wide association study (PheWAS) of vitamin B12 status with 945 distinct phenotypes in 439,738 individuals from the UK Biobank using these 8 genetic instruments to proxy alterations in vitamin B12 status. We used external GWAS summary statistics for replication of significant findings. Correction for multiple testing was taken into consideration using a 5% false discovery rate (FDR) threshold. MR analysis identified an association between higher genetically predicted vitamin B12 status and lower risk of vitamin B deficiency (including all B vitamin deficiencies), serving as a positive control outcome. We further identified associations between higher genetically predicted vitamin B12 status and a reduced risk of megaloblastic anaemia (OR = 0.35, 95% CI: 0.20-0.50) and pernicious anaemia (0.29, 0.19-0.45), which was supported in replication analyses. Our study highlights that higher genetically predicted vitamin B12 status is potentially protective of risk of vitamin B12 deficiency associated with pernicious anaemia diagnosis, and reduces risk of megaloblastic anaemia. The potential use of genetically predicted vitamin B12 status in disease diagnosis, progression and management remains to be investigated.",,pdf:https://www.mdpi.com/2072-6643/14/23/5031/pdf?version=1669449806; doi:https://doi.org/10.3390/nu14235031; html:https://europepmc.org/articles/PMC9740080; pdf:https://europepmc.org/articles/PMC9740080?pdf=render 34859617,https://doi.org/10.1002/edm2.309,The clinical profile and associated mortality in people with and without diabetes with Coronavirus disease 2019 on admission to acute hospital services.,"Gokhale K, Mostafa SA, Wang J, Tahrani AA, Sainsbury CA, Toulis KA, Thomas GN, Hassan-Smith Z, Sapey E, Gallier S, Adderley NJ, Narendran P, Bellary S, Taverner T, Ghosh S, Nirantharakumar K, Hanif W.",,"Endocrinology, diabetes & metabolism",2022,2021-12-03,Y,Diabetes; Complications; Covid-19,,,"

Introduction

To assess if in adults with COVID-19, whether those with diabetes and complications (DM+C) present with a more severe clinical profile and if that relates to increased mortality, compared to those with diabetes with no complications (DM-NC) and those without diabetes.

Methods

Service-level data was used from 996 adults with laboratory confirmed COVID-19 who presented to the Queen Elizabeth Hospital Birmingham, UK, from March to June 2020. All individuals were categorized into DM+C, DM-NC, and non-diabetes groups. Physiological and laboratory measurements in the first 5 days after admission were collated and compared among groups. Cox proportional hazards regression models were used to evaluate associations between diabetes status and the risk of mortality.

Results

Among the 996 individuals, 104 (10.4%) were DM+C, 295 (29.6%) DM-NC and 597 (59.9%) non-diabetes. There were 309 (31.0%) in-hospital deaths documented, 40 (4.0% of total cohort) were DM+C, 99 (9.9%) DM-NC and 170 (17.0%) non-diabetes. Individuals with DM+C were more likely to present with high anion gap/metabolic acidosis, features of renal impairment, and low albumin/lymphocyte count than those with DM-NC or those without diabetes. There was no significant difference in mortality rates among the groups: compared to individuals without diabetes, the adjusted HRs were 1.39 (95% CI 0.95-2.03, p = 0.093) and 1.18 (95% CI 0.90-1.54, p = 0.226) in DM+C and DM-C, respectively.

Conclusions

Those with COVID-19 and DM+C presented with a more severe clinical and biochemical profile, but this did not associate with increased mortality in this study.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/edm2.309; doi:https://doi.org/10.1002/edm2.309; html:https://europepmc.org/articles/PMC8754243; pdf:https://europepmc.org/articles/PMC8754243?pdf=render +38660106,https://doi.org/10.1016/j.jacasi.2024.02.003,Depression and Incident Cardiovascular Disease.,"Pennells L, Mascie-Taylor CGN.",,JACC. Asia,2024,2024-04-03,Y,Sex difference; Depression; Cardiovascular disease; epidemiology,,,,,doi:https://doi.org/10.1016/j.jacasi.2024.02.003; html:https://europepmc.org/articles/PMC11035929; pdf:https://europepmc.org/articles/PMC11035929?pdf=render +32301135,https://doi.org/10.1111/opo.12685,Delayed attendance at routine eye examinations is associated with increased probability of general practitioner referral: a record linkage study in Northern Ireland.,"Wright DM, O'Reilly D, Azuara-Blanco A, Curran R, McMullan M, Hogg RE.",,Ophthalmic & physiological optics : the journal of the British College of Ophthalmic Opticians (Optometrists),2020,2020-04-16,N,epidemiology; Public Health; Optometry Services,,,"

Purpose

To investigate relationships between health and socio-economic status with delayed attendance at routine eye examinations and risk of subsequent general practitioner (GP) referral in Northern Ireland.

Methods

We constructed a cohort of 132 046 community dwelling individuals aged ≥60 years, drawing contextual information from the 2011 Northern Ireland Census. Using linked administrative records of routine eye examinations between 2009 and 2014, we calculated 311 999 examination intervals. Multinomial models were used to estimate associations between contextual factors and examination interval (classified into three groups: early recall, on-time, delayed attendance). Associations between examination interval and referral risk were estimated using logistic regression.

Results

Delayed attendance was recorded for 129 857 (41.6%) examination intervals, 53 759 (17.2%) delayed by ≥6 months. Female sex, poor general or mental health were each associated with delay, as were longer distances to optometry services among those aged ≥70 years (longest vs shortest: Relative Risk Ratio = 1.21 [1.14, 1.28]). Low income and residence in social housing were associated with reduced delay risk. There were 3347 (3.5%) and 11 401 (5.3%) GP referrals in the 60-69 and ≥70 years age groups respectively. Delayed attendance was associated with increased referral risk in both groups (Odds Ratios: 60-69 years = 1.30 [1.04, 1.61]; ≥70 years = 1.07 [1.01, 1.13]).

Conclusions

Poor health and longer distances to optometry services were associated with delayed attendance at routine eye examinations but low income was not. Delayed attendance was associated with increased GP referral risk, indicative of missed opportunities to detect potentially serious eye conditions.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/opo.12685; doi:https://doi.org/10.1111/opo.12685 37309807,https://doi.org/10.1093/ehjci/jead123,Characterizing the hypertensive cardiovascular phenotype in the UK Biobank.,"Elghazaly H, McCracken C, Szabo L, Malcolmson J, Manisty CH, Davies AH, Piechnik SK, Harvey NC, Neubauer S, Mohiddin SA, Petersen SE, Raisi-Estabragh Z.",,European heart journal. Cardiovascular Imaging,2023,2023-09-01,Y,Ethnicity; Cardiovascular Magnetic Resonance; Population Health; Women’s Health; Antihypertensive Therapies,,,"

Aims

To describe hypertension-related cardiovascular magnetic resonance (CMR) phenotypes in the UK Biobank considering variations across patient populations.

Methods and results

We studied 39 095 (51.5% women, mean age: 63.9 ± 7.7 years, 38.6% hypertensive) participants with CMR data available. Hypertension status was ascertained through health record linkage. Associations between hypertension and CMR metrics were estimated using multivariable linear regression adjusting for major vascular risk factors. Stratified analyses were performed by sex, ethnicity, time since hypertension diagnosis, and blood pressure (BP) control. Results are standardized beta coefficients, 95% confidence intervals, and P-values corrected for multiple testing. Hypertension was associated with concentric left ventricular (LV) hypertrophy (increased LV mass, wall thickness, concentricity index), poorer LV function (lower global function index, worse global longitudinal strain), larger left atrial (LA) volumes, lower LA ejection fraction, and lower aortic distensibility. Hypertension was linked to significantly lower myocardial native T1 and increased LV ejection fraction. Women had greater hypertension-related reduction in aortic compliance than men. The degree of hypertension-related LV hypertrophy was greatest in Black ethnicities. Increasing time since diagnosis of hypertension was linked to adverse remodelling. Hypertension-related remodelling was substantially attenuated in hypertensives with good BP control.

Conclusion

Hypertension was associated with concentric LV hypertrophy, reduced LV function, dilated poorer functioning LA, and reduced aortic compliance. Whilst the overall pattern of remodelling was consistent across populations, women had greater hypertension-related reduction in aortic compliance and Black ethnicities showed the greatest LV mass increase. Importantly, adverse cardiovascular remodelling was markedly attenuated in hypertensives with good BP control.",,pdf:https://academic.oup.com/ehjcimaging/advance-article-pdf/doi/10.1093/ehjci/jead123/50578622/jead123.pdf; doi:https://doi.org/10.1093/ehjci/jead123; html:https://europepmc.org/articles/PMC10531143; pdf:https://europepmc.org/articles/PMC10531143?pdf=render 37337639,https://doi.org/10.1002/ctm2.1291,Trans-ethnic polygenic risk scores for body mass index: An international hundred K+ cohorts consortium study.,"Qu HQ, Connolly JJ, Kraft P, Long J, Pereira A, Flatley C, Turman C, Prins B, Mentch F, Lotufo PA, Magnus P, Stampfer MJ, Tamimi R, Eliassen AH, Zheng W, Knudsen GPS, Helgeland O, Butterworth AS, Hakonarson H, Sleiman PM, IHCC consortium.",,Clinical and translational medicine,2023,2023-06-01,Y,Obesity; Population admixture; body mass index; Polygenic Risk Score; Trans-ethnic,,,"

Background

While polygenic risk scores hold significant promise in estimating an individual's risk of developing a complex trait such as obesity, their application in the clinic has, to date, been limited by a lack of data from non-European populations. As a collaboration model of the International Hundred K+ Cohorts Consortium (IHCC), we endeavored to develop a globally applicable trans-ethnic PRS for body mass index (BMI) through this relatively new international effort.

Methods

The polygenic risk score (PRS) model was developed, trained and tested at the Center for Applied Genomics (CAG) of The Children's Hospital of Philadelphia (CHOP) based on a BMI meta-analysis from the GIANT consortium. The validated PRS models were subsequently disseminated to the participating sites. Scores were generated by each site locally on their cohorts and summary statistics returned to CAG for final analysis.

Results

We show that in the absence of a well powered trans-ethnic GWAS from which to derive marker SNPs and effect estimates for PRS, trans-ethnic scores can be generated from European ancestry GWAS using Bayesian approaches such as LDpred, by adjusting the summary statistics using trans-ethnic linkage disequilibrium reference panels. The ported trans-ethnic scores outperform population specific-PRS across all non-European ancestry populations investigated including East Asians and three-way admixed Brazilian cohort.

Conclusions

Here we show that for a truly polygenic trait such as BMI adjusting the summary statistics of a well powered European ancestry study using trans-ethnic LD reference results in a score that is predictive across a range of ancestries including East Asians and three-way admixed Brazilians.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ctm2.1291; doi:https://doi.org/10.1002/ctm2.1291; html:https://europepmc.org/articles/PMC10280047; pdf:https://europepmc.org/articles/PMC10280047?pdf=render -32301135,https://doi.org/10.1111/opo.12685,Delayed attendance at routine eye examinations is associated with increased probability of general practitioner referral: a record linkage study in Northern Ireland.,"Wright DM, O'Reilly D, Azuara-Blanco A, Curran R, McMullan M, Hogg RE.",,Ophthalmic & physiological optics : the journal of the British College of Ophthalmic Opticians (Optometrists),2020,2020-04-16,N,epidemiology; Public Health; Optometry Services,,,"

Purpose

To investigate relationships between health and socio-economic status with delayed attendance at routine eye examinations and risk of subsequent general practitioner (GP) referral in Northern Ireland.

Methods

We constructed a cohort of 132 046 community dwelling individuals aged ≥60 years, drawing contextual information from the 2011 Northern Ireland Census. Using linked administrative records of routine eye examinations between 2009 and 2014, we calculated 311 999 examination intervals. Multinomial models were used to estimate associations between contextual factors and examination interval (classified into three groups: early recall, on-time, delayed attendance). Associations between examination interval and referral risk were estimated using logistic regression.

Results

Delayed attendance was recorded for 129 857 (41.6%) examination intervals, 53 759 (17.2%) delayed by ≥6 months. Female sex, poor general or mental health were each associated with delay, as were longer distances to optometry services among those aged ≥70 years (longest vs shortest: Relative Risk Ratio = 1.21 [1.14, 1.28]). Low income and residence in social housing were associated with reduced delay risk. There were 3347 (3.5%) and 11 401 (5.3%) GP referrals in the 60-69 and ≥70 years age groups respectively. Delayed attendance was associated with increased referral risk in both groups (Odds Ratios: 60-69 years = 1.30 [1.04, 1.61]; ≥70 years = 1.07 [1.01, 1.13]).

Conclusions

Poor health and longer distances to optometry services were associated with delayed attendance at routine eye examinations but low income was not. Delayed attendance was associated with increased GP referral risk, indicative of missed opportunities to detect potentially serious eye conditions.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/opo.12685; doi:https://doi.org/10.1111/opo.12685 31666244,https://doi.org/10.1136/archdischild-2019-317271,Behavioural difficulties in early childhood and risk of adolescent injury.,"Bandyopadhyay A, Tingay K, Akbari A, Griffiths L, Bedford H, Cortina-Borja M, Walton S, Dezateux C, Lyons RA, Brophy S.",,Archives of disease in childhood,2020,2019-10-30,Y,Hospital Admission; Routine Data; Strengths And Difficulties Questionnaire; A&e Attendance; Longitudinal Data Linkage,,,"

Objective

To evaluate long-term associations between early childhood hyperactivity and conduct problems (CP), measured using Strengths and Difficulties Questionnaire (SDQ) and risk of injury in early adolescence.

Design

Data linkage between a longitudinal birth cohort and routinely collected electronic health records.

Setting

Consenting Millennium Cohort Study (MCS) participants residing in Wales and Scotland.

Patients

3119 children who participated in the age 5 MCS interview.

Main outcome measures

Children with parent-reported SDQ scores were linked with hospital admission and Accident & Emergency (A&E) department records for injuries between ages 9 and 14 years. Negative binomial regression models adjusting for number of people in the household, lone parent, residential area, household poverty, maternal age and academic qualification, child sex, physical activity level and country of interview were fitted in the models.

Results

46% of children attended A&E or were admitted to hospital for injury, and 11% had high/abnormal scores for hyperactivity and CP. High/abnormal or borderline hyperactivity were not significantly associated with risk of injury, incidence rate ratio (IRR) with 95% CI of the high/abnormal and borderline were 0.92 (95% CI 0.74 to 1.14) and 1.16 (95% CI 0.88 to 1.52), respectively. Children with borderline CP had higher injury rates compared with those without CP (IRR 1.31, 95% CI 1.09 to 1.57).

Conclusions

Children with high/abnormal hyperactivity or CP scores were not at increased risk of injury; however, those with borderline CP had higher injury rates. Further research is needed to understand if those with difficulties receive treatment and support, which may reduce the likelihood of injuries.",,pdf:https://adc.bmj.com/content/archdischild/105/3/282.full.pdf; doi:https://doi.org/10.1136/archdischild-2019-317271; html:https://europepmc.org/articles/PMC7041499; pdf:https://europepmc.org/articles/PMC7041499?pdf=render 37395705,https://doi.org/10.1167/tvst.12.7.3,Reliability of Optical Coherence Tomography Angiography Retinal Blood Flow Analyses.,"Courtie EF, Gilani A, Capewell N, Kale AU, Hui BTK, Liu X, Montesano G, Teussink M, Denniston AK, Veenith T, Blanch RJ.",,Translational vision science & technology,2023,2023-07-01,Y,,,,"

Purpose

Investigate the association between the optical coherence tomography angiography (OCTA) metrics derived from different analysis programs to understand the comparability of studies using these different approaches.

Methods

Secondary analysis of a prospective observational study (March 2018-September 2021). Forty-four right eyes and 42 left eyes from 44 patients were included. Patients were either undergoing upper gastrointestinal surgery with a critical care stay planned or were already in the critical care unit with sepsis. OCTA scans were obtained in an ophthalmology department or critical care setting. Fourteen OCTA metrics were compared within and between the programs, and agreement was measured by Pearson's R coefficient and intraclass correlation coefficient.

Results

Correlation was highest between all Heidelberg metrics and Fractalyse (all >0.84), and lowest between Matlab skeletonized or foveal avascular zone metrics and all other measures (e.g., skeletal fractal dimension and vessel density at -0.02). Agreement between eyes was moderate to excellent in all metrics (0.60-0.90).

Conclusions

The significant variability between metrics and programs used for OCTA analysis demonstrates that they are not interchangeable and supports a recommendation for perfusion density metrics to be reported as standard.

Translational relevance

Agreement between different OCTA analyses is variable and not interchangeable. The high agreement between non-skeletonized vessel density metrics suggests that these should be routinely reported.",,doi:https://doi.org/10.1167/tvst.12.7.3; doi:https://doi.org/10.1167/tvst.12.7.3; html:https://europepmc.org/articles/PMC10324418; pdf:https://europepmc.org/articles/PMC10324418?pdf=render 36991119,https://doi.org/10.1038/s41586-023-05844-9,An atlas of genetic scores to predict multi-omic traits.,"Xu Y, Ritchie SC, Liang Y, Timmers PRHJ, Pietzner M, Lannelongue L, Lambert SA, Tahir UA, May-Wilson S, Foguet C, Johansson Å, Surendran P, Nath AP, Persyn E, Peters JE, Oliver-Williams C, Deng S, Prins B, Luan J, Bomba L, Soranzo N, Di Angelantonio E, Pirastu N, Tai ES, van Dam RM, Parkinson H, Davenport EE, Paul DS, Yau C, Gerszten RE, Mälarstig A, Danesh J, Sim X, Langenberg C, Wilson JF, Butterworth AS, Inouye M.",,Nature,2023,2023-03-29,N,,,,"The use of omic modalities to dissect the molecular underpinnings of common diseases and traits is becoming increasingly common. But multi-omic traits can be genetically predicted, which enables highly cost-effective and powerful analyses for studies that do not have multi-omics1. Here we examine a large cohort (the INTERVAL study2; n = 50,000 participants) with extensive multi-omic data for plasma proteomics (SomaScan, n = 3,175; Olink, n = 4,822), plasma metabolomics (Metabolon HD4, n = 8,153), serum metabolomics (Nightingale, n = 37,359) and whole-blood Illumina RNA sequencing (n = 4,136), and use machine learning to train genetic scores for 17,227 molecular traits, including 10,521 that reach Bonferroni-adjusted significance. We evaluate the performance of genetic scores through external validation across cohorts of individuals of European, Asian and African American ancestries. In addition, we show the utility of these multi-omic genetic scores by quantifying the genetic control of biological pathways and by generating a synthetic multi-omic dataset of the UK Biobank3 to identify disease associations using a phenome-wide scan. We highlight a series of biological insights with regard to genetic mechanisms in metabolism and canonical pathway associations with disease; for example, JAK-STAT signalling and coronary atherosclerosis. Finally, we develop a portal ( https://www.omicspred.org/ ) to facilitate public access to all genetic scores and validation results, as well as to serve as a platform for future extensions and enhancements of multi-omic genetic scores.",,pdf:https://www.pure.ed.ac.uk/ws/files/337957796/An_atlas_of_genetic_scores_to_predict_multi_omic_traits_s41586_023_05844_9.pdf; doi:https://doi.org/10.1038/s41586-023-05844-9; html:https://europepmc.org/articles/PMC10323211; pdf:https://europepmc.org/articles/PMC10323211?pdf=render; doi:https://doi.org/10.1038/s41586-023-05844-9 @@ -1215,9 +1215,9 @@ PMC10686417,https://doi.org/,The impact of restricted provision of publicly fund 38526449,https://doi.org/10.1002/clt2.12348,Ethnic differences in depression and anxiety among adults with atopic eczema: Population-based matched cohort studies within UK primary care.,"Adesanya EI, Henderson A, Hayes JF, Lewin A, Mathur R, Mulick A, Morton C, Smith C, Langan SM, Mansfield KE.",,Clinical and translational allergy,2024,2024-03-01,Y,Depression; Anxiety; epidemiology; Atopic Eczema; Ethnicity,,,"

Background

Evidence demonstrates that individuals with atopic eczema (eczema) have increased depression and anxiety; however, the role of ethnicity in these associations is poorly understood. We aimed to investigate whether associations between eczema and depression or anxiety differed between adults from white and minority ethnic groups in the UK.

Methods

We used UK Clinical Practice Research Datalink GOLD to conduct matched cohort studies of adults (≥18 years) with ethnicity recorded in primary care electronic health records (April 2006-January 2020). We matched (age, sex, practice) adults with eczema to up to five adults without. We used stratified Cox regression with an interaction between eczema and ethnicity, to estimate hazard ratios (HRs) for associations between eczema and incident depression and anxiety in individuals from white ethnic groups and a pooled minority ethnic group (adults from Black, South Asian, Mixed and Other groups).

Results

We identified separate cohorts for depression (215,073 with eczema matched to 646,539 without) and anxiety (242,598 with eczema matched to 774,113 without). After adjusting for matching variables and potential confounders (age, sex, practice, deprivation, calendar period), we found strong evidence (p < 0.01) of ethnic differences in associations between eczema and depression (minority ethnic groups: HR = 1.33, 95% CI = 1.22,1.45; white ethnic groups: HR = 1.15, 95% CI = 1.12,1.17) and anxiety (minority ethnic groups: HR = 1.41, 95% CI = 1.28,1.55; white ethnic groups: HR = 1.17, 95% CI = 1.14,1.19).

Conclusions

Adults with eczema from minority ethnic groups appear to be at increased depression and anxiety risk compared with their white counterparts. Culturally adapted mental health promotion and prevention strategies should be considered in individuals with eczema from minority ethnic groups.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/clt2.12348; doi:https://doi.org/10.1002/clt2.12348; html:https://europepmc.org/articles/PMC10962487; pdf:https://europepmc.org/articles/PMC10962487?pdf=render 37997097,https://doi.org/10.1016/s0140-6736(23)02103-7,The impact of risk stratification by polygenic risk and age on breast cancer screening in women aged 40-49 years: a modelling study.,"Huntley C, Torr B, Sud A, Houlston RS, Hingorani AD, Jones ME, Turnbull C.",,"Lancet (London, England)",2023,2023-11-01,N,,,,"

Background

Polygenic Risk Scores (PRSs) have been proposed as a mechanism for risk-stratification of screening, increasing efficiency and enabling extension of existing programmes to improve survival in our aging population. We sought to model the impact of three hypothetical programmes of annual breast cancer screening in women aged 40-49 years: screening the PRS-defined high-risk quintile, screening the oldest quintile, and screening the full population.

Methods

In this UK-based modelling study, we used the published estimate of the area under the curve (AUC) of a currently available breast cancer PRS (0·64) to calculate the proportion of cancers captured by the PRS-defined high-risk quintile. We used population size estimates from the Office for National Statistics alongside age-stratified incidence rates of breast cancer, and age or stage-specific survival data from the National Cancer Registry, to build our model. We used stage-specific route-to-diagnosis data to reassign stage-specific survival for screen-detected cancers. Ethics approval was not required.

Findings

The PRS-defined high-risk quintile, oldest quintile, and full population capture 37% (n=2811), 29% (n=2198), and 100% (n=7533) of breast cancers occurring in women aged 40-49 each year. Annual screening of each group using digital mammography (sensitivity 70%, specificity 92%) would identify 1968, 1538, and 5273 breast cancers per year, respectively. This corresponds to an improvement in survival of 1·4% (102 deaths averted), 1·1% (80 deaths averted) and 3·6% (274 deaths averted) compared with baseline (no screening). Full population screening would require 4 369 703 mammograms and 354 246 confirmatory tests (breast biopsies) every year, while screening the oldest quintile would require 937 850 mammograms and 76 390 biopsies. Screening the PRS-defined high-risk quintile would require 873 941 mammograms and 71 658 biopsies, in addition to a PRS for all women in the age group (4 369 703).

Interpretation

Under favourable assumptions, stratifying screening by PRS rather than age results in modest gains in survival but increases overdiagnoses, logistical complexity, and economic costs. Our study is limited by our modelling parameters (anticipated to maximise survival estimates), including complete uptake of PRS profiling and cancer screening, no interval cancers, and application of screening tools superior to those currently available in the UK. Only with randomised controlled trials, can the uptake, clinical impact, costs, and harms of PRS-stratified screening be definitively assessed.

Funding

The Wellcome Trust.",,doi:https://doi.org/10.1016/S0140-6736(23)02103-7 33990383,https://doi.org/10.1136/gutjnl-2020-323546,Multicentre derivation and validation of a colitis-associated colorectal cancer risk prediction web tool.,"Curtius K, Kabir M, Al Bakir I, Choi CHR, Hartono JL, Johnson M, East JE, Oxford IBD Cohort Study Investigators, Lindsay JO, Vega R, Thomas-Gibson S, Warusavitarne J, Wilson A, Graham TA, Hart A.",,Gut,2022,2021-05-14,Y,Dysplasia; Ulcerative colitis; Colorectal Cancer; Clinical Decision Making,,,"

Objective

Patients with ulcerative colitis (UC) diagnosed with low-grade dysplasia (LGD) have increased risk of developing advanced neoplasia (AN: high-grade dysplasia or colorectal cancer). We aimed to develop and validate a predictor of AN risk in patients with UC with LGD and create a visual web tool to effectively communicate the risk.

Design

In our retrospective multicentre validated cohort study, adult patients with UC with an index diagnosis of LGD, identified from four UK centres between 2001 and 2019, were followed until progression to AN. In the discovery cohort (n=246), a multivariate risk prediction model was derived from clinicopathological features using Cox regression. Validation used data from three external centres (n=198). The validated model was embedded in a web tool to calculate patient-specific risk.

Results

Four clinicopathological variables were significantly associated with AN progression in the discovery cohort: endoscopically visible LGD >1 cm (HR 2.7; 95% CI 1.2 to 5.9), unresectable or incomplete endoscopic resection (HR 3.4; 95% CI 1.6 to 7.4), moderate/severe histological inflammation within 5 years of LGD diagnosis (HR 3.1; 95% CI 1.5 to 6.7) and multifocality (HR 2.9; 95% CI 1.3 to 6.2). In the validation cohort, this four-variable model accurately predicted future AN cases with overall calibration Observed/Expected=1.01 (95% CI 0.64 to 1.52), and achieved 100% specificity for the lowest risk group over 13 years of available follow-up.

Conclusion

Multicohort validation confirms that patients with large, unresected, multifocal LGD and recent moderate/severe inflammation are at highest risk of developing AN. Personalised risk prediction provided via the Ulcerative Colitis-Cancer Risk Estimator ( www.UC-CaRE.uk ) can support treatment decision-making.",,pdf:https://gut.bmj.com/content/gutjnl/71/4/705.full.pdf; doi:https://doi.org/10.1136/gutjnl-2020-323546; html:https://europepmc.org/articles/PMC8921573; pdf:https://europepmc.org/articles/PMC8921573?pdf=render -37645022,https://doi.org/10.1183/20734735.0058-2023,The impact of poor housing and indoor air quality on respiratory health in children.,"Holden KA, Lee AR, Hawcutt DB, Sinha IP.",,"Breathe (Sheffield, England)",2023,2023-06-01,Y,,,,"It is becoming increasingly apparent that poor housing quality affects indoor air quality, significantly impacting on respiratory health in children and young people. Exposure to damp and/or mould in the home, cold homes and the presence of pests and pollutants all have a significant detrimental impact on child respiratory health. There is a complex relationship between features of poor-quality housing, such as being in a state of disrepair, poor ventilation, overcrowding and being cold, that favour an environment resulting in poor indoor air quality. Children living in rented (private or public) housing are more likely to come from lower-income backgrounds and are most at risk of living in substandard housing posing a serious threat to respiratory health. Children have the right to safe and adequate housing, and research has shown that either rehousing or making modifications to poor-quality housing to improve indoor air quality results in improved respiratory health. Urgent action is needed to address this threat to health. All stakeholders should understand the relationship between poor-quality housing and respiratory health in children and act, working with families, to redress this modifiable risk factor.

Educational aims

The reader should understand how housing quality and indoor air quality affect respiratory health in children.The reader should understand which children are at most risk of living in poor-quality housing.The reader should understand what policy recommendations have been made and what actions need to be undertaken to improve housing quality and respiratory health in children and young people.",,doi:https://doi.org/10.1183/20734735.0058-2023; html:https://europepmc.org/articles/PMC10461733; pdf:https://europepmc.org/articles/PMC10461733?pdf=render -35589356,https://doi.org/10.1136/bmjopen-2021-057343,"Linkage of National Congenital Heart Disease Audit data to hospital, critical care and mortality national data sets to enable research focused on quality improvement.","Espuny Pujol F, Pagel C, Brown KL, Doidge JC, Feltbower RG, Franklin RC, Gonzalez-Izquierdo A, Gould DW, Norman LJ, Stickley J, Taylor JA, Crowe S.",,BMJ open,2022,2022-05-19,Y,Congenital heart disease; Audit; Health Informatics; Statistics & Research Methods; Quality In Health Care,,,"

Objectives

To link five national data sets (three registries, two administrative) and create longitudinal healthcare trajectories for patients with congenital heart disease (CHD), describing the quality and the summary statistics of the linked data set.

Design

Bespoke linkage of record-level patient identifiers across five national data sets. Generation of spells of care defined as periods of time-overlapping events across the data sets.

Setting

National Congenital Heart Disease Audit (NCHDA) procedures in public (National Health Service; NHS) hospitals in England and Wales, paediatric and adult intensive care data sets (Paediatric Intensive Care Audit Network; PICANet and the Case Mix Programme from the Intensive Care National Audit & Research Centre; ICNARC-CMP), administrative hospital episodes (hospital episode statistics; HES inpatient, outpatient, accident and emergency; A&E) and mortality registry data.

Participants

Patients with any CHD procedure recorded in NCHDA between April 2000 and March 2017 from public hospitals.

Primary and secondary outcome measures

Primary: number of linked records, number of unique patients and number of generated spells of care. Secondary: quality and completeness of linkage.

Results

There were 143 862 records in NCHDA relating to 96 041 unique patients. We identified 65 797 linked PICANet patient admissions, 4664 linked ICNARC-CMP admissions and over 6 million linked HES episodes of care (1.1M inpatient, 4.7M outpatient). The linked data set had 4 908 153 spells of care after quality checks, with a median (IQR) of 3.4 (1.8-6.3) spells per patient-year. Where linkage was feasible (in terms of year and centre), 95.6% surgical procedure records were linked to a corresponding HES record, 93.9% paediatric (cardiac) surgery procedure records to a corresponding PICANet admission and 76.8% adult surgery procedure records to a corresponding ICNARC-CMP record.

Conclusions

We successfully linked four national data sets to the core data set of all CHD procedures performed between 2000 and 2017. This will enable a much richer analysis of longitudinal patient journeys and outcomes. We hope that our detailed description of the linkage process will be useful to others looking to link national data sets to address important research priorities.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/5/e057343.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-057343; html:https://europepmc.org/articles/PMC9121475; pdf:https://europepmc.org/articles/PMC9121475?pdf=render 34230034,https://doi.org/10.1136/bmjresp-2021-000967,Increase in recruitment upon integration of trial into a clinical care pathway: an observational study.,"Yip KP, Gompertz S, Snelson C, Willson J, Madathil S, Huq SS, Rauf F, Salmon N, Tengende J, Tracey J, Cooper B, Filby K, Ball S, Parekh D, Dosanjh DPS.",,BMJ open respiratory research,2021,2021-07-01,Y,Covid-19,,,"

Introduction

Many respiratory clinical trials fail to reach their recruitment target and this problem exacerbates existing funding issues. Integration of the clinical trial recruitment process into a clinical care pathway (CCP) may represent an effective way to significantly increase recruitment numbers.

Methods

A respiratory support unit and a CCP for escalation of patients with severe COVID-19 were established on 11 January 2021. The recruitment process for the Randomised Evaluation of COVID-19 Therapy-Respiratory Support trial was integrated into the CCP on the same date. Recruitment data for the trial were collected before and after integration into the CCP.

Results

On integration of the recruitment process into a CCP, there was a significant increase in recruitment numbers. Fifty patients were recruited over 266 days before this process occurred whereas 108 patients were recruited over 49 days after this process. There was a statistically significant increase in both the proportion of recruited patients relative to the number of COVID-19 hospital admissions (change from 2.8% to 9.1%, p<0.0001) and intensive therapy unit admissions (change from 17.8% to 50.2%, p<0.001) over the same period, showing that this increase in recruitment was independent of COVID-19 prevalence.

Discussion

Integrating the trial recruitment process into a CCP can significantly boost recruitment numbers. This represents an innovative model that can be used to maximise recruitment without impacting on the financial and labour costs associated with the running of a respiratory clinical trial.",,pdf:https://bmjopenrespres.bmj.com/content/bmjresp/8/1/e000967.full.pdf; doi:https://doi.org/10.1136/bmjresp-2021-000967; html:https://europepmc.org/articles/PMC8261886; pdf:https://europepmc.org/articles/PMC8261886?pdf=render +35589356,https://doi.org/10.1136/bmjopen-2021-057343,"Linkage of National Congenital Heart Disease Audit data to hospital, critical care and mortality national data sets to enable research focused on quality improvement.","Espuny Pujol F, Pagel C, Brown KL, Doidge JC, Feltbower RG, Franklin RC, Gonzalez-Izquierdo A, Gould DW, Norman LJ, Stickley J, Taylor JA, Crowe S.",,BMJ open,2022,2022-05-19,Y,Congenital heart disease; Audit; Health Informatics; Statistics & Research Methods; Quality In Health Care,,,"

Objectives

To link five national data sets (three registries, two administrative) and create longitudinal healthcare trajectories for patients with congenital heart disease (CHD), describing the quality and the summary statistics of the linked data set.

Design

Bespoke linkage of record-level patient identifiers across five national data sets. Generation of spells of care defined as periods of time-overlapping events across the data sets.

Setting

National Congenital Heart Disease Audit (NCHDA) procedures in public (National Health Service; NHS) hospitals in England and Wales, paediatric and adult intensive care data sets (Paediatric Intensive Care Audit Network; PICANet and the Case Mix Programme from the Intensive Care National Audit & Research Centre; ICNARC-CMP), administrative hospital episodes (hospital episode statistics; HES inpatient, outpatient, accident and emergency; A&E) and mortality registry data.

Participants

Patients with any CHD procedure recorded in NCHDA between April 2000 and March 2017 from public hospitals.

Primary and secondary outcome measures

Primary: number of linked records, number of unique patients and number of generated spells of care. Secondary: quality and completeness of linkage.

Results

There were 143 862 records in NCHDA relating to 96 041 unique patients. We identified 65 797 linked PICANet patient admissions, 4664 linked ICNARC-CMP admissions and over 6 million linked HES episodes of care (1.1M inpatient, 4.7M outpatient). The linked data set had 4 908 153 spells of care after quality checks, with a median (IQR) of 3.4 (1.8-6.3) spells per patient-year. Where linkage was feasible (in terms of year and centre), 95.6% surgical procedure records were linked to a corresponding HES record, 93.9% paediatric (cardiac) surgery procedure records to a corresponding PICANet admission and 76.8% adult surgery procedure records to a corresponding ICNARC-CMP record.

Conclusions

We successfully linked four national data sets to the core data set of all CHD procedures performed between 2000 and 2017. This will enable a much richer analysis of longitudinal patient journeys and outcomes. We hope that our detailed description of the linkage process will be useful to others looking to link national data sets to address important research priorities.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/5/e057343.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-057343; html:https://europepmc.org/articles/PMC9121475; pdf:https://europepmc.org/articles/PMC9121475?pdf=render +37645022,https://doi.org/10.1183/20734735.0058-2023,The impact of poor housing and indoor air quality on respiratory health in children.,"Holden KA, Lee AR, Hawcutt DB, Sinha IP.",,"Breathe (Sheffield, England)",2023,2023-06-01,Y,,,,"It is becoming increasingly apparent that poor housing quality affects indoor air quality, significantly impacting on respiratory health in children and young people. Exposure to damp and/or mould in the home, cold homes and the presence of pests and pollutants all have a significant detrimental impact on child respiratory health. There is a complex relationship between features of poor-quality housing, such as being in a state of disrepair, poor ventilation, overcrowding and being cold, that favour an environment resulting in poor indoor air quality. Children living in rented (private or public) housing are more likely to come from lower-income backgrounds and are most at risk of living in substandard housing posing a serious threat to respiratory health. Children have the right to safe and adequate housing, and research has shown that either rehousing or making modifications to poor-quality housing to improve indoor air quality results in improved respiratory health. Urgent action is needed to address this threat to health. All stakeholders should understand the relationship between poor-quality housing and respiratory health in children and act, working with families, to redress this modifiable risk factor.

Educational aims

The reader should understand how housing quality and indoor air quality affect respiratory health in children.The reader should understand which children are at most risk of living in poor-quality housing.The reader should understand what policy recommendations have been made and what actions need to be undertaken to improve housing quality and respiratory health in children and young people.",,doi:https://doi.org/10.1183/20734735.0058-2023; html:https://europepmc.org/articles/PMC10461733; pdf:https://europepmc.org/articles/PMC10461733?pdf=render 38355192,https://doi.org/10.1136/bmjopen-2023-080678,How far back do we need to look to capture diagnoses in electronic health records? A retrospective observational study of hospital electronic health record data.,"Lewis J, Evison F, Doal R, Field J, Gallier S, Harris S, le Roux P, Osman M, Plummer C, Sapey E, Singer M, Sayer AA, Witham MD, ADMISSION Research Collaborative.",,BMJ open,2024,2024-02-13,Y,Hospitals; Electronic Health Records; Information Extraction,,,"

Objectives

Analysis of routinely collected electronic health data is a key tool for long-term condition research and practice for hospitalised patients. This requires accurate and complete ascertainment of a broad range of diagnoses, something not always recorded on an admission document at a single point in time. This study aimed to ascertain how far back in time electronic hospital records need to be interrogated to capture long-term condition diagnoses.

Design

Retrospective observational study of routinely collected hospital electronic health record data.

Setting

Queen Elizabeth Hospital Birmingham (UK)-linked data held by the PIONEER acute care data hub.

Participants

Patients whose first recorded admission for chronic obstructive pulmonary disease (COPD) exacerbation (n=560) or acute stroke (n=2142) was between January and December 2018 and who had a minimum of 10 years of data prior to the index date.

Outcome measures

We identified the most common International Classification of Diseases version 10-coded diagnoses received by patients with COPD and acute stroke separately. For each diagnosis, we derived the number of patients with the diagnosis recorded at least once over the full 10-year lookback period, and then compared this with shorter lookback periods from 1 year to 9 years prior to the index admission.

Results

Seven of the top 10 most common diagnoses in the COPD dataset reached >90% completeness by 6 years of lookback. Atrial fibrillation and diabetes were >90% coded with 2-3 years of lookback, but hypertension and asthma completeness continued to rise all the way out to 10 years of lookback. For stroke, 4 of the top 10 reached 90% completeness by 5 years of lookback; angina pectoris was >90% coded at 7 years and previous transient ischaemic attack completeness continued to rise out to 10 years of lookback.

Conclusion

A 7-year lookback captures most, but not all, common diagnoses. Lookback duration should be tailored to the conditions being studied.",,pdf:https://bmjopen.bmj.com/content/bmjopen/14/2/e080678.full.pdf; doi:https://doi.org/10.1136/bmjopen-2023-080678; html:https://europepmc.org/articles/PMC10868273; pdf:https://europepmc.org/articles/PMC10868273?pdf=render 33653753,https://doi.org/10.1136/bmjopen-2020-043290,Temporal trends in heart failure medication prescription in a population-based cohort study.,"Uijl A, Vaartjes I, Denaxas S, Hemingway H, Shah A, Cleland J, Grobbee D, Hoes A, Asselbergs FW, Koudstaal S.",,BMJ open,2021,2021-03-02,Y,Heart Failure; Public Health; Cardiac Epidemiology,,,"

Objective

We examined temporal heart failure (HF) prescription patterns in a large representative sample of real-world patients in the UK, using electronic health records (EHR).

Methods

From primary and secondary care EHR, we identified 85 732 patients with a HF diagnosis between 2002 and 2015. Almost 50% of patients with HF were women and the median age was 79.1 (IQR 70.2-85.7) years, with age at diagnosis increasing over time.

Results

We found several trends in pharmacological HF management, including increased beta blocker prescriptions over time (29% in 2002-2005 and 54% in 2013-2015), which was not observed for mineralocorticoid receptor-antagonists (MR-antagonists) (18% in 2002-2005 and 18% in 2013-2015); higher prescription rates of loop diuretics in women and elderly patients together with lower prescription rates of angiotensin-converting enzyme inhibitors and/or angiotensin II receptor blockers, beta blockers or MR-antagonists in these patients; little change in medication prescription rates occurred after 6 months of HF diagnosis and, finally, patients hospitalised for HF who had no recorded follow-up in primary care had considerably lower prescription rates compared with patients with a HF diagnosis in primary care with or without HF hospitalisation.

Conclusion

In the general population, the use of MR-antagonists for HF remained low and did not change throughout 13 years of follow-up. For most patients, few changes were seen in pharmacological management of HF in the 6 months following diagnosis.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/3/e043290.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-043290; html:https://europepmc.org/articles/PMC7929882; pdf:https://europepmc.org/articles/PMC7929882?pdf=render 37532769,https://doi.org/10.1038/s42003-023-05171-9,Direct inference and control of genetic population structure from RNA sequencing data.,"Fachrul M, Karkey A, Shakya M, Judd LM, Harshegyi T, Sim KS, Tonks S, Dongol S, Shrestha R, Salim A, STRATAA study group, Baker S, Pollard AJ, Khor CC, Dolecek C, Basnyat B, Dunstan SJ, Holt KE, Inouye M.",,Communications biology,2023,2023-08-02,Y,,,,"RNAseq data can be used to infer genetic variants, yet its use for estimating genetic population structure remains underexplored. Here, we construct a freely available computational tool (RGStraP) to estimate RNAseq-based genetic principal components (RG-PCs) and assess whether RG-PCs can be used to control for population structure in gene expression analyses. Using whole blood samples from understudied Nepalese populations and the Geuvadis study, we show that RG-PCs had comparable results to paired array-based genotypes, with high genotype concordance and high correlations of genetic principal components, capturing subpopulations within the dataset. In differential gene expression analysis, we found that inclusion of RG-PCs as covariates reduced test statistic inflation. Our paper demonstrates that genetic population structure can be directly inferred and controlled for using RNAseq data, thus facilitating improved retrospective and future analyses of transcriptomic data.",,pdf:https://www.nature.com/articles/s42003-023-05171-9.pdf; doi:https://doi.org/10.1038/s42003-023-05171-9; html:https://europepmc.org/articles/PMC10397182; pdf:https://europepmc.org/articles/PMC10397182?pdf=render @@ -1226,9 +1226,9 @@ PMC10686417,https://doi.org/,The impact of restricted provision of publicly fund 33168126,https://doi.org/10.1192/bjo.2020.42,Impact of schizophrenia genetic liability on the association between schizophrenia and physical illness: data-linkage study.,"Kendall KM, John A, Lee SC, Rees E, Pardiñas AF, Banos MDP, Owen MJ, O'Donovan MC, Kirov G, Lloyd K, Jones I, Legge SE, Walters JTR.",,BJPsych open,2020,2020-11-10,Y,Genetics; Schizophrenia; Physical Health; Psychotic Disorders,,,"

Background

Individuals with schizophrenia are at higher risk of physical illnesses, which are a major contributor to their 20-year reduced life expectancy. It is currently unknown what causes the increased risk of physical illness in schizophrenia.

Aims

To link genetic data from a clinically ascertained sample of individuals with schizophrenia to anonymised National Health Service (NHS) records. To assess (a) rates of physical illness in those with schizophrenia, and (b) whether physical illness in schizophrenia is associated with genetic liability.

Method

We linked genetic data from a clinically ascertained sample of individuals with schizophrenia (Cardiff Cognition in Schizophrenia participants, n = 896) to anonymised NHS records held in the Secure Anonymised Information Linkage (SAIL) databank. Physical illnesses were defined from the General Practice Database and Patient Episode Database for Wales. Genetic liability for schizophrenia was indexed by (a) rare copy number variants (CNVs), and (b) polygenic risk scores.

Results

Individuals with schizophrenia in SAIL had increased rates of epilepsy (standardised rate ratio (SRR) = 5.34), intellectual disability (SRR = 3.11), type 2 diabetes (SRR = 2.45), congenital disorders (SRR = 1.77), ischaemic heart disease (SRR = 1.57) and smoking (SRR = 1.44) in comparison with the general SAIL population. In those with schizophrenia, carrier status for schizophrenia-associated CNVs and neurodevelopmental disorder-associated CNVs was associated with height (P = 0.015-0.017), with carriers being 7.5-7.7 cm shorter than non-carriers. We did not find evidence that the increased rates of poor physical health outcomes in schizophrenia were associated with genetic liability for the disorder.

Conclusions

This study demonstrates the value of and potential for linking genetic data from clinically ascertained research studies to anonymised health records. The increased risk for physical illness in schizophrenia is not caused by genetic liability for the disorder.",,pdf:https://www.cambridge.org/core/services/aop-cambridge-core/content/view/A00360A347FCC91E2E9D0B39FBDCE887/S2056472420000423a.pdf/div-class-title-impact-of-schizophrenia-genetic-liability-on-the-association-between-schizophrenia-and-physical-illness-data-linkage-study-div.pdf; doi:https://doi.org/10.1192/bjo.2020.42; html:https://europepmc.org/articles/PMC7745237; pdf:https://europepmc.org/articles/PMC7745237?pdf=render 35271547,https://doi.org/10.1097/ta.0000000000003592,Does patient preference for online or telephone follow-up impact on response rates and data completeness following injury?,"Gabbe BJ, Hart MJ, Brown A, McLellan S, Morgan MJ, Beck B, de Steiger RS, Cameron PA.",,The journal of trauma and acute care surgery,2022,2022-03-08,N,,,,"

Background

Routine collection of patient-reported outcomes is needed to better understand recovery, benchmark between trauma centers and systems, and monitor outcomes over time. A key component of follow-up methodology is the mode of administration of outcome measures with multiple options available. We aimed to quantify patient preference and compare the response rates and data completeness for telephone and online completion in trauma patients.

Methods

A registry-based cohort study of adult (16 years and older) patients registered to the Victorian State Trauma Registry and Victorian Orthopedic Trauma Outcomes Registry from April 2020 to December 2020 was undertaken. Survivors to discharge were contacted by telephone and offered the option of telephone or online completion of 6-month follow-up using the five-level EuroQol five-dimension (EQ-5D-5L) questionnaire and the 12-item World Health Organization Disability Assessment Schedule (WHODAS). The online and telephone groups were compared for differences in characteristics, follow-up rates, and data completeness. Multivariable logistic regression was used to identify predictors of choosing online completion.

Results

Of the 3,886 patients, 51% (n = 1,994) chose online follow-up, and the follow-up rates were lower for online (77%), compared with telephone (89%), follow-up. Younger age, higher socioeconomic status, and preferred language other than English were associated with higher adjusted odds of choosing online completion. Admission to intensive care was associated with lower adjusted odds of choosing online completion. Completion rate for the EQ-5D-5L utility score was 97% for both groups. A valid total 12-WHODAS score could be calculated for 63% of online respondents compared with 86% for the telephone group.

Conclusion

More than half of trauma patients opted for online completion. Completion rates did differ depending on the questionnaire and telephone follow-up rates were higher. Nevertheless, given the wide diversity of the trauma population, the high rate of online uptake, and potential resource constraints, the study findings largely support the use of dual methods for follow-up.

Level of evidence

Prognostic/Epidemiological, Level III.",,doi:https://doi.org/10.1097/TA.0000000000003592 38643104,https://doi.org/10.1186/s12891-024-07446-6,"Predictors of quality of life, functional status, depression and fatigue in early arthritis: comparison between clinically suspect arthralgia, unclassified arthritis and rheumatoid arthritis.","Torlinska B, Raza K, Filer A, Jutley G, Sahbudin I, Singh R, de Pablo P, Rankin E, Rhodes B, Amft N, Justice E, McGrath C, Baskar S, Trickey J, Calvert M, Falahee M.",,BMC musculoskeletal disorders,2024,2024-04-20,Y,Rheumatoid arthritis; Depression; Fatigue; Functional Status; Health Related Quality Of Life; Undifferentiated Arthritis; Unclassified Arthritis; Clinically Suspect Arthralgia; Pre-ra Stages; Patient-reported Outcomes Measures,,,"

Background

Rheumatoid arthritis (RA) is often preceded by symptomatic phases during which classification criteria are not fulfilled. The health burden of these ""at-risk"" stages is not well described. This study assessed health-related quality of life (HRQoL), function, fatigue and depression in newly presenting patients with clinically suspect arthralgia (CSA), unclassified arthritis (UA) or RA.

Methods

Cross-sectional analysis of baseline Patient-Reported Outcome Measures (PROMs) was conducted in patients from the Birmingham Early Arthritis Cohort. HRQoL, function, depression and fatigue at presentation were assessed using EQ-5D, HAQ-DI, PHQ-9 and FACIT-F. PROMs were compared across CSA, UA and RA and with population averages from the HSE with descriptive statistics. Multivariate linear regression assessed associations between PROMs and clinical and sociodemographic variables.

Results

Of 838 patients included in the analysis, 484 had RA, 200 had CSA and 154 had UA. Patients with RA reported worse outcomes for all PROMs than those with CSA or UA. However, ""mean EQ-5D utilities were 0.65 (95%CI: 0.61 to 0.69) in CSA, 0.61 (0.56 to 0.66) in UA and 0.47 (0.44 to 0.50) in RA, which was lower than in general and older (≥ 65 years) background populations."" In patients with CSA or UA, HRQoL was comparable to chronic conditions such as heart failure, severe COPD or mild angina. Higher BMI and older age (≥ 60 years) predicted worse depression (PHQ-9: -2.47 (-3.85 to -1.09), P < 0.001) and fatigue (FACIT-F: 5.05 (2.37 to 7.73), P < 0.001). Women were more likely to report worse function (HAQ-DI: 0.13 (0.03 to 0.21), P = 0.01) and fatigue (FACIT-F: -3.64 (-5.59 to -1.70), P < 0.001), and residents of more deprived areas experienced decreased function (HAQ-DI: 0.23 (0.10 to 0.36), P = 0.001), greater depression (PHQ-9: 1.89 (0.59 to 3.18), P = 0.004) and fatigue (FACIT-F: -2.60 (-5.11 to 0.09), P = 0.04). After adjustments for confounding factors, diagnostic category was not associated with PROMs, but disease activity and polypharmacy were associated with poorer performance across all PROMs.

Conclusions

Patient-reported outcomes were associated with disease activity and sociodemographic characteristics. Patients presenting with RA reported a higher health burden than those with CSA or UA, however HRQoL in the pre-RA groups was significantly lower than population averages.",,doi:https://doi.org/10.1186/s12891-024-07446-6; html:https://europepmc.org/articles/PMC11031996; pdf:https://europepmc.org/articles/PMC11031996?pdf=render -37516479,https://doi.org/10.1016/s2468-2667(23)00126-3,"Insights from linking police domestic abuse data and health data in South Wales, UK: a linked routine data analysis using decision tree classification.","Kennedy N, Win TL, Bandyopadhyay A, Kennedy J, Rowe B, McNerney C, Evans J, Hughes K, Bellis MA, Jones A, Harrington K, Moore S, Brophy S.",,The Lancet. Public health,2023,2023-08-01,N,,,,"

Background

Exposure to domestic abuse can lead to long-term negative impacts on the victim's physical and psychological wellbeing. The 1998 Crime and Disorder Act requires agencies to collaborate on crime reduction strategies, including data sharing. Although data sharing is feasible for individuals, rarely are whole-agency data linked. This study aimed to examine the knowledge obtained by integrating information from police and health-care datasets through data linkage and analyse associated risk factor clusters.

Methods

This retrospective cohort study analyses data from residents of South Wales who were victims of domestic abuse resulting in a Public Protection Notification (PPN) submission between Aug 12, 2015 and March 31, 2020. The study links these data with the victims' health records, collated within the Secure Anonymised Information Linkage databank, to examine factors associated with the outcome of an Emergency Department attendance, emergency hospital admission, or death within 12 months of the PPN submission. To assess the time to outcome for domestic abuse victims after the index PPN submission, we used Kaplan-Meier survival analysis. We used multivariable Cox regression models to identify which factors contributed the highest risk of experiencing an outcome after the index PPN submission. Finally, we created decision trees to describe specific groups of individuals who are at risk of experiencing a domestic abuse incident and subsequent outcome.

Findings

After excluding individuals with multiple PPN records, duplicates, and records with a poor matching score or missing fields, the resulting clean dataset consisted of 8709 domestic abuse victims, of whom 6257 (71·8%) were female. Within a year of a domestic abuse incident, 3650 (41·9%) individuals had an outcome. Factors associated with experiencing an outcome within 12 months of the PPN included younger victim age (hazard ratio 1·183 [95% CI 1·053-1·329], p=0·0048), further PPN submissions after the initial referral (1·383 [1·295-1·476]; p<0·0001), injury at the scene (1·484 [1·368-1·609]; p<0·0001), assessed high risk (1·600 [1·444-1·773]; p<0·0001), referral to other agencies (1·518 [1·358-1·697]; p<0·0001), history of violence (1·229 [1·134-1·333]; p<0·0001), attempted strangulation (1·311 [1·148-1·497]; p<0·0001), and pregnancy (1·372 [1·142-1·648]; p=0·0007). Health-care data before the index PPN established that previous Emergency Department and hospital admissions, smoking, smoking cessation advice, obstetric codes, and prescription of antidepressants and antibiotics were associated with having a future outcome following a domestic abuse incident.

Interpretation

The results indicate that vulnerable individuals are detectable in multiple datasets before and after involvement of the police. Operationalising these findings could reduce police callouts and future Emergency Department or hospital admissions, and improve outcomes for those who are vulnerable. Strategies include querying previous Emergency Department and hospital admissions, giving a high-risk assessment for a pregnant victim, and facilitating data linkage to identify vulnerable individuals.

Funding

National Institute for Health Research.",,pdf:http://www.thelancet.com/article/S2468266723001263/pdf; doi:https://doi.org/10.1016/S2468-2667(23)00126-3 33475522,https://doi.org/10.2196/18229,Risk Factors and Prevalence of Dilated Cardiomyopathy in Sub-Saharan Africa: Protocol for a Systematic Review.,"Fundikira LS, Chillo P, van Laake LW, Mutagaywa RK, Schmidt AF, Kamuhabwa A, Kwesigabo G, Asselbergs FW.",,JMIR research protocols,2021,2021-01-21,Y,Dilated cardiomyopathy; Sub-Saharan Africa; Cardiomyopathy; Cardiovascular risk factors; Heart Failure,,,"

Background

Cardiomyopathies, defined as diseases involving mainly the heart muscles, are linked to an estimated 5.9 of 100,000 deaths globally. In sub-Saharan Africa, cardiomyopathies constitute 21.4% of heart failure cases, with dilated cardiomyopathy (DCM) being the most common form. The etiology of DCM is heterogeneous and is broadly categorized as genetic or nongenetic, as well as a mixed disease in which genetics interact with intrinsic and environmental factors. Factors such as age, gender, family history, and ethnicity are nonmodifiable, whereas modifiable risk factors include poor nutrition, physical inactivity, and excessive alcohol consumption, among others. However, the relative contribution of the different risk factors to the etiology of DCM is not known in sub-Saharan Africa, and the prevalence of DCM among heart failure patients has not been systematically studied in the region.

Objective

The aim of this review is to synthesize available literature from sub-Saharan Africa on the prevalence of DCM among patients with heart failure, as well as the literature on factors associated with DCM. This paper outlines the protocol that will be followed to conduct the systematic review.

Methods

A limited search of the PubMed database will be performed to identify relevant keywords contained in the title, abstract, and subject descriptors using initial search terms ""heart failure,"" ""cardiomyopathy,"" and ""sub-Saharan Africa."" These search terms and their synonyms will then be used in an extensive search in PubMed, and will address the first research question on prevalence. To address the second research question on risk factors, the terms ""heart failure,"" ""cardiomyopathy,"" and ""cardiovascular risk factors"" in ""Sub-Saharan Africa"" will be used, listing them one by one. Articles published from 2000 and in the English language will be included. Indexed articles in PubMed and Embase will be included, as well as the first 300 articles retrieved from a Google Scholar search. Collected data will be organized in Endnote and then uploaded to the Rayyan web app for systematic reviews. Two reviewers will independently select articles against the inclusion criteria. Discrepancies in reviewer selections will be resolved by an arbitrator. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines for reporting systematic reviews will be applied. A map of sub-Saharan Africa with colors to show disease prevalence in each country will be included. For quantitative data, where possible, odds ratios (for categorical outcome data) or standardized mean differences (for continuous data) and their 95% CIs will be calculated.

Results

The primary outcomes will be the prevalence of DCM among patients with heart failure and cardiovascular risk factors associated with DCM in sub-Saharan Africa. The literature search will begin on January 1, 2021, and data analysis is expected to be completed by April 30, 2021.

Conclusions

This review will provide information on the current status of the prevalence and associated factors of DCM, and possibly identify gaps, including paucity of data or conflicting results that need to be addressed to improve our understanding of DCM in sub-Saharan Africa.

International registered report identifier (irrid)

PRR1-10.2196/18229.",,pdf:https://jmir.org/api/download?alt_name=resprot_v10i1e18229_app1.pdf&filename=7e28e6f3581cda60eb7faa74a1bb7968.pdf; doi:https://doi.org/10.2196/18229; html:https://europepmc.org/articles/PMC7862000 31744503,https://doi.org/10.1186/s12916-019-1438-y,"Bleeding in cardiac patients prescribed antithrombotic drugs: electronic health record phenotyping algorithms, incidence, trends and prognosis.","Pasea L, Chung SC, Pujades-Rodriguez M, Shah AD, Alvarez-Madrazo S, Allan V, Teo JT, Bean D, Sofat R, Dobson R, Banerjee A, Patel RS, Timmis A, Denaxas S, Hemingway H.",,BMC medicine,2019,2019-11-20,Y,Phenotype; Bleeding; Prognosis; Antithrombotic Therapy; Electronic Health Records,The Human Phenome,,"

Background

Clinical guidelines and public health authorities lack recommendations on scalable approaches to defining and monitoring the occurrence and severity of bleeding in populations prescribed antithrombotic therapy.

Methods

We examined linked primary care, hospital admission and death registry electronic health records (CALIBER 1998-2010, England) of patients with newly diagnosed atrial fibrillation, acute myocardial infarction, unstable angina or stable angina with the aim to develop algorithms for bleeding events. Using the developed bleeding phenotypes, Kaplan-Meier plots were used to estimate the incidence of bleeding events and we used Cox regression models to assess the prognosis for all-cause mortality, atherothrombotic events and further bleeding.

Results

We present electronic health record phenotyping algorithms for bleeding based on bleeding diagnosis in primary or hospital care, symptoms, transfusion, surgical procedures and haemoglobin values. In validation of the phenotype, we estimated a positive predictive value of 0.88 (95% CI 0.64, 0.99) for hospitalised bleeding. Amongst 128,815 patients, 27,259 (21.2%) had at least 1 bleeding event, with 5-year risks of bleeding of 29.1%, 21.9%, 25.3% and 23.4% following diagnoses of atrial fibrillation, acute myocardial infarction, unstable angina and stable angina, respectively. Rates of hospitalised bleeding per 1000 patients more than doubled from 1.02 (95% CI 0.83, 1.22) in January 1998 to 2.68 (95% CI 2.49, 2.88) in December 2009 coinciding with the increased rates of antiplatelet and vitamin K antagonist prescribing. Patients with hospitalised bleeding and primary care bleeding, with or without markers of severity, were at increased risk of all-cause mortality and atherothrombotic events compared to those with no bleeding. For example, the hazard ratio for all-cause mortality was 1.98 (95% CI 1.86, 2.11) for primary care bleeding with markers of severity and 1.99 (95% CI 1.92, 2.05) for hospitalised bleeding without markers of severity, compared to patients with no bleeding.

Conclusions

Electronic health record bleeding phenotyping algorithms offer a scalable approach to monitoring bleeding in the population. Incidence of bleeding has doubled in incidence since 1998, affects one in four cardiovascular disease patients, and is associated with poor prognosis. Efforts are required to tackle this iatrogenic epidemic.",A phenotyping algorithm is presented to monitor bleeding in primary and hospital care. Model is well presented in the document and has potential to be scalable and applied to other conditions.,pdf:https://bmcmedicine.biomedcentral.com/track/pdf/10.1186/s12916-019-1438-y; doi:https://doi.org/10.1186/s12916-019-1438-y; html:https://europepmc.org/articles/PMC6864929; pdf:https://europepmc.org/articles/PMC6864929?pdf=render +37516479,https://doi.org/10.1016/s2468-2667(23)00126-3,"Insights from linking police domestic abuse data and health data in South Wales, UK: a linked routine data analysis using decision tree classification.","Kennedy N, Win TL, Bandyopadhyay A, Kennedy J, Rowe B, McNerney C, Evans J, Hughes K, Bellis MA, Jones A, Harrington K, Moore S, Brophy S.",,The Lancet. Public health,2023,2023-08-01,N,,,,"

Background

Exposure to domestic abuse can lead to long-term negative impacts on the victim's physical and psychological wellbeing. The 1998 Crime and Disorder Act requires agencies to collaborate on crime reduction strategies, including data sharing. Although data sharing is feasible for individuals, rarely are whole-agency data linked. This study aimed to examine the knowledge obtained by integrating information from police and health-care datasets through data linkage and analyse associated risk factor clusters.

Methods

This retrospective cohort study analyses data from residents of South Wales who were victims of domestic abuse resulting in a Public Protection Notification (PPN) submission between Aug 12, 2015 and March 31, 2020. The study links these data with the victims' health records, collated within the Secure Anonymised Information Linkage databank, to examine factors associated with the outcome of an Emergency Department attendance, emergency hospital admission, or death within 12 months of the PPN submission. To assess the time to outcome for domestic abuse victims after the index PPN submission, we used Kaplan-Meier survival analysis. We used multivariable Cox regression models to identify which factors contributed the highest risk of experiencing an outcome after the index PPN submission. Finally, we created decision trees to describe specific groups of individuals who are at risk of experiencing a domestic abuse incident and subsequent outcome.

Findings

After excluding individuals with multiple PPN records, duplicates, and records with a poor matching score or missing fields, the resulting clean dataset consisted of 8709 domestic abuse victims, of whom 6257 (71·8%) were female. Within a year of a domestic abuse incident, 3650 (41·9%) individuals had an outcome. Factors associated with experiencing an outcome within 12 months of the PPN included younger victim age (hazard ratio 1·183 [95% CI 1·053-1·329], p=0·0048), further PPN submissions after the initial referral (1·383 [1·295-1·476]; p<0·0001), injury at the scene (1·484 [1·368-1·609]; p<0·0001), assessed high risk (1·600 [1·444-1·773]; p<0·0001), referral to other agencies (1·518 [1·358-1·697]; p<0·0001), history of violence (1·229 [1·134-1·333]; p<0·0001), attempted strangulation (1·311 [1·148-1·497]; p<0·0001), and pregnancy (1·372 [1·142-1·648]; p=0·0007). Health-care data before the index PPN established that previous Emergency Department and hospital admissions, smoking, smoking cessation advice, obstetric codes, and prescription of antidepressants and antibiotics were associated with having a future outcome following a domestic abuse incident.

Interpretation

The results indicate that vulnerable individuals are detectable in multiple datasets before and after involvement of the police. Operationalising these findings could reduce police callouts and future Emergency Department or hospital admissions, and improve outcomes for those who are vulnerable. Strategies include querying previous Emergency Department and hospital admissions, giving a high-risk assessment for a pregnant victim, and facilitating data linkage to identify vulnerable individuals.

Funding

National Institute for Health Research.",,pdf:http://www.thelancet.com/article/S2468266723001263/pdf; doi:https://doi.org/10.1016/S2468-2667(23)00126-3 35616501,https://doi.org/10.1177/14791641221088824,Sleep behaviours and associated habits and the progression of pre-diabetes to type 2 diabetes mellitus in adults: A systematic review and meta-analysis.,"Mostafa SA, Mena SC, Antza C, Balanos G, Nirantharakumar K, Tahrani AA.",,Diabetes & vascular disease research,2022,2022-05-01,Y,Type 2 diabetes mellitus; Sleep disorders; Systematic review; Pre-diabetes,,,"

Introduction

Certain sleep behaviours increase risk of type 2 diabetes mellitus (T2DM) in the general population, but whether they contribute to the progression from pre-diabetes to T2DM is uncertain. We conducted a systematic review to assess this.

Methods

Structured searches were performed on bibliographic databases (MEDLINE, EMBASE and CINAHL) from inception to 26/04/2021 for longitudinal studies/trials consisting of adults⩾18 years with pre-diabetes and sleep behaviours (short or long sleep duration (SD), late chronotype, insomnia, obstructive sleep apnoea, daytime napping and/or night-shift employment) that reported on incident T2DM or glycaemic changes. The Newcastle-Ottawa Scale was used for quality assessment.

Results

Six studies were included. Meta-analysis of three studies (n = 20,139) demonstrated that short SD was associated with greater risk of progression to T2DM, hazard ratio (HR) 1.59 (95% CI 1.29-1.97), I2 heterogeneity score 0%, p < 0.0001, but not for long SD, HR 1.50 (0.86-2.62), I2 heterogeneity 77%, p = 0.15. The systematic review showed insomnia and night-shift duty were associated with higher progression to T2DM. Studies were rated as moderate-to-high quality.

Conclusions

Progression from pre-diabetes to T2DM increases with short SD, but only limited data exists for insomnia and night-shift duty. Whether manipulating sleep could reduce progression from pre-diabetes to T2DM needs to be examined.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9152198; doi:https://doi.org/10.1177/14791641221088824; html:https://europepmc.org/articles/PMC9152198; pdf:https://europepmc.org/articles/PMC9152198?pdf=render 30729733,https://doi.org/10.1111/ijpo.12512,Predictors of objectively measured physical activity in 12-month-old infants: A study of linked birth cohort data with electronic health records.,"Raza H, Zhou SM, Todd C, Christian D, Marchant E, Morgan K, Khanom A, Hill R, Lyons RA, Brophy S.",,Pediatric obesity,2019,2019-02-06,Y,Gestation; Infants; postnatal development; Physical Activity,Improving Public Health,,"

Background

Physical activity (PA) levels are associated with long-term health, and levels of PA when young are predictive of adult activity levels.

Objectives

This study examines factors associated with PA levels in 12-month infants.

Method

One hundred forty-one mother-infant pairs were recruited via a longitudinal birth cohort study (April 2010 to March 2013). The PA level was collected using accelerometers and linked to postnatal notes and electronic medical records via the Secure Anonymised Information Linkage databank. Univariable and multivariable linear regressions were used to examine the factors associated with PA levels.

Results

Using univariable analysis, higher PA was associated with the following (P value less than 0.05): being male, larger infant size, healthy maternal blood pressure levels, full-term gestation period, higher consumption of vegetables (infant), lower consumption of juice (infant), low consumption of adult crisps (infant), longer breastfeeding duration, and more movement during sleep (infant) but fewer night wakings. Combined into a multivariable regression model (R2  = 0.654), all factors remained significant, showing lower PA levels were associated with female gender, smaller infant, preterm birth, higher maternal blood pressure, low vegetable consumption, high crisp consumption, and less night movement.

Conclusion

The PA levels of infants were strongly associated with both gestational and postnatal environmental factors. Healthy behaviours appear to cluster, and a healthy diet was associated with a more active infant. Boys were substantially more active than girls, even at age 12 months. These findings can help inform interventions to promote healthier lives for infants and to understand the determinants of their PA levels.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/ijpo.12512; doi:https://doi.org/10.1111/ijpo.12512; html:https://europepmc.org/articles/PMC6563068; pdf:https://europepmc.org/articles/PMC6563068?pdf=render 35260393,https://doi.org/10.1136/bmjgh-2021-008099,Overcoming disruptions in essential health services during the COVID-19 pandemic in Mexico.,"Doubova SV, Robledo-Aburto ZA, Duque-Molina C, Borrayo-Sánchez G, González-León M, Avilés-Hernández R, Contreras-Sánchez SE, Leslie HH, Kruk M, Pérez-Cuevas R, Arsenault C.",,BMJ global health,2022,2022-03-01,Y,Health Policy; Health Systems; Covid-19,,,,,pdf:https://gh.bmj.com/content/bmjgh/7/3/e008099.full.pdf; doi:https://doi.org/10.1136/bmjgh-2021-008099; html:https://europepmc.org/articles/PMC8905410; pdf:https://europepmc.org/articles/PMC8905410?pdf=render @@ -1240,22 +1240,22 @@ PMC10686417,https://doi.org/,The impact of restricted provision of publicly fund 37119604,https://doi.org/10.1016/j.canep.2023.102367,"Whole-population trends in pathology-confirmed cancer incidence in Northern Ireland, Scotland and Wales during the SARS-CoV-2 pandemic: A retrospective observational study.","Greene GJ, Thomson CS, Donnelly D, Chung D, Bhatti L, Gavin AT, Lawler M, Huws DW, Rolles MJ, Bennée F, Morrison DS.",,Cancer epidemiology,2023,2023-04-21,Y,Pandemic; Population-based Incidence; Covid-19; Sars-cov-2; Pathology-Confirmed Cancer,,,"

Introduction

The COVID-19 epidemic interrupted normal cancer diagnosis procedures. Population-based cancer registries report incidence at least 18 months after it happens. Our goal was to make more timely estimates by using pathologically confirmed cancers (PDC) as a proxy for incidence. We compared the 2020 and 2021 PDC with the 2019 pre-pandemic baseline in Scotland, Wales, and Northern Ireland (NI).

Methods

Numbers of female breast (ICD-10 C50), lung (C33-34), colorectal (C18-20), gynaecological (C51-58), prostate (C61), head and neck (C00-C14, C30-32), upper gastro-intestinal (C15-16), urological (C64-68), malignant melanoma (C43), and non-melanoma skin (NMSC) (C44) cancers were counted. Multiple pairwise comparisons generated incidence rate ratios (IRR).

Results

Data were accessible within 5 months of the pathological diagnosis date. Between 2019 and 2020, the number of pathologically confirmed malignancies (excluding NMSC) decreased by 7315 (14.1 %). Scotland experienced early monthly declines of up to 64 % (colorectal cancers, April 2020 versus April 2019). Wales experienced the greatest overall change in 2020, but Northern Ireland experienced the quickest recovery. The pandemic's effects varied by cancer type, with no significant change in lung cancer diagnoses in Wales in 2020 (IRR 0.97 (95 % CI 0.90-1.05)), followed by an increase in 2021 (IRR 1.11 (1.03-1.20).

Conclusion

PDC are useful in reporting cancer incidence quicker than cancer registrations. Temporal and geographical differences between participating countries mirrored differences in responses to the COVID-19 pandemic, indicating face validity and the potential for quick cancer diagnosis assessment. To verify their sensitivity and specificity against the gold standard of cancer registrations, however, additional research is required.",,doi:https://doi.org/10.1016/j.canep.2023.102367; html:https://europepmc.org/articles/PMC10121133; pdf:https://europepmc.org/articles/PMC10121133?pdf=render 34639581,https://doi.org/10.3390/ijerph181910265,Identifying Prenatal and Postnatal Determinants of Infant Growth: A Structural Equation Modelling Based Cohort Analysis.,"Morgan K, Zhou SM, Hill R, Lyons RA, Paranjothy S, Brophy ST.",,International journal of environmental research and public health,2021,2021-09-29,Y,Pregnancy; Obesity; Public Health; postnatal development; Paediatrics; Physical Activity; Infant Growth; Structural Equation Modelling,,,"

Background

The growth and maturation of infants reflect their overall health and nutritional status. The purpose of this study is to examine the associations of prenatal and early postnatal factors with infant growth (IG).

Methods

A data-driven model was constructed by structural equation modelling to examine the relationships between pre- and early postnatal environmental factors and IG at age 12 months. The IG was a latent variable created from infant weight and waist circumference. Data were obtained on 274 mother-child pairs during pregnancy and the postnatal periods.

Results

Maternal pre-pregnancy BMI emerged as an important predictor of IG with both direct and indirect (mediated through infant birth weight) effects. Infants who gained more weight from birth to 6 months and consumed starchy foods daily at age 12 months, were more likely to be larger by age 12 months. Infant physical activity (PA) levels also emerged as a determinant. The constructed model provided a reasonable fit (χ2 (11) = 21.5, p < 0.05; RMSEA = 0.07; CFI = 0.94; SRMR = 0.05) to the data with significant pathways for all examined variables.

Conclusion

Promoting healthy weight amongst women of child bearing age is important in preventing childhood obesity, and increasing daily infant PA is as important as a healthy infant diet.",,pdf:https://www.mdpi.com/1660-4601/18/19/10265/pdf?version=1633013750; doi:https://doi.org/10.3390/ijerph181910265; html:https://europepmc.org/articles/PMC8507693; pdf:https://europepmc.org/articles/PMC8507693?pdf=render 36194451,https://doi.org/10.2196/40667,Associations Between Depression Symptom Severity and Daily-Life Gait Characteristics Derived From Long-Term Acceleration Signals in Real-World Settings: Retrospective Analysis.,"Zhang Y, Folarin AA, Sun S, Cummins N, Vairavan S, Qian L, Ranjan Y, Rashid Z, Conde P, Stewart C, Laiou P, Sankesara H, Matcham F, White KM, Oetzmann C, Ivan A, Lamers F, Siddi S, Simblett S, Rintala A, Mohr DC, Myin-Germeys I, Wykes T, Haro JM, Penninx BWJH, Narayan VA, Annas P, Hotopf M, Dobson RJB, RADAR-CNS Consortium.",,JMIR mHealth and uHealth,2022,2022-10-04,Y,Monitoring; Depression; Gait; Mental health; Mobile Phones; Mhealth; Mobile Health; Wearable Devices; Acceleration Signals,,,"

Background

Gait is an essential manifestation of depression. However, the gait characteristics of daily walking and their relationships with depression have yet to be fully explored.

Objective

The aim of this study was to explore associations between depression symptom severity and daily-life gait characteristics derived from acceleration signals in real-world settings.

Methods

We used two ambulatory data sets (N=71 and N=215) with acceleration signals collected by wearable devices and mobile phones, respectively. We extracted 12 daily-life gait features to describe the distribution and variance of gait cadence and force over a long-term period. Spearman coefficients and linear mixed-effects models were used to explore the associations between daily-life gait features and depression symptom severity measured by the 15-item Geriatric Depression Scale (GDS-15) and 8-item Patient Health Questionnaire (PHQ-8) self-reported questionnaires. The likelihood-ratio (LR) test was used to test whether daily-life gait features could provide additional information relative to the laboratory gait features.

Results

Higher depression symptom severity was significantly associated with lower gait cadence of high-performance walking (segments with faster walking speed) over a long-term period in both data sets. The linear regression model with long-term daily-life gait features (R2=0.30) fitted depression scores significantly better (LR test P=.001) than the model with only laboratory gait features (R2=0.06).

Conclusions

This study indicated that the significant links between daily-life walking characteristics and depression symptom severity could be captured by both wearable devices and mobile phones. The daily-life gait patterns could provide additional information for predicting depression symptom severity relative to laboratory walking. These findings may contribute to developing clinical tools to remotely monitor mental health in real-world settings.",,pdf:https://mhealth.jmir.org/2022/10/e40667/PDF; doi:https://doi.org/10.2196/40667; html:https://europepmc.org/articles/PMC9579931 -37751239,https://doi.org/10.2196/49438,Design and Evaluation of an Intensive Care Unit Dashboard Built in Response to the COVID-19 Pandemic: Semistructured Interview Study.,"Wac M, Craddock I, Chantziara S, Campbell T, Santos-Rodriguez R, Davidson B, McWilliams C.",,JMIR human factors,2023,2023-09-26,Y,Design; Health; ICU; EPR; intensive care unit; Interview; Intensive Care; Critical Care; Electronic Patient Record; Participatory Design; Ehr; Electronic Health Record; Software Engineering; Clinical Information System; Cis; Thematic Analysis; Dashboard; Human-centered Design; Covid-19; Interactive Display,,,"

Background

Dashboards and interactive displays are becoming increasingly prevalent in most health care settings and have the potential to streamline access to information, consolidate disparate data sources and deliver new insights. Our research focuses on intensive care units (ICUs) which are heavily instrumented, critical care environments that generate vast amounts of data and frequently require individualized support for each patient. Consequently, clinicians experience a high cognitive load, which can translate to suboptimal performance. The global COVID-19 pandemic exacerbated this problem by generating a large number of additional hospitalizations, which necessitated a new tool that would help manage ICUs' census. In a previous study, we interviewed clinicians at the University Hospitals Bristol and Weston National Health Service Foundation Trust to capture the requirements for bespoke dashboards that would alleviate this problem.

Objective

This study aims to design, implement, and evaluate an ICU dashboard to allow for monitoring of the high volume of patients in need of critical care, particularly tailored to high-demand situations, such as those seen during the COVID-19 pandemic.

Methods

Building upon the previously gathered requirements, we developed a dashboard, integrated it within the ICU of a National Health Service trust, and allowed all staff to access our tool. For evaluation purposes, participants were recruited and interviewed following a 25-day period during which they were able to use the dashboard clinically. The semistructured interviews followed a topic guide aimed at capturing the usability of the dashboard, supplemented with additional questions asked post hoc to probe themes established during the interview. Interview transcripts were analyzed using a thematic analysis framework that combined inductive and deductive approaches and integrated the Technology Acceptance Model.

Results

A total of 10 participants with 4 different roles in the ICU (6 consultants, 2 junior doctors, 1 nurse, and 1 advanced clinical practitioner) participated in the interviews. Our analysis generated 4 key topics that prevailed across the data: our dashboard met the usability requirements of the participants and was found useful and intuitive; participants perceived that it impacted their delivery of patient care by improving the access to the information and better equipping them to do their job; the tool was used in a variety of ways and for different reasons and tasks; and there were barriers to integration of our dashboard into practice, including familiarity with existing systems, which stifled the adoption of our tool.

Conclusions

Our findings show that the perceived utility of the dashboard had a positive impact on the clinicians' workflows in the ICU. Improving access to information translated into more efficient patient care and transformed some of the existing processes. The introduction of our tool was met with positive reception, but its integration during the COVID-19 pandemic limited its adoption into practice.",,doi:https://doi.org/10.2196/49438; doi:https://doi.org/10.2196/49438; html:https://europepmc.org/articles/PMC10565627 32518842,https://doi.org/10.12688/wellcomeopenres.15786.1,Inferring the number of COVID-19 cases from recently reported deaths.,"Jombart T, van Zandvoort K, Russell TW, Jarvis CI, Gimma A, Abbott S, Clifford S, Funk S, Gibbs H, Liu Y, Pearson CAB, Bosse NI, Centre for the Mathematical Modelling of Infectious Diseases COVID-19 Working Group, Eggo RM, Kucharski AJ, Edmunds WJ.",,Wellcome open research,2020,2020-04-27,Y,Estimation; Statistics; epidemics; outbreak; Modelling; Covid-19; Sars-cov-2,,,"We estimate the number of COVID-19 cases from newly reported deaths in a population without previous reports. Our results suggest that by the time a single death occurs, hundreds to thousands of cases are likely to be present in that population. This suggests containment via contact tracing will be challenging at this point, and other response strategies should be considered. Our approach is implemented in a publicly available, user-friendly, online tool.",,doi:https://doi.org/10.12688/wellcomeopenres.15786.1; html:https://europepmc.org/articles/PMC7255910; pdf:https://europepmc.org/articles/PMC7255910?pdf=render +37751239,https://doi.org/10.2196/49438,Design and Evaluation of an Intensive Care Unit Dashboard Built in Response to the COVID-19 Pandemic: Semistructured Interview Study.,"Wac M, Craddock I, Chantziara S, Campbell T, Santos-Rodriguez R, Davidson B, McWilliams C.",,JMIR human factors,2023,2023-09-26,Y,Design; Health; ICU; EPR; intensive care unit; Interview; Intensive Care; Critical Care; Electronic Patient Record; Participatory Design; Ehr; Electronic Health Record; Software Engineering; Clinical Information System; Cis; Thematic Analysis; Dashboard; Human-centered Design; Covid-19; Interactive Display,,,"

Background

Dashboards and interactive displays are becoming increasingly prevalent in most health care settings and have the potential to streamline access to information, consolidate disparate data sources and deliver new insights. Our research focuses on intensive care units (ICUs) which are heavily instrumented, critical care environments that generate vast amounts of data and frequently require individualized support for each patient. Consequently, clinicians experience a high cognitive load, which can translate to suboptimal performance. The global COVID-19 pandemic exacerbated this problem by generating a large number of additional hospitalizations, which necessitated a new tool that would help manage ICUs' census. In a previous study, we interviewed clinicians at the University Hospitals Bristol and Weston National Health Service Foundation Trust to capture the requirements for bespoke dashboards that would alleviate this problem.

Objective

This study aims to design, implement, and evaluate an ICU dashboard to allow for monitoring of the high volume of patients in need of critical care, particularly tailored to high-demand situations, such as those seen during the COVID-19 pandemic.

Methods

Building upon the previously gathered requirements, we developed a dashboard, integrated it within the ICU of a National Health Service trust, and allowed all staff to access our tool. For evaluation purposes, participants were recruited and interviewed following a 25-day period during which they were able to use the dashboard clinically. The semistructured interviews followed a topic guide aimed at capturing the usability of the dashboard, supplemented with additional questions asked post hoc to probe themes established during the interview. Interview transcripts were analyzed using a thematic analysis framework that combined inductive and deductive approaches and integrated the Technology Acceptance Model.

Results

A total of 10 participants with 4 different roles in the ICU (6 consultants, 2 junior doctors, 1 nurse, and 1 advanced clinical practitioner) participated in the interviews. Our analysis generated 4 key topics that prevailed across the data: our dashboard met the usability requirements of the participants and was found useful and intuitive; participants perceived that it impacted their delivery of patient care by improving the access to the information and better equipping them to do their job; the tool was used in a variety of ways and for different reasons and tasks; and there were barriers to integration of our dashboard into practice, including familiarity with existing systems, which stifled the adoption of our tool.

Conclusions

Our findings show that the perceived utility of the dashboard had a positive impact on the clinicians' workflows in the ICU. Improving access to information translated into more efficient patient care and transformed some of the existing processes. The introduction of our tool was met with positive reception, but its integration during the COVID-19 pandemic limited its adoption into practice.",,doi:https://doi.org/10.2196/49438; doi:https://doi.org/10.2196/49438; html:https://europepmc.org/articles/PMC10565627 30969971,https://doi.org/10.1371/journal.pone.0213435,Are active children and young people at increased risk of injuries resulting in hospital admission or accident and emergency department attendance? Analysis of linked cohort and electronic hospital records in Wales and Scotland.,"Griffiths LJ, Cortina-Borja M, Tingay K, Bandyopadhyay A, Akbari A, DeStavola BL, Bedford H, Lyons RA, Dezateux C.",,PloS one,2019,2019-04-10,Y,,Improving Public Health,,"

Introduction

Children and young people (CYP) are encouraged to increase time spent being physically active, especially in moderate and vigorous intensity pursuits. However, there is limited evidence on the prospective association of activity levels with injuries resulting in use of hospital services. We examined the relationship between objectively-measured physical activity (PA) and subsequent injuries resulting in hospital admissions or accident and emergency department (A&E) attendances, using linked electronic hospital records (EHR) from a nationally representative prospective cohort of CYP in Wales and Scotland.

Methods

We analysed accelerometer-based estimates of moderate to vigorous (MVPA) and vigorous PA (VPA) from 1,585 (777 [46%] boys) seven-year-old Millennium Cohort Study members, living in Wales or Scotland, whose parents consented to linkage of cohort records to EHRs up until their 14th birthday. Negative binomial regression models adjusted by potential individual, household and area-level confounders, were fitted to estimate associations between average daily minutes of MVPA, and VPA (in 10-minute increments), and number of injury-related hospital admissions and/or A&E attendances from age nine to 14 years.

Results

CYP spent a median of 59.5 and 18.1 minutes in MVPA and VPA/day respectively, with boys significantly more active than girls; 47.3% of children experienced at least one injury-related admission or A&E attendance during the study period. Rates of injury-related hospital admission and/or A&E attendance were positively associated with MVPA and VPA in boys but not in girls: respective adjusted incidence rate ratios (95% CI) for boys: 1.09 (1.01, 1.17) and 1.16 (1.00, 1.34), and for girls: 0.94 (0.86, 1.03) and 0.85 (0.69, 1.04).

Conclusion

Boys but not girls who engage in more intense PA at age seven years are at higher risk of injury-related hospital admission or A&E attendance when aged nine to 14 years than their less active peers. This may reflect gender differences in the type and associated risks of activities undertaken. EHRs can make a useful contribution to injury surveillance and prevention if routinely augmented with information on context and setting of the injuries sustained. Injury prevention initiatives should not discourage engagement in PA and outdoor play given their over-riding health and social benefits.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0213435&type=printable; doi:https://doi.org/10.1371/journal.pone.0213435; html:https://europepmc.org/articles/PMC6457613; pdf:https://europepmc.org/articles/PMC6457613?pdf=render 34304048,https://doi.org/10.1016/j.ebiom.2021.103485,Shorter leukocyte telomere length is associated with adverse COVID-19 outcomes: A cohort study in UK Biobank.,"Wang Q, Codd V, Raisi-Estabragh Z, Musicha C, Bountziouka V, Kaptoge S, Allara E, Angelantonio ED, Butterworth AS, Wood AM, Thompson JR, Petersen SE, Harvey NC, Danesh JN, Samani NJ, Nelson CP.",,EBioMedicine,2021,2021-07-23,Y,,,,"Background Older age is the most powerful risk factor for adverse coronavirus disease-19 (COVID-19) outcomes. It is uncertain whether leucocyte telomere length (LTL), previously proposed as a marker of biological age, is also associated with COVID-19 outcomes. Methods We associated LTL values obtained from participants recruited into UK Biobank (UKB) during 2006-2010 with adverse COVID-19 outcomes recorded by 30 November 2020, defined as a composite of any of the following: hospital admission, need for critical care, respiratory support, or mortality. Using information on 130 LTL-associated genetic variants, we conducted exploratory Mendelian randomisation (MR) analyses in UKB to evaluate whether observational associations might reflect cause-and-effect relationships. Findings Of 6775 participants in UKB who tested positive for infection with SARS-CoV-2 in the community, there were 914 (13.5%) with adverse COVID-19 outcomes. The odds ratio (OR) for adverse COVID-19 outcomes was 1·17 (95% CI 1·05-1·30; P = 0·004) per 1-SD shorter usual LTL, after adjustment for age, sex and ethnicity. Similar ORs were observed in analyses that: adjusted for additional risk factors; disaggregated the composite outcome and reduced the scope for selection or collider bias. In MR analyses, the OR for adverse COVID-19 outcomes was directionally concordant but non-significant. Interpretation Shorter LTL is associated with higher risk of adverse COVID-19 outcomes, independent of several major risk factors for COVID-19 including age. Further data are needed to determine whether this association reflects causality. Funding UK Medical Research Council, Biotechnology and Biological Sciences Research Council and British Heart Foundation.",,pdf:http://www.thelancet.com/article/S2352396421002784/pdf; doi:https://doi.org/10.1016/j.ebiom.2021.103485; html:https://europepmc.org/articles/PMC8299112; pdf:https://europepmc.org/articles/PMC8299112?pdf=render 32249120,https://doi.org/10.1016/j.schres.2020.03.044,"Area deprivation, urbanicity, severe mental illness and social drift - A population-based linkage study using routinely collected primary and secondary care data.","Lee SC, DelPozo-Banos M, Lloyd K, Jones I, Walters JTR, Owen MJ, O'Donovan M, John A.",,Schizophrenia research,2020,2020-04-02,N,Schizophrenia; Bipolar disorder; Deprivation; Severe Mental Illness; Urbanicity; Social Drift,Improving Public Health,mental health,"We investigated whether associations between area deprivation, urbanicity and elevated risk of severe mental illnesses (SMIs, including schizophrenia and bipolar disorder) is accounted for by social drift or social causation. We extracted primary and secondary care electronic health records from 2004 to 2015 from a population of 3.9 million. We identified prevalent and incident individuals with SMIs and their level of deprivation and urbanicity using the Welsh Index of Multiple Deprivation (WIMD) and urban/rural indicator. The presence of social drift was determined by whether odds ratios (ORs) from logistic regression is greater than the incidence rate ratios (IRRs) from Poisson regression. Additionally, we performed longitudinal analysis to measure the proportion of change in deprivation level and rural/urban residence 10 years after an incident diagnosis of SMI and compared it to the general population using standardised rate ratios (SRRs). Prevalence and incidence of SMIs were significantly associated with deprivation and urbanicity (all ORs and IRRs significantly >1). ORs and IRRs were similar across all conditions and cohorts (ranging from 1.1 to 1.4). Results from the longitudinal analysis showed individuals with SMIs are more likely to move compared to the general population. However, they did not preferentially move to more deprived or urban areas. There was little evidence of downward social drift over a 10-year period. These findings have implications for the allocation of resources, service configuration and access to services in deprived communities, as well as, for broader public health interventions addressing poverty, and social and environmental contexts.",,doi:https://doi.org/10.1016/j.schres.2020.03.044; doi:https://doi.org/10.1016/j.schres.2020.03.044 35650647,https://doi.org/10.1186/s41512-022-00124-y,A scoping methodological review of simulation studies comparing statistical and machine learning approaches to risk prediction for time-to-event data.,"Smith H, Sweeting M, Morris T, Crowther MJ.",,Diagnostic and prognostic research,2022,2022-06-02,Y,Survival analysis; Machine Learning; Simulation Studies; Clinical Risk Prediction; Prognostic Modelling,,,"

Background

There is substantial interest in the adaptation and application of so-called machine learning approaches to prognostic modelling of censored time-to-event data. These methods must be compared and evaluated against existing methods in a variety of scenarios to determine their predictive performance. A scoping review of how machine learning methods have been compared to traditional survival models is important to identify the comparisons that have been made and issues where they are lacking, biased towards one approach or misleading.

Methods

We conducted a scoping review of research articles published between 1 January 2000 and 2 December 2020 using PubMed. Eligible articles were those that used simulation studies to compare statistical and machine learning methods for risk prediction with a time-to-event outcome in a medical/healthcare setting. We focus on data-generating mechanisms (DGMs), the methods that have been compared, the estimands of the simulation studies, and the performance measures used to evaluate them.

Results

A total of ten articles were identified as eligible for the review. Six of the articles evaluated a method that was developed by the authors, four of which were machine learning methods, and the results almost always stated that this developed method's performance was equivalent to or better than the other methods compared. Comparisons were often biased towards the novel approach, with the majority only comparing against a basic Cox proportional hazards model, and in scenarios where it is clear it would not perform well. In many of the articles reviewed, key information was unclear, such as the number of simulation repetitions and how performance measures were calculated.

Conclusion

It is vital that method comparisons are unbiased and comprehensive, and this should be the goal even if realising it is difficult. Fully assessing how newly developed methods perform and how they compare to a variety of traditional statistical methods for prognostic modelling is imperative as these methods are already being applied in clinical contexts. Evaluations of the performance and usefulness of recently developed methods for risk prediction should be continued and reporting standards improved as these methods become increasingly popular.",,pdf:https://diagnprognres.biomedcentral.com/track/pdf/10.1186/s41512-022-00124-y; doi:https://doi.org/10.1186/s41512-022-00124-y; html:https://europepmc.org/articles/PMC9161606; pdf:https://europepmc.org/articles/PMC9161606?pdf=render 34781301,https://doi.org/10.1159/000520674,"Identification and Mapping Real-World Data Sources for Heart Failure, Acute Coronary Syndrome, and Atrial Fibrillation.","Studer R, Sartini C, Suzart-Woischnik K, Agrawal R, Natani H, Gill SK, Wirta SB, Asselbergs FW, Dobson R, Denaxas S, Kotecha D.",,Cardiology,2022,2021-11-15,N,Data Sources; cardiovascular; Real-world Data; Real-world Evidence,,,"

Background

Transparent and robust real-world evidence sources are increasingly important for global health, including cardiovascular (CV) diseases. We aimed to identify global real-world data (RWD) sources for heart failure (HF), acute coronary syndrome (ACS), and atrial fibrillation (AF).

Methods

We conducted a systematic review of publications with RWD pertaining to HF, ACS, and AF (2010-2018), generating a list of unique data sources. Metadata were extracted based on the source type (e.g., electronic health records, genomics, and clinical data), study design, population size, clinical characteristics, follow-up duration, outcomes, and assessment of data availability for future studies and linkage.

Results

Overall, 11,889 publications were retrieved for HF, 10,729 for ACS, and 6,262 for AF. From these, 322 (HF), 287 (ACS), and 220 (AF) data sources were selected for detailed review. The majority of data sources had near complete data on demographic variables (HF: 94%, ACS: 99%, and AF: 100%) and considerable data on comorbidities (HF: 77%, ACS: 93%, and AF: 97%). The least reported data categories were drug codes (HF, ACS, and AF: 10%) and caregiver involvement (HF: 6%, ACS: 1%, and AF: 1%). Only a minority of data sources provided information on access to data for other researchers (11%) or whether data could be linked to other data sources to maximize clinical impact (20%). The list and metadata for the RWD sources are publicly available at www.escardio.org/bigdata.

Conclusions

This review has created a comprehensive resource of CV data sources, providing new avenues to improve future real-world research and to achieve better patient outcomes.",,pdf:https://www.karger.com/Article/Pdf/520674; doi:https://doi.org/10.1159/000520674; html:https://europepmc.org/articles/PMC8985014; doi:https://doi.org/10.1159/000520674 29457906,https://doi.org/10.1021/acs.jproteome.7b00879,Optimized Phenotypic Biomarker Discovery and Confounder Elimination via Covariate-Adjusted Projection to Latent Structures from Metabolic Spectroscopy Data.,"Posma JM, Garcia-Perez I, Ebbels TMD, Lindon JC, Stamler J, Elliott P, Holmes E, Nicholson JK.",,Journal of proteome research,2018,2018-02-27,Y,Chemometrics; multivariate data analysis; Biomarker Discovery; Sampling Bias; Covariate Adjustment; Metabolic Phenotyping; Random Matrix Theory; Reanalysis; Monte Carlo Cross-validation; Confounder Elimination,Applied Analytics,,"Metabolism is altered by genetics, diet, disease status, environment, and many other factors. Modeling either one of these is often done without considering the effects of the other covariates. Attributing differences in metabolic profile to one of these factors needs to be done while controlling for the metabolic influence of the rest. We describe here a data analysis framework and novel confounder-adjustment algorithm for multivariate analysis of metabolic profiling data. Using simulated data, we show that similar numbers of true associations and significantly less false positives are found compared to other commonly used methods. Covariate-adjusted projections to latent structures (CA-PLS) are exemplified here using a large-scale metabolic phenotyping study of two Chinese populations at different risks for cardiovascular disease. Using CA-PLS, we find that some previously reported differences are actually associated with external factors and discover a number of previously unreported biomarkers linked to different metabolic pathways. CA-PLS can be applied to any multivariate data where confounding may be an issue and the confounder-adjustment procedure is translatable to other multivariate regression techniques.",,pdf:https://pubs.acs.org/doi/pdf/10.1021/acs.jproteome.7b00879; doi:https://doi.org/10.1021/acs.jproteome.7b00879; html:https://europepmc.org/articles/PMC5891819; pdf:https://europepmc.org/articles/PMC5891819?pdf=render -37389932,https://doi.org/10.2196/44126,Barriers to and Facilitators of Using Remote Measurement Technology in the Long-Term Monitoring of Individuals With ADHD: Interview Study.,"Denyer H, Deng Q, Adanijo A, Asherson P, Bilbow A, Folarin A, Groom MJ, Hollis C, Wykes T, Dobson RJ, Kuntsi J, Simblett S.",,JMIR formative research,2023,2023-06-30,Y,Mobile phone; ADHD; Qualitative analysis; Engagement; Attention-deficit/hyperactivity Disorder; Barriers And Facilitators; Remote Measurement Technology,,,"

Background

Remote measurement technology (RMT) has the potential to address current research and clinical challenges of attention-deficit/hyperactivity disorder (ADHD) symptoms and its co-occurring mental health problems. Despite research using RMT already being successfully applied to other populations, adherence and attrition are potential obstacles when applying RMT to a disorder such as ADHD. Hypothetical views and attitudes toward using RMT in a population with ADHD have previously been explored; however, to our knowledge, there is no previous research that has used qualitative methods to understand the barriers to and facilitators of using RMT in individuals with ADHD following participation in a remote monitoring period.

Objective

We aimed to evaluate the barriers to and facilitators of using RMT in individuals with ADHD compared with a group of people who did not have a diagnosis of ADHD. We also aimed to explore participants' views on using RMT for 1 or 2 years in future studies.

Methods

In total, 20 individuals with ADHD and 20 individuals without ADHD were followed up for 10 weeks using RMT that involved active (questionnaires and cognitive tasks) and passive (smartphone sensors and wearable devices) monitoring; 10 adolescents and adults with ADHD and 12 individuals in a comparison group completed semistructured qualitative interviews at the end of the study period. The interviews focused on potential barriers to and facilitators of using RMT in adults with ADHD. A framework methodology was used to explore the data qualitatively.

Results

Barriers to and facilitators of using RMT were categorized as health-related, user-related, and technology-related factors across both participant groups. When comparing themes that emerged across the participant groups, both individuals with and without ADHD experienced similar barriers and facilitators in using RMT. The participants agreed that RMT can provide useful objective data. However, slight differences between the participant groups were identified as barriers to RMT across all major themes. Individuals with ADHD described the impact that their ADHD symptoms had on participating (health-related theme), commented on the perceived cost of completing the cognitive tasks (user-related theme), and described more technical challenges (technology-related theme) than individuals without ADHD. Hypothetical views on future studies using RMT in individuals with ADHD for 1 or 2 years were positive.

Conclusions

Individuals with ADHD agreed that RMT, which uses repeated measurements with ongoing active and passive monitoring, can provide useful objective data. Although themes overlapped with previous research on barriers to and facilitators of engagement with RMT (eg, depression and epilepsy) and with a comparison group, there are unique considerations for people with ADHD, for example, understanding the impact that ADHD symptoms may have on engaging with RMT. Researchers need to continue working with people with ADHD to develop future RMT studies for longer periods.",,pdf:https://formative.jmir.org/2023/1/e44126/PDF; doi:https://doi.org/10.2196/44126; html:https://europepmc.org/articles/PMC10365629; pdf:https://europepmc.org/articles/PMC10365629?pdf=render 35471746,https://doi.org/10.1186/s13613-022-01011-x,The resilient intensive care unit.,"Salluh JIF, Kurtz P, Bastos LSL, Quintairos A, Zampieri FG, Bozza FA.",,Annals of intensive care,2022,2022-04-26,Y,,,,"

Background

The COVID-19 pandemic tested the capacity of intensive care units (ICU) to respond to a crisis and demonstrated their fragility. Unsurprisingly, higher than usual mortality rates, lengths of stay (LOS), and ICU-acquired complications occurred during the pandemic. However, worse outcomes were not universal nor constant across ICUs and significant variation in outcomes was reported, demonstrating that some ICUs could adequately manage the surge of COVID-19.

Methods

In the present editorial, we discuss the concept of a resilient Intensive Care Unit, including which metrics can be used to address the capacity to respond, sustain results and incorporate new practices that lead to improvement.

Results

We believe that a resiliency analysis adds a component of preparedness to the usual ICU performance evaluation and outcomes metrics to be used during the crisis and in regular times.

Conclusions

The COVID-19 pandemic demonstrated the need for a resilient health system. Although this concept has been discussed for health systems, it was not tested in intensive care. Future studies should evaluate this concept to improve ICU organization for standard and pandemic times.",,pdf:https://annalsofintensivecare.springeropen.com/track/pdf/10.1186/s13613-022-01011-x; doi:https://doi.org/10.1186/s13613-022-01011-x; html:https://europepmc.org/articles/PMC9038989; pdf:https://europepmc.org/articles/PMC9038989?pdf=render +37389932,https://doi.org/10.2196/44126,Barriers to and Facilitators of Using Remote Measurement Technology in the Long-Term Monitoring of Individuals With ADHD: Interview Study.,"Denyer H, Deng Q, Adanijo A, Asherson P, Bilbow A, Folarin A, Groom MJ, Hollis C, Wykes T, Dobson RJ, Kuntsi J, Simblett S.",,JMIR formative research,2023,2023-06-30,Y,Mobile phone; ADHD; Qualitative analysis; Engagement; Attention-deficit/hyperactivity Disorder; Barriers And Facilitators; Remote Measurement Technology,,,"

Background

Remote measurement technology (RMT) has the potential to address current research and clinical challenges of attention-deficit/hyperactivity disorder (ADHD) symptoms and its co-occurring mental health problems. Despite research using RMT already being successfully applied to other populations, adherence and attrition are potential obstacles when applying RMT to a disorder such as ADHD. Hypothetical views and attitudes toward using RMT in a population with ADHD have previously been explored; however, to our knowledge, there is no previous research that has used qualitative methods to understand the barriers to and facilitators of using RMT in individuals with ADHD following participation in a remote monitoring period.

Objective

We aimed to evaluate the barriers to and facilitators of using RMT in individuals with ADHD compared with a group of people who did not have a diagnosis of ADHD. We also aimed to explore participants' views on using RMT for 1 or 2 years in future studies.

Methods

In total, 20 individuals with ADHD and 20 individuals without ADHD were followed up for 10 weeks using RMT that involved active (questionnaires and cognitive tasks) and passive (smartphone sensors and wearable devices) monitoring; 10 adolescents and adults with ADHD and 12 individuals in a comparison group completed semistructured qualitative interviews at the end of the study period. The interviews focused on potential barriers to and facilitators of using RMT in adults with ADHD. A framework methodology was used to explore the data qualitatively.

Results

Barriers to and facilitators of using RMT were categorized as health-related, user-related, and technology-related factors across both participant groups. When comparing themes that emerged across the participant groups, both individuals with and without ADHD experienced similar barriers and facilitators in using RMT. The participants agreed that RMT can provide useful objective data. However, slight differences between the participant groups were identified as barriers to RMT across all major themes. Individuals with ADHD described the impact that their ADHD symptoms had on participating (health-related theme), commented on the perceived cost of completing the cognitive tasks (user-related theme), and described more technical challenges (technology-related theme) than individuals without ADHD. Hypothetical views on future studies using RMT in individuals with ADHD for 1 or 2 years were positive.

Conclusions

Individuals with ADHD agreed that RMT, which uses repeated measurements with ongoing active and passive monitoring, can provide useful objective data. Although themes overlapped with previous research on barriers to and facilitators of engagement with RMT (eg, depression and epilepsy) and with a comparison group, there are unique considerations for people with ADHD, for example, understanding the impact that ADHD symptoms may have on engaging with RMT. Researchers need to continue working with people with ADHD to develop future RMT studies for longer periods.",,pdf:https://formative.jmir.org/2023/1/e44126/PDF; doi:https://doi.org/10.2196/44126; html:https://europepmc.org/articles/PMC10365629; pdf:https://europepmc.org/articles/PMC10365629?pdf=render 38346686,https://doi.org/10.1093/ageing/afae004,The impact of digital technology in care homes on unplanned secondary care usage and associated costs.,"Garner A, Lewis J, Dixon S, Preston N, Caiado CCS, Hanratty B, Jones M, Knight J, Mason SM.",,Age and ageing,2024,2024-02-01,Y,Older People; Emergency Medicine; Care Homes; Long-term Care; Telehealth; Routinely Collected Data,,,"

Background

A substantial number of Emergency Department (ED) attendances by care home residents are potentially avoidable. Health Call Digital Care Homes is an app-based technology that aims to streamline residents' care by recording their observations such as vital parameters electronically. Observations are triaged by remote clinical staff. This study assessed the effectiveness of the Health Call technology to reduce unplanned secondary care usage and associated costs.

Methods

A retrospective analysis of health outcomes and economic impact based on an intervention. The study involved 118 care homes across the North East of UK from 2018 to 2021. Routinely collected NHS secondary care data from County Durham and Darlington NHS Foundation Trust was linked with data from the Health Call app. Three outcomes were modelled monthly using Generalised Linear Mixed Models: counts of emergency attendances, emergency admissions and length of stay of emergency admissions. A similar approach was taken for costs. The impact of Health Call was tested on each outcome using the models.

Findings

Data from 8,702 residents were used in the analysis. Results show Health Call reduces the number of emergency attendances by 11% [6-15%], emergency admissions by 25% [20-39%] and length of stay by 11% [3-18%] (with an additional month-by-month decrease of 28% [24-34%]). The cost analysis found a cost reduction of £57 per resident in 2018, increasing to £113 in 2021.

Interpretation

The introduction of a digital technology, such as Health Call, could significantly reduce contacts with and costs resulting from unplanned secondary care usage by care home residents.",,pdf:https://academic.oup.com/ageing/article-pdf/53/2/afae004/56661196/afae004.pdf; doi:https://doi.org/10.1093/ageing/afae004; html:https://europepmc.org/articles/PMC10861323; pdf:https://europepmc.org/articles/PMC10861323?pdf=render 35487738,https://doi.org/10.1136/bmjopen-2021-057017,Variation in the estimated prevalence of multimorbidity: systematic review and meta-analysis of 193 international studies.,"Ho IS, Azcoaga-Lorenzo A, Akbari A, Davies J, Hodgins P, Khunti K, Kadam U, Lyons R, McCowan C, Mercer SW, Nirantharakumar K, Guthrie B.",,BMJ open,2022,2022-04-29,Y,epidemiology; Geriatric Medicine; General Medicine (See Internal Medicine),,,"

Objective

(1) To estimate the pooled prevalence of multimorbidity in all age groups, globally. (2) To examine how measurement of multimorbidity impacted the estimated prevalence.

Methods

In this systematic review and meta-analysis, we conducted searches in nine bibliographic databases (PsycINFO, Embase, Global Health, Medline, Scopus, Web of Science, Cochrane Library, CINAHL and ProQuest Dissertations and Theses Global) for prevalence studies published between database inception and 21 January 2020. Studies reporting the prevalence of multimorbidity (in all age groups and in community, primary care, care home and hospital settings) were included. Studies with an index condition or those that did not include people with no long-term conditions in the denominator were excluded. Retrieved studies were independently reviewed by two reviewers, and relevant data were extracted using predesigned pro forma. We used meta-analysis to pool the estimated prevalence of multimorbidity across studies, and used random-effects meta-regression and subgroup analysis to examine the association of heterogeneous prevalence estimates with study and measure characteristics.

Results

13 807 titles were screened, of which 193 met inclusion criteria for meta-analysis. The pooled prevalence of multimorbidity was 42.4% (95% CI 38.9% to 46.0%) with high heterogeneity (I2 >99%). In adjusted meta-regression models, participant mean age and the number of conditions included in a measure accounted for 47.8% of heterogeneity in effect sizes. The estimated prevalence of multimorbidity was significantly higher in studies with older adults and those that included larger numbers of conditions. There was no significant difference in estimated prevalence between low-income or middle-income countries (36.8%) and high-income countries (44.3%), or between self-report (40.0%) and administrative/clinical databases (52.7%).

Conclusions

The pooled prevalence of multimorbidity was significantly higher in older populations and when studies included a larger number of baseline conditions. The findings suggest that, to improve study comparability and quality of reporting, future studies should use a common core conditions set for multimorbidity measurement and report multimorbidity prevalence stratified by sociodemographics.PROSPERO registration numberCRD42020172409.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/4/e057017.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-057017; html:https://europepmc.org/articles/PMC9058768; pdf:https://europepmc.org/articles/PMC9058768?pdf=render 34459398,https://doi.org/10.3233/jad-210462,Assessing Genetic Overlap and Causality Between Blood Plasma Proteins and Alzheimer's Disease.,"Handy A, Lord J, Green R, Xu J, Aarsland D, Velayudhan L, Hye A, Dobson R, Proitsi P, Alzheimer’s Disease Neuroimaging initiative, AddNeuroMed, and the GERAD1 Consortium.",,Journal of Alzheimer's disease : JAD,2021,2021-01-01,Y,Apolipoprotein E; Blood proteins; Alzheimer’s disease; C-reactive Protein; Apolipoprotein B-100; Insulin-like Growth Factor Binding Protein 2; Vitamin D-binding Protein; Mendelian Randomization Analysis; Polygenic Trait,,,"

Background

Blood plasma proteins have been associated with Alzheimer's disease (AD), but understanding which proteins are on the causal pathway remains challenging.

Objective

Investigate the genetic overlap between candidate proteins and AD using polygenic risk scores (PRS) and interrogate their causal relationship using bi-directional Mendelian randomization (MR).

Methods

Following a literature review, 31 proteins were selected for PRS analysis. PRS were constructed for prioritized proteins with and without the apolipoprotein E region (APOE+/-PRS) and tested for association with AD status across three cohorts (n = 6,244). An AD PRS was also tested for association with protein levels in one cohort (n = 410). Proteins showing association with AD were taken forward for MR.

Results

For APOE ɛ3, apolipoprotein B-100, and C-reactive protein (CRP), protein APOE+ PRS were associated with AD below Bonferroni significance (pBonf, p < 0.00017). No protein APOE- PRS or AD PRS (APOE+/-) passed pBonf. However, vitamin D-binding protein (protein PRS APOE-, p = 0.009) and insulin-like growth factor-binding protein 2 (AD APOE- PRS p = 0.025, protein APOE- PRS p = 0.045) displayed suggestive signals and were selected for MR. In bi-directional MR, none of the five proteins demonstrated a causal association (p < 0.05) in either direction.

Conclusion

Apolipoproteins and CRP PRS are associated with AD and provide a genetic signal linked to a specific, accessible risk factor. While evidence of causality was limited, this study was conducted in a moderate sample size and provides a framework for larger samples with greater statistical power.",,pdf:https://content.iospress.com:443/download/journal-of-alzheimers-disease/jad210462?id=journal-of-alzheimers-disease%2Fjad210462; doi:https://doi.org/10.3233/JAD-210462; html:https://europepmc.org/articles/PMC8609677; pdf:https://europepmc.org/articles/PMC8609677?pdf=render 34639458,https://doi.org/10.3390/ijerph181910156,Health-Related Quality of Life (HRQoL) Outcomes Following Injury in Childhood and Adolescence Using EuroQol (EQ-5D) Responses with Pooled Longitudinal Data.,"Dipnall JF, Rivara FP, Lyons RA, Ameratunga S, Brussoni M, Lecky FE, Bradley C, Beck B, Lyons J, Schneeberg A, Harrison JE, Gabbe BJ.",,International journal of environmental research and public health,2021,2021-09-27,Y,Trauma; Children; Injury; Pediatric; Adolescents; Disability; Health-related Quality Of Life; Health Outcomes; Eq-5d,,,"

Background

Injury is a leading contributor to the global disease burden in children, affecting their health-related quality of life (HRQoL)-yet valid estimates of burden are absent.

Methods

This study pooled longitudinal data from five cohort studies of pediatric injury survivors (5-17 years) at baseline, 1-, 4-, 6-, 12-, and 24- months (n = 2334). HRQoL post-injury was measured using the 3-level EQ-5D utility score (EQ-5D) and five health states (mobility, self-care, activity, pain, anxiety and depression (anxiety)).

Results

Mean EQ-5D post-injury did not return to baseline level (0.95) by 24 months (0.88) and was lower for females over time (-0.04, 95%CI -0.05, -0.02). A decreased adjusted risk ratio over time (ARR) was observed for intentional injuries (pain: 0.85, 95%CI 0.73,0.98; anxiety: 0.62, 95%CI 0.49,0.78); spinal cord injuries (mobility: 0.61, 95%CI 0.45,0.83), self-care: 0.76, 95%CI 0.63,0.91, activity: 0.64, 95%CI 0.47,0.88); moderate/severe traumatic brain injury (activity: 0.83, 95%CI 0.71,0.96). ARRs were also low for certain fractures, with various health states affected.

Conclusions

HRQoL outcomes over time for children and adolescents post-injury differed across key demographic and injury related attributes. HRQoL did not reach levels consistent with full health by 24 months with recovery plateauing from 6 to 24 months. Tailored interventions are required to respond to the varying post-injury recovery trajectories in this population.",,doi:https://doi.org/10.3390/ijerph181910156; html:https://europepmc.org/articles/PMC8507627; pdf:https://europepmc.org/articles/PMC8507627?pdf=render -38388919,https://doi.org/10.1186/s12913-024-10716-7,"Spatio-temporal modelling of referrals to outpatient respiratory clinics in the integrated care system of the Morecambe Bay area, England.","Mountain R, Knight J, Heys K, Giorgi E, Gatheral T.",,BMC health services research,2024,2024-02-22,Y,Spatio-temporal; Integrated Care; Chronic Respiratory Disease; Routinely Collected Data; Outpatient Referrals,,,"

Background

Promoting integrated care is a key goal of the NHS Long Term Plan to improve population respiratory health, yet there is limited data-driven evidence of its effectiveness. The Morecambe Bay Respiratory Network is an integrated care initiative operating in the North-West of England since 2017. A key target area has been reducing referrals to outpatient respiratory clinics by upskilling primary care teams. This study aims to explore space-time patterns in referrals from general practice in the Morecambe Bay area to evaluate the impact of the initiative.

Methods

Data on referrals to outpatient clinics and chronic respiratory disease patient counts between 2012-2020 were obtained from the Morecambe Bay Community Data Warehouse, a large store of routinely collected healthcare data. For analysis, the data is aggregated by year and small area geography. The methodology comprises of two parts. The first explores the issues that can arise when using routinely collected primary care data for space-time analysis and applies spatio-temporal conditional autoregressive modelling to adjust for data complexities. The second part models the rate of outpatient referral via a Poisson generalised linear mixed model that adjusts for changes in demographic factors and number of respiratory disease patients.

Results

The first year of the Morecambe Bay Respiratory Network was not associated with a significant difference in referral rate. However, the second and third years saw significant reductions in areas that had received intervention, with full intervention associated with a 31.8% (95% CI 17.0-43.9) and 40.5% (95% CI 27.5-50.9) decrease in referral rate in 2018 and 2019, respectively.

Conclusions

Routinely collected data can be used to robustly evaluate key outcome measures of integrated care. The results demonstrate that effective integrated care has real potential to ease the burden on respiratory outpatient services by reducing the need for an onward referral. This is of great relevance given the current pressure on outpatient services globally, particularly long waiting lists following the COVID-19 pandemic and the need for more innovative models of care.",,doi:https://doi.org/10.1186/s12913-024-10716-7; html:https://europepmc.org/articles/PMC10882730; pdf:https://europepmc.org/articles/PMC10882730?pdf=render 30999919,https://doi.org/10.1186/s12911-019-0805-0,Identifying clinically important COPD sub-types using data-driven approaches in primary care population based electronic health records.,"Pikoula M, Quint JK, Nissen F, Hemingway H, Smeeth L, Denaxas S.",,BMC medical informatics and decision making,2019,2019-04-18,Y,Cluster analysis; Electronic Health Records; Copd Exacerbations; Copd Epidemiology,The Human Phenome,,"

Background

COPD is a highly heterogeneous disease composed of different phenotypes with different aetiological and prognostic profiles and current classification systems do not fully capture this heterogeneity. In this study we sought to discover, describe and validate COPD subtypes using cluster analysis on data derived from electronic health records.

Methods

We applied two unsupervised learning algorithms (k-means and hierarchical clustering) in 30,961 current and former smokers diagnosed with COPD, using linked national structured electronic health records in England available through the CALIBER resource. We used 15 clinical features, including risk factors and comorbidities and performed dimensionality reduction using multiple correspondence analysis. We compared the association between cluster membership and COPD exacerbations and respiratory and cardiovascular death with 10,736 deaths recorded over 146,466 person-years of follow-up. We also implemented and tested a process to assign unseen patients into clusters using a decision tree classifier.

Results

We identified and characterized five COPD patient clusters with distinct patient characteristics with respect to demographics, comorbidities, risk of death and exacerbations. The four subgroups were associated with 1) anxiety/depression; 2) severe airflow obstruction and frailty; 3) cardiovascular disease and diabetes and 4) obesity/atopy. A fifth cluster was associated with low prevalence of most comorbid conditions.

Conclusions

COPD patients can be sub-classified into groups with differing risk factors, comorbidities, and prognosis, based on data included in their primary care records. The identified clusters confirm findings of previous clustering studies and draw attention to anxiety and depression as important drivers of the disease in young, female patients.",,pdf:https://bmcmedinformdecismak.biomedcentral.com/track/pdf/10.1186/s12911-019-0805-0; doi:https://doi.org/10.1186/s12911-019-0805-0; html:https://europepmc.org/articles/PMC6472089; pdf:https://europepmc.org/articles/PMC6472089?pdf=render +38388919,https://doi.org/10.1186/s12913-024-10716-7,"Spatio-temporal modelling of referrals to outpatient respiratory clinics in the integrated care system of the Morecambe Bay area, England.","Mountain R, Knight J, Heys K, Giorgi E, Gatheral T.",,BMC health services research,2024,2024-02-22,Y,Spatio-temporal; Integrated Care; Chronic Respiratory Disease; Routinely Collected Data; Outpatient Referrals,,,"

Background

Promoting integrated care is a key goal of the NHS Long Term Plan to improve population respiratory health, yet there is limited data-driven evidence of its effectiveness. The Morecambe Bay Respiratory Network is an integrated care initiative operating in the North-West of England since 2017. A key target area has been reducing referrals to outpatient respiratory clinics by upskilling primary care teams. This study aims to explore space-time patterns in referrals from general practice in the Morecambe Bay area to evaluate the impact of the initiative.

Methods

Data on referrals to outpatient clinics and chronic respiratory disease patient counts between 2012-2020 were obtained from the Morecambe Bay Community Data Warehouse, a large store of routinely collected healthcare data. For analysis, the data is aggregated by year and small area geography. The methodology comprises of two parts. The first explores the issues that can arise when using routinely collected primary care data for space-time analysis and applies spatio-temporal conditional autoregressive modelling to adjust for data complexities. The second part models the rate of outpatient referral via a Poisson generalised linear mixed model that adjusts for changes in demographic factors and number of respiratory disease patients.

Results

The first year of the Morecambe Bay Respiratory Network was not associated with a significant difference in referral rate. However, the second and third years saw significant reductions in areas that had received intervention, with full intervention associated with a 31.8% (95% CI 17.0-43.9) and 40.5% (95% CI 27.5-50.9) decrease in referral rate in 2018 and 2019, respectively.

Conclusions

Routinely collected data can be used to robustly evaluate key outcome measures of integrated care. The results demonstrate that effective integrated care has real potential to ease the burden on respiratory outpatient services by reducing the need for an onward referral. This is of great relevance given the current pressure on outpatient services globally, particularly long waiting lists following the COVID-19 pandemic and the need for more innovative models of care.",,doi:https://doi.org/10.1186/s12913-024-10716-7; html:https://europepmc.org/articles/PMC10882730; pdf:https://europepmc.org/articles/PMC10882730?pdf=render 36932161,https://doi.org/10.1038/s41433-023-02478-z,Evaluating patient-reported outcome measures (PROMs) for future clinical trials in adult patients with optic neuritis.,"Panthagani J, O'Donovan C, Aiyegbusi OL, Liu X, Bayliss S, Calvert M, Pesudovs K, Denniston AK, Moore DJ, Braithwaite T.",,"Eye (London, England)",2023,2023-03-17,Y,,,,"

Objective

To search for and critically appraise the psychometric quality of patient-reported outcome measures (PROMs) developed or validated in optic neuritis, in order to support high-quality research and care.

Methods

We systematically searched MEDLINE(Ovid), Embase(Ovid), PsycINFO(Ovid) and CINAHLPlus(EBSCO), and additional grey literature to November 2021, to identify PROM development or validation studies applicable to optic neuritis associated with any systemic or neurologic disease in adults. We included instruments developed using classic test theory or Rasch analysis approaches. We used established quality criteria to assess content development, validity, reliability, and responsiveness, grading multiple domains from A (high quality) to C (low quality).

Results

From 3142 screened abstracts we identified five PROM instruments potentially applicable to optic neuritis: three differing versions of the National Eye Institute (NEI)-Visual Function Questionnaire (VFQ): the 51-item VFQ; the 25-item VFQ and a 10-item neuro-ophthalmology supplement; and the Impact of Visual Impairment Scale (IVIS), a constituent of the Multiple Sclerosis Quality of Life Inventory (MSQLI) handbook, derived from the Functional Assessment of Multiple Sclerosis (FAMS). Psychometric appraisal revealed the NEI-VFQ-51 and 10-item neuro module had some relevant content development but weak psychometric development, and the FAMS had stronger psychometric development using Rasch Analysis, but was only somewhat relevant to optic neuritis. We identified no content or psychometric development for IVIS.

Conclusion

There is unmet need for a PROM with strong content and psychometric development applicable to optic neuritis for use in virtual care pathways and clinical trials to support drug marketing authorisation.",,pdf:https://www.nature.com/articles/s41433-023-02478-z.pdf; doi:https://doi.org/10.1038/s41433-023-02478-z; html:https://europepmc.org/articles/PMC10022552; pdf:https://europepmc.org/articles/PMC10022552?pdf=render 37225263,https://doi.org/10.1136/bmjgast-2023-001139,Delphi consensus survey: the opinions of patients living with refractory ulcerative proctitis and the health care professionals who care for them.,"Kyriacou M, Radford S, Moran GW, Focus group collaborators group.",,BMJ open gastroenterology,2023,2023-05-01,Y,Ulcerative colitis; Inflammatory Bowel Disease; Adjuvant Treatment,,,"

Background

Refractory ulcerative proctitis presents a huge clinical challenge not only for the patients living with this chronic, progressive condition but also for the professionals who care for them. Currently, there is limited research and evidence-based guidance, resulting in many patients living with the symptomatic burden of disease and reduced quality of life. The aim of this study was to establish a consensus on the thoughts and opinions related to refractory proctitis disease burden and best practice for management.

Methods

A three-round Delphi consensus survey was conducted among patients living with refractory proctitis and the healthcare experts with knowledge on this disease from the UK. A brainstorming stage involving a focus group where the participants came up with an initial list of statements was completed. Following this, there were three rounds of Delphi surveys in which the participants were asked to rank the importance of the statements and provide any additional comments or clarifications. Calculation of mean scores, analysis of comments and revisions were performed to produce a final list of statements.

Results

In total, 14 statements were suggested by the focus group at the initial brainstorming stage. Following completion of three Delphi survey rounds, all 14 statements reached consensus following appropriate revision.

Conclusions

We established consensus on the thoughts and opinions related to refractory proctitis from both the experts who manage this disease and the patients living with it. This represents the first step towards developing clinical research data and ultimately the evidence needed for best practice management guidance of this condition.",,pdf:https://bmjopengastro.bmj.com/content/bmjgast/10/1/e001139.full.pdf; doi:https://doi.org/10.1136/bmjgast-2023-001139; html:https://europepmc.org/articles/PMC10230891; pdf:https://europepmc.org/articles/PMC10230891?pdf=render 37394283,https://doi.org/10.1002/ehf2.14444,Survival after HeartMate 3 left ventricular assist device implantation: real-world data from Europe.,"Numan L, Schramm R, Oerlemans MIFJ, van der Kaaij NP, Aarts E, Ramjankhan FZ, Oppelaar AM, Morshuis M, Guenther SPW, Zimpfer D, Riebandt J, Wiedemann D, Asselbergs FW, Van Laake LW.",,ESC heart failure,2023,2023-07-02,Y,,,,,,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ehf2.14444; doi:https://doi.org/10.1002/ehf2.14444; html:https://europepmc.org/articles/PMC10375103; pdf:https://europepmc.org/articles/PMC10375103?pdf=render @@ -1277,8 +1277,8 @@ PMC10686417,https://doi.org/,The impact of restricted provision of publicly fund 34125897,https://doi.org/10.1093/nar/gkab449,DGLinker: flexible knowledge-graph prediction of disease-gene associations.,"Hu J, Lepore R, Dobson RJB, Al-Chalabi A, M Bean D, Iacoangeli A.",,Nucleic acids research,2021,2021-07-01,Y,,,,"As a result of the advent of high-throughput technologies, there has been rapid progress in our understanding of the genetics underlying biological processes. However, despite such advances, the genetic landscape of human diseases has only marginally been disclosed. Exploiting the present availability of large amounts of biological and phenotypic data, we can use our current understanding of disease genetics to train machine learning models to predict novel genetic factors associated with the disease. To this end, we developed DGLinker, a webserver for the prediction of novel candidate genes for human diseases given a set of known disease genes. DGLinker has a user-friendly interface that allows non-expert users to exploit biomedical information from a wide range of biological and phenotypic databases, and/or to upload their own data, to generate a knowledge-graph and use machine learning to predict new disease-associated genes. The webserver includes tools to explore and interpret the results and generates publication-ready figures. DGLinker is available at https://dglinker.rosalind.kcl.ac.uk. The webserver is free and open to all users without the need for registration.",,doi:https://doi.org/10.1093/nar/gkab449; doi:https://doi.org/10.1093/nar/gkab449; html:https://europepmc.org/articles/PMC8262728; pdf:https://europepmc.org/articles/PMC8262728?pdf=render 32894757,https://doi.org/10.1093/ageing/afaa138,Short physical performance battery as a practical tool to assess mortality risk in chronic obstructive pulmonary disease.,"Fermont JM, Mohan D, Fisk M, Bolton CE, Macnee W, Cockcroft JR, McEniery C, Fuld J, Cheriyan J, Tal-Singer R, Müllerova H, Wood AM, Wilkinson IB, Polkey MI, ERICA consortium.",,Age and ageing,2021,2021-05-01,Y,Mortality; Skeletal muscle; Biomarkers; Older People; chronic obstructive pulmonary disease,,,"

Rationale

chronic obstructive pulmonary disease (COPD) is a leading cause of mortality and common in older adults. The BODE Index is the most recognised mortality risk score in COPD but includes a 6-minute walk test (6MWT) that is seldom available in practise; the BODE Index may be better adopted if the 6MWT was replaced.

Objectives

we investigated whether a modified BODE Index in which 6MWT was replaced by an alternative measure of physical capacity, specifically the short physical performance battery (SPPB) or components, retained its predictive ability for mortality in individuals with COPD.

Methods

we analysed 630 COPD patients from the ERICA cohort study for whom UK Office for National Statistics verified mortality data were available. Variables tested at baseline included spirometry, 6MWT, SPPB and its components (4-m gait speed test [4MGS], chair stand and balance). Predictive models were developed using stratified multivariable Cox regression, and assessed by C-indices and calibration plots with 10-fold cross-validation and replication.

Results

during median 2 years of follow-up, 60 (10%) individuals died. There was no significant difference between the discriminative ability of BODE6MWT (C-index 0.709, 95% confidence interval [CI], 0.680-0.737), BODESPPB (C-index 0.683, 95% CI, 0.647-0.712), BODE4MGS (C-index 0.676, 95% CI, 0.643-0.700) and BODEBALANCE (C-index 0.686, 95% CI, 0.651-0.713) for predicting mortality.

Conclusions

the SPPB, and its 4MGS and balance components, can potentially be used as an alternative to the 6MWT in the BODE Index without significant loss of predictive ability in all-cause mortality.",,pdf:https://academic.oup.com/ageing/article-pdf/50/3/795/37807880/afaa138.pdf; doi:https://doi.org/10.1093/ageing/afaa138; html:https://europepmc.org/articles/PMC8098797; pdf:https://europepmc.org/articles/PMC8098797?pdf=render 38778017,https://doi.org/10.1038/s41541-024-00878-0,Influence of individuals' determinants including vaccine type on cellular and humoral responses to SARS-CoV-2 vaccination.,"Chambers ES, Cai W, Vivaldi G, Jolliffe DA, Perdek N, Li W, Faustini SE, Gibbons JM, Pade C, Richter AG, Coussens AK, Martineau AR.",,NPJ vaccines,2024,2024-05-22,Y,,,,"Vaccine development targeting SARS-CoV-2 in 2020 was of critical importance in reducing COVID-19 severity and mortality. In the U.K. during the initial roll-out most individuals either received two doses of Pfizer COVID-19 vaccine (BNT162b2) or the adenovirus-based vaccine from Oxford/AstraZeneca (ChAdOx1-nCoV-19). There are conflicting data as to the impact of age, sex and body habitus on cellular and humoral responses to vaccination, and most studies in this area have focused on determinants of mRNA vaccine immunogenicity. Here, we studied a cohort of participants in a population-based longitudinal study (COVIDENCE UK) to determine the influence of age, sex, body mass index (BMI) and pre-vaccination anti-Spike (anti-S) antibody status on vaccine-induced humoral and cellular immune responses to two doses of BNT162b2 or ChAdOx-n-CoV-19 vaccination. Younger age and pre-vaccination anti-S seropositivity were both associated with stronger antibody responses to vaccination. BNT162b2 generated higher neutralising and anti-S antibody titres to vaccination than ChAdOx1-nCoV-19, but cellular responses to the two vaccines were no different. Irrespective of vaccine type, increasing age was also associated with decreased frequency of cytokine double-positive CD4+T cells. Increasing BMI was associated with reduced frequency of SARS-CoV-2-specific TNF+CD8% T cells for both vaccines. Together, our findings demonstrate that increasing age and BMI are associated with attenuated cellular and humoral responses to SARS-CoV-2 vaccination. Whilst both vaccines induced T cell responses, BNT162b2 induced significantly elevated humoral immune response as compared to ChAdOx-n-CoV-19.",,pdf:https://www.nature.com/articles/s41541-024-00878-0.pdf; doi:https://doi.org/10.1038/s41541-024-00878-0; html:https://europepmc.org/articles/PMC11111746; pdf:https://europepmc.org/articles/PMC11111746?pdf=render -36660920,https://doi.org/10.1093/ehjci/jeac270,The role of obesity-related cardiovascular remodelling in mediating incident cardiovascular outcomes: a population-based observational study.,"Szabo L, McCracken C, Cooper J, Rider OJ, Vago H, Merkely B, Harvey NC, Neubauer S, Petersen SE, Raisi-Estabragh Z.",,European heart journal. Cardiovascular Imaging,2023,2023-06-01,Y,Obesity; body mass index; Mediation; Cardiac Magnetic Resonance Imaging; Cardiovascular Remodelling; Waist-to-hip Ratio; Disease Mechanisms; Incident Cardiovascular Outcomes,,,"

Aims

We examined associations of obesity with incident cardiovascular outcomes and cardiovascular magnetic resonance (CMR) phenotypes, integrating information from body mass index (BMI) and waist-to-hip ratio (WHR). Then, we used multiple mediation to define the role of obesity-related cardiac remodelling in driving obesity-outcome associations, independent of cardiometabolic diseases.

Methods and results

In 491 606 UK Biobank participants, using Cox proportional hazard models, greater obesity (higher WHR, higher BMI) was linked to significantly greater risk of incident ischaemic heart disease, atrial fibrillation (AF), heart failure (HF), all-cause mortality, and cardiovascular disease (CVD) mortality. In combined stratification by BMI and WHR thresholds, elevated WHR was associated with greater risk of adverse outcomes at any BMI level. Individuals with overweight BMI but normal WHR had weaker disease associations. In the subset of participants with CMR (n = 31 107), using linear regression, greater obesity was associated with higher left ventricular (LV) mass, greater LV concentricity, poorer LV systolic function, lower myocardial native T1, larger left atrial (LA) volumes, poorer LA function, and lower aortic distensibility. Of note, higher BMI was linked to higher, whilst greater WHR was linked to lower LV end-diastolic volume (LVEDV). In Cox models, greater LVEDV and LV mass (LVM) were linked to increased risk of CVD, most importantly HF and an increased LA maximal volume was the key predictive measure of new-onset AF. In multiple mediation analyses, hypertension and adverse LV remodelling (higher LVM, greater concentricity) were major independent mediators of the obesity-outcome associations. Atrial remodelling and native T1 were additional mediators in the associations of obesity with AF and HF, respectively.

Conclusions

We demonstrate associations of obesity with adverse cardiovascular phenotypes and their significant independent role in mediating obesity-outcome relationships. In addition, our findings support the integrated use of BMI and WHR to evaluate obesity-related cardiovascular risk.",,pdf:https://academic.oup.com/ehjcimaging/advance-article-pdf/doi/10.1093/ehjci/jeac270/48798234/jeac270.pdf; doi:https://doi.org/10.1093/ehjci/jeac270; html:https://europepmc.org/articles/PMC10284050; pdf:https://europepmc.org/articles/PMC10284050?pdf=render 33655501,https://doi.org/10.1111/bjd.19885,Four childhood atopic dermatitis subtypes identified from trajectory and severity of disease and internally validated in a large UK birth cohort.,"Mulick AR, Mansfield KE, Silverwood RJ, Budu-Aggrey A, Roberts A, Custovic A, Pearce N, Irvine AD, Smeeth L, Abuabara K, Langan SM.",,The British journal of dermatology,2021,2021-05-09,N,,,,"

Background

Atopic dermatitis (AD) disease activity and severity is highly variable during childhood. Early attempts to identify subtypes based on disease trajectory have assessed AD presence over time without incorporating severity.

Objectives

To identify childhood AD subtypes from symptom severity and trajectories, and determine associations with genetic risk factors, comorbidities and demographic and environmental variables.

Methods

We split data from children in the Avon Longitudinal Study of Parents and Children birth cohort into development and validation sets. To identify subtypes, we ran latent class analyses in the development set on AD symptom reports up to age 14 years. We regressed identified subtypes on nongenetic variables in mutually adjusted, multiply imputed (genetic: unadjusted, complete case) multinomial regression analyses. We repeated analyses in the validation set and report confirmed results.

Results

There were 11 866 children who contributed to analyses. We identified one Unaffected/Rare class (66% of children) and four AD subtypes: Severe-Frequent (4%), Moderate-Frequent (7%), Moderate-Declining (11%) and Mild-Intermittent (12%). Symptom patterns within the first two subtypes appeared more homogeneous than the last two. Filaggrin (FLG) null mutations, an AD polygenic risk score (PRS), being female, parental AD and comorbid asthma were associated with higher risk for some or all subtypes; FLG, AD-PRS and asthma associations were stronger along a subtype gradient arranged by increasing severity and frequency; FLG and AD-PRS further differentiated some phenotypes from each other.

Conclusions

Considering severity and AD trajectories leads to four well-defined and recognizable subtypes. The differential associations of risk factors among and between subtypes is novel and requires further research.",,pdf:https://researchonline.lshtm.ac.uk/id/eprint/4660846/7/Mulick_etal_2021_Four-childhood-atopic-dermatitis-subtypes.pdf; doi:https://doi.org/10.1111/bjd.19885; html:https://europepmc.org/articles/PMC8410876; pdf:https://europepmc.org/articles/PMC8410876?pdf=render; doi:https://doi.org/10.1111/bjd.19885 +36660920,https://doi.org/10.1093/ehjci/jeac270,The role of obesity-related cardiovascular remodelling in mediating incident cardiovascular outcomes: a population-based observational study.,"Szabo L, McCracken C, Cooper J, Rider OJ, Vago H, Merkely B, Harvey NC, Neubauer S, Petersen SE, Raisi-Estabragh Z.",,European heart journal. Cardiovascular Imaging,2023,2023-06-01,Y,Obesity; body mass index; Mediation; Cardiac Magnetic Resonance Imaging; Cardiovascular Remodelling; Waist-to-hip Ratio; Disease Mechanisms; Incident Cardiovascular Outcomes,,,"

Aims

We examined associations of obesity with incident cardiovascular outcomes and cardiovascular magnetic resonance (CMR) phenotypes, integrating information from body mass index (BMI) and waist-to-hip ratio (WHR). Then, we used multiple mediation to define the role of obesity-related cardiac remodelling in driving obesity-outcome associations, independent of cardiometabolic diseases.

Methods and results

In 491 606 UK Biobank participants, using Cox proportional hazard models, greater obesity (higher WHR, higher BMI) was linked to significantly greater risk of incident ischaemic heart disease, atrial fibrillation (AF), heart failure (HF), all-cause mortality, and cardiovascular disease (CVD) mortality. In combined stratification by BMI and WHR thresholds, elevated WHR was associated with greater risk of adverse outcomes at any BMI level. Individuals with overweight BMI but normal WHR had weaker disease associations. In the subset of participants with CMR (n = 31 107), using linear regression, greater obesity was associated with higher left ventricular (LV) mass, greater LV concentricity, poorer LV systolic function, lower myocardial native T1, larger left atrial (LA) volumes, poorer LA function, and lower aortic distensibility. Of note, higher BMI was linked to higher, whilst greater WHR was linked to lower LV end-diastolic volume (LVEDV). In Cox models, greater LVEDV and LV mass (LVM) were linked to increased risk of CVD, most importantly HF and an increased LA maximal volume was the key predictive measure of new-onset AF. In multiple mediation analyses, hypertension and adverse LV remodelling (higher LVM, greater concentricity) were major independent mediators of the obesity-outcome associations. Atrial remodelling and native T1 were additional mediators in the associations of obesity with AF and HF, respectively.

Conclusions

We demonstrate associations of obesity with adverse cardiovascular phenotypes and their significant independent role in mediating obesity-outcome relationships. In addition, our findings support the integrated use of BMI and WHR to evaluate obesity-related cardiovascular risk.",,pdf:https://academic.oup.com/ehjcimaging/advance-article-pdf/doi/10.1093/ehjci/jeac270/48798234/jeac270.pdf; doi:https://doi.org/10.1093/ehjci/jeac270; html:https://europepmc.org/articles/PMC10284050; pdf:https://europepmc.org/articles/PMC10284050?pdf=render 35038301,https://doi.org/10.2196/30523,Requirements for a Bespoke Intensive Care Unit Dashboard in Response to the COVID-19 Pandemic: Semistructured Interview Study.,"Davidson B, Ferrer Portillo KM, Wac M, McWilliams C, Bourdeaux C, Craddock I.",,JMIR human factors,2022,2022-04-13,Y,Development; Monitoring; Design; Disease monitoring; ICU; Interview; Intensive Care; Critical Care; Ehealth; Dashboard; Human-centered Design; Covid-19,,,"

Background

Intensive care units (ICUs) around the world are in high demand due to patients with COVID-19 requiring hospitalization. As researchers at the University of Bristol, we were approached to develop a bespoke data visualization dashboard to assist two local ICUs during the pandemic that will centralize disparate data sources in the ICU to help reduce the cognitive load on busy ICU staff in the ever-evolving pandemic.

Objective

The aim of this study was to conduct interviews with ICU staff in University Hospitals Bristol and Weston National Health Service Foundation Trust to elicit requirements for a bespoke dashboard to monitor the high volume of patients, particularly during the COVID-19 pandemic.

Methods

We conducted six semistructured interviews with clinical staff to obtain an overview of their requirements for the dashboard and to ensure its ultimate suitability for end users. Interview questions aimed to understand the job roles undertaken in the ICU, potential uses of the dashboard, specific issues associated with managing COVID-19 patients, key data of interest, and any concerns about the introduction of a dashboard into the ICU.

Results

From our interviews, we found the following design requirements: (1) a flexible dashboard, where the functionality can be updated quickly and effectively to respond to emerging information about the management of this new disease; (2) a mobile dashboard, which allows staff to move around on wards with a dashboard, thus potentially replacing paper forms to enable detailed and consistent data entry; (3) a customizable and intuitive dashboard, where individual users would be able to customize the appearance of the dashboard to suit their role; (4) real-time data and trend analysis via informative data visualizations that help busy ICU staff to understand a patient's clinical trajectory; and (5) the ability to manage tasks and staff, tracking both staff and patient movements, handovers, and task monitoring to ensure the highest quality of care.

Conclusions

The findings of this study confirm that digital solutions for ICU use would potentially reduce the cognitive load of ICU staff and reduce clinical errors at a time of notably high demand of intensive health care.",,pdf:https://humanfactors.jmir.org/2022/2/e30523/PDF; doi:https://doi.org/10.2196/30523; html:https://europepmc.org/articles/PMC9009380 31194737,https://doi.org/10.1371/journal.pgen.1008164,Genome-wide association study of multisite chronic pain in UK Biobank.,"Johnston KJA, Adams MJ, Nicholl BI, Ward J, Strawbridge RJ, Ferguson A, McIntosh AM, Bailey MES, Smith DJ.",,PLoS genetics,2019,2019-06-13,Y,,Understanding the Causes of Disease,,"Chronic pain is highly prevalent worldwide and represents a significant socioeconomic and public health burden. Several aspects of chronic pain, for example back pain and a severity-related phenotype 'chronic pain grade', have been shown previously to be complex heritable traits with a polygenic component. Additional pain-related phenotypes capturing aspects of an individual's overall sensitivity to experiencing and reporting chronic pain have also been suggested as a focus for investigation. We made use of a measure of the number of sites of chronic pain in individuals within the UK general population. This measure, termed Multisite Chronic Pain (MCP), is a complex trait and its genetic architecture has not previously been investigated. To address this, we carried out a large-scale genome-wide association study (GWAS) of MCP in ~380,000 UK Biobank participants. Our findings were consistent with MCP having a significant polygenic component, with a Single Nucleotide Polymorphism (SNP) heritability of 10.2%. In total 76 independent lead SNPs at 39 risk loci were associated with MCP. Additional gene-level association analyses identified neurogenesis, synaptic plasticity, nervous system development, cell-cycle progression and apoptosis genes as enriched for genetic association with MCP. Genetic correlations were observed between MCP and a range of psychiatric, autoimmune and anthropometric traits, including major depressive disorder (MDD), asthma and Body Mass Index (BMI). Furthermore, in Mendelian randomisation (MR) analyses a causal effect of MCP on MDD was observed. Additionally, a polygenic risk score (PRS) for MCP was found to significantly predict chronic widespread pain (pain all over the body), indicating the existence of genetic variants contributing to both of these pain phenotypes. Overall, our findings support the proposition that chronic pain involves a strong nervous system component with implications for our understanding of the physiology of chronic pain. These discoveries may also inform the future development of novel treatment approaches.",,pdf:https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1008164&type=printable; doi:https://doi.org/10.1371/journal.pgen.1008164; html:https://europepmc.org/articles/PMC6592570; pdf:https://europepmc.org/articles/PMC6592570?pdf=render 35277454,https://doi.org/10.1136/heartjnl-2021-320417,Smartphone detection of atrial fibrillation using photoplethysmography: a systematic review and meta-analysis.,"Gill S, Bunting KV, Sartini C, Cardoso VR, Ghoreishi N, Uh HW, Williams JA, Suzart-Woischnik K, Banerjee A, Asselbergs FW, Eijkemans M, Gkoutos GV, Kotecha D.",,Heart (British Cardiac Society),2022,2022-09-26,Y,Atrial fibrillation; Photoplethysmography; Smartphone,,,"

Objectives

Timely diagnosis of atrial fibrillation (AF) is essential to reduce complications from this increasingly common condition. We sought to assess the diagnostic accuracy of smartphone camera photoplethysmography (PPG) compared with conventional electrocardiogram (ECG) for AF detection.

Methods

This is a systematic review of MEDLINE, EMBASE and Cochrane (1980-December 2020), including any study or abstract, where smartphone PPG was compared with a reference ECG (1, 3 or 12-lead). Random effects meta-analysis was performed to pool sensitivity/specificity and identify publication bias, with study quality assessed using the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies-2) risk of bias tool.

Results

28 studies were included (10 full-text publications and 18 abstracts), providing 31 comparisons of smartphone PPG versus ECG for AF detection. 11 404 participants were included (2950 in AF), with most studies being small and based in secondary care. Sensitivity and specificity for AF detection were high, ranging from 81% to 100%, and from 85% to 100%, respectively. 20 comparisons from 17 studies were meta-analysed, including 6891 participants (2299 with AF); the pooled sensitivity was 94% (95% CI 92% to 95%) and specificity 97% (96%-98%), with substantial heterogeneity (p<0.01). Studies were of poor quality overall and none met all the QUADAS-2 criteria, with particular issues regarding selection bias and the potential for publication bias.

Conclusion

PPG provides a non-invasive, patient-led screening tool for AF. However, current evidence is limited to small, biased, low-quality studies with unrealistically high sensitivity and specificity. Further studies are needed, preferably independent from manufacturers, in order to advise clinicians on the true value of PPG technology for AF detection.",,pdf:https://heart.bmj.com/content/heartjnl/early/2022/03/10/heartjnl-2021-320417.full.pdf; doi:https://doi.org/10.1136/heartjnl-2021-320417; html:https://europepmc.org/articles/PMC9554073; pdf:https://europepmc.org/articles/PMC9554073?pdf=render @@ -1288,13 +1288,13 @@ PMC10686417,https://doi.org/,The impact of restricted provision of publicly fund 37230417,https://doi.org/10.1016/j.jtha.2023.05.012,C1-inhibitor levels and venous thromboembolism: results from a Mendelian randomization study.,"Cupido AJ, Petersen RS, Schmidt AF, Levi M, Cohn DM, Fijen LM.",,Journal of thrombosis and haemostasis : JTH,2023,2023-05-23,N,,,,,,doi:https://doi.org/10.1016/j.jtha.2023.05.012 35210898,https://doi.org/10.2147/por.s353400,Deriving a Standardised Recommended Respiratory Disease Codelist Repository for Future Research.,"MacRae C, Whittaker H, Mukherjee M, Daines L, Morgan A, Iwundu C, Alsallakh M, Vasileiou E, O'Rourke E, Williams AT, Stone PW, Sheikh A, Quint JK.",,Pragmatic and observational research,2022,2022-02-16,Y,Asthma; COPD; Respiratory Tract Infections; Electronic Healthcare Records,,,"

Background

Electronic health record (EHR) databases provide rich, longitudinal data on interactions with healthcare providers and can be used to advance research into respiratory conditions. However, since these data are primarily collected to support health care delivery, clinical coding can be inconsistent, resulting in inherent challenges in using these data for research purposes.

Methods

We systematically searched existing international literature and UK code repositories to find respiratory disease codelists for asthma from January 2018, and chronic obstructive pulmonary disease and respiratory tract infections from January 2020, based on prior searches. Medline searches using key terms provided in article lists. Full-text articles, supplementary files, and reference lists were examined for codelists, and codelists repositories were searched. A reproducible methodology for codelists creation was developed with recommended lists for each disease created based on multidisciplinary expert opinion and previously published literature.

Results

Medline searches returned 1126 asthma articles, 70 COPD articles, and 90 respiratory infection articles, with 3%, 22% and 5% including codelists, respectively. Repository searching returned 12 asthma, 23 COPD, and 64 respiratory infection codelists. We have systematically compiled respiratory disease codelists and from these derived recommended lists for use by researchers to find the most up-to-date and relevant respiratory disease codelists that can be tailored to individual research questions.

Conclusion

Few published papers include codelists, and where published diverse codelists were used, even when answering similar research questions. Whilst some advances have been made, greater consistency and transparency across studies using routine data to study respiratory diseases are needed.",,pdf:https://www.dovepress.com/getfile.php?fileID=78337; doi:https://doi.org/10.2147/POR.S353400; html:https://europepmc.org/articles/PMC8859726; pdf:https://europepmc.org/articles/PMC8859726?pdf=render 30181555,https://doi.org/10.1038/s41398-018-0236-1,"Genetics of self-reported risk-taking behaviour, trans-ethnic consistency and relevance to brain gene expression.","Strawbridge RJ, Ward J, Lyall LM, Tunbridge EM, Cullen B, Graham N, Ferguson A, Johnston KJA, Lyall DM, Mackay D, Cavanagh J, Howard DM, Adams MJ, Deary I, Escott-Price V, O'Donovan M, McIntosh AM, Bailey MES, Pell JP, Harrison PJ, Smith DJ.",,Translational psychiatry,2018,2018-09-04,Y,,Understanding the Causes of Disease,,"Risk-taking behaviour is an important component of several psychiatric disorders, including attention-deficit hyperactivity disorder, schizophrenia and bipolar disorder. Previously, two genetic loci have been associated with self-reported risk taking and significant genetic overlap with psychiatric disorders was identified within a subsample of UK Biobank. Using the white British participants of the full UK Biobank cohort (n = 83,677 risk takers versus 244,662 controls) for our primary analysis, we conducted a genome-wide association study of self-reported risk-taking behaviour. In secondary analyses, we assessed sex-specific effects, trans-ethnic heterogeneity and genetic overlap with psychiatric traits. We also investigated the impact of risk-taking-associated SNPs on both gene expression and structural brain imaging. We identified 10 independent loci for risk-taking behaviour, of which eight were novel and two replicated previous findings. In addition, we found two further sex-specific risk-taking loci. There were strong positive genetic correlations between risk-taking and attention-deficit hyperactivity disorder, bipolar disorder and schizophrenia. Index genetic variants demonstrated effects generally consistent with the discovery analysis in individuals of non-British White, South Asian, African-Caribbean or mixed ethnicity. Polygenic risk scores comprising alleles associated with increased risk taking were associated with lower white matter integrity. Genotype-specific expression pattern analyses highlighted DPYSL5, CGREF1 and C15orf59 as plausible candidate genes. Overall, our findings substantially advance our understanding of the biology of risk-taking behaviour, including the possibility of sex-specific contributions, and reveal consistency across ethnicities. We further highlight several putative novel candidate genes, which may mediate these genetic effects.",,pdf:https://www.nature.com/articles/s41398-018-0236-1.pdf; doi:https://doi.org/10.1038/s41398-018-0236-1; html:https://europepmc.org/articles/PMC6123450; pdf:https://europepmc.org/articles/PMC6123450?pdf=render -37489768,https://doi.org/10.1161/jaha.122.029296,Using Polygenic Risk Scores for Prioritizing Individuals at Greatest Need of a Cardiovascular Disease Risk Assessment.,"Chung R, Xu Z, Arnold M, Ip S, Harrison H, Barrett J, Pennells L, Kim LG, Di Angelantonio E, Paige E, Ritchie SC, Inouye M, Usher-Smith JA, Wood AM.",,Journal of the American Heart Association,2023,2023-07-25,Y,Screening; Genomics; Cardiovascular disease; Electronic Health Records; Primary Care Records,,,"Background The aim of this study was to provide quantitative evidence of the use of polygenic risk scores for systematically identifying individuals for invitation for full formal cardiovascular disease (CVD) risk assessment. Methods and Results A total of 108 685 participants aged 40 to 69 years, with measured biomarkers, linked primary care records, and genetic data in UK Biobank were used for model derivation and population health modeling. Prioritization tools using age, polygenic risk scores for coronary artery disease and stroke, and conventional risk factors for CVD available within longitudinal primary care records were derived using sex-specific Cox models. We modeled the implications of initiating guideline-recommended statin therapy after prioritizing individuals for invitation to a formal CVD risk assessment. If primary care records were used to prioritize individuals for formal risk assessment using age- and sex-specific thresholds corresponding to 5% false-negative rates, then the numbers of men and women needed to be screened to prevent 1 CVD event are 149 and 280, respectively. In contrast, adding polygenic risk scores to both prioritization and formal assessments, and selecting thresholds to capture the same number of events, resulted in a number needed to screen of 116 for men and 180 for women. Conclusions Using both polygenic risk scores and primary care records to prioritize individuals at highest risk of a CVD event for a formal CVD risk assessment can efficiently prioritize those who need interventions the most than using primary care records alone. This could lead to better allocation of resources by reducing the number of risk assessments in primary care while still preventing the same number of CVD events.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/JAHA.122.029296; doi:https://doi.org/10.1161/JAHA.122.029296; html:https://europepmc.org/articles/PMC7614905; pdf:https://europepmc.org/articles/PMC7614905?pdf=render 35595677,https://doi.org/10.1016/s2589-7500(22)00061-9,Identifying adverse childhood experiences with electronic health records of linked mothers and children in England: a multistage development and validation study.,"Syed S, Gonzalez-Izquierdo A, Allister J, Feder G, Li L, Gilbert R.",,The Lancet. Digital health,2022,2022-05-17,N,,,,"

Background

Electronic health records (EHRs) of mothers and children provide an opportunity to identify adverse childhood experiences (ACEs) during crucial periods of childhood development, yet well developed indicators of ACEs remain scarce. We aimed to develop clinically relevant indicators of ACEs for linked EHRs of mothers and children using a multistage prediction model of child maltreatment and maternal intimate partner violence (IPV).

Methods

In this multistage development and validation study, we developed a representative population-based birth cohort of mothers and children in England, followed from up to 2 years before birth to up to 5 years after birth across the Clinical Practice Research Datalink (CPRD) GOLD (primary care), Hospital Episode Statistics (secondary care), and the Office for National Statistics mortality register. We included livebirths in England between July 1, 2004, and June 30, 2016, to mothers aged 16-55 years, who had registered with a general practitioner (GP) that met CPRD quality standards before 21 weeks of gestation. The primary outcome (reference standard) was any child maltreatment or maternal IPV in either the mother's or child's record from 2 years before birth (maternal IPV only) to 5 years after birth. We used seven prediction models, combined with expert ratings, to systematically develop indicators. We validated the final indicators by integrating results from machine learning models, survival analyses, and clustering analyses in the validation cohort.

Findings

We included data collected between July 1, 2002, and June 27, 2018. Of 376 006 eligible births, we included 211 393 mother-child pairs (422 786 patients) from 400 practices, of whom 126 837 mother-child pairs (60·0%; 240 practices) were randomly assigned to a derivation cohort and 84 556 pairs (40·0%; 160 practices) to a validation cohort. We included 63 indicators in six ACE domains: maternal mental health problems, maternal substance misuse, adverse family environments, child maltreatment, maternal IPV, and high-risk presentations of child maltreatment. Excluding the seven indicators in the reference standard, 56 indicators showed high discriminative validity for the reference standard of any child maltreatment or maternal IPV between 2 years before and 5 years after birth (validation cohort, area under the receiver operating characteristic curve 0·85 [95% CI 0·84-0·86]). During the 2 years before birth and 5 years after birth, the overall period prevalence of maternal IPV and child maltreatment (reference standard) was 2·3% (2876 of 126 837 pairs) in the derivation cohort and 2·3% (1916 of 84 556 pairs) in the validation cohort. During the 2 years before and after birth, the period prevalence was 39·1% (95% CI 38·7-39·5; 34 773 pairs) for any of the 63 ACE indicators, 22·2% (21·8-22·5%; 20 122 pairs) for maternal mental health problems, 15·7% (15·4-16·0%; 14 549 pairs) for adverse family environments, 8·1% (7·8-8·3%; 6808 pairs) for high-risk presentations of child maltreatment, 6·9% (6·7-7·2%; 7856 pairs) for maternal substance misuse, and 3·0% (2·9-3·2%; 2540 pairs) for any child maltreatment (2·4% [2·3-5·6%; 2051 pairs]) and maternal IPV (1·0% [0·8-1·0%; 875 pairs]). 62·6% (21 785 of 34 773 pairs) of ACEs were recorded in primary care only, and 72·3% (25 140 cases) were recorded in the maternal record only.

Interpretation

We developed clinically relevant indicators for identifying ACEs using the EHRs of mothers and children presenting to general practices and hospital admissions. Over 70% of ACEs were identified via maternal records and were recorded in primary care by GPs within 2 years of birth, reinforcing the importance of reviewing parental and carer records to inform clinical responses to children. ACE indicators can contribute to longitudinal surveillance informing public health policy and resource allocation. Further evaluation is required to determine how ACE indicators can be used in clinical practice.

Funding

None.",,pdf:http://www.thelancet.com/article/S2589750022000619/pdf; doi:https://doi.org/10.1016/S2589-7500(22)00061-9 -37679551,https://doi.org/10.1038/s41590-023-01635-6,Author Correction: Genetics of circulating inflammatory proteins identifies drivers of immune-mediated disease risk and therapeutic targets.,"Zhao JH, Stacey D, Eriksson N, Macdonald-Dunlop E, Hedman ÅK, Kalnapenkis A, Enroth S, Cozzetto D, Digby-Bell J, Marten J, Folkersen L, Herder C, Jonsson L, Bergen SE, Gieger C, Needham EJ, Surendran P, Estonian Biobank Research Team, Paul DS, Polasek O, Thorand B, Grallert H, Roden M, Võsa U, Esko T, Hayward C, Johansson Å, Gyllensten U, Powell N, Hansson O, Mattsson-Carlgren N, Joshi PK, Danesh J, Padyukov L, Klareskog L, Landén M, Wilson JF, Siegbahn A, Wallentin L, Mälarstig A, Butterworth AS, Peters JE.",,Nature immunology,2023,2023-11-01,Y,,,,,,doi:https://doi.org/10.1038/s41590-023-01635-6; html:https://europepmc.org/articles/PMC10602847; pdf:https://europepmc.org/articles/PMC10602847?pdf=render +37489768,https://doi.org/10.1161/jaha.122.029296,Using Polygenic Risk Scores for Prioritizing Individuals at Greatest Need of a Cardiovascular Disease Risk Assessment.,"Chung R, Xu Z, Arnold M, Ip S, Harrison H, Barrett J, Pennells L, Kim LG, Di Angelantonio E, Paige E, Ritchie SC, Inouye M, Usher-Smith JA, Wood AM.",,Journal of the American Heart Association,2023,2023-07-25,Y,Screening; Genomics; Cardiovascular disease; Electronic Health Records; Primary Care Records,,,"Background The aim of this study was to provide quantitative evidence of the use of polygenic risk scores for systematically identifying individuals for invitation for full formal cardiovascular disease (CVD) risk assessment. Methods and Results A total of 108 685 participants aged 40 to 69 years, with measured biomarkers, linked primary care records, and genetic data in UK Biobank were used for model derivation and population health modeling. Prioritization tools using age, polygenic risk scores for coronary artery disease and stroke, and conventional risk factors for CVD available within longitudinal primary care records were derived using sex-specific Cox models. We modeled the implications of initiating guideline-recommended statin therapy after prioritizing individuals for invitation to a formal CVD risk assessment. If primary care records were used to prioritize individuals for formal risk assessment using age- and sex-specific thresholds corresponding to 5% false-negative rates, then the numbers of men and women needed to be screened to prevent 1 CVD event are 149 and 280, respectively. In contrast, adding polygenic risk scores to both prioritization and formal assessments, and selecting thresholds to capture the same number of events, resulted in a number needed to screen of 116 for men and 180 for women. Conclusions Using both polygenic risk scores and primary care records to prioritize individuals at highest risk of a CVD event for a formal CVD risk assessment can efficiently prioritize those who need interventions the most than using primary care records alone. This could lead to better allocation of resources by reducing the number of risk assessments in primary care while still preventing the same number of CVD events.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/JAHA.122.029296; doi:https://doi.org/10.1161/JAHA.122.029296; html:https://europepmc.org/articles/PMC7614905; pdf:https://europepmc.org/articles/PMC7614905?pdf=render 34137744,https://doi.org/10.1097/ta.0000000000003317,Association between type 2 diabetes and long-term outcomes in middle-aged and older trauma patients.,"Daly SL, Gabbe BJ, Climie RE, Ekegren CL.",,The journal of trauma and acute care surgery,2022,2022-01-01,N,,,,"

Background

Diabetes is associated with increased hospital complications and mortality following trauma. However, there is limited research on the longer-term recovery of trauma patients with diabetes. The aim of this study was to explore the association between type 2 diabetes (T2D) and in-hospital and 24-month outcomes in major trauma patients.

Methods

In this cohort study using the Victorian State Trauma Registry, middle-aged and older adults (≥45 years) with major trauma were followed up at 24 months postinjury. Logistic regression (univariable and multivariable) analyses were used to determine the association between diabetes status and 24-month patient-reported outcomes. In-hospital outcomes were compared between groups using χ2 tests.

Results

Of the 11,490 participants who survived to hospital discharge, 8,493 survived to 24 months postinjury and were followed up at that time point: 953 people (11%) with and 7540 (89%) without T2D. People with T2D had a higher in-hospital death rate (19%) compared with people without T2D (16%; p < 0.001). After adjusting for confounders, people with T2D had poorer outcomes 24 months postinjury than people without T2D, with respect to functional recovery (Glasgow Outcome Scale Extended) (adjusted odds ratio [AOR], 0.58; 95% confidence interval [CI], 0.48-0.69) and return to work/study (AOR, 0.51; 95% CI, 0.37-0.71]). People with T2D experienced higher odds of problems with mobility (AOR, 1.92; 95% CI, 1.60-2.30), self-care (AOR, 1.94; 95% CI, 1.64, 2.29), usual activities (AOR, 1.50; 95% CI, 1.26-1.79), pain and discomfort (AOR, 1.75; 95% CI, 1.49-2.07), anxiety and depression (AOR, 1.45; 95% CI, 1.24, 1.70), and self-reported disability (AOR, 1.51; 95% CI, 1.28-1.79) than people without T2D.

Conclusion

Major trauma patients with T2D have a poorer prognosis than patients without T2D, both during their hospital admission and 24 months postinjury. Patients with T2D may need additional health care and support following trauma to reach their recovery potential.

Level of evidence

Prognostic, level III.",,doi:https://doi.org/10.1097/TA.0000000000003317 +37679551,https://doi.org/10.1038/s41590-023-01635-6,Author Correction: Genetics of circulating inflammatory proteins identifies drivers of immune-mediated disease risk and therapeutic targets.,"Zhao JH, Stacey D, Eriksson N, Macdonald-Dunlop E, Hedman ÅK, Kalnapenkis A, Enroth S, Cozzetto D, Digby-Bell J, Marten J, Folkersen L, Herder C, Jonsson L, Bergen SE, Gieger C, Needham EJ, Surendran P, Estonian Biobank Research Team, Paul DS, Polasek O, Thorand B, Grallert H, Roden M, Võsa U, Esko T, Hayward C, Johansson Å, Gyllensten U, Powell N, Hansson O, Mattsson-Carlgren N, Joshi PK, Danesh J, Padyukov L, Klareskog L, Landén M, Wilson JF, Siegbahn A, Wallentin L, Mälarstig A, Butterworth AS, Peters JE.",,Nature immunology,2023,2023-11-01,Y,,,,,,doi:https://doi.org/10.1038/s41590-023-01635-6; html:https://europepmc.org/articles/PMC10602847; pdf:https://europepmc.org/articles/PMC10602847?pdf=render 35025917,https://doi.org/10.1371/journal.pone.0261142,Inpatient COVID-19 mortality has reduced over time: Results from an observational cohort.,"Bechman K, Yates M, Mann K, Nagra D, Smith LJ, Rutherford AI, Patel A, Periselneris J, Walder D, Dobson RJB, Kraljevic Z, Teo JHT, Bernal W, Barker R, Galloway JB, Norton S.",,PloS one,2022,2022-01-13,Y,,,,"

Background

The Covid-19 pandemic in the United Kingdom has seen two waves; the first starting in March 2020 and the second in late October 2020. It is not known whether outcomes for those admitted with severe Covid were different in the first and second waves.

Methods

The study population comprised all patients admitted to a 1,500-bed London Hospital Trust between March 2020 and March 2021, who tested positive for Covid-19 by PCR within 3-days of admissions. Primary outcome was death within 28-days of admission. Socio-demographics (age, sex, ethnicity), hypertension, diabetes, obesity, baseline physiological observations, CRP, neutrophil, chest x-ray abnormality, remdesivir and dexamethasone were incorporated as co-variates. Proportional subhazards models compared mortality risk between wave 1 and wave 2. Cox-proportional hazard model with propensity score adjustment were used to compare mortality in patients prescribed remdesivir and dexamethasone.

Results

There were 3,949 COVID-19 admissions, 3,195 hospital discharges and 733 deaths. There were notable differences in age, ethnicity, comorbidities, and admission disease severity between wave 1 and wave 2. Twenty-eight-day mortality was higher during wave 1 (26.1% versus 13.1%). Mortality risk adjusted for co-variates was significantly lower in wave 2 compared to wave 1 [adjSHR 0.49 (0.37, 0.65) p<0.001]. Analysis of treatment impact did not show statistically different effects of remdesivir [HR 0.84 (95%CI 0.65, 1.08), p = 0.17] or dexamethasone [HR 0.97 (95%CI 0.70, 1.35) p = 0.87].

Conclusion

There has been substantial improvements in COVID-19 mortality in the second wave, even accounting for demographics, comorbidity, and disease severity. Neither dexamethasone nor remdesivir appeared to be key explanatory factors, although there may be unmeasured confounding present.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0261142&type=printable; doi:https://doi.org/10.1371/journal.pone.0261142; html:https://europepmc.org/articles/PMC8757902; pdf:https://europepmc.org/articles/PMC8757902?pdf=render -37750555,https://doi.org/10.1161/jaha.123.030766,Impact of New Cardiovascular Events on Quality of Life and Hospital Costs in People With Cardiovascular Disease in the United Kingdom and United States.,"Lui JNM, Williams C, Keng MJ, Hopewell JC, Sammons E, Chen F, Gray A, Bowman L, Landray SMJ, Mihaylova B, REVEAL Collaborative Group.",,Journal of the American Heart Association,2023,2023-09-26,Y,Cardiovascular diseases; Quality of life; United States; United Kingdom; Secondary Prevention; Health Care Costs,,,"

Background

Despite optimized risk factor control, people with prior cardiovascular disease remain at high cardiovascular disease risk. We assess the immediate- and longer-term impacts of new vascular and nonvascular events on quality of life (QoL) and hospital costs among participants in the REVEAL (Randomized Evaluation of the Effects of Anacetrapib Through Lipid Modification) trial in secondary prevention.

Methods and results

Data on demographic and clinical characteristics, health-related quality of life (QoL: EuroQoL 5-Dimension-5-Level), adverse events, and hospital admissions during the 4-year follow-up of the 21 820 participants recruited in Europe and North America informed assessments of the impacts of new adverse events on QoL and hospital costs from the UK and US health systems' perspectives using generalized linear regression models. Reductions in QoL were estimated in the years of event occurrence for nonhemorrhagic stroke (-0.067 [United Kingdom], -0.069 [US]), heart failure admission (-0.072 [United Kingdom], -0.103 [US]), incident cancer (-0.064 [United Kingdom], -0.068 [US]), and noncoronary revascularization (-0.071 [United Kingdom], -0.061 [US]), as well as in subsequent years following these events. Myocardial infarction and coronary revascularization (CRV) procedures were not found to affect QoL. All adverse events were associated with additional hospital costs in the years of events and in subsequent years, with the highest additional costs in the years of noncoronary revascularization (£5830 [United Kingdom], $14 133 [US Medicare]), of myocardial infarction with urgent CRV procedure (£5614, $24722), and of urgent/nonurgent CRV procedure without myocardial infarction (£4674/£4651 and $15 251/$17 539).

Conclusions

Stroke, heart failure, and noncoronary revascularization procedures substantially reduce QoL, and all cardiovascular disease events increase hospital costs. These estimates are useful in informing cost-effectiveness of interventions to reduce cardiovascular disease risk in secondary prevention.

Registration

URL: https://www.clinicaltrials.gov; Unique identifier: NCT01252953; https://www.Isrctn.com. Unique identifier: ISRCTN48678192; https://www.clinicaltrialsregister.eu. Unique identifier: 2010-023467-18.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/JAHA.123.030766; doi:https://doi.org/10.1161/JAHA.123.030766; html:https://europepmc.org/articles/PMC7615160; pdf:https://europepmc.org/articles/PMC7615160?pdf=render 37124165,https://doi.org/10.1016/j.ufug.2023.127934,"Effects of the onset of the COVID-19 pandemic restrictions on park crime in London, England: An interrupted time series analysis.","Hajna S, Cummins S.",,Urban forestry & urban greening,2023,2023-04-11,Y,Parks; Crimes; Covid-19,,,"

Introduction

Park crimes may have increased during the COVID-19 pandemic as a result of lockdowns that limited the number of capable guardians in public spaces. Despite this, the impacts of the lockdowns on park crimes remain unknown. To help us understand the societal impacts of policies implemented during this period, we assessed how the onset of the COVID-19 restrictions impacted urban park crime levels in London, England.

Methods

We identified crimes that occurred in publicly accessible parks and gardens in the Greater London Authority (England, UK) between March 1, 2019 and February 28, 2021 by overlaying open-access crime data with greenspace data supplied by the Greater Information for Greater London service. Using interrupted time series analyses, we estimated seasonality-adjusted associations between the onset of COVID-19 restrictions and park crimes.

Results

Overall (1565.7, 95% confidence intervals [CI] 1021.9 to 2109.5) and antisocial behaviour crimes (1772.7, 95% CI 823.6-2721.7) increased in London parks during the first full month of COVID-19 restrictions (April 2020). There were no notable trends in park crimes in London prior to the onset of restrictions, but overall and antisocial behaviour crimes decreased after the onset of restrictions at a rate of 156.4 (95% CI -220.25 to -92.51) and 164.7 (95% CI -280.68 to -48.74) crimes/months, respectively.

Conclusions

Overall park crimes increased during the first full month of the COVID-19 restrictions, largely driven by an increase in antisocial behaviours. Additional research is needed to identify the specific misdemeanours that accounted for this rise in antisocial behaviours and to investigate their downstream impacts (e.g. increases in policing costs or decreases in perceived park safety).",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10088280; doi:https://doi.org/10.1016/j.ufug.2023.127934; html:https://europepmc.org/articles/PMC10088280; pdf:https://europepmc.org/articles/PMC10088280?pdf=render +37750555,https://doi.org/10.1161/jaha.123.030766,Impact of New Cardiovascular Events on Quality of Life and Hospital Costs in People With Cardiovascular Disease in the United Kingdom and United States.,"Lui JNM, Williams C, Keng MJ, Hopewell JC, Sammons E, Chen F, Gray A, Bowman L, Landray SMJ, Mihaylova B, REVEAL Collaborative Group.",,Journal of the American Heart Association,2023,2023-09-26,Y,Cardiovascular diseases; Quality of life; United States; United Kingdom; Secondary Prevention; Health Care Costs,,,"

Background

Despite optimized risk factor control, people with prior cardiovascular disease remain at high cardiovascular disease risk. We assess the immediate- and longer-term impacts of new vascular and nonvascular events on quality of life (QoL) and hospital costs among participants in the REVEAL (Randomized Evaluation of the Effects of Anacetrapib Through Lipid Modification) trial in secondary prevention.

Methods and results

Data on demographic and clinical characteristics, health-related quality of life (QoL: EuroQoL 5-Dimension-5-Level), adverse events, and hospital admissions during the 4-year follow-up of the 21 820 participants recruited in Europe and North America informed assessments of the impacts of new adverse events on QoL and hospital costs from the UK and US health systems' perspectives using generalized linear regression models. Reductions in QoL were estimated in the years of event occurrence for nonhemorrhagic stroke (-0.067 [United Kingdom], -0.069 [US]), heart failure admission (-0.072 [United Kingdom], -0.103 [US]), incident cancer (-0.064 [United Kingdom], -0.068 [US]), and noncoronary revascularization (-0.071 [United Kingdom], -0.061 [US]), as well as in subsequent years following these events. Myocardial infarction and coronary revascularization (CRV) procedures were not found to affect QoL. All adverse events were associated with additional hospital costs in the years of events and in subsequent years, with the highest additional costs in the years of noncoronary revascularization (£5830 [United Kingdom], $14 133 [US Medicare]), of myocardial infarction with urgent CRV procedure (£5614, $24722), and of urgent/nonurgent CRV procedure without myocardial infarction (£4674/£4651 and $15 251/$17 539).

Conclusions

Stroke, heart failure, and noncoronary revascularization procedures substantially reduce QoL, and all cardiovascular disease events increase hospital costs. These estimates are useful in informing cost-effectiveness of interventions to reduce cardiovascular disease risk in secondary prevention.

Registration

URL: https://www.clinicaltrials.gov; Unique identifier: NCT01252953; https://www.Isrctn.com. Unique identifier: ISRCTN48678192; https://www.clinicaltrialsregister.eu. Unique identifier: 2010-023467-18.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/JAHA.123.030766; doi:https://doi.org/10.1161/JAHA.123.030766; html:https://europepmc.org/articles/PMC7615160; pdf:https://europepmc.org/articles/PMC7615160?pdf=render 36713101,https://doi.org/10.1093/ehjdh/ztab082,A data mining-based cross-industry process for predicting major bleeding in mechanical circulatory support.,"Felix SEA, Bagheri A, Ramjankhan FR, Spruit MR, Oberski D, de Jonge N, van Laake LW, Suyker WJL, Asselbergs FW.",,European heart journal. Digital health,2021,2021-10-01,Y,Prediction; Bleeding; data mining; Mechanical Circulatory Support; Cross-Industry Standard Process For Data Mining (Crisp-Dm),,,"

Aims

Over a third of patients, treated with mechanical circulatory support (MCS) for end-stage heart failure, experience major bleeding. Currently, the prediction of a major bleeding in the near future is difficult because of many contributing factors. Predictive analytics using data mining could help calculating the risk of bleeding; however, its application is generally reserved for experienced researchers on this subject. We propose an easily applicable data mining tool to predict major bleeding in MCS patients.

Methods and results

All data of electronic health records of MCS patients in the University Medical Centre Utrecht were included. Based on the cross-industry standard process for data mining (CRISP-DM) methodology, an application named Auto-Crisp was developed. Auto-Crisp was used to evaluate the predictive models for a major bleeding in the next 3, 7, and 30 days after the first 30 days post-operatively following MCS implantation. The performance of the predictive models is investigated by the area under the curve (AUC) evaluation measure. In 25.6% of 273 patients, a total of 142 major bleedings occurred during a median follow-up period of 542 [interquartile range (IQR) 205-1044] days. The best predictive models assessed by Auto-Crisp had AUC values of 0.792, 0.788, and 0.776 for bleedings in the next 3, 7, and 30 days, respectively.

Conclusion

The Auto-Crisp-based predictive model created in this study had an acceptable performance to predict major bleeding in MCS patients in the near future. However, further validation of the application is needed to evaluate Auto-Crisp in other research projects.",,pdf:https://academic.oup.com/ehjdh/article-pdf/2/4/635/41972750/ztab082.pdf; doi:https://doi.org/10.1093/ehjdh/ztab082; html:https://europepmc.org/articles/PMC9707970; pdf:https://europepmc.org/articles/PMC9707970?pdf=render 33543581,https://doi.org/10.1111/ans.16578,Outcomes of surgical site infections following spinal column trauma.,"Baroun-Agob L, Liew S, Gabbe B.",,ANZ journal of surgery,2021,2021-02-05,N,Spine; Trauma; Surgical Wound Infection; Orthopaedic Surgery; Patient-reported Outcome Measures,,,"

Background

Surgical site infections (SSI) are an undesirable outcome of spinal surgery for both the patient and healthcare system. To date, few studies have investigated the impact of SSI on patient-reported and clinical outcomes. Sepsis and readmission are potential sequelae of SSI, with sepsis potentially being life threatening. This study aimed to assess the association between SSI and patient outcomes in a spinal trauma cohort.

Methods

Adult (16+ years) patients who underwent emergency spinal surgery due to trauma between January 2010 and December 2016 at a major trauma centre in Melbourne, Australia, were identified through the Victorian Orthopaedic Trauma Outcomes Registry. The presence of an SSI was abstracted from the electronic medical record and outcomes were compared between patients with and without an SSI. Clinical outcomes were obtained from the medical record, and patient-reported outcomes at 6 and 12 months were obtained from the Victorian Orthopaedic Trauma Outcomes Registry. Chi-squared tests were used to compare patient outcomes between groups.

Results

Of the 458 included patients, 26 (5.7%) developed an SSI. Patient-reported outcomes at 6 and 12 months were not different between the groups. An SSI was associated with sepsis (χ21 = 24.20, P < 0.01), readmission (χ21 = 215.34, P < 0.01), revision surgery (χ21 = 171.21, P < 0.01) and removal of implants (χ21 = 4.31, P = 0.04) within 12 months of discharge.

Conclusion

These findings indicate that spine trauma SSIs are not associated with patient-reported outcomes and may not have lasting effects on patients. Larger studies are required to assess further follow-up and support our findings and possibly distinguish outcomes between superficial and deep SSI.",,doi:https://doi.org/10.1111/ans.16578 35816976,https://doi.org/10.1016/j.jpsychires.2022.06.044,Anticoagulation for atrial fibrillation in people with serious mental illness in the general hospital setting.,"Farran D, Bean D, Wang T, Msosa Y, Casetta C, Dobson R, Teo JT, Scott P, Gaughran F.",,Journal of psychiatric research,2022,2022-06-28,N,Atrial fibrillation; Warfarin; Serious Mental Illness; Oral Anticoagulation; Doacs,,,"

Objective

People with serious mental illnesses (SMI) have an increased risk of stroke compared to the general population. This study aims to evaluate oral anticoagulation prescription trends in atrial fibrillation (AF) patients with and without a comorbid SMI.

Methods

An open-source retrieval system for clinical data (CogStack) was used to identify a cohort of AF patients with SMI who ever had an inpatient admission to King's College Hospital from 2011 to 2020. A Natural Language Processing pipeline was used to calculate CHA2DS2-VASc and HASBLED risk scores from Electronic Health Records free text. Antithrombotic prescriptions of warfarin and Direct acting oral anti-coagulants (DOACs) (apixaban, rivaroxaban, dabigatran, edoxaban) were extracted from discharge summaries.

Results

Among patients included in the study (n = 16 916), 2.7% had a recorded co-morbid SMI diagnosis. Compared to non-SMI patients, those with SMI had significantly higher CHA2DS2-VASc (mean (SD): 5.3 (1.96) vs 4.7 (2.08), p < 0.001) and HASBLED scores (mean (SD): 3.2 (1.27) vs 2.5 (1.29), p < 0.001). Among AF patients having a CHA2DS2-VASc ≥2, those with co-morbid SMI were less likely than non-SMI patients to be prescribed an OAC (44% vs 54%, p < 0.001). However, there was no evidence of a significant difference between the two groups since 2019.

Conclusion

Over recent years, DOAC prescription rates have increased among AF patients with SMI in acute hospitals. More research is needed to confirm whether the introduction of DOACs has reduced OAC treatment gaps in people with serious mental illness and to assess whether the use of DOACs has improved health outcomes in this population.",,doi:https://doi.org/10.1016/j.jpsychires.2022.06.044; doi:https://doi.org/10.1016/j.jpsychires.2022.06.044 @@ -1310,10 +1310,10 @@ PMC10686417,https://doi.org/,The impact of restricted provision of publicly fund 34868617,https://doi.org/10.1177/20552076211048654,Towards nationally curated data archives for clinical radiology image analysis at scale: Learnings from national data collection in response to a pandemic.,"Cushnan D, Berka R, Bertolli O, Williams P, Schofield D, Joshi I, Favaro A, Halling-Brown M, Imreh G, Jefferson E, Sebire NJ, Reilly G, Rodrigues JCL, Robinson G, Copley S, Malik R, Bloomfield C, Gleeson F, Crotty M, Denton E, Dickson J, Leeming G, Hardwick HE, Baillie K, Openshaw PJ, Semple MG, Rubin C, Howlett A, Rockall AG, Bhayat A, Fascia D, Sudlow C, NCCID Collaborative, Jacob J.",,Digital health,2021,2021-01-01,Y,Artificial intelligence; Medicine; Imaging; general; Radiology; Respiratory; Machine Learning; Coronavirus Sars-Cov-2 Disease,,,"The prevalence of the coronavirus SARS-CoV-2 disease has resulted in the unprecedented collection of health data to support research. Historically, coordinating the collation of such datasets on a national scale has been challenging to execute for several reasons, including issues with data privacy, the lack of data reporting standards, interoperable technologies, and distribution methods. The coronavirus SARS-CoV-2 disease pandemic has highlighted the importance of collaboration between government bodies, healthcare institutions, academic researchers and commercial companies in overcoming these issues during times of urgency. The National COVID-19 Chest Imaging Database, led by NHSX, British Society of Thoracic Imaging, Royal Surrey NHS Foundation Trust and Faculty, is an example of such a national initiative. Here, we summarise the experiences and challenges of setting up the National COVID-19 Chest Imaging Database, and the implications for future ambitions of national data curation in medical imaging to advance the safe adoption of artificial intelligence in healthcare.",,pdf:https://journals.sagepub.com/doi/pdf/10.1177/20552076211048654; doi:https://doi.org/10.1177/20552076211048654; html:https://europepmc.org/articles/PMC8637703; pdf:https://europepmc.org/articles/PMC8637703?pdf=render 31353050,https://doi.org/10.1016/s0140-6736(19)31359-5,Eligibility and subsequent burden of cardiovascular disease of four strategies for blood pressure-lowering treatment: a retrospective cohort study.,"Herrett E, Gadd S, Jackson R, Bhaskaran K, Williamson E, van Staa T, Sofat R, Timmis A, Smeeth L.",,"Lancet (London, England)",2019,2019-07-25,Y,,Better Care,,"

Background

Worldwide treatment recommendations for lowering blood pressure continue to be guided predominantly by blood pressure thresholds, despite strong evidence that the benefits of blood pressure reduction are observed in patients across the blood pressure spectrum. In this study, we aimed to investigate the implications of alternative strategies for offering blood pressure treatment, using the UK as an illustrative example.

Methods

We did a retrospective cohort study in primary care patients aged 30-79 years without cardiovascular disease, using data from the UK's Clinical Practice Research Datalink linked to Hospital Episode Statistics and Office for National Statistics mortality. We assessed and compared four different strategies to determine eligibility for treatment: using 2011 UK National Institute for Health and Care Excellence (NICE) guideline, or proposed 2019 NICE guideline, or blood pressure alone (threshold ≥140/90 mm Hg), or predicted 10-year cardiovascular risk alone (QRISK2 score ≥10%). Patients were followed up until the earliest occurrence of a cardiovascular disease diagnosis, death, or end of follow-up period (March 31, 2016). For each strategy, we estimated the proportion of patients eligible for treatment and number of cardiovascular events that could be prevented with treatment. We then estimated eligibility and number of events that would occur during 10 years in the UK general population.

Findings

Between Jan 1, 2011, and March 31, 2016, 1 222 670 patients in the cohort were followed up for a median of 4·3 years (IQR 2·5-5·2). 271 963 (22·2%) patients were eligible for treatment under the 2011 NICE guideline, 327 429 (26·8%) under the proposed 2019 NICE guideline, 481 859 (39·4%) on the basis of a blood pressure threshold of 140/90 mm Hg or higher, and 357 840 (29·3%) on the basis of a QRISK2 threshold of 10% or higher. During follow-up, 32 183 patients were diagnosed with cardiovascular disease (overall rate 7·1 per 1000 person-years, 95% CI 7·0-7·2). Cardiovascular event rates in patients eligible for each strategy were 15·2 per 1000 person-years (95% CI 15·0-15·5) under the 2011 NICE guideline, 14·9 (14·7-15·1) under the proposed 2019 NICE guideline, 11·4 (11·3-11·6) with blood pressure threshold alone, and 16·9 (16·7-17·1) with QRISK2 threshold alone. Scaled to the UK population, we estimated that 233 152 events would be avoided under the 2011 NICE guideline (28 patients needed to treat for 10 years to avoid one event), 270 233 under the 2019 NICE guideline (29 patients), 301 523 using a blood pressure threshold (38 patients), and 322 921 using QRISK2 threshold (27 patients).

Interpretation

A cardiovascular risk-based strategy (QRISK2 ≥10%) could prevent over a third more cardiovascular disease events than the 2011 NICE guideline and a fifth more than the 2019 NICE guideline, with similar efficiency regarding number treated per event avoided.

Funding

National Institute for Health Research.",,pdf:http://www.thelancet.com/article/S0140673619313595/pdf; doi:https://doi.org/10.1016/S0140-6736(19)31359-5; html:https://europepmc.org/articles/PMC6717081 32321827,https://doi.org/10.1073/pnas.1912957117,Testing for dependence on tree structures.,"Behr M, Ansari MA, Munk A, Holmes C.",,Proceedings of the National Academy of Sciences of the United States of America,2020,2020-04-22,Y,Hypothesis Testing; Change-point Detection; Subgroup Detection; Tree Structures,,,"Tree structures, showing hierarchical relationships and the latent structures between samples, are ubiquitous in genomic and biomedical sciences. A common question in many studies is whether there is an association between a response variable measured on each sample and the latent group structure represented by some given tree. Currently, this is addressed on an ad hoc basis, usually requiring the user to decide on an appropriate number of clusters to prune out of the tree to be tested against the response variable. Here, we present a statistical method with statistical guarantees that tests for association between the response variable and a fixed tree structure across all levels of the tree hierarchy with high power while accounting for the overall false positive error rate. This enhances the robustness and reproducibility of such findings.",,pdf:https://www.pnas.org/content/pnas/117/18/9787.full.pdf; doi:https://doi.org/10.1073/pnas.1912957117; html:https://europepmc.org/articles/PMC7211961; pdf:https://europepmc.org/articles/PMC7211961?pdf=render -38552911,https://doi.org/10.1016/j.jad.2024.03.106,Identifying depression-related topics in smartphone-collected free-response speech recordings using an automatic speech recognition system and a deep learning topic model.,"Zhang Y, Folarin AA, Dineley J, Conde P, de Angel V, Sun S, Ranjan Y, Rashid Z, Stewart C, Laiou P, Sankesara H, Qian L, Matcham F, White K, Oetzmann C, Lamers F, Siddi S, Simblett S, Schuller BW, Vairavan S, Wykes T, Haro JM, Penninx BWJH, Narayan VA, Hotopf M, Dobson RJB, Cummins N, RADAR-CNS consortium.",,Journal of affective disorders,2024,2024-03-27,N,Depression; Speech; Smartphone; Automatic Speech Recognition; Topic Modeling,,,"

Background

Prior research has associated spoken language use with depression, yet studies often involve small or non-clinical samples and face challenges in the manual transcription of speech. This paper aimed to automatically identify depression-related topics in speech recordings collected from clinical samples.

Methods

The data included 3919 English free-response speech recordings collected via smartphones from 265 participants with a depression history. We transcribed speech recordings via automatic speech recognition (Whisper tool, OpenAI) and identified principal topics from transcriptions using a deep learning topic model (BERTopic). To identify depression risk topics and understand the context, we compared participants' depression severity and behavioral (extracted from wearable devices) and linguistic (extracted from transcribed texts) characteristics across identified topics.

Results

From the 29 topics identified, we identified 6 risk topics for depression: 'No Expectations', 'Sleep', 'Mental Therapy', 'Haircut', 'Studying', and 'Coursework'. Participants mentioning depression risk topics exhibited higher sleep variability, later sleep onset, and fewer daily steps and used fewer words, more negative language, and fewer leisure-related words in their speech recordings.

Limitations

Our findings were derived from a depressed cohort with a specific speech task, potentially limiting the generalizability to non-clinical populations or other speech tasks. Additionally, some topics had small sample sizes, necessitating further validation in larger datasets.

Conclusion

This study demonstrates that specific speech topics can indicate depression severity. The employed data-driven workflow provides a practical approach for analyzing large-scale speech data collected from real-world settings.",,doi:https://doi.org/10.1016/j.jad.2024.03.106 36587850,https://doi.org/10.1016/j.jaci.2022.12.810,The gut microbiome is a significant risk factor for future chronic lung disease.,"Liu Y, Teo SM, Méric G, Tang HHF, Zhu Q, Sanders JG, Vázquez-Baeza Y, Verspoor K, Vartiainen VA, Jousilahti P, Lahti L, Niiranen T, Havulinna AS, Knight R, Salomaa V, Inouye M.",,The Journal of allergy and clinical immunology,2023,2022-12-29,Y,Gut; Asthma; COPD; Metagenomics; Microbiome,,,"

Background

The gut-lung axis is generally recognized, but there are few large studies of the gut microbiome and incident respiratory disease in adults.

Objective

We sought to investigate the association and predictive capacity of the gut microbiome for incident asthma and chronic obstructive pulmonary disease (COPD).

Methods

Shallow metagenomic sequencing was performed for stool samples from a prospective, population-based cohort (FINRISK02; N = 7115 adults) with linked national administrative health register-derived classifications for incident asthma and COPD up to 15 years after baseline. Generalized linear models and Cox regressions were used to assess associations of microbial taxa and diversity with disease occurrence. Predictive models were constructed using machine learning with extreme gradient boosting. Models considered taxa abundances individually and in combination with other risk factors, including sex, age, body mass index, and smoking status.

Results

A total of 695 and 392 statistically significant associations were found between baseline taxonomic groups and incident asthma and COPD, respectively. Gradient boosting decision trees of baseline gut microbiome abundance predicted incident asthma and COPD in the validation data sets with mean area under the curves of 0.608 and 0.780, respectively. Cox analysis showed that the baseline gut microbiome achieved higher predictive performance than individual conventional risk factors, with C-indices of 0.623 for asthma and 0.817 for COPD. The integration of the gut microbiome and conventional risk factors further improved prediction capacities.

Conclusions

The gut microbiome is a significant risk factor for incident asthma and incident COPD and is largely independent of conventional risk factors.",,doi:https://doi.org/10.1016/j.jaci.2022.12.810; doi:https://doi.org/10.1016/j.jaci.2022.12.810; html:https://europepmc.org/articles/PMC10109092; pdf:https://europepmc.org/articles/PMC10109092?pdf=render -37964568,https://doi.org/10.1192/bjo.2023.547,"The association of anxiety disorders and depression with facial scarring: population-based, data linkage, matched cohort analysis of 358 158 patients.","Gibson JAG, Dobbs TD, Griffiths R, Song J, Akbari A, Bodger O, Hutchings HA, Lyons RA, John A, Whitaker IS.",,BJPsych open,2023,2023-11-15,Y,epidemiology; risk assessment; Depressive Disorders; Trauma And Stressor-related Disorders; Anxiety Or Fear-related Disorders,,,"

Background

Estimates suggest that 1 in 100 people in the UK live with facial scarring. Despite this incidence, psychological support is limited.

Aims

The aim of this study was to strengthen the case for improving such support by determining the incidence and risk factors for anxiety and depression disorders in patients with facial scarring.

Method

A matched cohort study was performed. Patients were identified via secondary care data sources, using clinical codes for conditions resulting in facial scarring. A diagnosis of anxiety or depression was determined by linkage with the patient's primary care general practice data. Incidence was calculated per 1000 person-years at risk (PYAR). Logistic regression was used to determine risk factors.

Results

Between 2009 and 2018, 179 079 patients met the study criteria and were identified as having a facial scar, and matched to 179 079 controls. The incidence of anxiety in the facial scarring group was 10.05 per 1000 PYAR compared with 7.48 per 1000 PYAR for controls. The incidence of depression in the facial scarring group was 16.28 per 1000 PYAR compared with 9.56 per 1000 PYAR for controls. Age at the time of scarring, previous history of anxiety or depression, female gender, socioeconomic status and classification of scarring increased the risk of both anxiety disorders and depression.

Conclusions

There is a high burden of anxiety disorders and depression in this patient group. Risk of these mental health disorders is very much determined by factors apparent at the time of injury, supporting the need for psychological support.",,pdf:https://www.cambridge.org/core/services/aop-cambridge-core/content/view/269D54BC172655C337E4E02E05E0A4FB/S2056472423005471a.pdf/div-class-title-the-association-of-anxiety-disorders-and-depression-with-facial-scarring-population-based-data-linkage-matched-cohort-analysis-of-358-158-patients-div.pdf; doi:https://doi.org/10.1192/bjo.2023.547; html:https://europepmc.org/articles/PMC10753955; pdf:https://europepmc.org/articles/PMC10753955?pdf=render +38552911,https://doi.org/10.1016/j.jad.2024.03.106,Identifying depression-related topics in smartphone-collected free-response speech recordings using an automatic speech recognition system and a deep learning topic model.,"Zhang Y, Folarin AA, Dineley J, Conde P, de Angel V, Sun S, Ranjan Y, Rashid Z, Stewart C, Laiou P, Sankesara H, Qian L, Matcham F, White K, Oetzmann C, Lamers F, Siddi S, Simblett S, Schuller BW, Vairavan S, Wykes T, Haro JM, Penninx BWJH, Narayan VA, Hotopf M, Dobson RJB, Cummins N, RADAR-CNS consortium.",,Journal of affective disorders,2024,2024-03-27,N,Depression; Speech; Smartphone; Automatic Speech Recognition; Topic Modeling,,,"

Background

Prior research has associated spoken language use with depression, yet studies often involve small or non-clinical samples and face challenges in the manual transcription of speech. This paper aimed to automatically identify depression-related topics in speech recordings collected from clinical samples.

Methods

The data included 3919 English free-response speech recordings collected via smartphones from 265 participants with a depression history. We transcribed speech recordings via automatic speech recognition (Whisper tool, OpenAI) and identified principal topics from transcriptions using a deep learning topic model (BERTopic). To identify depression risk topics and understand the context, we compared participants' depression severity and behavioral (extracted from wearable devices) and linguistic (extracted from transcribed texts) characteristics across identified topics.

Results

From the 29 topics identified, we identified 6 risk topics for depression: 'No Expectations', 'Sleep', 'Mental Therapy', 'Haircut', 'Studying', and 'Coursework'. Participants mentioning depression risk topics exhibited higher sleep variability, later sleep onset, and fewer daily steps and used fewer words, more negative language, and fewer leisure-related words in their speech recordings.

Limitations

Our findings were derived from a depressed cohort with a specific speech task, potentially limiting the generalizability to non-clinical populations or other speech tasks. Additionally, some topics had small sample sizes, necessitating further validation in larger datasets.

Conclusion

This study demonstrates that specific speech topics can indicate depression severity. The employed data-driven workflow provides a practical approach for analyzing large-scale speech data collected from real-world settings.",,doi:https://doi.org/10.1016/j.jad.2024.03.106 32895316,https://doi.org/10.1136/thoraxjnl-2020-215566,We need a robust evidence base to unravel the relationship between sex hormones and asthma.,"Sheikh A, Mukherjee M.",,Thorax,2020,2020-09-07,N,Asthma,,,,,pdf:https://thorax.bmj.com/content/thoraxjnl/75/10/826.full.pdf; doi:https://doi.org/10.1136/thoraxjnl-2020-215566 +37964568,https://doi.org/10.1192/bjo.2023.547,"The association of anxiety disorders and depression with facial scarring: population-based, data linkage, matched cohort analysis of 358 158 patients.","Gibson JAG, Dobbs TD, Griffiths R, Song J, Akbari A, Bodger O, Hutchings HA, Lyons RA, John A, Whitaker IS.",,BJPsych open,2023,2023-11-15,Y,epidemiology; risk assessment; Depressive Disorders; Trauma And Stressor-related Disorders; Anxiety Or Fear-related Disorders,,,"

Background

Estimates suggest that 1 in 100 people in the UK live with facial scarring. Despite this incidence, psychological support is limited.

Aims

The aim of this study was to strengthen the case for improving such support by determining the incidence and risk factors for anxiety and depression disorders in patients with facial scarring.

Method

A matched cohort study was performed. Patients were identified via secondary care data sources, using clinical codes for conditions resulting in facial scarring. A diagnosis of anxiety or depression was determined by linkage with the patient's primary care general practice data. Incidence was calculated per 1000 person-years at risk (PYAR). Logistic regression was used to determine risk factors.

Results

Between 2009 and 2018, 179 079 patients met the study criteria and were identified as having a facial scar, and matched to 179 079 controls. The incidence of anxiety in the facial scarring group was 10.05 per 1000 PYAR compared with 7.48 per 1000 PYAR for controls. The incidence of depression in the facial scarring group was 16.28 per 1000 PYAR compared with 9.56 per 1000 PYAR for controls. Age at the time of scarring, previous history of anxiety or depression, female gender, socioeconomic status and classification of scarring increased the risk of both anxiety disorders and depression.

Conclusions

There is a high burden of anxiety disorders and depression in this patient group. Risk of these mental health disorders is very much determined by factors apparent at the time of injury, supporting the need for psychological support.",,pdf:https://www.cambridge.org/core/services/aop-cambridge-core/content/view/269D54BC172655C337E4E02E05E0A4FB/S2056472423005471a.pdf/div-class-title-the-association-of-anxiety-disorders-and-depression-with-facial-scarring-population-based-data-linkage-matched-cohort-analysis-of-358-158-patients-div.pdf; doi:https://doi.org/10.1192/bjo.2023.547; html:https://europepmc.org/articles/PMC10753955; pdf:https://europepmc.org/articles/PMC10753955?pdf=render 33644414,https://doi.org/10.23889/ijpds.v5i3.1371,Public involvement & engagement in the work of a data safe haven: a case study of the SAIL Databank.,"Jones KH, Heys S, Thompson R, Cross L, Ford D.",,International journal of population data science,2020,2020-08-24,Y,Public Engagement; Data Safe Haven,,,"

Background

The SAIL Databank is a data safe haven established in 2007 at Swansea University (Wales). It was set up to create new opportunities for research using routinely-collected health and other public service datasets in linkable anonymised form. SAIL forms the bedrock of other Population Data Science initiatives made possible by the data and safe haven environment.

Aim

The aim of this paper is to provide an overview of public involvement & engagement in connection with the SAIL Databank and related Population Data Science initiatives.

Approach

We have a public involvement & engagement policy for SAIL in the context of Population Data Science. We established a Consumer Panel to provide advice on the work of SAIL and associated initiatives, including on proposed uses of SAIL data. We reviewed the topics discussed and provide examples of advice to researchers. We carried out a survey with members on their experiences of being on the Panel and their perceptions of the work of SAIL. We have a programme of wider public engagement and provide illustrations of this work.

Discussion

We summarise what this paper adds and some lessons learned. In the rapidly developing area of Population Data Science it is important that people feel welcome, that they are encouraged to ask questions and are provided with digestible information and adequate consideration time. Citizens have provided us with valuable anticipated and unanticipated opinions and novel viewpoints. We seek to take a pragmatic approach, prioritising the communication modes that allow maximum public input commensurate with the purpose of the activity.

Conclusion

This paper has set out our policy, rationale, scope and practical approaches to public involvement & engagement for SAIL and our related Population Data Science initiatives. Although there will be jurisdictional, cultural and organizational differences, we believe that the material covered in this paper will be of interest to other data focused enterprises across the world.",,pdf:https://ijpds.org/article/download/1371/2815; doi:https://doi.org/10.23889/ijpds.v5i3.1371; html:https://europepmc.org/articles/PMC7893854; pdf:https://europepmc.org/articles/PMC7893854?pdf=render 38142238,https://doi.org/10.1093/ije/dyad175,Cohort Profile: The Cardiovascular Research Data Catalogue.,"Reinikainen J, Palosaari T, Canosa-Valls AJ, Schmidt CO, Wissa R, Chadalavada S, Codó L, Gelpí JL, Joseph B, van der Lugt A, Pacella E, Petersen SE, Pujadas ER, Szabo L, Zeller T, Niiranen T, Lekadir K, Kuulasmaa K.",,International journal of epidemiology,2024,2024-02-01,N,,,,,,doi:https://doi.org/10.1093/ije/dyad175 33789468,https://doi.org/10.1302/0301-620x.103b4.bjj-2020-1647.r1,Outcomes of severe lower limb injury with Mangled Extremity Severity Score ≥ 7.,"Hoogervorst LA, Hart MJ, Simpson PM, Kimmel LA, Oppy A, Edwards ER, Gabbe BJ.",,The bone & joint journal,2021,2021-04-01,N,Injury; Lower limb; Return To Work; Salvage; Functional Outcomes; Mess; Gos-e; Eq-5d-3l; Surgical Amputation; 2-Year,,,"

Aims

Complex fractures of the femur and tibia with associated severe soft tissue injury are often devastating for the individual. The aim of this study was to describe the two-year patient-reported outcomes of patients in a civilian population who sustained a complex fracture of the femur or tibia with a Mangled Extremity Severity Score (MESS) of ≥ 7, whereby the score ranges from 2 (lowest severity) to 11 (highest severity).

Methods

Patients aged ≥ 16 years with a fractured femur or tibia and a MESS of ≥ 7 were extracted from the Victorian Orthopaedic Trauma Outcomes Registry (January 2007 to December 2018). Cases were grouped into surgical amputation or limb salvage. Descriptive analysis were used to examine return to work rates, three-level EuroQol five-dimension questionnaire (EQ-5D-3L), and Glasgow Outcome Scale-Extended (GOS-E) outcomes at 12 and 24 months post-injury.

Results

In all, 111 patients were included: 90 (81%) patients who underwent salvage and 21 (19%) patients with surgical amputation. The mean age of patients was 45.8 years (SD 15.8), 93 (84%) were male, 37 (33%) were involved in motor vehicle collisions, and the mean MESS score was 8.2 (SD 1.4). Two-year outcomes in the cohort were poor: six (7%) patients achieved a GOS-E good recovery, the mean EQ-5D-3L summary score was 0.52 (SD 0.27), and 17 (20%) patients had returned to work.

Conclusion

A small proportion of patients with severe lower limb injury (MESS ≥ 7) achieved a good level of function 24 months post-injury. Further follow-up is needed to better understand the long-term trajectory of these patients, including delayed amputation, hospital readmissions, and healthcare utilization. Cite this article: Bone Joint J 2021;103-B(4):769-774.",,doi:https://doi.org/10.1302/0301-620X.103B4.BJJ-2020-1647.R1 @@ -1331,13 +1331,13 @@ PMC8855010,https://doi.org/,POS-894 PREDICTING PANDEMIC-RELATED EXCESS-DEATH USI 35264566,https://doi.org/10.1038/s41467-022-28729-3,Elucidating mechanisms of genetic cross-disease associations at the PROCR vascular disease locus.,"Stacey D, Chen L, Stanczyk PJ, Howson JMM, Mason AM, Burgess S, MacDonald S, Langdown J, McKinney H, Downes K, Farahi N, Peters JE, Basu S, Pankow JS, Tang W, Pankratz N, Sabater-Lleal M, de Vries PS, Smith NL, CHARGE Hemostasis Working Group, Gelinas AD, Schneider DJ, Janjic N, Samani NJ, Ye S, Summers C, Chilvers ER, Danesh J, Paul DS.",,Nature communications,2022,2022-03-09,Y,,,,"Many individual genetic risk loci have been associated with multiple common human diseases. However, the molecular basis of this pleiotropy often remains unclear. We present an integrative approach to reveal the molecular mechanism underlying the PROCR locus, associated with lower coronary artery disease (CAD) risk but higher venous thromboembolism (VTE) risk. We identify PROCR-p.Ser219Gly as the likely causal variant at the locus and protein C as a causal factor. Using genetic analyses, human recall-by-genotype and in vitro experimentation, we demonstrate that PROCR-219Gly increases plasma levels of (activated) protein C through endothelial protein C receptor (EPCR) ectodomain shedding in endothelial cells, attenuating leukocyte-endothelial cell adhesion and vascular inflammation. We also associate PROCR-219Gly with an increased pro-thrombotic state via coagulation factor VII, a ligand of EPCR. Our study, which links PROCR-219Gly to CAD through anti-inflammatory mechanisms and to VTE through pro-thrombotic mechanisms, provides a framework to reveal the mechanisms underlying similar cross-phenotype associations.",,pdf:https://www.nature.com/articles/s41467-022-28729-3.pdf; doi:https://doi.org/10.1038/s41467-022-28729-3; html:https://europepmc.org/articles/PMC8907312; pdf:https://europepmc.org/articles/PMC8907312?pdf=render 29944675,https://doi.org/10.1371/journal.pone.0199026,"The diagnosis, burden and prognosis of dementia: A record-linkage cohort study in England.","Pujades-Rodriguez M, Assi V, Gonzalez-Izquierdo A, Wilkinson T, Schnier C, Sudlow C, Hemingway H, Whiteley WN.",,PloS one,2018,2018-06-26,Y,,The Human Phenome,,"

Objectives

Electronic health records (EHR) might be a useful resource to study the risk factors and clinical care of people with dementia. We sought to determine the diagnostic validity of dementia captured in linked EHR.

Methods and findings

A cohort of adults in linked primary care, hospital, disease registry and mortality records in England, [CALIBER (CArdiovascular disease research using LInked Bespoke studies and Electronic health Records)]. The proportion of individuals with dementia, Alzheimer's disease, vascular and rare dementia in each data source was determined. A comparison was made of symptoms and care between people with dementia and age-, sex- and general practice-matched controls, using conditional logistic regression. The lifetime risk and prevalence of dementia and mortality rates in people with and without dementia were estimated with random-effects Poisson models. There were 47,386 people with dementia: 12,633 with Alzheimer's disease, 9540 with vascular and 1539 with rare dementia. Seventy-four percent of cases had corroborating evidence of dementia. People with dementia were more likely to live in a deprived area (conditional OR 1.26;95%CI:1.20-1.31 most vs least deprived), have documented memory impairment (cOR = 11.97;95%CI:11.24-12.75), falls (cOR = 2.36;95%CI:2.31-2.41), depression (cOR = 2.03; 95%CI:1.98-2.09) or anxiety (cOR = 1.27; 95%CI:1.23-1.32). The lifetime risk of dementia at age 65 was 9.2% (95%CI:9.0%-9.4%), in men and 14.9% (95%CI:14.7%-15.1%) in women. The population prevalence of recorded dementia increased from 0.3% in 2000 to 0.7% in 2010. A higher mortality rate was observed in people with than without dementia (IRR = 1.56;95%CI:1.54-1.58).

Conclusions

Most people with a record of dementia in linked UK EHR had some corroborating evidence for diagnosis. The estimated 10-year risk of dementia was higher than published population-based estimations. EHR are therefore a promising source of data for dementia research.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0199026&type=printable; doi:https://doi.org/10.1371/journal.pone.0199026; html:https://europepmc.org/articles/PMC6019102; pdf:https://europepmc.org/articles/PMC6019102?pdf=render 33130851,https://doi.org/10.1093/ije/dyaa216,High-throughput multivariable Mendelian randomization analysis prioritizes apolipoprotein B as key lipid risk factor for coronary artery disease.,"Zuber V, Gill D, Ala-Korpela M, Langenberg C, Butterworth A, Bottolo L, Burgess S.",,International journal of epidemiology,2021,2021-07-01,Y,Lipoproteins; Apolipoprotein B; Metabolomics; blood lipids; coronary artery disease; Mendelian Randomization; Risk Factor Selection,,,"

Background

Genetic variants can be used to prioritize risk factors as potential therapeutic targets via Mendelian randomization (MR). An agnostic statistical framework using Bayesian model averaging (MR-BMA) can disentangle the causal role of correlated risk factors with shared genetic predictors. Here, our objective is to identify lipoprotein measures as mediators between lipid-associated genetic variants and coronary artery disease (CAD) for the purpose of detecting therapeutic targets for CAD.

Methods

As risk factors we consider 30 lipoprotein measures and metabolites derived from a high-throughput metabolomics study including 24 925 participants. We fit multivariable MR models of genetic associations with CAD estimated in 453 595 participants (including 113 937 cases) regressed on genetic associations with the risk factors. MR-BMA assigns to each combination of risk factors a model score quantifying how well the genetic associations with CAD are explained. Risk factors are ranked by their marginal score and selected using false-discovery rate (FDR) criteria. We perform supplementary and sensitivity analyses varying the dataset for genetic associations with CAD.

Results

In the main analysis, the top combination of risk factors ranked by the model score contains apolipoprotein B (ApoB) only. ApoB is also the highest ranked risk factor with respect to the marginal score (FDR <0.005). Additionally, ApoB is selected in all sensitivity analyses. No other measure of cholesterol or triglyceride is consistently selected otherwise.

Conclusions

Our agnostic genetic investigation prioritizes ApoB across all datasets considered, suggesting that ApoB, representing the total number of hepatic-derived lipoprotein particles, is the primary lipid determinant of CAD.",,doi:https://doi.org/10.1093/ije/dyaa216; doi:https://doi.org/10.1093/ije/dyaa216; html:https://europepmc.org/articles/PMC8271202; pdf:https://europepmc.org/articles/PMC8271202?pdf=render -37987834,https://doi.org/10.1007/s00330-023-10311-0,Radiomics of pericardial fat: a new frontier in heart failure discrimination and prediction.,"Szabo L, Salih A, Pujadas ER, Bard A, McCracken C, Ardissino M, Antoniades C, Vago H, Maurovich-Horvat P, Merkely B, Neubauer S, Lekadir K, Petersen SE, Raisi-Estabragh Z.",,European radiology,2023,2023-11-21,N,Pericardium; Adipose tissue; Magnetic Resonance Imaging; Machine Learning; Radiomics,,,"

Objectives

To use pericardial adipose tissue (PAT) radiomics phenotyping to differentiate existing and predict future heart failure (HF) cases in the UK Biobank.

Methods

PAT segmentations were derived from cardiovascular magnetic resonance (CMR) studies using an automated quality-controlled model to define the region-of-interest for radiomics analysis. Prevalent (present at time of imaging) and incident (first occurrence after imaging) HF were ascertained using health record linkage. We created balanced cohorts of non-HF individuals for comparison. PyRadiomics was utilised to extract 104 radiomics features, of which 28 were chosen after excluding highly correlated ones (0.8). These features, plus sex and age, served as predictors in binary classification models trained separately to detect (1) prevalent and (2) incident HF. We tested seven modeling methods using tenfold nested cross-validation and examined feature importance with explainability methods.

Results

We studied 1204 participants in total, 297 participants with prevalent (60 ± 7 years, 21% female) and 305 with incident (61 ± 6 years, 32% female) HF, and an equal number of non-HF comparators. We achieved good discriminative performance for both prevalent (voting classifier; AUC: 0.76; F1 score: 0.70) and incident (light gradient boosting machine: AUC: 0.74; F1 score: 0.68) HF. Our radiomics models showed marginally better performance compared to PAT area alone. Increased PAT size (maximum 2D diameter in a given column or slice) and texture heterogeneity (sum entropy) were important features for prevalent and incident HF classification models.

Conclusions

The amount and character of PAT discriminate individuals with prevalent HF and predict incidence of future HF.

Clinical relevance statement

This study presents an innovative application of pericardial adipose tissue (PAT) radiomics phenotyping as a predictive tool for heart failure (HF), a major public health concern. By leveraging advanced machine learning methods, the research uncovers that the quantity and characteristics of PAT can be used to identify existing cases of HF and predict future occurrences. The enhanced performance of these radiomics models over PAT area alone supports the potential for better personalised care through earlier detection and prevention of HF.

Key points

•PAT radiomics applied to CMR was used for the first time to derive binary machine learning classifiers to develop models for discrimination of prevalence and prediction of incident heart failure. •Models using PAT area provided acceptable discrimination between cases of prevalent or incident heart failure and comparator groups. •An increased PAT volume (increased diameter using shape features) and greater texture heterogeneity captured by radiomics texture features (increased sum entropy) can be used as an additional classifier marker for heart failure.",,pdf:https://link.springer.com/content/pdf/10.1007/s00330-023-10311-0.pdf; doi:https://doi.org/10.1007/s00330-023-10311-0 37285143,https://doi.org/10.1001/jamacardio.2023.1290,Diagnostic and Prognostic Value of Stress Cardiovascular Magnetic Resonance Imaging in Patients With Known or Suspected Coronary Artery Disease: A Systematic Review and Meta-analysis.,"Ricci F, Khanji MY, Bisaccia G, Cipriani A, Di Cesare A, Ceriello L, Mantini C, Zimarino M, Fedorowski A, Gallina S, Petersen SE, Bucciarelli-Ducci C.",,JAMA cardiology,2023,2023-07-01,N,,,,"

Importance

The clinical utility of stress cardiovascular magnetic resonance imaging (CMR) in stable chest pain is still debated, and the low-risk period for adverse cardiovascular (CV) events after a negative test result is unknown.

Objective

To provide contemporary quantitative data synthesis of the diagnostic accuracy and prognostic value of stress CMR in stable chest pain.

Data sources

PubMed and Embase databases, the Cochrane Database of Systematic Reviews, PROSPERO, and the ClinicalTrials.gov registry were searched for potentially relevant articles from January 1, 2000, through December 31, 2021.

Study selection

Selected studies evaluated CMR and reported estimates of diagnostic accuracy and/or raw data of adverse CV events for participants with either positive or negative stress CMR results. Prespecified combinations of keywords related to the diagnostic accuracy and prognostic value of stress CMR were used. A total of 3144 records were evaluated for title and abstract; of those, 235 articles were included in the full-text assessment of eligibility. After exclusions, 64 studies (74 470 total patients) published from October 29, 2002, through October 19, 2021, were included.

Data extraction and synthesis

This systematic review and meta-analysis adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses.

Main outcomes and measures

Diagnostic odds ratios (DORs), sensitivity, specificity, area under the receiver operating characteristic curve (AUROC), odds ratio (OR), and annualized event rate (AER) for all-cause death, CV death, and major adverse cardiovascular events (MACEs) defined as the composite of myocardial infarction and CV death.

Results

A total of 33 diagnostic studies pooling 7814 individuals and 31 prognostic studies pooling 67 080 individuals (mean [SD] follow-up, 3.5 [2.1] years; range, 0.9-8.8 years; 381 357 person-years) were identified. Stress CMR yielded a DOR of 26.4 (95% CI, 10.6-65.9), a sensitivity of 81% (95% CI, 68%-89%), a specificity of 86% (95% CI, 75%-93%), and an AUROC of 0.84 (95% CI, 0.77-0.89) for the detection of functionally obstructive coronary artery disease. In the subgroup analysis, stress CMR yielded higher diagnostic accuracy in the setting of suspected coronary artery disease (DOR, 53.4; 95% CI, 27.7-103.0) or when using 3-T imaging (DOR, 33.2; 95% CI, 19.9-55.4). The presence of stress-inducible ischemia was associated with higher all-cause mortality (OR, 1.97; 95% CI, 1.69-2.31), CV mortality (OR, 6.40; 95% CI, 4.48-9.14), and MACEs (OR, 5.33; 95% CI, 4.04-7.04). The presence of late gadolinium enhancement (LGE) was associated with higher all-cause mortality (OR, 2.22; 95% CI, 1.99-2.47), CV mortality (OR, 6.03; 95% CI, 2.76-13.13), and increased risk of MACEs (OR, 5.42; 95% CI, 3.42-8.60). After a negative test result, pooled AERs for CV death were less than 1.0%.

Conclusion and relevance

In this study, stress CMR yielded high diagnostic accuracy and delivered robust prognostication, particularly when 3-T scanners were used. While inducible myocardial ischemia and LGE were associated with higher mortality and risk of MACEs, normal stress CMR results were associated with a lower risk of MACEs for at least 3.5 years.",,doi:https://doi.org/10.1001/jamacardio.2023.1290 35684987,https://doi.org/10.1111/camh.12571,Assessing the feasibility of a web-based outcome measurement system in child and adolescent mental health services - myHealthE a randomised controlled feasibility pilot study.,"Morris AC, Ibrahim Z, Heslin M, Moghraby OS, Stringaris A, Grant IM, Zalewski L, Pritchard M, Stewart R, Hotopf M, Pickles A, Dobson RJB, Simonoff E, Downs J.",,Child and adolescent mental health,2023,2022-06-09,Y,Child And Adolescent Mental Health; Remote Monitoring; Acceptability; Patient-reported Outcome Measures,,,"

Background

Interest in internet-based patient reported outcome measure (PROM) collection is increasing. The NHS myHealthE (MHE) web-based monitoring system was developed to address the limitations of paper-based PROM completion. MHE provides a simple and secure way for families accessing Child and Adolescent Mental Health Services to report clinical information and track their child's progress. This study aimed to assess whether MHE improves the completion of the Strengths and Difficulties Questionnaire (SDQ) compared with paper collection. Secondary objectives were to explore caregiver satisfaction and application acceptability.

Methods

A 12-week single-blinded randomised controlled feasibility pilot trial of MHE was conducted with 196 families accessing neurodevelopmental services in south London to examine whether electronic questionnaires are completed more readily than paper-based questionnaires over a 3-month period. Follow up process evaluation phone calls with a subset (n = 8) of caregivers explored system satisfaction and usability.

Results

MHE group assignment was significantly associated with an increased probability of completing an SDQ-P in the study period (adjusted hazard ratio (HR) 12.1, 95% CI 4.7-31.0; p = <.001). Of those caregivers' who received the MHE invitation (n = 68) 69.1% completed an SDQ using the platform compared to 8.8% in the control group (n = 68). The system was well received by caregivers, who cited numerous benefits of using MHE, for example, real-time feedback and ease of completion.

Conclusions

MHE holds promise for improving PROM completion rates. Research is needed to refine MHE, evaluate large-scale MHE implementation, cost effectiveness and explore factors associated with differences in electronic questionnaire uptake.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/camh.12571; doi:https://doi.org/10.1111/camh.12571; html:https://europepmc.org/articles/PMC10083915; pdf:https://europepmc.org/articles/PMC10083915?pdf=render +37987834,https://doi.org/10.1007/s00330-023-10311-0,Radiomics of pericardial fat: a new frontier in heart failure discrimination and prediction.,"Szabo L, Salih A, Pujadas ER, Bard A, McCracken C, Ardissino M, Antoniades C, Vago H, Maurovich-Horvat P, Merkely B, Neubauer S, Lekadir K, Petersen SE, Raisi-Estabragh Z.",,European radiology,2023,2023-11-21,N,Pericardium; Adipose tissue; Magnetic Resonance Imaging; Machine Learning; Radiomics,,,"

Objectives

To use pericardial adipose tissue (PAT) radiomics phenotyping to differentiate existing and predict future heart failure (HF) cases in the UK Biobank.

Methods

PAT segmentations were derived from cardiovascular magnetic resonance (CMR) studies using an automated quality-controlled model to define the region-of-interest for radiomics analysis. Prevalent (present at time of imaging) and incident (first occurrence after imaging) HF were ascertained using health record linkage. We created balanced cohorts of non-HF individuals for comparison. PyRadiomics was utilised to extract 104 radiomics features, of which 28 were chosen after excluding highly correlated ones (0.8). These features, plus sex and age, served as predictors in binary classification models trained separately to detect (1) prevalent and (2) incident HF. We tested seven modeling methods using tenfold nested cross-validation and examined feature importance with explainability methods.

Results

We studied 1204 participants in total, 297 participants with prevalent (60 ± 7 years, 21% female) and 305 with incident (61 ± 6 years, 32% female) HF, and an equal number of non-HF comparators. We achieved good discriminative performance for both prevalent (voting classifier; AUC: 0.76; F1 score: 0.70) and incident (light gradient boosting machine: AUC: 0.74; F1 score: 0.68) HF. Our radiomics models showed marginally better performance compared to PAT area alone. Increased PAT size (maximum 2D diameter in a given column or slice) and texture heterogeneity (sum entropy) were important features for prevalent and incident HF classification models.

Conclusions

The amount and character of PAT discriminate individuals with prevalent HF and predict incidence of future HF.

Clinical relevance statement

This study presents an innovative application of pericardial adipose tissue (PAT) radiomics phenotyping as a predictive tool for heart failure (HF), a major public health concern. By leveraging advanced machine learning methods, the research uncovers that the quantity and characteristics of PAT can be used to identify existing cases of HF and predict future occurrences. The enhanced performance of these radiomics models over PAT area alone supports the potential for better personalised care through earlier detection and prevention of HF.

Key points

•PAT radiomics applied to CMR was used for the first time to derive binary machine learning classifiers to develop models for discrimination of prevalence and prediction of incident heart failure. •Models using PAT area provided acceptable discrimination between cases of prevalent or incident heart failure and comparator groups. •An increased PAT volume (increased diameter using shape features) and greater texture heterogeneity captured by radiomics texture features (increased sum entropy) can be used as an additional classifier marker for heart failure.",,pdf:https://link.springer.com/content/pdf/10.1007/s00330-023-10311-0.pdf; doi:https://doi.org/10.1007/s00330-023-10311-0 36264615,https://doi.org/10.1161/circgen.122.003704,Prevalence and Disease Expression of Pathogenic and Likely Pathogenic Variants Associated With Inherited Cardiomyopathies in the General Population.,"Bourfiss M, van Vugt M, Alasiri AI, Ruijsink B, van Setten J, Schmidt AF, Dooijes D, Puyol-Antón E, Velthuis BK, van Tintelen JP, Te Riele ASJM, Baas AF, Asselbergs FW.",,Circulation. Genomic and precision medicine,2022,2022-10-20,Y,Genetics; Dilated cardiomyopathy; hypertrophic cardiomyopathy; Arrhythmogenic Right Ventricular Cardiomyopathy; Whole Exome Sequencing,,,"

Background

Pathogenic and likely pathogenic variants associated with arrhythmogenic right ventricular cardiomyopathy (ARVC), dilated cardiomyopathy (DCM), and hypertrophic cardiomyopathy (HCM) are recommended to be reported as secondary findings in genome sequencing studies. This provides opportunities for early diagnosis, but also fuels uncertainty in variant carriers (G+), since disease penetrance is incomplete. We assessed the prevalence and disease expression of G+ in the general population.

Methods

We identified pathogenic and likely pathogenic variants associated with ARVC, DCM and/or HCM in 200 643 UK Biobank individuals, who underwent whole exome sequencing. We calculated the prevalence of G+ and analyzed the frequency of cardiomyopathy/heart failure diagnosis. In undiagnosed individuals, we analyzed early signs of disease expression using available electrocardiography and cardiac magnetic resonance imaging data.

Results

We found a prevalence of 1:578, 1:251, and 1:149 for pathogenic and likely pathogenic variants associated with ARVC, DCM and HCM respectively. Compared with controls, cardiovascular mortality was higher in DCM G+ (odds ratio 1.67 [95% CI 1.04; 2.59], P=0.030), but similar in ARVC and HCM G+ (P≥0.100). Cardiomyopathy or heart failure diagnosis were more frequent in DCM G+ (odds ratio 3.66 [95% CI 2.24; 5.81], P=4.9×10-7) and HCM G+ (odds ratio 3.03 [95% CI 1.98; 4.56], P=5.8×10-7), but comparable in ARVC G+ (P=0.172). In contrast, ARVC G+ had more ventricular arrhythmias (P=3.3×10-4). In undiagnosed individuals, left ventricular ejection fraction was reduced in DCM G+ (P=0.009).

Conclusions

In the general population, pathogenic and likely pathogenic variants associated with ARVC, DCM, or HCM are not uncommon. Although G+ have increased mortality and morbidity, disease penetrance in these carriers from the general population remains low (1.2-3.1%). Follow-up decisions in case of incidental findings should not be based solely on a variant, but on multiple factors, including family history and disease expression.",,pdf:https://discovery.ucl.ac.uk/10160737/3/Asselbergs_hcg-15-e003704.pdf; doi:https://doi.org/10.1161/CIRCGEN.122.003704; html:https://europepmc.org/articles/PMC9770140; pdf:https://europepmc.org/articles/PMC9770140?pdf=render 37990330,https://doi.org/10.1186/s13063-023-07763-6,"Correction: Medicines and Healthcare products Regulatory Agency's ""Consultation on proposals for legislative changes for clinical trials"": a response from the Trials Methodology Research Partnership Adaptive Designs Working Group, with a focus on data sharing.","Law M, Couturier DL, Choodari-Oskooei B, Crout P, Gamble C, Jacko P, Pallmann P, Pilling M, Robertson DS, Robling M, Sydes MR, Villar SS, Wason J, Wheeler G, Williamson SF, Yap C, Jaki T.",,Trials,2023,2023-11-21,Y,,,,,,pdf:https://trialsjournal.biomedcentral.com/counter/pdf/10.1186/s13063-023-07763-6; doi:https://doi.org/10.1186/s13063-023-07763-6; html:https://europepmc.org/articles/PMC10664262; pdf:https://europepmc.org/articles/PMC10664262?pdf=render -37706486,https://doi.org/10.1080/09638288.2023.2254235,Stepped collaborative care for pain and posttraumatic stress disorder after major trauma: a randomized controlled feasibility trial.,"Giummarra MJ, Reeder S, Williams S, Devlin A, Knol R, Ponsford J, Arnold CA, Konstantatos A, Gabbe BJ, Clarke H, Katz J, Mitchell F, Robinson E, Zatzick D.",,Disability and rehabilitation,2023,2023-09-14,N,Trauma; Injury; Recovery; Pain; Hospitalization; Ptsd; Brief Intervention,,,"

Purpose

To examine feasibility and acceptability of providing stepped collaborative care case management targeting posttraumatic stress disorder (PTSD) and pain symptoms after major traumatic injury.

Materials and methods

Participants were major trauma survivors in Victoria, Australia, at risk of persistent pain or PTSD with high baseline symptoms. Participants were block-randomized, stratified by compensation-status, to the usual care (n = 15) or intervention (n = 17) group (46% of eligible patients). The intervention was adapted from existing stepped collaborative care interventions with input from interdisciplinary experts and people with lived experience in trauma and disability. The proactive case management intervention targeted PTSD and pain management for 6-months using motivational interviewing, cognitive behavioral therapy strategies, and collaborative care. Qualitative interviews explored intervention acceptability.

Results

Intervention participants received a median of 7 h case manager contact and reported that they valued the supportive and non-judgmental listening, and timely access to effective strategies, resources, and treatments post-injury from the case manager. Participants reported few disadvantages from participation, and positive impacts on symptoms and recovery outcomes consistent with the reduction in PTSD and pain symptoms measured at 1-, 3- and 6-months.

Conclusions

Stepped collaborative care was low-cost, feasible, and acceptable to people at risk of PTSD or pain after major trauma.IMPLICATIONS FOR REHABILITATIONAfter hospitalization for injury, people can experience difficulty accessing timely support to manage posttraumatic stress, pain and other concerns.Stepped case management-based interventions that provide individualized support and collaborative care have reduced posttraumatic stress symptom severity for patients admitted to American trauma centers.We showed that this model of care could be adapted to target pain and mental health in the trauma system in Victoria, Australia.The intervention was low cost, acceptable and highly valued by most participants who perceived that it helped them use strategies to better manage post-traumatic symptoms, and to access clinicians and treatments relevant to their needs.",,pdf:https://www.tandfonline.com/doi/pdf/10.1080/09638288.2023.2254235?needAccess=true; doi:https://doi.org/10.1080/09638288.2023.2254235 33382071,https://doi.org/10.1093/schbul/sbaa176,Corrigendum to: Using Natural Language Processing on Electronic Health Records to Enhance Detection and Prediction of Psychosis Risk.,,,Schizophrenia bulletin,2021,2021-03-01,N,,,,,,pdf:https://academic.oup.com/schizophreniabulletin/article-pdf/47/2/575/36620724/sbaa176.pdf; doi:https://doi.org/10.1093/schbul/sbaa176; html:https://europepmc.org/articles/PMC7965055; pdf:https://europepmc.org/articles/PMC7965055?pdf=render; doi:https://doi.org/10.1093/schbul/sbaa176 +37706486,https://doi.org/10.1080/09638288.2023.2254235,Stepped collaborative care for pain and posttraumatic stress disorder after major trauma: a randomized controlled feasibility trial.,"Giummarra MJ, Reeder S, Williams S, Devlin A, Knol R, Ponsford J, Arnold CA, Konstantatos A, Gabbe BJ, Clarke H, Katz J, Mitchell F, Robinson E, Zatzick D.",,Disability and rehabilitation,2023,2023-09-14,N,Trauma; Injury; Recovery; Pain; Hospitalization; Ptsd; Brief Intervention,,,"

Purpose

To examine feasibility and acceptability of providing stepped collaborative care case management targeting posttraumatic stress disorder (PTSD) and pain symptoms after major traumatic injury.

Materials and methods

Participants were major trauma survivors in Victoria, Australia, at risk of persistent pain or PTSD with high baseline symptoms. Participants were block-randomized, stratified by compensation-status, to the usual care (n = 15) or intervention (n = 17) group (46% of eligible patients). The intervention was adapted from existing stepped collaborative care interventions with input from interdisciplinary experts and people with lived experience in trauma and disability. The proactive case management intervention targeted PTSD and pain management for 6-months using motivational interviewing, cognitive behavioral therapy strategies, and collaborative care. Qualitative interviews explored intervention acceptability.

Results

Intervention participants received a median of 7 h case manager contact and reported that they valued the supportive and non-judgmental listening, and timely access to effective strategies, resources, and treatments post-injury from the case manager. Participants reported few disadvantages from participation, and positive impacts on symptoms and recovery outcomes consistent with the reduction in PTSD and pain symptoms measured at 1-, 3- and 6-months.

Conclusions

Stepped collaborative care was low-cost, feasible, and acceptable to people at risk of PTSD or pain after major trauma.IMPLICATIONS FOR REHABILITATIONAfter hospitalization for injury, people can experience difficulty accessing timely support to manage posttraumatic stress, pain and other concerns.Stepped case management-based interventions that provide individualized support and collaborative care have reduced posttraumatic stress symptom severity for patients admitted to American trauma centers.We showed that this model of care could be adapted to target pain and mental health in the trauma system in Victoria, Australia.The intervention was low cost, acceptable and highly valued by most participants who perceived that it helped them use strategies to better manage post-traumatic symptoms, and to access clinicians and treatments relevant to their needs.",,pdf:https://www.tandfonline.com/doi/pdf/10.1080/09638288.2023.2254235?needAccess=true; doi:https://doi.org/10.1080/09638288.2023.2254235 31529100,https://doi.org/10.1093/pm/pnz209,"Pain, Anxiety, and Depression in the First Two Years Following Transport-Related Major Trauma: A Population-Based, Prospective Registry Cohort Study.","Giummarra MJ, Simpson P, Gabbe BJ.",,"Pain medicine (Malden, Mass.)",2020,2020-02-01,N,Trauma; Injury; Prognostic; Recovery; Motor Vehicle,,,"

Objectives

This study aimed to characterize the population prevalence of pain and mental health problems postinjury and to identify risk factors that could improve service delivery to optimize recovery of at-risk patients.

Methods

This population-based registry cohort study included 5,350 adult survivors of transport-related major trauma injuries from the Victorian State Trauma Registry. Outcome profiles were generated separately for pain and mental health outcomes using the ""pain or discomfort"" and ""anxiety or depression"" items of the EuroQol Five Dimensions Three-Level questionnaire at six, 12, and 24 months postinjury. Profiles were ""resilient"" (no problems at every follow-up), ""recovered"" (problems at six- and/or 12-month follow-up that later resolved), ""worsening"" (problems at 12 and/or 24 months after no problems at six and/or 12 months), and ""persistent"" (problems at every follow-up).

Results

Most participants had persistent (pain/discomfort, N = 2,171, 39.7%; anxiety/depression, N = 1,428, 26.2%) and resilient profiles (pain/discomfort, N = 1,220, 22.3%; anxiety/depression, N = 2,055, 37.7%), followed by recovered (pain/discomfort, N = 1,116, 20.4%; anxiety/depression, N = 1,025, 18.8%) and worsening profiles (pain/discomfort, N = 956, 17.5%; anxiety/depression, N = 948, 17.4%). Adjusted multinomial logistic regressions showed increased risk of problems (persistent, worsening, or resolved) vs no problems (resilient) in relation to female sex, middle age, neighborhood disadvantage, pre-injury unemployment, pre-injury disability, and spinal cord injury. People living in rural areas, motorcyclists, pedal cyclists, and people with head, chest, and abdominal injuries had lower risk of problems.

Discussion

Targeted interventions delivered to people with the risk factors identified may help to attenuate the severity and impact of pain and mental health problems after transport injury.",,pdf:https://academic.oup.com/painmedicine/article-pdf/21/2/291/32739506/pnz209.pdf; doi:https://doi.org/10.1093/pm/pnz209 34000735,https://doi.org/10.1093/ije/dyab025,Commentary: Obstetric oxytocin exposure and risk of attention-deficit hyperactivity disorder and autism spectrum disorder in offspring-case closed.,"Morales DR, Nordeng HM.",,International journal of epidemiology,2021,2021-05-01,N,,,,,,pdf:https://academic.oup.com/ije/article-pdf/50/2/457/37947593/dyab025.pdf; doi:https://doi.org/10.1093/ije/dyab025 35487318,https://doi.org/10.1016/j.ijcard.2022.04.067,Implications of elevated troponin on time-to-surgery in non-ST elevation myocardial infarction (NIHR Health Informatics Collaborative: TROP-CABG study).,"Benedetto U, Sinha S, Mulla A, Glampson B, Davies J, Panoulas V, Gautama S, Papadimitriou D, Woods K, Elliott P, Hemingway H, Williams B, Asselbergs FW, Melikian N, Krasopoulos G, Sayeed R, Wendler O, Baig K, Chukwuemeka A, Angelini GD, Sterne JAC, Johnson T, Shah AM, Perera D, Patel RS, Kharbanda R, Channon KM, Mayet J, Kaura A.",,International journal of cardiology,2022,2022-04-27,N,Troponin; Myocardial infarction; Coronary Artery Bypass Grafting; Timing-to-surgery,,,"Implications of elevated troponin on time-to-surgery in non-ST elevation myocardial infarction(NIHR Health Informatics Collaborative:TROP-CABG study). Benedetto et al. BACKGROUND: The optimal timing of coronary artery bypass grafting (CABG) in patients with non-ST elevation myocardial infarction (NSTEMI) and the utility of pre-operative troponin levels in decision-making remains unclear. We investigated (a) the association between peak pre-operative troponin and survival post-CABG in a large cohort of NSTEMI patients and (b) the interaction between troponin and time-to-surgery. METHODS AND RESULTS: Our cohort consisted of 1746 patients (1684 NSTEMI; 62 unstable angina) (mean age 69 ± 11 years,21% female) with recorded troponins that had CABG at five United Kingdom centers between 2010 and 2017. Time-segmented Cox regression was used to investigate the interaction of peak troponin and time-to-surgery on early (within 30 days) and late (beyond 30 days) survival. Average interval from peak troponin to surgery was 9 ± 15 days, with 1466 (84.0%) patients having CABG during the same admission. Sixty patients died within 30-days and another 211 died after a mean follow-up of 4 ± 2 years (30-day survival 0.97 ± 0.004 and 5-year survival 0.83 ± 0.01). Peak troponin was a strong predictor of early survival (adjusted P = 0.002) with a significant interaction with time-to-surgery (P interaction = 0.007). For peak troponin levels <100 times the upper limit of normal, there was no improvement in early survival with longer time-to-surgery. However, in patients with higher troponins, early survival increased progressively with a longer time-to-surgery, till day 10. Peak troponin did not influence survival beyond 30 days (adjusted P = 0.64). CONCLUSIONS: Peak troponin in NSTEMI patients undergoing CABG was a significant predictor of early mortality, strongly influenced the time-to-surgery and may prove to be a clinically useful biomarker in the management of these patients.",,doi:https://doi.org/10.1016/j.ijcard.2022.04.067 @@ -1346,26 +1346,26 @@ PMC8855010,https://doi.org/,POS-894 PREDICTING PANDEMIC-RELATED EXCESS-DEATH USI 37286615,https://doi.org/10.1038/s41598-023-36214-0,Combining machine learning with Cox models to identify predictors for incident post-menopausal breast cancer in the UK Biobank.,"Liu X, Morelli D, Littlejohns TJ, Clifton DA, Clifton L.",,Scientific reports,2023,2023-06-07,Y,,,,"We aimed to identify potential novel predictors for breast cancer among post-menopausal women, with pre-specified interest in the role of polygenic risk scores (PRS) for risk prediction. We utilised an analysis pipeline where machine learning was used for feature selection, prior to risk prediction by classical statistical models. An ""extreme gradient boosting"" (XGBoost) machine with Shapley feature-importance measures were used for feature selection among [Formula: see text] 1.7 k features in 104,313 post-menopausal women from the UK Biobank. We constructed and compared the ""augmented"" Cox model (incorporating the two PRS, known and novel predictors) with a ""baseline"" Cox model (incorporating the two PRS and known predictors) for risk prediction. Both of the two PRS were significant in the augmented Cox model ([Formula: see text]). XGBoost identified 10 novel features, among which five showed significant associations with post-menopausal breast cancer: plasma urea (HR = 0.95, 95% CI 0.92-0.98, [Formula: see text]), plasma phosphate (HR = 0.68, 95% CI 0.53-0.88, [Formula: see text]), basal metabolic rate (HR = 1.17, 95% CI 1.11-1.24, [Formula: see text]), red blood cell count (HR = 1.21, 95% CI 1.08-1.35, [Formula: see text]), and creatinine in urine (HR = 1.05, 95% CI 1.01-1.09, [Formula: see text]). Risk discrimination was maintained in the augmented Cox model, yielding C-index 0.673 vs 0.667 (baseline Cox model) with the training data and 0.665 vs 0.664 with the test data. We identified blood/urine biomarkers as potential novel predictors for post-menopausal breast cancer. Our findings provide new insights to breast cancer risk. Future research should validate novel predictors, investigate using multiple PRS and more precise anthropometry measures for better breast cancer risk prediction.",,doi:https://doi.org/10.1038/s41598-023-36214-0; doi:https://doi.org/10.1038/s41598-023-36214-0; html:https://europepmc.org/articles/PMC10247810; pdf:https://europepmc.org/articles/PMC10247810?pdf=render 35104366,https://doi.org/10.1111/bjd.21042,Vaccine hesitancy and access to psoriasis care during the COVID-19 pandemic: findings from a global patient-reported cross-sectional survey.,"Bechman K, Cook ES, Dand N, Yiu ZZN, Tsakok T, Meynell F, Coker B, Vincent A, Bachelez H, Barbosa I, Brown MA, Capon F, Contreras CR, De La Cruz C, Meglio PD, Gisondi P, Jullien D, Kelly J, Lambert J, Lancelot C, Langan SM, Mason KJ, McAteer H, Moorhead L, Naldi L, Norton S, Puig L, Spuls PI, Torres T, Urmston D, Vesty A, Warren RB, Waweru H, Weinman J, Griffiths CEM, Barker JN, Smith CH, Galloway JB, Mahil SK, PsoProtect study group.",,The British journal of dermatology,2022,2022-05-03,Y,,,,,,pdf:https://biblio.ugent.be/publication/8757812/file/8757816.pdf; doi:https://doi.org/10.1111/bjd.21042; html:https://europepmc.org/articles/PMC9545500; pdf:https://europepmc.org/articles/PMC9545500?pdf=render 35156082,https://doi.org/10.3389/fdgth.2022.833912,Artificial Intelligence and Statistics: Just the Old Wine in New Wineskins?,"Faes L, Sim DA, van Smeden M, Held U, Bossuyt PM, Bachmann LM.",,Frontiers in digital health,2022,2022-01-26,Y,Methodology; Statistics; Reporting Guideline; Machine Learning (Ml); Artificial Intelligence (Ai),,,,,pdf:https://www.frontiersin.org/articles/10.3389/fdgth.2022.833912/pdf; doi:https://doi.org/10.3389/fdgth.2022.833912; html:https://europepmc.org/articles/PMC8825497; pdf:https://europepmc.org/articles/PMC8825497?pdf=render -35022215,https://doi.org/10.1136/bmj-2021-067519,Indirect effects of the covid-19 pandemic on childhood infection in England: population based observational study.,"Kadambari S, Goldacre R, Morris E, Goldacre MJ, Pollard AJ.",,BMJ (Clinical research ed.),2022,2022-01-12,Y,,,,"

Objective

To assess the impact of the covid-19 pandemic on hospital admission rates and mortality outcomes for childhood respiratory infections, severe invasive infections, and vaccine preventable disease in England.

Design

Population based observational study of 19 common childhood respiratory, severe invasive, and vaccine preventable infections, comparing hospital admission rates and mortality outcomes before and after the onset of the pandemic in England.

Setting

Hospital admission data from every NHS hospital in England from 1 March 2017 to 30 June 2021 with record linkage to national mortality data.

Population

Children aged 0-14 years admitted to an NHS hospital with a selected childhood infection from 1 March 2017 to 30 June 2021.

Main outcome measures

For each infection, numbers of hospital admissions every month from 1 March 2017 to 30 June 2021, percentage changes in the number of hospital admissions before and after 1 March 2020, and adjusted odds ratios to compare 60 day case fatality outcomes before and after 1 March 2020.

Results

After 1 March 2020, substantial and sustained reductions in hospital admissions were found for all but one of the 19 infective conditions studied. Among the respiratory infections, the greatest percentage reductions were for influenza (mean annual number admitted between 1 March 2017 and 29 February 2020 was 5379 and number of children admitted from 1 March 2020 to 28 February 2021 was 304, 94% reduction, 95% confidence interval 89% to 97%), and bronchiolitis (from 51 655 to 9423, 82% reduction, 95% confidence interval 79% to 84%). Among the severe invasive infections, the greatest reduction was for meningitis (50% reduction, 47% to 52%). For the vaccine preventable infections, reductions ranged from 53% (32% to 68%) for mumps to 90% (80% to 95%) for measles. Reductions were seen across all demographic subgroups and in children with underlying comorbidities. Corresponding decreases were also found for the absolute numbers of 60 day case fatalities, although the proportion of children admitted for pneumonia who died within 60 days increased (age-sex adjusted odds ratio 1.71, 95% confidence interval 1.43 to 2.05). More recent data indicate that some respiratory infections increased to higher levels than usual after May 2021.

Conclusions

During the covid-19 pandemic, a range of behavioural changes (adoption of non-pharmacological interventions) and societal strategies (school closures, lockdowns, and restricted travel) were used to reduce transmission of SARS-CoV-2, which also reduced admissions for common and severe childhood infections. Continued monitoring of these infections is required as social restrictions evolve.",,pdf:https://www.bmj.com/content/bmj/376/bmj-2021-067519.full.pdf; doi:https://doi.org/10.1136/bmj-2021-067519; html:https://europepmc.org/articles/PMC8753487; pdf:https://europepmc.org/articles/PMC8753487?pdf=render 34356044,https://doi.org/10.3390/genes12071029,A Causal Web between Chronotype and Metabolic Health Traits.,"Williams JA, Russ D, Bravo-Merodio L, Cardoso VR, Pendleton SC, Aziz F, Acharjee A, Gkoutos GV.",,Genes,2021,2021-07-01,Y,Circadian rhythm; Diabetes; Bipolar disorder; Alcohol Intake; Mendelian Randomization; Chronotype,,,"Observational and experimental evidence has linked chronotype to both psychological and cardiometabolic traits. Recent Mendelian randomization (MR) studies have investigated direct links between chronotype and several of these traits, often in isolation of outside potential mediating or moderating traits. We mined the EpiGraphDB MR database for calculated chronotype-trait associations (p-value < 5 × 10-8). We then re-analyzed those relevant to metabolic or mental health and investigated for statistical evidence of horizontal pleiotropy. Analyses passing multiple testing correction were then investigated for confounders, colliders, intermediates, and reverse intermediates using the EpiGraphDB database, creating multiple chronotype-trait interactions among each of the the traits studied. We revealed 10 significant chronotype-exposure associations (false discovery rate < 0.05) exposed to 111 potential previously known confounders, 52 intermediates, 18 reverse intermediates, and 31 colliders. Chronotype-lipid causal associations collided with treatment and diabetes effects; chronotype-bipolar associations were mediated by breast cancer; and chronotype-alcohol intake associations were impacted by confounders and intermediate variables including known zeitgebers and molecular traits. We have reported the influence of chronotype on several cardiometabolic and behavioural traits, and identified potential confounding variables not reported on in studies while discovering new associations to drugs and disease.",,pdf:https://www.mdpi.com/2073-4425/12/7/1029/pdf?version=1625724795; doi:https://doi.org/10.3390/genes12071029; html:https://europepmc.org/articles/PMC8303793; pdf:https://europepmc.org/articles/PMC8303793?pdf=render +35022215,https://doi.org/10.1136/bmj-2021-067519,Indirect effects of the covid-19 pandemic on childhood infection in England: population based observational study.,"Kadambari S, Goldacre R, Morris E, Goldacre MJ, Pollard AJ.",,BMJ (Clinical research ed.),2022,2022-01-12,Y,,,,"

Objective

To assess the impact of the covid-19 pandemic on hospital admission rates and mortality outcomes for childhood respiratory infections, severe invasive infections, and vaccine preventable disease in England.

Design

Population based observational study of 19 common childhood respiratory, severe invasive, and vaccine preventable infections, comparing hospital admission rates and mortality outcomes before and after the onset of the pandemic in England.

Setting

Hospital admission data from every NHS hospital in England from 1 March 2017 to 30 June 2021 with record linkage to national mortality data.

Population

Children aged 0-14 years admitted to an NHS hospital with a selected childhood infection from 1 March 2017 to 30 June 2021.

Main outcome measures

For each infection, numbers of hospital admissions every month from 1 March 2017 to 30 June 2021, percentage changes in the number of hospital admissions before and after 1 March 2020, and adjusted odds ratios to compare 60 day case fatality outcomes before and after 1 March 2020.

Results

After 1 March 2020, substantial and sustained reductions in hospital admissions were found for all but one of the 19 infective conditions studied. Among the respiratory infections, the greatest percentage reductions were for influenza (mean annual number admitted between 1 March 2017 and 29 February 2020 was 5379 and number of children admitted from 1 March 2020 to 28 February 2021 was 304, 94% reduction, 95% confidence interval 89% to 97%), and bronchiolitis (from 51 655 to 9423, 82% reduction, 95% confidence interval 79% to 84%). Among the severe invasive infections, the greatest reduction was for meningitis (50% reduction, 47% to 52%). For the vaccine preventable infections, reductions ranged from 53% (32% to 68%) for mumps to 90% (80% to 95%) for measles. Reductions were seen across all demographic subgroups and in children with underlying comorbidities. Corresponding decreases were also found for the absolute numbers of 60 day case fatalities, although the proportion of children admitted for pneumonia who died within 60 days increased (age-sex adjusted odds ratio 1.71, 95% confidence interval 1.43 to 2.05). More recent data indicate that some respiratory infections increased to higher levels than usual after May 2021.

Conclusions

During the covid-19 pandemic, a range of behavioural changes (adoption of non-pharmacological interventions) and societal strategies (school closures, lockdowns, and restricted travel) were used to reduce transmission of SARS-CoV-2, which also reduced admissions for common and severe childhood infections. Continued monitoring of these infections is required as social restrictions evolve.",,pdf:https://www.bmj.com/content/bmj/376/bmj-2021-067519.full.pdf; doi:https://doi.org/10.1136/bmj-2021-067519; html:https://europepmc.org/articles/PMC8753487; pdf:https://europepmc.org/articles/PMC8753487?pdf=render 31827124,https://doi.org/10.1038/s41598-019-54849-w,Improving the odds of drug development success through human genomics: modelling study.,"Hingorani AD, Kuan V, Finan C, Kruger FA, Gaulton A, Chopade S, Sofat R, MacAllister RJ, Overington JP, Hemingway H, Denaxas S, Prieto D, Casas JP.",,Scientific reports,2019,2019-12-11,Y,,,,"Lack of efficacy in the intended disease indication is the major cause of clinical phase drug development failure. Explanations could include the poor external validity of pre-clinical (cell, tissue, and animal) models of human disease and the high false discovery rate (FDR) in preclinical science. FDR is related to the proportion of true relationships available for discovery (γ), and the type 1 (false-positive) and type 2 (false negative) error rates of the experiments designed to uncover them. We estimated the FDR in preclinical science, its effect on drug development success rates, and improvements expected from use of human genomics rather than preclinical studies as the primary source of evidence for drug target identification. Calculations were based on a sample space defined by all human diseases - the 'disease-ome' - represented as columns; and all protein coding genes - 'the protein-coding genome'- represented as rows, producing a matrix of unique gene- (or protein-) disease pairings. We parameterised the space based on 10,000 diseases, 20,000 protein-coding genes, 100 causal genes per disease and 4000 genes encoding druggable targets, examining the effect of varying the parameters and a range of underlying assumptions, on the inferences drawn. We estimated γ, defined mathematical relationships between preclinical FDR and drug development success rates, and estimated improvements in success rates based on human genomics (rather than orthodox preclinical studies). Around one in every 200 protein-disease pairings was estimated to be causal (γ = 0.005) giving an FDR in preclinical research of 92.6%, which likely makes a major contribution to the reported drug development failure rate of 96%. Observed success rate was only slightly greater than expected for a random pick from the sample space. Values for γ back-calculated from reported preclinical and clinical drug development success rates were also close to the a priori estimates. Substituting genome wide (or druggable genome wide) association studies for preclinical studies as the major information source for drug target identification was estimated to reverse the probability of late stage failure because of the more stringent type 1 error rate employed and the ability to interrogate every potential druggable target in the same experiment. Genetic studies conducted at much larger scale, with greater resolution of disease end-points, e.g. by connecting genomics and electronic health record data within healthcare systems has the potential to produce radical improvement in drug development success rate.","This study investigates the unreliability of target identification leading to low development sucess rates, inefficiency and escalating costs to healthcare users. The more targeted use of genomics couldimprove improved efficency.",pdf:https://www.nature.com/articles/s41598-019-54849-w.pdf; doi:https://doi.org/10.1038/s41598-019-54849-w; html:https://europepmc.org/articles/PMC6906499; pdf:https://europepmc.org/articles/PMC6906499?pdf=render 32717063,https://doi.org/10.1093/cvr/cvaa233,Gene expression profiling of hypertrophic cardiomyocytes identifies new players in pathological remodelling.,"Vigil-Garcia M, Demkes CJ, Eding JEC, Versteeg D, de Ruiter H, Perini I, Kooijman L, Gladka MM, Asselbergs FW, Vink A, Harakalova M, Bossu A, van Veen TAB, Boogerd CJ, van Rooij E.",,Cardiovascular research,2021,2021-05-01,Y,Cardiomyocyte; hypertrophy; Heart Failure; Rna Sequencing; Pfkp; Pathological Remodelling,,,"

Aims

Pathological cardiac remodelling is characterized by cardiomyocyte (CM) hypertrophy and fibroblast activation, which can ultimately lead to maladaptive hypertrophy and heart failure (HF). Genome-wide expression analysis on heart tissue has been instrumental for the identification of molecular mechanisms at play. However, these data were based on signals derived from all cardiac cell types. Here, we aimed for a more detailed view on molecular changes driving maladaptive CM hypertrophy to aid in the development of therapies to reverse pathological remodelling.

Methods and results

Utilizing CM-specific reporter mice exposed to pressure overload by transverse aortic banding and CM isolation by flow cytometry, we obtained gene expression profiles of hypertrophic CMs in the more immediate phase after stress, and CMs showing pathological hypertrophy. We identified subsets of genes differentially regulated and specific for either stage. Among the genes specifically up-regulated in the CMs during the maladaptive phase we found known stress markers, such as Nppb and Myh7, but additionally identified a set of genes with unknown roles in pathological hypertrophy, including the platelet isoform of phosphofructokinase (PFKP). Norepinephrine-angiotensin II treatment of cultured human CMs induced the secretion of N-terminal-pro-B-type natriuretic peptide (NT-pro-BNP) and recapitulated the up-regulation of these genes, indicating conservation of the up-regulation in failing CMs. Moreover, several genes induced during pathological hypertrophy were also found to be increased in human HF, with their expression positively correlating to the known stress markers NPPB and MYH7. Mechanistically, suppression of Pfkp in primary CMs attenuated stress-induced gene expression and hypertrophy, indicating that Pfkp is an important novel player in pathological remodelling of CMs.

Conclusion

Using CM-specific transcriptomic analysis, we identified novel genes induced during pathological hypertrophy that are relevant for human HF, and we show that PFKP is a conserved failure-induced gene that can modulate the CM stress response.",,doi:https://doi.org/10.1093/cvr/cvaa233; doi:https://doi.org/10.1093/cvr/cvaa233; html:https://europepmc.org/articles/PMC8152696; pdf:https://europepmc.org/articles/PMC8152696?pdf=render -33652931,https://doi.org/10.3390/jcm10050921,Diagnosis and Risk Prediction of Dilated Cardiomyopathy in the Era of Big Data and Genomics.,"Sammani A, Baas AF, Asselbergs FW, Te Riele ASJM.",,Journal of clinical medicine,2021,2021-02-26,Y,Artificial intelligence; Diagnosis; Prognosis; Genetic; Dilated cardiomyopathy; Big Data; Deep Learning,,,"Dilated cardiomyopathy (DCM) is a leading cause of heart failure and life-threatening ventricular arrhythmias (LTVA). Work-up and risk stratification of DCM is clinically challenging, as there is great heterogeneity in phenotype and genotype. Throughout the last decade, improved genetic testing of patients has identified genotype-phenotype associations and enhanced evaluation of at-risk relatives leading to better patient prognosis. The field is now ripe to explore opportunities to improve personalised risk assessments. Multivariable risk models presented as ""risk calculators"" can incorporate a multitude of clinical variables and predict outcome (such as heart failure hospitalisations or LTVA). In addition, genetic risk scores derived from genome/exome-wide association studies can estimate an individual's lifetime genetic risk of developing DCM. The use of clinically granular investigations, such as late gadolinium enhancement on cardiac magnetic resonance imaging, is warranted in order to increase predictive performance. To this end, constructing big data infrastructures improves accessibility of data by using electronic health records, existing research databases, and disease registries. By applying methods such as machine and deep learning, we can model complex interactions, identify new phenotype clusters, and perform prognostic modelling. This review aims to provide an overview of the evolution of DCM definitions as well as its clinical work-up and considerations in the era of genomics. In addition, we present exciting examples in the field of big data infrastructures, personalised prognostic assessment, and artificial intelligence.",,pdf:https://www.mdpi.com/2077-0383/10/5/921/pdf?version=1615467325; doi:https://doi.org/10.3390/jcm10050921; html:https://europepmc.org/articles/PMC7956169; pdf:https://europepmc.org/articles/PMC7956169?pdf=render 31349307,https://doi.org/10.3233/shti190058,Phenotyping UK Electronic Health Records from 15 Million Individuals for Precision Medicine: The CALIBER Resource.,"Denaxas S, Gonzalez-Izquierdo A, Fitzpatrick N, Direk K, Hemingway H.",,Studies in health technology and informatics,2019,2019-07-01,N,Prognosis; Phenotyping; Data Linkage; Electronic Health Records; Biomedical Informatics,,,"Electronic health records (EHR) are increasingly being used for observational research at scale. In the UK, we have established the CALIBER research resource which utilizes national primary and hospital EHR data sources and enables researchers to create and validate longitudinal disease phenotypes at scale. In this work, we will describe the core components of the resource and provide results from three exemplar research studies on high-resolution epidemiology, disease risk prediction and subtype discovery which demonstrate both the opportunities and challenges of using EHR for research.",,doi:https://doi.org/10.3233/SHTI190058 +33652931,https://doi.org/10.3390/jcm10050921,Diagnosis and Risk Prediction of Dilated Cardiomyopathy in the Era of Big Data and Genomics.,"Sammani A, Baas AF, Asselbergs FW, Te Riele ASJM.",,Journal of clinical medicine,2021,2021-02-26,Y,Artificial intelligence; Diagnosis; Prognosis; Genetic; Dilated cardiomyopathy; Big Data; Deep Learning,,,"Dilated cardiomyopathy (DCM) is a leading cause of heart failure and life-threatening ventricular arrhythmias (LTVA). Work-up and risk stratification of DCM is clinically challenging, as there is great heterogeneity in phenotype and genotype. Throughout the last decade, improved genetic testing of patients has identified genotype-phenotype associations and enhanced evaluation of at-risk relatives leading to better patient prognosis. The field is now ripe to explore opportunities to improve personalised risk assessments. Multivariable risk models presented as ""risk calculators"" can incorporate a multitude of clinical variables and predict outcome (such as heart failure hospitalisations or LTVA). In addition, genetic risk scores derived from genome/exome-wide association studies can estimate an individual's lifetime genetic risk of developing DCM. The use of clinically granular investigations, such as late gadolinium enhancement on cardiac magnetic resonance imaging, is warranted in order to increase predictive performance. To this end, constructing big data infrastructures improves accessibility of data by using electronic health records, existing research databases, and disease registries. By applying methods such as machine and deep learning, we can model complex interactions, identify new phenotype clusters, and perform prognostic modelling. This review aims to provide an overview of the evolution of DCM definitions as well as its clinical work-up and considerations in the era of genomics. In addition, we present exciting examples in the field of big data infrastructures, personalised prognostic assessment, and artificial intelligence.",,pdf:https://www.mdpi.com/2077-0383/10/5/921/pdf?version=1615467325; doi:https://doi.org/10.3390/jcm10050921; html:https://europepmc.org/articles/PMC7956169; pdf:https://europepmc.org/articles/PMC7956169?pdf=render 36810251,https://doi.org/10.1172/jci.insight.156643,Development of antidrug antibodies against adalimumab maps to variation within the HLA-DR peptide-binding groove.,"Tsakok T, Saklatvala J, Rispens T, Loeff FC, de Vries A, Allen MH, Barbosa IA, Baudry D, Dasandi T, Duckworth M, Meynell F, Russell A, Chapman A, McBride S, McKenna K, Perera G, Ramsay H, Ramesh R, Sands K, Shipman A, Biomarkers of Systemic Treatment Outcomes in Psoriasis (BSTOP) Study Group, Burden AD, Griffiths CE, Reynolds NJ, Warren RB, Mahil S, Barker J, Dand N, Smith C, Simpson MA.",,JCI insight,2023,2023-02-22,Y,Genetics; Drug therapy; Molecular genetics; Therapeutics; adaptive immunity,,,"Targeted biologic therapies can elicit an undesirable host immune response characterized by the development of antidrug antibodies (ADA), an important cause of treatment failure. The most widely used biologic across immune-mediated diseases is adalimumab, a tumor necrosis factor inhibitor. This study aimed to identify genetic variants that contribute to the development of ADA against adalimumab, thereby influencing treatment failure. In patients with psoriasis on their first course of adalimumab, in whom serum ADA had been evaluated 6-36 months after starting treatment, we observed a genome-wide association with ADA against adalimumab within the major histocompatibility complex (MHC). The association signal mapped to the presence of tryptophan at position 9 and lysine at position 71 of the HLA-DR peptide-binding groove, with both residues conferring protection against ADA. Underscoring their clinical relevance, these residues were also protective against treatment failure. Our findings highlight antigenic peptide presentation via MHC class II as a critical mechanism in the development of ADA against biologic therapies and downstream treatment response.",,pdf:http://insight.jci.org/articles/view/156643/files/pdf; doi:https://doi.org/10.1172/jci.insight.156643; html:https://europepmc.org/articles/PMC9977494; pdf:https://europepmc.org/articles/PMC9977494?pdf=render -36721180,https://doi.org/10.1186/s12961-022-00956-6,Tracking health system performance in times of crisis using routine health data: lessons learned from a multicountry consortium.,"Turcotte-Tremblay AM, Leerapan B, Akweongo P, Amponsah F, Aryal A, Asai D, Awoonor-Williams JK, Ayele W, Bauhoff S, Doubova SV, Gadeka DD, Dulal M, Gage A, Gordon-Strachan G, Haile-Mariam D, Joseph JP, Kaewkamjornchai P, Kapoor NR, Gelaw SK, Kim MK, Kruk ME, Kubota S, Margozzini P, Mehata S, Mthethwa L, Nega A, Oh J, Park SK, Passi-Solar A, Perez Cuevas RE, Reddy T, Rittiphairoj T, Sapag JC, Thermidor R, Tlou B, Arsenault C.",,Health research policy and systems,2023,2023-01-31,Y,Quality Of Care; Health Systems; Routine Health Information Systems; Covid-19,,,"COVID-19 has prompted the use of readily available administrative data to track health system performance in times of crisis and to monitor disruptions in essential healthcare services. In this commentary we describe our experience working with these data and lessons learned across countries. Since April 2020, the Quality Evidence for Health System Transformation (QuEST) network has used administrative data and routine health information systems (RHIS) to assess health system performance during COVID-19 in Chile, Ethiopia, Ghana, Haiti, Lao People's Democratic Republic, Mexico, Nepal, South Africa, Republic of Korea and Thailand. We compiled a large set of indicators related to common health conditions for the purpose of multicountry comparisons. The study compiled 73 indicators. A total of 43% of the indicators compiled pertained to reproductive, maternal, newborn and child health (RMNCH). Only 12% of the indicators were related to hypertension, diabetes or cancer care. We also found few indicators related to mental health services and outcomes within these data systems. Moreover, 72% of the indicators compiled were related to volume of services delivered, 18% to health outcomes and only 10% to the quality of processes of care. While several datasets were complete or near-complete censuses of all health facilities in the country, others excluded some facility types or population groups. In some countries, RHIS did not capture services delivered through non-visit or nonconventional care during COVID-19, such as telemedicine. We propose the following recommendations to improve the analysis of administrative and RHIS data to track health system performance in times of crisis: ensure the scope of health conditions covered is aligned with the burden of disease, increase the number of indicators related to quality of care and health outcomes; incorporate data on nonconventional care such as telehealth; continue improving data quality and expand reporting from private sector facilities; move towards collecting patient-level data through electronic health records to facilitate quality-of-care assessment and equity analyses; implement more resilient and standardized health information technologies; reduce delays and loosen restrictions for researchers to access the data; complement routine data with patient-reported data; and employ mixed methods to better understand the underlying causes of service disruptions.",,pdf:https://health-policy-systems.biomedcentral.com/counter/pdf/10.1186/s12961-022-00956-6; doi:https://doi.org/10.1186/s12961-022-00956-6; html:https://europepmc.org/articles/PMC9888332; pdf:https://europepmc.org/articles/PMC9888332?pdf=render 31446406,https://doi.org/10.1136/bmjopen-2018-027577,Global health competencies in UK postgraduate medical training: a scoping review and curricular content analysis.,"Al-Shakarchi N, Obolensky L, Walpole S, Hemingway H, Banerjee A.",,BMJ open,2019,2019-08-24,Y,Global Health; Competencies; Postgraduate Medical Training,,,"

Objective

To assess global health (GH) training in all postgraduate medical education in the UK.

Design

Mixed methodology: scoping review and curricular content analysis using two GH competency frameworks.

Setting and participants

A scoping review (until December 2017) was used to develop a framework of GH competencies for doctors. National postgraduate medical training curricula were analysed against this and a prior framework for GH competencies. The number of core competencies addressed and/or appearing in each programme was recorded.

Outcomes

The scoping review identified eight relevant publications. A 16-competency framework was developed and, with a prior 5-competency framework, used to analyse each of 71 postgraduate medical curricula. Curricula were examined by a team of researchers and relevant learning outcomes were coded as one of the 5 or 16 core competencies. The number of core competencies in each programme was recorded.

Results

Using the 5-competency and 16-competency frameworks, 23 and 20, respectively, out of 71 programmes contained no global health competencies, most notably the Foundation Programme (equivalent to internship), a compulsory programme for UK medical graduates. Of a possible 16 competencies, the mean number across all 71 programmes was 1.73 (95% CI 1.42 to 2.04) and the highest number were in paediatrics and infectious diseases, each with five competencies. Of the 16 core competencies, global burden of disease and socioeconomic determinants of health were the two most cited with 47 and 35 citations, respectively. 8/16 competencies were not cited in any curriculum.

Conclusions

Equity of care and the challenges of practising in an increasingly globalised world necessitate GH competencies for all doctors. Across the whole of postgraduate training, the majority of UK doctors are receiving minimal or no training in GH. Our GH competency framework can be used to map and plan integration across postgraduate programmes.",,pdf:https://bmjopen.bmj.com/content/bmjopen/9/8/e027577.full.pdf; doi:https://doi.org/10.1136/bmjopen-2018-027577; html:https://europepmc.org/articles/PMC6720244; pdf:https://europepmc.org/articles/PMC6720244?pdf=render -35396183,https://doi.org/10.1016/s2589-7500(22)00003-6,The medical algorithmic audit.,"Liu X, Glocker B, McCradden MM, Ghassemi M, Denniston AK, Oakden-Rayner L.",,The Lancet. Digital health,2022,2022-04-05,N,,,,"Artificial intelligence systems for health care, like any other medical device, have the potential to fail. However, specific qualities of artificial intelligence systems, such as the tendency to learn spurious correlates in training data, poor generalisability to new deployment settings, and a paucity of reliable explainability mechanisms, mean they can yield unpredictable errors that might be entirely missed without proactive investigation. We propose a medical algorithmic audit framework that guides the auditor through a process of considering potential algorithmic errors in the context of a clinical task, mapping the components that might contribute to the occurrence of errors, and anticipating their potential consequences. We suggest several approaches for testing algorithmic errors, including exploratory error analysis, subgroup testing, and adversarial testing, and provide examples from our own work and previous studies. The medical algorithmic audit is a tool that can be used to better understand the weaknesses of an artificial intelligence system and put in place mechanisms to mitigate their impact. We propose that safety monitoring and medical algorithmic auditing should be a joint responsibility between users and developers, and encourage the use of feedback mechanisms between these groups to promote learning and maintain safe deployment of artificial intelligence systems.",,pdf:http://www.thelancet.com/article/S2589750022000036/pdf; doi:https://doi.org/10.1016/S2589-7500(22)00003-6 +36721180,https://doi.org/10.1186/s12961-022-00956-6,Tracking health system performance in times of crisis using routine health data: lessons learned from a multicountry consortium.,"Turcotte-Tremblay AM, Leerapan B, Akweongo P, Amponsah F, Aryal A, Asai D, Awoonor-Williams JK, Ayele W, Bauhoff S, Doubova SV, Gadeka DD, Dulal M, Gage A, Gordon-Strachan G, Haile-Mariam D, Joseph JP, Kaewkamjornchai P, Kapoor NR, Gelaw SK, Kim MK, Kruk ME, Kubota S, Margozzini P, Mehata S, Mthethwa L, Nega A, Oh J, Park SK, Passi-Solar A, Perez Cuevas RE, Reddy T, Rittiphairoj T, Sapag JC, Thermidor R, Tlou B, Arsenault C.",,Health research policy and systems,2023,2023-01-31,Y,Quality Of Care; Health Systems; Routine Health Information Systems; Covid-19,,,"COVID-19 has prompted the use of readily available administrative data to track health system performance in times of crisis and to monitor disruptions in essential healthcare services. In this commentary we describe our experience working with these data and lessons learned across countries. Since April 2020, the Quality Evidence for Health System Transformation (QuEST) network has used administrative data and routine health information systems (RHIS) to assess health system performance during COVID-19 in Chile, Ethiopia, Ghana, Haiti, Lao People's Democratic Republic, Mexico, Nepal, South Africa, Republic of Korea and Thailand. We compiled a large set of indicators related to common health conditions for the purpose of multicountry comparisons. The study compiled 73 indicators. A total of 43% of the indicators compiled pertained to reproductive, maternal, newborn and child health (RMNCH). Only 12% of the indicators were related to hypertension, diabetes or cancer care. We also found few indicators related to mental health services and outcomes within these data systems. Moreover, 72% of the indicators compiled were related to volume of services delivered, 18% to health outcomes and only 10% to the quality of processes of care. While several datasets were complete or near-complete censuses of all health facilities in the country, others excluded some facility types or population groups. In some countries, RHIS did not capture services delivered through non-visit or nonconventional care during COVID-19, such as telemedicine. We propose the following recommendations to improve the analysis of administrative and RHIS data to track health system performance in times of crisis: ensure the scope of health conditions covered is aligned with the burden of disease, increase the number of indicators related to quality of care and health outcomes; incorporate data on nonconventional care such as telehealth; continue improving data quality and expand reporting from private sector facilities; move towards collecting patient-level data through electronic health records to facilitate quality-of-care assessment and equity analyses; implement more resilient and standardized health information technologies; reduce delays and loosen restrictions for researchers to access the data; complement routine data with patient-reported data; and employ mixed methods to better understand the underlying causes of service disruptions.",,pdf:https://health-policy-systems.biomedcentral.com/counter/pdf/10.1186/s12961-022-00956-6; doi:https://doi.org/10.1186/s12961-022-00956-6; html:https://europepmc.org/articles/PMC9888332; pdf:https://europepmc.org/articles/PMC9888332?pdf=render 34751629,https://doi.org/10.1080/09638288.2021.1998671,Long-term health and mobility of older adults following traumatic injury: a qualitative longitudinal study.,"Reeder S, Ameratunga S, Ponsford J, Fitzgerald M, Lyons R, Nunn A, Ekegren C, Cameron P, Gabbe B.",,Disability and rehabilitation,2022,2021-11-09,N,Ageing; Recovery; Qualitative; Disability; Older Adult; Traumatic Injury,,,"

Purpose

The aim of this study was to explore older adults' experiences of and approaches to managing their long-term health and mobility after traumatic injury.

Methods

A longitudinal qualitative study was undertaken with older adults following traumatic injury in Victoria, Australia. Fifteen participants (≥65 years) were interviewed at three years post-injury (n = 15), and re-interviewed at four (n = 14) and five years (n = 12) post-injury. Using a framework approach, a longitudinal thematic analysis was performed.

Results

Older age at the time of injury was identified by participants as a key factor influencing their recovery. Many participants reported actively attempting to regain their strength and fitness in the first five years following injury. However, their age, injury impacts, other health conditions, and weight gain made it difficult to achieve recovery goals. Many older adults reported a decline in their physical function over time. While these experiences and persistent disability constrained or changed the quality of social relationships, community participation, and independence, several participants described adapting to their functional limitations, and managing their secondary conditions over time.

Conclusion

In our cohort, the intertwined combination of ageing, injury, and comorbid conditions negatively affected health and mobility, reinforcing the need for preventative strategies.Implications for rehabilitationOlder adults recovering from traumatic injury may benefit from specialised care pathways that offer long-term and tailored therapies, with programs and services specific to their needs and goals.An integrated service approach by injury insurers, health care, primary care, disability, and aged care could more clearly identify and effectively address the individual needs and goals of older adults with complex conditions.Health and social services that work with people with injuries to develop personalised coping strategies can reduce anxiety related to uncertainty about the future, promote well-being, and support participation in valued activities.",,doi:https://doi.org/10.1080/09638288.2021.1998671 +35396183,https://doi.org/10.1016/s2589-7500(22)00003-6,The medical algorithmic audit.,"Liu X, Glocker B, McCradden MM, Ghassemi M, Denniston AK, Oakden-Rayner L.",,The Lancet. Digital health,2022,2022-04-05,N,,,,"Artificial intelligence systems for health care, like any other medical device, have the potential to fail. However, specific qualities of artificial intelligence systems, such as the tendency to learn spurious correlates in training data, poor generalisability to new deployment settings, and a paucity of reliable explainability mechanisms, mean they can yield unpredictable errors that might be entirely missed without proactive investigation. We propose a medical algorithmic audit framework that guides the auditor through a process of considering potential algorithmic errors in the context of a clinical task, mapping the components that might contribute to the occurrence of errors, and anticipating their potential consequences. We suggest several approaches for testing algorithmic errors, including exploratory error analysis, subgroup testing, and adversarial testing, and provide examples from our own work and previous studies. The medical algorithmic audit is a tool that can be used to better understand the weaknesses of an artificial intelligence system and put in place mechanisms to mitigate their impact. We propose that safety monitoring and medical algorithmic auditing should be a joint responsibility between users and developers, and encourage the use of feedback mechanisms between these groups to promote learning and maintain safe deployment of artificial intelligence systems.",,pdf:http://www.thelancet.com/article/S2589750022000036/pdf; doi:https://doi.org/10.1016/S2589-7500(22)00003-6 34139439,https://doi.org/10.1016/j.compbiomed.2021.104542,Development and application of the ocular immune-mediated inflammatory diseases ontology enhanced with synonyms from online patient support forum conversation.,"Pendleton SC, Slater K, Karwath A, Gilbert RM, Davis N, Pesudovs K, Liu X, Denniston AK, Gkoutos GV, Braithwaite T.",,Computers in biology and medicine,2021,2021-06-08,Y,Inflammation; Uveitis; Ontology; Patient Voice; Sentiment,,,"

Background

Unstructured text created by patients represents a rich, but relatively inaccessible resource for advancing patient-centred care. This study aimed to develop an ontology for ocular immune-mediated inflammatory diseases (OcIMIDo), as a tool to facilitate data extraction and analysis, illustrating its application to online patient support forum data.

Methods

We developed OcIMIDo using clinical guidelines, domain expertise, and cross-references to classes from other biomedical ontologies. We developed an approach to add patient-preferred synonyms text-mined from oliviasvision.org online forum, using statistical ranking. We validated the approach with split-sampling and comparison to manual extraction. Using OcIMIDo, we then explored the frequency of OcIMIDo classes and synonyms, and their potential association with natural language sentiment expressed in each online forum post.

Findings

OcIMIDo (version 1.2) includes 661 classes, describing anatomy, clinical phenotype, disease activity status, complications, investigations, interventions and functional impacts. It contains 1661 relationships and axioms, 2851 annotations, including 1131 database cross-references, and 187 patient-preferred synonyms. To illustrate OcIMIDo's potential applications, we explored 9031 forum posts, revealing frequent mention of different clinical phenotypes, treatments, and complications. Language sentiment analysis of each post was generally positive (median 0.12, IQR 0.01-0.24). In multivariable logistic regression, the odds of a post expressing negative sentiment were significantly associated with first posts as compared to replies (OR 3.3, 95% CI 2.8 to 3.9, p < 0.001).

Conclusion

We report the development and validation of a new ontology for inflammatory eye diseases, which includes patient-preferred synonyms, and can be used to explore unstructured patient or physician-reported text data, with many potential applications.",,doi:https://doi.org/10.1016/j.compbiomed.2021.104542; doi:https://doi.org/10.1016/j.compbiomed.2021.104542; html:https://europepmc.org/articles/PMC8404035 37438684,https://doi.org/10.1186/s12874-023-01935-3,Estimating medication adherence from Electronic Health Records: comparing methods for mining and processing asthma treatment prescriptions.,"Tibble H, Sheikh A, Tsanas A.",,BMC medical research methodology,2023,2023-07-12,Y,Adherence; Asthma; Compliance; corticosteroid; Electronic Health Records,,,"

Background

Medication adherence is usually defined as the extent of the agreement between the medication regimen agreed to by patients with their healthcare provider and the real-world implementation. Proactive identification of those with poor adherence may be useful to identify those with poor disease control and offers the opportunity for ameliorative action. Adherence can be estimated from Electronic Health Records (EHRs) by comparing medication dispensing records to the prescribed regimen. Several methods have been developed in the literature to infer adherence from EHRs, however there is no clear consensus on what should be considered the gold standard in each use case. Our objectives were to critically evaluate different measures of medication adherence in a large longitudinal Scottish EHR dataset. We used asthma, a chronic condition with high prevalence and high rates of non-adherence, as a case study.

Methods

Over 1.6 million asthma controllers were prescribed for our cohort of 91,334 individuals, between January 2009 and March 2017. Eight adherence measures were calculated, and different approaches to estimating the amount of medication supply available at any time were compared.

Results

Estimates from different measures of adherence varied substantially. Three of the main drivers of the differences between adherence measures were the expected duration (if taken as in accordance with the dose directions), whether there was overlapping supply between prescriptions, and whether treatment had been discontinued. However, there are also wider, study-related, factors which are crucial to consider when comparing the adherence measures.

Conclusions

We evaluated the limitations of various medication adherence measures, and highlight key considerations about the underlying data, condition, and population to guide researchers choose appropriate adherence measures. This guidance will enable researchers to make more informed decisions about the methodology they employ, ensuring that adherence is captured in the most meaningful way for their particular application needs.",,pdf:https://bmcmedresmethodol.biomedcentral.com/counter/pdf/10.1186/s12874-023-01935-3; doi:https://doi.org/10.1186/s12874-023-01935-3; html:https://europepmc.org/articles/PMC10337150; pdf:https://europepmc.org/articles/PMC10337150?pdf=render 37634573,https://doi.org/10.1016/j.cardfail.2023.08.008,Does Heterogeneity Exist in Treatment Associations With Renin-Angiotensin-System Inhibitors or Beta-blockers According to Phenotype Clusters in Heart Failure with Preserved Ejection Fraction?,"Uijl A, Koudstaal S, Stolfo D, Dahlström U, Vaartjes I, Grobbee RE, Asselbergs FW, Lund LH, Savarese G.",,Journal of cardiac failure,2024,2023-08-25,N,Personalized Medicine; Beta-blockers; Hfpef; Renin–angiotensin System Inhibitors; Phenotype Clusters,,,"

Background

We explored the association between use of renin-angiotensin system inhibitors and beta-blockers, with mortality/morbidity in 5 previously identified clusters of patients with heart failure with preserved ejection fraction (HFpEF).

Methods and results

We analyzed 20,980 patients with HFpEF from the Swedish HF registry, phenotyped into young-low comorbidity burden (12%), atrial fibrillation-hypertensive (32%), older-atrial fibrillation (24%), obese-diabetic (15%), and a cardiorenal cluster (17%). In Cox proportional hazard models with inverse probability weighting, there was no heterogeneity in the association between renin-angiotensin system inhibitor use and cluster membership for any of the outcomes: cardiovascular (CV) mortality, all-cause mortality, HF hospitalisation, CV hospitalisation, or non-CV hospitalisation. In contrast, we found a statistical interaction between beta-blocker use and cluster membership for all-cause mortality (P = .03) and non-CV hospitalisation (P = .001). In the young-low comorbidity burden and atrial fibrillation-hypertensive cluster, beta-blocker use was associated with statistically significant lower all-cause mortality and non-CV hospitalisation and in the obese-diabetic cluster beta-blocker use was only associated with a statistically significant lower non-CV hospitalisation. The interaction between beta-blocker use and cluster membership for all-cause mortality could potentially be driven by patients with improved EF. However, patient numbers were diminished when excluding those with improved EF and the direction of the associations remained similar.

Conclusions

In patients with HFpEF, the association with all-cause mortality and non-CV hospitalisation was heterogeneous across clusters for beta-blockers. It remains to be elucidated how heterogeneity in HFpEF could influence personalized medicine and future clinical trial design.",,pdf:http://www.onlinejcf.com/article/S1071916423003044/pdf; doi:https://doi.org/10.1016/j.cardfail.2023.08.008 37805492,https://doi.org/10.1186/s12864-023-09663-0,Mapping the epigenomic landscape of human monocytes following innate immune activation reveals context-specific mechanisms driving endotoxin tolerance.,"Amarasinghe HE, Zhang P, Whalley JP, Allcock A, Migliorini G, Brown AC, Scozzafava G, Knight JC.",,BMC genomics,2023,2023-10-07,Y,Chromatin Accessibility; Expression Quantitative Trait Loci; Endotoxin Tolerance; Human Monocytes; Enhancer Rna; Context-specificity,,,"

Background

Monocytes are key mediators of innate immunity to infection, undergoing profound and dynamic changes in epigenetic state and immune function which are broadly protective but may be dysregulated in disease. Here, we aimed to advance understanding of epigenetic regulation following innate immune activation, acutely and in endotoxin tolerant states.

Methods

We exposed human primary monocytes from healthy donors (n = 6) to interferon-γ or differing combinations of endotoxin (lipopolysaccharide), including acute response (2 h) and two models of endotoxin tolerance: repeated stimulations (6 + 6 h) and prolonged exposure to endotoxin (24 h). Another subset of monocytes was left untreated (naïve). We identified context-specific regulatory elements based on epigenetic signatures for chromatin accessibility (ATAC-seq) and regulatory non-coding RNAs from total RNA sequencing.

Results

We present an atlas of differential gene expression for endotoxin and interferon response, identifying widespread context specific changes. Across assayed states, only 24-29% of genes showing differential exon usage are also differential at the gene level. Overall, 19.9% (6,884 of 34,616) of repeatedly observed ATAC peaks were differential in at least one condition, the majority upregulated on stimulation and located in distal regions (64.1% vs 45.9% of non-differential peaks) within which sequences were less conserved than non-differential peaks. We identified enhancer-derived RNA signatures specific to different monocyte states that correlated with chromatin accessibility changes. The endotoxin tolerance models showed distinct chromatin accessibility and transcriptomic signatures, with integrated analysis identifying genes and pathways involved in the inflammatory response, detoxification, metabolism and wound healing. We leveraged eQTL mapping for the same monocyte activation states to link potential enhancers with specific genes, identifying 1,946 unique differential ATAC peaks with 1,340 expression associated genes. We further use this to inform understanding of reported GWAS, for example involving FCHO1 and coronary artery disease.

Conclusion

This study reports context-specific regulatory elements based on transcriptomic profiling and epigenetic signatures for enhancer-derived RNAs and chromatin accessibility in immune tolerant monocyte states, and demonstrates the informativeness of linking such elements and eQTL to inform future mechanistic studies aimed at defining therapeutic targets of immunosuppression and diseases.",,doi:https://doi.org/10.1186/s12864-023-09663-0; html:https://europepmc.org/articles/PMC10559536; pdf:https://europepmc.org/articles/PMC10559536?pdf=render -38383544,https://doi.org/10.1038/s41467-024-45761-7,The plasmidome associated with Gram-negative bloodstream infections: A large-scale observational study using complete plasmid assemblies.,"Lipworth S, Matlock W, Shaw L, Vihta KD, Rodger G, Chau K, Barker L, George S, Kavanagh J, Davies T, Vaughan A, Andersson M, Jeffery K, Oakley S, Morgan M, Hopkins S, Peto T, Crook D, Walker AS, Stoesser N.",,Nature communications,2024,2024-02-22,Y,,,,"Plasmids carry genes conferring antimicrobial resistance and other clinically important traits, and contribute to the rapid dissemination of such genes. Previous studies using complete plasmid assemblies, which are essential for reliable inference, have been small and/or limited to plasmids carrying antimicrobial resistance genes (ARGs). In this study, we sequenced 1,880 complete plasmids from 738 isolates from bloodstream infections in Oxfordshire, UK. The bacteria had been originally isolated in 2009 (194 isolates) and 2018 (368 isolates), plus a stratified selection from intervening years (176 isolates). We demonstrate that plasmids are largely, but not entirely, constrained to a single host species, although there is substantial overlap between species of plasmid gene-repertoire. Most ARGs are carried by a relatively small number of plasmid groups with biological features that are predictable. Plasmids carrying ARGs (including those encoding carbapenemases) share a putative 'backbone' of core genes with those carrying no such genes. These findings suggest that future surveillance should, in addition to tracking plasmids currently associated with clinically important genes, focus on identifying and monitoring the dissemination of high-risk plasmid groups with the potential to rapidly acquire and disseminate these genes.",,doi:https://doi.org/10.1038/s41467-024-45761-7; html:https://europepmc.org/articles/PMC10881496; pdf:https://europepmc.org/articles/PMC10881496?pdf=render 34598995,https://doi.org/10.1136/bmjopen-2021-055219,"wEight chanGes, caRdio-mEtabolic risks and morTality in patients with hyperthyroidism (EGRET): a protocol for a CPRD-HES linked cohort study.","Torlinska B, Hazlehurst JM, Nirantharakumar K, Thomas GN, Priestley JR, Finnikin SJ, Saunders P, Abrams KR, Boelaert K.",,BMJ open,2021,2021-10-01,Y,Thyroid disease; epidemiology; Cardiac Epidemiology,,,"

Introduction

Hyperthyroidism is a common condition affecting up to 3% of the UK population. Treatment improves symptoms and reduces the risk of atrial fibrillation and stroke that contribute to increased mortality. The most common symptom is weight loss, which is reversed during treatment. However, the weight regain may be excessive, contributing to increased risk of obesity. Current treatment options include antithyroid drugs, radioiodine and thyroidectomy. Whether there are differences in either weight change or the long-term cardiometabolic risk between the three treatments is unclear.

Methods and analysis

The study will establish the natural history of weight change in hyperthyroidism, investigate the risk of obesity and risks of cardiometabolic conditions and death relative to the treatment. The data on patients diagnosed with hyperthyroidism between 1 January 1996 and 31 December 2015 will come from Clinical Practice Research Datalink linked to Hospital Episode Statistics and Office of National Statistics Death Registry. The weight changes will be modelled using a flexible joint modelling, accounting for mortality. Obesity prevalence in the general population will be sourced from Health Survey for England and compared with the post-treatment prevalence of obesity in patients with hyperthyroidism. The incidence and time-to-event of major adverse cardiovascular events, other cardiometabolic outcomes and mortality will be compared between the treatments using the inverse propensity weighting model. Incidence rate ratios of outcomes will be modelled with Poisson regression. Time to event will be analysed using Cox proportional hazards model. A competing risks approach will be adopted to estimate comparative incidences to allow for the impact of mortality.

Ethics and dissemination

The study will bring new knowledge on the risk of developing obesity, cardiometabolic morbidity and mortality following treatment for hyperthyroidism to inform clinical practice and public health policies. The results will be disseminated via open-access peer-reviewed publications and directly to the patients and public groups (Independent Scientific Advisory Committee protocol approval #20_000185).",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/10/e055219.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-055219; html:https://europepmc.org/articles/PMC8488707; pdf:https://europepmc.org/articles/PMC8488707?pdf=render +38383544,https://doi.org/10.1038/s41467-024-45761-7,The plasmidome associated with Gram-negative bloodstream infections: A large-scale observational study using complete plasmid assemblies.,"Lipworth S, Matlock W, Shaw L, Vihta KD, Rodger G, Chau K, Barker L, George S, Kavanagh J, Davies T, Vaughan A, Andersson M, Jeffery K, Oakley S, Morgan M, Hopkins S, Peto T, Crook D, Walker AS, Stoesser N.",,Nature communications,2024,2024-02-22,Y,,,,"Plasmids carry genes conferring antimicrobial resistance and other clinically important traits, and contribute to the rapid dissemination of such genes. Previous studies using complete plasmid assemblies, which are essential for reliable inference, have been small and/or limited to plasmids carrying antimicrobial resistance genes (ARGs). In this study, we sequenced 1,880 complete plasmids from 738 isolates from bloodstream infections in Oxfordshire, UK. The bacteria had been originally isolated in 2009 (194 isolates) and 2018 (368 isolates), plus a stratified selection from intervening years (176 isolates). We demonstrate that plasmids are largely, but not entirely, constrained to a single host species, although there is substantial overlap between species of plasmid gene-repertoire. Most ARGs are carried by a relatively small number of plasmid groups with biological features that are predictable. Plasmids carrying ARGs (including those encoding carbapenemases) share a putative 'backbone' of core genes with those carrying no such genes. These findings suggest that future surveillance should, in addition to tracking plasmids currently associated with clinically important genes, focus on identifying and monitoring the dissemination of high-risk plasmid groups with the potential to rapidly acquire and disseminate these genes.",,doi:https://doi.org/10.1038/s41467-024-45761-7; html:https://europepmc.org/articles/PMC10881496; pdf:https://europepmc.org/articles/PMC10881496?pdf=render 30183734,https://doi.org/10.1371/journal.pone.0202359,Time spent at blood pressure target and the risk of death and cardiovascular diseases.,"Chung SC, Pujades-Rodriguez M, Duyx B, Denaxas SC, Pasea L, Hingorani A, Timmis A, Williams B, Hemingway H.",,PloS one,2018,2018-09-05,Y,,The Human Phenome,,"

Background

The time a patient spends with blood pressure at target level is an intuitive measure of successful BP management, but population studies on its effectiveness are as yet unavailable.

Method

We identified a population-based cohort of 169,082 individuals with newly identified high blood pressure who were free of cardiovascular disease from January 1997 to March 2010. We used 1.64 million clinical blood pressure readings to calculate the TIme at TaRgEt (TITRE) based on current target blood pressure levels.

Result

The median (Inter-quartile range) TITRE among all patients was 2.8 (0.3, 5.6) months per year, only 1077 (0.6%) patients had a TITRE ≥11 months. Compared to people with a 0% TITRE, patients with a TITRE of 3-5.9 months, and 6-8.9 months had 75% and 78% lower odds of the composite of cardiovascular death, myocardial infarction and stroke (adjusted odds ratios, 0.25 (95% confidence interval: 0.21, 0.31) and 0.22 (0.17, 0.27), respectively). These associations were consistent for heart failure and any cardiovascular disease and death (comparing a 3-5.9 month to 0% TITRE, 63% and 60% lower in odds, respectively), among people who did or did not have blood pressure 'controlled' on a single occasion during the first year of follow-up, and across groups defined by number of follow-up BP measure categories.

Conclusion

Based on the current frequency of measurement of blood pressure this study suggests that few newly hypertensive patients sustained a complete, year-round on target blood pressure over time. The inverse associations between a higher TITRE and lower risk of incident cardiovascular diseases were independent of widely-used blood pressure 'control' indicators. Randomized trials are required to evaluate interventions to increase a person's time spent at blood pressure target.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0202359&type=printable; doi:https://doi.org/10.1371/journal.pone.0202359; html:https://europepmc.org/articles/PMC6124703; pdf:https://europepmc.org/articles/PMC6124703?pdf=render -36835444,https://doi.org/10.3390/ijms24044031,Untargeted Metabolomics Identifies Potential Hypertrophic Cardiomyopathy Biomarkers in Carriers of MYBPC3 Founder Variants.,"Jansen M, Schuldt M, van Driel BO, Schmidt AF, Christiaans I, van der Crabben SN, Hoedemaekers YM, Dooijes D, Jongbloed JDH, Boven LG, Deprez RHL, Wilde AAM, Jans JJM, van der Velden J, de Boer RA, van Tintelen JP, Asselbergs FW, Baas AF.",,International journal of molecular sciences,2023,2023-02-17,Y,Biomarkers; hypertrophic cardiomyopathy; Metabolomics; Mybpc3,,,"Hypertrophic cardiomyopathy (HCM) is the most prevalent monogenic heart disease, commonly caused by pathogenic MYBPC3 variants, and a significant cause of sudden cardiac death. Severity is highly variable, with incomplete penetrance among genotype-positive family members. Previous studies demonstrated metabolic changes in HCM. We aimed to identify metabolite profiles associated with disease severity in carriers of MYBPC3 founder variants using direct-infusion high-resolution mass spectrometry in plasma of 30 carriers with a severe phenotype (maximum wall thickness ≥20 mm, septal reduction therapy, congestive heart failure, left ventricular ejection fraction <50%, or malignant ventricular arrhythmia) and 30 age- and sex-matched carriers with no or a mild phenotype. Of the top 25 mass spectrometry peaks selected by sparse partial least squares discriminant analysis, XGBoost gradient boosted trees, and Lasso logistic regression (42 total), 36 associated with severe HCM at a p < 0.05, 20 at p < 0.01, and 3 at p < 0.001. These peaks could be clustered to several metabolic pathways, including acylcarnitine, histidine, lysine, purine and steroid hormone metabolism, and proteolysis. In conclusion, this exploratory case-control study identified metabolites associated with severe phenotypes in MYBPC3 founder variant carriers. Future studies should assess whether these biomarkers contribute to HCM pathogenesis and evaluate their contribution to risk stratification.",,pdf:https://www.mdpi.com/1422-0067/24/4/4031/pdf?version=1676950066; doi:https://doi.org/10.3390/ijms24044031; html:https://europepmc.org/articles/PMC9961357; pdf:https://europepmc.org/articles/PMC9961357?pdf=render 32282926,https://doi.org/10.1111/bjd.19122,"Partner bereavement and risk of chronic urticaria, alopecia areata and vitiligo: cohort studies in the UK and Denmark.","Wong AYS, Kjaersgaard A, Frøslev T, Forbes HJ, Mansfield KE, Silverwood RJ, Sørensen HT, Smeeth L, Schmidt SAJ, Langan SM.",,The British journal of dermatology,2020,2020-06-10,N,,,,,,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/bjd.19122; doi:https://doi.org/10.1111/bjd.19122 +36835444,https://doi.org/10.3390/ijms24044031,Untargeted Metabolomics Identifies Potential Hypertrophic Cardiomyopathy Biomarkers in Carriers of MYBPC3 Founder Variants.,"Jansen M, Schuldt M, van Driel BO, Schmidt AF, Christiaans I, van der Crabben SN, Hoedemaekers YM, Dooijes D, Jongbloed JDH, Boven LG, Deprez RHL, Wilde AAM, Jans JJM, van der Velden J, de Boer RA, van Tintelen JP, Asselbergs FW, Baas AF.",,International journal of molecular sciences,2023,2023-02-17,Y,Biomarkers; hypertrophic cardiomyopathy; Metabolomics; Mybpc3,,,"Hypertrophic cardiomyopathy (HCM) is the most prevalent monogenic heart disease, commonly caused by pathogenic MYBPC3 variants, and a significant cause of sudden cardiac death. Severity is highly variable, with incomplete penetrance among genotype-positive family members. Previous studies demonstrated metabolic changes in HCM. We aimed to identify metabolite profiles associated with disease severity in carriers of MYBPC3 founder variants using direct-infusion high-resolution mass spectrometry in plasma of 30 carriers with a severe phenotype (maximum wall thickness ≥20 mm, septal reduction therapy, congestive heart failure, left ventricular ejection fraction <50%, or malignant ventricular arrhythmia) and 30 age- and sex-matched carriers with no or a mild phenotype. Of the top 25 mass spectrometry peaks selected by sparse partial least squares discriminant analysis, XGBoost gradient boosted trees, and Lasso logistic regression (42 total), 36 associated with severe HCM at a p < 0.05, 20 at p < 0.01, and 3 at p < 0.001. These peaks could be clustered to several metabolic pathways, including acylcarnitine, histidine, lysine, purine and steroid hormone metabolism, and proteolysis. In conclusion, this exploratory case-control study identified metabolites associated with severe phenotypes in MYBPC3 founder variant carriers. Future studies should assess whether these biomarkers contribute to HCM pathogenesis and evaluate their contribution to risk stratification.",,pdf:https://www.mdpi.com/1422-0067/24/4/4031/pdf?version=1676950066; doi:https://doi.org/10.3390/ijms24044031; html:https://europepmc.org/articles/PMC9961357; pdf:https://europepmc.org/articles/PMC9961357?pdf=render 33180769,https://doi.org/10.1371/journal.pone.0240902,"Probable PTSD, depression and anxiety in 40,299 UK police officers and staff: Prevalence, risk factors and associations with blood pressure.","Stevelink SAM, Opie E, Pernet D, Gao H, Elliott P, Wessely S, Fear NT, Hotopf M, Greenberg N.",,PloS one,2020,2020-11-12,Y,,,,"

Introduction

Police employees undertake challenging duties which may adversely impact their health. This study explored the prevalence of and risk factors for probable mental disorders amongst a representative sample of UK police employees. The association between mental illness and alterations in blood pressure was also explored.

Methods

Data were used from the Airwave Health Monitoring Study which was established to monitor the possible physical health impacts of a new communication system on police employees. Data included sociodemographic characteristics, lifestyle habits, depression, anxiety, and post-traumatic stress disorder (PTSD) symptoms and blood pressure. Descriptive statistics were used to explore the prevalence of probable mental disorders and associated factors. Stepwise linear regression was conducted, controlling for confounding variables, to examine associations between mental disorders and blood pressure.

Results

The sample included 40,299 police staff, police constable/sergeants and inspectors or above. Probable depression was most frequently reported (9.8%), followed by anxiety (8.5%) and PTSD (3.9%). Groups at risk for probable mental disorders included police staff, and police employees who reported drinking heavily. Police employees exposed to traumatic incidents in the past six months had a doubling in rates of anxiety or depression and a six-fold increase in PTSD compared to those with no recent trauma exposure. Adjusted logistic regression models did not reveal any significant association between probable mental disorders and systolic blood pressure but significantly elevated diastolic blood pressure (≈1mmHg) was found across mental disorders.

Conclusions

These results show lower rates of probable mental disorders, especially PTSD, than reported in other studies focusing on police employees. Although mental ill health was associated with increased diastolic blood pressure, this was unlikely to be clinically significant. These findings highlight the importance of continued health monitoring of members of the UK police forces, focusing on employees recently exposed to traumatic incidents, heavy drinkers and police staff.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0240902&type=printable; doi:https://doi.org/10.1371/journal.pone.0240902; html:https://europepmc.org/articles/PMC7660485; pdf:https://europepmc.org/articles/PMC7660485?pdf=render 37269003,https://doi.org/10.1186/s13643-023-02261-x,Non-adherence and non-persistence to intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy: a systematic review and meta-analysis.,"Shahzad H, Mahmood S, McGee S, Hubbard J, Haque S, Paudyal V, Denniston AK, Hill LJ, Jalal Z.",,Systematic reviews,2023,2023-06-02,Y,Meta-analysis; Intravitreal; Anti-vegf; Non-adherence; Macular; Non-persistence; Covid-19,,,"

Background

Intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections play a key role in treating a range of macular diseases. The effectiveness of these therapies is dependent on patients' adherence (the extent to which a patient takes their medicines as per agreed recommendations from the healthcare provider) and persistence (continuation of the treatment for the prescribed duration) to their prescribed treatment regimens. The aim of this systematic review was to demonstrate the need for further investigation into the prevalence of, and factors contributing to, patient-led non-adherence and non-persistence, thus facilitating improved clinical outcomes.

Methods

Systematic searches were conducted in Google Scholar, Web of Science, PubMed, MEDLINE, and the Cochrane Library. Studies in English conducted before February 2023 that reported the level of, and/or barriers to, non-adherence or non-persistence to intravitreal anti-VEGF ocular disease therapy were included. Duplicate papers, literature reviews, expert opinion articles, case studies, and case series were excluded following screening by two independent authors.

Results

Data from a total of 409,215 patients across 52 studies were analysed. Treatment regimens included pro re nata, monthly and treat-and-extend protocols; study durations ranged from 4 months to 8 years. Of the 52 studies, 22 included a breakdown of reasons for patient non-adherence/non-persistence. Patient-led non-adherence varied between 17.5 and 35.0% depending on the definition used. Overall pooled prevalence of patient-led treatment non-persistence was 30.0% (P = 0.000). Reasons for non-adherence/non-persistence included dissatisfaction with treatment results (29.9%), financial burden (19%), older age/comorbidities (15.5%), difficulty booking appointments (8.5%), travel distance/social isolation (7.9%), lack of time (5.8%), satisfaction with the perceived improvement in their condition (4.4%), fear of injection (4.0%), loss of motivation (4.0%), apathy towards eyesight (2.5%), dissatisfaction with facilities 2.3%, and discomfort/pain (0.3%). Three studies found non-adherence rates between 51.6 and 68.8% during the COVID-19 pandemic, in part due to fear of exposure to COVID-19 and difficulties travelling during lockdown.

Discussion

Results suggest high levels of patient-led non-adherence/non-persistence to anti-VEGF therapy, mostly due to dissatisfaction with treatment results, a combination of comorbidities, loss of motivation and the burden of travel. This study provides key information on prevalence and factors contributing to non-adherence/non-persistence in anti-VEGF treatment for macular diseases, aiding identification of at-risk individuals to improve real-world visual outcomes. Improvements in the literature can be achieved by establishing uniform definitions and standard timescales for what constitutes non-adherence/non-persistence.

Systematic review registration

PROSPERO CRD42020216205.",,doi:https://doi.org/10.1186/s13643-023-02261-x; doi:https://doi.org/10.1186/s13643-023-02261-x; html:https://europepmc.org/articles/PMC10237080; pdf:https://europepmc.org/articles/PMC10237080?pdf=render 36809311,https://doi.org/10.1093/ejendo/lvad024,The ultra-acute steroid response to traumatic injury: a cohort study.,"Bentley C, Hazeldine J, Bravo L, Taylor AE, Gilligan LC, Shaheen F, Acharjee A, Gkoutos G, Foster MA, Arlt W, Lord JM.",,European journal of endocrinology,2023,2023-03-01,N,Steroids; Mass spectrometry; Glucocorticoids; Major Trauma; 11-Oxygenated Androgens,,,"

Objective

Trauma-induced steroid changes have been studied post-hospital admission, resulting in a lack of understanding of the speed and extent of the immediate endocrine response to injury. The Golden Hour study was designed to capture the ultra-acute response to traumatic injury.

Design

We conducted an observational cohort study including adult male trauma patients <60 years, with blood samples drawn ≤1 h of major trauma by pre-hospital emergency responders.

Methods

We recruited 31 adult male trauma patients (mean age 28 [range 19-59] years) with a mean injury severity score (ISS) of 16 (IQR 10-21). The median time to first sample was 35 (range 14-56) min, with follow-up samples collected 4-12 and 48-72 h post-injury. Serum steroids in patients and age- and sex-matched healthy controls (HCs) (n = 34) were analysed by tandem mass spectrometry.

Results

Within 1 h of injury, we observed an increase in glucocorticoid and adrenal androgen biosynthesis. Cortisol and 11-hydroxyandrostendione increased rapidly, whilst cortisone and 11-ketoandrostenedione decreased, reflective of increased cortisol and 11-oxygenated androgen precursor biosynthesis by 11β-hydroxylase and increased cortisol activation by 11β-hydroxysteroid dehydrogenase type 1. Active classic gonadal androgens testosterone and 5α-dihydrotestosterone decreased, whilst the active 11-oxygenated androgen 11-ketotestosterone maintained pre-injury levels.

Conclusions

Changes in steroid biosynthesis and metabolism occur within minutes of traumatic injury. Studies that address whether ultra-early changes in steroid metabolism are associated with patient outcomes are now required.",,pdf:https://academic.oup.com/ejendo/article-pdf/188/3/290/49630912/lvad024.pdf; doi:https://doi.org/10.1093/ejendo/lvad024 @@ -1374,21 +1374,21 @@ PMC8855010,https://doi.org/,POS-894 PREDICTING PANDEMIC-RELATED EXCESS-DEATH USI 36289925,https://doi.org/10.3390/biomedicines10102662,"Temporal Evolution of Multiday, Epileptic Functional Networks Prior to Seizure Occurrence.","Laiou P, Biondi A, Bruno E, Viana PF, Winston JS, Rashid Z, Ranjan Y, Conde P, Stewart C, Sun S, Zhang Y, Folarin A, Dobson RJB, Schulze-Bonhage A, Dümpelmann M, Richardson MP, Radar-Cns Consortium.",,Biomedicines,2022,2022-10-21,Y,Epilepsy; EEG; Graph theory; ECG; Functional Network; Seizure Lateralization; Evolving Network,,,"Epilepsy is one of the most common neurological disorders, characterized by the occurrence of repeated seizures. Given that epilepsy is considered a network disorder, tools derived from network neuroscience may confer the valuable ability to quantify the properties of epileptic brain networks. In this study, we use well-established brain network metrics (i.e., mean strength, variance of strength, eigenvector centrality, betweenness centrality) to characterize the temporal evolution of epileptic functional networks over several days prior to seizure occurrence. We infer the networks using long-term electroencephalographic recordings from 12 people with epilepsy. We found that brain network metrics are variable across days and show a circadian periodicity. In addition, we found that in 9 out of 12 patients the distribution of the variance of strength in the day (or even two last days) prior to seizure occurrence is significantly different compared to the corresponding distributions on all previous days. Our results suggest that brain network metrics computed fromelectroencephalographic recordings could potentially be used to characterize brain network changes that occur prior to seizures, and ultimately contribute to seizure warning systems.",,pdf:https://www.mdpi.com/2227-9059/10/10/2662/pdf?version=1666684470; doi:https://doi.org/10.3390/biomedicines10102662; html:https://europepmc.org/articles/PMC9599905; pdf:https://europepmc.org/articles/PMC9599905?pdf=render 34386668,https://doi.org/10.1016/j.ekir.2021.05.031,Impact of Using Risk-Based Stratification on Referral of Patients With Chronic Kidney Disease From Primary Care to Specialist Care in the United Kingdom.,"Bhachu HK, Cockwell P, Subramanian A, Adderley NJ, Gokhale K, Fenton A, Kyte D, Nirantharakumar K, Calvert M.",,Kidney international reports,2021,2021-06-01,Y,Cross-sectional study; Chronic Kidney Disease; Guidelines; Disease Progression; Patient Referral; Kidney Failure Risk Equation,,,"

Introduction

The externally validated Kidney Failure Risk Equation (KFRE) for predicting risk of end-stage renal disease (ESRD) has been developed, but its potential impact in a population on referrals for patients with chronic kidney disease (CKD) from primary to specialty nephrology care is not known.

Methods

A cross-sectional population-based study of individuals in United Kingdom primary care registered in The Health Improvement Network database was conducted. National Institute of Health and Care Excellence (NICE) 2014 CKD guidelines versus the 4-variable KFRE set at a >3% risk of ESRD at 5 years were applied to patients identified with CKD stage 3-5 between January 1, 2016, and March 31, 2017.

Results

In all, 39,476 (36.6%) of 107,962 adults with CKD stage 3-5 had a urine albumin:creatinine ratio (ACR) available and entered into the primary analysis. Of that, 7566 (19.2%) patients fulfilled NICE criteria for referral, 2386 (31.5%) of whom had a ≤3% 5-year risk of ESRD. Also 8663 (21.9%) patients had a >3% 5-year risk of ESRD, 3483 (40.2%) of whom did not fulfill NICE criteria; this represents 8.8% of the primary population. By using the KFRE threshold rather than NICE criteria for referral, 5869 patients (14.9% of the primary analysis population) would have been reallocated between primary and specialist care. Imputational analysis was used for missing ACR measurements and showed similar results.

Conclusions

A risk-based referral approach would lead to a substantial reallocation of patients between primary care and specialist nephrology care with only a small increase in numbers eligible, ensuring those at higher risk of progression are identified.",,pdf:http://pure-oai.bham.ac.uk/ws/files/145543032/1_s2.0_S2468024921012146_main.pdf; doi:https://doi.org/10.1016/j.ekir.2021.05.031; html:https://europepmc.org/articles/PMC8343777; pdf:https://europepmc.org/articles/PMC8343777?pdf=render 35440446,https://doi.org/10.1136/bmjopen-2021-052514,Protocol for the COG-UK hospital-onset COVID-19 infection (HOCI) multicentre interventional clinical study: evaluating the efficacy of rapid genome sequencing of SARS-CoV-2 in limiting the spread of COVID-19 in UK NHS hospitals.,"Blackstone J, Stirrup O, Mapp F, Panca M, Copas A, Flowers P, Hockey L, Price J, Partridge D, Peters C, de Silva T, Nebbia G, Snell LB, McComish R, COVID-19 Genomics UK (COG-UK) Consortium, Breuer J.",,BMJ open,2022,2022-04-19,Y,Molecular biology; Infection control; epidemiology; Covid-19,,,"

Objectives

Nosocomial transmission of SARS-CoV-2 has been a significant cause of mortality in National Health Service (NHS) hospitals during the COVID-19 pandemic. The COG-UK Consortium Hospital-Onset COVID-19 Infections (COG-UK HOCI) study aims to evaluate whether the use of rapid whole-genome sequencing of SARS-CoV-2, supported by a novel probabilistic reporting methodology, can inform infection prevention and control (IPC) practice within NHS hospital settings.

Design

Multicentre, prospective, interventional, superiority study.

Setting

14 participating NHS hospitals over winter-spring 2020/2021 in the UK.

Participants

Eligible patients must be admitted to hospital with first-confirmed SARS-CoV-2 PCR-positive test result >48 hour from time of admission, where COVID-19 diagnosis not suspected on admission. The projected sample size is 2380 patients.

Intervention

The intervention is the return of a sequence report, within 48 hours in one phase (rapid local lab processing) and within 5-10 days in a second phase (mimicking central lab), comparing the viral genome from an eligible study participant with others within and outside the hospital site.

Primary and secondary outcome measures

The primary outcomes are incidence of Public Health England (PHE)/IPC-defined SARS-CoV-2 hospital-acquired infection during the baseline and two interventional phases, and proportion of hospital-onset cases with genomic evidence of transmission linkage following implementation of the intervention where such linkage was not suspected by initial IPC investigation. Secondary outcomes include incidence of hospital outbreaks, with and without sequencing data; actual and desirable changes to IPC actions; periods of healthcare worker (HCW) absence. Health economic analysis will be conducted to determine cost benefit of the intervention. A process evaluation using qualitative interviews with HCWs will be conducted alongside the study.

Trial registration number

ISRCTN50212645. Pre-results stage. This manuscript is based on protocol V.6.0. 2 September 2021.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/4/e052514.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-052514; html:https://europepmc.org/articles/PMC9019828; pdf:https://europepmc.org/articles/PMC9019828?pdf=render -36285341,https://doi.org/10.1080/17434440.2022.2132147,Data-driven monitoring in patients on left ventricular assist device support.,"Numan L, Moazeni M, Oerlemans MIFJ, Aarts E, Van Der Kaaij NP, Asselbergs FW, Van Laake LW.",,Expert review of medical devices,2022,2022-09-01,N,Prediction; Circadian rhythm; Algorithms; Remote Monitoring; Left Ventricular Assist Device; Lvad,,,"

Introduction

Despite an increasing population of patients supported with a left ventricular assist device (LVAD), it remains a complex therapy, and patients are frequently admitted. Therefore, a strict follow-up including frequent hospital visits, patient self-management and telemonitoring is needed.

Areas covered

The current review describes the principles of LVADs, the possibilities of (tele)monitoring using noninvasive and invasive devices. Furthermore, possibilities, challenges, and future perspectives in this emerging field are discussed.

Expert opinion

Several studies described initial experiences on telemonitoring in LVAD patients, using mobile phone applications to collect clinical data and pump data. This may replace frequent hospital visits in near future. In addition, algorithms were developed aiming to early detect pump thrombosis or driveline infections. Since not all complications are reflected by pump parameters, data from different sources should be combined to detect a broader spectrum of complications in an early stage. We need to focus on the development of sophisticated but understandable algorithms and infrastructure combining different data sources, while addressing essential aspects such as data safety, privacy, and cost-effectiveness.",,doi:https://doi.org/10.1080/17434440.2022.2132147; doi:https://doi.org/10.1080/17434440.2022.2132147 32861307,https://doi.org/10.1016/s0140-6736(20)30930-2,Invasive versus non-invasive management of older patients with non-ST elevation myocardial infarction (SENIOR-NSTEMI): a cohort study based on routine clinical data.,"Kaura A, Sterne JAC, Trickey A, Abbott S, Mulla A, Glampson B, Panoulas V, Davies J, Woods K, Omigie J, Shah AD, Channon KM, Weber JN, Thursz MR, Elliott P, Hemingway H, Williams B, Asselbergs FW, O'Sullivan M, Lord GM, Melikian N, Johnson T, Francis DP, Shah AM, Perera D, Kharbanda R, Patel RS, Mayet J.",,"Lancet (London, England)",2020,2020-08-01,Y,,,,"

Background

Previous trials suggest lower long-term risk of mortality after invasive rather than non-invasive management of patients with non-ST elevation myocardial infarction (NSTEMI), but the trials excluded very elderly patients. We aimed to estimate the effect of invasive versus non-invasive management within 3 days of peak troponin concentration on the survival of patients aged 80 years or older with NSTEMI.

Methods

Routine clinical data for this study were obtained from five collaborating hospitals hosting NIHR Biomedical Research Centres in the UK (all tertiary centres with emergency departments). Eligible patients were 80 years old or older when they underwent troponin measurements and were diagnosed with NSTEMI between 2010 (2008 for University College Hospital) and 2017. Propensity scores (patients' estimated probability of receiving invasive management) based on pretreatment variables were derived using logistic regression; patients with high probabilities of non-invasive or invasive management were excluded. Patients who died within 3 days of peak troponin concentration without receiving invasive management were assigned to the invasive or non-invasive management groups based on their propensity scores, to mitigate immortal time bias. We estimated mortality hazard ratios comparing invasive with non-invasive management, and compared the rate of hospital admissions for heart failure.

Findings

Of the 1976 patients with NSTEMI, 101 died within 3 days of their peak troponin concentration and 375 were excluded because of extreme propensity scores. The remaining 1500 patients had a median age of 86 (IQR 82-89) years of whom (845 [56%] received non-invasive management. During median follow-up of 3·0 (IQR 1·2-4·8) years, 613 (41%) patients died. The adjusted cumulative 5-year mortality was 36% in the invasive management group and 55% in the non-invasive management group (adjusted hazard ratio 0·68, 95% CI 0·55-0·84). Invasive management was associated with lower incidence of hospital admissions for heart failure (adjusted rate ratio compared with non-invasive management 0·67, 95% CI 0·48-0·93).

Interpretation

The survival advantage of invasive compared with non-invasive management appears to extend to patients with NSTEMI who are aged 80 years or older.

Funding

NIHR Imperial Biomedical Research Centre, as part of the NIHR Health Informatics Collaborative.",,pdf:http://www.thelancet.com/article/S0140673620309302/pdf; doi:https://doi.org/10.1016/S0140-6736(20)30930-2; html:https://europepmc.org/articles/PMC7456783; pdf:https://europepmc.org/articles/PMC7456783?pdf=render -38692709,https://doi.org/10.1136/bmjresp-2023-001746,"Risk factors for asthma-related hospital and intensive care admissions in children, adolescents and adults: a cohort study using primary and secondary care data.","Simms-Williams N, Nagakumar P, Thayakaran R, Adderley NJ, Hotham R, Mansur AH, Nirantharakumar K, Haroon S.",,BMJ open respiratory research,2024,2024-05-01,Y,Asthma; Asthma Epidemiology,,,"

Background

Asthma remains a common cause of hospital admissions across the life course. We estimated the contribution of key risk factors to asthma-related hospital and intensive care unit (ICU) admissions in children, adolescents and adults.

Methods

This was a UK-based cohort study using linked primary care (Clinical Practice Research Datalink Aurum) and secondary care (Hospital Episode Statistics Admitted Patient Care) data. Patients were eligible if they were aged 5 years and older and had been diagnosed with asthma. This included 90 989 children aged 5-11 years, 114 927 adolescents aged 12-17 years and 1 179 410 adults aged 18 years or older. The primary outcome was asthma-related hospital admissions from 1 January 2017 to 31 December 2019. The secondary outcome was asthma-related ICU admissions. Incidence rate ratios adjusted for demographic and clinical risk factors were estimated using negative binomial models. Population attributable fraction (PAF) was estimated for modifiable risk factors.

Results

Younger age groups, females and those from ethnic minority and lower socioeconomic backgrounds had an increased risk of asthma-related hospital admissions. Increasing medication burden, including excessive use of short-acting bronchodilators, was also strongly associated with the primary outcome. Similar risk factors were observed for asthma-related ICU admissions. The key potentially modifiable or treatable risk factors were smoking in adolescents and adults (PAF 6.8%, 95% CI 0.9% to 12.3% and 4.3%, 95% CI 3.0% to 5.7%, respectively), and obesity (PAF 23.3%, 95% CI 20.5% to 26.1%), depression (11.1%, 95% CI 9.1% to 13.1%), gastro-oesophageal reflux disease (2.3%, 95% CI 1.2% to 3.4%), anxiety (2.0%, 95% CI 0.5% to 3.6%) and chronic rhinosinusitis (0.8%, 95% CI 0.3% to 1.3%) in adults.

Conclusions

There are significant sociodemographic inequalities in the rates of asthma-related hospital and ICU admissions. Treating age-specific modifiable risk factors should be considered an integral part of asthma management, which could potentially reduce the rate of avoidable hospital admissions.",,pdf:https://bmjopenrespres.bmj.com/content/bmjresp/11/1/e001746.full.pdf; doi:https://doi.org/10.1136/bmjresp-2023-001746; html:https://europepmc.org/articles/PMC11086188; pdf:https://europepmc.org/articles/PMC11086188?pdf=render +36285341,https://doi.org/10.1080/17434440.2022.2132147,Data-driven monitoring in patients on left ventricular assist device support.,"Numan L, Moazeni M, Oerlemans MIFJ, Aarts E, Van Der Kaaij NP, Asselbergs FW, Van Laake LW.",,Expert review of medical devices,2022,2022-09-01,N,Prediction; Circadian rhythm; Algorithms; Remote Monitoring; Left Ventricular Assist Device; Lvad,,,"

Introduction

Despite an increasing population of patients supported with a left ventricular assist device (LVAD), it remains a complex therapy, and patients are frequently admitted. Therefore, a strict follow-up including frequent hospital visits, patient self-management and telemonitoring is needed.

Areas covered

The current review describes the principles of LVADs, the possibilities of (tele)monitoring using noninvasive and invasive devices. Furthermore, possibilities, challenges, and future perspectives in this emerging field are discussed.

Expert opinion

Several studies described initial experiences on telemonitoring in LVAD patients, using mobile phone applications to collect clinical data and pump data. This may replace frequent hospital visits in near future. In addition, algorithms were developed aiming to early detect pump thrombosis or driveline infections. Since not all complications are reflected by pump parameters, data from different sources should be combined to detect a broader spectrum of complications in an early stage. We need to focus on the development of sophisticated but understandable algorithms and infrastructure combining different data sources, while addressing essential aspects such as data safety, privacy, and cost-effectiveness.",,doi:https://doi.org/10.1080/17434440.2022.2132147; doi:https://doi.org/10.1080/17434440.2022.2132147 36576811,https://doi.org/10.1001/jamacardio.2022.4466,Predictive Utility of a Coronary Artery Disease Polygenic Risk Score in Primary Prevention.,"Marston NA, Pirruccello JP, Melloni GEM, Koyama S, Kamanu FK, Weng LC, Roselli C, Kamatani Y, Komuro I, Aragam KG, Butterworth AS, Ito K, Lubitz SA, Ellinor PT, Sabatine MS, Ruff CT.",,JAMA cardiology,2023,2023-02-01,N,,,,"

Importance

The clinical utility of polygenic risk scores (PRS) for coronary artery disease (CAD) has not yet been established.

Objective

To investigate the ability of a CAD PRS to potentially guide statin initiation in primary prevention after accounting for age and clinical risk.

Design, setting, and participants

This was a longitudinal cohort study with enrollment starting on January 1, 2006, and ending on December 31, 2010, with data updated to mid-2021, using data from the UK Biobank, a long-term population study of UK citizens. A replication analysis was performed in Biobank Japan. The analysis included all patients without a history of CAD and who were not taking lipid-lowering therapy. Data were analyzed from January 1 to June 30, 2022.

Exposures

Polygenic risk for CAD was defined as low (bottom 20%), intermediate, and high (top 20%) using a CAD PRS including 241 genome-wide significant single-nucleotide variations (SNVs). The pooled cohort equations were used to estimate 10-year atherosclerotic cardiovascular disease (ASCVD) risk and classify individuals as low (<5%), borderline (5-<7.5%), intermediate (7.5-<20%), or high risk (≥20%).

Main outcomes and measures

Myocardial infarction (MI) and ASCVD events (defined as incident clinical CAD [including MI], stroke, or CV death).

Results

A total of 330 201 patients (median [IQR] age, 57 [40-74] years; 189 107 female individuals [57%]) were included from the UK Biobank. Over the 10-year follow-up, 4454 individuals had an MI. The CAD PRS was significantly associated with the risk of MI in all age groups but had significantly stronger risk prediction at younger ages (age <50 years: hazard ratio [HR] per 1 SD of PRS, 1.72; 95% CI, 1.56-1.89; age 50-60 years: HR, 1.46; 95% CI, 1.38-1.53; age >60 years: HR, 1.42; 95% CI, 1.37-1.48; P for interaction <.001). In patients younger than 50 years, those with high PRS had a 3- to 4-fold increased associated risk of MI compared with those in the low PRS category. A significant interaction between CAD PRS and age was replicated in Biobank Japan. When CAD PRS testing was added to the clinical ASCVD risk score in individuals younger than 50 years, 591 of 4373 patients (20%) with borderline risk were risk stratified into intermediate risk, warranting initiation of statin therapy and 3198 of 7477 patients (20%) with both borderline or intermediate risk were stratified as low risk, thus not warranting therapy.

Conclusions and relevance

Results of this cohort study suggest that the predictive ability of a CAD PRS was greater in younger individuals and can be used to better identify patients with borderline and intermediate clinical risk who should initiate statin therapy.",,doi:https://doi.org/10.1001/jamacardio.2022.4466; html:https://europepmc.org/articles/PMC9857431; doi:https://doi.org/10.1001/jamacardio.2022.4466 +38692709,https://doi.org/10.1136/bmjresp-2023-001746,"Risk factors for asthma-related hospital and intensive care admissions in children, adolescents and adults: a cohort study using primary and secondary care data.","Simms-Williams N, Nagakumar P, Thayakaran R, Adderley NJ, Hotham R, Mansur AH, Nirantharakumar K, Haroon S.",,BMJ open respiratory research,2024,2024-05-01,Y,Asthma; Asthma Epidemiology,,,"

Background

Asthma remains a common cause of hospital admissions across the life course. We estimated the contribution of key risk factors to asthma-related hospital and intensive care unit (ICU) admissions in children, adolescents and adults.

Methods

This was a UK-based cohort study using linked primary care (Clinical Practice Research Datalink Aurum) and secondary care (Hospital Episode Statistics Admitted Patient Care) data. Patients were eligible if they were aged 5 years and older and had been diagnosed with asthma. This included 90 989 children aged 5-11 years, 114 927 adolescents aged 12-17 years and 1 179 410 adults aged 18 years or older. The primary outcome was asthma-related hospital admissions from 1 January 2017 to 31 December 2019. The secondary outcome was asthma-related ICU admissions. Incidence rate ratios adjusted for demographic and clinical risk factors were estimated using negative binomial models. Population attributable fraction (PAF) was estimated for modifiable risk factors.

Results

Younger age groups, females and those from ethnic minority and lower socioeconomic backgrounds had an increased risk of asthma-related hospital admissions. Increasing medication burden, including excessive use of short-acting bronchodilators, was also strongly associated with the primary outcome. Similar risk factors were observed for asthma-related ICU admissions. The key potentially modifiable or treatable risk factors were smoking in adolescents and adults (PAF 6.8%, 95% CI 0.9% to 12.3% and 4.3%, 95% CI 3.0% to 5.7%, respectively), and obesity (PAF 23.3%, 95% CI 20.5% to 26.1%), depression (11.1%, 95% CI 9.1% to 13.1%), gastro-oesophageal reflux disease (2.3%, 95% CI 1.2% to 3.4%), anxiety (2.0%, 95% CI 0.5% to 3.6%) and chronic rhinosinusitis (0.8%, 95% CI 0.3% to 1.3%) in adults.

Conclusions

There are significant sociodemographic inequalities in the rates of asthma-related hospital and ICU admissions. Treating age-specific modifiable risk factors should be considered an integral part of asthma management, which could potentially reduce the rate of avoidable hospital admissions.",,pdf:https://bmjopenrespres.bmj.com/content/bmjresp/11/1/e001746.full.pdf; doi:https://doi.org/10.1136/bmjresp-2023-001746; html:https://europepmc.org/articles/PMC11086188; pdf:https://europepmc.org/articles/PMC11086188?pdf=render 37101398,https://doi.org/10.1002/ejhf.2868,Sex differences in the generalizability of randomized clinical trials in heart failure with reduced ejection fraction.,"Schroeder M, Lim YMF, Savarese G, Suzart-Woischnik K, Baudier C, Dyszynski T, Vaartjes I, Eijkemans MJC, Uijl A, Herrera R, Vradi E, Brugts JJ, Brunner-La Rocca HP, Blanc-Guillemaud V, Waechter S, Couvelard F, Tyl B, Fatoba S, Hoes AW, Lund LH, Gerlinger C, Asselbergs FW, Grobbee DE, Cronin M, Koudstaal S.",,European journal of heart failure,2023,2023-05-18,N,Heart Failure; Randomized Clinical Trial; Females; Enrichment Strategies; Standardized Mortality Ratios; Real-world Evidence,,,"

Aims

In order to understand how sex differences impact the generalizability of randomized clinical trials (RCTs) in patients with heart failure (HF) and reduced ejection fraction (HFrEF), we sought to compare clinical characteristics and clinical outcomes between RCTs and HF observational registries stratified by sex.

Methods and results

Data from two HF registries and five HFrEF RCTs were used to create three subpopulations: one RCT population (n = 16 917; 21.7% females), registry patients eligible for RCT inclusion (n = 26 104; 31.8% females), and registry patients ineligible for RCT inclusion (n = 20 810; 30.2% females). Clinical endpoints included all-cause mortality, cardiovascular mortality, and first HF hospitalization at 1 year. Males and females were equally eligible for trial enrolment (56.9% of females and 55.1% of males in the registries). One-year mortality rates were 5.6%, 14.0%, and 28.6% for females and 6.9%, 10.7%, and 24.6% for males in the RCT, RCT-eligible, and RCT-ineligible groups, respectively. After adjusting for 11 HF prognostic variables, RCT females showed higher survival compared to RCT-eligible females (standardized mortality ratio [SMR] 0.72; 95% confidence interval [CI] 0.62-0.83), while RCT males showed higher adjusted mortality rates compared to RCT-eligible males (SMR 1.16; 95% CI 1.09-1.24). Similar results were also found for cardiovascular mortality (SMR 0.89; 95% CI 0.76-1.03 for females, SMR 1.43; 95% CI 1.33-1.53 for males).

Conclusion

Generalizability of HFrEF RCTs differed substantially between the sexes, with females having lower trial participation and female trial participants having lower mortality rates compared to similar females in the registries, while males had higher than expected cardiovascular mortality rates in RCTs compared to similar males in registries.",,doi:https://doi.org/10.1002/ejhf.2868; doi:https://doi.org/10.1002/ejhf.2868 35452565,https://doi.org/10.1002/cpz1.373,The COPILOT Raw Illumina Genotyping QC Protocol.,"Patel H, Lee SH, Breen G, Menzel S, Ojewunmi O, Dobson RJB.",,Current protocols,2022,2022-04-01,N,Genotyping; Gwas; Illumina; Docker; Qc Pipeline,,,"The Illumina genotyping microarrays generate data in image format, which is processed by the platform-specific software GenomeStudio, followed by an array of complex bioinformatics analyses that rely on various software, different programming languages, and numerous dependencies to be installed and configured correctly. The entire process can be time-consuming, can lead to reproducibility errors, and can be a daunting task for bioinformaticians. To address this, we introduce the COPILOT protocol, which has been successfully used to transform raw Illumina genotype intensity data into high-quality analysis-ready data on tens of thousands of human patient samples that have been genotyped on a variety of Illumina genotyping arrays. This includes processing both mainstream and custom content genotyping chips with over 4 million markers per sample. The COPILOT QC protocol consists of two distinct tandem procedures to process raw Illumina genotyping data. The first protocol is an up-to-date process to systematically QC raw Illumina microarray genotyping data using the Illumina-specific GenomeStudio software. The second protocol takes the output from the first protocol and further processes the data through the COPILOT (Containerised wOrkflow for Processing ILlumina genOtyping daTa) containerized QC pipeline, to automate an array of complex bioinformatics analyses to improve data quality through a secondary clustering algorithm and to automatically identify typical Genome-Wide Association Study (GWAS) data issues, including gender discrepancies, heterozygosity outliers, related individuals, and population outliers, through ancestry estimation. The data is returned to the user in analysis-ready PLINK binary format and is accompanied by a comprehensive and interactive HTML summary report file which quickly helps the user understand the data and guides the user for further data analyses. The COPILOT protocol and containerized pipeline are also available at https://khp-informatics.github.io/COPILOT/index.html. © 2022 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Processing raw Illumina genotyping data using GenomeStudio Basic Protocol 2: COPILOT: A containerised workflow for processing Illumina genotyping data.",,pdf:https://discovery.ucl.ac.uk/10149151/1/Dobson_The%20COPILOT%20Raw%20Illumina%20Genotyping%20QC%20Protocol_VoR.pdf; doi:https://doi.org/10.1002/cpz1.373 36729586,https://doi.org/10.2196/42965,Assessing the Feasibility of a Text-Based Conversational Agent for Asthma Support: Protocol for a Mixed Methods Observational Study.,"Calvo RA, Peters D, Moradbakhti L, Cook D, Rizos G, Schuller B, Kallis C, Wong E, Quint J.",,JMIR research protocols,2023,2023-02-02,Y,Artificial intelligence; Health; Asthma; Health education; Well-being; Behavior Change; Conversational Agent; Chatbot,,,"

Background

Despite efforts, the UK death rate from asthma is the highest in Europe, and 65% of people with asthma in the United Kingdom do not receive the professional care they are entitled to. Experts have recommended the use of digital innovations to help address the issues of poor outcomes and lack of care access. An automated SMS text messaging-based conversational agent (ie, chatbot) created to provide access to asthma support in a familiar format via a mobile phone has the potential to help people with asthma across demographics and at scale. Such a chatbot could help improve the accuracy of self-assessed risk, improve asthma self-management, increase access to professional care, and ultimately reduce asthma attacks and emergencies.

Objective

The aims of this study are to determine the feasibility and usability of a text-based conversational agent that processes a patient's text responses and short sample voice recordings to calculate an estimate of their risk for an asthma exacerbation and then offers follow-up information for lowering risk and improving asthma control; assess the levels of engagement for different groups of users, particularly those who do not access professional services and those with poor asthma control; and assess the extent to which users of the chatbot perceive it as helpful for improving their understanding and self-management of their condition.

Methods

We will recruit 300 adults through four channels for broad reach: Facebook, YouGov, Asthma + Lung UK social media, and the website Healthily (a health self-management app). Participants will be screened, and those who meet inclusion criteria (adults diagnosed with asthma and who use WhatsApp) will be provided with a link to access the conversational agent through WhatsApp on their mobile phones. Participants will be sent scheduled and randomly timed messages to invite them to engage in dialogue about their asthma risk during the period of study. After a data collection period (28 days), participants will respond to questionnaire items related to the quality of the interaction. A pre- and postquestionnaire will measure asthma control before and after the intervention.

Results

This study was funded in March 2021 and started in January 2022. We developed a prototype conversational agent, which was iteratively improved with feedback from people with asthma, asthma nurses, and specialist doctors. Fortnightly reviews of iterations by the clinical team began in September 2022 and are ongoing. This feasibility study will start recruitment in January 2023. The anticipated completion of the study is July 2023. A future randomized controlled trial will depend on the outcomes of this study and funding.

Conclusions

This feasibility study will inform a follow-up pilot and larger randomized controlled trial to assess the impact of a conversational agent on asthma outcomes, self-management, behavior change, and access to care.

International registered report identifier (irrid)

PRR1-10.2196/42965.",,pdf:https://www.researchprotocols.org/2023/1/e42965/PDF; doi:https://doi.org/10.2196/42965; html:https://europepmc.org/articles/PMC9936366 -35103964,https://doi.org/10.1007/978-1-0716-2140-0_6,Chromatin Immunoprecipitation Sequencing (ChIP-seq) Protocol for Small Amounts of Frozen Biobanked Cardiac Tissue.,"Pei J, van den Dungen NAM, Asselbergs FW, Mokry M, Harakalova M.",,"Methods in molecular biology (Clifton, N.J.)",2022,2022-01-01,N,Sequencing; Antibody; Promoters; Cardiac Tissues; Chromatin Immunoprecipitation; Enhancers; Small Biopsy,,,"Chromatin immunoprecipitation and sequencing (ChIP-seq) is a well-established method to study the epigenetic profile at the genome-wide scale, including histone modifications and DNA-protein interactions. It provides valuable insights to better understand disease mechanisms. Here we present an optimized ChIP-seq protocol suitable for human cardiac tissues, especially the frozen biobanked small biopsy samples.",,doi:https://doi.org/10.1007/978-1-0716-2140-0_6 33328048,https://doi.org/10.1016/s2589-7500(20)30218-1,Reporting guidelines for clinical trial reports for interventions involving artificial intelligence: the CONSORT-AI extension.,"Liu X, Cruz Rivera S, Moher D, Calvert MJ, Denniston AK, SPIRIT-AI and CONSORT-AI Working Group.",,The Lancet. Digital health,2020,2020-09-09,N,,,,"The CONSORT 2010 statement provides minimum guidelines for reporting randomised trials. Its widespread use has been instrumental in ensuring transparency in the evaluation of new interventions. More recently, there has been a growing recognition that interventions involving artificial intelligence (AI) need to undergo rigorous, prospective evaluation to demonstrate impact on health outcomes. The CONSORT-AI (Consolidated Standards of Reporting Trials-Artificial Intelligence) extension is a new reporting guideline for clinical trials evaluating interventions with an AI component. It was developed in parallel with its companion statement for clinical trial protocols: SPIRIT-AI (Standard Protocol Items: Recommendations for Interventional Trials-Artificial Intelligence). Both guidelines were developed through a staged consensus process involving literature review and expert consultation to generate 29 candidate items, which were assessed by an international multi-stakeholder group in a two-stage Delphi survey (103 stakeholders), agreed upon in a two-day consensus meeting (31 stakeholders), and refined through a checklist pilot (34 participants). The CONSORT-AI extension includes 14 new items that were considered sufficiently important for AI interventions that they should be routinely reported in addition to the core CONSORT 2010 items. CONSORT-AI recommends that investigators provide clear descriptions of the AI intervention, including instructions and skills required for use, the setting in which the AI intervention is integrated, the handling of inputs and outputs of the AI intervention, the human-AI interaction and provision of an analysis of error cases. CONSORT-AI will help promote transparency and completeness in reporting clinical trials for AI interventions. It will assist editors and peer reviewers, as well as the general readership, to understand, interpret, and critically appraise the quality of clinical trial design and risk of bias in the reported outcomes.",,pdf:http://www.thelancet.com/article/S2589750020302181/pdf; doi:https://doi.org/10.1016/S2589-7500(20)30218-1; html:https://europepmc.org/articles/PMC8183333; pdf:https://europepmc.org/articles/PMC8183333?pdf=render; doi:https://doi.org/10.1016/s2589-7500(20)30218-1 +35103964,https://doi.org/10.1007/978-1-0716-2140-0_6,Chromatin Immunoprecipitation Sequencing (ChIP-seq) Protocol for Small Amounts of Frozen Biobanked Cardiac Tissue.,"Pei J, van den Dungen NAM, Asselbergs FW, Mokry M, Harakalova M.",,"Methods in molecular biology (Clifton, N.J.)",2022,2022-01-01,N,Sequencing; Antibody; Promoters; Cardiac Tissues; Chromatin Immunoprecipitation; Enhancers; Small Biopsy,,,"Chromatin immunoprecipitation and sequencing (ChIP-seq) is a well-established method to study the epigenetic profile at the genome-wide scale, including histone modifications and DNA-protein interactions. It provides valuable insights to better understand disease mechanisms. Here we present an optimized ChIP-seq protocol suitable for human cardiac tissues, especially the frozen biobanked small biopsy samples.",,doi:https://doi.org/10.1007/978-1-0716-2140-0_6 32929109,https://doi.org/10.1038/s41598-020-72060-0,A data-driven typology of asthma medication adherence using cluster analysis.,"Tibble H, Chan A, Mitchell EA, Horne E, Doudesis D, Horne R, Mizani MA, Sheikh A, Tsanas A.",,Scientific reports,2020,2020-09-14,Y,,,,"Asthma preventer medication non-adherence is strongly associated with poor asthma control. One-dimensional measures of adherence may ignore clinically important patterns of medication-taking behavior. We sought to construct a data-driven multi-dimensional typology of medication non-adherence in children with asthma. We analyzed data from an intervention study of electronic inhaler monitoring devices, comprising 211 patients yielding 35,161 person-days of data. Five adherence measures were extracted: the percentage of doses taken, the percentage of days on which zero doses were taken, the percentage of days on which both doses were taken, the number of treatment intermissions per 100 study days, and the duration of treatment intermissions per 100 study days. We applied principal component analysis on the measures and subsequently applied k-means to determine cluster membership. Decision trees identified the measure that could predict cluster assignment with the highest accuracy, increasing interpretability and increasing clinical utility. We demonstrate the use of adherence measures towards a three-group categorization of medication non-adherence, which succinctly describes the diversity of patient medication taking patterns in asthma. The percentage of prescribed doses taken during the study contributed to the prediction of cluster assignment most accurately (84% in out-of-sample data).",,pdf:https://www.nature.com/articles/s41598-020-72060-0.pdf; doi:https://doi.org/10.1038/s41598-020-72060-0; html:https://europepmc.org/articles/PMC7490405; pdf:https://europepmc.org/articles/PMC7490405?pdf=render 32991065,https://doi.org/10.1111/dom.14203,Sodium-glucose co-transporter-2 inhibitors and susceptibility to COVID-19: A population-based retrospective cohort study.,"Sainsbury C, Wang J, Gokhale K, Acosta-Mena D, Dhalla S, Byne N, Chandan JS, Anand A, Cooper J, Okoth K, Subramanian A, Bangash MN, Taverner T, Hanif W, Ghosh S, Narendran P, Cheng KK, Marshall T, Gkoutos G, Toulis K, Thomas N, Tahrani A, Adderley NJ, Haroon S, Nirantharakumar K.",,"Diabetes, obesity & metabolism",2021,2020-10-19,Y,Type 2 diabetes; Dpp-4 Inhibitor; Pharmaco-epidemiology; Sglt2 Inhibitor; Antidiabetic Drug,,,"Sodium-glucose co-transporter-2 (SGLT2) inhibitors are widely prescribed in people with type 2 diabetes. We aimed to investigate whether SGLT2 inhibitor prescription is associated with COVID-19, when compared with an active comparator. We performed a propensity-score-matched cohort study with active comparators and a negative control outcome in a large UK-based primary care dataset. Participants prescribed SGLT2 inhibitors (n = 9948) and a comparator group prescribed dipeptidyl peptidase-4 (DPP-4) inhibitors (n = 14 917) were followed up from January 30 to July 27, 2020. The primary outcome was confirmed or clinically suspected COVID-19. The incidence rate of COVID-19 was 19.7/1000 person-years among users of SGLT2 inhibitors and 24.7/1000 person-years among propensity-score-matched users of DPP-4 inhibitors. The adjusted hazard ratio was 0.92 (95% confidence interval 0.66 to 1.29), and there was no evidence of residual confounding in the negative control analysis. We did not observe an increased risk of COVID-19 in primary care amongst those prescribed SGLT2 inhibitors compared to DPP-4 inhibitors, suggesting that clinicians may safely use these agents in the everyday care of people with type 2 diabetes during the COVID-19 pandemic.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/dom.14203; doi:https://doi.org/10.1111/dom.14203; html:https://europepmc.org/articles/PMC7537530; pdf:https://europepmc.org/articles/PMC7537530?pdf=render 37798805,https://doi.org/10.1186/s13063-023-07576-7,"Medicines and Healthcare products Regulatory Agency's ""Consultation on proposals for legislative changes for clinical trials"": a response from the Trials Methodology Research Partnership Adaptive Designs Working Group, with a focus on data sharing.","Law M, Couturier DL, Choodari-Oskooei B, Crout P, Gamble C, Jacko P, Pallmann P, Pilling M, Robertson DS, Robling M, Sydes MR, Villar SS, Wason J, Wheeler G, Williamson SF, Yap C, Jaki T.",,Trials,2023,2023-10-05,Y,Legislation; data sharing; Consultation,,,"In the UK, the Medicines and Healthcare products Regulatory Agency consulted on proposals ""to improve and strengthen the UK clinical trials legislation to help us make the UK the best place to research and develop safe and innovative medicines"". The purpose of the consultation was to help finalise the proposals and contribute to the drafting of secondary legislation. We discussed these proposals as members of the Trials Methodology Research Partnership Adaptive Designs Working Group, which is jointly funded by the Medical Research Council and the National Institute for Health and Care Research. Two topics arose frequently in the discussion: the emphasis on legislation, and the absence of questions on data sharing. It is our opinion that the proposals rely heavily on legislation to change practice. However, clinical trials are heterogeneous, and as a result some trials will struggle to comply with all of the proposed legislation. Furthermore, adaptive design clinical trials are even more heterogeneous than their non-adaptive counterparts, and face more challenges. Consequently, it is possible that increased legislation could have a greater negative impact on adaptive designs than non-adaptive designs. Overall, we are sceptical that the introduction of legislation will achieve the desired outcomes, with some exceptions. Meanwhile the topic of data sharing - making anonymised individual-level clinical trial data available to other investigators for further use - is entirely absent from the proposals and the consultation in general. However, as an aspect of the wider concept of open science and reproducible research, data sharing is an increasingly important aspect of clinical trials. The benefits of data sharing include faster innovation, improved surveillance of drug safety and effectiveness and decreasing participant exposure to unnecessary risk. There are already a number of UK-focused documents that discuss and encourage data sharing, for example, the Concordat on Open Research Data and the Medical Research Council's Data Sharing Policy. We strongly suggest that data sharing should be the norm rather than the exception, and hope that the forthcoming proposals on clinical trials invite discussion on this important topic.",,pdf:https://trialsjournal.biomedcentral.com/counter/pdf/10.1186/s13063-023-07576-7; doi:https://doi.org/10.1186/s13063-023-07576-7; html:https://europepmc.org/articles/PMC10552399; pdf:https://europepmc.org/articles/PMC10552399?pdf=render 31302040,https://doi.org/10.1016/j.jchf.2019.03.009,Risk for Heart Failure: The Opportunity for Prevention With the American Heart Association's Life's Simple 7.,"Uijl A, Koudstaal S, Vaartjes I, Boer JMA, Verschuren WMM, van der Schouw YT, Asselbergs FW, Hoes AW, Sluijs I.",,JACC. Heart failure,2019,2019-07-10,N,Heart Failure; Cardiovascular Disease Risk Factors; Healthy Lifestyle; Life’s Simple 7,,,"

Objectives

The aim of this study is to determine whether combinations of specific Life's Simple 7 (LS7) components are associated with reduced risk for heart failure (HF).

Background

The American Heart Association recommends the concept of LS7: healthy behaviors that have been shown to reduce cardiovascular disease.

Methods

A total of 37,803 participants from the EPIC-NL (European Prospective Investigation Into Cancer and Nutrition-Netherlands) cohort were included (mean age: 49.4 ± 11.9 years, 74.7% women). The LS7 score ranged from 0 to 14 and was calculated by assigning 0, 1, or 2 points for smoking, physical activity, body mass index, diet, blood pressure, total cholesterol, and blood glucose. An overall ideal score (11 to 14 points) was present in 23.2% of participants, an intermediate score (9 or 10 points) in 35.3%, and an inadequate score (0 to 8 points) in 41.5%.

Results

Over a median follow-up period of 15.2 years (interquartile range: 14.1 to 16.5 years), 690 participants (1.8%) developed HF. In Cox proportional hazards models, ideal and intermediate LS7 scores were associated with reduced risk for HF compared with the inadequate category (hazard ratio: 0.45 [95% confidence interval (CI): 0.34 to 0.60] and hazard ratio: 0.53 [95% CI: 0.44 to 0.64], respectively). Our analyses show that combinations with specific LS7 components, notably glucose, body mass index, smoking, and blood pressure, are associated with a lower incidence of HF.

Conclusions

A healthy lifestyle, as reflected in an ideal LS7 score, was associated with a 55% lower risk for HF compared with an inadequate LS7 score. Preventive strategies that target combinations of specific LS7 components could have a significant impact on decreasing incident HF in the population at large.",,doi:https://doi.org/10.1016/j.jchf.2019.03.009 -37563721,https://doi.org/10.1186/s13063-023-07473-z,Evaluation of interventions to prevent vasovagal reactions among whole blood donors: rationale and design of a large cluster randomised trial.,"McMahon A, Kaptoge S, Walker M, Mehenny S, Gilchrist PT, Sambrook J, Akhtar N, Sweeting M, Wood AM, Stirrups K, Chung R, Fahle S, Johnson E, Cullen D, Godfrey R, Duthie S, Allen L, Harvey P, Berkson M, Allen E, Watkins NA, Bradley JR, Kingston N, Miflin G, Armitage J, Roberts DJ, Danesh J, Di Angelantonio E.",,Trials,2023,2023-08-10,Y,Cross-over; Blood donors; Blood Donation; Factorial Design; Vasovagal Reactions; Cluster Randomised Trial; Stepped-wedge,,,"

Background

Vasovagal reactions (VVRs) are the most common acute complications of blood donation. Responsible for substantial morbidity, they also reduce the likelihood of repeated donations and are disruptive and costly for blood services. Although blood establishments worldwide have adopted different strategies to prevent VVRs (including water loading and applied muscle tension [AMT]), robust evidence is limited. The Strategies to Improve Donor Experiences (STRIDES) trial aims to reliably assess the impact of four different interventions to prevent VVRs among blood donors.

Methods

STRIDES is a cluster-randomised cross-over/stepped-wedge factorial trial of four interventions to reduce VVRs involving about 1.4 million whole blood donors enrolled from all 73 blood donation sites (mobile teams and donor centres) of National Health Service Blood and Transplant (NHSBT) in England. Each site (""cluster"") has been randomly allocated to receive one or more interventions during a 36-month period, using principles of cross-over, stepped-wedge and factorial trial design to assign the sequence of interventions. Each of the four interventions is compared to NHSBT's current practices: (i) 500-ml isotonic drink before donation (vs current 500-ml plain water); (ii) 3-min rest on donation chair after donation (vs current 2 min); (iii) new modified AMT (vs current practice of AMT); and (iv) psychosocial intervention using preparatory materials (vs current practice of nothing). The primary outcome is the number of in-session VVRs with loss of consciousness (i.e. episodes involving loss of consciousness of any duration, with or without additional complications). Secondary outcomes include all in-session VVRs (i.e. with and without loss of consciousness), all delayed VVRs (i.e. those occurring after leaving the venue) and any in-session non-VVR adverse events or reactions.

Discussion

The STRIDES trial should yield novel information about interventions, singly and in combination, for the prevention of VVRs, with the aim of generating policy-shaping evidence to help inform blood services to improve donor health, donor experience, and service efficiency.

Trial registration

ISRCTN: 10412338. Registration date: October 24, 2019.",,doi:https://doi.org/10.1186/s13063-023-07473-z; html:https://europepmc.org/articles/PMC10413586; pdf:https://europepmc.org/articles/PMC10413586?pdf=render 35242820,https://doi.org/10.3389/fcvm.2021.816985,A Systematic Quality Scoring Analysis to Assess Automated Cardiovascular Magnetic Resonance Segmentation Algorithms.,"Rauseo E, Omer M, Amir-Khalili A, Sojoudi A, Le TT, Cook SA, Hausenloy DJ, Ang B, Toh DF, Bryant J, Chin CWL, Paiva JM, Fung K, Cooper J, Khanji MY, Aung N, Petersen SE.",,Frontiers in cardiovascular medicine,2021,2022-02-15,Y,Quality control; Assessment; Machine Learning; Cardiac Segmentation; Cardiac Magnetic Resonance (Cmr); Automated Contouring,,,"

Background

The quantitative measures used to assess the performance of automated methods often do not reflect the clinical acceptability of contouring. A quality-based assessment of automated cardiac magnetic resonance (CMR) segmentation more relevant to clinical practice is therefore needed.

Objective

We propose a new method for assessing the quality of machine learning (ML) outputs. We evaluate the clinical utility of the proposed method as it is employed to systematically analyse the quality of an automated contouring algorithm.

Methods

A dataset of short-axis (SAX) cine CMR images from a clinically heterogeneous population (n = 217) were manually contoured by a team of experienced investigators. On the same images we derived automated contours using a ML algorithm. A contour quality scoring application randomly presented manual and automated contours to four blinded clinicians, who were asked to assign a quality score from a predefined rubric. Firstly, we analyzed the distribution of quality scores between the two contouring methods across all clinicians. Secondly, we analyzed the interobserver reliability between the raters. Finally, we examined whether there was a variation in scores based on the type of contour, SAX slice level, and underlying disease.

Results

The overall distribution of scores between the two methods was significantly different, with automated contours scoring better than the manual (OR (95% CI) = 1.17 (1.07-1.28), p = 0.001; n = 9401). There was substantial scoring agreement between raters for each contouring method independently, albeit it was significantly better for automated segmentation (automated: AC2 = 0.940, 95% CI, 0.937-0.943 vs manual: AC2 = 0.934, 95% CI, 0.931-0.937; p = 0.006). Next, the analysis of quality scores based on different factors was performed. Our approach helped identify trends patterns of lower segmentation quality as observed for left ventricle epicardial and basal contours with both methods. Similarly, significant differences in quality between the two methods were also found in dilated cardiomyopathy and hypertension.

Conclusions

Our results confirm the ability of our systematic scoring analysis to determine the clinical acceptability of automated contours. This approach focused on the contours' clinical utility could ultimately improve clinicians' confidence in artificial intelligence and its acceptability in the clinical workflow.",,pdf:https://www.frontiersin.org/articles/10.3389/fcvm.2021.816985/pdf; doi:https://doi.org/10.3389/fcvm.2021.816985; html:https://europepmc.org/articles/PMC8886212; pdf:https://europepmc.org/articles/PMC8886212?pdf=render +37563721,https://doi.org/10.1186/s13063-023-07473-z,Evaluation of interventions to prevent vasovagal reactions among whole blood donors: rationale and design of a large cluster randomised trial.,"McMahon A, Kaptoge S, Walker M, Mehenny S, Gilchrist PT, Sambrook J, Akhtar N, Sweeting M, Wood AM, Stirrups K, Chung R, Fahle S, Johnson E, Cullen D, Godfrey R, Duthie S, Allen L, Harvey P, Berkson M, Allen E, Watkins NA, Bradley JR, Kingston N, Miflin G, Armitage J, Roberts DJ, Danesh J, Di Angelantonio E.",,Trials,2023,2023-08-10,Y,Cross-over; Blood donors; Blood Donation; Factorial Design; Vasovagal Reactions; Cluster Randomised Trial; Stepped-wedge,,,"

Background

Vasovagal reactions (VVRs) are the most common acute complications of blood donation. Responsible for substantial morbidity, they also reduce the likelihood of repeated donations and are disruptive and costly for blood services. Although blood establishments worldwide have adopted different strategies to prevent VVRs (including water loading and applied muscle tension [AMT]), robust evidence is limited. The Strategies to Improve Donor Experiences (STRIDES) trial aims to reliably assess the impact of four different interventions to prevent VVRs among blood donors.

Methods

STRIDES is a cluster-randomised cross-over/stepped-wedge factorial trial of four interventions to reduce VVRs involving about 1.4 million whole blood donors enrolled from all 73 blood donation sites (mobile teams and donor centres) of National Health Service Blood and Transplant (NHSBT) in England. Each site (""cluster"") has been randomly allocated to receive one or more interventions during a 36-month period, using principles of cross-over, stepped-wedge and factorial trial design to assign the sequence of interventions. Each of the four interventions is compared to NHSBT's current practices: (i) 500-ml isotonic drink before donation (vs current 500-ml plain water); (ii) 3-min rest on donation chair after donation (vs current 2 min); (iii) new modified AMT (vs current practice of AMT); and (iv) psychosocial intervention using preparatory materials (vs current practice of nothing). The primary outcome is the number of in-session VVRs with loss of consciousness (i.e. episodes involving loss of consciousness of any duration, with or without additional complications). Secondary outcomes include all in-session VVRs (i.e. with and without loss of consciousness), all delayed VVRs (i.e. those occurring after leaving the venue) and any in-session non-VVR adverse events or reactions.

Discussion

The STRIDES trial should yield novel information about interventions, singly and in combination, for the prevention of VVRs, with the aim of generating policy-shaping evidence to help inform blood services to improve donor health, donor experience, and service efficiency.

Trial registration

ISRCTN: 10412338. Registration date: October 24, 2019.",,doi:https://doi.org/10.1186/s13063-023-07473-z; html:https://europepmc.org/articles/PMC10413586; pdf:https://europepmc.org/articles/PMC10413586?pdf=render 36243582,https://doi.org/10.1016/j.injury.2022.09.052,Older trauma patients with isolated chest injuries have low rates of complications.,"Ferrah N, Beck B, Ibrahim J, Gabbe B, McLellan MS, Cameron P.",,Injury,2022,2022-10-07,N,Geriatric; Complication; Pneumonia; Chest Trauma; Older; Trauma Centre,,,"

Introduction

The number of older adults hospitalised for injury is growing rapidly. The population-adjusted incidence of isolated thoracic injuries in older adults is also growing. While some older adults are at high risk of post-traumatic complications, not all older adults will need treatment in a major trauma service (MTS). The aim of this study was to characterise older patients with isolated chest injuries, determine the rates of post-traumatic complications, including respiratory failure and pneumonia, and the factors associated with the risk of developing these complications.

Patients and methods

This was a retrospective review of patients aged 65 years and over with isolated chest trauma, from January 2007 to June 2017, using data from the Victorian State Trauma Registry. Patient characteristics and rates of complications were compared between patients with 1. isolated rib fractures, and 2. complex chest injury. Multivariable logistic regression was used to identify predictors of respiratory failure, and pneumonia.

Results

The study population comprised 5401 patients aged 65 years or more, with isolated chest injuries. Two-thirds (65%) of all patients had isolated rib fractures, and 58% of patients (n = 3156) were directly admitted to a non-major trauma centre. Complications were uncommon, with 5.45% of all patients (n = 295) having pneumonia and 3.2% (n = 175) having respiratory failure. Factors associated with increased risk of pneumonia and respiratory failure included advancing age, smoking, chronic obstructive pulmonary disease, congestive heart failure, and more severe and complex chest injury. The adjusted odds of complications were lowest amongst patients not classified as major trauma and receiving definitive treatment in non-MTS.

Discussion

Our findings suggest that rates of complications in older patients with isolated chest trauma in this study were low, and that there is a large group of patients with isolated, uncomplicated rib fractures, who may not need to be treated in a major trauma centre. Further work should be undertaken to appropriately risk stratify and manage older adults with isolated chest trauma.",,doi:https://doi.org/10.1016/j.injury.2022.09.052 36355406,https://doi.org/10.2196/40707,Effectiveness of a Web-Based Intervention to Prevent Anxiety in the Children of Parents With Anxiety: Protocol for a Randomized Controlled Trial.,"Dunn A, Alvarez J, Arbon A, Bremner S, Elsby-Pearson C, Emsley R, Jones C, Lawrence P, Lester KJ, Majdandžić M, Morson N, Perry N, Simner J, Thomson A, Cartwright-Hatton S.",,JMIR research protocols,2022,2022-11-10,Y,Child; Parent; Youth; Anxiety; Pediatric; Mental health; Randomized controlled trial; Parenting; Rct; Online; Mental Well-being; Online Intervention; Digital Intervention,,,"

Background

Anxiety is the most common childhood mental health condition and is associated with impaired child outcomes, including increased risk of mental health difficulties in adulthood. Anxiety runs in families: when a parent has anxiety, their child has a 50% higher chance of developing it themselves. Environmental factors are predominant in the intergenerational transmission of anxiety and, of these, parenting processes play a major role. Interventions that target parents to support them to limit the impact of any anxiogenic parenting behaviors are associated with reduced anxiety in their children. A brief UK-based group intervention delivered to parents within the UK National Health Service led to a 16% reduction in children meeting the criteria for an anxiety disorder. However, this intervention is not widely accessible. To widen access, a 9-module web-based version of this intervention has been developed. This course comprises psychoeducation and home practice delivered through text, video, animations, and practice tasks.

Objective

This study seeks to evaluate the feasibility of delivering this web-based intervention and assess its effectiveness in reducing child anxiety symptoms.

Methods

 This is the protocol for a randomized controlled trial (RCT) of a community sample of 1754 parents with self-identified high levels of anxiety with a child aged 2-11 years. Parents in the intervention arm will receive access to the web-based course, which they undertake at a self-determined rate. The control arm receives no intervention. Follow-up data collection is at months 6 and months 9-21. Intention-to-treat analysis will be conducted on outcomes including child anxiety, child mental health symptoms, and well-being; parental anxiety and well-being; and parenting behaviors.

Results

Funding was received in April 2020, and recruitment started in February 2021 and is projected to end in October 2022. A total of 1350 participants have been recruited as of May 2022.

Conclusions

The results of this RCT will provide evidence on the utility of a web-based course in preventing intergenerational transmission of anxiety and increase the understanding of familial anxiety.

Trial registration

ClinicalTrials.gov NCT04755933; https://clinicaltrials.gov/ct2/show/NCT04755933.

International registered report identifier (irrid)

DERR1-10.2196/40707.",,pdf:https://jmir.org/api/download?alt_name=resprot_v11i11e40707_app2.pdf&filename=4e6914231a45b12439d1932b760a7c34.pdf; doi:https://doi.org/10.2196/40707; html:https://europepmc.org/articles/PMC9693706 37757876,https://doi.org/10.1097/ede.0000000000001649,Comparative Effectiveness of Dynamic Treatment Strategies for Medication Use and Dosage: Emulating a Target Trial Using Observational Data.,"Birnie K, Tomson C, Caskey FJ, Ben-Shlomo Y, Nitsch D, Casula A, Murray EJ, Sterne JAC.",,"Epidemiology (Cambridge, Mass.)",2023,2023-09-26,N,,,,"

Background

Availability of detailed data from electronic health records (EHRs) has increased the potential to examine the comparative effectiveness of dynamic treatment strategies using observational data. Inverse probability (IP) weighting of dynamic marginal structural models can control for time-varying confounders. However, IP weights for continuous treatments may be sensitive to model choice.

Methods

We describe a target trial comparing strategies for treating anemia with darbepoetin in hemodialysis patients using EHR data from the UK Renal Registry 2004 to 2016. Patients received a specified dose (microgram/week) or did not receive darbepoetin. We compared 4 methods for modeling time-varying treatment: (A) logistic regression for zero dose, standard linear regression for log dose; (B) logistic regression for zero dose, heteroscedastic linear regression for log dose; (C) logistic regression for zero dose, heteroscedastic linear regression for log dose, multinomial regression for patients who recently received very low or high doses; and (D) ordinal logistic regression.

Results

For this dataset, method (C) was the only approach that provided a robust estimate of the mortality hazard ratio (HR), with less-extreme weights in a fully weighted analysis and no substantial change of the HR point estimate after weight truncation. After truncating IP weights at the 95th percentile, estimates were similar across the methods.

Conclusions

EHR data can be used to emulate target trials estimating the comparative effectiveness of dynamic strategies adjusting treatment to evolving patient characteristics. However, model checking, monitoring of large weights, and adaptation of model strategies to account for these is essential if an aspect of treatment is continuous.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7615288; doi:https://doi.org/10.1097/EDE.0000000000001649; html:https://europepmc.org/articles/PMC7615288; pdf:https://europepmc.org/articles/PMC7615288?pdf=render; doi:https://doi.org/10.1097/ede.0000000000001649 @@ -1401,15 +1401,15 @@ PMC8855010,https://doi.org/,POS-894 PREDICTING PANDEMIC-RELATED EXCESS-DEATH USI 35202588,https://doi.org/10.1016/s2213-8587(22)00015-8,Dose-response relationships for vitamin D and all-cause mortality - Authors' reply.,"Burgess S, Butterworth AS.",,The lancet. Diabetes & endocrinology,2022,2022-03-01,N,,,,,,pdf:http://www.thelancet.com/article/S2213858722000158/pdf; doi:https://doi.org/10.1016/S2213-8587(22)00015-8 37730605,https://doi.org/10.1186/s12889-023-16523-9,Inequalities and mental health during the Coronavirus pandemic in the UK: a mixed-methods exploration.,"Lombardo C, Guo L, Solomon S, Crepaz-Keay D, McDaid S, Thorpe L, Martin S, John A, Morton A, Davidson G, Kousoulis AA, Van Bortel T.",,BMC public health,2023,2023-09-20,Y,Coronavirus; Mental health; Pandemic; United Kingdom; Inequalities; Social Determinants; Inequity; Adult Population; Covid-19,,,"

Background

The World Health Organisation declared the novel Coronavirus disease (COVID-19) a global pandemic on 11th March 2020. Since then, the world has been firmly in its grip. At the time of writing, there were more than 767,972,961 million confirmed cases and over 6,950,655 million deaths. While the main policy focus has been on controlling the virus and ensuring vaccine roll-out and uptake, the population mental health impacts of the pandemic are expected to be long-term, with certain population groups affected more than others.

Methods

The overall objectives of our 'Coronavirus: Mental Health and the Pandemic' study were to explore UK adults' experiences of the Coronavirus pandemic and to gain insights into the mental health impacts, population-level changes over time, current and future mental health needs, and how these can best be addressed. The wider mixed-methods study consisted of repeated cross-sectional surveys and embedded qualitative sub-studies including in-depth interviews and focus group discussions with the wider UK adult population. For this particular inequalities and mental health sub-study, we used mixed methods data from our cross-sectional surveys and we carried out three Focus Group Discussions with a maximum variation sample from across the UK adult population. The discussions covered the broader topic of 'Inequalities and mental health during the Coronavirus pandemic in the UK' and took place online between April and August 2020. Focus Groups transcripts were analysed using thematic analysis in NVIVO. Cross-sectional survey data were analysed using STATA for descriptive statistics.

Results

Three broad main themes emerged, each supporting a number of sub-themes: (1) Impacts of the pandemic; (2) Moving forward: needs and recommendations; (3) Coping mechanisms and resilience. Findings showed that participants described their experiences of the pandemic in relation to its impact on themselves and on different groups of people. Their experiences illustrated how the pandemic and subsequent measures had exacerbated existing inequalities and created new ones, and triggered various emotional responses. Participants also described their coping strategies and what worked and did not work for them, as well as support needs and recommendations for moving forward through, and out of, the pandemic; all of which are valuable learnings to be considered in policy making for improving mental health and for ensuring future preparedness.

Conclusions

The pandemic is taking a long-term toll on the nations' mental health which will continue to have impacts for years to come. It is therefore crucial to learn the vital lessons learned from this pandemic. Specific as well as whole-government policies need to respond to this, address inequalities and the different needs across the life-course and across society, and take a holistic approach to mental health improvement across the UK.",,pdf:https://bmcpublichealth.biomedcentral.com/counter/pdf/10.1186/s12889-023-16523-9; doi:https://doi.org/10.1186/s12889-023-16523-9; html:https://europepmc.org/articles/PMC10510114; pdf:https://europepmc.org/articles/PMC10510114?pdf=render 34145643,https://doi.org/10.1111/jdv.17450,Describing the burden of the COVID-19 pandemic in people with psoriasis: findings from a global cross-sectional study.,"Mahil SK, Yates M, Yiu ZZN, Langan SM, Tsakok T, Dand N, Mason KJ, McAteer H, Meynell F, Coker B, Vincent A, Urmston D, Vesty A, Kelly J, Lancelot C, Moorhead L, Bachelez H, Capon F, Contreras CR, De La Cruz C, Di Meglio P, Gisondi P, Jullien D, Lambert J, Naldi L, Norton S, Puig L, Spuls P, Torres T, Warren RB, Waweru H, Weinman J, Brown MA, Galloway JB, Griffiths CM, Barker JN, Smith CH, PsoProtect study group.",,Journal of the European Academy of Dermatology and Venereology : JEADV,2021,2021-08-19,Y,,,,,,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/jdv.17450; doi:https://doi.org/10.1111/jdv.17450; html:https://europepmc.org/articles/PMC8447018; pdf:https://europepmc.org/articles/PMC8447018?pdf=render -37884627,https://doi.org/10.1038/s41591-023-02608-w,The value of standards for health datasets in artificial intelligence-based applications.,"Arora A, Alderman JE, Palmer J, Ganapathi S, Laws E, McCradden MD, Oakden-Rayner L, Pfohl SR, Ghassemi M, McKay F, Treanor D, Rostamzadeh N, Mateen B, Gath J, Adebajo AO, Kuku S, Matin R, Heller K, Sapey E, Sebire NJ, Cole-Lewis H, Calvert M, Denniston A, Liu X.",,Nature medicine,2023,2023-10-26,Y,,,,"Artificial intelligence as a medical device is increasingly being applied to healthcare for diagnosis, risk stratification and resource allocation. However, a growing body of evidence has highlighted the risk of algorithmic bias, which may perpetuate existing health inequity. This problem arises in part because of systemic inequalities in dataset curation, unequal opportunity to participate in research and inequalities of access. This study aims to explore existing standards, frameworks and best practices for ensuring adequate data diversity in health datasets. Exploring the body of existing literature and expert views is an important step towards the development of consensus-based guidelines. The study comprises two parts: a systematic review of existing standards, frameworks and best practices for healthcare datasets; and a survey and thematic analysis of stakeholder views of bias, health equity and best practices for artificial intelligence as a medical device. We found that the need for dataset diversity was well described in literature, and experts generally favored the development of a robust set of guidelines, but there were mixed views about how these could be implemented practically. The outputs of this study will be used to inform the development of standards for transparency of data diversity in health datasets (the STANDING Together initiative).",,pdf:https://www.nature.com/articles/s41591-023-02608-w.pdf; doi:https://doi.org/10.1038/s41591-023-02608-w; html:https://europepmc.org/articles/PMC10667100; pdf:https://europepmc.org/articles/PMC10667100?pdf=render 34642218,https://doi.org/10.1136/bcr-2021-243424,Neurological injury from virtual reality mishap.,"Warner N, Teo JT.",,BMJ case reports,2021,2021-10-12,Y,Cranial nerves; Neurology; Neurological Injury; Trauma Cns /Pns,,,"Consumer virtual reality systems are becoming increasingly popular with the increasing availability of devices and gamified technologies. Self-sustained injury risks exist with the use of this technology in the uncontrolled home environment, however, the public awareness of these risks may not be recognised. We present a case of a low- impact virtual reality fall resulting in spinal cord injury, hypoglossal nerve injury, vertebral artery dissection and traumatic brain injury.",,pdf:https://casereports.bmj.com/content/bmjcr/14/10/e243424.full.pdf; doi:https://doi.org/10.1136/bcr-2021-243424; html:https://europepmc.org/articles/PMC8513217; pdf:https://europepmc.org/articles/PMC8513217?pdf=render +37884627,https://doi.org/10.1038/s41591-023-02608-w,The value of standards for health datasets in artificial intelligence-based applications.,"Arora A, Alderman JE, Palmer J, Ganapathi S, Laws E, McCradden MD, Oakden-Rayner L, Pfohl SR, Ghassemi M, McKay F, Treanor D, Rostamzadeh N, Mateen B, Gath J, Adebajo AO, Kuku S, Matin R, Heller K, Sapey E, Sebire NJ, Cole-Lewis H, Calvert M, Denniston A, Liu X.",,Nature medicine,2023,2023-10-26,Y,,,,"Artificial intelligence as a medical device is increasingly being applied to healthcare for diagnosis, risk stratification and resource allocation. However, a growing body of evidence has highlighted the risk of algorithmic bias, which may perpetuate existing health inequity. This problem arises in part because of systemic inequalities in dataset curation, unequal opportunity to participate in research and inequalities of access. This study aims to explore existing standards, frameworks and best practices for ensuring adequate data diversity in health datasets. Exploring the body of existing literature and expert views is an important step towards the development of consensus-based guidelines. The study comprises two parts: a systematic review of existing standards, frameworks and best practices for healthcare datasets; and a survey and thematic analysis of stakeholder views of bias, health equity and best practices for artificial intelligence as a medical device. We found that the need for dataset diversity was well described in literature, and experts generally favored the development of a robust set of guidelines, but there were mixed views about how these could be implemented practically. The outputs of this study will be used to inform the development of standards for transparency of data diversity in health datasets (the STANDING Together initiative).",,pdf:https://www.nature.com/articles/s41591-023-02608-w.pdf; doi:https://doi.org/10.1038/s41591-023-02608-w; html:https://europepmc.org/articles/PMC10667100; pdf:https://europepmc.org/articles/PMC10667100?pdf=render 34143303,https://doi.org/10.1007/s00787-021-01817-3,National record-linkage study of hospital admissions for schizophrenia in childhood and adolescence in England.,"Seminog O, Hoang U, Goldacre M, James A.",,European child & adolescent psychiatry,2022,2021-06-18,Y,Schizophrenia; Children; epidemiology; Electronic Records; Childhood Onset,,,"

Background

There is a lack of information on changes in hospital admission rates for childhood-onset schizophrenia (COS), or on patient characteristics, to inform clinical research and health service provision.

Aims

To report age- and sex-specific incidence rates of hospital admissions and day patient care for schizophrenia (ICD-10 F20) and non-affective psychosis (ICD-10 F20-29), by year of occurrence and age, in childhood and adolescence.

Methods

Population-based study using person-linked data for England (available 2001-2016); time-periods in single years and 4-year groups.

Results

Hospitalised incidence for schizophrenia increased with increasing age, from 0.03 (95% confidence interval (CI) 0.02-0.05) and 0.01 (0-0.01) per 100,000 in, respectively, males and females aged 5-12 years, to 3.67 (3.44-3.91) in males and 1.58 (1.43-1.75) in females aged 13-17 years. There was no gender difference in hospitalised incidence rates in children aged 5-12, but in 13-17 years old, there was a male excess. Rates for schizophrenia were stable over time in 5-12 years old. In ages 13-17, rates for schizophrenia decreased between 2001-2004 and 2013-2016 in males, from 6.65 (6.04-7.31) down to 1.40 (1.13-1.73), and in females from 2.42 (2.05-2.83) to 1.18 (0.92-1.48). The hospitalisation rates for schizophrenia and non-affective psychosis, combined, in 13-17 years old decreased in males from 14.20 (13.30-15.14) in 2001-2004 to 10.77 (9.97-11.60) in 2013-2016, but increased in females from 7.49 (6.83-8.20) to 10.16 (9.38-11.00).

Conclusions

The study confirms that childhood-onset schizophrenia is extremely rare, with only 32 cases identified over a 15-year period in the whole of England. The incidence of schizophrenia and non-affective psychosis increased substantially in adolescence; however, the marked reduction in the proportion of those diagnosed with schizophrenia in this age group suggests a possible change in diagnostic practice.",,pdf:https://link.springer.com/content/pdf/10.1007/s00787-021-01817-3.pdf; doi:https://doi.org/10.1007/s00787-021-01817-3; html:https://europepmc.org/articles/PMC9663394; pdf:https://europepmc.org/articles/PMC9663394?pdf=render 32355555,https://doi.org/10.7189/jogh.10.010104,COVID-19 must catalyse key global natural experiments.,"Been JV, Sheikh A.",,Journal of global health,2020,2020-06-01,Y,,,,,"""Been and Sheikh’s editorial about COVID-19, outlines the importance of two natural experiments: a- how different countries responded to the pandemic and its effects and b- impact of improvements in air quality on human and planetary health.""",doi:https://doi.org/10.7189/jogh.10.010104; doi:https://doi.org/10.7189/jogh.10.010104; html:https://europepmc.org/articles/PMC7179980; pdf:https://europepmc.org/articles/PMC7179980?pdf=render -35048949,https://doi.org/10.1093/eurjpc/zwac008,Light to moderate coffee consumption is associated with lower risk of death: a UK Biobank study.,"Simon J, Fung K, Raisi-Estabragh Z, Aung N, Khanji MY, Kolossváry M, Merkely B, Munroe PB, Harvey NC, Piechnik SK, Neubauer S, Petersen SE, Maurovich-Horvat P.",,European journal of preventive cardiology,2022,2022-05-01,N,Cardiac Magnetic Resonance; Cardiovascular Health; Coffee Consumption,,,"

Aims

To study the association of daily coffee consumption with all-cause and cardiovascular (CV) mortality and major CV outcomes. In a subgroup of participants who underwent cardiovascular magnetic resonance (CMR) imaging, we evaluated the association between regular coffee intake and cardiac structure and function.

Methods and results

UK Biobank participants without clinically manifested heart disease at the time of recruitment were included. Regular coffee intake was categorized into three groups: zero, light-to-moderate (0.5-3 cups/day), and high (>3 cups/day). In the multivariate analysis, we adjusted for the main CV risk factors. We included 468 629 individuals (56.2 ± 8.1 years, 44.2% male), of whom 22.1% did not consume coffee regularly, 58.4% had 0.5-3 cups per day, and 19.5% had >3 cups per day. Compared to non-coffee drinkers, light-to-moderate (0.5-3 cups per day) coffee drinking was associated with lower risk of all-cause mortality [multivariate hazard ratio (HR) = 0.88, 95% confidence interval (CI): 0.83-0.92; P < 0.001] and CV mortality (multivariate HR = 0.83, 95% CI: 0.74-0.94; P = 0.006), and incident stroke (multivariate HR = 0.79, 95% CI: 0.63-0.99 P = 0.037) after a median follow-up of 11 years. CMR data were available in 30 650 participants. Both light-to-moderate and high coffee consuming categories were associated with dose-dependent increased left and right ventricular end-diastolic, end-systolic and stroke volumes, and greater left ventricular mass.

Conclusion

Coffee consumption of up to three cups per day was associated with favourable CV outcomes. Regular coffee consumption was also associated with a likely healthy pattern of CMR metrics in keeping with the reverse of age-related cardiac alterations.",,pdf:https://academic.oup.com/eurjpc/article-pdf/29/6/982/43589594/zwac008.pdf; doi:https://doi.org/10.1093/eurjpc/zwac008 34306597,https://doi.org/10.1155/2021/6663884,Automatic Prediction of Recurrence of Major Cardiovascular Events: A Text Mining Study Using Chest X-Ray Reports.,"Bagheri A, Groenhof TKJ, Asselbergs FW, Haitjema S, Bots ML, Veldhuis WB, de Jong PA, Oberski DL.",,Journal of healthcare engineering,2021,2021-07-09,Y,,,,"

Methods

We used EHR data of patients included in the Second Manifestations of ARTerial disease (SMART) study. We propose a deep learning-based multimodal architecture for our text mining pipeline that integrates neural text representation with preprocessed clinical predictors for the prediction of recurrence of major cardiovascular events in cardiovascular patients. Text preprocessing, including cleaning and stemming, was first applied to filter out the unwanted texts from X-ray radiology reports. Thereafter, text representation methods were used to numerically represent unstructured radiology reports with vectors. Subsequently, these text representation methods were added to prediction models to assess their clinical relevance. In this step, we applied logistic regression, support vector machine (SVM), multilayer perceptron neural network, convolutional neural network, long short-term memory (LSTM), and bidirectional LSTM deep neural network (BiLSTM).

Results

We performed various experiments to evaluate the added value of the text in the prediction of major cardiovascular events. The two main scenarios were the integration of radiology reports (1) with classical clinical predictors and (2) with only age and sex in the case of unavailable clinical predictors. In total, data of 5603 patients were used with 5-fold cross-validation to train the models. In the first scenario, the multimodal BiLSTM (MI-BiLSTM) model achieved an area under the curve (AUC) of 84.7%, misclassification rate of 14.3%, and F1 score of 83.8%. In this scenario, the SVM model, trained on clinical variables and bag-of-words representation, achieved the lowest misclassification rate of 12.2%. In the case of unavailable clinical predictors, the MI-BiLSTM model trained on radiology reports and demographic (age and sex) variables reached an AUC, F1 score, and misclassification rate of 74.5%, 70.8%, and 20.4%, respectively.

Conclusions

Using the case study of routine care chest X-ray radiology reports, we demonstrated the clinical relevance of integrating text features and classical predictors in our text mining pipeline for cardiovascular risk prediction. The MI-BiLSTM model with word embedding representation appeared to have a desirable performance when trained on text data integrated with the clinical variables from the SMART study. Our results mined from chest X-ray reports showed that models using text data in addition to laboratory values outperform those using only known clinical predictors.",,pdf:https://downloads.hindawi.com/journals/jhe/2021/6663884.pdf; doi:https://doi.org/10.1155/2021/6663884; html:https://europepmc.org/articles/PMC8285182; pdf:https://europepmc.org/articles/PMC8285182?pdf=render +35048949,https://doi.org/10.1093/eurjpc/zwac008,Light to moderate coffee consumption is associated with lower risk of death: a UK Biobank study.,"Simon J, Fung K, Raisi-Estabragh Z, Aung N, Khanji MY, Kolossváry M, Merkely B, Munroe PB, Harvey NC, Piechnik SK, Neubauer S, Petersen SE, Maurovich-Horvat P.",,European journal of preventive cardiology,2022,2022-05-01,N,Cardiac Magnetic Resonance; Cardiovascular Health; Coffee Consumption,,,"

Aims

To study the association of daily coffee consumption with all-cause and cardiovascular (CV) mortality and major CV outcomes. In a subgroup of participants who underwent cardiovascular magnetic resonance (CMR) imaging, we evaluated the association between regular coffee intake and cardiac structure and function.

Methods and results

UK Biobank participants without clinically manifested heart disease at the time of recruitment were included. Regular coffee intake was categorized into three groups: zero, light-to-moderate (0.5-3 cups/day), and high (>3 cups/day). In the multivariate analysis, we adjusted for the main CV risk factors. We included 468 629 individuals (56.2 ± 8.1 years, 44.2% male), of whom 22.1% did not consume coffee regularly, 58.4% had 0.5-3 cups per day, and 19.5% had >3 cups per day. Compared to non-coffee drinkers, light-to-moderate (0.5-3 cups per day) coffee drinking was associated with lower risk of all-cause mortality [multivariate hazard ratio (HR) = 0.88, 95% confidence interval (CI): 0.83-0.92; P < 0.001] and CV mortality (multivariate HR = 0.83, 95% CI: 0.74-0.94; P = 0.006), and incident stroke (multivariate HR = 0.79, 95% CI: 0.63-0.99 P = 0.037) after a median follow-up of 11 years. CMR data were available in 30 650 participants. Both light-to-moderate and high coffee consuming categories were associated with dose-dependent increased left and right ventricular end-diastolic, end-systolic and stroke volumes, and greater left ventricular mass.

Conclusion

Coffee consumption of up to three cups per day was associated with favourable CV outcomes. Regular coffee consumption was also associated with a likely healthy pattern of CMR metrics in keeping with the reverse of age-related cardiac alterations.",,pdf:https://academic.oup.com/eurjpc/article-pdf/29/6/982/43589594/zwac008.pdf; doi:https://doi.org/10.1093/eurjpc/zwac008 37408046,https://doi.org/10.1186/s40545-023-00590-9,Delivering the precision oncology paradigm: reduced R&D costs and greater return on investment through a companion diagnostic informed precision oncology medicines approach.,"Henderson RH, French D, Stewart E, Smart D, Idica A, Redmond S, Eckstein M, Clark J, Sullivan R, Keeling P, Lawler M.",,Journal of pharmaceutical policy and practice,2023,2023-07-05,Y,,,,"

Background

Precision oncology medicines represent a paradigm shift compared to non-precision oncology medicines in cancer therapy, in some situations delivering more clinical benefit, and potentially lowering healthcare costs. We determined whether employing a companion diagnostic (CDx) approach during oncology medicines development delivers effective therapies that are within the cost constraints of current health systems. R&D costs of developing a medicine are subject to debate, with average estimates ranging from $765 million (m) to $4.6 billion (b). Our aim was to determine whether precision oncology medicines are cheaper to bring from R&D to market; a secondary goal was to determine whether precision oncology medicines have a greater return on investment (ROI).

Method

Data on oncology medicines approved between 1997 and 2020 by the US Food and Drug Administration (FDA) were analysed from the Securities and Exchange Commission (SEC) filings. Data were compiled from 10-K, 10-Q, and 20-F financial performance filings on medicines' development costs through their R&D lifetime. Clinical trial data were split into clinical trial phases 1-3 and probability of success (POS) of trials was calculated, along with preclinical costs. Cost-of-capital (CoC) approach was applied and, if appropriate, a tax rebate was subtracted from the total.

Results

Data on 42 precision and 29 non-precision oncology medicines from 56 companies listed by the National Cancer Institute which had complete data available were analysed. Estimated mean cost to deliver a new oncology medicine was $4.4b (95% CI, $3.6-5.2b). Costs to bring a precision oncology medicine to market were $1.1b less ($3.5b; 95% CI, $2.7-4.5b) compared to non-precision oncology medicines ($4.6b; 95% CI, $3.5-6.1b). The key driver of costs was POS of clinical trials, accounting for a difference of $591.3 m. Additional data analysis illustrated that there was a 27% increase in return on investment (ROI) of precision oncology medicines over non-precision oncology medicines.

Conclusion

Our results provide an accurate estimate of the R&D spend required to bring an oncology medicine to market. Deployment of a CDx at the earliest stage substantially lowers the cost associated with oncology medicines development, potentially making them available to more patients, while staying within the cost constraints of cancer health systems.",,pdf:https://joppp.biomedcentral.com/counter/pdf/10.1186/s40545-023-00590-9; doi:https://doi.org/10.1186/s40545-023-00590-9; html:https://europepmc.org/articles/PMC10320864; pdf:https://europepmc.org/articles/PMC10320864?pdf=render -38279797,https://doi.org/10.1089/neu.2023.0465,The Australian Traumatic Brain Injury Initiative: Systematic Review of the Effect of Acute Interventions on Outcome for People With Moderate-Severe Traumatic Brain Injury.,"Keeves J, Gadowski A, McKimmie A, Bagg MK, Antonic-Baker A, Hicks AJ, Clarke N, Brown A, McNamara R, Reeder S, Roman C, Jeffcote T, Romero L, Hill R, Ponsford JL, Lannin NA, O'Brien TJ, Cameron PA, Rushworth N, Fitzgerald M, Gabbe BJ, Cooper DJ.",,Journal of neurotrauma,2024,2024-04-08,N,"Common Data Elements; Brain Injuries, Traumatic; Outcome Assessment, Health Care; Systematic Review [Publication Type]; Emergency Medical Services, Critical Care, Early Medical Intervention",,,"The Australian Traumatic Brain Injury Initiative (AUS-TBI) is developing a data resource to enable improved outcome prediction for people with moderate-severe TBI (msTBI) across Australia. Fundamental to this resource is the collaboratively designed data dictionary. This systematic review and consultation aimed to identify acute interventions with potential to modify clinical outcomes for people after msTBI, for inclusion in a data dictionary. Standardized searches were implemented across bibliographic databases from inception through April 2022. English-language reports of randomized controlled trials (RCTs) evaluating any association between any acute intervention and clinical outcome in at least 100 patients with msTBI, were included. A predefined algorithm was used to assign a value to each observed association. Consultation with AUS-TBI clinicians and researchers formed the consensus process for interventions to be included in a single data dictionary. Searches retrieved 14,455 records, of which 124 full-length RCTs were screened, with 35 studies included. These studies evaluated 26 unique acute interventions across 21 unique clinical outcomes. Only 4 interventions were considered to have medium modifying value for any outcome from the review, with an additional 8 interventions agreed upon through the consensus process. The interventions with medium value were tranexamic acid and phenytoin, which had a positive effect on an outcome; and decompressive craniectomy surgery and hypothermia, which negatively affected outcomes. From the systematic review and consensus process, 12 interventions were identified as potential modifiers to be included in the AUS-TBI national data resource.",,doi:https://doi.org/10.1089/neu.2023.0465 37190768,https://doi.org/10.1017/s2045796023000276,The mental health of all children in contact with social services: a population-wide record-linkage study in Northern Ireland.,"McKenna S, O'Reilly D, Maguire A.",,Epidemiology and psychiatric sciences,2023,2023-05-16,Y,Mental health; Data Linkage; Children’s Social Care,,,"

Aims

Children in contact with social services are at high risk for mental ill health, but it is not known what proportion of the child population has contact with social services or how risk varies within this group compared to unexposed peers. We aim to quantify the extent and nature of contact with social services within the child population in Northern Ireland (NI) and the association with mental ill health. We also examine which social care experiences identify those most at risk.

Methods

This is a population-based record-linkage study of 497,269 children (aged under 18 years) alive and resident in NI in 2015 using routinely collected health and social care data. Exposure was categorized as (1) no contact, (2) referred but assessed as not in need (NIN), (3) child in need (CIN) and (4) child in care (CIC). Multilevel logistic regression analyses estimated odds ratios (ORs) for mental ill health indicated by receipt of psychotropic medication (antidepressants, anxiolytics, antipsychotics and hypnotics), psychiatric hospital admission and hospital-presenting self-harm or ideation.

Results

Over one in six children (17.2%, n = 85,792) were currently or previously in contact with social services, and almost one child in every 20 (4.8%, n = 23,975) had contact in 2015. Likelihood of any mental ill health outcome increased incrementally with the level of contact with social services relative to unexposed peers: NIN (OR 5.90 [95% confidence interval (CI) 5.10-6.83]), CIN (OR 5.99 [95% CI 5.50-6.53]) and CIC (OR 12.60 [95% CI 10.63-14.95]). All tiers of contact, number of referrals, number of care episodes and placement type were strongly associated with the likelihood of mental ill health.

Conclusion

Children who have contact with social services account for a large and disproportionate amount of mental ill health in the child population. Likelihood of poor mental health across indicators is highest in care experienced children but also extends to the much larger population of children in contact with social services but never in care. Findings suggest a need for targeted mental health screening and enhanced support for all children in contact with social services.",,pdf:https://www.cambridge.org/core/services/aop-cambridge-core/content/view/A60E6D761449A937DCE08F3A075B236D/S2045796023000276a.pdf/div-class-title-the-mental-health-of-all-children-in-contact-with-social-services-a-population-wide-record-linkage-study-in-northern-ireland-div.pdf; doi:https://doi.org/10.1017/S2045796023000276; html:https://europepmc.org/articles/PMC10227534; pdf:https://europepmc.org/articles/PMC10227534?pdf=render +38279797,https://doi.org/10.1089/neu.2023.0465,The Australian Traumatic Brain Injury Initiative: Systematic Review of the Effect of Acute Interventions on Outcome for People With Moderate-Severe Traumatic Brain Injury.,"Keeves J, Gadowski A, McKimmie A, Bagg MK, Antonic-Baker A, Hicks AJ, Clarke N, Brown A, McNamara R, Reeder S, Roman C, Jeffcote T, Romero L, Hill R, Ponsford JL, Lannin NA, O'Brien TJ, Cameron PA, Rushworth N, Fitzgerald M, Gabbe BJ, Cooper DJ.",,Journal of neurotrauma,2024,2024-04-08,N,"Common Data Elements; Brain Injuries, Traumatic; Outcome Assessment, Health Care; Systematic Review [Publication Type]; Emergency Medical Services, Critical Care, Early Medical Intervention",,,"The Australian Traumatic Brain Injury Initiative (AUS-TBI) is developing a data resource to enable improved outcome prediction for people with moderate-severe TBI (msTBI) across Australia. Fundamental to this resource is the collaboratively designed data dictionary. This systematic review and consultation aimed to identify acute interventions with potential to modify clinical outcomes for people after msTBI, for inclusion in a data dictionary. Standardized searches were implemented across bibliographic databases from inception through April 2022. English-language reports of randomized controlled trials (RCTs) evaluating any association between any acute intervention and clinical outcome in at least 100 patients with msTBI, were included. A predefined algorithm was used to assign a value to each observed association. Consultation with AUS-TBI clinicians and researchers formed the consensus process for interventions to be included in a single data dictionary. Searches retrieved 14,455 records, of which 124 full-length RCTs were screened, with 35 studies included. These studies evaluated 26 unique acute interventions across 21 unique clinical outcomes. Only 4 interventions were considered to have medium modifying value for any outcome from the review, with an additional 8 interventions agreed upon through the consensus process. The interventions with medium value were tranexamic acid and phenytoin, which had a positive effect on an outcome; and decompressive craniectomy surgery and hypothermia, which negatively affected outcomes. From the systematic review and consensus process, 12 interventions were identified as potential modifiers to be included in the AUS-TBI national data resource.",,doi:https://doi.org/10.1089/neu.2023.0465 36198485,https://doi.org/10.1136/jech-2021-217986,Characteristics of enrolment in an intensive home-visiting programme among eligible first-time adolescent mothers in England: a linked administrative data cohort study.,"Cavallaro FL, Gilbert R, Wijlaars LP, Kennedy E, Howarth E, Kendall S, van der Meulen J, Calin MA, Reed L, Harron K.",,Journal of epidemiology and community health,2022,2022-10-05,Y,Adolescent; Public Health; Child Health,,,"

Background

Intensive home visiting for adolescent mothers may help reduce health disparities. Given limited resources, such interventions need to be effectively targeted. We evaluated which mothers were enrolled in the Family Nurse Partnership (FNP), an intensive home-visiting service for first-time young mothers commissioned in >130 local authorities in England since 2007.

Methods

We created a population-based cohort of first-time mothers aged 13-19 years giving birth in English National Health Service hospitals between 1 April 2010 and 31 March 2017, using administrative hospital data linked with FNP programme, educational and social care data. Mothers living in a local authority with an active FNP site were eligible. We described variation in enrolment rates across sites, and identified maternal and FNP site characteristics associated with enrolment.

Results

Of 110 520 eligible mothers, 25 680 (23.2% (95% CI: 23.0% to 23.5%)) were enrolled. Enrolment rates varied substantially across 122 sites (range: 11%-68%), and areas with greater numbers of first-time adolescent mothers achieved lower enrolment rates. Mothers aged 13-15 years were most likely to be enrolled (52%). However, only 26% of adolescent mothers with markers of vulnerability (including living in the most deprived areas and ever having been looked after as a child) were enrolled.

Conclusion

A substantial proportion of first-time adolescent mothers with vulnerability markers were not enrolled in FNP. Variation in enrolment across sites indicates insufficient commissioning of places that is not proportional to level of need, with mothers in areas with large numbers of other adolescent mothers least likely to receive support.",,pdf:https://jech.bmj.com/content/jech/76/12/991.full.pdf; doi:https://doi.org/10.1136/jech-2021-217986; html:https://europepmc.org/articles/PMC9664100; pdf:https://europepmc.org/articles/PMC9664100?pdf=render 33240510,https://doi.org/10.15420/aer.2020.26,Big Data and Artificial Intelligence: Opportunities and Threats in Electrophysiology.,"van de Leur RR, Boonstra MJ, Bagheri A, Roudijk RW, Sammani A, Taha K, Doevendans PA, van der Harst P, van Dam PM, Hassink RJ, van Es R, Asselbergs FW.",,Arrhythmia & electrophysiology review,2020,2020-11-01,Y,Artificial intelligence; Electrophysiology; Neural networks; ECG; Cardiology; Big Data; Deep Learning,,,"The combination of big data and artificial intelligence (AI) is having an increasing impact on the field of electrophysiology. Algorithms are created to improve the automated diagnosis of clinical ECGs or ambulatory rhythm devices. Furthermore, the use of AI during invasive electrophysiological studies or combining several diagnostic modalities into AI algorithms to aid diagnostics are being investigated. However, the clinical performance and applicability of created algorithms are yet unknown. In this narrative review, opportunities and threats of AI in the field of electrophysiology are described, mainly focusing on ECGs. Current opportunities are discussed with their potential clinical benefits as well as the challenges. Challenges in data acquisition, model performance, (external) validity, clinical implementation, algorithm interpretation as well as the ethical aspects of AI research are discussed. This article aims to guide clinicians in the evaluation of new AI applications for electrophysiology before their clinical implementation.",,doi:https://doi.org/10.15420/aer.2020.26; doi:https://doi.org/10.15420/aer.2020.26; html:https://europepmc.org/articles/PMC7675143; pdf:https://europepmc.org/articles/PMC7675143?pdf=render 38326875,https://doi.org/10.1186/s13059-024-03172-3,"IDHwt glioblastomas can be stratified by their transcriptional response to standard treatment, with implications for targeted therapy.","Tanner G, Barrow R, Ajaib S, Al-Jabri M, Ahmed N, Pollock S, Finetti M, Rippaus N, Bruns AF, Syed K, Poulter JA, Matthews L, Hughes T, Wilson E, Johnson C, Varn FS, Brüning-Richardson A, Hogg C, Droop A, Gusnanto A, Care MA, Cutillo L, Westhead DR, Short SC, Jenkinson MD, Brodbelt A, Chakrabarty A, Ismail A, Verhaak RGW, Stead LF.",,Genome biology,2024,2024-02-07,Y,,,,"

Background

Glioblastoma (GBM) brain tumors lacking IDH1 mutations (IDHwt) have the worst prognosis of all brain neoplasms. Patients receive surgery and chemoradiotherapy but tumors almost always fatally recur.

Results

Using RNA sequencing data from 107 pairs of pre- and post-standard treatment locally recurrent IDHwt GBM tumors, we identify two responder subtypes based on longitudinal changes in gene expression. In two thirds of patients, a specific subset of genes is upregulated from primary to recurrence (Up responders), and in one third, the same genes are downregulated (Down responders), specifically in neoplastic cells. Characterization of the responder subtypes indicates subtype-specific adaptive treatment resistance mechanisms that are associated with distinct changes in the tumor microenvironment. In Up responders, recurrent tumors are enriched in quiescent proneural GBM stem cells and differentiated neoplastic cells, with increased interaction with the surrounding normal brain and neurotransmitter signaling, whereas Down responders commonly undergo mesenchymal transition. ChIP-sequencing data from longitudinal GBM tumors suggests that the observed transcriptional reprogramming could be driven by Polycomb-based chromatin remodeling rather than DNA methylation.

Conclusions

We show that the responder subtype is cancer-cell intrinsic, recapitulated in in vitro GBM cell models, and influenced by the presence of the tumor microenvironment. Stratifying GBM tumors by responder subtype may lead to more effective treatment.",,pdf:https://genomebiology.biomedcentral.com/counter/pdf/10.1186/s13059-024-03172-3; doi:https://doi.org/10.1186/s13059-024-03172-3; html:https://europepmc.org/articles/PMC10848526; pdf:https://europepmc.org/articles/PMC10848526?pdf=render @@ -1417,38 +1417,38 @@ PMC8855010,https://doi.org/,POS-894 PREDICTING PANDEMIC-RELATED EXCESS-DEATH USI 37072241,https://doi.org/10.1136/heartjnl-2022-321888,Incident cardiovascular events and imaging phenotypes in UK Biobank participants with past cancer.,"Raisi-Estabragh Z, Cooper J, McCracken C, Crosbie EJ, Walter FM, Manisty CH, Robson J, Mamas MA, Harvey NC, Neubauer S, Petersen SE.",,Heart (British Cardiac Society),2023,2023-06-14,Y,epidemiology; Magnetic Resonance Imaging,,,"

Objectives

To evaluate incident cardiovascular outcomes and imaging phenotypes in UK Biobank participants with previous cancer.

Methods

Cancer and cardiovascular disease (CVD) diagnoses were ascertained using health record linkage. Participants with cancer history (breast, lung, prostate, colorectal, uterus, haematological) were propensity matched on vascular risk factors to non-cancer controls. Competing risk regression was used to calculate subdistribution HRs (SHRs) for associations of cancer history with incident CVD (ischaemic heart disease (IHD), non-ischaemic cardiomyopathy (NICM), heart failure (HF), atrial fibrillation/flutter, stroke, pericarditis, venous thromboembolism (VTE)) and mortality outcomes (any CVD, IHD, HF/NICM, stroke, hypertensive disease) over 11.8±1.7 years of prospective follow-up. Linear regression was used to assess associations of cancer history with left ventricular (LV) and left atrial metrics.

Results

We studied 18 714 participants (67% women, age: 62 (IQR: 57-66) years, 97% white ethnicities) with cancer history, including 1354 individuals with cardiovascular magnetic resonance. Participants with cancer had high burden of vascular risk factors and prevalent CVDs. Haematological cancer was associated with increased risk of all incident CVDs considered (SHRs: 1.92-3.56), larger chamber volumes, lower ejection fractions, and poorer LV strain. Breast cancer was associated with increased risk of selected CVDs (NICM, HF, pericarditis and VTE; SHRs: 1.34-2.03), HF/NICM death, hypertensive disease death, lower LV ejection fraction, and lower LV global function index. Lung cancer was associated with increased risk of pericarditis, HF, and CVD death. Prostate cancer was linked to increased VTE risk.

Conclusions

Cancer history is linked to increased risk of incident CVDs and adverse cardiac remodelling independent of shared vascular risk factors.",,pdf:https://heart.bmj.com/content/heartjnl/early/2023/03/21/heartjnl-2022-321888.full.pdf; doi:https://doi.org/10.1136/heartjnl-2022-321888; html:https://europepmc.org/articles/PMC10314020; pdf:https://europepmc.org/articles/PMC10314020?pdf=render 35477524,https://doi.org/10.1136/bmj-2022-070230,Development and validation of the symptom burden questionnaire for long covid (SBQ-LC): Rasch analysis.,"Hughes SE, Haroon S, Subramanian A, McMullan C, Aiyegbusi OL, Turner GM, Jackson L, Davies EH, Frost C, McNamara G, Price G, Matthews K, Camaradou J, Ormerod J, Walker A, Calvert MJ.",,BMJ (Clinical research ed.),2022,2022-04-27,Y,,,,"

Objective

To describe the development and validation of a novel patient reported outcome measure for symptom burden from long covid, the symptom burden questionnaire for long covid (SBQ-LC).

Design

Multiphase, prospective mixed methods study.

Setting

Remote data collection and social media channels in the United Kingdom, 14 April to 1 August 2021.

Participants

13 adults (aged ≥18 years) with self-reported long covid and 10 clinicians evaluated content validity. 274 adults with long covid field tested the draft questionnaire.

Main outcome measures

Published systematic reviews informed development of SBQ-LC's conceptual framework and initial item pool. Thematic analysis of transcripts from cognitive debriefing interviews and online clinician surveys established content validity. Consensus discussions with the patient and public involvement group of the Therapies for Long COVID in non-hospitalised individuals: From symptoms, patient reported outcomes and immunology to targeted therapies (TLC Study) confirmed face validity. Rasch analysis of field test data guided item and scale refinement and provided initial evidence of the SBQ-LC's measurement properties.

Results

SBQ-LC (version 1.0) is a modular instrument measuring patient reported outcomes and is composed of 17 independent scales with promising psychometric properties. Respondents rate their symptom burden during the past seven days using a dichotomous response or 4 point rating scale. Each scale provides coverage of a different symptom domain and returns a summed raw score that can be transformed to a linear (0-100) score. Higher scores represent higher symptom burden. After rating scale refinement and item reduction, all scales satisfied the Rasch model requirements for unidimensionality (principal component analysis of residuals: first residual contrast values <2.00 eigenvalue units) and item fit (outfit mean square values within 0.5 -1.5 logits). Rating scale categories were ordered with acceptable category fit statistics (outfit mean square values <2.0 logits). 14 item pairs had evidence of local dependency (residual correlation values >0.4). Across the 17 scales, person reliability ranged from 0.34 to 0.87, person separation ranged from 0.71 to 2.56, item separation ranged from 1.34 to 13.86, and internal consistency reliability (Cronbach's alpha) ranged from 0.56 to 0.91.

Conclusions

SBQ-LC (version 1.0) is a comprehensive patient reported outcome instrument developed using modern psychometric methods. It measures symptoms of long covid important to people with lived experience of the condition and may be used to evaluate the impact of interventions and inform best practice in clinical management.",,pdf:https://www.bmj.com/content/bmj/377/bmj-2022-070230.full.pdf; doi:https://doi.org/10.1136/bmj-2022-070230; html:https://europepmc.org/articles/PMC9043395; pdf:https://europepmc.org/articles/PMC9043395?pdf=render 35765237,https://doi.org/10.1111/1747-0080.12746,An investigation of early enteral nutrition provision in major burn patients in Australia and New Zealand.,"Kurmis R, Nicholls C, Singer Y, Edgar DW, Wood FM, Gabbe BJ, Tracy LM.",,Nutrition & dietetics: the journal of the Dietitians Association of Australia,2022,2022-06-28,Y,Burns; Parenteral nutrition; enteral nutrition,,,"

Aims

Early enteral nutrition (provided within 24 h of admission) is the optimal form of nutritional support for major burn injuries. The aim of this study was to (i) audit early enteral nutrition practices, (ii) identify characteristics of patients who received early enteral nutrition, and (iii) investigate whether early enteral nutrition was associated with in-hospital outcomes.

Methods

An analysis of prospectively collected data from the Burns Registry of Australia and New Zealand was conducted. Specifically, this study focused on major burns patients (defined as burns affecting more than 20% and 15% total body surface area for adult paediatric patients, respectively) admitted to a specialist burn service between 1 July 2016 and 30 June 2019.

Results

Data from 474 major burns patients (88 paediatric patients) revealed 69% received early enteral nutrition. Paediatric patients who received early enteral nutrition were younger than their counterparts who did not receive the same support (p = 0.04). Adult patients who received early enteral nutrition sustained larger burns (p < 0.001). Early enteral nutrition was not associated with in-hospital mortality following major burn injury in adult patients in either unadjusted (p = 0.77) or confounder-adjusted (p = 0.69) analyses.

Conclusions

Approximately two-thirds of patients with major burn injuries received early enteral nutrition. Early enteral nutrition was not associated with in-hospital mortality following major burn injury. Further research should focus on modifiable reasons why major burns patients do not receive enteral nutrition within 24 h of admission.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9796319; doi:https://doi.org/10.1111/1747-0080.12746; html:https://europepmc.org/articles/PMC9796319; pdf:https://europepmc.org/articles/PMC9796319?pdf=render -34849869,https://doi.org/10.1093/gigascience/giab076,An overview of the National COVID-19 Chest Imaging Database: data quality and cohort analysis.,"Cushnan D, Bennett O, Berka R, Bertolli O, Chopra A, Dorgham S, Favaro A, Ganepola T, Halling-Brown M, Imreh G, Jacob J, Jefferson E, Lemarchand F, Schofield D, Wyatt JC, NCCID Collaborative.",,GigaScience,2021,2021-11-01,Y,Medical imaging; Machine Learning; Thoracic Imaging; Covid-19; Sars-cov2,,,"

Background

The National COVID-19 Chest Imaging Database (NCCID) is a centralized database containing mainly chest X-rays and computed tomography scans from patients across the UK. The objective of the initiative is to support a better understanding of the coronavirus SARS-CoV-2 disease (COVID-19) and the development of machine learning technologies that will improve care for patients hospitalized with a severe COVID-19 infection. This article introduces the training dataset, including a snapshot analysis covering the completeness of clinical data, and availability of image data for the various use-cases (diagnosis, prognosis, longitudinal risk). An additional cohort analysis measures how well the NCCID represents the wider COVID-19-affected UK population in terms of geographic, demographic, and temporal coverage.

Findings

The NCCID offers high-quality DICOM images acquired across a variety of imaging machinery; multiple time points including historical images are available for a subset of patients. This volume and variety make the database well suited to development of diagnostic/prognostic models for COVID-associated respiratory conditions. Historical images and clinical data may aid long-term risk stratification, particularly as availability of comorbidity data increases through linkage to other resources. The cohort analysis revealed good alignment to general UK COVID-19 statistics for some categories, e.g., sex, whilst identifying areas for improvements to data collection methods, particularly geographic coverage.

Conclusion

The NCCID is a growing resource that provides researchers with a large, high-quality database that can be leveraged both to support the response to the COVID-19 pandemic and as a test bed for building clinically viable medical imaging models.",,pdf:https://academic.oup.com/gigascience/article-pdf/10/11/giab076/41395024/giab076.pdf; doi:https://doi.org/10.1093/gigascience/giab076; html:https://europepmc.org/articles/PMC8633457; pdf:https://europepmc.org/articles/PMC8633457?pdf=render 33560181,https://doi.org/10.1177/0272989x21994035,The Value of Triage during Periods of Intense COVID-19 Demand: Simulation Modeling Study.,"Wood RM, Pratt AC, Kenward C, McWilliams CJ, Booton RD, Thomas MJ, Bourdeaux CP, Vasilakis C.",,Medical decision making : an international journal of the Society for Medical Decision Making,2021,2021-02-09,N,Computer simulation; Coronavirus; Intensive Care; Critical Care; Triage; Covid-19,,,"

Background

During the COVID-19 pandemic, many intensive care units have been overwhelmed by unprecedented levels of demand. Notwithstanding ethical considerations, the prioritization of patients with better prognoses may support a more effective use of available capacity in maximizing aggregate outcomes. This has prompted various proposed triage criteria, although in none of these has an objective assessment been made in terms of impact on number of lives and life-years saved.

Design

An open-source computer simulation model was constructed for approximating the intensive care admission and discharge dynamics under triage. The model was calibrated from observational data for 9505 patient admissions to UK intensive care units. To explore triage efficacy under various conditions, scenario analysis was performed using a range of demand trajectories corresponding to differing nonpharmaceutical interventions.

Results

Triaging patients at the point of expressed demand had negligible effect on deaths but reduces life-years lost by up to 8.4% (95% confidence interval: 2.6% to 18.7%). Greater value may be possible through ""reverse triage"", that is, promptly discharging any patient not meeting the criteria if admission cannot otherwise be guaranteed for one who does. Under such policy, life-years lost can be reduced by 11.7% (2.8% to 25.8%), which represents 23.0% (5.4% to 50.1%) of what is operationally feasible with no limit on capacity and in the absence of improved clinical treatments.

Conclusions

The effect of simple triage is limited by a tradeoff between reduced deaths within intensive care (due to improved outcomes) and increased deaths resulting from declined admission (due to lower throughput given the longer lengths of stay of survivors). Improvements can be found through reverse triage, at the expense of potentially complex ethical considerations.",,pdf:https://journals.sagepub.com/doi/pdf/10.1177/0272989X21994035; doi:https://doi.org/10.1177/0272989X21994035 +34849869,https://doi.org/10.1093/gigascience/giab076,An overview of the National COVID-19 Chest Imaging Database: data quality and cohort analysis.,"Cushnan D, Bennett O, Berka R, Bertolli O, Chopra A, Dorgham S, Favaro A, Ganepola T, Halling-Brown M, Imreh G, Jacob J, Jefferson E, Lemarchand F, Schofield D, Wyatt JC, NCCID Collaborative.",,GigaScience,2021,2021-11-01,Y,Medical imaging; Machine Learning; Thoracic Imaging; Covid-19; Sars-cov2,,,"

Background

The National COVID-19 Chest Imaging Database (NCCID) is a centralized database containing mainly chest X-rays and computed tomography scans from patients across the UK. The objective of the initiative is to support a better understanding of the coronavirus SARS-CoV-2 disease (COVID-19) and the development of machine learning technologies that will improve care for patients hospitalized with a severe COVID-19 infection. This article introduces the training dataset, including a snapshot analysis covering the completeness of clinical data, and availability of image data for the various use-cases (diagnosis, prognosis, longitudinal risk). An additional cohort analysis measures how well the NCCID represents the wider COVID-19-affected UK population in terms of geographic, demographic, and temporal coverage.

Findings

The NCCID offers high-quality DICOM images acquired across a variety of imaging machinery; multiple time points including historical images are available for a subset of patients. This volume and variety make the database well suited to development of diagnostic/prognostic models for COVID-associated respiratory conditions. Historical images and clinical data may aid long-term risk stratification, particularly as availability of comorbidity data increases through linkage to other resources. The cohort analysis revealed good alignment to general UK COVID-19 statistics for some categories, e.g., sex, whilst identifying areas for improvements to data collection methods, particularly geographic coverage.

Conclusion

The NCCID is a growing resource that provides researchers with a large, high-quality database that can be leveraged both to support the response to the COVID-19 pandemic and as a test bed for building clinically viable medical imaging models.",,pdf:https://academic.oup.com/gigascience/article-pdf/10/11/giab076/41395024/giab076.pdf; doi:https://doi.org/10.1093/gigascience/giab076; html:https://europepmc.org/articles/PMC8633457; pdf:https://europepmc.org/articles/PMC8633457?pdf=render 35028631,https://doi.org/10.1016/s2666-7568(21)00281-6,The importance of blood pressure thresholds versus predicted cardiovascular risk on subsequent rates of cardiovascular disease: a cohort study in English primary care.,"Herrett E, Strongman H, Gadd S, Tomlinson L, Nitsch D, Bhaskaran K, Williamson E, van Staa T, Sofat R, Timmis A, Wells S, Smeeth L, Jackson R.",,The lancet. Healthy longevity,2022,2022-01-01,Y,,,,"

Background

For five decades, blood pressure lowering treatment has been recommended for patients with hypertension (currently defined as blood pressure of ≥140/90 mm Hg). In the past 20 years, guidelines for treatment began incorporating predicted absolute cardiovascular disease risk (predicted risk) and reducing blood pressure thresholds. The blood pressure threshold at which to start treatment has become a secondary consideration in some countries. We aimed to provide descriptive data to assess the relative importance of blood pressure thresholds versus predicted risk on the subsequent rate of cardiovascular disease to inform treatment decisions.

Methods

In this English population-based cohort study, we used linked data from the Clinical Practice Research Datalink (CPRD) GOLD, Hospital Episode Statistics Admitted Patient Care, and the Office for National Statistics mortality data, and area-based deprivation indices (Townsend scores). Eligible patients were aged 30-79 years on Jan 1, 2011 (cohort entry date) and could be linked to hospital, mortality, and deprivation data. Patients were followed up until death, end of CPRD follow-up, or Nov 31, 2018. We examined three outcomes: cardiovascular disease, markers of potential target organ damage, and incident dementia without a known cause. The rate of each outcome was estimated and stratified by systolic blood pressure and predicted 10-year risk of cardiovascular disease (QRISK2 algorithm).

Findings

Between Jan 1, 2011, and Nov 31, 2018, 1 098 991 patients were included in the cohort and followed up for a median of 4·3 years (IQR 2·6-6·0; total follow-up of 4·6 million person-years). Median age at entry was 52 years (IQR 42-62) and 629 711 (57·3%) patients were female. There were 51 996 cardiovascular disease events and the overall rate of cardiovascular disease was 11·2 per 1000 person-years (95% CI 11·1-11·3). Median QRISK2 10-year predicted risk was 4·6% (IQR 1·4-12·0) and mean systolic blood pressure before cohort entry was 129·1 mm Hg (SD 15·7). Within strata of predicted risk, the effect of increasing systolic blood pressure on outcomes was small. For example, in the group with 10·0-19·9% predicted risk, rates of all cardiovascular disease rose from 20·1 to 23·6 per 1000 person-years between systolic blood pressures less than 110 mm Hg and 180 and higher mm Hg. But among patients with systolic blood pressure 140·0-149·9 mm Hg, rates rose from 6·9 to 52·3 per 1000 person-years between those with less than 10·0% risk and those with 30·0% or higher predicted risk.

Interpretation

For a wide range of blood pressures, the rate of cardiovascular disease and effectiveness of blood pressure drug treatment was mainly determined by predicted risk, with blood pressure thresholds 140/90 mm Hg or 160/100 mm Hg-ubiquitous in most countries-adding little useful information. When medium-term predicted risk is low, there is no urgency to initiate drug treatment, allowing time to attempt non-pharmacological blood pressure reduction.

Funding

National Institute for Health Research.",,pdf:http://www.thelancet.com/article/S2666756821002816/pdf; doi:https://doi.org/10.1016/S2666-7568(21)00281-6; html:https://europepmc.org/articles/PMC8732286 -37217302,https://doi.org/10.1136/emermed-2022-212827,External validation of triage tools for adults with suspected COVID-19 in a middle-income setting: an observational cohort study.,"Marincowitz C, Sbaffi L, Hasan M, Hodkinson P, McAlpine D, Fuller G, Goodacre S, Bath PA, Bath PA, Omer Y, Wallis LA.",,Emergency medicine journal : EMJ,2023,2023-05-22,Y,risk management; Triage; Covid-19,,,"

Background

Tools proposed to triage ED acuity in suspected COVID-19 were derived and validated in higher income settings during early waves of the pandemic. We estimated the accuracy of seven risk-stratification tools recommended to predict severe illness in the Western Cape, South Africa.

Methods

An observational cohort study using routinely collected data from EDs across the Western Cape, from 27 August 2020 to 11 March 2022, was conducted to assess the performance of the PRIEST (Pandemic Respiratory Infection Emergency System Triage) tool, NEWS2 (National Early Warning Score, version 2), TEWS (Triage Early Warning Score), the WHO algorithm, CRB-65, Quick COVID-19 Severity Index and PMEWS (Pandemic Medical Early Warning Score) in suspected COVID-19. The primary outcome was intubation or non-invasive ventilation, death or intensive care unit admission at 30 days.

Results

Of the 446 084 patients, 15 397 (3.45%, 95% CI 34% to 35.1%) experienced the primary outcome. Clinical decision-making for inpatient admission achieved a sensitivity of 0.77 (95% CI 0.76 to 0.78), specificity of 0.88 (95% CI 0.87 to 0.88) and the negative predictive value (NPV) of 0.99 (95% CI 0.99 to 0.99). NEWS2, PMEWS and PRIEST scores achieved good estimated discrimination (C-statistic 0.79 to 0.82) and identified patients at risk of adverse outcomes at recommended cut-offs with moderate sensitivity (>0.8) and specificity ranging from 0.41 to 0.64. Use of the tools at recommended thresholds would have more than doubled admissions, with only a 0.01% reduction in false negative triage.

Conclusion

No risk score outperformed existing clinical decision-making in determining the need for inpatient admission based on prediction of the primary outcome in this setting. Use of the PRIEST score at a threshold of one point higher than the previously recommended best approximated existing clinical accuracy.",,pdf:https://emj.bmj.com/content/emermed/early/2023/05/22/emermed-2022-212827.full.pdf; doi:https://doi.org/10.1136/emermed-2022-212827; html:https://europepmc.org/articles/PMC10359554; pdf:https://europepmc.org/articles/PMC10359554?pdf=render 33289226,https://doi.org/10.1111/ans.16426,Association between gender and outcomes of acute burns patients.,"Perkins M, Abesamis GM, Cleland H, Gabbe BJ, Tracy LM.",,ANZ journal of surgery,2020,2020-12-01,N,Burns; Gender; Outcomes,,,"

Background

Burn injuries are a complex and serious public health concern. Where the total body surface area of the burn exceeds 50%, mortality rates as high as 48% have been reported. While the association between gender and burn injury outcomes has been explored, findings are inconsistent.

Methods

Adult patients (>15 years) admitted between 1 July 2009 and 30 June 2018 to intensive care units of burn centres that provide specialist burn care in Australia and New Zealand were included. Raw mortality rates were examined and a multivariable Cox proportional hazards regression was used to investigate the association between gender and time to in-hospital death.

Results

There were 2227 eligible burn injury admissions. Men comprised the majority (77.6%). The proportion of women who died in hospital was greater than men and the adjusted odds of in-hospital mortality were 34% lower in men (odds ratio 0.66; 95% confidence interval (CI) 0.45-0.98). The unadjusted rate of in-hospital mortality for men was 44% lower than women (hazard ratio 0.56; 95% CI 0.41-0.76). After adjusting for confounders, there was no association between gender and survival time (hazard ratio 0.76; 95% CI 0.54-1.06).

Conclusion

After adjustment for key differences in case-mix between men and women, there was an association between gender and in-hospital mortality and no association between gender and time to death. Our findings indicate that the worse outcomes observed for women are associated with different age and patterns of injury, and provide further information to direct and inform targeted prevention measures for vulnerable populations.",,doi:https://doi.org/10.1111/ans.16426 34095541,https://doi.org/10.23889/ijpds.v4i2.1134,A Profile of the SAIL Databank on the UK Secure Research Platform.,"Jones KH, Ford DV, Thompson S, Lyons RA.",,International journal of population data science,2019,2019-11-20,Y,,,,"

Background

The Secure Anonymised Information Linkage (SAIL) Databank is a national data safe haven of de identified datasets principally about the population of Wales, made available in anonymised form to researchers across the world. It was established to enable the vast arrays of data collected about individuals in the course of health and other public service delivery to be made available to answer important questions that could not otherwise be addressed without prohibitive effort. The SAIL Databank is the bedrock of other funded centres relying on the data for research.

Approach

SAIL is a data repository surrounded by a suite of physical, technical and procedural control measures embodying a proportionate privacy-by-design governance model, informed by public engagement, to safeguard the data and facilitate data utility. SAIL operates on the UK Secure Research Platform (SeRP), which is a customisable technology and analysis platform. Researchers access anonymised data via this secure research environment, from which results can be released following scrutiny for disclosure risk. SAIL data are being used in multiple research areas to evaluate the impact of health and social exposures and policy interventions.

Discussion

Lessons learned and their applications include: managing evolving legislative and regulatory requirements; employing multiple, tiered security mechanisms; working hard to increase analytical capacity efficiency; and developing a multi-faceted programme of public engagement. Further work includes: incorporating new data types; enabling alternative means of data access; and developing further efficiencies across our operations.

Conclusion

SAIL represents an ongoing programme of work to develop and maintain an extensive, whole population data resource for research. Its privacy-by-design model and UK SeRP technology have received international acclaim, and we continually endeavour to demonstrate trustworthiness to support data provider assurance and public acceptability in data use. We strive for further improvement and continue a mutual learning process with our contemporaries in this rapidly developing field.",,pdf:https://ijpds.org/article/download/1134/2643; doi:https://doi.org/10.23889/ijpds.v4i2.1134; html:https://europepmc.org/articles/PMC8142954; pdf:https://europepmc.org/articles/PMC8142954?pdf=render +37217302,https://doi.org/10.1136/emermed-2022-212827,External validation of triage tools for adults with suspected COVID-19 in a middle-income setting: an observational cohort study.,"Marincowitz C, Sbaffi L, Hasan M, Hodkinson P, McAlpine D, Fuller G, Goodacre S, Bath PA, Bath PA, Omer Y, Wallis LA.",,Emergency medicine journal : EMJ,2023,2023-05-22,Y,risk management; Triage; Covid-19,,,"

Background

Tools proposed to triage ED acuity in suspected COVID-19 were derived and validated in higher income settings during early waves of the pandemic. We estimated the accuracy of seven risk-stratification tools recommended to predict severe illness in the Western Cape, South Africa.

Methods

An observational cohort study using routinely collected data from EDs across the Western Cape, from 27 August 2020 to 11 March 2022, was conducted to assess the performance of the PRIEST (Pandemic Respiratory Infection Emergency System Triage) tool, NEWS2 (National Early Warning Score, version 2), TEWS (Triage Early Warning Score), the WHO algorithm, CRB-65, Quick COVID-19 Severity Index and PMEWS (Pandemic Medical Early Warning Score) in suspected COVID-19. The primary outcome was intubation or non-invasive ventilation, death or intensive care unit admission at 30 days.

Results

Of the 446 084 patients, 15 397 (3.45%, 95% CI 34% to 35.1%) experienced the primary outcome. Clinical decision-making for inpatient admission achieved a sensitivity of 0.77 (95% CI 0.76 to 0.78), specificity of 0.88 (95% CI 0.87 to 0.88) and the negative predictive value (NPV) of 0.99 (95% CI 0.99 to 0.99). NEWS2, PMEWS and PRIEST scores achieved good estimated discrimination (C-statistic 0.79 to 0.82) and identified patients at risk of adverse outcomes at recommended cut-offs with moderate sensitivity (>0.8) and specificity ranging from 0.41 to 0.64. Use of the tools at recommended thresholds would have more than doubled admissions, with only a 0.01% reduction in false negative triage.

Conclusion

No risk score outperformed existing clinical decision-making in determining the need for inpatient admission based on prediction of the primary outcome in this setting. Use of the PRIEST score at a threshold of one point higher than the previously recommended best approximated existing clinical accuracy.",,pdf:https://emj.bmj.com/content/emermed/early/2023/05/22/emermed-2022-212827.full.pdf; doi:https://doi.org/10.1136/emermed-2022-212827; html:https://europepmc.org/articles/PMC10359554; pdf:https://europepmc.org/articles/PMC10359554?pdf=render 38746859,https://doi.org/10.1183/23120541.00430-2023,"Prevalence, incidence and healthcare burden of eosinophilic granulomatosis with polyangiitis in the UK.","Hwee J, Harper L, Fu Q, Nirantharakumar K, Mu G, Jakes RW.",,ERJ open research,2024,2024-05-13,Y,,,,"

Background

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare but serious disease characterised by the combination of small-to-medium vessel vasculitis, blood and tissue eosinophilia, and asthma and/or sinonasal disease. This study estimated the prevalence and incidence of diagnosed EGPA in the United Kingdom (UK), and described the demographics, clinical characteristics and healthcare resource utilisation (HCRU) of this population.

Methods

This retrospective longitudinal study of patients with newly diagnosed EGPA (index) (2005-2019) used the Clinical Practice Research Datalink AURUM and Hospital Episode Statistics databases. The primary outcomes were the annual prevalence (2005-2019) and incidence (2006-2019) of EGPA, and secondary outcomes included patient demographics and clinical characteristics, and HCRU in the year pre- and post-index (diagnosis).

Results

Populations of patients with EGPA comprised 940 prevalent cases and 502 incident cases, of which 377 were linked to Hospital Episode Statistics. EGPA prevalence increased from 22.7 to 45.6 cases per 1 000 000 (2005-2019), driven by patients aged ≥18 years. Incidence ranged from 2.3 to 4.0 per 1 000 000 person-years (2006-2019). Pre-index, the most common clinical symptoms were respiratory related, and the most common comorbidities were asthma (80.6%) and nasal polyps (32.1%). Post-index, 19.1% had an EGPA-related inpatient stay (median length of stay 11.0 days) and 38.7% had five or more oral corticosteroid (OCS) prescriptions with a mean OCS possession ratio per patient of 47.0%.

Conclusions

Although EGPA incidence in the UK remains relatively stable, prevalence is increasing, and HCRU and OCS use remain frequent, suggesting considerable healthcare burden for patients with EGPA.",,doi:https://doi.org/10.1183/23120541.00430-2023; html:https://europepmc.org/articles/PMC11089387; pdf:https://europepmc.org/articles/PMC11089387?pdf=render 33830993,https://doi.org/10.1371/journal.pgen.1009428,Sex-stratified genome-wide association study of multisite chronic pain in UK Biobank.,"Johnston KJA, Ward J, Ray PR, Adams MJ, McIntosh AM, Smith BH, Strawbridge RJ, Price TJ, Smith DJ, Nicholl BI, Bailey MES.",,PLoS genetics,2021,2021-04-08,Y,,,,"Chronic pain is highly prevalent worldwide and imparts a significant socioeconomic and public health burden. Factors influencing susceptibility to, and mechanisms of, chronic pain development, are not fully understood, but sex is thought to play a significant role, and chronic pain is more prevalent in women than in men. To investigate sex differences in chronic pain, we carried out a sex-stratified genome-wide association study of Multisite Chronic Pain (MCP), a derived chronic pain phenotype, in UK Biobank on 178,556 men and 209,093 women, as well as investigating sex-specific genetic correlations with a range of psychiatric, autoimmune and anthropometric phenotypes and the relationship between sex-specific polygenic risk scores for MCP and chronic widespread pain. We also assessed whether MCP-associated genes showed expression pattern enrichment across tissues. A total of 123 SNPs at five independent loci were significantly associated with MCP in men. In women, a total of 286 genome-wide significant SNPs at ten independent loci were discovered. Meta-analysis of sex-stratified GWAS outputs revealed a further 87 independent associated SNPs. Gene-level analyses revealed sex-specific MCP associations, with 31 genes significantly associated in females, 37 genes associated in males, and a single gene, DCC, associated in both sexes. We found evidence for sex-specific pleiotropy and risk for MCP was found to be associated with chronic widespread pain in a sex-differential manner. Male and female MCP were highly genetically correlated, but at an rg of significantly less than 1 (0.92). All 37 male MCP-associated genes and all but one of 31 female MCP-associated genes were found to be expressed in the dorsal root ganglion, and there was a degree of enrichment for expression in sex-specific tissues. Overall, the findings indicate that sex differences in chronic pain exist at the SNP, gene and transcript abundance level, and highlight possible sex-specific pleiotropy for MCP. Results support the proposition of a strong central nervous-system component to chronic pain in both sexes, additionally highlighting a potential role for the DRG and nociception.",,pdf:https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1009428&type=printable; doi:https://doi.org/10.1371/journal.pgen.1009428; html:https://europepmc.org/articles/PMC8031124; pdf:https://europepmc.org/articles/PMC8031124?pdf=render 35536740,https://doi.org/10.1136/bmjopen-2021-052884,Gaps in antihypertensive and statin treatments and benefits of optimisation: a modelling study in a 1 million ethnically diverse urban population in UK.,"Wu R, Rison SCG, Raisi-Estabragh Z, Dostal I, Carvalho C, Robson J, Mihaylova B.",,BMJ open,2021,2021-12-30,Y,Hypertension; Preventive Medicine; Ischaemic Heart Disease; Primary Care; Health Policy; Quality In Health Care,,,"

Objectives

To characterise gaps in antihypertensive treatment in people with hypertension and statin treatment in people with cardiovascular diseases (CVD) in a large urban population and quantify the health and economic impacts of their optimisation.

Design

A cross-sectional population study and a long-term CVD decision model.

Setting

Primary care, UK.

Participants

All adults with diagnosed hypertension or CVD in a population of about 1 million people, served by 123 primary care practices in London, UK in 2019.

Interventions

Following UK clinical guidelines, all adults with diagnosed hypertension were categorised into optimal, suboptimal and untreated groups with respect to their antihypertensive treatment, and all adults with diagnosed CVD were categorised in the same manner with respect to their statin treatment.

Outcomes

Proportion of patients suboptimally treated or untreated. Projected cardiovascular events avoided, years and quality-adjusted life years (QALYs) gained and healthcare costs saved with optimised treatments.

Results

21 954 of the 91 828 adults with hypertension (24%; mean age 59 years; 49% women) and 9062 of the 23 723 adults with CVD (38%; mean age 69 years; 43% women) were not optimally treated with antihypertensive or statin treatment, respectively. Per 1000 additional patients optimised over 5 years, hypertension treatment is projected to prevent 25 (95% CI 16 to 32) major vascular events (MVEs) and 7 (3 to 10) vascular deaths, statin treatment, 28 (22 to 33) MVEs and 6 (4 to 7) vascular deaths. Over their lifespan, a patient with uncontrolled hypertension aged 60-69 years is projected to gain 0.64 (95% CI 0.36 to 0.87) QALYs with optimised hypertension treatment, and a similarly aged patient with previous CVD not optimally treated with statin is projected to gain 0.3 (0.24 to 0.37) QALYs with optimised statin treatment. In both cases, the hospital cost savings minus extra medication costs were about £1100 per person over remaining lifespan.

Conclusions

Optimising cardiovascular treatments can cost-effectively reduce cardiovascular risk and improve life expectancy.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/12/e052884.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-052884; html:https://europepmc.org/articles/PMC8719215; pdf:https://europepmc.org/articles/PMC8719215?pdf=render 33531486,https://doi.org/10.1038/s41467-021-21370-6,Author Correction: Genetic architecture of host proteins involved in SARS-CoV-2 infection.,"Pietzner M, Wheeler E, Carrasco-Zanini J, Raffler J, Kerrison ND, Oerton E, Auyeung VPW, Luan J, Finan C, Casas JP, Ostroff R, Williams SA, Kastenmüller G, Ralser M, Gamazon ER, Wareham NJ, Hingorani AD, Langenberg C.",,Nature communications,2021,2021-02-02,Y,,,,,,pdf:https://www.nature.com/articles/s41467-021-21370-6.pdf; doi:https://doi.org/10.1038/s41467-021-21370-6; html:https://europepmc.org/articles/PMC7854714; pdf:https://europepmc.org/articles/PMC7854714?pdf=render 38725371,https://doi.org/10.1192/bjo.2024.23,"Contacts with primary and secondary healthcare before suicide by those under the care of mental health services: case-control, whole-population-based study using person-level linked routine data in Wales, UK during 2000-2015.","DelPozo-Banos M, Rodway C, Lee SC, Rouquette OY, Ibrahim S, Lloyd K, Appleby L, Kapur N, John A.",,BJPsych open,2024,2024-05-10,Y,Suicide; Mental Health Services; Primary Care; Secondary Care; Electronic Health Records,,,"

Background

People under the care of mental health services are at increased risk of suicide. Existing studies are small in scale and lack comparisons.

Aims

To identify opportunities for suicide prevention and underpinning data enhancement in people with recent contact with mental health services.

Method

This population-based study includes people who died by suicide in the year following a mental health services contact in Wales, 2001-2015 (cases), paired with similar patients who did not die by suicide (controls). We linked the National Confidential Inquiry into Suicide and Safety in Mental Health and the Suicide Information Database - Cymru with primary and secondary healthcare records. We present results of conditional logistic regression.

Results

We matched 1031 cases with 5155 controls. In the year before their death, 98.3% of cases were in contact with healthcare services, and 28.5% presented with self-harm. Cases had more emergency department contacts (odds ratio 2.4, 95% CI 2.1-2.7) and emergency hospital admissions (odds ratio 1.5, 95% CI 1.4-1.7), but fewer primary care contacts (odds ratio 0.7, 95% CI 0.6-0.9) and out-patient appointments (odds ratio 0.2, 95% CI 0.2-0.3) than controls. Odds ratios were larger in females than males for injury and poisoning (odds ratio: 3.3 (95% CI 2.5-4.5) v. 2.6 (95% CI 2.1-3.1)).

Conclusions

We may be missing existing opportunities to intervene, particularly in emergency departments and hospital admissions with self-harm presentations and with unattributed self-harm, especially in females. Prevention efforts should focus on strengthening routine care contacts, responding to emergency contacts and better self-harm care. There are benefits to enhancing clinical audit systems with routinely collected data.",,pdf:https://www.cambridge.org/core/services/aop-cambridge-core/content/view/4C20CD00C92C75F4F0B4FACD8418B244/S2056472424000231a.pdf/div-class-title-contacts-with-primary-and-secondary-healthcare-before-suicide-by-those-under-the-care-of-mental-health-services-case-control-whole-population-based-study-using-person-level-linked-routine-data-in-wales-uk-during-2000-2015-div.pdf; doi:https://doi.org/10.1192/bjo.2024.23; html:https://europepmc.org/articles/PMC11094447; pdf:https://europepmc.org/articles/PMC11094447?pdf=render 36929968,https://doi.org/10.1016/s0140-6736(22)02235-8,Impact of the temporary suspension of the Bowel Screening Wales programme on inequalities during the COVID-19 pandemic: a retrospective register-based study.,"Bright D, Song J, Hillier S, Huws DW, Greene G, Hodgson K, Akbari A, Griffiths R, Davies AR, Gjini A.",,"Lancet (London, England)",2022,2022-11-24,Y,,,,"

Background

Response to the COVID-19 pandemic resulted in the temporary disruption of routine services in the UK National Health Service, including cancer screening. Following the reintroduction of services, we explored the impact on inequalities in uptake of the Bowel Screening Wales (BSW) programme to identify groups who might benefit from tailored intervention.

Methods

BSW records were linked to electronic health record and administrative data within the Secured Anonymised Information Linkage (SAIL) Databank Trusted Research Environment. We examined uptake in the first 3 months (from August to October, 2020) of invitations following the reintroduction of the BSW programme compared with the same period in the preceding 3 years. We analysed inequalities in uptake by sex, age group, income deprivation quintile, urban and rural location, ethnic group, and uptake between different periods using logistic regression models.

Findings

Overall uptake remained above the 60% Welsh standard during the COVID-19 pandemic period of 2020-21 but declined compared with the pre-pandemic period of 2019-20 (60·4% vs 62·7%; p<0·001). During the COVID-19 pandemic period of 2020-21, uptake declined for most demographic groups, except for older individuals (70-74 years) and those in the most deprived quintile. Variation by sex, age, income deprivation, and ethnic groups was observed in all periods studied. Among low-uptake groups, including males, younger individuals (60-64 years), those living in most deprived areas, and ethnic minorities, uptake remains below the 60% Welsh standard.

Interpretation

Despite the disruption, uptake remained above the Welsh standard and inequalities did not worsen after the programme resumed activities. However, variations associated with sex, age, deprivation, and ethnicity remain. These findings need to be considered in targeting strategies to improve uptake and informed choice in colorectal cancer screening such as co-producing information products with low-uptake groups and upscaling the use of GP-endorsed invitations and reminder letters for bowel screening.

Funding

Health Data Research UK, UK Medical Research Council, Administrative Data Research UK, and Health and Care Research Wales.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9691043; doi:https://doi.org/10.1016/S0140-6736(22)02235-8; html:https://europepmc.org/articles/PMC9691043; pdf:https://europepmc.org/articles/PMC9691043?pdf=render -38345865,https://doi.org/10.1113/jp284597,Reduced plakoglobin increases the risk of sodium current defects and atrial conduction abnormalities in response to androgenic anabolic steroid abuse.,"Sommerfeld LC, Holmes AP, Yu TY, O'Shea C, Kavanagh DM, Pike JM, Wright T, Syeda F, Aljehani A, Kew T, Cardoso VR, Kabir SN, Hepburn C, Menon PR, Broadway-Stringer S, O'Reilly M, Witten A, Fortmueller L, Lutz S, Kulle A, Gkoutos GV, Pavlovic D, Arlt W, Lavery GG, Steeds R, Gehmlich K, Stoll M, Kirchhof P, Fabritz L.",,The Journal of physiology,2024,2024-02-12,N,Testosterone; Conduction velocity; Nav1.5; Desmosome; Arrhythmogenic Right Ventricular Cardiomyopathy; Cardiac Atria,,,"Androgenic anabolic steroids (AAS) are commonly abused by young men. Male sex and increased AAS levels are associated with earlier and more severe manifestation of common cardiac conditions, such as atrial fibrillation, and rare ones, such as arrhythmogenic right ventricular cardiomyopathy (ARVC). Clinical observations suggest a potential atrial involvement in ARVC. Arrhythmogenic right ventricular cardiomyopathy is caused by desmosomal gene defects, including reduced plakoglobin expression. Here, we analysed clinical records from 146 ARVC patients to identify that ARVC is more common in males than females. Patients with ARVC also had an increased incidence of atrial arrhythmias and P wave changes. To study desmosomal vulnerability and the effects of AAS on the atria, young adult male mice, heterozygously deficient for plakoglobin (Plako+/- ), and wild type (WT) littermates were chronically exposed to 5α-dihydrotestosterone (DHT) or placebo. The DHT increased atrial expression of pro-hypertrophic, fibrotic and inflammatory transcripts. In mice with reduced plakoglobin, DHT exaggerated P wave abnormalities, atrial conduction slowing, sodium current depletion, action potential amplitude reduction and the fall in action potential depolarization rate. Super-resolution microscopy revealed a decrease in NaV 1.5 membrane clustering in Plako+/- atrial cardiomyocytes after DHT exposure. In summary, AAS combined with plakoglobin deficiency cause pathological atrial electrical remodelling in young male hearts. Male sex is likely to increase the risk of atrial arrhythmia, particularly in those with desmosomal gene variants. This risk is likely to be exaggerated further by AAS use. KEY POINTS: Androgenic male sex hormones, such as testosterone, might increase the risk of atrial fibrillation in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC), which is often caused by desmosomal gene defects (e.g. reduced plakoglobin expression). In this study, we observed a significantly higher proportion of males who had ARVC compared with females, and atrial arrhythmias and P wave changes represented a common observation in advanced ARVC stages. In mice with reduced plakoglobin expression, chronic administration of 5α-dihydrotestosterone led to P wave abnormalities, atrial conduction slowing, sodium current depletion and a decrease in membrane-localized NaV 1.5 clusters. 5α-Dihydrotestosterone, therefore, represents a stimulus aggravating the pro-arrhythmic phenotype in carriers of desmosomal mutations and can affect atrial electrical function.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1113/JP284597; doi:https://doi.org/10.1113/JP284597 33728815,https://doi.org/10.1002/art.41709,Epidemiology of Scleritis in the United Kingdom From 1997 to 2018: Population-Based Analysis of 11 Million Patients and Association Between Scleritis and Infectious and Immune-Mediated Inflammatory Disease.,"Braithwaite T, Adderley NJ, Subramanian A, Galloway J, Kempen JH, Gokhale K, Cope AP, Dick AD, Nirantharakumar K, Denniston AK.",,"Arthritis & rheumatology (Hoboken, N.J.)",2021,2021-06-06,N,,,,"

Objective

To estimate 22-year trends in the prevalence and incidence of scleritis, and the associations of scleritis with infectious and immune-mediated inflammatory diseases (I-IMIDs) in the UK.

Methods

The retrospective cross-sectional and population cohort study (1997-2018) included 10,939,823 patients (2,946 incident scleritis cases) in The Health Improvement Network, a nationally representative primary care records database. The case-control and matched cohort study (1995-2019) included 3,005 incident scleritis cases and 12,020 control patients matched by age, sex, region, and Townsend deprivation index. Data were analyzed using multivariable Poisson regression, multivariable logistic regression, and Cox proportional hazards multivariable models adjusted for age, sex, Townsend deprivation index, race/ethnicity, smoking status, nation within the UK, and body mass index. Incidence rate ratios (IRRs) and 95% confidence intervals (95% CIs) were calculated.

Results

Scleritis incidence rates per 100,000 person-years declined from 4.23 (95% CI 2.16-6.31) to 2.79 (95% CI 2.19-3.39) between 1997 and 2018. The prevalence of scleritis per 100,000 person-years was 93.62 (95% CI 90.17-97.07) in 2018 (61,650 UK patients). Among 2,946 patients with incident scleritis, 1,831 (62.2%) were female, the mean ± SD age was 44.9 ± 17.6 years (range 1-93), and 1,257 (88.8%) were White. Higher risk of incident scleritis was associated with female sex (adjusted IRR 1.53 [95% CI 1.43-1.66], P < 0.001), Black race/ethnicity (adjusted IRR 1.52 [95% CI 1.14-2.01], P = 0.004 compared to White race/ethnicity), or South Asian race/ethnicity (adjusted IRR 1.50 [95% CI 1.19-1.90], P < 0.001 compared to White race/ethnicity), and older age (peak adjusted IRR 4.95 [95% CI 3.99-6.14], P < 0.001 for patients ages 51-60 years versus those ages ≤10 years). Compared to controls, scleritis patients had a 2-fold increased risk of a prior I-IMID diagnosis (17 I-IMIDs, P < 0.001) and significantly increased risk of subsequent diagnosis (13 I-IMIDs). The I-IMIDs most strongly associated with scleritis included granulomatosis with polyangiitis, Behçet's disease, and Sjögren's syndrome.

Conclusion

From 1997 through 2018, the UK incidence of scleritis declined from 4.23 to 2.79/100,000 person-years. Incident scleritis was associated with 19 I-IMIDs, providing data for rational investigation and cross-specialty engagement.",,doi:https://doi.org/10.1002/art.41709; doi:https://doi.org/10.1002/art.41709 +38345865,https://doi.org/10.1113/jp284597,Reduced plakoglobin increases the risk of sodium current defects and atrial conduction abnormalities in response to androgenic anabolic steroid abuse.,"Sommerfeld LC, Holmes AP, Yu TY, O'Shea C, Kavanagh DM, Pike JM, Wright T, Syeda F, Aljehani A, Kew T, Cardoso VR, Kabir SN, Hepburn C, Menon PR, Broadway-Stringer S, O'Reilly M, Witten A, Fortmueller L, Lutz S, Kulle A, Gkoutos GV, Pavlovic D, Arlt W, Lavery GG, Steeds R, Gehmlich K, Stoll M, Kirchhof P, Fabritz L.",,The Journal of physiology,2024,2024-02-12,N,Testosterone; Conduction velocity; Nav1.5; Desmosome; Arrhythmogenic Right Ventricular Cardiomyopathy; Cardiac Atria,,,"Androgenic anabolic steroids (AAS) are commonly abused by young men. Male sex and increased AAS levels are associated with earlier and more severe manifestation of common cardiac conditions, such as atrial fibrillation, and rare ones, such as arrhythmogenic right ventricular cardiomyopathy (ARVC). Clinical observations suggest a potential atrial involvement in ARVC. Arrhythmogenic right ventricular cardiomyopathy is caused by desmosomal gene defects, including reduced plakoglobin expression. Here, we analysed clinical records from 146 ARVC patients to identify that ARVC is more common in males than females. Patients with ARVC also had an increased incidence of atrial arrhythmias and P wave changes. To study desmosomal vulnerability and the effects of AAS on the atria, young adult male mice, heterozygously deficient for plakoglobin (Plako+/- ), and wild type (WT) littermates were chronically exposed to 5α-dihydrotestosterone (DHT) or placebo. The DHT increased atrial expression of pro-hypertrophic, fibrotic and inflammatory transcripts. In mice with reduced plakoglobin, DHT exaggerated P wave abnormalities, atrial conduction slowing, sodium current depletion, action potential amplitude reduction and the fall in action potential depolarization rate. Super-resolution microscopy revealed a decrease in NaV 1.5 membrane clustering in Plako+/- atrial cardiomyocytes after DHT exposure. In summary, AAS combined with plakoglobin deficiency cause pathological atrial electrical remodelling in young male hearts. Male sex is likely to increase the risk of atrial arrhythmia, particularly in those with desmosomal gene variants. This risk is likely to be exaggerated further by AAS use. KEY POINTS: Androgenic male sex hormones, such as testosterone, might increase the risk of atrial fibrillation in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC), which is often caused by desmosomal gene defects (e.g. reduced plakoglobin expression). In this study, we observed a significantly higher proportion of males who had ARVC compared with females, and atrial arrhythmias and P wave changes represented a common observation in advanced ARVC stages. In mice with reduced plakoglobin expression, chronic administration of 5α-dihydrotestosterone led to P wave abnormalities, atrial conduction slowing, sodium current depletion and a decrease in membrane-localized NaV 1.5 clusters. 5α-Dihydrotestosterone, therefore, represents a stimulus aggravating the pro-arrhythmic phenotype in carriers of desmosomal mutations and can affect atrial electrical function.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1113/JP284597; doi:https://doi.org/10.1113/JP284597 34948912,https://doi.org/10.3390/ijerph182413304,Development and Validation of a Primary Care Electronic Health Record Phenotype to Study Migration and Health in the UK.,"Pathak N, Zhang CX, Boukari Y, Burns R, Mathur R, Gonzalez-Izquierdo A, Denaxas S, Sonnenberg P, Hayward A, Aldridge RW.",,International journal of environmental research and public health,2021,2021-12-17,Y,Migration; Phenotype; Validation; Algorithm; Primary Care; Clinical Practice Research Datalink,,,"International migrants comprised 14% of the UK's population in 2020; however, their health is rarely studied at a population level using primary care electronic health records due to difficulties in their identification. We developed a migration phenotype using country of birth, visa status, non-English main/first language and non-UK-origin codes and applied it to the Clinical Practice Research Datalink (CPRD) GOLD database of 16,071,111 primary care patients between 1997 and 2018. We compared the completeness and representativeness of the identified migrant population to Office for National Statistics (ONS) country-of-birth and 2011 census data by year, age, sex, geographic region of birth and ethnicity. Between 1997 to 2018, 403,768 migrants (2.51% of the CPRD GOLD population) were identified: 178,749 (1.11%) had foreign-country-of-birth or visa -status codes, 216,731 (1.35%) non-English-main/first-language codes, and 8288 (0.05%) non-UK-origin codes. The cohort was similarly distributed versus ONS data by sex and region of birth. Migration recording improved over time and younger migrants were better represented than those aged ≥50. The validated phenotype identified a large migrant cohort for use in migration health research in CPRD GOLD to inform healthcare policy and practice. The under-recording of migration status in earlier years and older ages necessitates cautious interpretation of future studies in these groups.",,pdf:https://www.mdpi.com/1660-4601/18/24/13304/pdf?version=1639728813; doi:https://doi.org/10.3390/ijerph182413304; html:https://europepmc.org/articles/PMC8707886; pdf:https://europepmc.org/articles/PMC8707886?pdf=render 34378227,https://doi.org/10.1111/tri.14010,"Health-related quality of life, uncertainty and coping strategies in solid organ transplant recipients during shielding for the COVID-19 pandemic.","McKay SC, Lembach H, Hann A, Okoth K, Anderton J, Nirantharakumar K, Magill L, Torlinska B, Armstrong M, Mascaro J, Inston N, Pinkney T, Ranasinghe A, Borrows R, Ferguson J, Isaac J, Calvert M, Perera MTPR, Hartog H.",,Transplant international : official journal of the European Society for Organ Transplantation,2021,2021-09-16,Y,Isolation; Transplant; Mental health; Health-related Quality Of Life; Shielding; Covid-19,,,"Strict isolation of vulnerable individuals has been a strategy implemented by authorities to protect people from COVID-19. Our objective was to investigate health-related quality of life (HRQoL), uncertainty and coping behaviours in solid organ transplant (SOT) recipients during the COVID-19 pandemic. A cross-sectional survey of adult SOT recipients undergoing follow-up at our institution was performed. Perceived health status, uncertainty and coping strategies were assessed using the EQ-5D-5L, Short-form Mishel Uncertainty in Illness Scale (SF-MUIS) and Brief Cope, respectively. Interactions with COVID-19 risk perception, access to health care, demographic and clinical variables were assessed. The survey was completed by 826 of 3839 (21.5%) invited participants. Overall, low levels of uncertainty in illness were reported, and acceptance was the major coping strategy (92%). Coping by acceptance, feeling protected, self-perceived susceptibility to COVID-19 were associated with lower levels of uncertainty. Health status index scores were significantly lower for those with mental health illness, compromised access to health care, a perceived high risk of severe COVID-19 infection and higher levels of uncertainty. A history of mental health illness, risk perceptions, restricted healthcare access, uncertainty and coping strategies was associated with poorer HRQoL in SOT recipients during strict isolation. These findings may allow identification of strategies to improve HRQoL in SOT recipients during the pandemic.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/tri.14010; doi:https://doi.org/10.1111/tri.14010; html:https://europepmc.org/articles/PMC8420473; pdf:https://europepmc.org/articles/PMC8420473?pdf=render 34038519,https://doi.org/10.1093/ageing/afab084,Developing a UK sarcopenia registry: recruitment and baseline characteristics of the SarcNet pilot.,"Witham MD, Heslop P, Dodds RM, Clegg AP, Hope SV, McDonald C, Smithard D, Storey B, Tan AL, Thornhill A, Sayer AA.",,Age and ageing,2021,2021-09-01,Y,Recruitment; Older People; Registry; Sarcopenia,,,"

Background

sarcopenia registries are a potential method to meet the challenge of recruitment to sarcopenia trials. We tested the feasibility of setting up a UK sarcopenia registry, the feasibility of recruitment methods and sought to characterise the pilot registry population.

Methods

six diverse UK sites took part, with potential participants aged 65 and over approached via mailshots from local primary care practices. Telephone pre-screening using the SARC-F score was followed by in-person screening and baseline visit. Co-morbidities, medications, grip strength, Short Physical Performance Battery, bioimpedance analysis, Geriatric Depression Score, Montreal Cognitive Assessment, Sarcopenia Quality of Life score were performed and permission sought for future recontact. Descriptive statistics for recruitment rates and baseline measures were generated; an embedded randomised trial examined the effect of a University logo on the primary care mailshot on recruitment rates.

Results

sixteen practices contributed a total of 3,508 letters. In total, 428 replies were received (12% response rate); 380 underwent telephone pre-screening of whom 215 (57%) were eligible to attend a screening visit; 150 participants were recruited (40% of those pre-screened) with 147 contributing baseline data. No significant difference was seen in response rates between mailshots with and without the logo (between-group difference 1.1% [95% confidence interval -1.0% to 3.4%], P = 0.31). The mean age of enrollees was 78 years; 72 (49%) were women. In total, 138/147 (94%) had probable sarcopenia on European Working Group on Sarcopenia 2019 criteria and 145/147 (98%) agreed to be recontacted about future studies.

Conclusion

recruitment to a multisite UK sarcopenia registry is feasible, with high levels of consent for recontact.",,pdf:https://academic.oup.com/ageing/article-pdf/50/5/1762/40349116/afab084.pdf; doi:https://doi.org/10.1093/ageing/afab084; html:https://europepmc.org/articles/PMC8437066; pdf:https://europepmc.org/articles/PMC8437066?pdf=render 35016872,https://doi.org/10.1016/j.apmr.2021.12.014,Chronic Physical Health Conditions After Injury: A Comparison of Prevalence and Risk in People With Orthopedic Major Trauma and Other Types of Injury.,"Gelaw AY, Gabbe BJ, Ekegren CL.",,Archives of physical medicine and rehabilitation,2022,2022-01-10,N,Cardiovascular diseases; Rehabilitation; Chronic disease; wounds and injuries; Multiple Trauma,,,"

Objectives

To determine (1) the prevalence of chronic physical health conditions reported preinjury, at the time of injury, up to 1 year postinjury, and 1 to 5 years postinjury; and (2) the risk of chronic physical health conditions reported 1 to 5 years postinjury in people with orthopedic and other types of major trauma.

Design

Cohort study using linked trauma registry and health administrative datasets.

Setting

This study used linked data from the Victorian State Trauma Registry (VSTR), the Victorian Registry of Births, Deaths and Marriages (BDM), the Victorian Admitted Episodes Dataset (VAED), and the Victorian Emergency Minimum Dataset (VEMD).

Participants

Major trauma patients (N=28,522) aged 18 years and older who were registered by the VSTR, with dates of injury from 2007 to 2016, and who survived to at least 1 year after injury, were included in this study. Major trauma cases were classified into 4 groups: (1) orthopedic injury, (2) severe traumatic brain injury (s-TBI), (3) spinal cord injury, and (4) other major trauma.

Intervention

Not applicable.

Main outcome measure

Prevalence of chronic physical health conditions.

Results

The cumulative prevalence of any chronic physical health condition for all participants was 69.3%. The s-TBI group had the highest cumulative prevalence of conditions. The most common conditions were arthritis and arthropathies, cancer, and cardiovascular diseases. Preinjury chronic conditions were most common in people with s-TBI (19.3%) and were least common in people with other types of major trauma (6.6%). The highest prevalence of new-onset conditions after injury was found in people with s-TBI (21.7%) and orthopedic major trauma (21.4%), whereas the lowest prevalence was found in people with other types of major trauma (9.2%). For the orthopedic injury group, there were no significant differences in the adjusted risk of conditions reported 1 to 5 years postinjury compared with other major trauma groups.

Conclusions

Chronic physical health conditions were common among all injury groups. There was no significant difference in the risk of chronic conditions among injury groups. Rehabilitation practitioners should be aware of the risk of chronic conditions in people with orthopedic and other types of major trauma. Long-term follow-up care after injury should include prevention and treatment of chronic conditions.",,doi:https://doi.org/10.1016/j.apmr.2021.12.014 36669843,https://doi.org/10.1136/bmjopen-2022-064364,Implementation of a quality improvement programme using the Active Patient Link call and recall system to improve timeliness and equity of childhood vaccinations: protocol for a mixed-methods evaluation.,"Marszalek M, Hawking MKD, Gutierrez A, Dostal I, Ahmed Z, Firman N, Robson J, Bedford H, Billington A, Moss N, Dezateux C.",,BMJ open,2023,2023-01-20,Y,immunology; Public Health; Preventive Medicine; Community Child Health; Quality In Health Care; Paediatric Infectious Disease & Immunisation,,,"

Introduction

Call and recall systems provide actionable intelligence to improve equity and timeliness of childhood vaccinations, which have been disrupted during the COVID-19 pandemic. We will evaluate the effectiveness, fidelity and sustainability of a data-enabled quality improvement programme delivered in primary care using an Active Patient Link Immunisation (APL-Imms) call and recall system to improve timeliness and equity of uptake in a multiethnic disadvantaged urban population. We will use qualitative methods to evaluate programme delivery, focusing on uptake and use, implementation barriers and service improvements for clinical and non-clinical primary care staff, its fidelity and sustainability.

Methods and analysis

This is a mixed-methods observational study in 284 general practices in north east London (NEL). The target population will be preschool-aged children eligible to receive diphtheria, tetanus and pertussis (DTaP) or measles, mumps and rubella (MMR) vaccinations and registered with an NEL general practice. The intervention comprises an in-practice call and recall tool, facilitation and training, and financial incentives. The quantitative evaluation will include interrupted time Series analyses and Slope Index of Inequality. The primary outcomes will be the proportion of children receiving at least one dose of a DTaP-containing or MMR vaccination defined, respectively, as administered between age 6 weeks and 6 months or between 12 and 18 months of age. The qualitative evaluation will involve a 'Think Aloud' method and semistructured interviews of stakeholders to assess impact, fidelity and sustainability of the APL-Imms tool, and fidelity of the implementation by facilitators.

Ethics and dissemination

The research team has been granted permission from data controllers in participating practices to use deidentified data for audit purposes. As findings will be specific to the local context, research ethics approval is not required. Results will be disseminated in a peer-reviewed journal and to stakeholders, including parents, health providers and commissioners.",,pdf:https://bmjopen.bmj.com/content/bmjopen/13/1/e064364.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-064364; html:https://europepmc.org/articles/PMC9872487; pdf:https://europepmc.org/articles/PMC9872487?pdf=render -36828608,https://doi.org/10.1016/s2589-7500(22)00249-7,The role of patient-reported outcome measures in trials of artificial intelligence health technologies: a systematic evaluation of ClinicalTrials.gov records (1997-2022).,"Pearce FJ, Cruz Rivera S, Liu X, Manna E, Denniston AK, Calvert MJ.",,The Lancet. Digital health,2023,2023-03-01,N,,,,"The extent to which patient-reported outcome measures (PROMs) are used in clinical trials for artificial intelligence (AI) technologies is unknown. In this systematic evaluation, we aim to establish how PROMs are being used to assess AI health technologies. We searched ClinicalTrials.gov for interventional trials registered from inception to Sept 20, 2022, and included trials that tested an AI health technology. We excluded observational studies, patient registries, and expanded access reports. We extracted data regarding the form, function, and intended use population of the AI health technology, in addition to the PROMs used and whether PROMs were incorporated as an input or output in the AI model. The search identified 2958 trials, of which 627 were included in the analysis. 152 (24%) of the included trials used one or more PROM, visual analogue scale, patient-reported experience measure, or usability measure as a trial endpoint. The type of AI health technologies used by these trials included AI-enabled smart devices, clinical decision support systems, and chatbots. The number of clinical trials of AI health technologies registered on ClinicalTrials.gov and the proportion of trials that used PROMs increased from registry inception to 2022. The most common clinical areas AI health technologies were designed for were digestive system health for non-PROM trials and musculoskeletal health (followed by mental and behavioural health) for PROM trials, with PROMs commonly used in clinical areas for which assessment of health-related quality of life and symptom burden is particularly important. Additionally, AI-enabled smart devices were the most common applications tested in trials that used at least one PROM. 24 trials tested AI models that captured PROM data as an input for the AI model. PROM use in clinical trials of AI health technologies falls behind PROM use in all clinical trials. Trial records having inadequate detail regarding the PROMs used or the type of AI health technology tested was a limitation of this systematic evaluation and might have contributed to inaccuracies in the data synthesised. Overall, the use of PROMs in the function and assessment of AI health technologies is not only possible, but is a powerful way of showing that, even in the most technologically advanced health-care systems, patients' perspectives remain central.",,doi:https://doi.org/10.1016/s2589-7500(22)00249-7; doi:https://doi.org/10.1016/S2589-7500(22)00249-7 35144240,https://doi.org/10.2196/32543,Artificial Intelligence-Enabled Social Media Analysis for Pharmacovigilance of COVID-19 Vaccinations in the United Kingdom: Observational Study.,"Hussain Z, Sheikh Z, Tahir A, Dashtipour K, Gogate M, Sheikh A, Hussain A.",,JMIR public health and surveillance,2022,2022-05-27,Y,Artificial intelligence; Vaccination; Public Health; Health Informatics; Natural Language Processing; Facebook; Social Media; Twitter; Sentiment Analysis; Infodemiology; Deep Learning; Covid-19,,,"

Background

The rollout of vaccines for COVID-19 in the United Kingdom started in December 2020. Uptake has been high, and there has been a subsequent reduction in infections, hospitalizations, and deaths among vaccinated individuals. However, vaccine hesitancy remains a concern, in particular relating to adverse effects following immunization (AEFIs). Social media analysis has the potential to inform policy makers about AEFIs being discussed by the public as well as public attitudes toward the national immunization campaign.

Objective

We sought to assess the frequency and nature of AEFI-related mentions on social media in the United Kingdom and to provide insights on public sentiments toward COVID-19 vaccines.

Methods

We extracted and analyzed over 121,406 relevant Twitter and Facebook posts, from December 8, 2020, to April 30, 2021. These were thematically filtered using a 2-step approach, initially using COVID-19-related keywords and then using vaccine- and manufacturer-related keywords. We identified AEFI-related keywords and modeled their word frequency to monitor their trends over 2-week periods. We also adapted and utilized our recently developed hybrid ensemble model, which combines state-of-the-art lexicon rule-based and deep learning-based approaches, to analyze sentiment trends relating to the main vaccines available in the United Kingdom.

Results

Our COVID-19 AEFI search strategy identified 46,762 unique Facebook posts by 14,346 users and 74,644 tweets (excluding retweets) by 36,446 users over the 4-month period. We identified an increasing trend in the number of mentions for each AEFI on social media over the study period. The most frequent AEFI mentions were found to be symptoms related to appetite (n=79,132, 14%), allergy (n=53,924, 9%), injection site (n=56,152, 10%), and clots (n=43,907, 8%). We also found some rarely reported AEFIs such as Bell palsy (n=11,909, 2%) and Guillain-Barre syndrome (n=9576, 2%) being discussed as frequently as more well-known side effects like headache (n=10,641, 2%), fever (n=12,707, 2%), and diarrhea (n=16,559, 3%). Overall, we found public sentiment toward vaccines and their manufacturers to be largely positive (58%), with a near equal split between negative (22%) and neutral (19%) sentiments. The sentiment trend was relatively steady over time and had minor variations, likely based on political and regulatory announcements and debates.

Conclusions

The most frequently discussed COVID-19 AEFIs on social media were found to be broadly consistent with those reported in the literature and by government pharmacovigilance. We also detected potential safety signals from our analysis that have been detected elsewhere and are currently being investigated. As such, we believe our findings support the use of social media analysis to provide a complementary data source to conventional knowledge sources being used for pharmacovigilance purposes.",,pdf:https://publichealth.jmir.org/2022/5/e32543/PDF; doi:https://doi.org/10.2196/32543; html:https://europepmc.org/articles/PMC9150729 +36828608,https://doi.org/10.1016/s2589-7500(22)00249-7,The role of patient-reported outcome measures in trials of artificial intelligence health technologies: a systematic evaluation of ClinicalTrials.gov records (1997-2022).,"Pearce FJ, Cruz Rivera S, Liu X, Manna E, Denniston AK, Calvert MJ.",,The Lancet. Digital health,2023,2023-03-01,N,,,,"The extent to which patient-reported outcome measures (PROMs) are used in clinical trials for artificial intelligence (AI) technologies is unknown. In this systematic evaluation, we aim to establish how PROMs are being used to assess AI health technologies. We searched ClinicalTrials.gov for interventional trials registered from inception to Sept 20, 2022, and included trials that tested an AI health technology. We excluded observational studies, patient registries, and expanded access reports. We extracted data regarding the form, function, and intended use population of the AI health technology, in addition to the PROMs used and whether PROMs were incorporated as an input or output in the AI model. The search identified 2958 trials, of which 627 were included in the analysis. 152 (24%) of the included trials used one or more PROM, visual analogue scale, patient-reported experience measure, or usability measure as a trial endpoint. The type of AI health technologies used by these trials included AI-enabled smart devices, clinical decision support systems, and chatbots. The number of clinical trials of AI health technologies registered on ClinicalTrials.gov and the proportion of trials that used PROMs increased from registry inception to 2022. The most common clinical areas AI health technologies were designed for were digestive system health for non-PROM trials and musculoskeletal health (followed by mental and behavioural health) for PROM trials, with PROMs commonly used in clinical areas for which assessment of health-related quality of life and symptom burden is particularly important. Additionally, AI-enabled smart devices were the most common applications tested in trials that used at least one PROM. 24 trials tested AI models that captured PROM data as an input for the AI model. PROM use in clinical trials of AI health technologies falls behind PROM use in all clinical trials. Trial records having inadequate detail regarding the PROMs used or the type of AI health technology tested was a limitation of this systematic evaluation and might have contributed to inaccuracies in the data synthesised. Overall, the use of PROMs in the function and assessment of AI health technologies is not only possible, but is a powerful way of showing that, even in the most technologically advanced health-care systems, patients' perspectives remain central.",,doi:https://doi.org/10.1016/s2589-7500(22)00249-7; doi:https://doi.org/10.1016/S2589-7500(22)00249-7 36854461,https://doi.org/10.1136/bmj-2022-073149,Realistic expectations are key to realising the benefits of polygenic scores.,"Sud A, Horton RH, Hingorani AD, Tzoulaki I, Turnbull C, Houlston RS, Lucassen A.",,BMJ (Clinical research ed.),2023,2023-02-28,Y,,,,,,pdf:https://www.bmj.com/content/bmj/380/bmj-2022-073149.full.pdf; doi:https://doi.org/10.1136/bmj-2022-073149; html:https://europepmc.org/articles/PMC9973128 34409990,https://doi.org/10.1093/dote/doab058,Demographic and lifestyle risk factors for gastroesophageal reflux disease and Barrett's esophagus in Australia.,"Wang SE, Kendall BJ, Hodge AM, Dixon-Suen SC, Dashti SG, Makalic E, Williamson EM, Thomas RJS, Giles GG, English DR.",,Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus,2022,2022-01-01,N,Risk factor; Barrett’s esophagus; epidemiology; Gastroesophageal Reflux (Gerd),,,"We examined demographic and lifestyle risk factors for incidence of gastroesophageal reflux disease (GERD) and Barrett's esophagus (BE) in an Australian cohort of 20,975 participants aged 40-63 at recruitment (1990-1994). Information on GERD and BE was collected between 2007 and 2010. GERD symptoms were defined as self-reported heartburn or acid regurgitation. BE was defined as endoscopically confirmed columnar-lined esophagus. Risk factors for developing GERD symptoms, BE diagnosis, age at symptom onset, and age at BE diagnosis were quantified using regression. During a mean follow-up of 15.8 years, risk of GERD symptoms was 7.5% (n = 1,318) for daily, 7.5% (n = 1,333) for 2-6 days/week, and 4.3% (n = 751) for 1 day/week. There were 210 (1.0%) endoscopically diagnosed BE cases, of whom 141 had histologically confirmed esophageal intestinal metaplasia. Female sex, younger age, lower socioeconomic position (SEP) and educational attainment, and former smoking were associated with higher GERD risk. Male sex and smoking were associated with earlier GERD symptom onset. Men, older participants, those with higher SEP, and former smokers were at higher BE risk. There was some evidence higher SEP was associated with earlier BE diagnosis. GERD and BE had different demographic risk factors but shared similar lifestyle factors. Earlier GERD symptom onset for men and smokers might have contributed to higher BE risk. The SEP patterns observed for GERD and BE suggest potential inequity in access to care. These findings would be important in the development of clinical risk prediction models for early detection of BE.",,pdf:https://academic.oup.com/dote/article-pdf/35/1/doab058/42098674/doab058.pdf; doi:https://doi.org/10.1093/dote/doab058 33500288,https://doi.org/10.1136/bmjopen-2020-042945,Hospital bed capacity and usage across secondary healthcare providers in England during the first wave of the COVID-19 pandemic: a descriptive analysis.,"Mateen BA, Wilde H, Dennis JM, Duncan A, Thomas N, McGovern A, Denaxas S, Keeling M, Vollmer S.",,BMJ open,2021,2021-01-26,Y,Public Health; Health Policy; Intensive & Critical Care; Covid-19,,,"

Objective

In this study, we describe the pattern of bed occupancy across England during the peak of the first wave of the COVID-19 pandemic.

Design

Descriptive survey.

Setting

All non-specialist secondary care providers in England from 27 March27to 5 June 2020.

Participants

Acute (non-specialist) trusts with a type 1 (ie, 24 hours/day, consultant-led) accident and emergency department (n=125), Nightingale (field) hospitals (n=7) and independent sector secondary care providers (n=195).

Main outcome measures

Two thresholds for 'safe occupancy' were used: 85% as per the Royal College of Emergency Medicine and 92% as per NHS Improvement.

Results

At peak availability, there were 2711 additional beds compatible with mechanical ventilation across England, reflecting a 53% increase in capacity, and occupancy never exceeded 62%. A consequence of the repurposing of beds meant that at the trough there were 8.7% (8508) fewer general and acute beds across England, but occupancy never exceeded 72%. The closest to full occupancy of general and acute bed (surge) capacity that any trust in England reached was 99.8% . For beds compatible with mechanical ventilation there were 326 trust-days (3.7%) spent above 85% of surge capacity and 154 trust-days (1.8%) spent above 92%. 23 trusts spent a cumulative 81 days at 100% saturation of their surge ventilator bed capacity (median number of days per trust=1, range: 1-17). However, only three sustainability and transformation partnerships (aggregates of geographically co-located trusts) reached 100% saturation of their mechanical ventilation beds.

Conclusions

Throughout the first wave of the pandemic, an adequate supply of all bed types existed at a national level. However, due to an unequal distribution of bed utilisation, many trusts spent a significant period operating above 'safe-occupancy' thresholds despite substantial capacity in geographically co-located trusts, a key operational issue to address in preparing for future waves.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/1/e042945.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-042945; html:https://europepmc.org/articles/PMC7843315; pdf:https://europepmc.org/articles/PMC7843315?pdf=render -37813531,https://doi.org/10.1136/bmjopen-2023-073162,Detection and evaluation of signals associated with exposure to individual and combination of medications in pregnancy: a signal detection study protocol.,"Subramanian A, Lee SI, Hemali Sudasinghe SPB, Wambua S, Phillips K, Singh M, Azcoaga-Lorenzo A, Cockburn N, Wang J, Fagbamigbe A, Usman M, Damase-Michel C, Yau C, Kent L, McCowan C, OReilly D, Santorelli G, Hope H, Kennedy J, Mhereeg M, Abel KM, Eastwood KA, Black M, Loane M, Moss N, Brophy S, Brocklehurst P, Dolk H, Nelson-Piercy C, Nirantharakumar K, MuM-PreDiCT Group.",,BMJ open,2023,2023-10-09,Y,Obstetrics; epidemiology; Maternal Medicine,,,"

Introduction

Considering the high prevalence of polypharmacy in pregnant women and the knowledge gap in the risk-benefit safety profile of their often-complex treatment plan, more research is needed to optimise prescribing. In this study, we aim to detect adverse and protective effect signals of exposure to individual and pairwise combinations of medications during pregnancy.

Methods and analysis

Using a range of real-world data sources from the UK, we aim to conduct a pharmacovigilance study to assess the safety of medications prescribed during the preconception period (3 months prior to conception) and first trimester of pregnancy. Women aged between 15 and 49 years with a record of pregnancy within the Clinical Practice Research Datalink (CPRD) Pregnancy Register, the Welsh Secure Anonymised Information Linkage (SAIL), the Scottish Morbidity Record (SMR) data sets and the Northern Ireland Maternity System (NIMATS) will be included. A series of case control studies will be conducted to estimate measures of disproportionality, detecting signals of association between a range of pregnancy outcomes and exposure to individual and combinations of medications. A multidisciplinary expert team will be invited to a signal detection workshop. By employing a structured framework, signals will be transparently assessed by each member of the team using a questionnaire appraising the signals on aspects of temporality, selection, time and measurement-related biases and confounding by underlying disease or comedications. Through group discussion, the expert team will reach consensus on each of the medication exposure-outcome signal, thereby excluding spurious signals, leaving signals suggestive of causal associations for further evaluation.

Ethics and dissemination

Ethical approval has been obtained from the Independent Scientific Advisory Committee, SAIL Information Governance Review Panel, University of St. Andrews Teaching and Research Ethics Committee and Office for Research Ethics Committees Northern Ireland (ORECNI) for access and use of CPRD, SAIL, SMR and NIMATS data, respectively.",,pdf:https://bmjopen.bmj.com/content/bmjopen/13/10/e073162.full.pdf; doi:https://doi.org/10.1136/bmjopen-2023-073162; html:https://europepmc.org/articles/PMC10565241; pdf:https://europepmc.org/articles/PMC10565241?pdf=render 34734970,https://doi.org/10.1001/jamaophthalmol.2021.4601,"Association of Smoking, Alcohol Consumption, Blood Pressure, Body Mass Index, and Glycemic Risk Factors With Age-Related Macular Degeneration: A Mendelian Randomization Study.","Kuan V, Warwick A, Hingorani A, Tufail A, Cipriani V, Burgess S, Sofat R, International AMD Genomics Consortium (IAMDGC).",,JAMA ophthalmology,2021,2021-12-01,Y,,,,"

Importance

Advanced age-related macular degeneration (AMD) is a leading cause of blindness in Western countries. Causal, modifiable risk factors need to be identified to develop preventive measures for advanced AMD.

Objective

To assess whether smoking, alcohol consumption, blood pressure, body mass index, and glycemic traits are associated with increased risk of advanced AMD.

Design, setting, participants

This study used 2-sample mendelian randomization. Genetic instruments composed of variants associated with risk factors at genome-wide significance (P < 5 × 10-8) were obtained from published genome-wide association studies. Summary-level statistics for these instruments were obtained for advanced AMD from the International AMD Genomics Consortium 2016 data set, which consisted of 16 144 individuals with AMD and 17 832 control individuals. Data were analyzed from July 2020 to September 2021.

Exposures

Smoking initiation, smoking cessation, lifetime smoking, age at smoking initiation, alcoholic drinks per week, body mass index, systolic and diastolic blood pressure, type 2 diabetes, glycated hemoglobin, fasting glucose, and fasting insulin.

Main outcomes and measures

Advanced AMD and its subtypes, geographic atrophy (GA), and neovascular AMD.

Results

A 1-SD increase in logodds of genetically predicted smoking initiation was associated with higher risk of advanced AMD (odds ratio [OR], 1.26; 95% CI, 1.13-1.40; P < .001), while a 1-SD increase in logodds of genetically predicted smoking cessation (former vs current smoking) was associated with lower risk of advanced AMD (OR, 0.66; 95% CI, 0.50-0.87; P = .003). Genetically predicted increased lifetime smoking was associated with increased risk of advanced AMD (OR per 1-SD increase in lifetime smoking behavior, 1.32; 95% CI, 1.09-1.59; P = .004). Genetically predicted alcohol consumption was associated with higher risk of GA (OR per 1-SD increase of log-transformed alcoholic drinks per week, 2.70; 95% CI, 1.48-4.94; P = .001). There was insufficient evidence to suggest that genetically predicted blood pressure, body mass index, and glycemic traits were associated with advanced AMD.

Conclusions and relevance

This study provides genetic evidence that increased alcohol intake may be a causal risk factor for GA. As there are currently no known treatments for GA, this finding has important public health implications. These results also support previous observational studies associating smoking behavior with risk of advanced AMD, thus reinforcing existing public health messages regarding the risk of blindness associated with smoking.",,pdf:https://jamanetwork.com/journals/jamaophthalmology/articlepdf/2785704/jamaophthalmology_kuan_2021_oi_210068_1639510445.31311.pdf; doi:https://doi.org/10.1001/jamaophthalmol.2021.4601; html:https://europepmc.org/articles/PMC8569599 -35869974,https://doi.org/10.1093/ndt/gfac224,Care processes and outcomes of deprivation across the clinical course of kidney disease: findings from a high-income country with universal healthcare.,"Sawhney S, Blakeman T, Blana D, Boyers D, Fluck N, Nath M, Methven S, Rzewuska M, Black C.",,"Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association",2023,2023-05-01,Y,Prognosis; epidemiology; Health Inequalities; Ckd; Aki; Care Processes,,,"

Background

No single study contrasts the extent and consequences of inequity of kidney care across the clinical course of kidney disease.

Methods

This population study of Grampian (UK) followed incident presentations of acute kidney injury (AKI) and incident estimated glomerular filtration rate (eGFR) thresholds of <60, <45 and <30 mL/min/1.73 m2 in separate cohorts (2011-2021). The key exposure was area-level deprivation (lowest quintile of the Scottish Index of Multiple Deprivation). Outcomes were care processes (monitoring, prescribing, appointments, unscheduled care), long-term mortality and kidney failure. Modelling involved multivariable logistic regression, negative binomial regression and cause-specific Cox models with and without adjustment of comorbidities.

Results

There were 41 313, 51 190, 32 171 and 17 781 new presentations of AKI and eGFR thresholds <60, <45 and <30  mL/min/1.73 m2. A total of 6.1-7.8% of the population was from deprived areas and (versus all others) presented on average 5 years younger, with more diabetes and pulmonary and liver disease. Those from deprived areas were more likely to present initially in hospital, less likely to receive community monitoring, less likely to attend appointments and more likely to have an unplanned emergency department or hospital admission episode. Deprivation had the greatest association with long-term kidney failure at the eGFR <60 mL/min/1.73 m2 threshold {adjusted hazard ratio [HR] 1.48 [95% confidence interval (CI) 1.17-1.87]} and this association decreased with advancing disease severity [HR 1.09 (95% CI 0.93-1.28) at eGFR <30 mL/min/1.73 m2), with a similar pattern for mortality. Across all analyses the most detrimental associations of deprivation were an eGFR threshold <60 mL/min/1.73 m2, AKI, males and those <65 years of age.

Conclusions

Even in a high-income country with universal healthcare, serious and consistent inequities in kidney care exist. The poorer care and outcomes with area-level deprivation were greater earlier in the disease course.",,pdf:https://academic.oup.com/ndt/advance-article-pdf/doi/10.1093/ndt/gfac224/45505736/gfac224.pdf; doi:https://doi.org/10.1093/ndt/gfac224; html:https://europepmc.org/articles/PMC10157789; pdf:https://europepmc.org/articles/PMC10157789?pdf=render +37813531,https://doi.org/10.1136/bmjopen-2023-073162,Detection and evaluation of signals associated with exposure to individual and combination of medications in pregnancy: a signal detection study protocol.,"Subramanian A, Lee SI, Hemali Sudasinghe SPB, Wambua S, Phillips K, Singh M, Azcoaga-Lorenzo A, Cockburn N, Wang J, Fagbamigbe A, Usman M, Damase-Michel C, Yau C, Kent L, McCowan C, OReilly D, Santorelli G, Hope H, Kennedy J, Mhereeg M, Abel KM, Eastwood KA, Black M, Loane M, Moss N, Brophy S, Brocklehurst P, Dolk H, Nelson-Piercy C, Nirantharakumar K, MuM-PreDiCT Group.",,BMJ open,2023,2023-10-09,Y,Obstetrics; epidemiology; Maternal Medicine,,,"

Introduction

Considering the high prevalence of polypharmacy in pregnant women and the knowledge gap in the risk-benefit safety profile of their often-complex treatment plan, more research is needed to optimise prescribing. In this study, we aim to detect adverse and protective effect signals of exposure to individual and pairwise combinations of medications during pregnancy.

Methods and analysis

Using a range of real-world data sources from the UK, we aim to conduct a pharmacovigilance study to assess the safety of medications prescribed during the preconception period (3 months prior to conception) and first trimester of pregnancy. Women aged between 15 and 49 years with a record of pregnancy within the Clinical Practice Research Datalink (CPRD) Pregnancy Register, the Welsh Secure Anonymised Information Linkage (SAIL), the Scottish Morbidity Record (SMR) data sets and the Northern Ireland Maternity System (NIMATS) will be included. A series of case control studies will be conducted to estimate measures of disproportionality, detecting signals of association between a range of pregnancy outcomes and exposure to individual and combinations of medications. A multidisciplinary expert team will be invited to a signal detection workshop. By employing a structured framework, signals will be transparently assessed by each member of the team using a questionnaire appraising the signals on aspects of temporality, selection, time and measurement-related biases and confounding by underlying disease or comedications. Through group discussion, the expert team will reach consensus on each of the medication exposure-outcome signal, thereby excluding spurious signals, leaving signals suggestive of causal associations for further evaluation.

Ethics and dissemination

Ethical approval has been obtained from the Independent Scientific Advisory Committee, SAIL Information Governance Review Panel, University of St. Andrews Teaching and Research Ethics Committee and Office for Research Ethics Committees Northern Ireland (ORECNI) for access and use of CPRD, SAIL, SMR and NIMATS data, respectively.",,pdf:https://bmjopen.bmj.com/content/bmjopen/13/10/e073162.full.pdf; doi:https://doi.org/10.1136/bmjopen-2023-073162; html:https://europepmc.org/articles/PMC10565241; pdf:https://europepmc.org/articles/PMC10565241?pdf=render 31361079,https://doi.org/10.1111/1742-6723.13361,"Animal-vehicle collisions in Victoria, Australia: An under-recognised cause of road traffic crashes.","Ang JY, Gabbe B, Cameron P, Beck B.",,Emergency medicine Australasia : EMA,2019,2019-07-30,N,Injury; Prevention; Traffic; Motor Vehicle,,,"

Objective

Non-fatal injuries sustained from animal-vehicle collisions are a globally under-recognised road safety issue, with limited data on these crash types. The present study aimed to quantify the number and causes of major trauma events resulting from animal-vehicle collisions.

Methods

The study was a retrospective analysis of major trauma cases occurring in Victoria, Australia, between 2007 and 2016, using data from the population-based Victorian State Trauma Registry. To identify animal-vehicle collisions, Victorian State Trauma Registry injury codes were combined with text-mining of the text description of the injury event.

Results

Over the 10 year period, there were 152 major trauma patients who were admitted to Victorian trauma-receiving hospitals due to vehicle collisions with animals. The crude population-based incidence rate for animal-vehicle collisions increased by 6.7% per year (incidence rate ratio 1.07; 95% confidence interval 1.01-1.13; P = 0.02).

Conclusion

Development of systematic recording methods of animal-vehicle collisions will improve reporting of these crash types to assist future studies in implementing effective countermeasures.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/1742-6723.13361; doi:https://doi.org/10.1111/1742-6723.13361 -35435219,https://doi.org/10.1093/ehjqcco/qcac016,Temporal trends in disease-specific causes of cardiovascular mortality amongst patients with cancer in the USA between 1999 and 2019.,"Raisi-Estabragh Z, Kobo O, Freeman P, Petersen SE, Kolman L, Miller RJH, Roguin A, Van Spall HGC, Vuong J, Yang EH, Mamas MA.",,European heart journal. Quality of care & clinical outcomes,2022,2022-12-01,Y,Cancer; Cardiovascular disease; epidemiology; Cardiovascular Mortality; Mortality Trends; Cardio-oncology,,,"

Aims

We report disease-specific cardiovascular causes of mortality among cancer patients in the USA between 1999 and 2019, considering temporal trends by age, sex, and cancer site.

Methods and results

We used the Multiple Cause of Death database, accessed through the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research resource. We included 629 308 decedents with cardiovascular disease (CVD) recorded as the primary cause of death and active malignancy listed as a contributing cause of death. We created disease-specific CVD categories and grouped cancers by site. We calculated the proportion of CVD deaths attributed to each disease category stratified by sex, age, and cancer site. We also examined disease-specific temporal trends by cancer site. Ischaemic heart disease (IHD) was the most common cardiovascular cause of death across all cancer types (55.6%), being more common in men (59.8%), older ages, and in those with lung (67.8%) and prostate (58.3%) cancers. Cerebrovascular disease (12.9%) and hypertensive diseases (7.6%) were other common causes of death. The proportion of deaths due to heart failure was greatest in haematological (7.7%) and breast (6.3%) cancers. There was a decreasing temporal trend in the proportion of cardiovascular deaths attributed to IHD across all cancer types. The proportion of deaths due to hypertensive diseases showed the greatest percentage increase, with the largest change in breast cancer patients (+191.1%).

Conclusion

We demonstrate differential cardiovascular mortality risk by cancer site and demographics, providing insight into the evolving healthcare needs of this growing high-cardiovascular risk population.",,pdf:https://academic.oup.com/ehjqcco/advance-article-pdf/doi/10.1093/ehjqcco/qcac016/43887262/qcac016.pdf; doi:https://doi.org/10.1093/ehjqcco/qcac016; html:https://europepmc.org/articles/PMC9745666; pdf:https://europepmc.org/articles/PMC9745666?pdf=render -34127232,https://doi.org/10.1016/j.artmed.2021.102083,Multi-domain clinical natural language processing with MedCAT: The Medical Concept Annotation Toolkit.,"Kraljevic Z, Searle T, Shek A, Roguski L, Noor K, Bean D, Mascio A, Zhu L, Folarin AA, Roberts A, Bendayan R, Richardson MP, Stewart R, Shah AD, Wong WK, Ibrahim Z, Teo JT, Dobson RJB.",,Artificial intelligence in medicine,2021,2021-05-01,N,Clinical Natural Language Processing; Clinical Concept Embeddings; Clinical Ontology Embeddings; Electronic Health Record Information Extraction,,,"Electronic health records (EHR) contain large volumes of unstructured text, requiring the application of information extraction (IE) technologies to enable clinical analysis. We present the open source Medical Concept Annotation Toolkit (MedCAT) that provides: (a) a novel self-supervised machine learning algorithm for extracting concepts using any concept vocabulary including UMLS/SNOMED-CT; (b) a feature-rich annotation interface for customizing and training IE models; and (c) integrations to the broader CogStack ecosystem for vendor-agnostic health system deployment. We show improved performance in extracting UMLS concepts from open datasets (F1:0.448-0.738 vs 0.429-0.650). Further real-world validation demonstrates SNOMED-CT extraction at 3 large London hospitals with self-supervised training over ∼8.8B words from ∼17M clinical records and further fine-tuning with ∼6K clinician annotated examples. We show strong transferability (F1 > 0.94) between hospitals, datasets and concept types indicating cross-domain EHR-agnostic utility for accelerated clinical and research use cases.",,pdf:http://arxiv.org/pdf/2010.01165; doi:https://doi.org/10.1016/j.artmed.2021.102083 32119825,https://doi.org/10.1016/s2214-109x(20)30074-7,Feasibility of controlling COVID-19 outbreaks by isolation of cases and contacts.,"Hellewell J, Abbott S, Gimma A, Bosse NI, Jarvis CI, Russell TW, Munday JD, Kucharski AJ, Edmunds WJ, Centre for the Mathematical Modelling of Infectious Diseases COVID-19 Working Group, Funk S, Eggo RM.",,The Lancet. Global health,2020,2020-02-28,Y,,Improving Public Health,COVID-19,"

Background

Isolation of cases and contact tracing is used to control outbreaks of infectious diseases, and has been used for coronavirus disease 2019 (COVID-19). Whether this strategy will achieve control depends on characteristics of both the pathogen and the response. Here we use a mathematical model to assess if isolation and contact tracing are able to control onwards transmission from imported cases of COVID-19.

Methods

We developed a stochastic transmission model, parameterised to the COVID-19 outbreak. We used the model to quantify the potential effectiveness of contact tracing and isolation of cases at controlling a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-like pathogen. We considered scenarios that varied in the number of initial cases, the basic reproduction number (R0), the delay from symptom onset to isolation, the probability that contacts were traced, the proportion of transmission that occurred before symptom onset, and the proportion of subclinical infections. We assumed isolation prevented all further transmission in the model. Outbreaks were deemed controlled if transmission ended within 12 weeks or before 5000 cases in total. We measured the success of controlling outbreaks using isolation and contact tracing, and quantified the weekly maximum number of cases traced to measure feasibility of public health effort.

Findings

Simulated outbreaks starting with five initial cases, an R0 of 1·5, and 0% transmission before symptom onset could be controlled even with low contact tracing probability; however, the probability of controlling an outbreak decreased with the number of initial cases, when R0 was 2·5 or 3·5 and with more transmission before symptom onset. Across different initial numbers of cases, the majority of scenarios with an R0 of 1·5 were controllable with less than 50% of contacts successfully traced. To control the majority of outbreaks, for R0 of 2·5 more than 70% of contacts had to be traced, and for an R0 of 3·5 more than 90% of contacts had to be traced. The delay between symptom onset and isolation had the largest role in determining whether an outbreak was controllable when R0 was 1·5. For R0 values of 2·5 or 3·5, if there were 40 initial cases, contact tracing and isolation were only potentially feasible when less than 1% of transmission occurred before symptom onset.

Interpretation

In most scenarios, highly effective contact tracing and case isolation is enough to control a new outbreak of COVID-19 within 3 months. The probability of control decreases with long delays from symptom onset to isolation, fewer cases ascertained by contact tracing, and increasing transmission before symptoms. This model can be modified to reflect updated transmission characteristics and more specific definitions of outbreak control to assess the potential success of local response efforts.

Funding

Wellcome Trust, Global Challenges Research Fund, and Health Data Research UK.",,pdf:http://www.thelancet.com/article/S2214109X20300747/pdf; doi:https://doi.org/10.1016/S2214-109X(20)30074-7; html:https://europepmc.org/articles/PMC7097845; pdf:https://europepmc.org/articles/PMC7097845?pdf=render +35869974,https://doi.org/10.1093/ndt/gfac224,Care processes and outcomes of deprivation across the clinical course of kidney disease: findings from a high-income country with universal healthcare.,"Sawhney S, Blakeman T, Blana D, Boyers D, Fluck N, Nath M, Methven S, Rzewuska M, Black C.",,"Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association",2023,2023-05-01,Y,Prognosis; epidemiology; Health Inequalities; Ckd; Aki; Care Processes,,,"

Background

No single study contrasts the extent and consequences of inequity of kidney care across the clinical course of kidney disease.

Methods

This population study of Grampian (UK) followed incident presentations of acute kidney injury (AKI) and incident estimated glomerular filtration rate (eGFR) thresholds of <60, <45 and <30 mL/min/1.73 m2 in separate cohorts (2011-2021). The key exposure was area-level deprivation (lowest quintile of the Scottish Index of Multiple Deprivation). Outcomes were care processes (monitoring, prescribing, appointments, unscheduled care), long-term mortality and kidney failure. Modelling involved multivariable logistic regression, negative binomial regression and cause-specific Cox models with and without adjustment of comorbidities.

Results

There were 41 313, 51 190, 32 171 and 17 781 new presentations of AKI and eGFR thresholds <60, <45 and <30  mL/min/1.73 m2. A total of 6.1-7.8% of the population was from deprived areas and (versus all others) presented on average 5 years younger, with more diabetes and pulmonary and liver disease. Those from deprived areas were more likely to present initially in hospital, less likely to receive community monitoring, less likely to attend appointments and more likely to have an unplanned emergency department or hospital admission episode. Deprivation had the greatest association with long-term kidney failure at the eGFR <60 mL/min/1.73 m2 threshold {adjusted hazard ratio [HR] 1.48 [95% confidence interval (CI) 1.17-1.87]} and this association decreased with advancing disease severity [HR 1.09 (95% CI 0.93-1.28) at eGFR <30 mL/min/1.73 m2), with a similar pattern for mortality. Across all analyses the most detrimental associations of deprivation were an eGFR threshold <60 mL/min/1.73 m2, AKI, males and those <65 years of age.

Conclusions

Even in a high-income country with universal healthcare, serious and consistent inequities in kidney care exist. The poorer care and outcomes with area-level deprivation were greater earlier in the disease course.",,pdf:https://academic.oup.com/ndt/advance-article-pdf/doi/10.1093/ndt/gfac224/45505736/gfac224.pdf; doi:https://doi.org/10.1093/ndt/gfac224; html:https://europepmc.org/articles/PMC10157789; pdf:https://europepmc.org/articles/PMC10157789?pdf=render +34127232,https://doi.org/10.1016/j.artmed.2021.102083,Multi-domain clinical natural language processing with MedCAT: The Medical Concept Annotation Toolkit.,"Kraljevic Z, Searle T, Shek A, Roguski L, Noor K, Bean D, Mascio A, Zhu L, Folarin AA, Roberts A, Bendayan R, Richardson MP, Stewart R, Shah AD, Wong WK, Ibrahim Z, Teo JT, Dobson RJB.",,Artificial intelligence in medicine,2021,2021-05-01,N,Clinical Natural Language Processing; Clinical Concept Embeddings; Clinical Ontology Embeddings; Electronic Health Record Information Extraction,,,"Electronic health records (EHR) contain large volumes of unstructured text, requiring the application of information extraction (IE) technologies to enable clinical analysis. We present the open source Medical Concept Annotation Toolkit (MedCAT) that provides: (a) a novel self-supervised machine learning algorithm for extracting concepts using any concept vocabulary including UMLS/SNOMED-CT; (b) a feature-rich annotation interface for customizing and training IE models; and (c) integrations to the broader CogStack ecosystem for vendor-agnostic health system deployment. We show improved performance in extracting UMLS concepts from open datasets (F1:0.448-0.738 vs 0.429-0.650). Further real-world validation demonstrates SNOMED-CT extraction at 3 large London hospitals with self-supervised training over ∼8.8B words from ∼17M clinical records and further fine-tuning with ∼6K clinician annotated examples. We show strong transferability (F1 > 0.94) between hospitals, datasets and concept types indicating cross-domain EHR-agnostic utility for accelerated clinical and research use cases.",,pdf:http://arxiv.org/pdf/2010.01165; doi:https://doi.org/10.1016/j.artmed.2021.102083 33749694,https://doi.org/,The evidence for assessing frailty and sarcopenia in an acute medical unit: a systematic review.,"Kamwa V, Seccombe A, Sapey E.",,Acute medicine,2021,2021-01-01,N,,,,"

Background/objectives

A systematic review was conducted to assess if frailty and sarcopenia were associated with poorer outcomes in older adults admitted to an acute medical unit (AMU).

Methods

Eligible studies included older adults with an unplanned admission to an AMU and included a measure of frailty or sarcopenia, completed within 72 hours of admission. Risk of bias was assessed.

Results

Of 1659 identified articles, 16 were included (4 on sarcopenia and 12 on frailty). There was significant study heterogeneity. Overall, frailty and sarcopenia were associated with worse outcomes. Targeted interventions appeared to improve outcomes.

Conclusion

Current evidence suggests some benefit in screening older adults admitted to an AMU for frailty and sarcopenia. However, further studies are required before clinical adoption.",, +35435219,https://doi.org/10.1093/ehjqcco/qcac016,Temporal trends in disease-specific causes of cardiovascular mortality amongst patients with cancer in the USA between 1999 and 2019.,"Raisi-Estabragh Z, Kobo O, Freeman P, Petersen SE, Kolman L, Miller RJH, Roguin A, Van Spall HGC, Vuong J, Yang EH, Mamas MA.",,European heart journal. Quality of care & clinical outcomes,2022,2022-12-01,Y,Cancer; Cardiovascular disease; epidemiology; Cardiovascular Mortality; Mortality Trends; Cardio-oncology,,,"

Aims

We report disease-specific cardiovascular causes of mortality among cancer patients in the USA between 1999 and 2019, considering temporal trends by age, sex, and cancer site.

Methods and results

We used the Multiple Cause of Death database, accessed through the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research resource. We included 629 308 decedents with cardiovascular disease (CVD) recorded as the primary cause of death and active malignancy listed as a contributing cause of death. We created disease-specific CVD categories and grouped cancers by site. We calculated the proportion of CVD deaths attributed to each disease category stratified by sex, age, and cancer site. We also examined disease-specific temporal trends by cancer site. Ischaemic heart disease (IHD) was the most common cardiovascular cause of death across all cancer types (55.6%), being more common in men (59.8%), older ages, and in those with lung (67.8%) and prostate (58.3%) cancers. Cerebrovascular disease (12.9%) and hypertensive diseases (7.6%) were other common causes of death. The proportion of deaths due to heart failure was greatest in haematological (7.7%) and breast (6.3%) cancers. There was a decreasing temporal trend in the proportion of cardiovascular deaths attributed to IHD across all cancer types. The proportion of deaths due to hypertensive diseases showed the greatest percentage increase, with the largest change in breast cancer patients (+191.1%).

Conclusion

We demonstrate differential cardiovascular mortality risk by cancer site and demographics, providing insight into the evolving healthcare needs of this growing high-cardiovascular risk population.",,pdf:https://academic.oup.com/ehjqcco/advance-article-pdf/doi/10.1093/ehjqcco/qcac016/43887262/qcac016.pdf; doi:https://doi.org/10.1093/ehjqcco/qcac016; html:https://europepmc.org/articles/PMC9745666; pdf:https://europepmc.org/articles/PMC9745666?pdf=render 30972781,https://doi.org/10.1111/apt.15232,Early and late mortality following unscheduled admissions for severe liver disease across England and Wales.,"Roberts SE, John A, Brown J, Napier DJ, Lyons RA, Williams JG.",,Alimentary pharmacology & therapeutics,2019,2019-04-11,Y,,,,"

Background

There is a known shortfall in hepatology service resources across England and Wales.

Aim

To investigate early and late mortality following unscheduled admissions for severe liver disease, overall and by cause of death, and to determine how mortality is related to admissions to transplant centres, transplant surgery, hospital size, consultant specialty, patient socio-demographics, seasonal and geographical factors.

Methods

Cohorts of people with a first unscheduled admission for severe liver disease across England and Wales from 2004, based on record linkage of national inpatient and mortality data.

Findings

Mortality for alcoholic liver disease and hepatic failure was 23.4% and 35.4% respectively at 60 days and 61.8% and 57.1% at 5 years. Standardised mortality ratios (SMRs) were extremely high at 60 days (184 and 117 respectively) and remained highly increased at 5 years (16.7 and 6.3). Mortality at 5 years was most elevated from liver disease, viral hepatitis and varices. The 60-day mortality was significantly lower for patients seen by consultant hepatologists and gastroenterologists. Both early and late mortality were significantly reduced for patients admitted to transplant centres or larger hospitals, who received a liver transplant, or were resident in London. Early mortality was significantly higher for patients admitted in winter and autumn, while elevated mortality among the most vs least deprived quintile increased with longer follow-up.

Conclusions

The study shows a very poor prognosis for people with unscheduled hospitalisation for severe liver disease. The findings suggest that access to specialist expertise and services improves survival, both in the short and long term.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/apt.15232; doi:https://doi.org/10.1111/apt.15232; html:https://europepmc.org/articles/PMC6519290; pdf:https://europepmc.org/articles/PMC6519290?pdf=render 33536532,https://doi.org/10.1038/s41598-021-82459-y,Data-driven identification of ageing-related diseases from electronic health records.,"Kuan V, Fraser HC, Hingorani M, Denaxas S, Gonzalez-Izquierdo A, Direk K, Nitsch D, Mathur R, Parisinos CA, Lumbers RT, Sofat R, Wong ICK, Casas JP, Thornton JM, Hemingway H, Partridge L, Hingorani AD.",,Scientific reports,2021,2021-02-03,Y,,,,"Reducing the burden of late-life morbidity requires an understanding of the mechanisms of ageing-related diseases (ARDs), defined as diseases that accumulate with increasing age. This has been hampered by the lack of formal criteria to identify ARDs. Here, we present a framework to identify ARDs using two complementary methods consisting of unsupervised machine learning and actuarial techniques, which we applied to electronic health records (EHRs) from 3,009,048 individuals in England using primary care data from the Clinical Practice Research Datalink (CPRD) linked to the Hospital Episode Statistics admitted patient care dataset between 1 April 2010 and 31 March 2015 (mean age 49.7 years (s.d. 18.6), 51% female, 70% white ethnicity). We grouped 278 high-burden diseases into nine main clusters according to their patterns of disease onset, using a hierarchical agglomerative clustering algorithm. Four of these clusters, encompassing 207 diseases spanning diverse organ systems and clinical specialties, had rates of disease onset that clearly increased with chronological age. However, the ages of onset for these four clusters were strikingly different, with median age of onset 82 years (IQR 82-83) for Cluster 1, 77 years (IQR 75-77) for Cluster 2, 69 years (IQR 66-71) for Cluster 3 and 57 years (IQR 54-59) for Cluster 4. Fitting to ageing-related actuarial models confirmed that the vast majority of these 207 diseases had a high probability of being ageing-related. Cardiovascular diseases and cancers were highly represented, while benign neoplastic, skin and psychiatric conditions were largely absent from the four ageing-related clusters. Our framework identifies and clusters ARDs and can form the basis for fundamental and translational research into ageing pathways.",,pdf:https://www.nature.com/articles/s41598-021-82459-y.pdf; doi:https://doi.org/10.1038/s41598-021-82459-y; html:https://europepmc.org/articles/PMC7859412; pdf:https://europepmc.org/articles/PMC7859412?pdf=render 37519214,https://doi.org/10.1177/09622802231188518,Multiple imputation approaches for epoch-level accelerometer data in trials.,"Tackney MS, Williamson E, Cook DG, Limb E, Harris T, Carpenter J.",,Statistical methods in medical research,2023,2023-07-31,Y,Missing Data; Accelerometer; Multiple Imputation; Wearables; Physical Activity Trial,,,"Clinical trials that investigate physical activity interventions often use accelerometers to measure step count at a very granular level, for example in 5-second epochs. Participants typically wear the accelerometer for a week-long period at baseline, and for one or more week-long follow-up periods after the intervention. The data is aggregated to provide daily or weekly step counts for the primary analysis. Missing data are common as participants may not wear the device as per protocol. Approaches to handling missing data in the literature have defined missingness on the day level using a threshold on daily weartime, which leads to loss of information on the time of day when data are missing. We propose an approach to identifying and classifying missingness at the finer epoch-level and present two approaches to handling missingness using multiple imputation. Firstly, we present a parametric approach which accounts for the number of missing epochs per day. Secondly, we describe a non-parametric approach where missing periods during the day are replaced by donor data from the same person where possible, or data from a different person who is matched on demographic and physical activity-related variables. Our simulation studies show that the non-parametric approach leads to estimates of the effect of treatment that are least biased while maintaining small standard errors. We illustrate the application of these different multiple imputation strategies to the analysis of the 2017 PACE-UP trial. The proposed framework is likely to be applicable to other digital health outcomes and to other wearable devices.",,pdf:https://journals.sagepub.com/doi/pdf/10.1177/09622802231188518; doi:https://doi.org/10.1177/09622802231188518; html:https://europepmc.org/articles/PMC10563375; pdf:https://europepmc.org/articles/PMC10563375?pdf=render @@ -1466,8 +1466,8 @@ PMC8855010,https://doi.org/,POS-894 PREDICTING PANDEMIC-RELATED EXCESS-DEATH USI 36346654,https://doi.org/10.2196/38168,Developing an Automated Assessment of In-session Patient Activation for Psychological Therapy: Codevelopment Approach.,"Malins S, Figueredo G, Jilani T, Long Y, Andrews J, Rawsthorne M, Manolescu C, Clos J, Higton F, Waldram D, Hunt D, Perez Vallejos E, Moghaddam N.",,JMIR medical informatics,2022,2022-11-08,Y,Mental health; Machine Learning; Cognitive Behavioral Therapy; Natural Language Processing; Multimorbidity; Responsible Artificial Intelligence,,,"

Background

Patient activation is defined as a patient's confidence and perceived ability to manage their own health. Patient activation has been a consistent predictor of long-term health and care costs, particularly for people with multiple long-term health conditions. However, there is currently no means of measuring patient activation from what is said in health care consultations. This may be particularly important for psychological therapy because most current methods for evaluating therapy content cannot be used routinely due to time and cost restraints. Natural language processing (NLP) has been used increasingly to classify and evaluate the contents of psychological therapy. This aims to make the routine, systematic evaluation of psychological therapy contents more accessible in terms of time and cost restraints. However, comparatively little attention has been paid to algorithmic trust and interpretability, with few studies in the field involving end users or stakeholders in algorithm development.

Objective

This study applied a responsible design to use NLP in the development of an artificial intelligence model to automate the ratings assigned by a psychological therapy process measure: the consultation interactions coding scheme (CICS). The CICS assesses the level of patient activation observable from turn-by-turn psychological therapy interactions.

Methods

With consent, 128 sessions of remotely delivered cognitive behavioral therapy from 53 participants experiencing multiple physical and mental health problems were anonymously transcribed and rated by trained human CICS coders. Using participatory methodology, a multidisciplinary team proposed candidate language features that they thought would discriminate between high and low patient activation. The team included service-user researchers, psychological therapists, applied linguists, digital research experts, artificial intelligence ethics researchers, and NLP researchers. Identified language features were extracted from the transcripts alongside demographic features, and machine learning was applied using k-nearest neighbors and bagged trees algorithms to assess whether in-session patient activation and interaction types could be accurately classified.

Results

The k-nearest neighbors classifier obtained 73% accuracy (82% precision and 80% recall) in a test data set. The bagged trees classifier obtained 81% accuracy for test data (87% precision and 75% recall) in differentiating between interactions rated high in patient activation and those rated low or neutral.

Conclusions

Coproduced language features identified through a multidisciplinary collaboration can be used to discriminate among psychological therapy session contents based on patient activation among patients experiencing multiple long-term physical and mental health conditions.",,pdf:https://medinform.jmir.org/2022/11/e38168/PDF; doi:https://doi.org/10.2196/38168; html:https://europepmc.org/articles/PMC9682451 35804579,https://doi.org/10.3390/ani12131679,Genetic Basis of Dilated Cardiomyopathy in Dogs and Its Potential as a Bidirectional Model.,"Gaar-Humphreys KR, Spanjersberg TCF, Santarelli G, Grinwis GCM, Szatmári V, Roelen BAJ, Vink A, van Tintelen JP, Asselbergs FW, Fieten H, Harakalova M, van Steenbeek FG.",,Animals : an open access journal from MDPI,2022,2022-06-29,Y,cardiovascular; Human Induced Pluripotent Stem Cells; Fibrofatty Infiltration; Canine Induced Pluripotent Stem Cells; Attenuated Wavy Fibers,,,"Cardiac disease is a leading cause of death for both humans and dogs. Genetic cardiomyopathies, including dilated cardiomyopathy (DCM), account for a proportion of these cases in both species. Patients may suffer from ventricular enlargement and systolic dysfunction resulting in congestive heart failure and ventricular arrhythmias with high risk for sudden cardiac death. Although canine DCM has similar disease progression and subtypes as in humans, only a few candidate genes have been found to be associated with DCM while the genetic background of human DCM has been more thoroughly studied. Additionally, experimental disease models using induced pluripotent stem cells have been widely adopted in the study of human genetic cardiomyopathy but have not yet been fully adapted for the in-depth study of canine genetic cardiomyopathies. The clinical presentation of DCM is extremely heterogeneous for both species with differences occurring based on sex predisposition, age of onset, and the rate of disease progression. Both genetic predisposition and environmental factors play a role in disease development which are identical in dogs and humans in contrast to other experimental animals. Interestingly, different dog breeds have been shown to develop distinct DCM phenotypes, and this presents a unique opportunity for modeling as there are multiple breed-specific models for DCM with less genetic variance than human DCM. A better understanding of DCM in dogs has the potential for improved selection for breeding and could lead to better overall care and treatment for human and canine DCM patients. At the same time, progress in research made for human DCM can have a positive impact on the care given to dogs affected by DCM. Therefore, this review will analyze the feasibility of canines as a naturally occurring bidirectional disease model for DCM in both species. The histopathology of the myocardium in canine DCM will be evaluated in three different breeds compared to control tissue, and the known genetics that contributes to both canine and human DCM will be summarized. Lastly, the prospect of canine iPSCs as a novel method to uncover the contributions of genetic variants to the pathogenesis of canine DCM will be introduced along with the applications for disease modeling and treatment.",,pdf:https://www.mdpi.com/2076-2615/12/13/1679/pdf?version=1656561768; doi:https://doi.org/10.3390/ani12131679; html:https://europepmc.org/articles/PMC9265105; pdf:https://europepmc.org/articles/PMC9265105?pdf=render 37612010,https://doi.org/10.1016/j.jacc.2023.05.065,Monitoring of Myocardial Involvement in Early Arrhythmogenic Right Ventricular Cardiomyopathy Across the Age Spectrum.,"Kirkels FP, van Osta N, Rootwelt-Norberg C, Chivulescu M, van Loon T, Aabel EW, Castrini AI, Lie ØH, Asselbergs FW, Delhaas T, Cramer MJ, Teske AJ, Haugaa KH, Lumens J.",,Journal of the American College of Cardiology,2023,2023-08-01,N,Early Detection; Arvc; Family Screening; Deformation Imaging; Digital Twin; Arrhythmogenic Cardiomyopathy,,,"

Background

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by fibrofatty replacement of primarily the right ventricular myocardium, a substrate for life-threatening ventricular arrhythmias (VAs). Repeated cardiac imaging of at-risk relatives is important for early disease detection. However, it is not known whether screening should be age-tailored.

Objectives

The goal of this study was to assess the need for age-tailoring of follow-up protocols in early ARVC by evaluating myocardial disease progression in different age groups.

Methods

We divided patients with early-stage ARVC and genotype-positive relatives without overt structural disease and VA at first evaluation into 3 groups: age <30 years, 30 to 50 years, and ≥50 years. Longitudinal biventricular deformation characteristics were used to monitor disease progression. To link deformation abnormalities to underlying myocardial disease substrates, Digital Twins were created using an imaging-based computational modeling framework.

Results

We included 313 echocardiographic assessments from 82 subjects (57% female, age 39 ± 17 years, 10% probands) during 6.7 ± 3.3 years of follow-up. Left ventricular global longitudinal strain slightly deteriorated similarly in all age groups (0.1%-point per year [95% CI: 0.05-0.15]). Disease progression in all age groups was more pronounced in the right ventricular lateral wall, expressed by worsening in longitudinal strain (0.6%-point per year [95% CI: 0.46-0.70]) and local differences in myocardial contractility, compliance, and activation delay in the Digital Twin. Six patients experienced VA during follow-up.

Conclusions

Disease progression was similar in all age groups, and sustained VA also occurred in patients aged >50 years without overt ARVC phenotype at first evaluation. Unlike recommended by current guidelines, our study suggests that follow-up of ARVC patients and relatives should not stop at older age.",,doi:https://doi.org/10.1016/j.jacc.2023.05.065 -38170504,https://doi.org/10.1001/jamacardio.2023.4994,Genetic Associations of Circulating Cardiovascular Proteins With Gestational Hypertension and Preeclampsia.,"Schuermans A, Truong B, Ardissino M, Bhukar R, Slob EAW, Nakao T, Dron JS, Small AM, Cho SMJ, Yu Z, Hornsby W, Antoine T, Lannery K, Postupaka D, Gray KJ, Yan Q, Butterworth AS, Burgess S, Wood MJ, Scott NS, Harrington CM, Sarma AA, Lau ES, Roh JD, Januzzi JL, Natarajan P, Honigberg MC.",,JAMA cardiology,2024,2024-03-01,Y,,,,"

Importance

Hypertensive disorders of pregnancy (HDPs), including gestational hypertension and preeclampsia, are important contributors to maternal morbidity and mortality worldwide. In addition, women with HDPs face an elevated long-term risk of cardiovascular disease.

Objective

To identify proteins in the circulation associated with HDPs.

Design, setting, and participants

Two-sample mendelian randomization (MR) tested the associations of genetic instruments for cardiovascular disease-related proteins with gestational hypertension and preeclampsia. In downstream analyses, a systematic review of observational data was conducted to evaluate the identified proteins' dynamics across gestation in hypertensive vs normotensive pregnancies, and phenome-wide MR analyses were performed to identify potential non-HDP-related effects associated with the prioritized proteins. Genetic association data for cardiovascular disease-related proteins were obtained from the Systematic and Combined Analysis of Olink Proteins (SCALLOP) consortium. Genetic association data for the HDPs were obtained from recent European-ancestry genome-wide association study meta-analyses for gestational hypertension and preeclampsia. Study data were analyzed October 2022 to October 2023.

Exposures

Genetic instruments for 90 candidate proteins implicated in cardiovascular diseases, constructed using cis-protein quantitative trait loci (cis-pQTLs).

Main outcomes and measures

Gestational hypertension and preeclampsia.

Results

Genetic association data for cardiovascular disease-related proteins were obtained from 21 758 participants from the SCALLOP consortium. Genetic association data for the HDPs were obtained from 393 238 female individuals (8636 cases and 384 602 controls) for gestational hypertension and 606 903 female individuals (16 032 cases and 590 871 controls) for preeclampsia. Seventy-five of 90 proteins (83.3%) had at least 1 valid cis-pQTL. Of those, 10 proteins (13.3%) were significantly associated with HDPs. Four were robust to sensitivity analyses for gestational hypertension (cluster of differentiation 40, eosinophil cationic protein [ECP], galectin 3, N-terminal pro-brain natriuretic peptide [NT-proBNP]), and 2 were robust for preeclampsia (cystatin B, heat shock protein 27 [HSP27]). Consistent with the MR findings, observational data revealed that lower NT-proBNP (0.76- to 0.88-fold difference vs no HDPs) and higher HSP27 (2.40-fold difference vs no HDPs) levels during the first trimester of pregnancy were associated with increased risk of HDPs, as were higher levels of ECP (1.60-fold difference vs no HDPs). Phenome-wide MR analyses identified 37 unique non-HDP-related protein-disease associations, suggesting potential on-target effects associated with interventions lowering HDP risk through the identified proteins.

Conclusions and relevance

Study findings suggest genetic associations of 4 cardiovascular disease-related proteins with gestational hypertension and 2 associated with preeclampsia. Future studies are required to test the efficacy of targeting the corresponding pathways to reduce HDP risk.",,doi:https://doi.org/10.1001/jamacardio.2023.4994; html:https://europepmc.org/articles/PMC10765315; pdf:https://europepmc.org/articles/PMC10765315?pdf=render 34772649,https://doi.org/10.1016/s2589-7500(21)00252-1,Characteristics of publicly available skin cancer image datasets: a systematic review.,"Wen D, Khan SM, Ji Xu A, Ibrahim H, Smith L, Caballero J, Zepeda L, de Blas Perez C, Denniston AK, Liu X, Matin RN.",,The Lancet. Digital health,2022,2021-11-09,N,,,,"Publicly available skin image datasets are increasingly used to develop machine learning algorithms for skin cancer diagnosis. However, the total number of datasets and their respective content is currently unclear. This systematic review aimed to identify and evaluate all publicly available skin image datasets used for skin cancer diagnosis by exploring their characteristics, data access requirements, and associated image metadata. A combined MEDLINE, Google, and Google Dataset search identified 21 open access datasets containing 106 950 skin lesion images, 17 open access atlases, eight regulated access datasets, and three regulated access atlases. Images and accompanying data from open access datasets were evaluated by two independent reviewers. Among the 14 datasets that reported country of origin, most (11 [79%]) originated from Europe, North America, and Oceania exclusively. Most datasets (19 [91%]) contained dermoscopic images or macroscopic photographs only. Clinical information was available regarding age for 81 662 images (76·4%), sex for 82 848 (77·5%), and body site for 79 561 (74·4%). Subject ethnicity data were available for 1415 images (1·3%), and Fitzpatrick skin type data for 2236 (2·1%). There was limited and variable reporting of characteristics and metadata among datasets, with substantial under-representation of darker skin types. This is the first systematic review to characterise publicly available skin image datasets, highlighting limited applicability to real-life clinical settings and restricted population representation, precluding generalisability. Quality standards for characteristics and metadata reporting for skin image datasets are needed.",,pdf:http://www.thelancet.com/article/S2589750021002521/pdf; doi:https://doi.org/10.1016/S2589-7500(21)00252-1 +38170504,https://doi.org/10.1001/jamacardio.2023.4994,Genetic Associations of Circulating Cardiovascular Proteins With Gestational Hypertension and Preeclampsia.,"Schuermans A, Truong B, Ardissino M, Bhukar R, Slob EAW, Nakao T, Dron JS, Small AM, Cho SMJ, Yu Z, Hornsby W, Antoine T, Lannery K, Postupaka D, Gray KJ, Yan Q, Butterworth AS, Burgess S, Wood MJ, Scott NS, Harrington CM, Sarma AA, Lau ES, Roh JD, Januzzi JL, Natarajan P, Honigberg MC.",,JAMA cardiology,2024,2024-03-01,Y,,,,"

Importance

Hypertensive disorders of pregnancy (HDPs), including gestational hypertension and preeclampsia, are important contributors to maternal morbidity and mortality worldwide. In addition, women with HDPs face an elevated long-term risk of cardiovascular disease.

Objective

To identify proteins in the circulation associated with HDPs.

Design, setting, and participants

Two-sample mendelian randomization (MR) tested the associations of genetic instruments for cardiovascular disease-related proteins with gestational hypertension and preeclampsia. In downstream analyses, a systematic review of observational data was conducted to evaluate the identified proteins' dynamics across gestation in hypertensive vs normotensive pregnancies, and phenome-wide MR analyses were performed to identify potential non-HDP-related effects associated with the prioritized proteins. Genetic association data for cardiovascular disease-related proteins were obtained from the Systematic and Combined Analysis of Olink Proteins (SCALLOP) consortium. Genetic association data for the HDPs were obtained from recent European-ancestry genome-wide association study meta-analyses for gestational hypertension and preeclampsia. Study data were analyzed October 2022 to October 2023.

Exposures

Genetic instruments for 90 candidate proteins implicated in cardiovascular diseases, constructed using cis-protein quantitative trait loci (cis-pQTLs).

Main outcomes and measures

Gestational hypertension and preeclampsia.

Results

Genetic association data for cardiovascular disease-related proteins were obtained from 21 758 participants from the SCALLOP consortium. Genetic association data for the HDPs were obtained from 393 238 female individuals (8636 cases and 384 602 controls) for gestational hypertension and 606 903 female individuals (16 032 cases and 590 871 controls) for preeclampsia. Seventy-five of 90 proteins (83.3%) had at least 1 valid cis-pQTL. Of those, 10 proteins (13.3%) were significantly associated with HDPs. Four were robust to sensitivity analyses for gestational hypertension (cluster of differentiation 40, eosinophil cationic protein [ECP], galectin 3, N-terminal pro-brain natriuretic peptide [NT-proBNP]), and 2 were robust for preeclampsia (cystatin B, heat shock protein 27 [HSP27]). Consistent with the MR findings, observational data revealed that lower NT-proBNP (0.76- to 0.88-fold difference vs no HDPs) and higher HSP27 (2.40-fold difference vs no HDPs) levels during the first trimester of pregnancy were associated with increased risk of HDPs, as were higher levels of ECP (1.60-fold difference vs no HDPs). Phenome-wide MR analyses identified 37 unique non-HDP-related protein-disease associations, suggesting potential on-target effects associated with interventions lowering HDP risk through the identified proteins.

Conclusions and relevance

Study findings suggest genetic associations of 4 cardiovascular disease-related proteins with gestational hypertension and 2 associated with preeclampsia. Future studies are required to test the efficacy of targeting the corresponding pathways to reduce HDP risk.",,doi:https://doi.org/10.1001/jamacardio.2023.4994; html:https://europepmc.org/articles/PMC10765315; pdf:https://europepmc.org/articles/PMC10765315?pdf=render 37477360,https://doi.org/10.1097/ypg.0000000000000349,Schizophrenia polygenic risk score and type 2 diabetes onset in older adults with no schizophrenia diagnosis.,"Shamsutdinova D, Ajnakina O, Roberts A, Stahl D.",,Psychiatric genetics,2023,2023-07-04,Y,,,,"

Objectives

An association between type 2 diabetes (T2DM) and schizophrenia has long been observed, and recent research revealed presence of shared genetic factors. However, epidemiological evidence was inconsistent, some reported insignificant contribution of genetic factors to T2DM-schizophrenia comorbidity. Prior works studied people with schizophrenia, particularly, antipsychotic-naive patients, or those during the first psychotic experience to limit schizophrenia-related environmental factors. In contrast, we controlled such factors by utilizing a general population sample of individuals undiagnosed with schizophrenia. We hypothesized that if schizophrenia genetics impact T2DM development and such impact is not fully mediated by schizophrenia-related environment, people with high polygenic schizophrenia risk would exhibit elevated T2DM incidence.

Methods

Using a population-representative sample of adults aged ≥50 from English Longitudinal Study of Ageing ( n  = 5968, 493 T2DM cases, average follow-up 8.7 years), we investigated if schizophrenia polygenic risk score (PGS-SZ) is associated with T2DM onset. A proportional hazards model with interval censoring was adjusted for age and sex (Model 1), and age, sex, BMI, hypertension, cardiovascular diseases, exercise, smoking, depressive symptoms and T2DM polygenic risk score (Model 2). According to the power calculations, hazard rates > 1.14 per standard deviation in PGS-SZ could be detected.

Results

We did not observe a significant association between PGS-SZ and T2DM incidence (hazard ratio 1.04; 95% CI 0.93-1.15; and 1.01, 95% CI 0.94-1.09).

Conclusion

Our results suggest low contribution of the intrinsic biological mechanisms driven by the polygenic risk of schizophrenia on future T2DM onset. Further research is needed.",,html:https://journals.lww.com/psychgenetics/fulltext/9900/schizophrenia_polygenic_risk_score_and_type_2.34.aspx; doi:https://doi.org/10.1097/YPG.0000000000000349; html:https://europepmc.org/articles/PMC10501355; pdf:https://europepmc.org/articles/PMC10501355?pdf=render 38045440,https://doi.org/10.1093/ehjdh/ztad056,Machine learning-based biomarker profile derived from 4210 serially measured proteins predicts clinical outcome of patients with heart failure.,"de Bakker M, Petersen TB, Rueten-Budde AJ, Akkerhuis KM, Umans VA, Brugts JJ, Germans T, Reinders MJT, Katsikis PD, van der Spek PJ, Ostroff R, She R, Lanfear D, Asselbergs FW, Boersma E, Rizopoulos D, Kardys I.",,European heart journal. Digital health,2023,2023-10-04,Y,Prediction; Proteomics; Heart Failure; NT-proBNP; Repeated Measurements; Elastic Net,,,"

Aims

Risk assessment tools are needed for timely identification of patients with heart failure (HF) with reduced ejection fraction (HFrEF) who are at high risk of adverse events. In this study, we aim to derive a small set out of 4210 repeatedly measured proteins, which, along with clinical characteristics and established biomarkers, carry optimal prognostic capacity for adverse events, in patients with HFrEF.

Methods and results

In 382 patients, we performed repeated blood sampling (median follow-up: 2.1 years) and applied an aptamer-based multiplex proteomic approach. We used machine learning to select the optimal set of predictors for the primary endpoint (PEP: composite of cardiovascular death, heart transplantation, left ventricular assist device implantation, and HF hospitalization). The association between repeated measures of selected proteins and PEP was investigated by multivariable joint models. Internal validation (cross-validated c-index) and external validation (Henry Ford HF PharmacoGenomic Registry cohort) were performed. Nine proteins were selected in addition to the MAGGIC risk score, N-terminal pro-hormone B-type natriuretic peptide, and troponin T: suppression of tumourigenicity 2, tryptophanyl-tRNA synthetase cytoplasmic, histone H2A Type 3, angiotensinogen, deltex-1, thrombospondin-4, ADAMTS-like protein 2, anthrax toxin receptor 1, and cathepsin D. N-terminal pro-hormone B-type natriuretic peptide and angiotensinogen showed the strongest associations [hazard ratio (95% confidence interval): 1.96 (1.17-3.40) and 0.66 (0.49-0.88), respectively]. The multivariable model yielded a c-index of 0.85 upon internal validation and c-indices up to 0.80 upon external validation. The c-index was higher than that of a model containing established risk factors (P = 0.021).

Conclusion

Nine serially measured proteins captured the most essential prognostic information for the occurrence of adverse events in patients with HFrEF, and provided incremental value for HF prognostication beyond established risk factors. These proteins could be used for dynamic, individual risk assessment in a prospective setting. These findings also illustrate the potential value of relatively 'novel' biomarkers for prognostication.

Clinical trial registration

https://clinicaltrials.gov/ct2/show/NCT01851538?term=nCT01851538&draw=2&rank=1 24.",,doi:https://doi.org/10.1093/ehjdh/ztad056; html:https://europepmc.org/articles/PMC10689916; pdf:https://europepmc.org/articles/PMC10689916?pdf=render 31500613,https://doi.org/10.1186/s12911-019-0908-7,A validated natural language processing algorithm for brain imaging phenotypes from radiology reports in UK electronic health records.,"Wheater E, Mair G, Sudlow C, Alex B, Grover C, Whiteley W.",,BMC medical informatics and decision making,2019,2019-09-09,Y,Stroke; Phenotyping; Brain imaging; Radiology; Natural Language Processing; Radiology Reports,"Applied Analytics, Better Care",,"

Background

Manual coding of phenotypes in brain radiology reports is time consuming. We developed a natural language processing (NLP) algorithm to enable automatic identification of brain imaging in radiology reports performed in routine clinical practice in the UK National Health Service (NHS).

Methods

We used anonymized text brain imaging reports from a cohort study of stroke/TIA patients and from a regional hospital to develop and test an NLP algorithm. Two experts marked up text in 1692 reports for 24 cerebrovascular and other neurological phenotypes. We developed and tested a rule-based NLP algorithm first within the cohort study, and further evaluated it in the reports from the regional hospital.

Results

The agreement between expert readers was excellent (Cohen's κ =0.93) in both datasets. In the final test dataset (n = 700) in unseen regional hospital reports, the algorithm had very good performance for a report of any ischaemic stroke [sensitivity 89% (95% CI:81-94); positive predictive value (PPV) 85% (76-90); specificity 100% (95% CI:0.99-1.00)]; any haemorrhagic stroke [sensitivity 96% (95% CI: 80-99), PPV 72% (95% CI:55-84); specificity 100% (95% CI:0.99-1.00)]; brain tumours [sensitivity 96% (CI:87-99); PPV 84% (73-91); specificity: 100% (95% CI:0.99-1.00)] and cerebral small vessel disease and cerebral atrophy (sensitivity, PPV and specificity all > 97%). We obtained few reports of subarachnoid haemorrhage, microbleeds or subdural haematomas. In 110,695 reports from NHS Tayside, atrophy (n = 28,757, 26%), small vessel disease (15,015, 14%) and old, deep ischaemic strokes (10,636, 10%) were the commonest findings.

Conclusions

An NLP algorithm can be developed in UK NHS radiology records to allow identification of cohorts of patients with important brain imaging phenotypes at a scale that would otherwise not be possible.",,pdf:https://bmcmedinformdecismak.biomedcentral.com/track/pdf/10.1186/s12911-019-0908-7; doi:https://doi.org/10.1186/s12911-019-0908-7; html:https://europepmc.org/articles/PMC6734359; pdf:https://europepmc.org/articles/PMC6734359?pdf=render @@ -1478,31 +1478,31 @@ PMC8855010,https://doi.org/,POS-894 PREDICTING PANDEMIC-RELATED EXCESS-DEATH USI PMC9023380,https://doi.org/,Assessing the spread risk of COVID-19 associated with multi-mode transportation networks in China,"Xu X, Liu X, Wang L, Wu Y, Lu X, Wang X, Pei S.",,Fundamental Research,2022,2022-04-22,Y,Complex Network; Spatial Spread; Human Mobility; Transportation Networks; Covid-19,,,"The spatial spread of COVID-19 during early 2020 in China was primarily driven by outbound travelers leaving the epicenter, Wuhan, Hubei province. Existing studies focus on the influence of aggregated out-bound population flows originating from Wuhan; however, the impacts of different modes of transportation and the network structure of transportation systems on the early spread of COVID-19 in China are not well understood. Here, we assess the roles of the road, railway, and air transportation networks in driving the spatial spread of COVID-19 in China. We find that the short-range spread within Hubei province was dominated by ground traffic, notably, the railway transportation. In contrast, long-range spread to cities in other provinces was mediated by multiple factors, including a higher risk of case importation associated with air transportation and a larger outbreak size in hub cities located at the center of transportation networks. We further show that, although the dissemination of SARS-CoV-2 across countries and continents is determined by the worldwide air transportation network, the early geographic dispersal of COVID-19 within China is better predicted by the railway traffic. Given the recent emergence of multiple more transmissible variants of SARS-CoV-2, our findings can support a better assessment of the spread risk of those variants and improve future pandemic preparedness and responses. Graphical abstract Image, graphical abstract.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9023380/?tool=EBI; pdf:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9023380/pdf/?tool=EBI; html:https://europepmc.org/articles/PMC9023380; pdf:https://europepmc.org/articles/PMC9023380?pdf=render 36798028,https://doi.org/10.1002/ehf2.14308,Identifying patients at risk: multi-centre comparison of HeartMate 3 and HeartWare left ventricular assist devices.,"Numan L, Zimpfer D, Zadok OIB, Aarts E, Morshuis M, Guenther SPW, Riebandt J, Wiedemann D, Ramjankhan FZ, Oppelaar AM, Ben-Gal T, Ben-Avraham B, Asselbergs FW, Schramm R, Van Laake LW.",,ESC heart failure,2023,2023-02-16,Y,Mechanical Circulatory Support; Left Ventricular Assist Device; End-stage Heart Failure; Lvad; Centrifugal Continuous Flow Pump,,,"

Aims

Since the withdrawal of HeartWare (HVAD) from the global market, there is an ongoing discussion if and which patients require prophylactically exchange for a HeartMate 3 (HM3). Therefore, it is important to study outcome differences between HVAD and HM3 patients. Because centres differ in patient selection and standard of care, we performed a propensity score (PS)-based study including centres that implanted both devices and aimed to identify which HVAD patients are at highest risk.

Methods and results

We performed an international multi-centre study (n = 1021) including centres that implanted HVAD and HM3. PS-matching was performed using clinical variables and the implanting centre. Survival and complications were compared. As a sensitivity analysis, PS-adjusted Cox regression was performed. Landmark analysis with conditional survival >2 years was conducted to evaluate long-term survival differences. To identify which HVAD patients may benefit from a HM3 upgrade, Cox regression using pre-operative variables and their interaction with device type was performed. Survival was significantly better for HM3 patients (P < 0.01) in 458 matched patients, with a median follow-up of 23 months. Within the matched cohort, HM3 patients had a median age of 58 years, and 83% were male, 80% of the HVAD patients were male, with a median age of 59 years. PS-adjusted Cox regression confirmed a significantly better survival for HM3 patients when compared with HVAD, with a HR of 1.46 (95% confidence interval 1.14-1.85, P < 0.01). Pump thrombosis (P < 0.01) and ischaemic stroke (P < 0.01) occurred less in HM3 patients. No difference was found for haemorrhagic stroke, right heart failure, driveline infection, and major bleeding. Landmark-analysis confirmed a significant difference in conditional survival >2 years after implantation (P = 0.03). None of the pre-operative variable interactions in the Cox regression were significant.

Conclusions

HM3 patients have a significantly better survival and a lower incidence of ischaemic strokes and pump thrombosis than HVAD patients. This survival difference persisted after 2 years of implantation. Additional research using post-operative variables is warranted to identify which HVAD patients need an upgrade to HM3 or expedited transplantation.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ehf2.14308; doi:https://doi.org/10.1002/ehf2.14308; html:https://europepmc.org/articles/PMC10192248; pdf:https://europepmc.org/articles/PMC10192248?pdf=render 33144367,https://doi.org/10.3399/bjgpopen20x101109,Evaluating a cardiovascular disease risk management care continuum within a learning healthcare system: a prospective cohort study.,"Groenhof TKJ, Lely AT, Haitjema S, Nathoe HM, Kortekaas MF, Asselbergs FW, Bots ML, Hollander M, UCC CVRM study group.",,BJGP open,2020,2020-12-15,Y,Cardiovascular diseases; Continuity Of Patient Care; Learning Healthcare System; Cardiovascular Risk Management,,,"

Background

Many patients now present with multimorbidity and chronicity of disease. This means that multidisciplinary management in a care continuum, integrating primary care and hospital care services, is needed to ensure high quality care.

Aim

To evaluate cardiovascular risk management (CVRM) via linkage of health data sources, as an example of a multidisciplinary continuum within a learning healthcare system (LHS).

Design & setting

In this prospective cohort study, data were linked from the Utrecht Cardiovascular Cohort (UCC) to the Julius General Practitioners' Network (JGPN) database. UCC offers structured CVRM at referral to the University Medical Centre (UMC) Utrecht. JGPN consists of electronic health record (EHR) data from referring GPs.

Method

The cardiovascular risk factors were extracted for each patient 13 months before referral (JGPN), at UCC inclusion, and during 12 months follow-up (JGPN). The following areas were assessed: registration of risk factors; detection of risk factor(s) requiring treatment at UCC; communication of risk factors and actionable suggestions from the specialist to the GP; and change of management during follow-up.

Results

In 52% of patients, ≥1 risk factors were registered (that is, extractable from structured fields within routine care health records) before UCC. In 12%-72% of patients, risk factor(s) existed that required (change or start of) treatment at UCC inclusion. Specialist communication included the complete risk profile in 67% of letters, but lacked actionable suggestions in 86%. In 29% of patients, at least one risk factor was registered after UCC. Change in management in GP records was seen in 21%-58% of them.

Conclusion

Evaluation of a multidisciplinary LHS is possible via linkage of health data sources. Efforts have to be made to improve registration in primary care, as well as communication on findings and actionable suggestions for follow-up to bridge the gap in the CVRM continuum.",,pdf:https://bjgpopen.org/content/bjgpoa/4/5/bjgpopen20X101109.full.pdf; doi:https://doi.org/10.3399/bjgpopen20X101109; html:https://europepmc.org/articles/PMC7880177; pdf:https://europepmc.org/articles/PMC7880177?pdf=render -36082669,https://doi.org/10.1161/hypertensionaha.122.19354,"Determining the Relationship Between Blood Pressure, Kidney Function, and Chronic Kidney Disease: Insights From Genetic Epidemiology.","Staplin N, Herrington WG, Murgia F, Ibrahim M, Bull KR, Judge PK, Ng SYA, Turner M, Zhu D, Emberson J, Landray MJ, Baigent C, Haynes R, Hopewell JC.",,"Hypertension (Dallas, Tex. : 1979)",2022,2022-09-09,Y,Blood pressure; Chronic; creatinine; epidemiology; Renal Insufficiency,,,"

Background

It is well established that decreased kidney function can increase blood pressure (BP), but it is unproven whether moderately elevated BP causes chronic kidney disease (CKD) or glomerular hyperfiltration.

Methods

311 119 White British UK Biobank participants were included in logistic regression analyses to estimate the odds of CKD (defined as long-term kidney replacement therapy, estimated glomerular filtration rate [eGFR]< 60mL/min/1.73m2, or urinary albumin:creatinine ratio ≥3 mg/mmol) associated with higher genetically predicted BP using genetic risk scores comprising 219 systolic and 223 diastolic BP loci. Analyses estimating associations with clinical categories of eGFR and urinary albumin:creatinine ratio were also conducted, with an eGFR ≥120 mL (min·1.73m2) considered evidence of glomerular hyperfiltration.

Results

21 623 participants had CKD: 7781 with reduced eGFR and 15 500 with albuminuria. 1828 participants had an eGFR ≥120 mL/min/1.73m2. Each genetically predicted 10 mmHg higher systolic BP and 5 mmHg higher diastolic BP were associated with a 37% (95% CI, 1.29-1.45) and 19% (1.14-1.25) higher odds of CKD, respectively. Associations were evident for both the reduced eGFR and albuminuria components of the CKD outcome. The odds of hyperfiltration (versus an eGFR ≥60 and <90 mL/min/1.73m2 were 49% higher (95% CI, 1.21-1.84) for each genetically predicted 10 mmHg higher systolic BP. Associations with CKD and hyperfiltration were similar irrespective of preexisting diabetes, vascular disease, or different levels of adiposity.

Conclusions

In this general population, genetic epidemiological evidence supports a causal role of life-long differences in BP for decreased kidney function, glomerular hyperfiltration, and albuminuria. Physiological autoregulation may not afford complete renal protection against the moderate BP elevations.",,pdf:https://ora.ox.ac.uk/objects/uuid:aefe90da-8a81-4cfa-981a-bb36eca6faa3/files/r6w924c60k; doi:https://doi.org/10.1161/HYPERTENSIONAHA.122.19354; html:https://europepmc.org/articles/PMC9640248; pdf:https://europepmc.org/articles/PMC9640248?pdf=render 30648344,https://doi.org/10.1002/cnm.3180,A semi-active human digital twin model for detecting severity of carotid stenoses from head vibration-A coupled computational mechanics and computer vision method.,"Chakshu NK, Carson J, Sazonov I, Nithiarasu P.",,International journal for numerical methods in biomedical engineering,2019,2019-02-20,Y,Computer vision; Blood flow; Systemic Circulation; Carotid Stenoses; Digital Twin; Biomechanical Vibrations; Face Video,Applied Analytics,,"In this work, we propose a methodology to detect the severity of carotid stenosis from a video of a human face with the help of a coupled blood flow and head vibration model. This semi-active digital twin model is an attempt to link noninvasive video of a patient face to the percentage of carotid occlusion. The pulsatile nature of blood flow through the carotid arteries induces a subtle head vibration. This vibration is a potential indicator of carotid stenosis severity, and it is exploited in the present study. A head vibration model has been proposed in the present work that is linked to the forces generated by blood flow with or without occlusion. The model is used to generate a large number of virtual head vibration data for different degrees of occlusion. In order to determine the in vivo head vibration, a computer vision algorithm is adopted to use human face videos. The in vivo vibrations are compared against the virtual vibration data generated from the coupled computational blood flow/vibration model. A comparison of the in vivo vibration is made against the virtual data to find the best fit between in vivo and virtual data. The preliminary results on healthy subjects and a patient clearly indicate that the model is accurate and it possesses the potential for detecting approximate severity of carotid artery stenoses.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/cnm.3180; doi:https://doi.org/10.1002/cnm.3180; html:https://europepmc.org/articles/PMC6593817; pdf:https://europepmc.org/articles/PMC6593817?pdf=render +36082669,https://doi.org/10.1161/hypertensionaha.122.19354,"Determining the Relationship Between Blood Pressure, Kidney Function, and Chronic Kidney Disease: Insights From Genetic Epidemiology.","Staplin N, Herrington WG, Murgia F, Ibrahim M, Bull KR, Judge PK, Ng SYA, Turner M, Zhu D, Emberson J, Landray MJ, Baigent C, Haynes R, Hopewell JC.",,"Hypertension (Dallas, Tex. : 1979)",2022,2022-09-09,Y,Blood pressure; Chronic; creatinine; epidemiology; Renal Insufficiency,,,"

Background

It is well established that decreased kidney function can increase blood pressure (BP), but it is unproven whether moderately elevated BP causes chronic kidney disease (CKD) or glomerular hyperfiltration.

Methods

311 119 White British UK Biobank participants were included in logistic regression analyses to estimate the odds of CKD (defined as long-term kidney replacement therapy, estimated glomerular filtration rate [eGFR]< 60mL/min/1.73m2, or urinary albumin:creatinine ratio ≥3 mg/mmol) associated with higher genetically predicted BP using genetic risk scores comprising 219 systolic and 223 diastolic BP loci. Analyses estimating associations with clinical categories of eGFR and urinary albumin:creatinine ratio were also conducted, with an eGFR ≥120 mL (min·1.73m2) considered evidence of glomerular hyperfiltration.

Results

21 623 participants had CKD: 7781 with reduced eGFR and 15 500 with albuminuria. 1828 participants had an eGFR ≥120 mL/min/1.73m2. Each genetically predicted 10 mmHg higher systolic BP and 5 mmHg higher diastolic BP were associated with a 37% (95% CI, 1.29-1.45) and 19% (1.14-1.25) higher odds of CKD, respectively. Associations were evident for both the reduced eGFR and albuminuria components of the CKD outcome. The odds of hyperfiltration (versus an eGFR ≥60 and <90 mL/min/1.73m2 were 49% higher (95% CI, 1.21-1.84) for each genetically predicted 10 mmHg higher systolic BP. Associations with CKD and hyperfiltration were similar irrespective of preexisting diabetes, vascular disease, or different levels of adiposity.

Conclusions

In this general population, genetic epidemiological evidence supports a causal role of life-long differences in BP for decreased kidney function, glomerular hyperfiltration, and albuminuria. Physiological autoregulation may not afford complete renal protection against the moderate BP elevations.",,pdf:https://ora.ox.ac.uk/objects/uuid:aefe90da-8a81-4cfa-981a-bb36eca6faa3/files/r6w924c60k; doi:https://doi.org/10.1161/HYPERTENSIONAHA.122.19354; html:https://europepmc.org/articles/PMC9640248; pdf:https://europepmc.org/articles/PMC9640248?pdf=render 34095527,https://doi.org/10.23889/ijpds.v4i1.581,Electronic Longitudinal Alcohol Study in Communities (ELAStiC) Wales - protocol for platform development.,"Trefan L, Akbari A, Paranjothy S, Farewell DM, Gartner A, Fone D, Greene J, Evans A, Smith A, Adekanmbi V, Kennedy J, Lyons RA, Moore SC.",,International journal of population data science,2019,2019-05-20,Y,,,,"

Introduction

Excessive alcohol consumption has adverse effects on health and there is a recognised need for the longitudinal analysis of population data to improve our understanding of the patterns of alcohol use, harms to consumers and those in their immediate environment. The UK has a number of linkable, longitudinal databases that if assembled properly could support valuable research on this topic.

Aims and objectives

This paper describes the development of a broad set of cross-linked cohorts, e-cohorts, surveys and linked electronic healthcare records (EHRs) to construct an alcohol-specific analytical platform in the United Kingdom using datasets on the population of Wales.The objective of this paper is to provide a description of existing key datasets integrated with existing, routinely collected electronic health data on a secure platform, and relevant derived variables to enable population-based research on alcohol-related harm in Wales. We illustrate our use of these data with some exemplar research questions that are currently under investigation.

Methods

Record-linkage of routine and observational datasets. Routine data includes hospital admissions, general practice, and cohorts specific to children. Two observational studies were included. Routine socioeconomic descriptors and mortality data were also linked.

Conclusion

We described a record-linked, population-based research protocol for alcohol related harm on a secure platform. As the datasets used here are available in many countries, ELAStiC provides a template for setting up similar initiatives in other countries. We have also defined a number of alcohol specific variables using routinely-collected available data that can be used in other epidemiological studies into alcohol related outcomes. With over 10 years of longitudinal data, it will help to understand alcohol-related disease and health trajectories across the lifespan.",,pdf:https://ijpds.org/article/download/581/2923; doi:https://doi.org/10.23889/ijpds.v4i1.581; html:https://europepmc.org/articles/PMC8142962; pdf:https://europepmc.org/articles/PMC8142962?pdf=render -38763167,https://doi.org/10.1164/rccm.202312-2289oc,Impact of High Dose Early Mobilization on Outcomes for Patients with Diabetes: A Secondary Analysis of the TEAM Trial.,"Serpa Neto A, Bailey M, Seller D, Agli A, Bellomo R, Brickell K, Broadley T, Buhr H, Gabbe BJ, Gould DW, Harrold M, Higgins AM, Hurford S, Iwashyna TJ, Nichol AD, Presneill JJ, Schaller SJ, Sivasuthan J, Tipping CJ, Poole A, Parke R, Bradley S, Webb S, Zoungas S, Young PJ, Hodgson CL.",,American journal of respiratory and critical care medicine,2024,2024-05-19,N,Mortality; Mechanical ventilation; Physiotherapy; Clinical Trial,,,"

Rationale

Patients with diabetes represent almost 20% of all ICU admissions and might respond differently to high dose early active mobilization.

Objectives

To assess whether diabetes modified the relationship between the dose of early mobilization on clinical outcomes in the TEAM trial.

Methods

All TEAM trial patients were included. The primary outcome was days alive and out of hospital at day 180. Secondary outcomes included 180-day mortality and long-term functional outcomes at day 180. Logistic and median regression models were used to explore the effect of high dose early mobilization on outcomes by diabetes status.

Measurements and main results

All 741 patients from the original trial were included. Of these, 159 patients (21.4%) had diabetes. Patients with diabetes had a lower number of days alive and out of hospital at day 180 (124 [0-153] vs. 147 [82-164], p = 0.013), and higher 180-day mortality (30% vs. 18%, p = 0.044). In patients receiving high dose early mobilization, days alive and out of hospital at day 180 was 73.0 (0.0 - 144.5) in patients with diabetes and 146.5 (95.8 - 163.0) in patients without diabetes (p for interaction = 0.108). However, in patients with diabetes, high dose early mobilization increased the odds of mortality at 180 days (adjusted odds ratio 3.47; 95% confidence interval [CI], 1.67-7.61, p value for interaction, 0.001).

Conclusions

In this secondary analysis of the TEAM trial, in patients with diabetes, a high dose early mobilization strategy did not significantly decrease the number of days alive and out of hospital at day 180 but it increased 180-day mortality.",,doi:https://doi.org/10.1164/rccm.202312-2289OC 34275648,https://doi.org/10.1016/j.injury.2021.06.037,Patterns and predictors of personal responsibility attributions after major trauma.,"Lau G, Gabbe BJ, Giummarra MJ.",,Injury,2021,2021-07-06,N,"wounds and injuries; Insurance, Accident; Violence; Guilt; Accidental Injuries; Liability, Legal",,,"

Background

External responsibility attributions after injury are associated with worse recovery. However, there remains limited understanding of who accepts personal responsibilityfor their injury and whether or how responsibility attributions change over time.

Methods

This prospective cohort study included patients who received care from recovery co-ordinators following serious injury and admission to a major trauma centre in Victoria, Australia (n=850). Self-reported personal responsibility attributions (totally, partially, not responsible, or did not know) were collected at three timepoints (admission, discharge, and six months post-injury) and linked to demographic, injury and clinical characteristics from the Victorian State Trauma Registry.

Results

Mixed effects multinomial analyses revealed that female sex (adjusted relative risk ratio, aRRR=3.11-4.66) and compensable injury (aRRR=7.83-15.27) were associated with reporting lower personal responsibility relative to total responsibility. Falls and motorcyclists had decreased risk of reporting lower personal responsibility than non-drivers (motor vehicle/motorcycle passengers, cyclists and pedestrians) (aRRR=0.11-0.19). More than one-third of participants changed their personal responsibility attribution within six months post-injury. Kappa analyses revealed fair to moderate agreement between the three timepoints (kappa=0.38-0.59), and Stuart-Maxwell tests showed unidirectional bias towards reporting lower levels of personal responsibility between admission and discharge (p<0.001). No demographic, health or injury characteristics predicted a change in responsibility attributions in logistic regression analyses.

Conclusions

Personal responsibility attributions often change over time. Therefore, responsibility attributions should not be considered static, and attributions made at different times post-injury should not be used interchangeably in research or clinical settings. Given that external responsibility attributions are associated with worse post-injury outcomes, potential interventions to optimise recovery should be prioritised for patients who predominantly report lower levels of personal responsibility, especially women and people with compensable injuries. Meanwhile, factors associated with high levels of personal responsibility highlight opportunities to implement targeted injury prevention strategies.",,doi:https://doi.org/10.1016/j.injury.2021.06.037 -37477803,https://doi.org/10.1007/s11897-023-00615-z,Discovering Distinct Phenotypical Clusters in Heart Failure Across the Ejection Fraction Spectrum: a Systematic Review.,"Meijs C, Handoko ML, Savarese G, Vernooij RWM, Vaartjes I, Banerjee A, Koudstaal S, Brugts JJ, Asselbergs FW, Uijl A.",,Current heart failure reports,2023,2023-07-21,Y,Clustering; Phenotyping; Heart Failure; Machine Learning; Precision Medicine,,,"

Review purpose

This systematic review aims to summarise clustering studies in heart failure (HF) and guide future clinical trial design and implementation in routine clinical practice.

Findings

34 studies were identified (n = 19 in HF with preserved ejection fraction (HFpEF)). There was significant heterogeneity invariables and techniques used. However, 149/165 described clusters could be assigned to one of nine phenotypes: 1) young, low comorbidity burden; 2) metabolic; 3) cardio-renal; 4) atrial fibrillation (AF); 5) elderly female AF; 6) hypertensive-comorbidity; 7) ischaemic-male; 8) valvular disease; and 9) devices. There was room for improvement on important methodological topics for all clustering studies such as external validation and transparency of the modelling process. The large overlap between the phenotypes of the clustering studies shows that clustering is a robust approach for discovering clinically distinct phenotypes. However, future studies should invest in a phenotype model that can be implemented in routine clinical practice and future clinical trial design. HF = heart failure, EF = ejection fraction, HFpEF = heart failure with preserved ejection fraction, HFrEF = heart failure with reduced ejection fraction, CKD = chronic kidney disease, AF = atrial fibrillation, IHD = ischaemic heart disease, CAD = coronary artery disease, ICD = implantable cardioverter-defibrillator, CRT = cardiac resynchronization therapy, NT-proBNP = N-terminal pro b-type natriuretic peptide, BMI = Body Mass Index, COPD = Chronic obstructive pulmonary disease.",,pdf:https://link.springer.com/content/pdf/10.1007/s11897-023-00615-z.pdf; doi:https://doi.org/10.1007/s11897-023-00615-z; html:https://europepmc.org/articles/PMC10589200; pdf:https://europepmc.org/articles/PMC10589200?pdf=render +38763167,https://doi.org/10.1164/rccm.202312-2289oc,Impact of High Dose Early Mobilization on Outcomes for Patients with Diabetes: A Secondary Analysis of the TEAM Trial.,"Serpa Neto A, Bailey M, Seller D, Agli A, Bellomo R, Brickell K, Broadley T, Buhr H, Gabbe BJ, Gould DW, Harrold M, Higgins AM, Hurford S, Iwashyna TJ, Nichol AD, Presneill JJ, Schaller SJ, Sivasuthan J, Tipping CJ, Poole A, Parke R, Bradley S, Webb S, Zoungas S, Young PJ, Hodgson CL.",,American journal of respiratory and critical care medicine,2024,2024-05-19,N,Mortality; Mechanical ventilation; Physiotherapy; Clinical Trial,,,"

Rationale

Patients with diabetes represent almost 20% of all ICU admissions and might respond differently to high dose early active mobilization.

Objectives

To assess whether diabetes modified the relationship between the dose of early mobilization on clinical outcomes in the TEAM trial.

Methods

All TEAM trial patients were included. The primary outcome was days alive and out of hospital at day 180. Secondary outcomes included 180-day mortality and long-term functional outcomes at day 180. Logistic and median regression models were used to explore the effect of high dose early mobilization on outcomes by diabetes status.

Measurements and main results

All 741 patients from the original trial were included. Of these, 159 patients (21.4%) had diabetes. Patients with diabetes had a lower number of days alive and out of hospital at day 180 (124 [0-153] vs. 147 [82-164], p = 0.013), and higher 180-day mortality (30% vs. 18%, p = 0.044). In patients receiving high dose early mobilization, days alive and out of hospital at day 180 was 73.0 (0.0 - 144.5) in patients with diabetes and 146.5 (95.8 - 163.0) in patients without diabetes (p for interaction = 0.108). However, in patients with diabetes, high dose early mobilization increased the odds of mortality at 180 days (adjusted odds ratio 3.47; 95% confidence interval [CI], 1.67-7.61, p value for interaction, 0.001).

Conclusions

In this secondary analysis of the TEAM trial, in patients with diabetes, a high dose early mobilization strategy did not significantly decrease the number of days alive and out of hospital at day 180 but it increased 180-day mortality.",,doi:https://doi.org/10.1164/rccm.202312-2289OC 35796550,https://doi.org/10.1093/hmg/ddac153,The impact of fatty acids biosynthesis on the risk of cardiovascular diseases in Europeans and East Asians: a Mendelian randomization study.,"Borges MC, Haycock P, Zheng J, Hemani G, Howe LJ, Schmidt AF, Staley JR, Lumbers RT, Henry A, Lemaitre RN, Gaunt TR, Holmes MV, Davey Smith G, Hingorani AD, Lawlor DA.",,Human molecular genetics,2022,2022-11-01,N,,,,"Despite early interest, the evidence linking fatty acids to cardiovascular diseases (CVDs) remains controversial. We used Mendelian randomization to explore the involvement of polyunsaturated (PUFA) and monounsaturated (MUFA) fatty acids biosynthesis in the etiology of several CVD endpoints in up to 1 153 768 European (maximum 123 668 cases) and 212 453 East Asian (maximum 29 319 cases) ancestry individuals. As instruments, we selected single nucleotide polymorphisms mapping to genes with well-known roles in PUFA (i.e. FADS1/2 and ELOVL2) and MUFA (i.e. SCD) biosynthesis. Our findings suggest that higher PUFA biosynthesis rate (proxied by rs174576 near FADS1/2) is related to higher odds of multiple CVDs, particularly ischemic stroke, peripheral artery disease and venous thromboembolism, whereas higher MUFA biosynthesis rate (proxied by rs603424 near SCD) is related to lower odds of coronary artery disease among Europeans. Results were unclear for East Asians as most effect estimates were imprecise. By triangulating multiple approaches (i.e. uni-/multi-variable Mendelian randomization, a phenome-wide scan, genetic colocalization and within-sibling analyses), our results are compatible with higher low-density lipoprotein (LDL) cholesterol (and possibly glucose) being a downstream effect of higher PUFA biosynthesis rate. Our findings indicate that PUFA and MUFA biosynthesis are involved in the etiology of CVDs and suggest LDL cholesterol as a potential mediating trait between PUFA biosynthesis and CVDs risk.",,pdf:https://academic.oup.com/hmg/advance-article-pdf/doi/10.1093/hmg/ddac153/45277324/ddac153.pdf; doi:https://doi.org/10.1093/hmg/ddac153 +37477803,https://doi.org/10.1007/s11897-023-00615-z,Discovering Distinct Phenotypical Clusters in Heart Failure Across the Ejection Fraction Spectrum: a Systematic Review.,"Meijs C, Handoko ML, Savarese G, Vernooij RWM, Vaartjes I, Banerjee A, Koudstaal S, Brugts JJ, Asselbergs FW, Uijl A.",,Current heart failure reports,2023,2023-07-21,Y,Clustering; Phenotyping; Heart Failure; Machine Learning; Precision Medicine,,,"

Review purpose

This systematic review aims to summarise clustering studies in heart failure (HF) and guide future clinical trial design and implementation in routine clinical practice.

Findings

34 studies were identified (n = 19 in HF with preserved ejection fraction (HFpEF)). There was significant heterogeneity invariables and techniques used. However, 149/165 described clusters could be assigned to one of nine phenotypes: 1) young, low comorbidity burden; 2) metabolic; 3) cardio-renal; 4) atrial fibrillation (AF); 5) elderly female AF; 6) hypertensive-comorbidity; 7) ischaemic-male; 8) valvular disease; and 9) devices. There was room for improvement on important methodological topics for all clustering studies such as external validation and transparency of the modelling process. The large overlap between the phenotypes of the clustering studies shows that clustering is a robust approach for discovering clinically distinct phenotypes. However, future studies should invest in a phenotype model that can be implemented in routine clinical practice and future clinical trial design. HF = heart failure, EF = ejection fraction, HFpEF = heart failure with preserved ejection fraction, HFrEF = heart failure with reduced ejection fraction, CKD = chronic kidney disease, AF = atrial fibrillation, IHD = ischaemic heart disease, CAD = coronary artery disease, ICD = implantable cardioverter-defibrillator, CRT = cardiac resynchronization therapy, NT-proBNP = N-terminal pro b-type natriuretic peptide, BMI = Body Mass Index, COPD = Chronic obstructive pulmonary disease.",,pdf:https://link.springer.com/content/pdf/10.1007/s11897-023-00615-z.pdf; doi:https://doi.org/10.1007/s11897-023-00615-z; html:https://europepmc.org/articles/PMC10589200; pdf:https://europepmc.org/articles/PMC10589200?pdf=render 35089148,https://doi.org/10.2196/28095,The Association Between Home Stay and Symptom Severity in Major Depressive Disorder: Preliminary Findings From a Multicenter Observational Study Using Geolocation Data From Smartphones.,"Laiou P, Kaliukhovich DA, Folarin AA, Ranjan Y, Rashid Z, Conde P, Stewart C, Sun S, Zhang Y, Matcham F, Ivan A, Lavelle G, Siddi S, Lamers F, Penninx BW, Haro JM, Annas P, Cummins N, Vairavan S, Manyakov NV, Narayan VA, Dobson RJ, Hotopf M, RADAR-CNS.",,JMIR mHealth and uHealth,2022,2022-01-28,Y,GPS; Mobile phone; Major Depressive Disorder; Smartphone; Phq-8; Home Stay,,,"

Background

Most smartphones and wearables are currently equipped with location sensing (using GPS and mobile network information), which enables continuous location tracking of their users. Several studies have reported that various mobility metrics, as well as home stay, that is, the amount of time an individual spends at home in a day, are associated with symptom severity in people with major depressive disorder (MDD). Owing to the use of small and homogeneous cohorts of participants, it is uncertain whether the findings reported in those studies generalize to a broader population of individuals with MDD symptoms.

Objective

The objective of this study is to examine the relationship between the overall severity of depressive symptoms, as assessed by the 8-item Patient Health Questionnaire, and median daily home stay over the 2 weeks preceding the completion of a questionnaire in individuals with MDD.

Methods

We used questionnaire and geolocation data of 164 participants with MDD collected in the observational Remote Assessment of Disease and Relapse-Major Depressive Disorder study. The participants were recruited from three study sites: King's College London in the United Kingdom (109/164, 66.5%); Vrije Universiteit Medisch Centrum in Amsterdam, the Netherlands (17/164, 10.4%); and Centro de Investigación Biomédica en Red in Barcelona, Spain (38/164, 23.2%). We used a linear regression model and a resampling technique (n=100 draws) to investigate the relationship between home stay and the overall severity of MDD symptoms. Participant age at enrollment, gender, occupational status, and geolocation data quality metrics were included in the model as additional explanatory variables. The 95% 2-sided CIs were used to evaluate the significance of model variables.

Results

Participant age and severity of MDD symptoms were found to be significantly related to home stay, with older (95% CI 0.161-0.325) and more severely affected individuals (95% CI 0.015-0.184) spending more time at home. The association between home stay and symptoms severity appeared to be stronger on weekdays (95% CI 0.023-0.178, median 0.098; home stay: 25th-75th percentiles 17.8-22.8, median 20.9 hours a day) than on weekends (95% CI -0.079 to 0.149, median 0.052; home stay: 25th-75th percentiles 19.7-23.5, median 22.3 hours a day). Furthermore, we found a significant modulation of home stay by occupational status, with employment reducing home stay (employed participants: 25th-75th percentiles 16.1-22.1, median 19.7 hours a day; unemployed participants: 25th-75th percentiles 20.4-23.5, median 22.6 hours a day).

Conclusions

Our findings suggest that home stay is associated with symptom severity in MDD and demonstrate the importance of accounting for confounding factors in future studies. In addition, they illustrate that passive sensing of individuals with depression is feasible and could provide clinically relevant information to monitor the course of illness in patients with MDD.",,pdf:https://mhealth.jmir.org/2022/1/e28095/PDF; doi:https://doi.org/10.2196/28095; html:https://europepmc.org/articles/PMC8838593 36692937,https://doi.org/10.2196/42866,The Feasibility of Implementing Remote Measurement Technologies in Psychological Treatment for Depression: Mixed Methods Study on Engagement.,"de Angel V, Adeleye F, Zhang Y, Cummins N, Munir S, Lewis S, Laporta Puyal E, Matcham F, Sun S, Folarin AA, Ranjan Y, Conde P, Rashid Z, Dobson R, Hotopf M.",,JMIR mental health,2023,2023-01-24,Y,Depression; Mobile phone; Anxiety; Smartphone; Mhealth; Mobile Health; Wearable Devices; Digital Health; Digital Phenotyping; Passive Sensing,,,"

Background

Remote measurement technologies (RMTs) such as smartphones and wearables can help improve treatment for depression by providing objective, continuous, and ecologically valid insights into mood and behavior. Engagement with RMTs is varied and highly context dependent; however, few studies have investigated their feasibility in the context of treatment.

Objective

A mixed methods design was used to evaluate engagement with active and passive data collection via RMT in people with depression undergoing psychotherapy. We evaluated the effects of treatment on 2 different types of engagement: study attrition (engagement with study protocol) and patterns of missing data (engagement with digital devices), which we termed data availability. Qualitative interviews were conducted to help interpret the differences in engagement.

Methods

A total of 66 people undergoing psychological therapy for depression were followed up for 7 months. Active data were gathered from weekly questionnaires and speech and cognitive tasks, and passive data were gathered from smartphone sensors and a Fitbit (Fitbit Inc) wearable device.

Results

The overall retention rate was 60%. Higher-intensity treatment (χ21=4.6; P=.03) and higher baseline anxiety (t56.28=-2.80, 2-tailed; P=.007) were associated with attrition, but depression severity was not (t50.4=-0.18; P=.86). A trend toward significance was found for the association between longer treatments and increased attrition (U=339.5; P=.05). Data availability was higher for active data than for passive data initially but declined at a sharper rate (90%-30% drop in 7 months). As for passive data, wearable data availability fell from a maximum of 80% to 45% at 7 months but showed higher overall data availability than smartphone-based data, which remained stable at the range of 20%-40% throughout. Missing data were more prevalent among GPS location data, followed by among Bluetooth data, then among accelerometry data. As for active data, speech and cognitive tasks had lower completion rates than clinical questionnaires. The participants in treatment provided less Fitbit data but more active data than those on the waiting list.

Conclusions

Different data streams showed varied patterns of missing data, despite being gathered from the same device. Longer and more complex treatments and clinical characteristics such as higher baseline anxiety may reduce long-term engagement with RMTs, and different devices may show opposite patterns of missingness during treatment. This has implications for the scalability and uptake of RMTs in health care settings, the generalizability and accuracy of the data collected by these methods, feature construction, and the appropriateness of RMT use in the long term.",,pdf:https://mental.jmir.org/2023/1/e42866/PDF; doi:https://doi.org/10.2196/42866; html:https://europepmc.org/articles/PMC9906314 38214281,https://doi.org/10.1161/jaha.123.031646,Acute Coronary Syndrome Subphenotypes Based on Repeated Biomarker Measurements in Relation to Long-Term Mortality Risk.,"de Bakker M, Scholte NTB, Oemrawsingh RM, Umans VA, Kietselaer B, Schotborgh C, Ronner E, Lenderink T, Aksoy I, van der Harst P, Asselbergs FW, Maas A, Oude Ophuis AJ, Krenning B, de Winter RJ, The SHK, Wardeh AJ, Hermans W, Cramer GE, van Schaik RH, de Rijke YB, Akkerhuis KM, Kardys I, Boersma E, BIOMArCS Investigators †.",,Journal of the American Heart Association,2024,2024-01-12,Y,Death; Phenotypes; acute coronary syndrome; Repeated Measurements; Cardiovascular Biomarkers,,,"

Background

We aimed to identify patients with subphenotypes of postacute coronary syndrome (ACS) using repeated measurements of high-sensitivity cardiac troponin T, N-terminal pro-B-type natriuretic peptide, high-sensitivity C-reactive protein, and growth differentiation factor 15 in the year after the index admission, and to investigate their association with long-term mortality risk.

Methods and results

BIOMArCS (BIOMarker Study to Identify the Acute Risk of a Coronary Syndrome) was an observational study of patients with ACS, who underwent high-frequency blood sampling for 1 year. Biomarkers were measured in a median of 16 repeated samples per individual. Cluster analysis was performed to identify biomarker-based subphenotypes in 723 patients without a repeat ACS in the first year. Patients with a repeat ACS (N=36) were considered a separate cluster. Differences in all-cause death were evaluated using accelerated failure time models (median follow-up, 9.1 years; 141 deaths). Three biomarker-based clusters were identified: cluster 1 showed low and stable biomarker concentrations, cluster 2 had elevated concentrations that subsequently decreased, and cluster 3 showed persistently elevated concentrations. The temporal biomarker patterns of patients in cluster 3 were similar to those with a repeat ACS during the first year. Clusters 1 and 2 had a similar and favorable long-term mortality risk. Cluster 3 had the highest mortality risk. The adjusted survival time ratio was 0.64 (95% CI, 0.44-0.93; P=0.018) compared with cluster 1, and 0.71 (95% CI, 0.39-1.32; P=0.281) compared with patients with a repeat ACS.

Conclusions

Patients with subphenotypes of post-ACS with different all-cause mortality risks during long-term follow-up can be identified on the basis of repeatedly measured cardiovascular biomarkers. Patients with persistently elevated biomarkers have the worst outcomes, regardless of whether they experienced a repeat ACS in the first year.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/JAHA.123.031646; doi:https://doi.org/10.1161/JAHA.123.031646; html:https://europepmc.org/articles/PMC10926784; pdf:https://europepmc.org/articles/PMC10926784?pdf=render 37993464,https://doi.org/10.1038/s41467-023-43434-5,Structure of the N-RNA/P interface indicates mode of L/P recruitment to the nucleocapsid of human metapneumovirus.,"Whitehead JD, Decool H, Leyrat C, Carrique L, Fix J, Eléouët JF, Galloux M, Renner M.",,Nature communications,2023,2023-11-22,Y,,,,"Human metapneumovirus (HMPV) is a major cause of respiratory illness in young children. The HMPV polymerase (L) binds an obligate cofactor, the phosphoprotein (P). During replication and transcription, the L/P complex traverses the viral RNA genome, which is encapsidated within nucleoproteins (N). An essential interaction between N and a C-terminal region of P tethers the L/P polymerase to the template. This N-P interaction is also involved in the formation of cytoplasmic viral factories in infected cells, called inclusion bodies. To define how the polymerase component P recognizes N-encapsidated RNA (N-RNA) we employed cryogenic electron microscopy (cryo-EM) and molecular dynamics simulations, coupled to activity assays and imaging of inclusion bodies in cells. We report a 2.9 Å resolution structure of a triple-complex between multimeric N, bound to both RNA and the C-terminal region of P. Furthermore, we also present cryo-EM structures of assembled N in different oligomeric states, highlighting the plasticity of N. Combined with our functional assays, these structural data delineate in molecular detail how P attaches to N-RNA whilst retaining substantial conformational dynamics. Moreover, the N-RNA-P triple complex structure provides a molecular blueprint for the design of therapeutics to potentially disrupt the attachment of L/P to its template.",,pdf:https://www.nature.com/articles/s41467-023-43434-5.pdf; doi:https://doi.org/10.1038/s41467-023-43434-5; html:https://europepmc.org/articles/PMC10665349; pdf:https://europepmc.org/articles/PMC10665349?pdf=render -37538742,https://doi.org/10.1098/rsos.221469,Bayesian inference of polymerase dynamics over the exclusion process.,"Cavallaro M, Wang Y, Hebenstreit D, Dutta R.",,Royal Society open science,2023,2023-08-02,Y,Gene Expression; Bayesian Statistics; Particle Transport; Non-equilbrium Physics,,,"Transcription is a complex phenomenon that permits the conversion of genetic information into phenotype by means of an enzyme called RNA polymerase, which erratically moves along and scans the DNA template. We perform Bayesian inference over a paradigmatic mechanistic model of non-equilibrium statistical physics, i.e. the asymmetric exclusion processes in the hydrodynamic limit, assuming a Gaussian process prior for the polymerase progression rate as a latent variable. Our framework allows us to infer the speed of polymerases during transcription given their spatial distribution, while avoiding the explicit inversion of the system's dynamics. The results, which show processing rates strongly varying with genomic position and minor role of traffic-like congestion, may have strong implications for the understanding of gene expression.",,doi:https://doi.org/10.1098/rsos.221469; doi:https://doi.org/10.1098/rsos.221469; html:https://europepmc.org/articles/PMC10394410; pdf:https://europepmc.org/articles/PMC10394410?pdf=render 31822919,https://doi.org/10.1093/pubmed/fdz172,"Unmet needs of women with GDM: a health needs assessment in Sandwell, West Midlands.","Plant N, Šumilo D, Chapman R, Webber J, Saravanan P, Nirantharakumar K.",,"Journal of public health (Oxford, England)",2020,2020-11-01,N,United Kingdom; Needs Assessment; Gestational Diabetes,,,"

Background

Gestational diabetes mellitus (GDM) affects over 4% of pregnancies in England. We investigated GDM epidemiology within ethnically diverse population and the current offer of services to women with previous GDM to reduce their type 2 diabetes mellitus (T2DM) risk.

Methods

(i) Analysis of routinely collected maternity data examining GDM incidence and risk factors; (ii) local authority self-assessment questionnaire on public health interventions targeting women with previous GDM and (iii) service development discussions regarding the current pathway and areas for improvement.

Results

Of 9390 births between 2014 and 2018, 6.8% had a record of GDM. High body mass index (BMI), maternal age, and ethnicity (South Asian and some mixed ethnic backgrounds) were independent predictors of GDM. There were no public health commissioned services specifically targeting women with previous GDM. Weaknesses in transition from secondary to primary care and areas for improvement when screening for GDM were identified.

Conclusions

GDM burden in this population was high. Awareness should be raised on the importance of regular glucose testing and lifestyle modification to delay or prevent progression to T2DM, particularly within high risk groups. The potential for health visitors to contribute to this should be explored. Commissioners should review evidence to develop a flexible lifestyle services model to meet the specific needs of these women.",,pdf:https://academic.oup.com/jpubhealth/article-pdf/42/4/e516/34469316/fdz172.pdf; doi:https://doi.org/10.1093/pubmed/fdz172 +37538742,https://doi.org/10.1098/rsos.221469,Bayesian inference of polymerase dynamics over the exclusion process.,"Cavallaro M, Wang Y, Hebenstreit D, Dutta R.",,Royal Society open science,2023,2023-08-02,Y,Gene Expression; Bayesian Statistics; Particle Transport; Non-equilbrium Physics,,,"Transcription is a complex phenomenon that permits the conversion of genetic information into phenotype by means of an enzyme called RNA polymerase, which erratically moves along and scans the DNA template. We perform Bayesian inference over a paradigmatic mechanistic model of non-equilibrium statistical physics, i.e. the asymmetric exclusion processes in the hydrodynamic limit, assuming a Gaussian process prior for the polymerase progression rate as a latent variable. Our framework allows us to infer the speed of polymerases during transcription given their spatial distribution, while avoiding the explicit inversion of the system's dynamics. The results, which show processing rates strongly varying with genomic position and minor role of traffic-like congestion, may have strong implications for the understanding of gene expression.",,doi:https://doi.org/10.1098/rsos.221469; doi:https://doi.org/10.1098/rsos.221469; html:https://europepmc.org/articles/PMC10394410; pdf:https://europepmc.org/articles/PMC10394410?pdf=render 32651323,https://doi.org/10.3233/jad-200338,"Alzheimer's Disease Susceptibility Gene Apolipoprotein E (APOE) and Blood Biomarkers in UK Biobank (N = 395,769).","Ferguson AC, Tank R, Lyall LM, Ward J, Celis-Morales C, Strawbridge R, Ho F, Whelan CD, Gill J, Welsh P, Anderson JJ, Mark PB, Mackay DF, Smith DJ, Pell JP, Cavanagh J, Sattar N, Lyall DM.",,Journal of Alzheimer's disease : JAD,2020,2020-01-01,N,Cholesterol; apoE; Alzheimer’s disease; Dementia; Uk Biobank,,,"

Background

Alzheimer's disease (AD) is a neurodegenerative condition where the underlying etiology is still unclear. Investigating the potential influence of apolipoprotein E (APOE), a major genetic risk factor, on common blood biomarkers could provide a greater understanding of the mechanisms of AD and dementia risk.

Objective

Our objective was to conduct the largest (to date) single-protocol investigation of blood biomarkers in the context of APOE genotype, in UK Biobank.

Methods

After quality control and exclusions, data on 395,769 participants of White European ancestry were available for analysis. Linear regressions were used to test potential associations between APOE genotypes and biomarkers.

Results

Several biomarkers significantly associated with APOEɛ4 'risk' and ɛ2 'protective' genotypes (versus neutral ɛ3/ɛ3). Most associations supported previous data: for example, ɛ4 genotype was associated with elevated low-density lipoprotein cholesterol (LDL) (standardized beta [b] = 0.150 standard deviations [SDs] per allele, p < 0.001) and ɛ2 with lower LDL (b = -0.456 SDs, p < 0.001). There were however instances of associations found in unexpected directions: e.g., ɛ4 and increased insulin-like growth factor (IGF-1) (b = 0.017, p < 0.001) where lower levels have been previously suggested as an AD risk factor.

Conclusion

These findings highlight biomarker differences in non-demented people at genetic risk for dementia. The evidence herein supports previous hypotheses of involvement from cardiometabolic and neuroinflammatory pathways.",,pdf:https://eprints.gla.ac.uk/217500/1/217500.pdf; doi:https://doi.org/10.3233/JAD-200338 33866023,https://doi.org/10.1016/j.oret.2021.04.001,Evolving Treatment Patterns and Outcomes of Neovascular Age-Related Macular Degeneration Over a Decade.,"Schwartz R, Warwick A, Olvera-Barrios A, Pikoula M, Lee AY, Denaxas S, Taylor P, Egan C, Chakravarthy U, Lip PL, Tufail A, of the UK EMR Users Group.",,Ophthalmology. Retina,2021,2021-04-16,N,AMD; Ranibizumab; Anti-vegf; Aflibercept; Electronic Health Records; Etdrs; Early Treatment Diabetic Retinopathy Study,,,"

Purpose

Management of neovascular age-related macular degeneration (nAMD) has evolved over the last decade with several treatment regimens and medications. This study describes the treatment patterns and visual outcomes over 10 years in a large cohort of patients.

Design

Retrospective analysis of electronic health records from 27 National Health Service secondary care healthcare providers in the UK.

Participants

Treatment-naïve patients receiving at least 3 intravitreal anti-vascular endothelial growth factor (VEGF) injections for nAMD in their first 6 months of follow-up were included. Patients with missing data for age or gender and those aged less than 55 years were excluded.

Methods

Eyes with at least 3 years of follow-up were grouped by years of treatment initiation, and 3-year outcomes were compared between the groups. Data were generated during routine clinical care between September 2008 and December 2018.

Main outcome measures

Visual acuity (VA), number of injections, and number of visits.

Results

A total of 15 810 eyes of 13 705 patients receiving 195 104 injections were included. Visual acuity improved from baseline during the first year, but decreased thereafter, resulting in loss of visual gains. This trend remained consistent throughout the past decade. Although an increasing proportion of eyes remained in the driving standard, this was driven by better presenting VA over the decade. The number of injections decreased substantially between the first and subsequent years, from a mean of 6.25 in year 1 to 3 in year 2 and 2.5 in year 3, without improvement over the decade. In a multivariable regression analysis, final VA improved by 0.24 letters for each year since 2008, and younger age and baseline VA were significantly associated with VA at 3 years.

Conclusions

Our findings show that despite improvement in functional VA over the years, primarily driven by improving baseline VA, patients continue to lose vision after the first year of treatment, with only marginal change over the past decade. The data suggest these results may be related to suboptimal treatment patterns, which have not improved over the years. Rethinking treatment strategies may be warranted, possibly on a national level or through the introduction of longer-acting therapies.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9165682; doi:https://doi.org/10.1016/j.oret.2021.04.001; html:https://europepmc.org/articles/PMC9165682; pdf:https://europepmc.org/articles/PMC9165682?pdf=render; doi:https://doi.org/10.1016/j.oret.2021.04.001 35748342,https://doi.org/10.1093/ije/dyac130,Linkage of multiple electronic health record datasets using a 'spine linkage' approach compared with all 'pairwise linkages'.,"Blake HA, Sharples LD, Harron K, van der Meulen JH, Walker K.",,International journal of epidemiology,2023,2023-02-01,Y,Electronic Health Records; Record Linkage; Pairwise Linkage; Spine Linkage Approach,,,"

Background

Methods for linking records between two datasets are well established. However, guidance is needed for linking more than two datasets. Using all 'pairwise linkages'-linking each dataset to every other dataset-is the most inclusive, but resource-intensive, approach. The 'spine' approach links each dataset to a designated 'spine dataset', reducing the number of linkages, but potentially reducing linkage quality.

Methods

We compared the pairwise and spine linkage approaches using real-world data on patients undergoing emergency bowel cancer surgery between 31 October 2013 and 30 April 2018. We linked an administrative hospital dataset (Hospital Episode Statistics; HES) capturing patients admitted to hospitals in England, and two clinical datasets comprising patients diagnosed with bowel cancer and patients undergoing emergency bowel surgery.

Results

The spine linkage approach, with HES as the spine dataset, created an analysis cohort of 15 826 patients, equating to 98.3% of the 16 100 patients identified using the pairwise linkage approach. There were no systematic differences in patient characteristics between these analysis cohorts. Associations of patient and tumour characteristics with mortality, complications and length of stay were not sensitive to the linkage approach. When eligibility criteria were applied before linkage, spine linkage included 14 509 patients (90.0% compared with pairwise linkage).

Conclusion

Spine linkage can be used as an efficient alternative to pairwise linkage if case ascertainment in the spine dataset and data quality of linkage variables are high. These aspects should be systematically evaluated in the nominated spine dataset before spine linkage is used to create the analysis cohort.",,pdf:https://academic.oup.com/ije/advance-article-pdf/doi/10.1093/ije/dyac130/44245961/dyac130.pdf; doi:https://doi.org/10.1093/ije/dyac130; html:https://europepmc.org/articles/PMC9908066; pdf:https://europepmc.org/articles/PMC9908066?pdf=render -36701266,https://doi.org/10.1371/journal.pmed.1004036,"Gestational age at birth and body size from infancy through adolescence: An individual participant data meta-analysis on 253,810 singletons in 16 birth cohort studies.","Vinther JL, Cadman T, Avraam D, Ekstrøm CT, Sørensen TIA, Elhakeem A, Santos AC, Pinot de Moira A, Heude B, Iñiguez C, Pizzi C, Simons E, Voerman E, Corpeleijn E, Zariouh F, Santorelli G, Inskip HM, Barros H, Carson J, Harris JR, Nader JL, Ronkainen J, Strandberg-Larsen K, Santa-Marina L, Calas L, Cederkvist L, Popovic M, Charles MA, Welten M, Vrijheid M, Azad M, Subbarao P, Burton P, Mandhane PJ, Huang RC, Wilson RC, Haakma S, Fernández-Barrés S, Turvey S, Santos S, Tough SC, Tough SC, Sebert S, Moraes TJ, Salika T, Jaddoe VWV, Lawlor DA, Nybo Andersen AM.",,PLoS medicine,2023,2023-01-26,Y,,,,"

Background

Preterm birth is the leading cause of perinatal morbidity and mortality and is associated with adverse developmental and long-term health outcomes, including several cardiometabolic risk factors and outcomes. However, evidence about the association of preterm birth with later body size derives mainly from studies using birth weight as a proxy of prematurity rather than an actual length of gestation. We investigated the association of gestational age (GA) at birth with body size from infancy through adolescence.

Methods and findings

We conducted a two-stage individual participant data (IPD) meta-analysis using data from 253,810 mother-child dyads from 16 general population-based cohort studies in Europe (Denmark, Finland, France, Italy, Norway, Portugal, Spain, the Netherlands, United Kingdom), North America (Canada), and Australasia (Australia) to estimate the association of GA with body mass index (BMI) and overweight (including obesity) adjusted for the following maternal characteristics as potential confounders: education, height, prepregnancy BMI, ethnic background, parity, smoking during pregnancy, age at child's birth, gestational diabetes and hypertension, and preeclampsia. Pregnancy and birth cohort studies from the LifeCycle and the EUCAN-Connect projects were invited and were eligible for inclusion if they had information on GA and minimum one measurement of BMI between infancy and adolescence. Using a federated analytical tool (DataSHIELD), we fitted linear and logistic regression models in each cohort separately with a complete-case approach and combined the regression estimates and standard errors through random-effects study-level meta-analysis providing an overall effect estimate at early infancy (>0.0 to 0.5 years), late infancy (>0.5 to 2.0 years), early childhood (>2.0 to 5.0 years), mid-childhood (>5.0 to 9.0 years), late childhood (>9.0 to 14.0 years), and adolescence (>14.0 to 19.0 years). GA was positively associated with BMI in the first decade of life, with the greatest increase in mean BMI z-score during early infancy (0.02, 95% confidence interval (CI): 0.00; 0.05, p < 0.05) per week of increase in GA, while in adolescence, preterm individuals reached similar levels of BMI (0.00, 95% CI: -0.01; 0.01, p 0.9) as term counterparts. The association between GA and overweight revealed a similar pattern of association with an increase in odds ratio (OR) of overweight from late infancy through mid-childhood (OR 1.01 to 1.02) per week increase in GA. By adolescence, however, GA was slightly negatively associated with the risk of overweight (OR 0.98 [95% CI: 0.97; 1.00], p 0.1) per week of increase in GA. Although based on only four cohorts (n = 32,089) that reached the age of adolescence, data suggest that individuals born very preterm may be at increased odds of overweight (OR 1.46 [95% CI: 1.03; 2.08], p < 0.05) compared with term counterparts. Findings were consistent across cohorts and sensitivity analyses despite considerable heterogeneity in cohort characteristics. However, residual confounding may be a limitation in this study, while findings may be less generalisable to settings in low- and middle-income countries.

Conclusions

This study based on data from infancy through adolescence from 16 cohort studies found that GA may be important for body size in infancy, but the strength of association attenuates consistently with age. By adolescence, preterm individuals have on average a similar mean BMI to peers born at term.",,pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1004036&type=printable; doi:https://doi.org/10.1371/journal.pmed.1004036; html:https://europepmc.org/articles/PMC9879424; pdf:https://europepmc.org/articles/PMC9879424?pdf=render 32142356,https://doi.org/10.1164/rccm.201902-0286oc,"Prenatal, Early-Life, and Childhood Exposure to Air Pollution and Lung Function: The ALSPAC Cohort.","Cai Y, Hansell AL, Granell R, Blangiardo M, Zottoli M, Fecht D, Gulliver J, Henderson AJ, Elliott P.",,American journal of respiratory and critical care medicine,2020,2020-07-01,N,Air pollution; Children; Traffic; Alspac; Respiratory Health,,,"Rationale: Exposure to air pollution during intrauterine development and through childhood may have lasting effects on respiratory health.Objectives: To investigate lung function at ages 8 and 15 years in relation to air pollution exposures during pregnancy, infancy, and childhood in a UK population-based birth cohort.Methods: Individual exposures to source-specific particulate matter ≤10 μm in aerodynamic diameter (PM10) during each trimester, 0-6 months, 7-12 months (1990-1993), and up to age 15 years (1991-2008) were examined in relation to FEV1% predicted and FVC% predicted at ages 8 (n = 5,276) and 15 (n = 3,446) years using linear regression models adjusted for potential confounders. A profile regression model was used to identify sensitive time periods.Measurements and Main Results: We did not find clear evidence of a sensitive exposure period for PM10 from road traffic. At age 8 years, 1 μg/m3 higher exposure during the first trimester was associated with lower FEV1% predicted (-0.826; 95% confidence interval [CI], -1.357 to -0.296) and FVC% predicted (-0.817; 95% CI, -1.357 to -0.276), but similar associations were seen for exposures for other trimesters, 0-6 months, 7-12 months, and 0-7 years. Associations were stronger among boys, as well as children whose mother had a lower education level or smoked during pregnancy. For PM10 from all sources, the third trimester was associated with lower FVC% predicted (-1.312; 95% CI, -2.100 to -0.525). At age 15 years, no adverse associations with lung function were seen.Conclusions: Exposure to road-traffic PM10 during pregnancy may result in small but significant reductions in lung function at age 8 years.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7328307; doi:https://doi.org/10.1164/rccm.201902-0286OC; html:https://europepmc.org/articles/PMC7328307; pdf:https://europepmc.org/articles/PMC7328307?pdf=render; doi:https://doi.org/10.1164/rccm.201902-0286oc 30745170,https://doi.org/10.1016/j.ebiom.2019.02.005,"Identification of novel genome-wide associations for suicidality in UK Biobank, genetic correlation with psychiatric disorders and polygenic association with completed suicide.","Strawbridge RJ, Ward J, Ferguson A, Graham N, Shaw RJ, Cullen B, Pearsall R, Lyall LM, Johnston KJA, Niedzwiedz CL, Pell JP, Mackay D, Martin JL, Lyall DM, Bailey MES, Smith DJ.",,EBioMedicine,2019,2019-02-08,Y,,Understanding the Causes of Disease,,"

Background

Suicide is a major issue for global public health. Suicidality describes a broad spectrum of thoughts and behaviours, some of which are common in the general population. Although suicide results from a complex interaction of multiple social and psychological factors, predisposition to suicidality is at least partly genetic.

Methods

Ordinal genome-wide association study of suicidality in the UK Biobank cohort comparing: 'no suicidality' controls (N = 83,557); 'thoughts that life was not worth living' (N = 21,063); 'ever contemplated self-harm' (N = 13,038); 'act of deliberate self-harm in the past' (N = 2498); and 'previous suicide attempt' (N = 2666).

Outcomes

We identified three novel genome-wide significant loci for suicidality (on chromosomes nine, 11 and 13) and moderate-to-strong genetic correlations between suicidality and a range of psychiatric disorders, most notably depression (rg 0·81).

Interpretation

These findings provide new information about genetic variants relating to increased risk of suicidal thoughts and behaviours. Future work should assess the extent to which polygenic risk scores for suicidality, in combination with non-genetic risk factors, may be useful for stratified approaches to suicide prevention at a population level. FUND: UKRI Innovation-HDR-UK Fellowship (MR/S003061/1). MRC Mental Health Data Pathfinder Award (MC_PC_17217). MRC Doctoral Training Programme Studentship at the University of Glasgow (MR/K501335/1). MRC Doctoral Training Programme Studentship at the Universities of Glasgow and Edinburgh. UKRI Innovation Fellowship (MR/R024774/1).",,pdf:http://www.thelancet.com/article/S2352396419300775/pdf; doi:https://doi.org/10.1016/j.ebiom.2019.02.005; html:https://europepmc.org/articles/PMC6442001; pdf:https://europepmc.org/articles/PMC6442001?pdf=render +36701266,https://doi.org/10.1371/journal.pmed.1004036,"Gestational age at birth and body size from infancy through adolescence: An individual participant data meta-analysis on 253,810 singletons in 16 birth cohort studies.","Vinther JL, Cadman T, Avraam D, Ekstrøm CT, Sørensen TIA, Elhakeem A, Santos AC, Pinot de Moira A, Heude B, Iñiguez C, Pizzi C, Simons E, Voerman E, Corpeleijn E, Zariouh F, Santorelli G, Inskip HM, Barros H, Carson J, Harris JR, Nader JL, Ronkainen J, Strandberg-Larsen K, Santa-Marina L, Calas L, Cederkvist L, Popovic M, Charles MA, Welten M, Vrijheid M, Azad M, Subbarao P, Burton P, Mandhane PJ, Huang RC, Wilson RC, Haakma S, Fernández-Barrés S, Turvey S, Santos S, Tough SC, Tough SC, Sebert S, Moraes TJ, Salika T, Jaddoe VWV, Lawlor DA, Nybo Andersen AM.",,PLoS medicine,2023,2023-01-26,Y,,,,"

Background

Preterm birth is the leading cause of perinatal morbidity and mortality and is associated with adverse developmental and long-term health outcomes, including several cardiometabolic risk factors and outcomes. However, evidence about the association of preterm birth with later body size derives mainly from studies using birth weight as a proxy of prematurity rather than an actual length of gestation. We investigated the association of gestational age (GA) at birth with body size from infancy through adolescence.

Methods and findings

We conducted a two-stage individual participant data (IPD) meta-analysis using data from 253,810 mother-child dyads from 16 general population-based cohort studies in Europe (Denmark, Finland, France, Italy, Norway, Portugal, Spain, the Netherlands, United Kingdom), North America (Canada), and Australasia (Australia) to estimate the association of GA with body mass index (BMI) and overweight (including obesity) adjusted for the following maternal characteristics as potential confounders: education, height, prepregnancy BMI, ethnic background, parity, smoking during pregnancy, age at child's birth, gestational diabetes and hypertension, and preeclampsia. Pregnancy and birth cohort studies from the LifeCycle and the EUCAN-Connect projects were invited and were eligible for inclusion if they had information on GA and minimum one measurement of BMI between infancy and adolescence. Using a federated analytical tool (DataSHIELD), we fitted linear and logistic regression models in each cohort separately with a complete-case approach and combined the regression estimates and standard errors through random-effects study-level meta-analysis providing an overall effect estimate at early infancy (>0.0 to 0.5 years), late infancy (>0.5 to 2.0 years), early childhood (>2.0 to 5.0 years), mid-childhood (>5.0 to 9.0 years), late childhood (>9.0 to 14.0 years), and adolescence (>14.0 to 19.0 years). GA was positively associated with BMI in the first decade of life, with the greatest increase in mean BMI z-score during early infancy (0.02, 95% confidence interval (CI): 0.00; 0.05, p < 0.05) per week of increase in GA, while in adolescence, preterm individuals reached similar levels of BMI (0.00, 95% CI: -0.01; 0.01, p 0.9) as term counterparts. The association between GA and overweight revealed a similar pattern of association with an increase in odds ratio (OR) of overweight from late infancy through mid-childhood (OR 1.01 to 1.02) per week increase in GA. By adolescence, however, GA was slightly negatively associated with the risk of overweight (OR 0.98 [95% CI: 0.97; 1.00], p 0.1) per week of increase in GA. Although based on only four cohorts (n = 32,089) that reached the age of adolescence, data suggest that individuals born very preterm may be at increased odds of overweight (OR 1.46 [95% CI: 1.03; 2.08], p < 0.05) compared with term counterparts. Findings were consistent across cohorts and sensitivity analyses despite considerable heterogeneity in cohort characteristics. However, residual confounding may be a limitation in this study, while findings may be less generalisable to settings in low- and middle-income countries.

Conclusions

This study based on data from infancy through adolescence from 16 cohort studies found that GA may be important for body size in infancy, but the strength of association attenuates consistently with age. By adolescence, preterm individuals have on average a similar mean BMI to peers born at term.",,pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1004036&type=printable; doi:https://doi.org/10.1371/journal.pmed.1004036; html:https://europepmc.org/articles/PMC9879424; pdf:https://europepmc.org/articles/PMC9879424?pdf=render 37735103,https://doi.org/10.1136/bmjresp-2023-001895,"Preterm birth, birth weight, infant weight gain and their associations with childhood asthma and spirometry: a cross-sectional observational study in Nairobi, Kenya.","Meme H, Amukoye E, Bowyer C, Chakaya J, Dobson R, Fuld J, Gray CM, Kiplimo R, Lesosky M, Mortimer K, Ndombi A, Obasi A, Orina F, Quint JK, Semple S, West SE, Zurba L, Devereux G.",,BMJ open respiratory research,2023,2023-09-01,Y,Asthma; Paediatric Lung Disaese; Asthma Epidemiology,,,"

Background

In sub-Saharan Africa, the origins of asthma and high prevalence of abnormal lung function remain unclear. In high-income countries (HICs), associations between birth measurements and childhood asthma and lung function highlight the importance of antenatal and early life factors in the aetiology of asthma and abnormal lung function in children. We present here the first study in sub-Saharan Africa to relate birth characteristics to both childhood respiratory symptoms and lung function.

Methods

Children attending schools in two socioeconomically contrasting but geographically close areas of Nairobi, Kenya, were recruited to a cross-sectional study of childhood asthma and lung function. Questionnaires quantified respiratory symptoms and preterm birth; lung function was measured by spirometry; and parents were invited to bring the child's immunisation booklet containing records of birth weight and serial weights in the first year.

Results

2373 children participated, 52% girls, median age (IQR), 10 years (8-13). Spirometry data were available for 1622. Child immunisation booklets were available for 500 and birth weight and infant weight gain data were available for 323 and 494 children, respectively. In multivariable analyses, preterm birth was associated with the childhood symptoms 'wheeze in the last 12 months'; OR 1.64, (95% CI 1.03 to 2.62), p=0.038; and 'trouble breathing' 3.18 (95% CI 2.27 to 4.45), p<0.001. Birth weight (kg) was associated with forced expiratory volume in 1 s z-score, regression coefficient (β) 0.30 (0.08, 0.52), p=0.008, FVC z-score 0.29 (95% CI 0.08 to 0.51); p=0.008 and restricted spirometry, OR 0.11 (95% CI 0.02 to 0.78), p=0.027.

Conclusion

These associations are in keeping with those in HICs and highlight antenatal factors in the aetiology of asthma and lung function abnormalities in sub-Saharan Africa.",,pdf:https://bmjopenrespres.bmj.com/content/bmjresp/10/1/e001895.full.pdf; doi:https://doi.org/10.1136/bmjresp-2023-001895; html:https://europepmc.org/articles/PMC10514609; pdf:https://europepmc.org/articles/PMC10514609?pdf=render 37653496,https://doi.org/10.1186/s12933-023-01963-9,Empagliflozin is associated with lower cardiovascular risk compared with dipeptidyl peptidase-4 inhibitors in adults with and without cardiovascular disease: EMPagliflozin compaRative effectIveness and SafEty (EMPRISE) study results from Europe and Asia.,"Vistisen D, Carstensen B, Elisabetta P, Lanzinger S, Tan EC, Yabe D, Kim DJ, Sheu WH, Melzer-Cohen C, Holl RW, Núñez J, Ha KH, Halvorsen S, Langslet G, Karasik A, Nyström T, Niskanen L, Guleria S, Klement R, Carrasco M, Foersch J, Shay C, Koeneman L, Hoti F, Farsani SF, Khunti K, Zaccardi F, Subramanian A, Nirantharakumar K, EMPRISE EU, East Asia Study Group.",,Cardiovascular diabetology,2023,2023-08-31,Y,Cardiovascular disease; Type 2 diabetes; Heart Failure; Comparative Effectiveness; Dipeptidyl Peptidase-4 Inhibitors; Empagliflozin,,,"

Background

Studies that have reported lower risk for cardiovascular outcomes in users of Sodium-Glucose Cotransporter-2 Inhibitors (SGLT-2i) are limited by residual cofounding and lack of information on prior cardiovascular disease (CVD). This study compared risk of cardiovascular events in patients within routine care settings in Europe and Asia with type 2 diabetes (T2D) initiating empagliflozin compared to dipeptidyl peptidase-4 inhibitors (DPP-4i) stratified by pre-existing CVD and history of heart failure (HF).

Methods and results

Adults initiating empagliflozin and DPP-4i in 2014-2018/19 from 11 countries in Europe and Asia were compared using propensity score matching and Cox proportional hazards regression to assess differences in rates of primary outcomes: hospitalisation for heart failure (HHF), myocardial infarction (MI), stroke; and secondary outcomes: cardiovascular mortality (CVM), coronary revascularisation procedure, composite outcome including HHF or CVM, and 3-point major adverse cardiovascular events (MACE: MI, stroke and CVM). Country-specific results were meta-analysed and pooled hazard ratios (HR) with 95% confidence intervals (CI) from random-effects models are presented. In total, 85,244 empagliflozin/DPP4i PS-matched patient pairs were included with overall mean follow-up of 0.7 years. Among those with pre-existing CVD, lower risk was observed for HHF (HR 0.74; 95% CI 0.64-0.86), CVM (HR 0.55; 95% CI 0.38-0.80), HHF or CVM (HR 0.57; 95% CI 0.48-0.67) and stroke (HR 0.79; 95% CI 0.67-0.94) in patients initiating empagliflozin vs DPP-4i. Similar patterns were observed among patients without pre-existing CVD and those with and without pre-existing HF.

Conclusion

These results from diverse patient populations in routine care settings across Europe and Asia demonstrate that initiation of empagliflozin compared to DPP-4i results in favourable cardioprotective effects regardless of pre-existing CVD or HF status.",,pdf:https://cardiab.biomedcentral.com/counter/pdf/10.1186/s12933-023-01963-9; doi:https://doi.org/10.1186/s12933-023-01963-9; html:https://europepmc.org/articles/PMC10472675; pdf:https://europepmc.org/articles/PMC10472675?pdf=render 35004880,https://doi.org/10.3389/fcvm.2021.763361,"Cardiac Magnetic Resonance Radiomics Reveal Differential Impact of Sex, Age, and Vascular Risk Factors on Cardiac Structure and Myocardial Tissue.","Raisi-Estabragh Z, Jaggi A, Gkontra P, McCracken C, Aung N, Munroe PB, Neubauer S, Harvey NC, Lekadir K, Petersen SE.",,Frontiers in cardiovascular medicine,2021,2021-12-22,Y,Hypertension; Diabetes; Smoking; Sex differences; High cholesterol; Cardiovascular Magnetic Resonance; Healthy Individuals; Radiomics,,,"Background: Cardiovascular magnetic resonance (CMR) radiomics analysis provides multiple quantifiers of ventricular shape and myocardial texture, which may be used for detailed cardiovascular phenotyping. Objectives: We studied variation in CMR radiomics phenotypes by age and sex in healthy UK Biobank participants. Then, we examined independent associations of classical vascular risk factors (VRFs: smoking, diabetes, hypertension, high cholesterol) with CMR radiomics features, considering potential sex and age differential relationships. Design: Image acquisition was with 1.5 Tesla scanners (MAGNETOM Aera, Siemens). Three regions of interest were segmented from short axis stack images using an automated pipeline: right ventricle, left ventricle, myocardium. We extracted 237 radiomics features from each study using Pyradiomics. In a healthy subset of participants (n = 14,902) without cardiovascular disease or VRFs, we estimated independent associations of age and sex with each radiomics feature using linear regression models adjusted for body size. We then created a sample comprising individuals with at least one VRF matched to an equal number of healthy participants (n = 27,400). We linearly modelled each radiomics feature against age, sex, body size, and all the VRFs. Bonferroni adjustment for multiple testing was applied to all p-values. To aid interpretation, we organised the results into six feature clusters. Results: Amongst the healthy subset, men had larger ventricles with dimmer and less texturally complex myocardium than women. Increasing age was associated with smaller ventricles and greater variation in myocardial intensities. Broadly, all the VRFs were associated with dimmer, less varied signal intensities, greater uniformity of local intensity levels, and greater relative presence of low signal intensity areas within the myocardium. Diabetes and high cholesterol were also associated with smaller ventricular size, this association was of greater magnitude in men than women. The pattern of alteration of radiomics features with the VRFs was broadly consistent in men and women. However, the associations between intensity based radiomics features with both diabetes and hypertension were more prominent in women than men. Conclusions: We demonstrate novel independent associations of sex, age, and major VRFs with CMR radiomics phenotypes. Further studies into the nature and clinical significance of these phenotypes are needed.",,pdf:https://www.frontiersin.org/articles/10.3389/fcvm.2021.763361/pdf; doi:https://doi.org/10.3389/fcvm.2021.763361; html:https://europepmc.org/articles/PMC8727756; pdf:https://europepmc.org/articles/PMC8727756?pdf=render 35743743,https://doi.org/10.3390/jpm12060958,Immune Cell Networks Uncover Candidate Biomarkers of Melanoma Immunotherapy Response.,"Vo DHT, McGleave G, Overton IM.",,Journal of personalized medicine,2022,2022-06-11,Y,Melanoma; Immunotherapy; Ovarian carcinoma; Biomarker; Network Biology; Systems Immunology; Nivolumab; Systems Medicine; Immune Checkpoint; Precision Oncology,,,"The therapeutic activation of antitumour immunity by immune checkpoint inhibitors (ICIs) is a significant advance in cancer medicine, not least due to the prospect of long-term remission. However, many patients are unresponsive to ICI therapy and may experience serious side effects; companion biomarkers are urgently needed to help inform ICI prescribing decisions. We present the IMMUNETS networks of gene coregulation in five key immune cell types and their application to interrogate control of nivolumab response in advanced melanoma cohorts. The results evidence a role for each of the IMMUNETS cell types in ICI response and in driving tumour clearance with independent cohorts from TCGA. As expected, 'immune hot' status, including T cell proliferation, correlates with response to first-line ICI therapy. Genes regulated in NK, dendritic, and B cells are the most prominent discriminators of nivolumab response in patients that had previously progressed on another ICI. Multivariate analysis controlling for tumour stage and age highlights CIITA and IKZF3 as candidate prognostic biomarkers. IMMUNETS provide a resource for network biology, enabling context-specific analysis of immune components in orthogonal datasets. Overall, our results illuminate the relationship between the tumour microenvironment and clinical trajectories, with potential implications for precision medicine.",,pdf:https://www.mdpi.com/2075-4426/12/6/958/pdf?version=1655284846; doi:https://doi.org/10.3390/jpm12060958; html:https://europepmc.org/articles/PMC9225330; pdf:https://europepmc.org/articles/PMC9225330?pdf=render -36469091,https://doi.org/10.1093/ageing/afac252,Prevalence and outcomes of atrial fibrillation in older people living in care homes in Wales: a routine data linkage study 2003-2018.,"Ritchie LA, Harrison SL, Penson PE, Akbari A, Torabi F, Hollinghurst J, Harris D, Oke OB, Akpan A, Halcox JP, Rodgers SE, Lip GYH, Lane DA.",,Age and ageing,2022,2022-12-01,N,Prevalence; Atrial fibrillation; Stroke; Older People; Care Homes; Health Outcomes,,,"

Objective

To determine atrial fibrillation (AF) prevalence and temporal trends, and examine associations between AF and risk of adverse health outcomes in older care home residents.

Methods

Retrospective cohort study using anonymised linked data from the Secure Anonymised Information Linkage Databank on CARE home residents in Wales with AF (SAIL CARE-AF) between 2003 and 2018. Fine-Gray competing risk models were used to estimate the risk of health outcomes with mortality as a competing risk. Cox regression analyses were used to estimate the risk of mortality.

Results

There were 86,602 older care home residents (median age 86.0 years [interquartile range 80.8-90.6]) who entered a care home between 2003 and 2018. When the pre-care home entry data extraction was standardised, the overall prevalence of AF was 17.4% (95% confidence interval 17.1-17.8) between 2010 and 2018. There was no significant change in the age- and sex-standardised prevalence of AF from 16.8% (15.9-17.9) in 2010 to 17.0% (16.1-18.0) in 2018. Residents with AF had a significantly higher risk of cardiovascular mortality (adjusted hazard ratio [HR] 1.27 [1.17-1.37], P < 0.001), all-cause mortality (adjusted HR 1.14 [1.11-1.17], P < 0.001), ischaemic stroke (adjusted sub-distribution HR 1.55 [1.36-1.76], P < 0.001) and cardiovascular hospitalisation (adjusted sub-distribution HR 1.28 [1.22-1.34], P < 0.001).

Conclusions

Older care home residents with AF have an increased risk of adverse health outcomes, even when higher mortality rates and other confounders are accounted for. This re-iterates the need for appropriate oral anticoagulant prescription and optimal management of cardiovascular co-morbidities, irrespective of frailty status and predicted life expectancy.",,pdf:https://academic.oup.com/ageing/article-pdf/51/12/afac252/47589319/afac252.pdf; doi:https://doi.org/10.1093/ageing/afac252 30940752,https://doi.org/10.1136/bmjopen-2018-023232,Using natural language processing to extract structured epilepsy data from unstructured clinic letters: development and validation of the ExECT (extraction of epilepsy clinical text) system.,"Fonferko-Shadrach B, Lacey AS, Roberts A, Akbari A, Thompson S, Ford DV, Lyons RA, Rees MI, Pickrell WO.",,BMJ open,2019,2019-04-01,Y,Epilepsy; Validation; Information Extraction; Natural Language Processing,Applied Analytics,,"

Objective

Routinely collected healthcare data are a powerful research resource but often lack detailed disease-specific information that is collected in clinical free text, for example, clinic letters. We aim to use natural language processing techniques to extract detailed clinical information from epilepsy clinic letters to enrich routinely collected data.

Design

We used the general architecture for text engineering (GATE) framework to build an information extraction system, ExECT (extraction of epilepsy clinical text), combining rule-based and statistical techniques. We extracted nine categories of epilepsy information in addition to clinic date and date of birth across 200 clinic letters. We compared the results of our algorithm with a manual review of the letters by an epilepsy clinician.

Setting

De-identified and pseudonymised epilepsy clinic letters from a Health Board serving half a million residents in Wales, UK.

Results

We identified 1925 items of information with overall precision, recall and F1 score of 91.4%, 81.4% and 86.1%, respectively. Precision and recall for epilepsy-specific categories were: epilepsy diagnosis (88.1%, 89.0%), epilepsy type (89.8%, 79.8%), focal seizures (96.2%, 69.7%), generalised seizures (88.8%, 52.3%), seizure frequency (86.3%-53.6%), medication (96.1%, 94.0%), CT (55.6%, 58.8%), MRI (82.4%, 68.8%) and electroencephalogram (81.5%, 75.3%).

Conclusions

We have built an automated clinical text extraction system that can accurately extract epilepsy information from free text in clinic letters. This can enhance routinely collected data for research in the UK. The information extracted with ExECT such as epilepsy type, seizure frequency and neurological investigations are often missing from routinely collected data. We propose that our algorithm can bridge this data gap enabling further epilepsy research opportunities. While many of the rules in our pipeline were tailored to extract epilepsy specific information, our methods can be applied to other diseases and also can be used in clinical practice to record patient information in a structured manner.",,pdf:https://bmjopen.bmj.com/content/bmjopen/9/4/e023232.full.pdf; doi:https://doi.org/10.1136/bmjopen-2018-023232; html:https://europepmc.org/articles/PMC6500195; pdf:https://europepmc.org/articles/PMC6500195?pdf=render +36469091,https://doi.org/10.1093/ageing/afac252,Prevalence and outcomes of atrial fibrillation in older people living in care homes in Wales: a routine data linkage study 2003-2018.,"Ritchie LA, Harrison SL, Penson PE, Akbari A, Torabi F, Hollinghurst J, Harris D, Oke OB, Akpan A, Halcox JP, Rodgers SE, Lip GYH, Lane DA.",,Age and ageing,2022,2022-12-01,N,Prevalence; Atrial fibrillation; Stroke; Older People; Care Homes; Health Outcomes,,,"

Objective

To determine atrial fibrillation (AF) prevalence and temporal trends, and examine associations between AF and risk of adverse health outcomes in older care home residents.

Methods

Retrospective cohort study using anonymised linked data from the Secure Anonymised Information Linkage Databank on CARE home residents in Wales with AF (SAIL CARE-AF) between 2003 and 2018. Fine-Gray competing risk models were used to estimate the risk of health outcomes with mortality as a competing risk. Cox regression analyses were used to estimate the risk of mortality.

Results

There were 86,602 older care home residents (median age 86.0 years [interquartile range 80.8-90.6]) who entered a care home between 2003 and 2018. When the pre-care home entry data extraction was standardised, the overall prevalence of AF was 17.4% (95% confidence interval 17.1-17.8) between 2010 and 2018. There was no significant change in the age- and sex-standardised prevalence of AF from 16.8% (15.9-17.9) in 2010 to 17.0% (16.1-18.0) in 2018. Residents with AF had a significantly higher risk of cardiovascular mortality (adjusted hazard ratio [HR] 1.27 [1.17-1.37], P < 0.001), all-cause mortality (adjusted HR 1.14 [1.11-1.17], P < 0.001), ischaemic stroke (adjusted sub-distribution HR 1.55 [1.36-1.76], P < 0.001) and cardiovascular hospitalisation (adjusted sub-distribution HR 1.28 [1.22-1.34], P < 0.001).

Conclusions

Older care home residents with AF have an increased risk of adverse health outcomes, even when higher mortality rates and other confounders are accounted for. This re-iterates the need for appropriate oral anticoagulant prescription and optimal management of cardiovascular co-morbidities, irrespective of frailty status and predicted life expectancy.",,pdf:https://academic.oup.com/ageing/article-pdf/51/12/afac252/47589319/afac252.pdf; doi:https://doi.org/10.1093/ageing/afac252 32524641,https://doi.org/10.1002/sim.8556,Selective recruitment designs for improving observational studies using electronic health records.,"Barrett JE, Cakiroglu A, Bunce C, Shah A, Denaxas S.",,Statistics in medicine,2020,2020-06-10,Y,Electronic Health Records; Observational Study; Optimal Experimental Design; Selective Recruitment,,,"Large-scale electronic health records (EHRs) present an opportunity to quickly identify suitable individuals in order to directly invite them to participate in an observational study. EHRs can contain data from millions of individuals, raising the question of how to optimally select a cohort of size n from a larger pool of size N. In this article, we propose a simple selective recruitment protocol that selects a cohort in which covariates of interest tend to have a uniform distribution. We show that selectively recruited cohorts potentially offer greater statistical power and more accurate parameter estimates than randomly selected cohorts. Our protocol can be applied to studies with multiple categorical and continuous covariates. We apply our protocol to a numerically simulated prospective observational study using an EHR database of stable acute coronary disease patients from 82 089 individuals in the U.K. Selective recruitment designs require a smaller sample size, leading to more efficient and cost-effective studies.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/sim.8556; doi:https://doi.org/10.1002/sim.8556; html:https://europepmc.org/articles/PMC8432147; pdf:https://europepmc.org/articles/PMC8432147?pdf=render 34426417,https://doi.org/10.1136/bmjhci-2021-100385,Review of study reporting guidelines for clinical studies using artificial intelligence in healthcare.,"Shelmerdine SC, Arthurs OJ, Denniston A, Sebire NJ.",,BMJ health & care informatics,2021,2021-08-01,Y,Medical Informatics; Healthcare Sector; Bmj Health Informatics,,,"High-quality research is essential in guiding evidence-based care, and should be reported in a way that is reproducible, transparent and where appropriate, provide sufficient detail for inclusion in future meta-analyses. Reporting guidelines for various study designs have been widely used for clinical (and preclinical) studies, consisting of checklists with a minimum set of points for inclusion. With the recent rise in volume of research using artificial intelligence (AI), additional factors need to be evaluated, which do not neatly conform to traditional reporting guidelines (eg, details relating to technical algorithm development). In this review, reporting guidelines are highlighted to promote awareness of essential content required for studies evaluating AI interventions in healthcare. These include published and in progress extensions to well-known reporting guidelines such as Standard Protocol Items: Recommendations for Interventional Trials-AI (study protocols), Consolidated Standards of Reporting Trials-AI (randomised controlled trials), Standards for Reporting of Diagnostic Accuracy Studies-AI (diagnostic accuracy studies) and Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis-AI (prediction model studies). Additionally there are a number of guidelines that consider AI for health interventions more generally (eg, Checklist for Artificial Intelligence in Medical Imaging (CLAIM), minimum information (MI)-CLAIM, MI for Medical AI Reporting) or address a specific element such as the 'learning curve' (Developmental and Exploratory Clinical Investigation of Decision-AI) . Economic evaluation of AI health interventions is not currently addressed, and may benefit from extension to an existing guideline. In the face of a rapid influx of studies of AI health interventions, reporting guidelines help ensure that investigators and those appraising studies consider both the well-recognised elements of good study design and reporting, while also adequately addressing new challenges posed by AI-specific elements.",,pdf:https://informatics.bmj.com/content/bmjhci/28/1/e100385.full.pdf; doi:https://doi.org/10.1136/bmjhci-2021-100385; html:https://europepmc.org/articles/PMC8383863; pdf:https://europepmc.org/articles/PMC8383863?pdf=render 31714636,https://doi.org/10.1002/ana.25642,Lipid lowering and Alzheimer disease risk: A mendelian randomization study.,"Williams DM, Finan C, Schmidt AF, Burgess S, Hingorani AD.",,Annals of neurology,2020,2020-01-01,Y,,,,"

Objective

To examine whether genetic variation affecting the expression or function of lipid-lowering drug targets is associated with Alzheimer disease (AD) risk, to evaluate the potential impact of long-term exposure to corresponding therapeutics.

Methods

We conducted Mendelian randomization analyses using variants in genes that encode the protein targets of several approved lipid-lowering drug classes: HMGCR (encoding the target for statins), PCSK9 (encoding the target for PCSK9 inhibitors, eg, evolocumab and alirocumab), NPC1L1 (encoding the target for ezetimibe), and APOB (encoding the target of mipomersen). Variants were weighted by associations with low-density lipoprotein cholesterol (LDL-C) using data from lipid genetics consortia (n up to 295,826). We meta-analyzed Mendelian randomization estimates for regional variants weighted by LDL-C on AD risk from 2 large samples (total n = 24,718 cases, 56,685 controls).

Results

Models for HMGCR, APOB, and NPC1L1 did not suggest that the use of related lipid-lowering drug classes would affect AD risk. In contrast, genetically instrumented exposure to PCSK9 inhibitors was predicted to increase AD risk in both of the AD samples (combined odds ratio per standard deviation lower LDL-C inducible by the drug target = 1.45, 95% confidence interval = 1.23-1.69). This risk increase was opposite to, although more modest than, the degree of protection from coronary artery disease predicted by these same methods for PCSK9 inhibition.

Interpretation

We did not identify genetic support for the repurposing of statins, ezetimibe, or mipomersen for AD prevention. Notwithstanding caveats to this genetic evidence, pharmacovigilance for AD risk among users of PCSK9 inhibitors may be warranted. ANN NEUROL 2020;87:30-39.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ana.25642; doi:https://doi.org/10.1002/ana.25642; html:https://europepmc.org/articles/PMC6944510; pdf:https://europepmc.org/articles/PMC6944510?pdf=render @@ -1513,25 +1513,25 @@ PMC9023380,https://doi.org/,Assessing the spread risk of COVID-19 associated wit 37573145,https://doi.org/10.1093/ndt/gfad180,Recovery of kidney function after acute kidney disease-a multi-cohort analysis.,"Sawhney S, Ball W, Bell S, Black C, Christiansen CF, Heide-Jørgensen U, Jensen SK, Lambourg E, Ronksley PE, Tan Z, Tonelli M, James MT.",,"Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association",2024,2024-02-01,Y,Recovery; Prognosis; epidemiology; Ckd; Aki,,,"

Background

There are no consensus definitions for evaluating kidney function recovery after acute kidney injury (AKI) and acute kidney disease (AKD), nor is it clear how recovery varies across populations and clinical subsets. We present a federated analysis of four population-based cohorts from Canada, Denmark and Scotland, 2011-18.

Methods

We identified incident AKD defined by serum creatinine changes within 48 h, 7 days and 90 days based on KDIGO AKI and AKD criteria. Separately, we applied changes up to 365 days to address widely used e-alert implementations that extend beyond the KDIGO AKI and AKD timeframes. Kidney recovery was based on resolution of AKD and a subsequent creatinine measurement below 1.2× baseline. We evaluated transitions between non-recovery, recovery and death up to 1 year; within age, sex and comorbidity subgroups; between subset AKD definitions; and across cohorts.

Results

There were 464 868 incident cases, median age 67-75 years. At 1 year, results were consistent across cohorts, with pooled mortalities for creatinine changes within 48 h, 7 days, 90 days and 365 days (and 95% confidence interval) of 40% (34%-45%), 40% (34%-46%), 37% (31%-42%) and 22% (16%-29%) respectively, and non-recovery of kidney function of 19% (15%-23%), 30% (24%-35%), 25% (21%-29%) and 37% (30%-43%), respectively. Recovery by 14 and 90 days was frequently not sustained at 1 year. Older males and those with heart failure or cancer were more likely to die than to experience sustained non-recovery, whereas the converse was true for younger females and those with diabetes.

Conclusion

Consistently across multiple cohorts, based on 1-year mortality and non-recovery, KDIGO AKD (up to 90 days) is at least prognostically similar to KDIGO AKI (7 days), and covers more people. Outcomes associated with AKD vary by age, sex and comorbidities such that older males are more likely to die, and younger females are less likely to recover.",,pdf:https://academic.oup.com/ndt/advance-article-pdf/doi/10.1093/ndt/gfad180/51104398/gfad180.pdf; doi:https://doi.org/10.1093/ndt/gfad180; html:https://europepmc.org/articles/PMC10899778; pdf:https://europepmc.org/articles/PMC10899778?pdf=render 37348153,https://doi.org/10.1016/j.amjcard.2023.05.039,Clinical and Prognostic Implications of Cardiopulmonary Exercise Stress Echocardiography in Asymptomatic Degenerative Mitral Regurgitation.,"Althunayyan A, Alborikan S, Badiani S, Wong K, Uppal R, Patel N, Petersen SE, Lloyd G, Bhattacharyya S.",,The American journal of cardiology,2023,2023-06-20,N,,,,"The current guidelines recommend intervention in severe degenerative mitral regurgitation (MR) in symptomatic patients or asymptomatic patients with left ventricular dilatation or dysfunction. The insidious onset of symptoms may mean that patients do not report their symptoms. The role of systematic exercise testing for symptoms in MR is not clearly defined. A total of 97 patients with moderate to severe asymptomatic MR underwent exercise echocardiography combined with cardiopulmonary exercise testing. The predictors of exercise-induced dyspnea, symptom-free survival, and mitral valve intervention were identified. A total of 18 patients (19%) developed limiting dyspnea on exercise. Spontaneous symptom-free survival at 24 months was significantly higher in those without exercise-induced symptoms than those with exercise-induced symptoms, p <0.0001. The only independent predictors of spontaneous symptoms at 2 years were effective regurgitant orifice area (odds ratio 27.45, 95% confidence interval [CI] 1.43 to 528.40, p = 0.03) and exercise-induced symptoms (odds ratio 11.56, 95% CI 1.71 to 78.09, p = 0.01). The only independent predictor of surgery was indexed left ventricular systolic volumes (odds ratio 1.17, 95% CI 1.04 to 1.30, p = 0.006). Where only the patients who underwent surgery due to symptoms were included, the only independent predictor was exercise-induced symptoms (odds ratio 13.94, 95% CI 1.39 to 140.27, p = 0.025). In conclusion, in patients with primary asymptomatic degenerative MR, 1/5 develop revealed symptoms during exercise. This predicts a subsequent development of spontaneous symptoms and mitral valve intervention due to symptoms.",,doi:https://doi.org/10.1016/j.amjcard.2023.05.039 33328453,https://doi.org/10.1038/s41467-020-19996-z,Genetic architecture of host proteins involved in SARS-CoV-2 infection.,"Pietzner M, Wheeler E, Carrasco-Zanini J, Raffler J, Kerrison ND, Oerton E, Auyeung VPW, Luan J, Finan C, Casas JP, Ostroff R, Williams SA, Kastenmüller G, Ralser M, Gamazon ER, Wareham NJ, Hingorani AD, Langenberg C.",,Nature communications,2020,2020-12-16,Y,,,,"Understanding the genetic architecture of host proteins interacting with SARS-CoV-2 or mediating the maladaptive host response to COVID-19 can help to identify new or repurpose existing drugs targeting those proteins. We present a genetic discovery study of 179 such host proteins among 10,708 individuals using an aptamer-based technique. We identify 220 host DNA sequence variants acting in cis (MAF 0.01-49.9%) and explaining 0.3-70.9% of the variance of 97 of these proteins, including 45 with no previously known protein quantitative trait loci (pQTL) and 38 encoding current drug targets. Systematic characterization of pQTLs across the phenome identified protein-drug-disease links and evidence that putative viral interaction partners such as MARK3 affect immune response. Our results accelerate the evaluation and prioritization of new drug development programmes and repurposing of trials to prevent, treat or reduce adverse outcomes. Rapid sharing and detailed interrogation of results is facilitated through an interactive webserver ( https://omicscience.org/apps/covidpgwas/ ).",,pdf:https://www.nature.com/articles/s41467-020-19996-z.pdf; doi:https://doi.org/10.1038/s41467-020-19996-z; html:https://europepmc.org/articles/PMC7744536; pdf:https://europepmc.org/articles/PMC7744536?pdf=render -37419925,https://doi.org/10.1038/s41467-023-38930-7,Optimal strategies for learning multi-ancestry polygenic scores vary across traits.,"Lehmann B, Mackintosh M, McVean G, Holmes C.",,Nature communications,2023,2023-07-07,Y,,,,"Polygenic scores (PGSs) are individual-level measures that aggregate the genome-wide genetic predisposition to a given trait. As PGS have predominantly been developed using European-ancestry samples, trait prediction using such European ancestry-derived PGS is less accurate in non-European ancestry individuals. Although there has been recent progress in combining multiple PGS trained on distinct populations, the problem of how to maximize performance given a multiple-ancestry cohort is largely unexplored. Here, we investigate the effect of sample size and ancestry composition on PGS performance for fifteen traits in UK Biobank. For some traits, PGS estimated using a relatively small African-ancestry training set outperformed, on an African-ancestry test set, PGS estimated using a much larger European-ancestry only training set. We observe similar, but not identical, results when considering other minority-ancestry groups within UK Biobank. Our results emphasise the importance of targeted data collection from underrepresented groups in order to address existing disparities in PGS performance.",,pdf:https://www.nature.com/articles/s41467-023-38930-7.pdf; doi:https://doi.org/10.1038/s41467-023-38930-7; html:https://europepmc.org/articles/PMC10328935; pdf:https://europepmc.org/articles/PMC10328935?pdf=render 31711543,https://doi.org/10.1186/s13326-019-0214-4,Natural language processing for disease phenotyping in UK primary care records for research: a pilot study in myocardial infarction and death.,"Shah AD, Bailey E, Williams T, Denaxas S, Dobson R, Hemingway H.",,Journal of biomedical semantics,2019,2019-11-12,Y,Myocardial infarction; Chest pain; Primary Care; Natural Language Processing; Free Text,Applied Analytics,,"

Background

Free text in electronic health records (EHR) may contain additional phenotypic information beyond structured (coded) information. For major health events - heart attack and death - there is a lack of studies evaluating the extent to which free text in the primary care record might add information. Our objectives were to describe the contribution of free text in primary care to the recording of information about myocardial infarction (MI), including subtype, left ventricular function, laboratory results and symptoms; and recording of cause of death. We used the CALIBER EHR research platform which contains primary care data from the Clinical Practice Research Datalink (CPRD) linked to hospital admission data, the MINAP registry of acute coronary syndromes and the death registry. In CALIBER we randomly selected 2000 patients with MI and 1800 deaths. We implemented a rule-based natural language engine, the Freetext Matching Algorithm, on site at CPRD to analyse free text in the primary care record without raw data being released to researchers. We analysed text recorded within 90 days before or 90 days after the MI, and on or after the date of death.

Results

We extracted 10,927 diagnoses, 3658 test results, 3313 statements of negation, and 850 suspected diagnoses from the myocardial infarction patients. Inclusion of free text increased the recorded proportion of patients with chest pain in the week prior to MI from 19 to 27%, and differentiated between MI subtypes in a quarter more patients than structured data alone. Cause of death was incompletely recorded in primary care; in 36% the cause was in coded data and in 21% it was in free text. Only 47% of patients had exactly the same cause of death in primary care and the death registry, but this did not differ between coded and free text causes of death.

Conclusions

Among patients who suffer MI or die, unstructured free text in primary care records contains much information that is potentially useful for research such as symptoms, investigation results and specific diagnoses. Access to large scale unstructured data in electronic health records (millions of patients) might yield important insights.", NLP methods were used to analyse free text from hospital records for people with MI. They analysed text recorded within 90 days bfore or 90 days after the MI and found that free text in hospital records contains unformation useful for diagnoses,pdf:https://jbiomedsem.biomedcentral.com/track/pdf/10.1186/s13326-019-0214-4; doi:https://doi.org/10.1186/s13326-019-0214-4; html:https://europepmc.org/articles/PMC6849160; pdf:https://europepmc.org/articles/PMC6849160?pdf=render 31413164,https://doi.org/10.1183/13993003.00476-2019,Allergic diseases and long-term risk of autoimmune disorders: longitudinal cohort study and cluster analysis.,"Krishna MT, Subramanian A, Adderley NJ, Zemedikun DT, Gkoutos GV, Nirantharakumar K.",,The European respiratory journal,2019,2019-11-14,N,,,,"

Introduction

The association between allergic diseases and autoimmune disorders is not well established. Our objective was to determine incidence rates of autoimmune disorders in allergic rhinitis/conjunctivitis (ARC), atopic eczema and asthma, and to investigate for co-occurring patterns.

Methods

This was a retrospective cohort study (1990-2018) employing data extracted from The Health Improvement Network (UK primary care database). The exposure group comprised ARC, atopic eczema and asthma (all ages). For each exposed patient, up to two randomly selected age- and sex-matched controls with no documented allergic disease were used. Adjusted incidence rate ratios (aIRRs) were calculated using Poisson regression. A cross-sectional study was also conducted employing Association Rule Mining (ARM) to investigate disease clusters.

Results

782 320, 1 393 570 and 1 049 868 patients with ARC, atopic eczema and asthma, respectively, were included. aIRRs of systemic lupus erythematosus (SLE), Sjögren's syndrome, vitiligo, rheumatoid arthritis, psoriasis, pernicious anaemia, inflammatory bowel disease, coeliac disease and autoimmune thyroiditis were uniformly higher in the three allergic diseases compared with controls. Specifically, aIRRs of SLE (1.45) and Sjögren's syndrome (1.88) were higher in ARC; aIRRs of SLE (1.44), Sjögren's syndrome (1.61) and myasthenia (1.56) were higher in asthma; and aIRRs of SLE (1.86), Sjögren's syndrome (1.48), vitiligo (1.54) and psoriasis (2.41) were higher in atopic eczema. There was no significant effect of the three allergic diseases on multiple sclerosis or of ARC and atopic eczema on myasthenia. Using ARM, allergic diseases clustered with multiple autoimmune disorders. Three age- and sex-related clusters were identified, with a relatively complex pattern in females ≥55 years old.

Conclusions

The long-term risks of autoimmune disorders are significantly higher in patients with allergic diseases. Allergic diseases and autoimmune disorders show age- and sex-related clustering patterns.",,pdf:https://erj.ersjournals.com/content/erj/54/5/1900476.full.pdf; doi:https://doi.org/10.1183/13993003.00476-2019 +37419925,https://doi.org/10.1038/s41467-023-38930-7,Optimal strategies for learning multi-ancestry polygenic scores vary across traits.,"Lehmann B, Mackintosh M, McVean G, Holmes C.",,Nature communications,2023,2023-07-07,Y,,,,"Polygenic scores (PGSs) are individual-level measures that aggregate the genome-wide genetic predisposition to a given trait. As PGS have predominantly been developed using European-ancestry samples, trait prediction using such European ancestry-derived PGS is less accurate in non-European ancestry individuals. Although there has been recent progress in combining multiple PGS trained on distinct populations, the problem of how to maximize performance given a multiple-ancestry cohort is largely unexplored. Here, we investigate the effect of sample size and ancestry composition on PGS performance for fifteen traits in UK Biobank. For some traits, PGS estimated using a relatively small African-ancestry training set outperformed, on an African-ancestry test set, PGS estimated using a much larger European-ancestry only training set. We observe similar, but not identical, results when considering other minority-ancestry groups within UK Biobank. Our results emphasise the importance of targeted data collection from underrepresented groups in order to address existing disparities in PGS performance.",,pdf:https://www.nature.com/articles/s41467-023-38930-7.pdf; doi:https://doi.org/10.1038/s41467-023-38930-7; html:https://europepmc.org/articles/PMC10328935; pdf:https://europepmc.org/articles/PMC10328935?pdf=render 33719753,https://doi.org/10.1080/13607863.2021.1893270,Cognition in informal caregivers: evidence from an English population study.,"García-Castro FJ, Bendayan R, Dobson RJB, Blanca MJ.",,Aging & mental health,2022,2021-03-14,N,Older Adults; Executive Function; Verbal Memory; Caregiving Duration,,,"

Background and objectives

The relationship between caregiving and cognition remains unclear. We investigate this association comparing four cognitive tasks and exploring the role of potential explanatory pathways such as healthy behaviours (healthy caregiver hypothesis) and depression (stress process model).

Research design and methods

Respondents were from English Longitudinal Study of Ageing (ELSA) (N = 8910). Cognitive tasks included immediate and delayed word recall, verbal fluency and serial 7 subtraction. Series of hierarchical linear regressions were performed. Adjustments included socio-demographics, health related variables, health behaviours and depression.

Results

Being a caregiver was positively associated with immediate and delayed recall, verbal fluency but not with serial 7. For immediate and delayed recall, these associations were partially attenuated when adjusting for health behaviours, and depression. For verbal fluency, associations were partially attenuated when adjusting for depression but fully attenuated when adjusting for health behaviours. No associations were found for serial 7.

Discussion and implications

Our findings show that caregivers have higher level of memory and executive function compared to non-caregivers. For memory, we found that although health behaviours and depression can have a role in this association, they do not fully explain it. However, health behaviours seem to have a clear role in the association with executive function. Public health and policy do not need to target specifically cognitive function but other areas as the promotion of healthy behaviours and psychological adjustment such as preventing depression and promoting physical activity in caregivers.",,pdf:https://www.tandfonline.com/doi/pdf/10.1080/13607863.2021.1893270?needAccess=true; doi:https://doi.org/10.1080/13607863.2021.1893270 32579178,https://doi.org/10.1001/jamadermatol.2020.1948,Association Between Atopic Eczema and Cancer in England and Denmark.,"Mansfield KE, Schmidt SAJ, Darvalics B, Mulick A, Abuabara K, Wong AYS, Sørensen HT, Smeeth L, Bhaskaran K, Dos Santos Silva I, Silverwood RJ, Langan SM.",,JAMA dermatology,2020,2020-10-01,Y,,,,"

Importance

Associations between atopic eczema and cancer are unclear, with competing theories that increased immune surveillance decreases cancer risk and that immune stimulation increases cancer risk. Establishing baseline cancer risk in people with atopic eczema is important before exploring the association between new biologic drugs for atopic eczema and cancer risk.

Objective

To investigate whether atopic eczema is associated with cancer.

Design, setting, and participants

Matched cohort studies were conducted from January 2, 1998, to March 31, 2016, in England and from January 1, 1982, to June 30, 2016, in Denmark. We conducted our analyses between July 2018 and July 2019. The setting was English primary care and nationwide Danish data. Participants with atopic eczema (adults only in England and any age in Denmark) were matched on age, sex, and calendar period (as well as primary care practice in England only) to those without atopic eczema.

Exposure

Atopic eczema.

Main outcomes and measures

Overall cancer risk and risk of specific cancers were compared in people with and without atopic eczema.

Results

In England, matched cohorts included 471 970 individuals with atopic eczema (median [IQR] age, 41.1 [24.9-60.7] years; 276 510 [58.6%] female) and 2 239 775 individuals without atopic eczema (median [IQR] age, 39.8 [25.9-58.4] years; 1 301 074 [58.1%] female). In Denmark, matched cohorts included 44 945 individuals with atopic eczema (median [IQR] age, 13.7 [1.7-21.1] years; 22 826 [50.8%] female) and 445 673 individuals without atopic eczema (median [IQR] age, 13.5 [1.7-20.8] years; 226 323 [50.8%] female). Little evidence was found of associations between atopic eczema and overall cancer (adjusted hazard ratio [HR], 1.04; 99% CI, 1.02-1.06 in England and 1.05; 99% CI, 0.95-1.16 in Denmark) or for most specific cancers. However, noncutaneous lymphoma risk was increased in people with atopic eczema in England (adjusted HR, 1.19; 99% CI, 1.07-1.34 for non-Hodgkin lymphoma [NHL] and 1.48; 99% CI, 1.07-2.04 for Hodgkin lymphoma). Lymphoma risk was increased in people with greater eczema severity vs those without atopic eczema (NHL adjusted HR, 1.06; 99% CI, 0.90-1.25 for mild eczema; 1.24; 99% CI, 1.04-1.48 for moderate eczema; and 2.08; 99% CI, 1.42-3.04 for severe eczema). Danish point estimates also showed increased lymphoma risk in people with moderate to severe eczema compared with those without atopic eczema (minimally adjusted HR, 1.31; 99% CI, 0.76-2.26 for NHL and 1.35; 99% CI, 0.65-2.82 for Hodgkin lymphoma), but the 99% CIs were wide.

Conclusions and relevance

The findings from 2 large population-based studies performed in different settings do not support associations between atopic eczema and most cancers. However, an association was observed between atopic eczema and lymphoma, particularly NHL, that increased with eczema severity. This finding warrants further study as new immunomodulatory systemic therapeutics are brought to market that may alter cancer risk.",,pdf:https://jamanetwork.com/journals/jamadermatology/articlepdf/2767601/jamadermatology_mansfield_2020_oi_200037_1602515656.45058.pdf; doi:https://doi.org/10.1001/jamadermatol.2020.1948; html:https://europepmc.org/articles/PMC7315391 32611631,https://doi.org/10.1212/wnl.0000000000009814,"Genetically determined blood pressure, antihypertensive drug classes, and risk of stroke subtypes.","Georgakis MK, Gill D, Webb AJS, Evangelou E, Elliott P, Sudlow CLM, Dehghan A, Malik R, Tzoulaki I, Dichgans M.",,Neurology,2020,2020-07-01,Y,,,,"

Objective

We employed Mendelian randomization to explore whether the effects of blood pressure (BP) and BP-lowering through different antihypertensive drug classes on stroke risk vary by stroke etiology.

Methods

We selected genetic variants associated with systolic and diastolic BP and BP-lowering variants in genes encoding antihypertensive drug targets from genome-wide association studies (GWAS) on 757,601 individuals. Applying 2-sample Mendelian randomization, we examined associations with any stroke (67,162 cases; 454,450 controls), ischemic stroke and its subtypes (large artery, cardioembolic, small vessel stroke), intracerebral hemorrhage (ICH, deep and lobar), and the related small vessel disease phenotype of white matter hyperintensities (WMH).

Results

Genetic predisposition to higher systolic and diastolic BP was associated with higher risk of any stroke, ischemic stroke, and ICH. We found associations between genetically determined BP and all ischemic stroke subtypes with a higher risk of large artery and small vessel stroke compared to cardioembolic stroke, as well as associations with deep, but not lobar ICH. Genetic proxies for calcium channel blockers, but not β-blockers, were associated with lower risk of any stroke and ischemic stroke. Proxies for calcium channel blockers showed particularly strong associations with small vessel stroke and the related radiologic phenotype of WMH.

Conclusions

This study supports a causal role of hypertension in all major stroke subtypes except lobar ICH. We find differences in the effects of BP and BP-lowering through antihypertensive drug classes between stroke subtypes and identify calcium channel blockade as a promising strategy for preventing manifestations of cerebral small vessel disease.",,pdf:https://n.neurology.org/content/neurology/95/4/e353.full.pdf; doi:https://doi.org/10.1212/WNL.0000000000009814; html:https://europepmc.org/articles/PMC7455321; pdf:https://europepmc.org/articles/PMC7455321?pdf=render -38416429,https://doi.org/10.1056/nejmoa2311330,Cognition and Memory after Covid-19 in a Large Community Sample.,"Hampshire A, Azor A, Atchison C, Trender W, Hellyer PJ, Giunchiglia V, Husain M, Cooke GS, Cooper E, Lound A, Donnelly CA, Chadeau-Hyam M, Ward H, Elliott P.",,The New England journal of medicine,2024,2024-02-01,Y,,,,"

Background

Cognitive symptoms after coronavirus disease 2019 (Covid-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are well-recognized. Whether objectively measurable cognitive deficits exist and how long they persist are unclear.

Methods

We invited 800,000 adults in a study in England to complete an online assessment of cognitive function. We estimated a global cognitive score across eight tasks. We hypothesized that participants with persistent symptoms (lasting ≥12 weeks) after infection onset would have objectively measurable global cognitive deficits and that impairments in executive functioning and memory would be observed in such participants, especially in those who reported recent poor memory or difficulty thinking or concentrating (""brain fog"").

Results

Of the 141,583 participants who started the online cognitive assessment, 112,964 completed it. In a multiple regression analysis, participants who had recovered from Covid-19 in whom symptoms had resolved in less than 4 weeks or at least 12 weeks had similar small deficits in global cognition as compared with those in the no-Covid-19 group, who had not been infected with SARS-CoV-2 or had unconfirmed infection (-0.23 SD [95% confidence interval {CI}, -0.33 to -0.13] and -0.24 SD [95% CI, -0.36 to -0.12], respectively); larger deficits as compared with the no-Covid-19 group were seen in participants with unresolved persistent symptoms (-0.42 SD; 95% CI, -0.53 to -0.31). Larger deficits were seen in participants who had SARS-CoV-2 infection during periods in which the original virus or the B.1.1.7 variant was predominant than in those infected with later variants (e.g., -0.17 SD for the B.1.1.7 variant vs. the B.1.1.529 variant; 95% CI, -0.20 to -0.13) and in participants who had been hospitalized than in those who had not been hospitalized (e.g., intensive care unit admission, -0.35 SD; 95% CI, -0.49 to -0.20). Results of the analyses were similar to those of propensity-score-matching analyses. In a comparison of the group that had unresolved persistent symptoms with the no-Covid-19 group, memory, reasoning, and executive function tasks were associated with the largest deficits (-0.33 to -0.20 SD); these tasks correlated weakly with recent symptoms, including poor memory and brain fog. No adverse events were reported.

Conclusions

Participants with resolved persistent symptoms after Covid-19 had objectively measured cognitive function similar to that in participants with shorter-duration symptoms, although short-duration Covid-19 was still associated with small cognitive deficits after recovery. Longer-term persistence of cognitive deficits and any clinical implications remain uncertain. (Funded by the National Institute for Health and Care Research and others.).",,pdf:https://www.nejm.org/doi/pdf/10.1056/NEJMoa2311330?articleTools=true; doi:https://doi.org/10.1056/NEJMoa2311330; html:https://europepmc.org/articles/PMC7615803; pdf:https://europepmc.org/articles/PMC7615803?pdf=render 35259281,https://doi.org/10.1111/acel.13524,Biological mechanisms of aging predict age-related disease co-occurrence in patients.,"Fraser HC, Kuan V, Johnen R, Zwierzyna M, Hingorani AD, Beyer A, Partridge L.",,Aging cell,2022,2022-03-08,Y,Aging; Genetics; Age-related Disease; Multimorbidity; Aging Hallmarks,,,"Genetic, environmental, and pharmacological interventions into the aging process can confer resistance to multiple age-related diseases in laboratory animals, including rhesus monkeys. These findings imply that individual mechanisms of aging might contribute to the co-occurrence of age-related diseases in humans and could be targeted to prevent these conditions simultaneously. To address this question, we text mined 917,645 literature abstracts followed by manual curation and found strong, non-random associations between age-related diseases and aging mechanisms in humans, confirmed by gene set enrichment analysis of GWAS data. Integration of these associations with clinical data from 3.01 million patients showed that age-related diseases associated with each of five aging mechanisms were more likely than chance to be present together in patients. Genetic evidence revealed that innate and adaptive immunity, the intrinsic apoptotic signaling pathway and activity of the ERK1/2 pathway were associated with multiple aging mechanisms and diverse age-related diseases. Mechanisms of aging hence contribute both together and individually to age-related disease co-occurrence in humans and could potentially be targeted accordingly to prevent multimorbidity.",,pdf:https://discovery.ucl.ac.uk/10145565/1/Hignorani_Biological%20mechanisms%20of%20aging%20predict%20age-related%20disease%20co-occurrence%20in%20patients_AOP.pdf; doi:https://doi.org/10.1111/acel.13524; html:https://europepmc.org/articles/PMC9009120; pdf:https://europepmc.org/articles/PMC9009120?pdf=render 33053479,https://doi.org/10.1016/j.chiabu.2020.104760,Characterizing newborn and older infant entries into care in England between 2006 and 2014.,"Pearson RJ, Jay MA, O'Donnell M, Wijlaars L, Gilbert R.",,Child abuse & neglect,2020,2020-10-11,Y,Longitudinal data; Infancy; Latent Class Analysis; Entry Into Care; Out-of-court Arrangements,,,"

Background

The risk of entry to state care during infancy is increasing, both here in England and abroad, with most entering within a week of birth ('newborns'). However, little is known about these infants or of their pathways through care over early childhood.

Objective

To characterize infant entries to care in England.

Participants and setting

All children in England who first entered care during infancy, between April 2006 and March 2014 (n = 42,000).

Methods

We compared sociodemographic and care characteristics for infants entering care over the study period by age at first entry (newborn: <1wks, older infant 1-51wks). Among those who entered before April 2010, we further characterized care over follow-up (i.e. 4 years from first entry) and employed latent class analysis to uncover any common pathways through care.

Results

Almost 40 % of infants first entered care as a newborn. Most infants first entered care under s 20 arrangements (i.e. out-of-court, 60 % of newborns vs 47 % of older infants). Among infants entering before April 2010, most were adopted over follow-up (60 % vs 37 %), though many were restored to parental care (20 % vs 32 %) or exited care to live with extended family (13 % vs 19 %). One in six infants (17.7 %) had particularly unstable care trajectories over early childhood, typified by three or more placements or failed reunification.

Conclusions

Evidence-based strengthening of pre-birth social work support is needed to improve preventive interventions before birth, to more effectively target infant placement into care. Linkages between child protection records and information on parents are needed to inform preventive strategies.",,doi:https://doi.org/10.1016/j.chiabu.2020.104760; doi:https://doi.org/10.1016/j.chiabu.2020.104760; html:https://europepmc.org/articles/PMC7718112 +38416429,https://doi.org/10.1056/nejmoa2311330,Cognition and Memory after Covid-19 in a Large Community Sample.,"Hampshire A, Azor A, Atchison C, Trender W, Hellyer PJ, Giunchiglia V, Husain M, Cooke GS, Cooper E, Lound A, Donnelly CA, Chadeau-Hyam M, Ward H, Elliott P.",,The New England journal of medicine,2024,2024-02-01,Y,,,,"

Background

Cognitive symptoms after coronavirus disease 2019 (Covid-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are well-recognized. Whether objectively measurable cognitive deficits exist and how long they persist are unclear.

Methods

We invited 800,000 adults in a study in England to complete an online assessment of cognitive function. We estimated a global cognitive score across eight tasks. We hypothesized that participants with persistent symptoms (lasting ≥12 weeks) after infection onset would have objectively measurable global cognitive deficits and that impairments in executive functioning and memory would be observed in such participants, especially in those who reported recent poor memory or difficulty thinking or concentrating (""brain fog"").

Results

Of the 141,583 participants who started the online cognitive assessment, 112,964 completed it. In a multiple regression analysis, participants who had recovered from Covid-19 in whom symptoms had resolved in less than 4 weeks or at least 12 weeks had similar small deficits in global cognition as compared with those in the no-Covid-19 group, who had not been infected with SARS-CoV-2 or had unconfirmed infection (-0.23 SD [95% confidence interval {CI}, -0.33 to -0.13] and -0.24 SD [95% CI, -0.36 to -0.12], respectively); larger deficits as compared with the no-Covid-19 group were seen in participants with unresolved persistent symptoms (-0.42 SD; 95% CI, -0.53 to -0.31). Larger deficits were seen in participants who had SARS-CoV-2 infection during periods in which the original virus or the B.1.1.7 variant was predominant than in those infected with later variants (e.g., -0.17 SD for the B.1.1.7 variant vs. the B.1.1.529 variant; 95% CI, -0.20 to -0.13) and in participants who had been hospitalized than in those who had not been hospitalized (e.g., intensive care unit admission, -0.35 SD; 95% CI, -0.49 to -0.20). Results of the analyses were similar to those of propensity-score-matching analyses. In a comparison of the group that had unresolved persistent symptoms with the no-Covid-19 group, memory, reasoning, and executive function tasks were associated with the largest deficits (-0.33 to -0.20 SD); these tasks correlated weakly with recent symptoms, including poor memory and brain fog. No adverse events were reported.

Conclusions

Participants with resolved persistent symptoms after Covid-19 had objectively measured cognitive function similar to that in participants with shorter-duration symptoms, although short-duration Covid-19 was still associated with small cognitive deficits after recovery. Longer-term persistence of cognitive deficits and any clinical implications remain uncertain. (Funded by the National Institute for Health and Care Research and others.).",,pdf:https://www.nejm.org/doi/pdf/10.1056/NEJMoa2311330?articleTools=true; doi:https://doi.org/10.1056/NEJMoa2311330; html:https://europepmc.org/articles/PMC7615803; pdf:https://europepmc.org/articles/PMC7615803?pdf=render 33824583,https://doi.org/10.2147/copd.s298585,There is No Fast Track to Identify Fast Decliners in Alpha-1 Antitrypsin Deficiency by Spirometry: A Longitudinal Study of Repeated Measurements.,"Stockley JA, Stockley RA, Sapey E.",,International journal of chronic obstructive pulmonary disease,2021,2021-03-29,Y,Lung function; decline; Alpha-1 Antitrypsin Deficiency; Obstructive Airways Disease,,,"

Background

It is known that lung function decline in Alpha-1 Antitrypsin Deficiency (AATD) varies. Those with a rapid decline are at highest risk of poorer outcomes but may benefit most from targeted treatments including augmentation therapy. Current evidence suggests rapid decliners can be identified after 3 years of serial follow-up. It would be advantageous to identify these patients over a shorter time period, especially in mild disease.

Methods

Post-bronchodilator spirometry was performed every 6 months for a total of 18 months (4 measurements) by PiZZ AATD patients (ex- or never-smokers) either without spirometric COPD or with mild COPD. Where possible, retrospective spirometry data were included. Decline was assessed using 2 (baseline and 6 month) or four measurements (including baseline, 6, 12 and 18 months) and compared to retrospective decline rates using annual measurements over 3 years.

Results

Seventy-two PiZZ AATD patients were included, with 27 having at least three years of retrospective, annual spirometry. 18-month progression obtained by linear regression showed variable degrees of change with 29 showing no decline, 8 showing slow decline and 35 showing rapid decline. Bland-Altman plots showed that there was no overall agreement between predicted rate of decline using data obtained over 6 months and that obtained over 18 months. Furthermore, there was no agreement between rate of decline from either 6 or 18 months' data when compared to data collected over 3 years. The positive predictive value for rapid decline with 18 months of data compared to 3 years was only 50.0%.

Conclusion

This study suggests serial lung function over 18 months cannot identify AATD patients who have rapidly declining lung function. There is an urgent need for different biomarkers to help identify these patients at the earliest opportunity.",,pdf:https://www.dovepress.com/getfile.php?fileID=68078; doi:https://doi.org/10.2147/COPD.S298585; html:https://europepmc.org/articles/PMC8018552; pdf:https://europepmc.org/articles/PMC8018552?pdf=render 37393610,https://doi.org/10.1016/j.xpro.2023.102392,Protocol for the automatic extraction of epidemiological information via a pre-trained language model.,"Wang Z, Liu XF, Du Z, Wang L, Wu Y, Holme P, Lachmann M, Lin H, Wang Z, Cao Y, Wong ZSY, Xu XK, Sun Y.",,STAR protocols,2023,2023-07-01,Y,Health Sciences; Clinical Protocol; Computer Sciences,,,"The lack of systems to automatically extract epidemiological fields from open-access COVID-19 cases restricts the timeliness of formulating prevention measures. Here we present a protocol for using CCIE, a COVID-19 Cases Information Extraction system based on the pre-trained language model.1 We describe steps for preparing supervised training data and executing python scripts for named entity recognition and text category classification. We then detail the use of machine evaluation and manual validation to illustrate the effectiveness of CCIE. For complete details on the use and execution of this protocol, please refer to Wang et al.2.",,doi:https://doi.org/10.1016/j.xpro.2023.102392; doi:https://doi.org/10.1016/j.xpro.2023.102392; html:https://europepmc.org/articles/PMC10328978; pdf:https://europepmc.org/articles/PMC10328978?pdf=render 35842920,https://doi.org/10.1002/ehf2.14073,Blood-based biomarkers for the prediction of hypertrophic cardiomyopathy prognosis: a systematic review and meta-analysis.,"Jansen M, Algül S, Bosman LP, Michels M, van der Velden J, de Boer RA, van Tintelen JP, Asselbergs FW, Baas AF.",,ESC heart failure,2022,2022-07-17,Y,Prognosis; Biomarker; hypertrophic cardiomyopathy; Systematic review; Heart Failure; Sudden Cardiac Death,,,"

Aims

Hypertrophic cardiomyopathy (HCM) is the most prevalent monogenic heart disease. HCM is an important cause of sudden cardiac death and may also lead to outflow tract obstruction and heart failure. Disease severity is highly variable and risk stratification remains limited. Therefore, we aimed to review current knowledge of prognostic blood-based biomarkers in HCM.

Methods and results

A systematic literature search was performed on PubMed, Embase, and the Cochrane library to identify studies assessing plasma or serum biomarkers for outcomes involving malignant ventricular arrhythmia, outflow tract obstruction, and heart failure. Risk of bias was assessed using the QUIPS tool. Meta-analyses were performed using the random effects method. A total of 26 unique cohort studies assessing 42 biomarkers were identified. Overall risk of bias was moderate. Thirty-two biomarkers were significantly associated to an HCM outcome in at least one study (nine biomarkers in at least two studies). In pooled analyses, cardiovascular mortality was predicted by N-terminal prohormone of brain natriuretic peptide (hazard ratio [HR] 5.38 per log[pg/mL], 95% confidence interval [CI] 2.07-14.03, P < 0.001, I2  = 0%) and high-sensitivity C-reactive protein (HR 1.30 per μg/mL, 95% CI 1.00-1.68, P = 0.05, I2  = 78%), all-cause mortality by low-density lipoprotein cholesterol (HR 0.63 per μmol/mL, 95% CI 0.49-0.80, P < 0.001, I2  = 0%), and a combined congestive heart failure, malignant ventricular arrhythmia, and stroke outcome by high-sensitivity cardiac troponin T (pooled HR 4.19 for ≥0.014 ng/mL, 95% CI 2.22-7.88, P < 0.001, I2  = 0%). Quality of evidence was low-moderate.

Conclusions

Several blood-based biomarkers were identified as predictors of HCM outcomes. Additional studies are required to validate their prognostic utility within current risk stratification models.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ehf2.14073; doi:https://doi.org/10.1002/ehf2.14073; html:https://europepmc.org/articles/PMC9715795; pdf:https://europepmc.org/articles/PMC9715795?pdf=render 34018481,https://doi.org/10.2807/1560-7917.es.2021.26.20.2100428,The potential for vaccination-induced herd immunity against the SARS-CoV-2 B.1.1.7 variant.,"Hodgson D, Flasche S, Jit M, Kucharski AJ, CMMID COVID-19 Working Group, Centre for Mathematical Modelling of Infectious Disease (CMMID) COVID-19 Working Group.",,Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin,2021,2021-05-01,Y,Vaccination; Herd immunity; Seroprevalence; Sars-cov-2,,,"We assess the feasibility of reaching the herd immunity threshold against SARS-CoV-2 through vaccination, considering vaccine effectiveness (VE), transmissibility of the virus and the level of pre-existing immunity in populations, as well as their age structure. If highly transmissible variants of concern become dominant in areas with low levels of naturally-acquired immunity and/or in populations with large proportions of < 15 year-olds, control of infection without non-pharmaceutical interventions may only be possible with a VE ≥ 80%, and coverage extended to children.",,pdf:https://www.eurosurveillance.org/deliver/fulltext/eurosurveillance/26/20/eurosurv-26-20-1.pdf?itemId=%2Fcontent%2F10.2807%2F1560-7917.ES.2021.26.20.2100428&mimeType=pdf&containerItemId=content/eurosurveillance; doi:https://doi.org/10.2807/1560-7917.ES.2021.26.20.2100428; html:https://europepmc.org/articles/PMC8138959; pdf:https://europepmc.org/articles/PMC8138959?pdf=render 36273236,https://doi.org/10.1038/s41746-022-00705-7,"Automated clinical coding: what, why, and where we are?","Dong H, Falis M, Whiteley W, Alex B, Matterson J, Ji S, Chen J, Wu H.",,NPJ digital medicine,2022,2022-10-22,Y,,,,"Clinical coding is the task of transforming medical information in a patient's health records into structured codes so that they can be used for statistical analysis. This is a cognitive and time-consuming task that follows a standard process in order to achieve a high level of consistency. Clinical coding could potentially be supported by an automated system to improve the efficiency and accuracy of the process. We introduce the idea of automated clinical coding and summarise its challenges from the perspective of Artificial Intelligence (AI) and Natural Language Processing (NLP), based on the literature, our project experience over the past two and half years (late 2019-early 2022), and discussions with clinical coding experts in Scotland and the UK. Our research reveals the gaps between the current deep learning-based approach applied to clinical coding and the need for explainability and consistency in real-world practice. Knowledge-based methods that represent and reason the standard, explainable process of a task may need to be incorporated into deep learning-based methods for clinical coding. Automated clinical coding is a promising task for AI, despite the technical and organisational challenges. Coders are needed to be involved in the development process. There is much to achieve to develop and deploy an AI-based automated system to support coding in the next five years and beyond.",,pdf:https://www.nature.com/articles/s41746-022-00705-7.pdf; doi:https://doi.org/10.1038/s41746-022-00705-7; html:https://europepmc.org/articles/PMC9588058; pdf:https://europepmc.org/articles/PMC9588058?pdf=render 37670953,https://doi.org/10.23889/ijpds.v8i1.2113,Lessons learned from using linked administrative data to evaluate the Family Nurse Partnership in England and Scotland.,"Cavallaro FL, Cannings-John R, Lugg-Widger F, Gilbert R, Kennedy E, Kendall S, Robling M, Harron KL.",,International journal of population data science,2023,2023-05-11,Y,Evaluation; Early Years; Administrative Data; Adolescent Motherhood; Cross-Sectoral Linkage,,,"

Introduction

""Big data"" - including linked administrative data - can be exploited to evaluate interventions for maternal and child health, providing time- and cost-effective alternatives to randomised controlled trials. However, using these data to evaluate population-level interventions can be challenging.

Objectives

We aimed to inform future evaluations of complex interventions by describing sources of bias, lessons learned, and suggestions for improvements, based on two observational studies using linked administrative data from health, education and social care sectors to evaluate the Family Nurse Partnership (FNP) in England and Scotland.

Methods

We first considered how different sources of potential bias within the administrative data could affect results of the evaluations. We explored how each study design addressed these sources of bias using maternal confounders captured in the data. We then determined what additional information could be captured at each step of the complex intervention to enable analysts to minimise bias and maximise comparability between intervention and usual care groups, so that any observed differences can be attributed to the intervention.

Results

Lessons learned include the need for i) detailed data on intervention activity (dates/geography) and usual care; ii) improved information on data linkage quality to accurately characterise control groups; iii) more efficient provision of linked data to ensure timeliness of results; iv) better measurement of confounding characteristics affecting who is eligible, approached and enrolled.

Conclusions

Linked administrative data are a valuable resource for evaluations of the FNP national programme and other complex population-level interventions. However, information on local programme delivery and usual care are required to account for biases that characterise those who receive the intervention, and to inform understanding of mechanisms of effect. National, ongoing, robust evaluations of complex public health evaluations would be more achievable if programme implementation was integrated with improved national and local data collection, and robust quasi-experimental designs.",,pdf:https://ijpds.org/article/download/2113/4170; doi:https://doi.org/10.23889/ijpds.v8i1.2113; html:https://europepmc.org/articles/PMC10476150; pdf:https://europepmc.org/articles/PMC10476150?pdf=render -38663408,https://doi.org/10.1016/j.xgen.2024.100541,Characterization of the genetic determinants of context-specific DNA methylation in primary monocytes.,"Gilchrist JJ, Fang H, Danielli S, Tomkova M, Nassiri I, Ng E, Tong O, Taylor C, Muldoon D, Cohen LRZ, Al-Mossawi H, Lau E, Neville M, Schuster-Boeckler B, Knight JC, Fairfax BP.",,Cell genomics,2024,2024-04-24,Y,Genetics; Monocytes; Cancer; LPS; DNA methylation; Innate Immune Activation; Mqtl; Epigenetic Aging,,,"To better understand inter-individual variation in sensitivity of DNA methylation (DNAm) to immune activity, we characterized effects of inflammatory stimuli on primary monocyte DNAm (n = 190). We find that monocyte DNAm is site-dependently sensitive to lipopolysaccharide (LPS), with LPS-induced demethylation occurring following hydroxymethylation. We identify 7,359 high-confidence immune-modulated CpGs (imCpGs) that differ in genomic localization and transcription factor usage according to whether they represent a gain or loss in DNAm. Demethylated imCpGs are profoundly enriched for enhancers and colocalize to genes enriched for disease associations, especially cancer. DNAm is age associated, and we find that 24-h LPS exposure triggers approximately 6 months of gain in epigenetic age, directly linking epigenetic aging with innate immune activity. By integrating LPS-induced changes in DNAm with genetic variation, we identify 234 imCpGs under local genetic control. Exploring shared causal loci between LPS-induced DNAm responses and human disease traits highlights examples of disease-associated loci that modulate imCpG formation.",,doi:https://doi.org/10.1016/j.xgen.2024.100541; html:https://europepmc.org/articles/PMC11099345; pdf:https://europepmc.org/articles/PMC11099345?pdf=render 36828609,https://doi.org/10.1016/s2589-7500(22)00252-7,Embedding patient-reported outcomes at the heart of artificial intelligence health-care technologies.,"Cruz Rivera S, Liu X, Hughes SE, Dunster H, Manna E, Denniston AK, Calvert MJ.",,The Lancet. Digital health,2023,2023-03-01,N,,,,"Integration of patient-reported outcome measures (PROMs) in artificial intelligence (AI) studies is a critical part of the humanisation of AI for health. It allows AI technologies to incorporate patients' own views of their symptoms and predict outcomes, reflecting a more holistic picture of health and wellbeing and ultimately helping patients and clinicians to make the best health-care decisions together. By positioning patient-reported outcomes (PROs) as a model input or output we propose a framework to embed PROMs within the function and evaluation of AI health care. However, the integration of PROs in AI systems presents several challenges. These challenges include (1) fragmentation of PRO data collection; (2) validation of AI systems trained and validated against clinician performance, rather than outcome data; (3) scarcity of large-scale PRO datasets; (4) inadequate selection of PROMs for the target population and inadequate infrastructure for collecting PROs; and (5) clinicians might not recognise the value of PROs and therefore not prioritise their adoption; and (6) studies involving PRO or AI frequently present suboptimal design. Notwithstanding these challenges, we propose considerations for the inclusion of PROs in AI health-care technologies to avoid promoting survival at the expense of wellbeing.",,doi:https://doi.org/10.1016/s2589-7500(22)00252-7; doi:https://doi.org/10.1016/S2589-7500(22)00252-7 -37563195,https://doi.org/10.1038/s41598-023-38880-6,Locational memory of macrovessel vascular cells is transcriptionally imprinted.,"Spanjersberg TCF, Oosterhoff LA, Kruitwagen HS, van den Dungen NAM, Vernooij JCM, Asselbergs FW, Mokry M, Spee B, Harakalova M, van Steenbeek FG.",,Scientific reports,2023,2023-08-10,Y,,,,"Vascular pathologies show locational predisposition throughout the body; further insights into the transcriptomics basis of this vascular heterogeneity are needed. We analyzed transcriptomes from cultured endothelial cells and vascular smooth muscle cells from nine adult canine macrovessels: the aorta, coronary artery, vena cava, portal vein, femoral artery, femoral vein, saphenous vein, pulmonary vein, and pulmonary artery. We observed that organ-specific expression patterns persist in vitro, indicating that these genes are not regulated by blood flow or surrounding cell types but are likely fixed in the epigenetic memory. We further demonstrated the preserved location-specific expression of GATA4 protein in cultured cells and in the primary adult vessel. On a functional level, arterial and venous endothelial cells differed in vascular network morphology as the arterial networks maintained a higher complexity. Our findings prompt the rethinking of the extrapolation of results from single-origin endothelial cell systems.",,pdf:https://www.nature.com/articles/s41598-023-38880-6.pdf; doi:https://doi.org/10.1038/s41598-023-38880-6; html:https://europepmc.org/articles/PMC10415317; pdf:https://europepmc.org/articles/PMC10415317?pdf=render 35504525,https://doi.org/10.1016/j.jclinepi.2022.04.025,How traditional informed consent impairs inclusivity in a learning healthcare system: lessons learned from the Utrecht Cardiovascular Cohort.,"Groenhof TKJ, Mostert M, Lea NC, Haitjema S, de Vries MC, van Dijk WB, Grobbee DE, Asselbergs FW, Bots ML, van der Graaf R.",,Journal of clinical epidemiology,2022,2022-04-30,N,,,,,,pdf:https://discovery.ucl.ac.uk/10160730/1/JCEPI-D-21-01101_R2-2%2022-40.pdf; doi:https://doi.org/10.1016/j.jclinepi.2022.04.025 +38663408,https://doi.org/10.1016/j.xgen.2024.100541,Characterization of the genetic determinants of context-specific DNA methylation in primary monocytes.,"Gilchrist JJ, Fang H, Danielli S, Tomkova M, Nassiri I, Ng E, Tong O, Taylor C, Muldoon D, Cohen LRZ, Al-Mossawi H, Lau E, Neville M, Schuster-Boeckler B, Knight JC, Fairfax BP.",,Cell genomics,2024,2024-04-24,Y,Genetics; Monocytes; Cancer; LPS; DNA methylation; Innate Immune Activation; Mqtl; Epigenetic Aging,,,"To better understand inter-individual variation in sensitivity of DNA methylation (DNAm) to immune activity, we characterized effects of inflammatory stimuli on primary monocyte DNAm (n = 190). We find that monocyte DNAm is site-dependently sensitive to lipopolysaccharide (LPS), with LPS-induced demethylation occurring following hydroxymethylation. We identify 7,359 high-confidence immune-modulated CpGs (imCpGs) that differ in genomic localization and transcription factor usage according to whether they represent a gain or loss in DNAm. Demethylated imCpGs are profoundly enriched for enhancers and colocalize to genes enriched for disease associations, especially cancer. DNAm is age associated, and we find that 24-h LPS exposure triggers approximately 6 months of gain in epigenetic age, directly linking epigenetic aging with innate immune activity. By integrating LPS-induced changes in DNAm with genetic variation, we identify 234 imCpGs under local genetic control. Exploring shared causal loci between LPS-induced DNAm responses and human disease traits highlights examples of disease-associated loci that modulate imCpG formation.",,doi:https://doi.org/10.1016/j.xgen.2024.100541; html:https://europepmc.org/articles/PMC11099345; pdf:https://europepmc.org/articles/PMC11099345?pdf=render +37563195,https://doi.org/10.1038/s41598-023-38880-6,Locational memory of macrovessel vascular cells is transcriptionally imprinted.,"Spanjersberg TCF, Oosterhoff LA, Kruitwagen HS, van den Dungen NAM, Vernooij JCM, Asselbergs FW, Mokry M, Spee B, Harakalova M, van Steenbeek FG.",,Scientific reports,2023,2023-08-10,Y,,,,"Vascular pathologies show locational predisposition throughout the body; further insights into the transcriptomics basis of this vascular heterogeneity are needed. We analyzed transcriptomes from cultured endothelial cells and vascular smooth muscle cells from nine adult canine macrovessels: the aorta, coronary artery, vena cava, portal vein, femoral artery, femoral vein, saphenous vein, pulmonary vein, and pulmonary artery. We observed that organ-specific expression patterns persist in vitro, indicating that these genes are not regulated by blood flow or surrounding cell types but are likely fixed in the epigenetic memory. We further demonstrated the preserved location-specific expression of GATA4 protein in cultured cells and in the primary adult vessel. On a functional level, arterial and venous endothelial cells differed in vascular network morphology as the arterial networks maintained a higher complexity. Our findings prompt the rethinking of the extrapolation of results from single-origin endothelial cell systems.",,pdf:https://www.nature.com/articles/s41598-023-38880-6.pdf; doi:https://doi.org/10.1038/s41598-023-38880-6; html:https://europepmc.org/articles/PMC10415317; pdf:https://europepmc.org/articles/PMC10415317?pdf=render 34364665,https://doi.org/10.1016/j.cardfail.2021.05.012,Empagliflozin in Heart Failure With Predicted Preserved Versus Reduced Ejection Fraction: Data From the EMPA-REG OUTCOME Trial.,"Savarese G, Uijl A, Lund LH, Anker SD, Asselbergs F, Fitchett D, Inzucchi SE, Koudstaal S, Ofstad AP, Schrage B, Vedin O, Wanner C, Zannad F, Zwiener I, Butler J.",,Journal of cardiac failure,2021,2021-08-01,N,Type 2 diabetes mellitus; Heart Failure With Preserved Ejection Fraction; Heart Failure With Reduced Ejection Fraction; Empagliflozin; Empa-reg Outcome; Heart Failure With Mid-range Ejection Fraction; Heart Failure With Mildly Reduced Ejection Fraction,,,"

Background

In the EMPA-REG OUTCOME trial, ejection fraction (EF) data were not collected. In the subpopulation with heart failure (HF), we applied a new predictive model for EF to determine the effects of empagliflozin in HF with predicted reduced (HFrEF) vs preserved (HFpEF) EF vs no HF.

Methods and results

We applied a validated EF predictive model based on patient baseline characteristics and treatments to categorize patients with HF as being likely to have HF with mid-range EF (HFmrEF)/HFrEF (EF <50%) or HFpEF (EF ≥50%). Cox regression was used to assess the effect of empagliflozin vs placebo on cardiovascular death/HF hospitalization (HHF), cardiovascular and all-cause mortality, and HHF in patients with predicted HFpEF, HFmrEF/HFrEF and no HF. Of 7001 EMPA-REG OUTCOME patients with data available for this analysis, 6314 (90%) had no history of HF. Of the 687 with history of HF, 479 (69.7%) were predicted to have HFmrEF/HFrEF and 208 (30.3%) to have HFpEF. Empagliflozin's treatment effect was consistent in predicted HFpEF, HFmrEF/HFrEF and no-HF for each outcome (HR [95% CI] for the primary outcome 0.60 [0.31-1.17], 0.79 [0.51-1.23], and 0.63 [0.50-0.78], respectively; P interaction = 0.62).

Conclusions

In EMPA-REG OUTCOME, one-third of the patients with HF had predicted HFpEF. The benefits of empagliflozin on HF and mortality outcomes were consistent in nonHF, predicted HFpEF and HFmrEF/HFrEF.",,pdf:https://hal.univ-lorraine.fr/hal-03320880/file/1-s2.0-S1071916421002025-main.pdf; doi:https://doi.org/10.1016/j.cardfail.2021.05.012 34769922,https://doi.org/10.3390/ijerph182111380,"Driver, Collision and Meteorological Characteristics of Motor Vehicle Collisions among Road Trauma Survivors.","Giummarra MJ, Xu R, Guo Y, Dipnall JF, Ponsford J, Cameron PA, Ameratunga S, Gabbe BJ.",,International journal of environmental research and public health,2021,2021-10-29,Y,Trauma; Prevention; Traffic; Motor Vehicle,,,"Road trauma remains a significant public health problem. We aimed to identify sub-groups of motor vehicle collisions in Victoria, Australia, and the association between collision characteristics and outcomes up to 24 months post-injury. Data were extracted from the Victorian State Trauma Registry for injured drivers aged ≥16 years, from 2010 to 2016, with a compensation claim who survived ≥12 months post-injury. People with intentional or severe head injury were excluded, resulting in 2735 cases. Latent class analysis was used to identify collision classes for driver fault and blood alcohol concentration (BAC), day and time of collision, weather conditions, single vs. multi-vehicle and regional vs. metropolitan injury location. Five classes were identified: (1) daytime multi-vehicle collisions, no other at fault; (2) daytime single-vehicle predominantly weekday collisions; (3) evening single-vehicle collisions, no other at fault, 36% with BAC ≥ 0.05; (4) sunrise or sunset weekday collisions; and (5) dusk and evening multi-vehicle in metropolitan areas with BAC < 0.05. Mixed linear and logistic regression analyses examined associations between collision class and return to work, health (EQ-5D-3L summary score) and independent function Glasgow Outcome Scale - Extended at 6, 12 and 24 months. After adjusting for demographic, health and injury characteristics, collision class was not associated with outcomes. Rather, risk of poor outcomes was associated with age, sex and socioeconomic disadvantage, education, pre-injury health and injury severity. People at risk of poor recovery may be identified from factors available during the hospital admission and may benefit from clinical assessment and targeted referrals and treatments.",,pdf:https://www.mdpi.com/1660-4601/18/21/11380/pdf?version=1635513758; doi:https://doi.org/10.3390/ijerph182111380; html:https://europepmc.org/articles/PMC8583338; pdf:https://europepmc.org/articles/PMC8583338?pdf=render 35177264,https://doi.org/10.1016/j.injury.2022.02.027,Chronic physical health conditions up to five years after serious orthopaedic injury.,"Gelaw AY, Gabbe BJ, Ekegren CL.",,Injury,2022,2022-02-09,N,Chronic Conditions; Cvd; Major Trauma; Orthopaedic Trauma; Physical Health Conditions; Orthopaedic Injury,,,"

Background

Information about the prevalence of chronic physical health conditions following serious orthopaedic injury is currently lacking in the general population and is essential for quantifying the burden of injury and improving outcomes.

Objectives

To determine the prevalence of chronic physical health conditions recorded within hospitalisations and emergency department presentations and associated factors five years following serious orthopaedic injury.

Methods

We conducted a registry-based cohort study using data from the Victorian State Trauma Registry (2007-2016) linked with hospital admissions and ED presentations for 16,249 adults with serious orthopaedic injuries. We considered that people who were admitted to hospital or presented to an emergency department with a chronic physical health condition one to five years post-injury had ""new-onset"" conditions. We applied Kaplan-Meier failure curves and Cox proportional hazard regression models to determine factors associated with new-onset conditions.

Results

There were 1420 people (11.0%) with at least one new-onset condition. Cancer (6.1%), cardiovascular disease (5.1%) and hypertension (6.2%) were the three most common ""new-onset"" chronic physical health conditions. Older adults, women, smokers, and people with mental health and alcohol and drug-related conditions had a higher risk of hospitalisation or emergency department presentation with new-onset conditions post-injury.

Conclusion

People with serious orthopaedic injuries experienced a significant additional burden of chronic physical health conditions up to five years after serious orthopaedic injury, posing a new challenge to post-trauma care. Early preventive interventions may be required in people with serious orthopaedic injuries to minimise modifiable risk factors such as smoking, excessive consumption of alcohol or drug use.",,doi:https://doi.org/10.1016/j.injury.2022.02.027 @@ -1554,17 +1554,17 @@ PMC9023380,https://doi.org/,Assessing the spread risk of COVID-19 associated wit 32345651,https://doi.org/10.2337/dc19-2116,"Obstructive Sleep Apnea, a Risk Factor for Cardiovascular and Microvascular Disease in Patients With Type 2 Diabetes: Findings From a Population-Based Cohort Study.","Adderley NJ, Subramanian A, Toulis K, Gokhale K, Taverner T, Hanif W, Haroon S, Thomas GN, Sainsbury C, Tahrani AA, Nirantharakumar K.",,Diabetes care,2020,2020-04-28,N,,,,"

Objective

To determine the risk of cardiovascular disease (CVD), microvascular complications, and mortality in patients with type 2 diabetes who subsequently develop obstructive sleep apnea (OSA) compared with patients with type 2 diabetes without a diagnosis of OSA.

Research design and methods

This age-, sex-, BMI-, and diabetes duration-matched cohort study used data from a U.K. primary care database from 1 January 2005 to 17 January 2018. Participants aged ≥16 years with type 2 diabetes were included. Exposed participants were those who developed OSA after their diabetes diagnosis; unexposed participants were those without diagnosed OSA. Outcomes were composite CVD (ischemic heart disease [IHD], stroke/transient ischemic attack [TIA], heart failure [HF]), peripheral vascular disease (PVD), atrial fibrillation (AF), peripheral neuropathy (PN), diabetes-related foot disease (DFD), referable retinopathy, chronic kidney disease (CKD), and all-cause mortality. The same outcomes were explored in patients with preexisting OSA before a diagnosis of type 2 diabetes versus diabetes without diagnosed OSA.

Results

A total of 3,667 exposed participants and 10,450 matched control participants were included. Adjusted hazard ratios for the outcomes were as follows: composite CVD 1.54 (95% CI 1.32, 1.79), IHD 1.55 (1.26, 1.90), HF 1.67 (1.35, 2.06), stroke/TIA 1.57 (1.27, 1.94), PVD 1.10 (0.91, 1.32), AF 1.53 (1.28, 1.83), PN 1.32 (1.14, 1.51), DFD 1.42 (1.16, 1.74), referable retinopathy 0.99 (0.82, 1.21), CKD (stage 3-5) 1.18 (1.02, 1.36), albuminuria 1.11 (1.01, 1.22), and all-cause mortality 1.24 (1.10, 1.40). In the prevalent OSA cohort, the results were similar, but some associations were not observed.

Conclusions

Patients with type 2 diabetes who develop OSA are at increased risk of CVD, AF, PN, DFD, CKD, and all-cause mortality compared with patients without diagnosed OSA. Patients with type 2 diabetes who develop OSA are a high-risk population, and strategies to detect OSA and prevent cardiovascular and microvascular complications should be implemented.",,pdf:https://care.diabetesjournals.org/content/diacare/43/8/1868.full.pdf; doi:https://doi.org/10.2337/dc19-2116 30863860,https://doi.org/10.1093/eurheartj/ehz089,Big data analytics in adult congenital heart disease: why coding matters.,"Asselbergs FW, Meijboom FJ.",,European heart journal,2019,2019-04-01,N,,,,,,pdf:https://discovery.ucl.ac.uk/10076628/1/Asselbergs_AAM_Big%20data%20analytics%20in%20adult%20congenital%20heart%20disease.pdf; doi:https://doi.org/10.1093/eurheartj/ehz089 36331190,https://doi.org/10.1056/nejmoa2204233,Empagliflozin in Patients with Chronic Kidney Disease.,"The EMPA-KIDNEY Collaborative Group, Herrington WG, Staplin N, Wanner C, Green JB, Hauske SJ, Emberson JR, Preiss D, Judge P, Mayne KJ, Ng SYA, Sammons E, Zhu D, Hill M, Stevens W, Wallendszus K, Brenner S, Cheung AK, Liu ZH, Li J, Hooi LS, Liu W, Kadowaki T, Nangaku M, Levin A, Cherney D, Maggioni AP, Pontremoli R, Deo R, Goto S, Rossello X, Tuttle KR, Steubl D, Petrini M, Massey D, Eilbracht J, Brueckmann M, Landray MJ, Baigent C, Haynes R.",,The New England journal of medicine,2023,2022-11-04,Y,,,,"

Background

The effects of empagliflozin in patients with chronic kidney disease who are at risk for disease progression are not well understood. The EMPA-KIDNEY trial was designed to assess the effects of treatment with empagliflozin in a broad range of such patients.

Methods

We enrolled patients with chronic kidney disease who had an estimated glomerular filtration rate (eGFR) of at least 20 but less than 45 ml per minute per 1.73 m2 of body-surface area, or who had an eGFR of at least 45 but less than 90 ml per minute per 1.73 m2 with a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of at least 200. Patients were randomly assigned to receive empagliflozin (10 mg once daily) or matching placebo. The primary outcome was a composite of progression of kidney disease (defined as end-stage kidney disease, a sustained decrease in eGFR to <10 ml per minute per 1.73 m2, a sustained decrease in eGFR of ≥40% from baseline, or death from renal causes) or death from cardiovascular causes.

Results

A total of 6609 patients underwent randomization. During a median of 2.0 years of follow-up, progression of kidney disease or death from cardiovascular causes occurred in 432 of 3304 patients (13.1%) in the empagliflozin group and in 558 of 3305 patients (16.9%) in the placebo group (hazard ratio, 0.72; 95% confidence interval [CI], 0.64 to 0.82; P<0.001). Results were consistent among patients with or without diabetes and across subgroups defined according to eGFR ranges. The rate of hospitalization from any cause was lower in the empagliflozin group than in the placebo group (hazard ratio, 0.86; 95% CI, 0.78 to 0.95; P = 0.003), but there were no significant between-group differences with respect to the composite outcome of hospitalization for heart failure or death from cardiovascular causes (which occurred in 4.0% in the empagliflozin group and 4.6% in the placebo group) or death from any cause (in 4.5% and 5.1%, respectively). The rates of serious adverse events were similar in the two groups.

Conclusions

Among a wide range of patients with chronic kidney disease who were at risk for disease progression, empagliflozin therapy led to a lower risk of progression of kidney disease or death from cardiovascular causes than placebo. (Funded by Boehringer Ingelheim and others; EMPA-KIDNEY ClinicalTrials.gov number, NCT03594110; EudraCT number, 2017-002971-24.).",,pdf:https://ora.ox.ac.uk/objects/uuid:f91f9722-f207-4d97-aa64-58636b323acc/files/r6969z144v; doi:https://doi.org/10.1056/NEJMoa2204233; html:https://europepmc.org/articles/PMC7614055; pdf:https://europepmc.org/articles/PMC7614055?pdf=render -38190103,https://doi.org/10.1016/j.xgen.2023.100469,Genome-wide classification of epigenetic activity reveals regions of enriched heritability in immune-related traits.,"Stricker M, Zhang W, Cheng WY, Gazal S, Dendrou C, Nahkuri S, Palamara PF.",,Cell genomics,2024,2023-12-28,Y,Immune system; Heritability; Epigenetics; Machine Learning,,,"Epigenetics underpins the regulation of genes known to play a key role in the adaptive and innate immune system (AIIS). We developed a method, EpiNN, that leverages epigenetic data to detect AIIS-relevant genomic regions and used it to detect 2,765 putative AIIS loci. Experimental validation of one of these loci, DNMT1, provided evidence for a novel AIIS-specific transcription start site. We built a genome-wide AIIS annotation and used linkage disequilibrium (LD) score regression to test whether it predicts regional heritability using association statistics for 176 traits. We detected significant heritability effects (average |τ∗|=1.65) for 20 out of 26 immune-relevant traits. In a meta-analysis, immune-relevant traits and diseases were 4.45× more enriched for heritability than other traits. The EpiNN annotation was also depleted of trans-ancestry genetic correlation, indicating ancestry-specific effects. These results underscore the effectiveness of leveraging supervised learning algorithms and epigenetic data to detect loci implicated in specific classes of traits and diseases.",,doi:https://doi.org/10.1016/j.xgen.2023.100469; html:https://europepmc.org/articles/PMC10794845; pdf:https://europepmc.org/articles/PMC10794845?pdf=render -35275087,https://doi.org/10.2196/34898,Longitudinal Relationships Between Depressive Symptom Severity and Phone-Measured Mobility: Dynamic Structural Equation Modeling Study.,"Zhang Y, Folarin AA, Sun S, Cummins N, Vairavan S, Bendayan R, Ranjan Y, Rashid Z, Conde P, Stewart C, Laiou P, Sankesara H, Matcham F, White KM, Oetzmann C, Ivan A, Lamers F, Siddi S, Vilella E, Simblett S, Rintala A, Bruce S, Mohr DC, Myin-Germeys I, Wykes T, Haro JM, Penninx BW, Narayan VA, Annas P, Hotopf M, Dobson RJ, RADAR-CNS consortium.",,JMIR mental health,2022,2022-03-11,Y,Modeling; Mobility; Depression; Mental health; Medical Informatics; Mhealth; Mobile Health; Dynamic Structural Equation Modeling; Location Data,,,"

Background

The mobility of an individual measured by phone-collected location data has been found to be associated with depression; however, the longitudinal relationships (the temporal direction of relationships) between depressive symptom severity and phone-measured mobility have yet to be fully explored.

Objective

We aimed to explore the relationships and the direction of the relationships between depressive symptom severity and phone-measured mobility over time.

Methods

Data used in this paper came from a major EU program, called the Remote Assessment of Disease and Relapse-Major Depressive Disorder, which was conducted in 3 European countries. Depressive symptom severity was measured with the 8-item Patient Health Questionnaire (PHQ-8) through mobile phones every 2 weeks. Participants' location data were recorded by GPS and network sensors in mobile phones every 10 minutes, and 11 mobility features were extracted from location data for the 2 weeks prior to the PHQ-8 assessment. Dynamic structural equation modeling was used to explore the longitudinal relationships between depressive symptom severity and phone-measured mobility.

Results

This study included 2341 PHQ-8 records and corresponding phone-collected location data from 290 participants (age: median 50.0 IQR 34.0, 59.0) years; of whom 215 (74.1%) were female, and 149 (51.4%) were employed. Significant negative correlations were found between depressive symptom severity and phone-measured mobility, and these correlations were more significant at the within-individual level than the between-individual level. For the direction of relationships over time, Homestay (time at home) (φ=0.09, P=.01), Location Entropy (time distribution on different locations) (φ=-0.04, P=.02), and Residential Location Count (reflecting traveling) (φ=0.05, P=.02) were significantly correlated with the subsequent changes in the PHQ-8 score, while changes in the PHQ-8 score significantly affected (φ=-0.07, P<.001) the subsequent periodicity of mobility.

Conclusions

Several phone-derived mobility features have the potential to predict future depression, which may provide support for future clinical applications, relapse prevention, and remote mental health monitoring practices in real-world settings.",,pdf:https://mental.jmir.org/2022/3/e34898/PDF; doi:https://doi.org/10.2196/34898; html:https://europepmc.org/articles/PMC8957008 32017129,https://doi.org/10.5694/mja2.50485,Discharge destination and patient-reported outcomes after inpatient treatment for isolated lower limb fractures.,"Kimmel LA, Simpson PM, Holland AE, Edwards ER, Cameron PA, de Steiger RS, Page RS, Hau R, Bucknill A, Kasza J, Gabbe BJ.",,The Medical journal of Australia,2020,2020-02-04,N,"Rehabilitation; Treatment outcome; Orthopedic Procedures; Fractures, Bone; Trauma Surgery",,,"

Objectives

To examine the association between discharge destination (home or inpatient rehabilitation) for adult patients treated in hospital for isolated lower limb fractures and patient-reported outcomes.

Design

Review of prospectively collected Victorian Orthopaedic Trauma Outcomes Registry (VOTOR) data.

Setting, participants

Adults (18-64 years old) treated for isolated lower limb fractures at four Melbourne trauma hospitals that contribute data to the VOTOR, 1 March 2007 - 31 March 2016.

Main outcome measures

Return to work and functional recovery (assessed with the extended Glasgow Outcomes Scale, GOS-E); propensity score analysis of association between discharge destination and outcome.

Results

Of 7961 eligible patients, 1432 (18%) were discharged to inpatient rehabilitation, and 6775 (85%) were followed up 12 months after their injuries. After propensity score adjustment, the odds of better functional recovery were 56% lower for patients discharged to inpatient rehabilitation than for those discharged directly home (odds ratio, 0.44; 95% CI, 0.37-0.51); for the 5057 people working before their accident, the odds of return to work were reduced by 66% (odds ratio, 0.34; 95% CI, 0.26-0.46). Propensity score analysis improved matching of the discharge destination groups, but imbalances in funding source remained for both outcome analyses, and for also for site and cause of injury in the GOS-E analysis (standardised differences, 10-16%).

Conclusions

Discharge to inpatient rehabilitation after treatment for isolated lower limb fractures was associated with poorer outcomes than discharge home. Factors that remained unbalanced after propensity score analysis could be assessed in controlled trials.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.5694/mja2.50485; doi:https://doi.org/10.5694/mja2.50485 +35275087,https://doi.org/10.2196/34898,Longitudinal Relationships Between Depressive Symptom Severity and Phone-Measured Mobility: Dynamic Structural Equation Modeling Study.,"Zhang Y, Folarin AA, Sun S, Cummins N, Vairavan S, Bendayan R, Ranjan Y, Rashid Z, Conde P, Stewart C, Laiou P, Sankesara H, Matcham F, White KM, Oetzmann C, Ivan A, Lamers F, Siddi S, Vilella E, Simblett S, Rintala A, Bruce S, Mohr DC, Myin-Germeys I, Wykes T, Haro JM, Penninx BW, Narayan VA, Annas P, Hotopf M, Dobson RJ, RADAR-CNS consortium.",,JMIR mental health,2022,2022-03-11,Y,Modeling; Mobility; Depression; Mental health; Medical Informatics; Mhealth; Mobile Health; Dynamic Structural Equation Modeling; Location Data,,,"

Background

The mobility of an individual measured by phone-collected location data has been found to be associated with depression; however, the longitudinal relationships (the temporal direction of relationships) between depressive symptom severity and phone-measured mobility have yet to be fully explored.

Objective

We aimed to explore the relationships and the direction of the relationships between depressive symptom severity and phone-measured mobility over time.

Methods

Data used in this paper came from a major EU program, called the Remote Assessment of Disease and Relapse-Major Depressive Disorder, which was conducted in 3 European countries. Depressive symptom severity was measured with the 8-item Patient Health Questionnaire (PHQ-8) through mobile phones every 2 weeks. Participants' location data were recorded by GPS and network sensors in mobile phones every 10 minutes, and 11 mobility features were extracted from location data for the 2 weeks prior to the PHQ-8 assessment. Dynamic structural equation modeling was used to explore the longitudinal relationships between depressive symptom severity and phone-measured mobility.

Results

This study included 2341 PHQ-8 records and corresponding phone-collected location data from 290 participants (age: median 50.0 IQR 34.0, 59.0) years; of whom 215 (74.1%) were female, and 149 (51.4%) were employed. Significant negative correlations were found between depressive symptom severity and phone-measured mobility, and these correlations were more significant at the within-individual level than the between-individual level. For the direction of relationships over time, Homestay (time at home) (φ=0.09, P=.01), Location Entropy (time distribution on different locations) (φ=-0.04, P=.02), and Residential Location Count (reflecting traveling) (φ=0.05, P=.02) were significantly correlated with the subsequent changes in the PHQ-8 score, while changes in the PHQ-8 score significantly affected (φ=-0.07, P<.001) the subsequent periodicity of mobility.

Conclusions

Several phone-derived mobility features have the potential to predict future depression, which may provide support for future clinical applications, relapse prevention, and remote mental health monitoring practices in real-world settings.",,pdf:https://mental.jmir.org/2022/3/e34898/PDF; doi:https://doi.org/10.2196/34898; html:https://europepmc.org/articles/PMC8957008 +38190103,https://doi.org/10.1016/j.xgen.2023.100469,Genome-wide classification of epigenetic activity reveals regions of enriched heritability in immune-related traits.,"Stricker M, Zhang W, Cheng WY, Gazal S, Dendrou C, Nahkuri S, Palamara PF.",,Cell genomics,2024,2023-12-28,Y,Immune system; Heritability; Epigenetics; Machine Learning,,,"Epigenetics underpins the regulation of genes known to play a key role in the adaptive and innate immune system (AIIS). We developed a method, EpiNN, that leverages epigenetic data to detect AIIS-relevant genomic regions and used it to detect 2,765 putative AIIS loci. Experimental validation of one of these loci, DNMT1, provided evidence for a novel AIIS-specific transcription start site. We built a genome-wide AIIS annotation and used linkage disequilibrium (LD) score regression to test whether it predicts regional heritability using association statistics for 176 traits. We detected significant heritability effects (average |τ∗|=1.65) for 20 out of 26 immune-relevant traits. In a meta-analysis, immune-relevant traits and diseases were 4.45× more enriched for heritability than other traits. The EpiNN annotation was also depleted of trans-ancestry genetic correlation, indicating ancestry-specific effects. These results underscore the effectiveness of leveraging supervised learning algorithms and epigenetic data to detect loci implicated in specific classes of traits and diseases.",,doi:https://doi.org/10.1016/j.xgen.2023.100469; html:https://europepmc.org/articles/PMC10794845; pdf:https://europepmc.org/articles/PMC10794845?pdf=render 35355205,https://doi.org/10.1007/s11897-022-00544-3,LVEF by Multigated Acquisition Scan Compared to Other Imaging Modalities in Cardio-Oncology: a Systematic Review.,"Printezi MI, Yousif LIE, Kamphuis JAM, van Laake LW, Cramer MJ, Hobbelink MGG, Asselbergs FW, Teske AJ.",,Current heart failure reports,2022,2022-03-30,Y,Cardiotoxicity; Echocardiography; Left ventricular ejection fraction; Cardiac Magnetic Resonance Imaging; Cardio-oncology; Multigated Acquisition Scan,,,"

Purpose of review

The prevalence of cancer therapy-related cardiac dysfunction (CTRCD) is increasing due to improved cancer survival. Serial monitoring of cardiac function is essential to detect CTRCD, guiding timely intervention strategies. Multigated radionuclide angiography (MUGA) has been the main screening tool using left ventricular ejection fraction (LVEF) to monitor cardiac dysfunction. However, transthoracic echocardiography (TTE) and cardiac magnetic resonance imaging (CMR) may be more suitable for serial assessment. We aimed to assess the concordance between different non-radiating imaging modalities with MUGA to determine whether they can be used interchangeably.

Recent findings

In order to identify relevant studies, a PubMed search was performed. We included cross-sectional studies comparing MUGA LVEF to that of 2D TTE, 3D TTE, and CMR. From 470 articles, 22 were selected, comprising 1017 patients in total. Among others, this included three 3D TTE, seven 2D harmonic TTE + contrast (2DHC), and seven CMR comparisons. The correlations and Bland-Altman limits of agreement varied for CMR but were stronger for 3D TTE and 2DHC. Our findings suggest that MUGA and CMR should not be used interchangeably whereas 3D TTE and 2DHC are appropriate alternatives following an initial MUGA scan. We propose a multimodality diagnostic imaging strategy for LVEF monitoring in patients undergoing cancer treatment.",,pdf:https://link.springer.com/content/pdf/10.1007/s11897-022-00544-3.pdf; doi:https://doi.org/10.1007/s11897-022-00544-3; html:https://europepmc.org/articles/PMC9177497; pdf:https://europepmc.org/articles/PMC9177497?pdf=render 34019073,https://doi.org/10.1093/ibd/izab059,Ultra-high Magnification Endocytoscopy and Molecular Markers for Defining Endoscopic and Histologic Remission in Ulcerative Colitis-An Exploratory Study to Define Deep Remission.,"Iacucci M, Jeffery L, Acharjee A, Nardone OM, Zardo D, Smith SCL, Bazarova A, Cannatelli R, Shivaji UN, Williams J, Gkoutos G, Ghosh S.",,Inflammatory bowel diseases,2021,2021-10-01,Y,Rna-sequencing; Mucosal Healing; Histological Healing; Noninvasive Markers; Endocytoscope,,,"

Background

Endoscopic and histological remission are both important treatment goals in patients with ulcerative colitis (UC). We aimed to define cellular architecture, expression of molecular markers, and their correlation with endoscopic scores assessed by ultra-high magnification endocytoscopy (ECS) and histological scores.

Methods

Patients with UC (n = 29) were prospectively recruited. The correlation among ECS score (ECSS), Mayo endoscopic score (MES), and histological scores were determined. Area under curve were plotted to determine the best thresholds for ECSS that predicted histological remission by Robarts (RHI) and Nancy Histological Index (NHI).Soluble analytes relevant to inflammation were measured in serum and mucosal culture supernatants using ProcartaPlex Luminex assays and studied by partial least square discriminant analysis and logistic model. Mucosal RNA sequencing and bioinformatics analysis were performed to define differentially expressed genes/pathways.

Results

Endocytoscope scoring system correlated strongly with RHI (r = 0.89; 95% CI, 0.51-0.98) and NHI (r = 0.86; 95% CI, 0.42-0.98) but correlated poorly with MES (r = 0.28; 95% CI, 0.27-0.70). We identified soluble brain-derived neurotrophic factors (BDNF), macrophage inflammatory proteins (MIP-1 α) and soluble vascular cell adhesion molecule 1 (sVCAM-1) predicted histological remission. Mucosal biopsy cultures also identified sVCAM-1 associated with healed mucosa. RNA-seq analysis identified gene expressions shared between ECSS, RHI, or NHI defined healing. A number of gene expressions and pathways were identified including inflammation and metabolic and tumor suppressors that discriminated healed from nonhealed mucosa.

Conclusions

Endocytoscopy represents an interesting tool that may sit between endoscopy and histology-but closer to the latter-identifying gene expression markers and pathways that are also identified by histology.",,pdf:https://academic.oup.com/ibdjournal/article-pdf/27/11/1719/40784408/izab059.pdf; doi:https://doi.org/10.1093/ibd/izab059; html:https://europepmc.org/articles/PMC8528147; pdf:https://europepmc.org/articles/PMC8528147?pdf=render 36240828,https://doi.org/10.1016/s2214-109x(22)00358-8,Prediction of upcoming global infection burden of influenza seasons after relaxation of public health and social measures during the COVID-19 pandemic: a modelling study.,"Ali ST, Lau YC, Shan S, Ryu S, Du Z, Wang L, Xu XK, Chen D, Xiong J, Tae J, Tsang TK, Wu P, Lau EHY, Cowling BJ.",,The Lancet. Global health,2022,2022-11-01,Y,,,,"

Background

The transmission dynamics of influenza were affected by public health and social measures (PHSMs) implemented globally since early 2020 to mitigate the COVID-19 pandemic. We aimed to assess the effect of COVID-19 PHSMs on the transmissibility of influenza viruses and to predict upcoming influenza epidemics.

Methods

For this modelling study, we used surveillance data on influenza virus activity for 11 different locations and countries in 2017-22. We implemented a data-driven mechanistic predictive modelling framework to predict future influenza seasons on the basis of pre-COVID-19 dynamics and the effect of PHSMs during the COVID-19 pandemic. We simulated the potential excess burden of upcoming influenza epidemics in terms of fold rise in peak magnitude and epidemic size compared with pre-COVID-19 levels. We also examined how a proactive influenza vaccination programme could mitigate this effect.

Findings

We estimated that COVID-19 PHSMs reduced influenza transmissibility by a maximum of 17·3% (95% CI 13·3-21·4) to 40·6% (35·2-45·9) and attack rate by 5·1% (1·5-7·2) to 24·8% (20·8-27·5) in the 2019-20 influenza season. We estimated a 10-60% increase in the population susceptibility for influenza, which might lead to a maximum of 1-5-fold rise in peak magnitude and 1-4-fold rise in epidemic size for the upcoming 2022-23 influenza season across locations, with a significantly higher fold rise in Singapore and Taiwan. The infection burden could be mitigated by additional proactive one-off influenza vaccination programmes.

Interpretation

Our results suggest the potential for substantial increases in infection burden in upcoming influenza seasons across the globe. Strengthening influenza vaccination programmes is the best preventive measure to reduce the effect of influenza virus infections in the community.

Funding

Health and Medical Research Fund, Hong Kong.",,pdf:https://www.repository.cam.ac.uk/bitstreams/bb5465bd-c08f-4c3d-ab0e-87fee39fc92b/download; doi:https://doi.org/10.1016/S2214-109X(22)00358-8; html:https://europepmc.org/articles/PMC9573849 -37046260,https://doi.org/10.1186/s12913-023-09363-1,Associations between the stringency of COVID-19 containment policies and health service disruptions in 10 countries.,"Reddy T, Kapoor NR, Kubota S, Doubova SV, Asai D, Mariam DH, Ayele W, Mebratie AD, Thermidor R, Sapag JC, Bedregal P, Passi-Solar Á, Gordon-Strachan G, Dulal M, Gadeka DD, Mehata S, Margozzini P, Leerapan B, Rittiphairoj T, Kaewkamjornchai P, Nega A, Awoonor-Williams JK, Kruk ME, Arsenault C.",,BMC health services research,2023,2023-04-12,Y,Health Services; Health Systems; Pandemic Response; Health System Resilience; Covid-19 Restrictions; Health Care Disruptions,,,"

Background

Disruptions in essential health services during the COVID-19 pandemic have been reported in several countries. Yet, patterns in health service disruption according to country responses remain unclear. In this paper, we investigate associations between the stringency of COVID-19 containment policies and disruptions in 31 health services in 10 low- middle- and high-income countries in 2020.

Methods

Using routine health information systems and administrative data from 10 countries (Chile, Ethiopia, Ghana, Haiti, Lao People's Democratic Republic, Mexico, Nepal, South Africa, South Korea, and Thailand) we estimated health service disruptions for the period of April to December 2020 by dividing monthly service provision at national levels by the average service provision in the 15 months pre-COVID (January 2019-March 2020). We used the Oxford COVID-19 Government Response Tracker (OxCGRT) index and multi-level linear regression analyses to assess associations between the stringency of restrictions and health service disruptions over nine months. We extended the analysis by examining associations between 11 individual containment or closure policies and health service disruptions. Models were adjusted for COVID caseload, health service category and country GDP and included robust standard errors.

Findings

Chronic disease care was among the most affected services. Regression analyses revealed that a 10% increase in the mean stringency index was associated with a 3.3 percentage-point (95% CI -3.9, -2.7) reduction in relative service volumes. Among individual policies, curfews, and the presence of a state of emergency, had the largest coefficients and were associated with 14.1 (95% CI -19.6, 8.7) and 10.7 (95% CI -12.7, -8.7) percentage-point lower relative service volumes, respectively. In contrast, number of COVID-19 cases in 2020 was not associated with health service disruptions in any model.

Conclusions

Although containment policies were crucial in reducing COVID-19 mortality in many contexts, it is important to consider the indirect effects of these restrictions. Strategies to improve the resilience of health systems should be designed to ensure that populations can continue accessing essential health care despite the presence of containment policies during future infectious disease outbreaks.",,pdf:https://bmchealthservres.biomedcentral.com/counter/pdf/10.1186/s12913-023-09363-1; doi:https://doi.org/10.1186/s12913-023-09363-1; html:https://europepmc.org/articles/PMC10096103; pdf:https://europepmc.org/articles/PMC10096103?pdf=render 31984563,https://doi.org/10.1111/jce.14368,Early recurrences of atrial tachyarrhythmias post pulmonary vein isolation.,"von Olshausen G, Uijl A, Jensen-Urstad M, Schwieler J, Drca N, Bastani H, Tapanainen J, Saluveer O, Bourke T, Kennebäck G, Insulander P, Deisenhofer I, Braunschweig F.",,Journal of cardiovascular electrophysiology,2020,2020-01-31,N,Atrial fibrillation; Catheter ablation; Late Recurrence; Early Recurrence; Blanking Period,,,"

Aims

To investigate the significance of early recurrence (ER) of atrial tachyarrhythmias after pulmonary vein isolation (PVI) on the development of late recurrence (LR) and to redefine the blanking period during which an ER is considered nonspecific.

Methods

Data of 713 patients undergoing their first PVI for paroxysmal or persistent atrial fibrillation between January 2012 and December 2017 were included. All patients were followed-up for 12 months according to clinical and outpatient routine and were screened for any atrial tachyarrhythmia lasting >30 seconds occurring during the first 3 months postablation (ER) and after the 3 months blanking period (LR).

Results

Patients with ER compared to those without ER had significantly more LR (74.5% vs 16.5% vs, P < .001). The occurrence of ER during the first, second and third months showed increasing LR rates of 35.2%, 67.9%, and 94.8%, respectively (P < .001). Receiver operator characteristic analysis revealed a blanking period of 46 days with the highest sensitivity (68.1%) and specificity (96.5%). Later timing and longer time span of ER were independent predictors for LR in multivariable analysis.

Conclusion

ER is a strong predictor for LR. Our study advocates a shortening of the post-PVI blanking period followed by a ""gray zone"" up to 3 months where individualized therapeutic decisions based on additional risk factors should be considered. We suggest that the ER time span might serve as such a predictor identifying patients at the highest risk for LR.",,doi:https://doi.org/10.1111/jce.14368 -37180793,https://doi.org/10.3389/fcvm.2023.1136764,Diabetes and heart failure associations in women and men: Results from the MORGAM consortium.,"Chadalavada S, Reinikainen J, Andersson J, Di Castelnuovo A, Iacoviello L, Jousilahti P, Kårhus LL, Linneberg A, Söderberg S, Tunstall-Pedoe H, Lekadir K, Aung N, Jensen MT, Kuulasmaa K, Niiranen TJ, Petersen SE.",,Frontiers in cardiovascular medicine,2023,2023-04-25,Y,Diabetes; Sex differences; epidemiology; Heart Failure; Morgam,,,"

Background

Diabetes and its cardiovascular complications are a growing concern worldwide. Recently, some studies have demonstrated that relative risk of heart failure (HF) is higher in women with type 1 diabetes (T1DM) than in men. This study aims to validate these findings in cohorts representing five countries across Europe.

Methods

This study includes 88,559 (51.8% women) participants, 3,281 (46.3% women) of whom had diabetes at baseline. Survival analysis was performed with the outcomes of interest being death and HF with a follow-up time of 12 years. Sub-group analysis according to sex and type of diabetes was also performed for the HF outcome.

Results

6,460 deaths were recorded, of which 567 were amongst those with diabetes. Additionally, HF was diagnosed in 2,772 individuals (446 with diabetes). A multivariable Cox proportional hazard analysis showed that there was an increased risk of death and HF (hazard ratio (HR) of 1.73 [1.58-1.89] and 2.12 [1.91-2.36], respectively) when comparing those with diabetes and those without. The HR for HF was 6.72 [2.75-16.41] for women with T1DM vs. 5.80 [2.72-12.37] for men with T1DM, but the interaction term for sex differences was insignificant (p for interaction 0.45). There was no significant difference in the relative risk of HF between men and women when both types of diabetes were combined (HR 2.22 [1.93-2.54] vs. 1.99 [1.67-2.38] respectively, p for interaction 0.80).

Conclusion

Diabetes is associated with increased risks of death and heart failure, and there was no difference in relative risk according to sex.",,pdf:https://www.frontiersin.org/articles/10.3389/fcvm.2023.1136764/pdf; doi:https://doi.org/10.3389/fcvm.2023.1136764; html:https://europepmc.org/articles/PMC10167048; pdf:https://europepmc.org/articles/PMC10167048?pdf=render -PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm during the COVID-19 pandemic: a repeat cross-sectional UK population survey","John A, Lee S, Solomon S, Crepaz-Keay D, McDaid S, Morton A, Davidson G, Van Bortel T, Kousoulis A.",,BMJ open,2021,2021-01-01,Y,Mental health; Public Health; Suicide & Self-harm; Covid-19,,,,,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8718341/?tool=EBI; pdf:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8718341/pdf/?tool=EBI; html:https://europepmc.org/articles/PMC8718341; pdf:https://europepmc.org/articles/PMC8718341?pdf=render +37046260,https://doi.org/10.1186/s12913-023-09363-1,Associations between the stringency of COVID-19 containment policies and health service disruptions in 10 countries.,"Reddy T, Kapoor NR, Kubota S, Doubova SV, Asai D, Mariam DH, Ayele W, Mebratie AD, Thermidor R, Sapag JC, Bedregal P, Passi-Solar Á, Gordon-Strachan G, Dulal M, Gadeka DD, Mehata S, Margozzini P, Leerapan B, Rittiphairoj T, Kaewkamjornchai P, Nega A, Awoonor-Williams JK, Kruk ME, Arsenault C.",,BMC health services research,2023,2023-04-12,Y,Health Services; Health Systems; Pandemic Response; Health System Resilience; Covid-19 Restrictions; Health Care Disruptions,,,"

Background

Disruptions in essential health services during the COVID-19 pandemic have been reported in several countries. Yet, patterns in health service disruption according to country responses remain unclear. In this paper, we investigate associations between the stringency of COVID-19 containment policies and disruptions in 31 health services in 10 low- middle- and high-income countries in 2020.

Methods

Using routine health information systems and administrative data from 10 countries (Chile, Ethiopia, Ghana, Haiti, Lao People's Democratic Republic, Mexico, Nepal, South Africa, South Korea, and Thailand) we estimated health service disruptions for the period of April to December 2020 by dividing monthly service provision at national levels by the average service provision in the 15 months pre-COVID (January 2019-March 2020). We used the Oxford COVID-19 Government Response Tracker (OxCGRT) index and multi-level linear regression analyses to assess associations between the stringency of restrictions and health service disruptions over nine months. We extended the analysis by examining associations between 11 individual containment or closure policies and health service disruptions. Models were adjusted for COVID caseload, health service category and country GDP and included robust standard errors.

Findings

Chronic disease care was among the most affected services. Regression analyses revealed that a 10% increase in the mean stringency index was associated with a 3.3 percentage-point (95% CI -3.9, -2.7) reduction in relative service volumes. Among individual policies, curfews, and the presence of a state of emergency, had the largest coefficients and were associated with 14.1 (95% CI -19.6, 8.7) and 10.7 (95% CI -12.7, -8.7) percentage-point lower relative service volumes, respectively. In contrast, number of COVID-19 cases in 2020 was not associated with health service disruptions in any model.

Conclusions

Although containment policies were crucial in reducing COVID-19 mortality in many contexts, it is important to consider the indirect effects of these restrictions. Strategies to improve the resilience of health systems should be designed to ensure that populations can continue accessing essential health care despite the presence of containment policies during future infectious disease outbreaks.",,pdf:https://bmchealthservres.biomedcentral.com/counter/pdf/10.1186/s12913-023-09363-1; doi:https://doi.org/10.1186/s12913-023-09363-1; html:https://europepmc.org/articles/PMC10096103; pdf:https://europepmc.org/articles/PMC10096103?pdf=render 31109684,https://doi.org/10.1016/j.injury.2019.05.004,Agreement between medical record and administrative coding of common comorbidities in orthopaedic trauma patients.,"Daly S, Nguyen TQ, Gabbe BJ, Braaf S, Simpson P, Ekegren CL.",,Injury,2019,2019-05-08,N,Trauma; Comorbidity; Agreement; Orthopaedic; Icd-10-am,,,"

Objective

To i) quantify the agreement between comorbidities documented within medical records and an orthopaedic trauma dataset; and ii) compare agreement between these sources before and after the introduction of new comorbidity coding rules in Australian hospitals.

Study design and setting

A random sample of adult (≥ 16 years) orthopaedic trauma patients (n = 400) were extracted from the Victorian Orthopaedic Trauma Outcomes Registry (VOTOR). Diagnoses of obesity, arthritis, diabetes and cardiac conditions documented within patients' medical records were compared to ICD-10-AM comorbidity codes (provided by hospitals) for the same admission. Agreement was calculated (Cohen's kappa) before and after the introduction of new coding rules.

Results

All comorbidities had the same or higher prevalence in medical record data compared to coded data. Kappa values ranged from <0.001 (poor agreement) for coronary artery disease to 0.94 (excellent agreement) for type 2 diabetes. There was improvement in agreement between sources for most conditions following the introduction of new coding rules.

Conclusion

There has been improvement in the coding of certain comorbidities since the introduction of new coding rules, suggesting that, since 2015, administrative data has improved capacity to capture patients' comorbidity profiles. Consideration must be taken when using the ICD-10-AM data due to its limitations.",,doi:https://doi.org/10.1016/j.injury.2019.05.004 +PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm during the COVID-19 pandemic: a repeat cross-sectional UK population survey","John A, Lee S, Solomon S, Crepaz-Keay D, McDaid S, Morton A, Davidson G, Van Bortel T, Kousoulis A.",,BMJ open,2021,2021-01-01,Y,Mental health; Public Health; Suicide & Self-harm; Covid-19,,,,,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8718341/?tool=EBI; pdf:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8718341/pdf/?tool=EBI; html:https://europepmc.org/articles/PMC8718341; pdf:https://europepmc.org/articles/PMC8718341?pdf=render +37180793,https://doi.org/10.3389/fcvm.2023.1136764,Diabetes and heart failure associations in women and men: Results from the MORGAM consortium.,"Chadalavada S, Reinikainen J, Andersson J, Di Castelnuovo A, Iacoviello L, Jousilahti P, Kårhus LL, Linneberg A, Söderberg S, Tunstall-Pedoe H, Lekadir K, Aung N, Jensen MT, Kuulasmaa K, Niiranen TJ, Petersen SE.",,Frontiers in cardiovascular medicine,2023,2023-04-25,Y,Diabetes; Sex differences; epidemiology; Heart Failure; Morgam,,,"

Background

Diabetes and its cardiovascular complications are a growing concern worldwide. Recently, some studies have demonstrated that relative risk of heart failure (HF) is higher in women with type 1 diabetes (T1DM) than in men. This study aims to validate these findings in cohorts representing five countries across Europe.

Methods

This study includes 88,559 (51.8% women) participants, 3,281 (46.3% women) of whom had diabetes at baseline. Survival analysis was performed with the outcomes of interest being death and HF with a follow-up time of 12 years. Sub-group analysis according to sex and type of diabetes was also performed for the HF outcome.

Results

6,460 deaths were recorded, of which 567 were amongst those with diabetes. Additionally, HF was diagnosed in 2,772 individuals (446 with diabetes). A multivariable Cox proportional hazard analysis showed that there was an increased risk of death and HF (hazard ratio (HR) of 1.73 [1.58-1.89] and 2.12 [1.91-2.36], respectively) when comparing those with diabetes and those without. The HR for HF was 6.72 [2.75-16.41] for women with T1DM vs. 5.80 [2.72-12.37] for men with T1DM, but the interaction term for sex differences was insignificant (p for interaction 0.45). There was no significant difference in the relative risk of HF between men and women when both types of diabetes were combined (HR 2.22 [1.93-2.54] vs. 1.99 [1.67-2.38] respectively, p for interaction 0.80).

Conclusion

Diabetes is associated with increased risks of death and heart failure, and there was no difference in relative risk according to sex.",,pdf:https://www.frontiersin.org/articles/10.3389/fcvm.2023.1136764/pdf; doi:https://doi.org/10.3389/fcvm.2023.1136764; html:https://europepmc.org/articles/PMC10167048; pdf:https://europepmc.org/articles/PMC10167048?pdf=render 31747863,https://doi.org/10.1161/jaha.119.012551,"UVA and Seasonal Patterning of 56 370 Myocardial Infarctions Across Scotland, 2000-2011.","Mackay DF, Clemens TL, Hastie CE, Cherrie MPC, Dibben C, Pell JP.",,Journal of the American Heart Association,2019,2019-11-21,Y,Environmental factors; UV radiation; Myocardial infarction; epidemiology,"Improving Public Health, Understanding the Causes of Disease",,"Background Myocardial infarction exhibits seasonal patterning, with higher amplitude at increased latitude. Epidemiological evidence suggests that sunlight is protective against cardiovascular disease, independent of ambient temperature, but ultraviolet B-mediated vitamin D production has been discounted as causal. We aimed to determine whether ultraviolet A is associated with the seasonal patterning of myocardial infarction. Methods and Results Routine hospitalization data were used to determine monthly incidence of myocardial infarction in Scotland between 2000 and 2011. Small-area-level aggregated data were obtained on ambient temperature from the Meteorological Office and ultraviolet A and ultraviolet B irradiance from NASA satellites. Autoregressive distributed lag models were run for ultraviolet A and myocardial infarction, including adjustment for ambient temperature and ultraviolet B. Monthly incidence of myocardial infarction displayed winter peaks and summer troughs superimposed on the underlying trend, with a mean amplitude of 0.31 (95% CI: 0.21, 0.41) myocardial infarctions per 100 000 population per month. Ultraviolet A exposure was inversely associated with myocardial infarction independent of ambient temperature (coefficient, -0.05; 95% CI, -0.09, -0.01; P=0.015) and ultraviolet B UVB (coefficient, -0.05; 95% CI, -0.09, -0.02; P=0.004). Conclusions Further research is required to explore whether an ultraviolet-mediated mechanism different to vitamin D, such as nitric oxide-mediated vasodilatation, may play a causal role in the seasonal and geographical patterning of myocardial infarction.",,doi:https://doi.org/10.1161/jaha.119.012551; doi:https://doi.org/10.1161/JAHA.119.012551; html:https://europepmc.org/articles/PMC6912961; pdf:https://europepmc.org/articles/PMC6912961?pdf=render 34688720,https://doi.org/10.1016/j.ijcard.2021.10.029,Methodological issues in meta-analyses of real-world clinical data to infer causality.,"Uijl A, Lund LH, Asselbergs FW, Savarese G.",,International journal of cardiology,2021,2021-10-22,N,Meta-analysis; Causality; Observational; Sacubitril/valsartan,,,,,doi:https://doi.org/10.1016/j.ijcard.2021.10.029 35802687,https://doi.org/10.1371/journal.pone.0270668,"Association between tocilizumab, sarilumab and all-cause mortality at 28 days in hospitalised patients with COVID-19: A network meta-analysis.","Godolphin PJ, Fisher DJ, Berry LR, Derde LPG, Diaz JV, Gordon AC, Lorenzi E, Marshall JC, Murthy S, Shankar-Hari M, Sterne JAC, Tierney JF, Vale CL.",,PloS one,2022,2022-07-08,Y,,,,"

Background

A recent prospective meta-analysis demonstrated that interleukin-6 antagonists are associated with lower all-cause mortality in hospitalised patients with COVID-19, compared with usual care or placebo. However, emerging evidence suggests that clinicians are favouring the use of tocilizumab over sarilumab. A new randomised comparison of these agents from the REMAP-CAP trial shows similar effects on in-hospital mortality. Therefore, we initiated a network meta-analysis, to estimate pairwise associations between tocilizumab, sarilumab and usual care or placebo with 28-day mortality, in COVID-19 patients receiving concomitant corticosteroids and ventilation, based on all available direct and indirect evidence.

Methods

Eligible trials randomised hospitalised patients with COVID-19 that compared tocilizumab or sarilumab with usual care or placebo in the prospective meta-analysis or that directly compared tocilizumab with sarilumab. Data were restricted to patients receiving corticosteroids and either non-invasive or invasive ventilation at randomisation. Pairwise associations between tocilizumab, sarilumab and usual care or placebo for all-cause mortality 28 days after randomisation were estimated using a frequentist contrast-based network meta-analysis of odds ratios (ORs), implementing multivariate fixed-effects models that assume consistency between the direct and indirect evidence.

Findings

One trial (REMAP-CAP) was identified that directly compared tocilizumab with sarilumab and supplied results on all-cause mortality at 28-days. This network meta-analysis was based on 898 eligible patients (278 deaths) from REMAP-CAP and 3710 eligible patients from 18 trials (1278 deaths) from the prospective meta-analysis. Summary ORs were similar for tocilizumab [0·82 [0·71-0·95, p = 0·008]] and sarilumab [0·80 [0·61-1·04, p = 0·09]] compared with usual care or placebo. The summary OR for 28-day mortality comparing tocilizumab with sarilumab was 1·03 [95%CI 0·81-1·32, p = 0·80]. The p-value for the global test of inconsistency was 0·28.

Conclusions

Administration of either tocilizumab or sarilumab was associated with lower 28-day all-cause mortality compared with usual care or placebo. The association is not dependent on the choice of interleukin-6 receptor antagonist.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0270668&type=printable; doi:https://doi.org/10.1371/journal.pone.0270668; html:https://europepmc.org/articles/PMC9269978; pdf:https://europepmc.org/articles/PMC9269978?pdf=render @@ -1572,23 +1572,23 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 32709646,https://doi.org/10.1136/bmjopen-2019-036099,"Predicting the risk of asthma attacks in children, adolescents and adults: protocol for a machine learning algorithm derived from a primary care-based retrospective cohort.","Hussain Z, Shah SA, Mukherjee M, Sheikh A.",,BMJ open,2020,2020-07-23,Y,Asthma; epidemiology; Public Health; Health Informatics,,,"

Introduction

Most asthma attacks and subsequent deaths are potentially preventable. We aim to develop a prognostic tool for identifying patients at high risk of asthma attacks in primary care by leveraging advances in machine learning.

Methods and analysis

Current prognostic tools use logistic regression to develop a risk scoring model for asthma attacks. We propose to build on this by systematically applying various well-known machine learning techniques to a large longitudinal deidentified primary care database, the Optimum Patient Care Research Database, and comparatively evaluate their performance with the existing logistic regression model and against each other. Machine learning algorithms vary in their predictive abilities based on the dataset and the approach to analysis employed. We will undertake feature selection, classification (both one-class and two-class classifiers) and performance evaluation. Patients who have had actively treated clinician-diagnosed asthma, aged 8-80 years and with 3 years of continuous data, from 2016 to 2018, will be selected. Risk factors will be obtained from the first year, while the next 2 years will form the outcome period, in which the primary endpoint will be the occurrence of an asthma attack.

Ethics and dissemination

We have obtained approval from OPCRD's Anonymous Data Ethics Protocols and Transparency (ADEPT) Committee. We will seek ethics approval from The University of Edinburgh's Research Ethics Group (UREG). We aim to present our findings at scientific conferences and in peer-reviewed journals.",,pdf:https://bmjopen.bmj.com/content/bmjopen/10/7/e036099.full.pdf; doi:https://doi.org/10.1136/bmjopen-2019-036099; html:https://europepmc.org/articles/PMC7380838; pdf:https://europepmc.org/articles/PMC7380838?pdf=render 35916366,https://doi.org/10.7554/elife.76272,Integrated analyses of growth differentiation factor-15 concentration and cardiometabolic diseases in humans.,"Lemmelä S, Wigmore EM, Benner C, Havulinna AS, Ong RMY, Kempf T, Wollert KC, Blankenberg S, Zeller T, Peters JE, Salomaa V, Fritsch M, March R, Palotie A, Daly M, Butterworth AS, Kinnunen M, Paul DS, Matakidou A.",,eLife,2022,2022-08-02,Y,Human; Genetics; Obesity; Genomics; BMI; epidemiology; Causality; Global Health; Gdf15; Mendelian Randomisation,,,"Growth differentiation factor-15 (GDF15) is a stress response cytokine that is elevated in several cardiometabolic diseases and has attracted interest as a potential therapeutic target. To further explore the association of GDF15 with human disease, we conducted a broad study into the phenotypic and genetic correlates of GDF15 concentration in up to 14,099 individuals. Assessment of 772 traits across 6610 participants in FINRISK identified associations of GDF15 concentration with a range of phenotypes including all-cause mortality, cardiometabolic disease, respiratory diseases and psychiatric disorders, as well as inflammatory markers. A meta-analysis of genome-wide association studies (GWAS) of GDF15 concentration across three different assay platforms (n=14,099) confirmed significant heterogeneity due to a common missense variant (rs1058587; p.H202D) in GDF15, potentially due to epitope-binding artefacts. After conditioning on rs1058587, statistical fine mapping identified four independent putative causal signals at the locus. Mendelian randomisation (MR) analysis found evidence of a causal relationship between GDF15 concentration and high-density lipoprotein (HDL) but not body mass index (BMI). Using reverse MR, we identified a potential causal association of BMI on GDF15 (IVW pFDR = 0.0040). Taken together, our data derived from human population cohorts do not support a role for moderately elevated GDF15 concentrations as a causal factor in human cardiometabolic disease but support its role as a biomarker of metabolic stress.",,doi:https://doi.org/10.7554/elife.76272; doi:https://doi.org/10.7554/eLife.76272; html:https://europepmc.org/articles/PMC9391041; pdf:https://europepmc.org/articles/PMC9391041?pdf=render 34870256,https://doi.org/10.1016/j.lanepe.2021.100267,Optimising health and economic impacts of COVID-19 vaccine prioritisation strategies in the WHO European Region: a mathematical modelling study.,"Liu Y, Sandmann FG, Barnard RC, Pearson CAB, Pastore R, Pebody R, Flasche S, Jit M.",,The Lancet regional health. Europe,2022,2021-11-30,Y,Europe; Health Economics; Mathematical Modelling; Policy Evaluation; Vaccine Policy; Multicountry Analysis; Covid-19,,,"

Background

Countries in the World Health Organization (WHO) European Region differ in terms of the COVID-19 vaccine supply conditions. We evaluated the health and economic impact of different age-based vaccine prioritisation strategies across this demographically and socio-economically diverse region.

Methods

We fitted age-specific compartmental models to the reported daily COVID-19 mortality in 2020 to inform the immunity level before vaccine roll-out. Models capture country-specific differences in population structures, contact patterns, epidemic history, life expectancy, and GDP per capita.We examined four strategies that prioritise: all adults (V+), younger (20-59 year-olds) followed by older adults (60+) (V20), older followed by younger adults (V60), and the oldest adults (75+) (V75) followed by incrementally younger age groups. We explored four roll-out scenarios (R1-4) - the slowest scenario (R1) reached 30% coverage by December 2022 and the fastest (R4) 80% by December 2021. Five decision-making metrics were summarised over 2021-22: mortality, morbidity, and losses in comorbidity-adjusted life expectancy, comorbidity- and quality-adjusted life years, and human capital. Six vaccine profiles were tested - the highest performing vaccine has 95% efficacy against both infection and disease, and the lowest 50% against diseases and 0% against infection.

Findings

Of the 20 decision-making metrics and roll-out scenario combinations, the same optimal strategy applied to all countries in only one combination; V60 was more or similarly desirable than V75 in 19 combinations. Of the 38 countries with fitted models, 11-37 countries had variable optimal strategies by decision-making metrics or roll-out scenarios. There are greater benefits in prioritising older adults when roll-out is slow and when vaccine profiles are less favourable.

Interpretation

The optimal age-based vaccine prioritisation strategies were sensitive to country characteristics, decision-making metrics, and roll-out speeds. A prioritisation strategy involving more age-based stages (V75) does not necessarily lead to better health and economic outcomes than targeting broad age groups (V60). Countries expecting a slow vaccine roll-out may particularly benefit from prioritising older adults.

Funding

World Health Organization, Bill and Melinda Gates Foundation, the Medical Research Council (United Kingdom), the National Institute of Health Research (United Kingdom), the European Commission, the Foreign, Commonwealth and Development Office (United Kingdom), Wellcome Trust.",,doi:https://doi.org/10.1016/j.lanepe.2021.100267; doi:https://doi.org/10.1016/j.lanepe.2021.100267; html:https://europepmc.org/articles/PMC8629724; pdf:https://europepmc.org/articles/PMC8629724?pdf=render -38479550,https://doi.org/10.1016/j.ajcnut.2024.03.006,Dietary intake of plant- and animal-derived protein and incident cardiovascular diseases: the pan-European EPIC-CVD case-cohort study.,"Zheng JS, Steur M, Imamura F, Freisling H, Johnson L, van der Schouw YT, Tong TY, Weiderpass E, Bajracharya R, Crous-Bou M, Dahm CC, Heath AK, Ibsen DB, Jannasch F, Katzke V, Masala G, Moreno-Iribas C, Sacerdote C, Schulze MB, Sieri S, Wareham NJ, Danesh J, Butterworth AS, Forouhi NG.",,The American journal of clinical nutrition,2024,2024-03-11,Y,Cardiovascular disease; Stroke; ischemic heart disease; Plant-derived Protein; Animal-derived Protein,,,"

Background

Epidemiological evidence suggests that a potential association between dietary protein intake and cardiovascular disease (CVD) may depend on the protein source, that is, plant- or animal-derived, but past research was limited and inconclusive.

Objectives

To evaluate the association of dietary plant- or animal-derived protein consumption with risk of CVD, and its components ischemic heart disease (IHD) and stroke.

Methods

This analysis in the European Prospective Investigation into Cancer and Nutrition (EPIC)-CVD case-cohort study included 16,244 incident CVD cases (10,784 IHD and 6423 stroke cases) and 15,141 subcohort members from 7 European countries. We investigated the association of estimated dietary protein intake with CVD, IHD, and stroke (total, fatal, and nonfatal) using multivariable-adjusted Prentice-weighted Cox regression. We estimated isocaloric substitutions of replacing fats and carbohydrates with plant- or animal-derived protein and replacing food-specific animal protein with plant protein. Multiplicative interactions between dietary protein and prespecified variables were tested.

Results

Neither plant- nor animal-derived protein intake was associated with incident CVD, IHD, or stroke in adjusted analyses without or with macronutrient-specified substitution analyses. Higher plant-derived protein intake was associated with 22% lower total stroke incidence among never smokers [HR 0.78, 95% confidence intervals (CI): 0.62, 0.99], but not among current smokers (HR 1.08, 95% CI: 0.83, 1.40, P-interaction = 0.004). Moreover, higher plant-derived protein (per 3% total energy) when replacing red meat protein (HR 0.52, 95% CI: 0.31, 0.88), processed meat protein (HR 0.39, 95% CI: 0.17, 0.90), and dairy protein (HR 0.54, 95% CI: 0.30, 0.98) was associated with lower incidence of fatal stroke.

Conclusion

Plant- or animal-derived protein intake was not associated with overall CVD. However, the association of plant-derived protein consumption with lower total stroke incidence among nonsmokers, and with lower incidence of fatal stroke highlights the importance of investigating CVD subtypes and potential interactions. These observations warrant further investigation in diverse populations with varying macronutrient intakes and dietary patterns.",,doi:https://doi.org/10.1016/j.ajcnut.2024.03.006; doi:https://doi.org/10.1016/j.ajcnut.2024.03.006; html:https://europepmc.org/articles/PMC11130694; pdf:https://europepmc.org/articles/PMC11130694?pdf=render 35477354,https://doi.org/10.1186/s12877-022-03077-5,Performance of the SarQoL quality of life tool in a UK population of older people with probable sarcopenia and implications for use in clinical trials: findings from the SarcNet registry.,"Witham MD, Heslop P, Dodds RM, Clegg AP, Hope SV, McDonald C, Smithard D, Storey B, Tan AL, Thornhill A, Sayer AA.",,BMC geriatrics,2022,2022-04-27,Y,Quality of life; Validity; Sarcopenia; Responsiveness; Minimum Clinical Important Difference,,,"

Background

The Sarcopenia Quality of Life (SarQoL) questionnaire is a disease-specific sarcopenia quality of life tool. We aimed to independently assess SarQoL with a particular focus on its suitability as a clinical trial outcome measure.

Methods

We analysed data from the UK Sarcopenia Network and Registry. Measures of physical performance and lean mass were collected at baseline. SarQoL and the Strength, Assistance, Rise, Climb - Falls (SARC-F) questionnaire (to assess functional ability) were collected at both baseline and six-month follow-up. Global changes in fitness and quality of life at 6 months were elicited on seven-point Likert scales. Internal consistency was assessed using Cronbach's alpha. Responsiveness (Cohen's d and Guyatt coefficients) and minimum clinically important differences were calculated for participants reporting slight improvement or worsening in their global scores. Concurrent validity was assessed by correlating baseline SarQoL scores with measures of physical performance and functional ability.

Results

We analysed data from 147 participants, 125 of whom underwent follow up assessment; mean age 78 years; 72 (49%) were women. Internal consistency was good; Cronbach's alpha was 0.944 at baseline and 0.732 at telephone follow-up. Correlation between baseline and follow-up SarQoL was weak (r = 0.27; p = 0.03). The minimum clinically important improvement ranged from 5 to 21 points giving trial sample size estimates of 25-100 participants. SarQoL scores were moderately correlated with handgrip (r = 0.37; p < 0.001), SARC-F (r = - 0.45; p < 0.001), short physical performance battery (r = 0.48; p < 0.001) and 4-m walk speed (r = 0.48; p < 0.001).

Conclusions

SarQoL has acceptable performance in older UK participants with probable sarcopenia and is sufficiently responsive for use in clinical trials for sarcopenia.",,pdf:https://bmcgeriatr.biomedcentral.com/track/pdf/10.1186/s12877-022-03077-5; doi:https://doi.org/10.1186/s12877-022-03077-5; html:https://europepmc.org/articles/PMC9043890; pdf:https://europepmc.org/articles/PMC9043890?pdf=render +38479550,https://doi.org/10.1016/j.ajcnut.2024.03.006,Dietary intake of plant- and animal-derived protein and incident cardiovascular diseases: the pan-European EPIC-CVD case-cohort study.,"Zheng JS, Steur M, Imamura F, Freisling H, Johnson L, van der Schouw YT, Tong TY, Weiderpass E, Bajracharya R, Crous-Bou M, Dahm CC, Heath AK, Ibsen DB, Jannasch F, Katzke V, Masala G, Moreno-Iribas C, Sacerdote C, Schulze MB, Sieri S, Wareham NJ, Danesh J, Butterworth AS, Forouhi NG.",,The American journal of clinical nutrition,2024,2024-03-11,Y,Cardiovascular disease; Stroke; ischemic heart disease; Plant-derived Protein; Animal-derived Protein,,,"

Background

Epidemiological evidence suggests that a potential association between dietary protein intake and cardiovascular disease (CVD) may depend on the protein source, that is, plant- or animal-derived, but past research was limited and inconclusive.

Objectives

To evaluate the association of dietary plant- or animal-derived protein consumption with risk of CVD, and its components ischemic heart disease (IHD) and stroke.

Methods

This analysis in the European Prospective Investigation into Cancer and Nutrition (EPIC)-CVD case-cohort study included 16,244 incident CVD cases (10,784 IHD and 6423 stroke cases) and 15,141 subcohort members from 7 European countries. We investigated the association of estimated dietary protein intake with CVD, IHD, and stroke (total, fatal, and nonfatal) using multivariable-adjusted Prentice-weighted Cox regression. We estimated isocaloric substitutions of replacing fats and carbohydrates with plant- or animal-derived protein and replacing food-specific animal protein with plant protein. Multiplicative interactions between dietary protein and prespecified variables were tested.

Results

Neither plant- nor animal-derived protein intake was associated with incident CVD, IHD, or stroke in adjusted analyses without or with macronutrient-specified substitution analyses. Higher plant-derived protein intake was associated with 22% lower total stroke incidence among never smokers [HR 0.78, 95% confidence intervals (CI): 0.62, 0.99], but not among current smokers (HR 1.08, 95% CI: 0.83, 1.40, P-interaction = 0.004). Moreover, higher plant-derived protein (per 3% total energy) when replacing red meat protein (HR 0.52, 95% CI: 0.31, 0.88), processed meat protein (HR 0.39, 95% CI: 0.17, 0.90), and dairy protein (HR 0.54, 95% CI: 0.30, 0.98) was associated with lower incidence of fatal stroke.

Conclusion

Plant- or animal-derived protein intake was not associated with overall CVD. However, the association of plant-derived protein consumption with lower total stroke incidence among nonsmokers, and with lower incidence of fatal stroke highlights the importance of investigating CVD subtypes and potential interactions. These observations warrant further investigation in diverse populations with varying macronutrient intakes and dietary patterns.",,doi:https://doi.org/10.1016/j.ajcnut.2024.03.006; doi:https://doi.org/10.1016/j.ajcnut.2024.03.006; html:https://europepmc.org/articles/PMC11130694; pdf:https://europepmc.org/articles/PMC11130694?pdf=render 36722341,https://doi.org/10.1093/cei/uxad008,Practical challenges for functional validation of STAT1 gain of function genetic variants.,"Albuquerque AS, Maimaris J, McKenna AJ, Lambourne J, Moreira F, Workman S, Megy K, Simeoni I, Lango Allen H, NIHR BioResource-Rare Disease Consortium, Morris EC, Burns SO.",,Clinical and experimental immunology,2023,2023-04-01,Y,Flow cytometry; STAT1; Primary Immunodeficiency; Gain Of Function; Chronic Mucocutaneous Candidiasis; Variants Of Unknown Significance,,,,,pdf:https://academic.oup.com/cei/advance-article-pdf/doi/10.1093/cei/uxad008/49549101/uxad008.pdf; doi:https://doi.org/10.1093/cei/uxad008; html:https://europepmc.org/articles/PMC10128160; pdf:https://europepmc.org/articles/PMC10128160?pdf=render 33148619,https://doi.org/10.1136/bmj.m3919,Consistency of variety of machine learning and statistical models in predicting clinical risks of individual patients: longitudinal cohort study using cardiovascular disease as exemplar.,"Li Y, Li Y, Sperrin M, Ashcroft DM, van Staa TP.",,BMJ (Clinical research ed.),2020,2020-11-04,Y,,,,"

Objective

To assess the consistency of machine learning and statistical techniques in predicting individual level and population level risks of cardiovascular disease and the effects of censoring on risk predictions.

Design

Longitudinal cohort study from 1 January 1998 to 31 December 2018.

Setting and participants

3.6 million patients from the Clinical Practice Research Datalink registered at 391 general practices in England with linked hospital admission and mortality records.

Main outcome measures

Model performance including discrimination, calibration, and consistency of individual risk prediction for the same patients among models with comparable model performance. 19 different prediction techniques were applied, including 12 families of machine learning models (grid searched for best models), three Cox proportional hazards models (local fitted, QRISK3, and Framingham), three parametric survival models, and one logistic model.

Results

The various models had similar population level performance (C statistics of about 0.87 and similar calibration). However, the predictions for individual risks of cardiovascular disease varied widely between and within different types of machine learning and statistical models, especially in patients with higher risks. A patient with a risk of 9.5-10.5% predicted by QRISK3 had a risk of 2.9-9.2% in a random forest and 2.4-7.2% in a neural network. The differences in predicted risks between QRISK3 and a neural network ranged between -23.2% and 0.1% (95% range). Models that ignored censoring (that is, assumed censored patients to be event free) substantially underestimated risk of cardiovascular disease. Of the 223 815 patients with a cardiovascular disease risk above 7.5% with QRISK3, 57.8% would be reclassified below 7.5% when using another model.

Conclusions

A variety of models predicted risks for the same patients very differently despite similar model performances. The logistic models and commonly used machine learning models should not be directly applied to the prediction of long term risks without considering censoring. Survival models that consider censoring and that are explainable, such as QRISK3, are preferable. The level of consistency within and between models should be routinely assessed before they are used for clinical decision making.",,pdf:https://www.bmj.com/content/bmj/371/bmj.m3919.full.pdf; doi:https://doi.org/10.1136/bmj.m3919; html:https://europepmc.org/articles/PMC7610202 35087703,https://doi.org/10.5334/aogh.3465,Household Air Pollution and Respiratory Symptoms a Month Before and During the Stringent COVID-19 Lockdown Levels 5 and 4 in South Africa.,"Wright CY, Kapwata T, Abdelatif N, Batini C, Wernecke B, Kunene Z, Millar DA, Mathee A, Street R, Panchal R, Hansell A, Cordell R, Hey JV.",,Annals of global health,2022,2022-01-10,Y,,,,"

Background

Household air pollution (HAP) is associated with adverse human health impacts. During COVID-19 Lockdown Levels 5 and 4 (the most stringent levels), South Africans remained at home, potentially increasing their exposure to HAP.

Objectives

To investigate changes in fuel use behaviours/patterns of use affecting HAP exposure and associated HAP-related respiratory health outcomes during COVID-19 Lockdown Levels 5 and 4.

Methods

This was a cross-sectional online and telephonic survey of participants from an existing database. Logistic regression and McNemar's test were used to analyse household-level data.

Results

Among 2 505 participants, while electricity was the main energy source for cooking and heating the month before and during Lockdown Levels 5 and 4, some households used less electricity during Lockdown Levels 5 and 4 or switched to ""dirty fuels."" One third of participants reported presence of environmental tobacco smoke in the home, a source of HAP associated with respiratory illnesses. Prevalence of HAP-related respiratory health outcomes were <10% (except dry cough). Majority of households reported cooking more, cleaning more and spending more time indoors during Lockdown Levels 5 and 4 - potentially exposed to HAP.

Conclusion

Should South Africa return to Lockdown Levels 5 or 4, awareness raising about the risks associated with HAP as well as messaging information for prevention of exposure to HAP, including environmental tobacco smoke, and associated adverse health impacts will be necessary.",,pdf:http://www.annalsofglobalhealth.org/articles/10.5334/aogh.3465/galley/3414/download/; doi:https://doi.org/10.5334/aogh.3465; html:https://europepmc.org/articles/PMC8757382; pdf:https://europepmc.org/articles/PMC8757382?pdf=render -37422075,https://doi.org/10.1016/j.jval.2023.06.019,Perspectives on Patient-Reported Outcome Data After Treatment Discontinuation in Cancer Clinical Trials.,"King-Kallimanis BL, Calvert M, Cella D, Cocks K, Coens C, Fairclough D, Howie L, Jonsson P, Mahendraratnam N, Maues J, Sarac S, Shaw J, Stigger N, Trask P, Wieseler B.",,Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research,2023,2023-07-06,N,Oncology; Clinical Trials; Patient-reported Outcomes; Multistakeholder Perspective,,,"

Objectives

Patient-reported outcome (PRO) data are critical in understanding treatments from the patient perspective in cancer clinical trials. The potential benefits and methodological approaches to the collection of PRO data after treatment discontinuation (eg, because of progressive disease or unacceptable drug toxicity) are less clear. The purpose of this article is to describe the Food and Drug Administration's Oncology Center of Excellence and the Critical Path Institute cosponsored 2-hour virtual roundtable, held in 2020, to discuss this specific issue.

Methods

We summarize key points from this discussion with 16 stakeholders representing academia, clinical practice, patients, international regulatory agencies, health technology assessment bodies/payers, industry, and PRO instrument development.

Results

Stakeholders recognized that any PRO data collection after treatment discontinuation should have clearly defined objectives to ensure that data can be analyzed and reported.

Conclusions

Data collection after discontinuation without a justification for its use wastes patients' time and effort and is unethical.",,doi:https://doi.org/10.1016/j.jval.2023.06.019 32234121,https://doi.org/10.2807/1560-7917.es.2020.25.12.2000256,"Estimating the infection and case fatality ratio for coronavirus disease (COVID-19) using age-adjusted data from the outbreak on the Diamond Princess cruise ship, February 2020.","Russell TW, Hellewell J, Jarvis CI, van Zandvoort K, Abbott S, Ratnayake R, CMMID COVID-19 working group, Flasche S, Eggo RM, Edmunds WJ, Kucharski AJ.",,Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin,2020,2020-03-01,Y,Coronavirus; outbreak; Severity; Asymptomatic; Case Fatality Ratio; Cruise Ship; Covid-19; Infection Fatality Ratio,"COVID-19, Improving Public Health","COVID-19, infection","Adjusting for delay from confirmation to death, we estimated case and infection fatality ratios (CFR, IFR) for coronavirus disease (COVID-19) on the Diamond Princess ship as 2.6% (95% confidence interval (CI): 0.89-6.7) and 1.3% (95% CI: 0.38-3.6), respectively. Comparing deaths on board with expected deaths based on naive CFR estimates from China, we estimated CFR and IFR in China to be 1.2% (95% CI: 0.3-2.7) and 0.6% (95% CI: 0.2-1.3), respectively.",,pdf:https://www.eurosurveillance.org/deliver/fulltext/eurosurveillance/25/12/eurosurv-25-12-3.pdf?itemId=%2Fcontent%2F10.2807%2F1560-7917.ES.2020.25.12.2000256&mimeType=pdf&containerItemId=content/eurosurveillance; doi:https://doi.org/10.2807/1560-7917.ES.2020.25.12.2000256; html:https://europepmc.org/articles/PMC7118348; pdf:https://europepmc.org/articles/PMC7118348?pdf=render +37422075,https://doi.org/10.1016/j.jval.2023.06.019,Perspectives on Patient-Reported Outcome Data After Treatment Discontinuation in Cancer Clinical Trials.,"King-Kallimanis BL, Calvert M, Cella D, Cocks K, Coens C, Fairclough D, Howie L, Jonsson P, Mahendraratnam N, Maues J, Sarac S, Shaw J, Stigger N, Trask P, Wieseler B.",,Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research,2023,2023-07-06,N,Oncology; Clinical Trials; Patient-reported Outcomes; Multistakeholder Perspective,,,"

Objectives

Patient-reported outcome (PRO) data are critical in understanding treatments from the patient perspective in cancer clinical trials. The potential benefits and methodological approaches to the collection of PRO data after treatment discontinuation (eg, because of progressive disease or unacceptable drug toxicity) are less clear. The purpose of this article is to describe the Food and Drug Administration's Oncology Center of Excellence and the Critical Path Institute cosponsored 2-hour virtual roundtable, held in 2020, to discuss this specific issue.

Methods

We summarize key points from this discussion with 16 stakeholders representing academia, clinical practice, patients, international regulatory agencies, health technology assessment bodies/payers, industry, and PRO instrument development.

Results

Stakeholders recognized that any PRO data collection after treatment discontinuation should have clearly defined objectives to ensure that data can be analyzed and reported.

Conclusions

Data collection after discontinuation without a justification for its use wastes patients' time and effort and is unethical.",,doi:https://doi.org/10.1016/j.jval.2023.06.019 32814581,https://doi.org/10.1186/s12916-020-01687-7,Seasonal influenza vaccination in Kenya: an economic evaluation using dynamic transmission modelling.,"Dawa J, Emukule GO, Barasa E, Widdowson MA, Anzala O, van Leeuwen E, Baguelin M, Chaves SS, Eggo RM.",,BMC medicine,2020,2020-08-20,Y,Economic evaluation; Influenza vaccine; Cost-effectiveness; Low- And Middle-income Countries; Dynamic Transmission Model; Vaccine Timing; Vaccine Target Group,,,"

Background

There is substantial burden of seasonal influenza in Kenya, which led the government to consider introducing a national influenza vaccination programme. Given the cost implications of a nationwide programme, local economic evaluation data are needed to inform policy on the design and benefits of influenza vaccination. We set out to estimate the cost-effectiveness of seasonal influenza vaccination in Kenya.

Methods

We fitted an age-stratified dynamic transmission model to active surveillance data from patients with influenza from 2010 to 2018. Using a societal perspective, we developed a decision tree cost-effectiveness model and estimated the incremental cost-effectiveness ratio (ICER) per disability-adjusted life year (DALY) averted for three vaccine target groups: children 6-23 months (strategy I), 2-5 years (strategy II) and 6-14 years (strategy III) with either the Southern Hemisphere influenza vaccine (Strategy A) or Northern Hemisphere vaccine (Strategy B) or both (Strategy C: twice yearly vaccination campaigns, or Strategy D: year-round vaccination campaigns). We assessed cost-effectiveness by calculating incremental net monetary benefits (INMB) using a willingness-to-pay (WTP) threshold of 1-51% of the annual gross domestic product per capita ($17-$872).

Results

The mean number of infections across all ages was 2-15 million per year. When vaccination was well timed to influenza activity, the annual mean ICER per DALY averted for vaccinating children 6-23 months ranged between $749 and $1385 for strategy IA, $442 and $1877 for strategy IB, $678 and $4106 for strategy IC and $1147 and $7933 for strategy ID. For children 2-5 years, it ranged between $945 and $1573 for strategy IIA, $563 and $1869 for strategy IIB, $662 and $4085 for strategy IIC, and $1169 and $7897 for strategy IID. For children 6-14 years, it ranged between $923 and $3116 for strategy IIIA, $1005 and $2223 for strategy IIIB, $883 and $4727 for strategy IIIC and $1467 and $6813 for strategy IIID. Overall, no vaccination strategy was cost-effective at the minimum ($17) and median ($445) WTP thresholds. Vaccinating children 6-23 months once a year had the highest mean INMB value at $872 (WTP threshold upper limit); however, this strategy had very low probability of the highest net benefit.

Conclusion

Vaccinating children 6-23 months once a year was the most favourable vaccination option; however, the strategy is unlikely to be cost-effective given the current WTP thresholds.",,pdf:https://bmcmedicine.biomedcentral.com/track/pdf/10.1186/s12916-020-01687-7; doi:https://doi.org/10.1186/s12916-020-01687-7; html:https://europepmc.org/articles/PMC7438179; pdf:https://europepmc.org/articles/PMC7438179?pdf=render 32478737,https://doi.org/10.3791/60794,Implementation of a Real-Time Psychosis Risk Detection and Alerting System Based on Electronic Health Records using CogStack.,"Wang T, Oliver D, Msosa Y, Colling C, Spada G, Roguski Ł, Folarin A, Stewart R, Roberts A, Dobson RJB, Fusar-Poli P.",,Journal of visualized experiments : JoVE,2020,2020-05-15,N,,,,"Recent studies have shown that an automated, lifespan-inclusive, transdiagnostic, and clinically based, individualized risk calculator provides a powerful system for supporting the early detection of individuals at-risk of psychosis at a large scale, by leveraging electronic health records (EHRs). This risk calculator has been externally validated twice and is undergoing feasibility testing for clinical implementation. Integration of this risk calculator in clinical routine should be facilitated by prospective feasibility studies, which are required to address pragmatic challenges, such as missing data, and the usability of this risk calculator in a real-world and routine clinical setting. Here, we present an approach for a prospective implementation of a real-time psychosis risk detection and alerting service in a real-world EHR system. This method leverages the CogStack platform, which is an open-source, lightweight, and distributed information retrieval and text extraction system. The CogStack platform incorporates a set of services that allow for full-text search of clinical data, lifespan-inclusive, real-time calculation of psychosis risk, early risk-alerting to clinicians, and the visual monitoring of patients over time. Our method includes: 1) ingestion and synchronization of data from multiple sources into the CogStack platform, 2) implementation of a risk calculator, whose algorithm was previously developed and validated, for timely computation of a patient's risk of psychosis, 3) creation of interactive visualizations and dashboards to monitor patients' health status over time, and 4) building automated alerting systems to ensure that clinicians are notified of patients at-risk, so that appropriate actions can be pursued. This is the first ever study that has developed and implemented a similar detection and alerting system in clinical routine for early detection of psychosis.",,pdf:https://www.jove.com/pdf/60794/implementation-real-time-psychosis-risk-detection-alerting-system; doi:https://doi.org/10.3791/60794; html:https://europepmc.org/articles/PMC7272223; pdf:https://europepmc.org/articles/PMC7272223?pdf=render; doi:https://doi.org/10.3791/60794 33905476,https://doi.org/10.1093/cid/ciab192,Model-Based Geostatistical Methods Enable Efficient Design and Analysis of Prevalence Surveys for Soil-Transmitted Helminth Infection and Other Neglected Tropical Diseases.,"Johnson O, Fronterre C, Amoah B, Montresor A, Giorgi E, Midzi N, Mutsaka-Makuvaza MJ, Kargbo-Labor I, Hodges MH, Zhang Y, Okoyo C, Mwandawiro C, Minnery M, Diggle PJ.",,Clinical infectious diseases : an official publication of the Infectious Diseases Society of America,2021,2021-06-01,Y,Geospatial Analysis; Prevalence Survey; Soil-transmitted Helminth Infection; Model-based Geostatistics; Control Of Neglected Tropical Diseases; Impact Survey,,,"Maps of the geographical variation in prevalence play an important role in large-scale programs for the control of neglected tropical diseases. Precontrol mapping is needed to establish the appropriate control intervention in each area of the country in question. Mapping is also needed postintervention to measure the success of control efforts. In the absence of comprehensive disease registries, mapping efforts can be informed by 2 kinds of data: empirical estimates of local prevalence obtained by testing individuals from a sample of communities within the geographical region of interest, and digital images of environmental factors that are predictive of local prevalence. In this article, we focus on the design and analysis of impact surveys, that is, prevalence surveys that are conducted postintervention with the aim of informing decisions on what further intervention, if any, is needed to achieve elimination of the disease as a public health problem. We show that geospatial statistical methods enable prevalence surveys to be designed and analyzed as efficiently as possible so as to make best use of hard-won field data. We use 3 case studies based on data from soil-transmitted helminth impact surveys in Kenya, Sierra Leone, and Zimbabwe to compare the predictive performance of model-based geostatistics with methods described in current World Health Organization (WHO) guidelines. In all 3 cases, we find that model-based geostatistics substantially outperforms the current WHO guidelines, delivering improved precision for reduced field-sampling effort. We argue from experience that similar improvements will hold for prevalence mapping of other neglected tropical diseases.",,pdf:https://academic.oup.com/cid/article-pdf/72/Supplement_3/S172/38618862/ciab192.pdf; doi:https://doi.org/10.1093/cid/ciab192; html:https://europepmc.org/articles/PMC8201574; pdf:https://europepmc.org/articles/PMC8201574?pdf=render 36819459,https://doi.org/10.1210/jendso/bvad020,"Polygenic Risk of Prediabetes, Undiagnosed Diabetes, and Incident Type 2 Diabetes Stratified by Diabetes Risk Factors.","Liu X, Collister JA, Clifton L, Hunter DJ, Littlejohns TJ.",,Journal of the Endocrine Society,2023,2023-01-30,Y,BMI; Family History; Polygenic Risk And Diabetes,,,"

Context

Early diagnosis of type 2 diabetes is crucial to reduce severe comorbidities and complications. Current screening recommendations for type 2 diabetes include traditional risk factors, primarily body mass index (BMI) and family history, however genetics also plays a key role in type 2 diabetes risk. It is important to understand whether genetic predisposition to type 2 diabetes modifies the effect of these traditional factors on type 2 diabetes risk.

Objective

This work aimed to investigate whether genetic risk of type 2 diabetes modifies associations between BMI and first-degree family history of diabetes with 1) prevalent prediabetes or undiagnosed diabetes; and 2) incident confirmed type 2 diabetes.

Methods

We included 431 658 individuals aged 40 to 69 years at baseline of multiethnic ancestry from the UK Biobank. We used a multiethnic polygenic risk score for type 2 diabetes (PRST2D) developed by Genomics PLC. Prediabetes or undiagnosed diabetes was defined as baseline glycated hemoglobin greater than or equal to 42 mmol/mol (6.0%), and incident type 2 diabetes was derived from medical records.

Results

At baseline, 43 472 participants had prediabetes or undiagnosed diabetes, and 17 259 developed type 2 diabetes over 15 years follow-up. Dose-response associations were observed for PRST2D with each outcome in each category of BMI or first-degree family history of diabetes. Those in the highest quintile of PRST2D with a normal BMI were at a similar risk as those in the middle quintile who were overweight. Participants who were in the highest quintile of PRST2D and did not have a first-degree family history of diabetes were at a similar risk as those with a family history who were in the middle category of PRST2D.

Conclusion

Genetic risk of type 2 diabetes remains strongly associated with risk of prediabetes, undiagnosed diabetes, and future type 2 diabetes within categories of nongenetic risk factors. This could have important implications for identifying individuals at risk of type 2 diabetes for prevention and early diagnosis programs.",,pdf:https://academic.oup.com/jes/article-pdf/7/4/bvad020/49229172/bvad020.pdf; doi:https://doi.org/10.1210/jendso/bvad020; html:https://europepmc.org/articles/PMC9933896; pdf:https://europepmc.org/articles/PMC9933896?pdf=render 35922433,https://doi.org/10.1038/s41467-022-32219-x,Genome-wide associations of aortic distensibility suggest causality for aortic aneurysms and brain white matter hyperintensities.,"Francis CM, Futschik ME, Huang J, Bai W, Sargurupremraj M, Teumer A, Breteler MMB, Petretto E, Ho ASR, Amouyel P, Engelter ST, Bülow R, Völker U, Völzke H, Dörr M, Imtiaz MA, Aziz NA, Lohner V, Ware JS, Debette S, Elliott P, Dehghan A, Matthews PM.",,Nature communications,2022,2022-08-03,Y,,,,"Aortic dimensions and distensibility are key risk factors for aortic aneurysms and dissections, as well as for other cardiovascular and cerebrovascular diseases. We present genome-wide associations of ascending and descending aortic distensibility and area derived from cardiac magnetic resonance imaging (MRI) data of up to 32,590 Caucasian individuals in UK Biobank. We identify 102 loci (including 27 novel associations) tagging genes related to cardiovascular development, extracellular matrix production, smooth muscle cell contraction and heritable aortic diseases. Functional analyses highlight four signalling pathways associated with aortic distensibility (TGF-β, IGF, VEGF and PDGF). We identify distinct sex-specific associations with aortic traits. We develop co-expression networks associated with aortic traits and apply phenome-wide Mendelian randomization (MR-PheWAS), generating evidence for a causal role for aortic distensibility in development of aortic aneurysms. Multivariable MR suggests a causal relationship between aortic distensibility and cerebral white matter hyperintensities, mechanistically linking aortic traits and brain small vessel disease.",,pdf:https://www.nature.com/articles/s41467-022-32219-x.pdf; doi:https://doi.org/10.1038/s41467-022-32219-x; html:https://europepmc.org/articles/PMC9349177; pdf:https://europepmc.org/articles/PMC9349177?pdf=render 34606520,https://doi.org/10.1371/journal.pmed.1003815,"COVID-19 vaccination in Sindh Province, Pakistan: A modelling study of health impact and cost-effectiveness.","Pearson CAB, Bozzani F, Procter SR, Davies NG, Huda M, Jensen HT, Keogh-Brown M, Khalid M, Sweeney S, Torres-Rueda S, CHiL COVID-19 Working Group, CMMID COVID-19 Working Group, Eggo RM, Vassall A, Jit M.",,PLoS medicine,2021,2021-10-04,Y,,,,"

Background

Multiple Coronavirus Disease 2019 (COVID-19) vaccines appear to be safe and efficacious, but only high-income countries have the resources to procure sufficient vaccine doses for most of their eligible populations. The World Health Organization has published guidelines for vaccine prioritisation, but most vaccine impact projections have focused on high-income countries, and few incorporate economic considerations. To address this evidence gap, we projected the health and economic impact of different vaccination scenarios in Sindh Province, Pakistan (population: 48 million).

Methods and findings

We fitted a compartmental transmission model to COVID-19 cases and deaths in Sindh from 30 April to 15 September 2020. We then projected cases, deaths, and hospitalisation outcomes over 10 years under different vaccine scenarios. Finally, we combined these projections with a detailed economic model to estimate incremental costs (from healthcare and partial societal perspectives), disability-adjusted life years (DALYs), and incremental cost-effectiveness ratio (ICER) for each scenario. We project that 1 year of vaccine distribution, at delivery rates consistent with COVAX projections, using an infection-blocking vaccine at $3/dose with 70% efficacy and 2.5-year duration of protection is likely to avert around 0.9 (95% credible interval (CrI): 0.9, 1.0) million cases, 10.1 (95% CrI: 10.1, 10.3) thousand deaths, and 70.1 (95% CrI: 69.9, 70.6) thousand DALYs, with an ICER of $27.9 per DALY averted from the health system perspective. Under a broad range of alternative scenarios, we find that initially prioritising the older (65+) population generally prevents more deaths. However, unprioritised distribution has almost the same cost-effectiveness when considering all outcomes, and both prioritised and unprioritised programmes can be cost-effective for low per-dose costs. High vaccine prices ($10/dose), however, may not be cost-effective, depending on the specifics of vaccine performance, distribution programme, and future pandemic trends. The principal drivers of the health outcomes are the fitted values for the overall transmission scaling parameter and disease natural history parameters from other studies, particularly age-specific probabilities of infection and symptomatic disease, as well as social contact rates. Other parameters are investigated in sensitivity analyses. This study is limited by model approximations, available data, and future uncertainty. Because the model is a single-population compartmental model, detailed impacts of nonpharmaceutical interventions (NPIs) such as household isolation cannot be practically represented or evaluated in combination with vaccine programmes. Similarly, the model cannot consider prioritising groups like healthcare or other essential workers. The model is only fitted to the reported case and death data, which are incomplete and not disaggregated by, e.g., age. Finally, because the future impact and implementation cost of NPIs are uncertain, how these would interact with vaccination remains an open question.

Conclusions

COVID-19 vaccination can have a considerable health impact and is likely to be cost-effective if more optimistic vaccine scenarios apply. Preventing severe disease is an important contributor to this impact. However, the advantage of prioritising older, high-risk populations is smaller in generally younger populations. This reduction is especially true in populations with more past transmission, and if the vaccine is likely to further impede transmission rather than just disease. Those conditions are typical of many low- and middle-income countries.",,pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1003815&type=printable; doi:https://doi.org/10.1371/journal.pmed.1003815; html:https://europepmc.org/articles/PMC8523052; pdf:https://europepmc.org/articles/PMC8523052?pdf=render -35410933,https://doi.org/10.1136/bmjopen-2021-057885,"Non-pharmacological therapies for postviral syndromes, including Long COVID: a systematic review and meta-analysis protocol.","Chandan JS, Brown K, Simms-Williams N, Camaradou J, Bashir N, Heining D, Aiyegbusi OL, Turner G, Cruz Rivera S, Hotham R, Nirantharakumar K, Sivan M, Khunti K, Raindi D, Marwaha S, Hughes SE, McMullan C, Calvert M, Haroon S.",,BMJ open,2022,2022-04-11,Y,Infectious diseases; Rehabilitation Medicine; Covid-19,,,"

Introduction

Postviral syndromes (PVS) describe the sustained presence of symptoms following an acute viral infection, for months or even years. Exposure to the SARS-CoV-2 virus and subsequent development of COVID-19 has shown to have similar effects with individuals continuing to exhibit symptoms for greater than 12 weeks. The sustained presence of symptoms is variably referred to as 'post COVID-19 syndrome', 'post-COVID condition' or more commonly 'Long COVID'. Knowledge of the long-term health impacts and treatments for Long COVID are evolving. To minimise overlap with existing work in the field exploring treatments of Long COVID, we have only chosen to focus on non-pharmacological treatments.

Aims

This review aims to summarise the effectiveness of non-pharmacological treatments for PVS, including Long COVID. A secondary aim is to summarise the symptoms and health impacts associated with PVS in individuals recruited to treatment studies.

Methods and analysis

Primary electronic searches will be performed in bibliographic databases including: Embase, MEDLINE, PyscINFO, CINAHL and MedRxiv from 1 January 2001 to 29 October 2021. At least two independent reviewers will screen each study for inclusion and data will be extracted from all eligible studies onto a data extraction form. The quality of all included studies will be assessed using Cochrane risk of bias tools and the Newcastle-Ottawa grading system. Non-pharmacological treatments for PVS and Long COVID will be narratively summarised and effect estimates will be pooled using random effects meta-analysis where there is sufficient methodological homogeneity. The symptoms and health impacts reported in the included studies on non-pharmacological interventions will be extracted and narratively reported.

Ethics and dissemination

This systematic review does not require ethical approval. The findings from this study will be submitted for peer-reviewed publication, shared at conference presentations and disseminated to both clinical and patient groups.

Prospero registration number

The review will adhere to this protocol which has also been registered with PROSPERO (CRD42021282074).",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/4/e057885.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-057885; html:https://europepmc.org/articles/PMC9002258; pdf:https://europepmc.org/articles/PMC9002258?pdf=render 31671849,https://doi.org/10.3390/ijerph16214178,Associations between the Home Physical Environment and Children's Home-Based Physical Activity and Sitting.,"Sheldrick MP, Maitland C, Mackintosh KA, Rosenberg M, Griffiths LJ, Fry R, Stratton G.",,International journal of environmental research and public health,2019,2019-10-29,Y,Families; Youth; Objective; Standing; House; Moderate-to-vigorous Physical Activity; Screen-time,,,"It is important to understand the correlates of children's physical activity (PA) and sitting at home, where children spend significant time. The home social environment has an important influence; however, much less is known about the home physical environment. Therefore, the study aimed to assess relationships between the physical environment and children's sitting and PA at home. In total, 235 child-parent dyads were included in the analyses. Children spent 67% of their time at home sitting. Linear regression analyses examined associations between physical home environmental factors obtained via an audit and children's (55% girl, 10.2 ± 0.7) objective PA and sitting at home. Following adjustment for socio-demographics and social environmental factors, an open plan living area (OPLA), musical instrument accessibility and availability, and perceived house size were negatively and positively associated, whereas media equipment accessibility and availability was positively and negatively associated with sitting and standing, respectively. Additionally, an OPLA was positively associated with total and moderate-to-vigorous PA. Furthermore, sitting breaks were positively associated with objective garden size and negatively associated with digital TV. The physical home environment may have an important influence on children's sitting, standing and PA at home; therefore, interventions that target this environment are needed.",,pdf:https://www.mdpi.com/1660-4601/16/21/4178/pdf?version=1573119054; doi:https://doi.org/10.3390/ijerph16214178; html:https://europepmc.org/articles/PMC6862192; pdf:https://europepmc.org/articles/PMC6862192?pdf=render -38106559,https://doi.org/10.1016/j.eclinm.2023.102251,Long-term symptom profiles after COVID-19 vs other acute respiratory infections: an analysis of data from the COVIDENCE UK study.,"Vivaldi G, Pfeffer PE, Talaei M, Basera TJ, Shaheen SO, Martineau AR.",,EClinicalMedicine,2023,2023-10-06,Y,Acute respiratory infections; Sars-cov-2; Long Covid; Post-acute Sequelae,,,"

Background

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

Methods

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

Findings

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

Interpretation

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

Funding

Barts Charity.",,doi:https://doi.org/10.1016/j.eclinm.2023.102251; html:https://europepmc.org/articles/PMC10721552; pdf:https://europepmc.org/articles/PMC10721552?pdf=render +35410933,https://doi.org/10.1136/bmjopen-2021-057885,"Non-pharmacological therapies for postviral syndromes, including Long COVID: a systematic review and meta-analysis protocol.","Chandan JS, Brown K, Simms-Williams N, Camaradou J, Bashir N, Heining D, Aiyegbusi OL, Turner G, Cruz Rivera S, Hotham R, Nirantharakumar K, Sivan M, Khunti K, Raindi D, Marwaha S, Hughes SE, McMullan C, Calvert M, Haroon S.",,BMJ open,2022,2022-04-11,Y,Infectious diseases; Rehabilitation Medicine; Covid-19,,,"

Introduction

Postviral syndromes (PVS) describe the sustained presence of symptoms following an acute viral infection, for months or even years. Exposure to the SARS-CoV-2 virus and subsequent development of COVID-19 has shown to have similar effects with individuals continuing to exhibit symptoms for greater than 12 weeks. The sustained presence of symptoms is variably referred to as 'post COVID-19 syndrome', 'post-COVID condition' or more commonly 'Long COVID'. Knowledge of the long-term health impacts and treatments for Long COVID are evolving. To minimise overlap with existing work in the field exploring treatments of Long COVID, we have only chosen to focus on non-pharmacological treatments.

Aims

This review aims to summarise the effectiveness of non-pharmacological treatments for PVS, including Long COVID. A secondary aim is to summarise the symptoms and health impacts associated with PVS in individuals recruited to treatment studies.

Methods and analysis

Primary electronic searches will be performed in bibliographic databases including: Embase, MEDLINE, PyscINFO, CINAHL and MedRxiv from 1 January 2001 to 29 October 2021. At least two independent reviewers will screen each study for inclusion and data will be extracted from all eligible studies onto a data extraction form. The quality of all included studies will be assessed using Cochrane risk of bias tools and the Newcastle-Ottawa grading system. Non-pharmacological treatments for PVS and Long COVID will be narratively summarised and effect estimates will be pooled using random effects meta-analysis where there is sufficient methodological homogeneity. The symptoms and health impacts reported in the included studies on non-pharmacological interventions will be extracted and narratively reported.

Ethics and dissemination

This systematic review does not require ethical approval. The findings from this study will be submitted for peer-reviewed publication, shared at conference presentations and disseminated to both clinical and patient groups.

Prospero registration number

The review will adhere to this protocol which has also been registered with PROSPERO (CRD42021282074).",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/4/e057885.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-057885; html:https://europepmc.org/articles/PMC9002258; pdf:https://europepmc.org/articles/PMC9002258?pdf=render 35585575,https://doi.org/10.1186/s12889-022-13219-4,The impact of COVID-19 vaccination in prisons in England and Wales: a metapopulation model.,"McCarthy CV, O'Mara O, van Leeuwen E, CMMID COVID-19 Working Group, Jit M, Sandmann F.",,BMC public health,2022,2022-05-18,Y,Vaccination; mathematical model; Public Health; Prisons; Covid-19,,,"

Background

High incidence of cases and deaths due to coronavirus disease 2019 (COVID-19) have been reported in prisons worldwide. This study aimed to evaluate the impact of different COVID-19 vaccination strategies in epidemiologically semi-enclosed settings such as prisons, where staff interact regularly with those incarcerated and the wider community.

Methods

We used a metapopulation transmission-dynamic model of a local prison in England and Wales. Two-dose vaccination strategies included no vaccination, vaccination of all individuals who are incarcerated and/or staff, and an age-based approach. Outcomes were quantified in terms of COVID-19-related symptomatic cases, losses in quality-adjusted life-years (QALYs), and deaths.

Results

Compared to no vaccination, vaccinating all people living and working in prison reduced cases, QALY loss and deaths over a one-year period by 41%, 32% and 36% respectively. However, if vaccine introduction was delayed until the start of an outbreak, the impact was negligible. Vaccinating individuals who are incarcerated and staff over 50 years old averted one death for every 104 vaccination courses administered. All-staff-only strategies reduced cases by up to 5%. Increasing coverage from 30 to 90% among those who are incarcerated reduced cases by around 30 percentage points.

Conclusions

The impact of vaccination in prison settings was highly dependent on early and rapid vaccine delivery. If administered to both those living and working in prison prior to an outbreak occurring, vaccines could substantially reduce COVID-19-related morbidity and mortality in prison settings.",,pdf:https://bmcpublichealth.biomedcentral.com/track/pdf/10.1186/s12889-022-13219-4; doi:https://doi.org/10.1186/s12889-022-13219-4; html:https://europepmc.org/articles/PMC9115545; pdf:https://europepmc.org/articles/PMC9115545?pdf=render +38106559,https://doi.org/10.1016/j.eclinm.2023.102251,Long-term symptom profiles after COVID-19 vs other acute respiratory infections: an analysis of data from the COVIDENCE UK study.,"Vivaldi G, Pfeffer PE, Talaei M, Basera TJ, Shaheen SO, Martineau AR.",,EClinicalMedicine,2023,2023-10-06,Y,Acute respiratory infections; Sars-cov-2; Long Covid; Post-acute Sequelae,,,"

Background

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

Methods

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

Findings

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

Interpretation

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

Funding

Barts Charity.",,doi:https://doi.org/10.1016/j.eclinm.2023.102251; html:https://europepmc.org/articles/PMC10721552; pdf:https://europepmc.org/articles/PMC10721552?pdf=render 33588321,https://doi.org/10.1016/j.retram.2021.103276,Biological responses to COVID-19: Insights from physiological and blood biomarker profiles.,"Zakeri R, Pickles A, Carr E, Bean DM, O'Gallagher K, Kraljewic Z, Searle T, Shek A, Galloway JB, Teo JTH, Shah AM, Dobson RJB, Bendayan R.",,Current research in translational medicine,2021,2021-02-03,Y,Inflammation; Biomarkers; Classes; Sars-cov-2,,,"

Background

Understanding the spectrum and course of biological responses to coronavirus disease 2019 (COVID-19) may have important therapeutic implications. We sought to characterise biological responses among patients hospitalised with severe COVID-19 based on serial, routinely collected, physiological and blood biomarker values.

Methods and findings

We performed a retrospective cohort study of 1335 patients hospitalised with laboratory-confirmed COVID-19 (median age 70 years, 56 % male), between 1st March and 30th April 2020. Latent profile analysis was performed on serial physiological and blood biomarkers. Patient characteristics, comorbidities and rates of death and admission to intensive care, were compared between the latent classes. A five class solution provided the best fit. Class 1 ""Typical response"" exhibited a moderately elevated and rising C-reactive protein (CRP), stable lymphopaenia, and the lowest rates of 14-day adverse outcomes. Class 2 ""Rapid hyperinflammatory response"" comprised older patients, with higher admission white cell and neutrophil counts, which declined over time, accompanied by a very high and rising CRP and platelet count, and exibited the highest mortality risk. Class 3 ""Progressive inflammatory response"" was similar to the typical response except for a higher and rising CRP, though similar mortality rate. Class 4 ""Inflammatory response with kidney injury"" had prominent lymphopaenia, moderately elevated (and rising) CRP, and severe renal failure. Class 5 ""Hyperinflammatory response with kidney injury"" comprised older patients, with a very high and rising CRP, and severe renal failure that attenuated over time. Physiological measures did not substantially vary between classes at baseline or early admission.

Conclusions and relevance

Our identification of five distinct classes of biomarker profiles provides empirical evidence for heterogeneous biological responses to COVID-19. Early hyperinflammatory responses and kidney injury may signify unique pathophysiology that requires targeted therapy.",,doi:https://doi.org/10.1016/j.retram.2021.103276; doi:https://doi.org/10.1016/j.retram.2021.103276; html:https://europepmc.org/articles/PMC7857048; pdf:https://europepmc.org/articles/PMC7857048?pdf=render 31409800,https://doi.org/10.1038/s41467-019-11451-y,GWAS for urinary sodium and potassium excretion highlights pathways shared with cardiovascular traits.,"Pazoki R, Evangelou E, Mosen-Ansorena D, Pinto RC, Karaman I, Blakeley P, Gill D, Zuber V, Elliott P, Tzoulaki I, Dehghan A.",,Nature communications,2019,2019-08-13,Y,,Understanding the Causes of Disease,,"Urinary sodium and potassium excretion are associated with blood pressure (BP) and cardiovascular disease (CVD). The exact biological link between these traits is yet to be elucidated. Here, we identify 50 loci for sodium and 13 for potassium excretion in a large-scale genome-wide association study (GWAS) on urinary sodium and potassium excretion using data from 446,237 individuals of European descent from the UK Biobank study. We extensively interrogate the results using multiple analyses such as Mendelian randomization, functional assessment, co localization, genetic risk score, and pathway analyses. We identify a shared genetic component between urinary sodium and potassium expression and cardiovascular traits. Ingenuity pathway analysis shows that urinary sodium and potassium excretion loci are over-represented in behavioural response to stimuli. Our study highlights pathways that are shared between urinary sodium and potassium excretion and cardiovascular traits.",,pdf:https://www.nature.com/articles/s41467-019-11451-y.pdf; doi:https://doi.org/10.1038/s41467-019-11451-y; html:https://europepmc.org/articles/PMC6692500; pdf:https://europepmc.org/articles/PMC6692500?pdf=render 35381001,https://doi.org/10.1371/journal.pgen.1010093,Analyzing human knockouts to validate GPR151 as a therapeutic target for reduction of body mass index.,"Gurtan A, Dominy J, Khalid S, Vong L, Caplan S, Currie T, Richards S, Lamarche L, Denning D, Shpektor D, Gurinovich A, Rasheed A, Hameed S, Saeed S, Saleem I, Jalal A, Abbas S, Sultana R, Rasheed SZ, Memon FU, Shah N, Ishaq M, Khera AV, Danesh J, Frossard P, Saleheen D.",,PLoS genetics,2022,2022-04-05,Y,,,,"Novel drug targets for sustained reduction in body mass index (BMI) are needed to curb the epidemic of obesity, which affects 650 million individuals worldwide and is a causal driver of cardiovascular and metabolic disease and mortality. Previous studies reported that the Arg95Ter nonsense variant of GPR151, an orphan G protein-coupled receptor, is associated with reduced BMI and reduced risk of Type 2 Diabetes (T2D). Here, we further investigate GPR151 with the Pakistan Genome Resource (PGR), which is one of the largest exome biobanks of human homozygous loss-of-function carriers (knockouts) in the world. Among PGR participants, we identify eleven GPR151 putative loss-of-function (plof) variants, three of which are present at homozygosity (Arg95Ter, Tyr99Ter, and Phe175LeufsTer7), with a cumulative allele frequency of 2.2%. We confirm these alleles in vitro as loss-of-function. We test if GPR151 plof is associated with BMI, T2D, or other metabolic traits and find that GPR151 deficiency in complete human knockouts is not associated with clinically significant differences in these traits. Relative to Gpr151+/+ mice, Gpr151-/- animals exhibit no difference in body weight on normal chow and higher body weight on a high-fat diet. Together, our findings indicate that GPR151 antagonism is not a compelling therapeutic approach to treatment of obesity.",,pdf:https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1010093&type=printable; doi:https://doi.org/10.1371/journal.pgen.1010093; html:https://europepmc.org/articles/PMC9022822; pdf:https://europepmc.org/articles/PMC9022822?pdf=render @@ -1609,16 +1609,16 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 31408247,https://doi.org/10.1002/hpja.287,An assessment of program evaluation methods and quality in Australian prevention agencies.,"Schwarzman J, Nau T, Bauman A, Gabbe BJ, Rissel C, Shilton T, Smith BJ.",,Health promotion journal of Australia : official journal of Australian Association of Health Promotion Professionals,2020,2019-08-13,N,Program Evaluation; Government; Primary Prevention; Health Promotion; Evidence-based Practice; Health Equity; Non-government Organisations,,,"

Issue addressed

This study aimed to examine evaluation methods and quality in Australian health promotion agencies and the factors associated with this. The evidence base for prevention strategies is limited, with the evidence generated through program evaluation by health promotion and disease prevention agencies lacking rigour. Despite the need to improve the quality of evaluation, there is limited evidence of what influences evaluation quality in the prevention field.

Methods

Data were collected using the Evaluation Practice Analysis Survey and an audit and appraisal of evaluation reports. Descriptive analysis was used to examine evaluation characteristics and multivariable regression was used to explore the association between evaluation and organisational attributes and evaluation quality.

Results

In total, 392 evaluation reports were reviewed from 78 government and non-government agencies. Process evaluation was conducted most frequently, followed by impact evaluation. Overall evaluation quality was low (median 24.5%). In multivariable regression analysis, only two factors were associated with evaluation quality: health promotion budget (ratio of geometric means 1.53 [95% CI 1.02-2.29]); and, conducting statewide or national prevention programs (1.38 [95% CI 1.05-1.82]).

Conclusions

The findings show that the potential to improve evaluation quality is greatest in smaller organisations that deliver health promotion at a local or regional scale. SO WHAT?: By improving the rigour of existing evaluation, there is opportunity to build the evidence base for prevention strategies, which highlights the importance of embedding the enablers of program learning and evidence generation within health promotion and prevention organisations.",,doi:https://doi.org/10.1002/hpja.287 32685698,https://doi.org/10.12688/wellcomeopenres.15842.3,Estimating the overdispersion in COVID-19 transmission using outbreak sizes outside China.,"Endo A, Centre for the Mathematical Modelling of Infectious Diseases COVID-19 Working Group, Abbott S, Kucharski AJ, Funk S.",,Wellcome open research,2020,2020-07-10,Y,Branching Process; Overdispersion; Novel Coronavirus; Superspreading; Covid-19; Sars-cov-2,,,"Background: A novel coronavirus disease (COVID-19) outbreak has now spread to a number of countries worldwide. While sustained transmission chains of human-to-human transmission suggest high basic reproduction number R 0, variation in the number of secondary transmissions (often characterised by so-called superspreading events) may be large as some countries have observed fewer local transmissions than others. Methods: We quantified individual-level variation in COVID-19 transmission by applying a mathematical model to observed outbreak sizes in affected countries. We extracted the number of imported and local cases in the affected countries from the World Health Organization situation report and applied a branching process model where the number of secondary transmissions was assumed to follow a negative-binomial distribution. Results: Our model suggested a high degree of individual-level variation in the transmission of COVID-19. Within the current consensus range of R 0 (2-3), the overdispersion parameter k of a negative-binomial distribution was estimated to be around 0.1 (median estimate 0.1; 95% CrI: 0.05-0.2 for R0 = 2.5), suggesting that 80% of secondary transmissions may have been caused by a small fraction of infectious individuals (~10%). A joint estimation yielded likely ranges for R 0 and k (95% CrIs: R 0 1.4-12; k 0.04-0.2); however, the upper bound of R 0 was not well informed by the model and data, which did not notably differ from that of the prior distribution. Conclusions: Our finding of a highly-overdispersed offspring distribution highlights a potential benefit to focusing intervention efforts on superspreading. As most infected individuals do not contribute to the expansion of an epidemic, the effective reproduction number could be drastically reduced by preventing relatively rare superspreading events.",,doi:https://doi.org/10.12688/wellcomeopenres.15842.3; html:https://europepmc.org/articles/PMC7338915; pdf:https://europepmc.org/articles/PMC7338915?pdf=render 35115689,https://doi.org/10.1038/s41588-021-00991-z,Combined effects of host genetics and diet on human gut microbiota and incident disease in a single population cohort.,"Qin Y, Havulinna AS, Liu Y, Jousilahti P, Ritchie SC, Tokolyi A, Sanders JG, Valsta L, Brożyńska M, Zhu Q, Tripathi A, Vázquez-Baeza Y, Loomba R, Cheng S, Jain M, Niiranen T, Lahti L, Knight R, Salomaa V, Inouye M, Méric G.",,Nature genetics,2022,2022-02-03,N,,,,"Human genetic variation affects the gut microbiota through a complex combination of environmental and host factors. Here we characterize genetic variations associated with microbial abundances in a single large-scale population-based cohort of 5,959 genotyped individuals with matched gut microbial metagenomes, and dietary and health records (prevalent and follow-up). We identified 567 independent SNP-taxon associations. Variants at the LCT locus associated with Bifidobacterium and other taxa, but they differed according to dairy intake. Furthermore, levels of Faecalicatena lactaris associated with ABO, and suggested preferential utilization of secreted blood antigens as energy source in the gut. Enterococcus faecalis levels associated with variants in the MED13L locus, which has been linked to colorectal cancer. Mendelian randomization analysis indicated a potential causal effect of Morganella on major depressive disorder, consistent with observational incident disease analysis. Overall, we identify and characterize the intricate nature of host-microbiota interactions and their association with disease.",,pdf:https://www.nature.com/articles/s41588-021-00991-z.pdf; doi:https://doi.org/10.1038/s41588-021-00991-z; html:https://europepmc.org/articles/PMC9883041; pdf:https://europepmc.org/articles/PMC9883041?pdf=render; doi:https://doi.org/10.1038/s41588-021-00991-z +35866236,https://doi.org/10.7189/jogh.12.05033,The road to recovery: an interrupted time series analysis of policy intervention to restore essential health services in Mexico during the COVID-19 pandemic.,"Doubova SV, Arsenault C, Contreras-Sánchez SE, Borrayo-Sánchez G, Leslie HH.",,Journal of global health,2022,2022-07-23,Y,,,,"

Background

Recovery of health services disrupted by the COVID-19 pandemic represents a significant challenge in low- and middle-income countries. In April 2021, the Mexican Institute of Social Security (IMSS), which provides health care to 68.5 million people, launched the National Strategy for Health Services Recovery (Recovery policy). The study objective was to evaluate whether the Recovery policy addressed COVID-related declines in maternal, child health, and non-communicable diseases (NCDs) services.

Methods

We analysed the data of 35 IMSS delegations from January 2019 to November 2021 on contraceptive visits, antenatal care consultations, deliveries, caesarean sections, sick children's consultations, child vaccination, breast and cervical cancer screening, diabetes and hypertension consultations, and control. We focused on the period before (April 2020 - March 2021) and during (April 2021 - November 2021) the Recovery policy and used an interrupted time series design and Poisson Generalized Estimating Equation models to estimate the association of this policy with service use and outcomes and change in their trends.

Results

Despite the third wave of the pandemic in 2021, service utilization increased in the Recovery period, reaching (at minimum) 49% of pre-pandemic levels for sick children's consultations and (at maximum) 106% of pre-pandemic levels for breast cancer screenings. Evidence for the Recovery policy role was mixed: the policy was associated with increased facility deliveries (IRR = 1.15, 95%CI = 1.11-1.19) with a growing trend over time (IRR = 1.04, 95%CI = 1.03-1.05); antenatal care and child health services saw strong level effects but decrease over time. Additionally, the Recovery policy was associated with diabetes and hypertension control. Services recovery varied across delegations.

Conclusions

Health service utilization and NCDs control demonstrated important gains in 2021, but evidence suggests the policy had inconsistent effects across services and decreasing impact over time. Further efforts to strengthen essential health services and ensure consistent recovery across delegations are warranted.",,pdf:https://jogh.org/wp-content/uploads/2022/07/jogh-12-05033.pdf; doi:https://doi.org/10.7189/jogh.12.05033; html:https://europepmc.org/articles/PMC9304921; pdf:https://europepmc.org/articles/PMC9304921?pdf=render 38642613,https://doi.org/10.1016/j.clinme.2024.100209,Addressing ethnic disparities in neurological research in the United Kingdom: An example from the prospective multicentre COVID-19 Clinical Neuroscience Study.,"van Wamelen DJ, Rota S, Hartmann M, Martin NH, Alam AM, Thomas RH, Dodd KC, Jenkins T, Smith CJ, Zandi MS, Easton A, Carr G, Benjamin LA, Lilleker JB, Saucer D, Coles AJ, Wood N, Ray Chaudhuri K, Breen G, Michael BD, COVID-CNS consortium.",,"Clinical medicine (London, England)",2024,2024-04-19,Y,Diversity; Recruitment; Neurology; Ethnicity; Covid-19,,,"

Background

Minority ethnic groups have often been underrepresented in research, posing a problem in relation to external validity and extrapolation of findings. Here, we aimed to assess recruitment and retainment strategies in a large observational study assessing neurological complications following SARS-CoV-2 infection.

Methods

Participants were recruited following confirmed infection with SARS-CoV-2 and hospitalisation. Self-reported ethnicity was recorded alongside other demographic data to identify potential barriers to recruitment.

Results

807 participants were recruited to COVID-CNS, and ethnicity data were available for 93.2%. We identified a proportionate representation of self-reported ethnicity categories, and distribution of broad ethnicity categories mirrored individual centres' catchment areas. White ethnicity within individual centres ranged between 44.5% and 89.1%, with highest percentage of participants with non-White ethnicity in London-based centres. Examples are provided how to reach potentially underrepresented minority ethnic groups.

Conclusions

Recruitment barriers in relation to potentially underrepresented ethnic groups may be overcome with strategies identified here.",,doi:https://doi.org/10.1016/j.clinme.2024.100209; html:https://europepmc.org/articles/PMC11091497; pdf:https://europepmc.org/articles/PMC11091497?pdf=render 38180742,https://doi.org/10.1097/qai.0000000000003326,Estimation of Improvements in Mortality in Spectrum Among Adults With HIV Receiving Antiretroviral Therapy in High-Income Countries.,"Trickey A, Glaubius R, Pantazis N, Zangerle R, Wittkop L, Vehreschild J, Grabar S, Cavassini M, Teira R, d'Arminio Monforte A, Casabona J, van Sighem A, Jarrin I, Ingle SM, Sterne JAC, Imai-Eaton JW, Johnson LF.",,Journal of acquired immune deficiency syndromes (1999),2024,2024-01-04,Y,,,,"

Introduction

Mortality rates for people living with HIV (PLHIV) on antiretroviral therapy (ART) in high-income countries continue to decline. We compared mortality rates among PLHIV on ART in Europe for 2016-2020 with Spectrum's estimates.

Methods

The AIDS Impact Module in Spectrum is a compartmental HIV epidemic model coupled with a demographic population projection model. We used national Spectrum projections developed for the 2022 HIV estimates round to calculate mortality rates among PLHIV on ART, adjusting to the age/country distribution of PLHIV starting ART from 1996 to 2020 in the Antiretroviral Therapy Cohort Collaboration (ART-CC)'s European cohorts.

Results

In the ART-CC, 11,504 of 162,835 PLHIV died. Between 1996-1999 and 2016-2020, AIDS-related mortality in the ART-CC decreased from 8.8 (95% CI: 7.6 to 10.1) to 1.0 (0.9-1.2) and from 5.9 (4.4-8.1) to 1.1 (0.9-1.4) deaths per 1000 person-years among men and women, respectively. Non-AIDS-related mortality decreased from 9.1 (7.9-10.5) to 6.1 (5.8-6.5) and from 7.0 (5.2-9.3) to 4.8 (4.3-5.2) deaths per 1000 person-years among men and women, respectively. Adjusted all-cause mortality rates in Spectrum among men were near ART-CC estimates for 2016-2020 (Spectrum: 7.02-7.47 deaths per 1000 person-years) but approximately 20% lower in women (Spectrum: 4.66-4.70). Adjusted excess mortality rates in Spectrum were 2.5-fold higher in women and 3.1-3.4-fold higher in men in comparison to the ART-CC's AIDS-specific mortality rates.

Discussion

Spectrum's all-cause mortality estimates among PLHIV are consistent with age/country-controlled mortality observed in ART-CC, with some underestimation of mortality among women. Comparing results suggest that 60%-70% of excess deaths among PLHIV on ART in Spectrum are from non-AIDS causes.",,html:https://journals.lww.com/jaids/fulltext/2024/01011/estimation_of_improvements_in_mortality_in.10.aspx; doi:https://doi.org/10.1097/QAI.0000000000003326; html:https://europepmc.org/articles/PMC10769170; pdf:https://europepmc.org/articles/PMC10769170?pdf=render -35866236,https://doi.org/10.7189/jogh.12.05033,The road to recovery: an interrupted time series analysis of policy intervention to restore essential health services in Mexico during the COVID-19 pandemic.,"Doubova SV, Arsenault C, Contreras-Sánchez SE, Borrayo-Sánchez G, Leslie HH.",,Journal of global health,2022,2022-07-23,Y,,,,"

Background

Recovery of health services disrupted by the COVID-19 pandemic represents a significant challenge in low- and middle-income countries. In April 2021, the Mexican Institute of Social Security (IMSS), which provides health care to 68.5 million people, launched the National Strategy for Health Services Recovery (Recovery policy). The study objective was to evaluate whether the Recovery policy addressed COVID-related declines in maternal, child health, and non-communicable diseases (NCDs) services.

Methods

We analysed the data of 35 IMSS delegations from January 2019 to November 2021 on contraceptive visits, antenatal care consultations, deliveries, caesarean sections, sick children's consultations, child vaccination, breast and cervical cancer screening, diabetes and hypertension consultations, and control. We focused on the period before (April 2020 - March 2021) and during (April 2021 - November 2021) the Recovery policy and used an interrupted time series design and Poisson Generalized Estimating Equation models to estimate the association of this policy with service use and outcomes and change in their trends.

Results

Despite the third wave of the pandemic in 2021, service utilization increased in the Recovery period, reaching (at minimum) 49% of pre-pandemic levels for sick children's consultations and (at maximum) 106% of pre-pandemic levels for breast cancer screenings. Evidence for the Recovery policy role was mixed: the policy was associated with increased facility deliveries (IRR = 1.15, 95%CI = 1.11-1.19) with a growing trend over time (IRR = 1.04, 95%CI = 1.03-1.05); antenatal care and child health services saw strong level effects but decrease over time. Additionally, the Recovery policy was associated with diabetes and hypertension control. Services recovery varied across delegations.

Conclusions

Health service utilization and NCDs control demonstrated important gains in 2021, but evidence suggests the policy had inconsistent effects across services and decreasing impact over time. Further efforts to strengthen essential health services and ensure consistent recovery across delegations are warranted.",,pdf:https://jogh.org/wp-content/uploads/2022/07/jogh-12-05033.pdf; doi:https://doi.org/10.7189/jogh.12.05033; html:https://europepmc.org/articles/PMC9304921; pdf:https://europepmc.org/articles/PMC9304921?pdf=render 31282950,https://doi.org/10.1001/jamaneurol.2019.1812,Association Between Idiopathic Intracranial Hypertension and Risk of Cardiovascular Diseases in Women in the United Kingdom.,"Adderley NJ, Subramanian A, Nirantharakumar K, Yiangou A, Gokhale KM, Mollan SP, Sinclair AJ.",,JAMA neurology,2019,2019-09-01,Y,,Understanding the Causes of Disease,,"

Importance

Cardiovascular disease (CVD) risk has not been previously evaluated in a large matched cohort study in idiopathic intracranial hypertension (IIH).

Objectives

To estimate the risk of composite cardiovascular events, heart failure, ischemic heart disease, stroke/transient ischemic attack (TIA), type 2 diabetes, and hypertension in women with idiopathic intracranial hypertension and compare it with the risk in women, matched on body mass index (BMI) and age, without the condition; and to evaluate the prevalence and incidence of IIH.

Design, setting, and participants

This population-based matched controlled cohort study used 28 years of data, from January 1, 1990, to January 17, 2018, from The Health Improvement Network (THIN), an anonymized, nationally representative electronic medical records database in the United Kingdom. All female patients aged 16 years or older were eligible for inclusion. Female patients with IIH (n = 2760) were included and randomly matched with up to 10 control patients (n = 27 125) by BMI and age.

Main outcomes and measures

Adjusted hazard ratios (aHRs) of cardiovascular outcomes were calculated using Cox regression models. The primary outcome was a composite of any CVD (heart failure, ischemic heart disease, and stroke/TIA), and the secondary outcomes were each CVD outcome, type 2 diabetes, and hypertension.

Results

In total, 2760 women with IIH and 27 125 women without IIH were included. Age and BMI were similar between the 2 groups, with a median (interquartile range) age of 32.1 (25.6-42.0) years in the exposed group and 32.1 (25.7-42.1) years in the control group; in the exposed group 1728 women (62.6%) were obese, and in the control group 16514 women (60.9%) were obese. Higher absolute risks for all cardiovascular outcomes were observed in women with IIH compared with control patients. The aHRs were as follows: composite cardiovascular events, 2.10 (95% CI, 1.61-2.74; P < .001); heart failure, 1.97 (95% CI, 1.16-3.37; P = .01); ischemic heart disease, 1.94 (95% CI, 1.27-2.94; P = .002); stroke/TIA, 2.27 (95% CI, 1.61-3.21; P < .001); type 2 diabetes, 1.30 (95% CI, 1.07-1.57; P = .009); and hypertension, 1.55 (95% CI, 1.30-1.84; P < .001). The incidence of IIH in female patients more than tripled between 2005 and 2017, from 2.5 to 9.3 per 100 000 person-years. Similarly, IIH prevalence increased in the same period, from 26 to 79 per 100 000 women. Incidence increased markedly with BMI higher than 30.

Conclusions and relevance

Idiopathic intracranial hypertension in women appeared to be associated with a 2-fold increase in CVD risk; change in patient care to modify risk factors for CVD may reduce long-term morbidity for women with IIH and warrants further evaluation.",,pdf:https://jamanetwork.com/journals/jamaneurology/articlepdf/2737044/jamaneurology_adderley_2019_oi_190046.pdf; doi:https://doi.org/10.1001/jamaneurol.2019.1812; html:https://europepmc.org/articles/PMC6618853 33372068,https://doi.org/10.1136/bmjopen-2020-038324,Risk factors for mental illness in adults with atopic eczema or psoriasis: protocol for a systematic review.,"Adesanya EI, Schonmann Y, Hayes JF, Mathur R, Mulick AR, Rayner L, Smeeth L, Smith CH, Langan SM, Mansfield KE.",,BMJ open,2020,2020-12-28,Y,Psoriasis; Mental health; Eczema; Anxiety Disorders; Schizophrenia & Psychotic Disorders; Depression & Mood Disorders,,,"

Introduction

Evidence indicates that people with the common inflammatory skin diseases atopic eczema or psoriasis are at increased risk of mental illness. However, the reasons for the relationship between skin disease and common mental disorders (ie, depression and anxiety) or severe mental illnesses (ie, schizophrenia, bipolar disorder and other psychoses) are unclear. Therefore, we aim to synthesise the available evidence regarding the risk factors for mental illness in adults with atopic eczema or psoriasis.

Methods and analysis

We will conduct a systematic review of randomised controlled trials, cohort, case-control and cross-sectional studies. We will search the following databases from inception to March 2020: Medline, Embase, Global Health, Scopus, the Cochrane Library, Web of Science, Base, PsycInfo, the Global Resource of Eczema Trials, and the grey literature databases Open Grey, PsycExtra and the New York Academy of Medicine Grey Literature Report. We will also search the bibliographies of eligible studies and relevant systematic reviews to identify additional relevant studies. Citation searching of large summary papers will be used to further identify relevant publications. Two reviewers will initially review study titles and abstracts for eligibility, followed by full text screening. We will extract data using a standardised data extraction form. We will assess the risk of bias of included studies using the Quality in Prognosis Studies tool. We will synthesise data narratively, and if studies are sufficiently homogenous, we will consider a meta-analysis. We will assess the quality of the evidence using the Grading of Recommendations, Assessment, Development and Evaluation framework.

Ethics and dissemination

Ethical approval is not required for a systematic review. Results of the review will be published in a peer-reviewed journal and disseminated through conferences.

Prospero registration number

CRD42020163941.",,pdf:https://bmjopen.bmj.com/content/bmjopen/10/12/e038324.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-038324; html:https://europepmc.org/articles/PMC7772326; pdf:https://europepmc.org/articles/PMC7772326?pdf=render 33521535,https://doi.org/10.1136/bmjnph-2020-000107,Genetic risk of obesity as a modifier of associations between neighbourhood environment and body mass index: an observational study of 335 046 UK Biobank participants.,"Mason KE, Palla L, Pearce N, Phelan J, Cummins S.",,"BMJ nutrition, prevention & health",2020,2020-10-05,Y,Malnutrition; Dietary Patterns,,,"

Background

There is growing recognition that recent global increases in obesity are the product of a complex interplay between genetic and environmental factors. However, in gene-environment studies of obesity, 'environment' usually refers to individual behavioural factors that influence energy balance, whereas more upstream environmental factors are overlooked. We examined gene-environment interactions between genetic risk of obesity and two neighbourhood characteristics likely to be associated with obesity (proximity to takeaway/fast-food outlets and availability of physical activity facilities).

Methods

We used data from 335 046 adults aged 40-70 in the UK Biobank cohort to conduct a population-based cross-sectional study of interactions between neighbourhood characteristics and genetic risk of obesity, in relation to body mass index (BMI). Proximity to a fast-food outlet was defined as distance from home address to nearest takeaway/fast-food outlet, and availability of physical activity facilities as the number of formal physical activity facilities within 1 km of home address. Genetic risk of obesity was operationalised by weighted Genetic Risk Scores of 91 or 69 single nucleotide polymorphisms (SNP), and by six individual SNPs considered separately. Multivariable, mixed-effects models with product terms for the gene-environment interactions were estimated.

Results

After accounting for likely confounding, the association between proximity to takeaway/fast-food outlets and BMI was stronger among those at increased genetic risk of obesity, with evidence of an interaction with polygenic risk scores (p=0.018 and p=0.028 for 69-SNP and 91-SNP scores, respectively) and in particular with a SNP linked to MC4R (p=0.009), a gene known to regulate food intake. We found very little evidence of gene-environment interaction for the availability of physical activity facilities.

Conclusions

Individuals at an increased genetic risk of obesity may be more sensitive to exposure to the local fast-food environment. Ensuring that neighbourhood residential environments are designed to promote a healthy weight may be particularly important for those with greater genetic susceptibility to obesity.",,pdf:https://nutrition.bmj.com/content/bmjnph/3/2/247.full.pdf; doi:https://doi.org/10.1136/bmjnph-2020-000107; html:https://europepmc.org/articles/PMC7841812; pdf:https://europepmc.org/articles/PMC7841812?pdf=render 34348396,https://doi.org/10.1097/ede.0000000000001393,Weight Change and the Onset of Cardiovascular Diseases: Emulating Trials Using Electronic Health Records.,"Katsoulis M, Stavola BD, Diaz-Ordaz K, Gomes M, Lai A, Lagiou P, Wannamethee G, Tsilidis K, Lumbers RT, Denaxas S, Banerjee A, Parisinos CA, Batterham R, Patel R, Langenberg C, Hemingway H.",,"Epidemiology (Cambridge, Mass.)",2021,2021-09-01,Y,,,,"

Background

Cross-sectional measures of body mass index (BMI) are associated with cardiovascular disease (CVD) incidence, but less is known about whether weight change affects the risk of CVD.

Methods

We estimated the effect of 2-y weight change interventions on 7-y risk of CVD (CVD death, myocardial infarction, stroke, hospitalization from coronary heart disease, and heart failure) by emulating hypothetical interventions using electronic health records. We identified 138,567 individuals with 45-69 years of age without chronic disease in England from 1998 to 2016. We performed pooled logistic regression, using inverse-probability weighting to adjust for baseline and time-varying confounders. We categorized each individual into a weight loss, maintenance, or gain group.

Results

Among those of normal weight, both weight loss [risk difference (RD) vs. weight maintenance = 1.5% (0.3% to 3.0%)] and gain [RD = 1.3% (0.5% to 2.2%)] were associated with increased risk for CVD compared with weight maintenance. Among overweight individuals, we observed moderately higher risk of CVD in both the weight loss [RD = 0.7% (-0.2% to 1.7%)] and the weight gain group [RD = 0.7% (-0.1% to 1.7%)], compared with maintenance. In the obese, those losing weight showed lower risk of coronary heart disease [RD = -1.4% (-2.4% to -0.6%)] but not of stroke. When we assumed that chronic disease occurred 1-3 years before the recorded date, estimates for weight loss and gain were attenuated among overweight individuals; estimates for loss were lower among obese individuals.

Conclusion

Among individuals with obesity, the weight-loss group had a lower risk of coronary heart disease but not of stroke. Weight gain was associated with increased risk of CVD across BMI groups. See video abstract at, http://links.lww.com/EDE/B838.",,html:https://journals.lww.com/epidem/Fulltext/2021/09000/Weight_Change_and_the_Onset_of_Cardiovascular.19.aspx; doi:https://doi.org/10.1097/EDE.0000000000001393; html:https://europepmc.org/articles/PMC8318567; pdf:https://europepmc.org/articles/PMC8318567?pdf=render -37777287,https://doi.org/10.1016/s2468-2667(23)00178-0,"All-cause hospitalisation among people living with HIV according to gender, mode of HIV acquisition, ethnicity, and geographical origin in Europe and North America: findings from the ART-CC cohort collaboration.","Rein SM, Lampe FC, Ingle SM, Sterne JAC, Trickey A, Gill MJ, Papastamopoulos V, Wittkop L, van der Valk M, Kitchen M, Guest JL, Satre DD, Wandeler G, Galindo P, Castilho J, Crane HM, Smith CJ.",,The Lancet. Public health,2023,2023-10-01,Y,,,,"

Background

Understanding demographic disparities in hospitalisation is crucial for the identification of vulnerable populations, interventions, and resource planning.

Methods

Data were from the Antiretroviral Therapy Cohort Collaboration (ART-CC) on people living with HIV in Europe and North America, followed up between January, 2007 and December, 2020. We investigated differences in all-cause hospitalisation according to gender and mode of HIV acquisition, ethnicity, and combined geographical origin and ethnicity, in people living with HIV on modern combination antiretroviral therapy (cART). Analyses were performed separately for European and North American cohorts. Hospitalisation rates were assessed using negative binomial multilevel regression, adjusted for age, time since cART intitiaion, and calendar year.

Findings

Among 23 594 people living with HIV in Europe and 9612 in North America, hospitalisation rates per 100 person-years were 16·2 (95% CI 16·0-16·4) and 13·1 (12·8-13·5). Compared with gay, bisexual, and other men who have sex with men, rates were higher for heterosexual men and women, and much higher for men and women who acquired HIV through injection drug use (adjusted incidence rate ratios ranged from 1·2 to 2·5 in Europe and from 1·2 to 3·3 in North America). In both regions, individuals with geographical origin other than the region of study generally had lower hospitalisation rates compared with those with geographical origin of the study country. In North America, Indigenous people and Black or African American individuals had higher rates than White individuals (adjusted incidence rate ratios 1·9 and 1·2), whereas Asian and Hispanic people living with HIV had somewhat lower rates. In Europe there was a lower rate in Asian individuals compared with White individuals.

Interpretation

Substantial disparities exist in all-cause hospitalisation between demographic groups of people living with HIV in the current cART era in high-income settings, highlighting the need for targeted support.

Funding

Royal Free Charity and the National Institute on Alcohol Abuse and Alcoholism.",,pdf:http://www.thelancet.com/article/S2468266723001780/pdf; doi:https://doi.org/10.1016/S2468-2667(23)00178-0; html:https://europepmc.org/articles/PMC10851157; pdf:https://europepmc.org/articles/PMC10851157?pdf=render -36689332,https://doi.org/10.1093/neuonc/noad021,GBMdeconvoluteR accurately infers proportions of neoplastic and immune cell populations from bulk glioblastoma transcriptomics data.,"Ajaib S, Lodha D, Pollock S, Hemmings G, Finetti MA, Gusnanto A, Chakrabarty A, Ismail A, Wilson E, Varn FS, Hunter B, Filby A, Brockman AA, McDonald D, Verhaak RGW, Ihrie RA, Stead LF.",,Neuro-oncology,2023,2023-07-01,Y,Immune; Deconvolution; Glioblastoma; Neoplastic; Transcriptomics,,,"

Background

Characterizing and quantifying cell types within glioblastoma (GBM) tumors at scale will facilitate a better understanding of the association between the cellular landscape and tumor phenotypes or clinical correlates. We aimed to develop a tool that deconvolutes immune and neoplastic cells within the GBM tumor microenvironment from bulk RNA sequencing data.

Methods

We developed an IDH wild-type (IDHwt) GBM-specific single immune cell reference consisting of B cells, T-cells, NK-cells, microglia, tumor associated macrophages, monocytes, mast and DC cells. We used this alongside an existing neoplastic single cell-type reference for astrocyte-like, oligodendrocyte- and neuronal progenitor-like and mesenchymal GBM cancer cells to create both marker and gene signature matrix-based deconvolution tools. We applied single-cell resolution imaging mass cytometry (IMC) to ten IDHwt GBM samples, five paired primary and recurrent tumors, to determine which deconvolution approach performed best.

Results

Marker-based deconvolution using GBM-tissue specific markers was most accurate for both immune cells and cancer cells, so we packaged this approach as GBMdeconvoluteR. We applied GBMdeconvoluteR to bulk GBM RNAseq data from The Cancer Genome Atlas and recapitulated recent findings from multi-omics single cell studies with regards associations between mesenchymal GBM cancer cells and both lymphoid and myeloid cells. Furthermore, we expanded upon this to show that these associations are stronger in patients with worse prognosis.

Conclusions

GBMdeconvoluteR accurately quantifies immune and neoplastic cell proportions in IDHwt GBM bulk RNA sequencing data and is accessible here: https://gbmdeconvoluter.leeds.ac.uk.",,pdf:https://academic.oup.com/neuro-oncology/advance-article-pdf/doi/10.1093/neuonc/noad021/49522012/noad021.pdf; doi:https://doi.org/10.1093/neuonc/noad021; html:https://europepmc.org/articles/PMC10326489; pdf:https://europepmc.org/articles/PMC10326489?pdf=render 33591280,https://doi.org/10.2196/16348,A Social Media Campaign (#datasaveslives) to Promote the Benefits of Using Health Data for Research Purposes: Mixed Methods Analysis.,"Hassan L, Nenadic G, Tully MP.",,Journal of medical Internet research,2021,2021-02-16,Y,Medical research; Public Engagement; Social Network Analysis; Social Media,,,"

Background

Social media provides the potential to engage a wide audience about scientific research, including the public. However, little empirical research exists to guide health scientists regarding what works and how to optimize impact. We examined the social media campaign #datasaveslives established in 2014 to highlight positive examples of the use and reuse of health data in research.

Objective

This study aims to examine how the #datasaveslives hashtag was used on social media, how often, and by whom; thus, we aim to provide insights into the impact of a major social media campaign in the UK health informatics research community and further afield.

Methods

We analyzed all publicly available posts (tweets) that included the hashtag #datasaveslives (N=13,895) on the microblogging platform Twitter between September 1, 2016, and August 31, 2017. Using a combination of qualitative and quantitative analyses, we determined the frequency and purpose of tweets. Social network analysis was used to analyze and visualize tweet sharing (retweet) networks among hashtag users.

Results

Overall, we found 4175 original posts and 9720 retweets featuring #datasaveslives by 3649 unique Twitter users. In total, 66.01% (2756/4175) of the original posts were retweeted at least once. Higher frequencies of tweets were observed during the weeks of prominent policy publications, popular conferences, and public engagement events. Cluster analysis based on retweet relationships revealed an interconnected series of groups of #datasaveslives users in academia, health services and policy, and charities and patient networks. Thematic analysis of tweets showed that #datasaveslives was used for a broader range of purposes than indexing information, including event reporting, encouraging participation and action, and showing personal support for data sharing.

Conclusions

This study shows that a hashtag-based social media campaign was effective in encouraging a wide audience of stakeholders to disseminate positive examples of health research. Furthermore, the findings suggest that the campaign supported community building and bridging practices within and between the interdisciplinary sectors related to the field of health data science and encouraged individuals to demonstrate personal support for sharing health data.",,pdf:https://www.jmir.org/2021/2/e16348/PDF; doi:https://doi.org/10.2196/16348; html:https://europepmc.org/articles/PMC7925154 +36689332,https://doi.org/10.1093/neuonc/noad021,GBMdeconvoluteR accurately infers proportions of neoplastic and immune cell populations from bulk glioblastoma transcriptomics data.,"Ajaib S, Lodha D, Pollock S, Hemmings G, Finetti MA, Gusnanto A, Chakrabarty A, Ismail A, Wilson E, Varn FS, Hunter B, Filby A, Brockman AA, McDonald D, Verhaak RGW, Ihrie RA, Stead LF.",,Neuro-oncology,2023,2023-07-01,Y,Immune; Deconvolution; Glioblastoma; Neoplastic; Transcriptomics,,,"

Background

Characterizing and quantifying cell types within glioblastoma (GBM) tumors at scale will facilitate a better understanding of the association between the cellular landscape and tumor phenotypes or clinical correlates. We aimed to develop a tool that deconvolutes immune and neoplastic cells within the GBM tumor microenvironment from bulk RNA sequencing data.

Methods

We developed an IDH wild-type (IDHwt) GBM-specific single immune cell reference consisting of B cells, T-cells, NK-cells, microglia, tumor associated macrophages, monocytes, mast and DC cells. We used this alongside an existing neoplastic single cell-type reference for astrocyte-like, oligodendrocyte- and neuronal progenitor-like and mesenchymal GBM cancer cells to create both marker and gene signature matrix-based deconvolution tools. We applied single-cell resolution imaging mass cytometry (IMC) to ten IDHwt GBM samples, five paired primary and recurrent tumors, to determine which deconvolution approach performed best.

Results

Marker-based deconvolution using GBM-tissue specific markers was most accurate for both immune cells and cancer cells, so we packaged this approach as GBMdeconvoluteR. We applied GBMdeconvoluteR to bulk GBM RNAseq data from The Cancer Genome Atlas and recapitulated recent findings from multi-omics single cell studies with regards associations between mesenchymal GBM cancer cells and both lymphoid and myeloid cells. Furthermore, we expanded upon this to show that these associations are stronger in patients with worse prognosis.

Conclusions

GBMdeconvoluteR accurately quantifies immune and neoplastic cell proportions in IDHwt GBM bulk RNA sequencing data and is accessible here: https://gbmdeconvoluter.leeds.ac.uk.",,pdf:https://academic.oup.com/neuro-oncology/advance-article-pdf/doi/10.1093/neuonc/noad021/49522012/noad021.pdf; doi:https://doi.org/10.1093/neuonc/noad021; html:https://europepmc.org/articles/PMC10326489; pdf:https://europepmc.org/articles/PMC10326489?pdf=render +37777287,https://doi.org/10.1016/s2468-2667(23)00178-0,"All-cause hospitalisation among people living with HIV according to gender, mode of HIV acquisition, ethnicity, and geographical origin in Europe and North America: findings from the ART-CC cohort collaboration.","Rein SM, Lampe FC, Ingle SM, Sterne JAC, Trickey A, Gill MJ, Papastamopoulos V, Wittkop L, van der Valk M, Kitchen M, Guest JL, Satre DD, Wandeler G, Galindo P, Castilho J, Crane HM, Smith CJ.",,The Lancet. Public health,2023,2023-10-01,Y,,,,"

Background

Understanding demographic disparities in hospitalisation is crucial for the identification of vulnerable populations, interventions, and resource planning.

Methods

Data were from the Antiretroviral Therapy Cohort Collaboration (ART-CC) on people living with HIV in Europe and North America, followed up between January, 2007 and December, 2020. We investigated differences in all-cause hospitalisation according to gender and mode of HIV acquisition, ethnicity, and combined geographical origin and ethnicity, in people living with HIV on modern combination antiretroviral therapy (cART). Analyses were performed separately for European and North American cohorts. Hospitalisation rates were assessed using negative binomial multilevel regression, adjusted for age, time since cART intitiaion, and calendar year.

Findings

Among 23 594 people living with HIV in Europe and 9612 in North America, hospitalisation rates per 100 person-years were 16·2 (95% CI 16·0-16·4) and 13·1 (12·8-13·5). Compared with gay, bisexual, and other men who have sex with men, rates were higher for heterosexual men and women, and much higher for men and women who acquired HIV through injection drug use (adjusted incidence rate ratios ranged from 1·2 to 2·5 in Europe and from 1·2 to 3·3 in North America). In both regions, individuals with geographical origin other than the region of study generally had lower hospitalisation rates compared with those with geographical origin of the study country. In North America, Indigenous people and Black or African American individuals had higher rates than White individuals (adjusted incidence rate ratios 1·9 and 1·2), whereas Asian and Hispanic people living with HIV had somewhat lower rates. In Europe there was a lower rate in Asian individuals compared with White individuals.

Interpretation

Substantial disparities exist in all-cause hospitalisation between demographic groups of people living with HIV in the current cART era in high-income settings, highlighting the need for targeted support.

Funding

Royal Free Charity and the National Institute on Alcohol Abuse and Alcoholism.",,pdf:http://www.thelancet.com/article/S2468266723001780/pdf; doi:https://doi.org/10.1016/S2468-2667(23)00178-0; html:https://europepmc.org/articles/PMC10851157; pdf:https://europepmc.org/articles/PMC10851157?pdf=render 37264679,https://doi.org/10.1093/eurjpc/zwad187,Improving 10-year cardiovascular risk prediction in apparently healthy people: flexible addition of risk modifiers on top of SCORE2.,"Hageman SHJ, Petitjaen C, Pennells L, Kaptoge S, Pajouheshnia R, Tillmann T, Blaha MJ, McClelland RL, Matsushita K, Nambi V, Klungel OH, Souverein PC, van der Schouw YT, Verschuren WMM, Lehmann N, Erbel R, Jöckel KH, Di Angelantonio E, Visseren FLJ, Dorresteijn JAN.",,European journal of preventive cardiology,2023,2023-10-01,Y,Biomarkers; Risk stratification; Risk Prediction; cardiovascular; Coronary Calcium Score; Score2,,,"

Aims

In clinical practice, factors associated with cardiovascular disease (CVD) like albuminuria, education level, or coronary artery calcium (CAC) are often known, but not incorporated in cardiovascular risk prediction models. The aims of the current study were to evaluate a methodology for the flexible addition of risk modifying characteristics on top of SCORE2 and to quantify the added value of several clinically relevant risk modifying characteristics.

Methods and results

Individuals without previous CVD or DM were included from the UK Biobank; Atherosclerosis Risk in Communities (ARIC); Multi-Ethnic Study of Atherosclerosis (MESA); European Prospective Investigation into Cancer, The Netherlands (EPIC-NL); and Heinz Nixdorf Recall (HNR) studies (n = 409 757) in whom 16 166 CVD events and 19 149 non-cardiovascular deaths were observed over exactly 10.0 years of follow-up. The effect of each possible risk modifying characteristic was derived using competing risk-adjusted Fine and Gray models. The risk modifying characteristics were applied to individual predictions with a flexible method using the population prevalence and the subdistribution hazard ratio (SHR) of the relevant predictor. Risk modifying characteristics that increased discrimination most were CAC percentile with 0.0198 [95% confidence interval (CI) 0.0115; 0.0281] and hs-Troponin-T with 0.0100 (95% CI 0.0063; 0.0137). External validation was performed in the Clinical Practice Research Datalink (CPRD) cohort (UK, n = 518 015, 12 675 CVD events). Adjustment of SCORE2-predicted risks with both single and multiple risk modifiers did not negatively affect calibration and led to a modest increase in discrimination [0.740 (95% CI 0.736-0.745) vs. unimproved SCORE2 risk C-index 0.737 (95% CI 0.732-0.741)].

Conclusion

The current paper presents a method on how to integrate possible risk modifying characteristics that are not included in existing CVD risk models for the prediction of CVD event risk in apparently healthy people. This flexible methodology improves the accuracy of predicted risks and increases applicability of prediction models for individuals with additional risk known modifiers.",,pdf:https://academic.oup.com/eurjpc/advance-article-pdf/doi/10.1093/eurjpc/zwad187/50506335/zwad187.pdf; doi:https://doi.org/10.1093/eurjpc/zwad187; html:https://europepmc.org/articles/PMC10600319; pdf:https://europepmc.org/articles/PMC10600319?pdf=render 37705296,https://doi.org/10.1002/sim.9898,Using temporal recalibration to improve the calibration of risk prediction models in competing risk settings when there are trends in survival over time.,"Booth S, Mozumder SI, Archer L, Ensor J, Riley RD, Lambert PC, Rutherford MJ.",,Statistics in medicine,2023,2023-09-13,Y,calibration; Risk Prediction; Competing Risks; Temporal Recalibration; Prognostic Models,,,"We have previously proposed temporal recalibration to account for trends in survival over time to improve the calibration of predictions from prognostic models for new patients. This involves first estimating the predictor effects using data from all individuals (full dataset) and then re-estimating the baseline using a subset of the most recent data whilst constraining the predictor effects to remain the same. In this article, we demonstrate how temporal recalibration can be applied in competing risk settings by recalibrating each cause-specific (or subdistribution) hazard model separately. We illustrate this using an example of colon cancer survival with data from the Surveillance Epidemiology and End Results (SEER) program. Data from patients diagnosed in 1995-2004 were used to fit two models for deaths due to colon cancer and other causes respectively. We discuss considerations that need to be made in order to apply temporal recalibration such as the choice of data used in the recalibration step. We also demonstrate how to assess the calibration of these models in new data for patients diagnosed subsequently in 2005. Comparison was made to a standard analysis (when improvements over time are not taken into account) and a period analysis which is similar to temporal recalibration but differs in the data used to estimate the predictor effects. The 10-year calibration plots demonstrated that using the standard approach over-estimated the risk of death due to colon cancer and the total risk of death and that calibration was improved using temporal recalibration or period analysis.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/sim.9898; doi:https://doi.org/10.1002/sim.9898; html:https://europepmc.org/articles/PMC10946485; pdf:https://europepmc.org/articles/PMC10946485?pdf=render 32846977,https://doi.org/10.3390/ijerph17176139,Agreement between the International Physical Activity Questionnaire and Accelerometry in Adults with Orthopaedic Injury.,"Veitch WG, Climie RE, Gabbe BJ, Dunstan DW, Owen N, Ekegren CL.",,International journal of environmental research and public health,2020,2020-08-24,Y,Activity; Validation; Sitting; Accelerometer; Sedentary Behaviour; Ipaq,,,"Orthopaedic injury can lead to decreased physical activity. Valid measures for assessing physical activity are therefore needed in this population. The aim of this study was to determine the agreement and concordance between the International Physical Activity Questionnaire-Short Form (IPAQ) and device-measured physical activity and sitting time in orthopaedic injury patients. Adults with isolated upper or lower limb fracture (n = 46; mean age of 40.5 years) wore two activity monitors (ActiGraph wGT3X-BT and activPAL) for 10 days, from 2 weeks post-discharge. The IPAQ was also completed for a concurrent 7-day period. Lin's concordance correlation coefficients and Bland-Altman plots were calculated to compare walking/stepping time, total METmins, and sitting time. The IPAQ overestimated device-derived walking time (mean difference = 2.34 ± 7.33 h/week) and total METmins (mean difference = 767 ± 1659 METmins/week) and underestimated sitting time (mean difference = -2.26 ± 3.87 h/day). There was fair concordance between IPAQ-reported and device-measured walking (ρ = 0.34) and sitting time (ρ = 0.38) and moderate concordance between IPAQ-reported and device-measured METmins (ρ = 0.43). In patients with orthopaedic injury, the IPAQ overestimates physical activity and underestimates sitting time. Higher agreement was observed in the forms of activity (walking, total PA and sitting) commonly performed by this patient group.",,pdf:https://www.mdpi.com/1660-4601/17/17/6139/pdf?version=1598511551; doi:https://doi.org/10.3390/ijerph17176139; html:https://europepmc.org/articles/PMC7504024; pdf:https://europepmc.org/articles/PMC7504024?pdf=render @@ -1641,33 +1641,33 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 30742608,https://doi.org/10.1371/journal.pcbi.1006785,"Assessing the performance of real-time epidemic forecasts: A case study of Ebola in the Western Area region of Sierra Leone, 2014-15.","Funk S, Camacho A, Kucharski AJ, Lowe R, Eggo RM, Edmunds WJ.",,PLoS computational biology,2019,2019-02-11,Y,,Applied Analytics,,"Real-time forecasts based on mathematical models can inform critical decision-making during infectious disease outbreaks. Yet, epidemic forecasts are rarely evaluated during or after the event, and there is little guidance on the best metrics for assessment. Here, we propose an evaluation approach that disentangles different components of forecasting ability using metrics that separately assess the calibration, sharpness and bias of forecasts. This makes it possible to assess not just how close a forecast was to reality but also how well uncertainty has been quantified. We used this approach to analyse the performance of weekly forecasts we generated in real time for Western Area, Sierra Leone, during the 2013-16 Ebola epidemic in West Africa. We investigated a range of forecast model variants based on the model fits generated at the time with a semi-mechanistic model, and found that good probabilistic calibration was achievable at short time horizons of one or two weeks ahead but model predictions were increasingly unreliable at longer forecasting horizons. This suggests that forecasts may have been of good enough quality to inform decision making based on predictions a few weeks ahead of time but not longer, reflecting the high level of uncertainty in the processes driving the trajectory of the epidemic. Comparing forecasts based on the semi-mechanistic model to simpler null models showed that the best semi-mechanistic model variant performed better than the null models with respect to probabilistic calibration, and that this would have been identified from the earliest stages of the outbreak. As forecasts become a routine part of the toolkit in public health, standards for evaluation of performance will be important for assessing quality and improving credibility of mathematical models, and for elucidating difficulties and trade-offs when aiming to make the most useful and reliable forecasts.",,pdf:https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1006785&type=printable; doi:https://doi.org/10.1371/journal.pcbi.1006785; html:https://europepmc.org/articles/PMC6386417; pdf:https://europepmc.org/articles/PMC6386417?pdf=render 33782427,https://doi.org/10.1038/s41598-021-86266-3,Analysis of temporal trends in potential COVID-19 cases reported through NHS Pathways England.,"Leclerc QJ, Nightingale ES, Abbott S, CMMID COVID-19 Working Group, Jombart T.",,Scientific reports,2021,2021-03-29,Y,,,,"The National Health Service (NHS) Pathways triage system collates data on enquiries to 111 and 999 services in England. Since the 18th of March 2020, these data have been made publically available for potential COVID-19 symptoms self-reported by members of the public. Trends in such reports over time are likely to reflect behaviour of the ongoing epidemic within the wider community, potentially capturing valuable information across a broader severity profile of cases than hospital admission data. We present a fully reproducible analysis of temporal trends in NHS Pathways reports until 14th May 2020, nationally and regionally, and demonstrate that rates of growth/decline and effective reproduction number estimated from these data may be useful in monitoring transmission. This is a particularly pressing issue as lockdown restrictions begin to be lifted and evidence of disease resurgence must be constantly reassessed. We further assess the correlation between NHS Pathways reports and a publicly available NHS dataset of COVID-19-associated deaths in England, finding that enquiries to 111/999 were strongly associated with daily deaths reported 16 days later. Our results highlight the potential of NHS Pathways as the basis of an early warning system. However, this dataset relies on self-reported symptoms, which are at risk of being severely biased. Further detailed work is therefore necessary to investigate potential behavioural issues which might otherwise explain our conclusions.",,pdf:https://www.nature.com/articles/s41598-021-86266-3.pdf; doi:https://doi.org/10.1038/s41598-021-86266-3; html:https://europepmc.org/articles/PMC8007605; pdf:https://europepmc.org/articles/PMC8007605?pdf=render 36462729,https://doi.org/10.1016/j.neuroimage.2022.119779,Amplitudes of resting-state functional networks - investigation into their correlates and biophysical properties.,"Lee S, Bijsterbosch JD, Almagro FA, Elliott L, McCarthy P, Taschler B, Sala-Llonch R, Beckmann CF, Duff EP, Smith SM, Douaud G.",,NeuroImage,2023,2022-12-01,Y,Dual regression; Gwas; Resting-state Fmri; Uk Biobank; Temporal Synchrony; Network Amplitude,,,"Resting-state fMRI studies have shown that multiple functional networks, which consist of distributed brain regions that share synchronised spontaneous activity, co-exist in the brain. As these resting-state networks (RSNs) have been thought to reflect the brain's intrinsic functional organization, intersubject variability in the networks' spontaneous fluctuations may be associated with individuals' clinical, physiological, cognitive, and genetic traits. Here, we investigated resting-state fMRI data along with extensive clinical, lifestyle, and genetic data collected from 37,842 UK Biobank participants, with the object of elucidating intersubject variability in the fluctuation amplitudes of RSNs. Functional properties of the RSN amplitudes were first examined by analyzing correlations with the well-established between-network functional connectivity. It was found that a network amplitude is highly correlated with the mean strength of the functional connectivity that the network has with the other networks. Intersubject clustering analysis showed the amplitudes are most strongly correlated with age, cardiovascular factors, body composition, blood cell counts, lung function, and sex, with some differences in the correlation strengths between sensory and cognitive RSNs. Genome-wide association studies (GWASs) of RSN amplitudes identified several significant genetic variants reported in previous GWASs for their implications in sleep duration. We provide insight into key factors determining RSN amplitudes and demonstrate that intersubject variability of the amplitudes primarily originates from differences in temporal synchrony between functionally linked brain regions, rather than differences in the magnitude of raw voxelwise BOLD signal changes. This finding additionally revealed intriguing differences between sensory and cognitive RSNs with respect to sex effects on temporal synchrony and provided evidence suggesting that synchronous coactivations of functionally linked brain regions, and magnitudes of BOLD signal changes, may be related to different genetic mechanisms. These results underscore that intersubject variability of the amplitudes in health and disease need to be interpreted largely as a measure of the sum of within-network temporal synchrony and amplitudes of BOLD signals, with a dominant contribution from the former.",,doi:https://doi.org/10.1016/j.neuroimage.2022.119779; doi:https://doi.org/10.1016/j.neuroimage.2022.119779; html:https://europepmc.org/articles/PMC10933815; pdf:https://europepmc.org/articles/PMC10933815?pdf=render -37722858,https://doi.org/10.3399/bjgp.2023.0077,Inequities in hypertension management: observational cross-sectional study in North East London using electronic health records.,"Rison S, Redfern O, Dostal I, Carvalho C, Mathur R, Raisi-Estabragh Z, Robson J.",,The British journal of general practice : the journal of the Royal College of General Practitioners,2023,2023-10-26,Y,Hypertension; Cardiovascular diseases; Blood pressure; General Practice; Antihypertensives; Health Inequities,,,"

Background

Hypertension is a key modifiable risk factor for cardiovascular disease - the leading cause of death in the UK. Good blood pressure (BP) control reduces mortality. However, health inequities may lead to variability in hypertension monitoring and control.

Aim

To investigate health inequities related to ethnicity, sex, age, and socioeconomic status in the monitoring, treatment, and control of BP in a large cohort of adult patients with hypertension.

Design and setting

A cross-sectional cohort study of adults with hypertension registered with general practices in North East London on 1 April 2019.

Method

Multivariable logistic regression was used to estimate associations of demographics and treatment intensity for the following hypertension management indicators: a) BP recording in past 12 months; b) BP on age- adjusted target; and c) BP on age-adjusted target and BP recorded in past 12 months.

Results

In total, 156 296 adults were included. The Black ethnicity group was less likely to have controlled BP than the White ethnicity group (odds ratio [OR] 0.87, 95% [confidence interval] CI = 0.84 to 0.91). The Asian ethnicity group was more likely to have controlled BP (OR 1.28, 95% CI = 1.23 to 1.32). Ethnicity differences in control could not be explained by the likelihood of having a recent BP recording, nor by treatment intensity differences. Older adults (aged ≥50 years) were more likely to have controlled hypertension than younger patients.

Conclusion

Individuals of Black ethnicity and younger people are less likely to have controlled hypertension and may warrant targeted interventions. Possible explanations for these findings are presented but further research is needed about reasons for ethnic differences.",,doi:https://doi.org/10.3399/BJGP.2023.0077; html:https://europepmc.org/articles/PMC10523336; pdf:https://europepmc.org/articles/PMC10523336?pdf=render 32400358,https://doi.org/10.2807/1560-7917.es.2020.25.18.2000632,"Estimating number of cases and spread of coronavirus disease (COVID-19) using critical care admissions, United Kingdom, February to March 2020.","Jit M, Jombart T, Nightingale ES, Endo A, Abbott S, LSHTM Centre for Mathematical Modelling of Infectious Diseases COVID-19 Working Group, Edmunds WJ.",,Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin,2020,2020-05-01,Y,Surveillance; intensive care unit; mathematical model; Reproduction Number; Sars-cov-2; Coronavirus Disease 2019,,,"An exponential growth model was fitted to critical care admissions from two surveillance databases to determine likely coronavirus disease (COVID-19) case numbers, critical care admissions and epidemic growth in the United Kingdom before the national lockdown. We estimate, on 23 March, a median of 114,000 (95% credible interval (CrI): 78,000-173,000) new cases and 258 (95% CrI: 220-319) new critical care reports, with 527,000 (95% CrI: 362,000-797,000) cumulative cases since 16 February.","The authors of this paper estimate the number of cases and spread of COVID-19 using data on critical care admissions within the UK, from a period of February to March 2020. Their results suggest that the UK had hundreds of thousands of COVID-19 cases by the time the national lockdown was implemented. They highlight the usefulness of surveilling critical care data to better understand the dynamics of the epidemic and better inform the response measures.",pdf:https://www.eurosurveillance.org/deliver/fulltext/eurosurveillance/25/18/eurosurv-25-18-2.pdf?itemId=%2Fcontent%2F10.2807%2F1560-7917.ES.2020.25.18.2000632&mimeType=pdf&containerItemId=content/eurosurveillance; doi:https://doi.org/10.2807/1560-7917.ES.2020.25.18.2000632; html:https://europepmc.org/articles/PMC7219029; pdf:https://europepmc.org/articles/PMC7219029?pdf=render +37722858,https://doi.org/10.3399/bjgp.2023.0077,Inequities in hypertension management: observational cross-sectional study in North East London using electronic health records.,"Rison S, Redfern O, Dostal I, Carvalho C, Mathur R, Raisi-Estabragh Z, Robson J.",,The British journal of general practice : the journal of the Royal College of General Practitioners,2023,2023-10-26,Y,Hypertension; Cardiovascular diseases; Blood pressure; General Practice; Antihypertensives; Health Inequities,,,"

Background

Hypertension is a key modifiable risk factor for cardiovascular disease - the leading cause of death in the UK. Good blood pressure (BP) control reduces mortality. However, health inequities may lead to variability in hypertension monitoring and control.

Aim

To investigate health inequities related to ethnicity, sex, age, and socioeconomic status in the monitoring, treatment, and control of BP in a large cohort of adult patients with hypertension.

Design and setting

A cross-sectional cohort study of adults with hypertension registered with general practices in North East London on 1 April 2019.

Method

Multivariable logistic regression was used to estimate associations of demographics and treatment intensity for the following hypertension management indicators: a) BP recording in past 12 months; b) BP on age- adjusted target; and c) BP on age-adjusted target and BP recorded in past 12 months.

Results

In total, 156 296 adults were included. The Black ethnicity group was less likely to have controlled BP than the White ethnicity group (odds ratio [OR] 0.87, 95% [confidence interval] CI = 0.84 to 0.91). The Asian ethnicity group was more likely to have controlled BP (OR 1.28, 95% CI = 1.23 to 1.32). Ethnicity differences in control could not be explained by the likelihood of having a recent BP recording, nor by treatment intensity differences. Older adults (aged ≥50 years) were more likely to have controlled hypertension than younger patients.

Conclusion

Individuals of Black ethnicity and younger people are less likely to have controlled hypertension and may warrant targeted interventions. Possible explanations for these findings are presented but further research is needed about reasons for ethnic differences.",,doi:https://doi.org/10.3399/BJGP.2023.0077; html:https://europepmc.org/articles/PMC10523336; pdf:https://europepmc.org/articles/PMC10523336?pdf=render 36060542,https://doi.org/10.3389/fdgth.2022.939292,Clinical deployment environments: Five pillars of translational machine learning for health.,"Harris S, Bonnici T, Keen T, Lilaonitkul W, White MJ, Swanepoel N.",,Frontiers in digital health,2022,2022-08-19,Y,Safety; Artificial intelligence; Machine Learning; Health Informatics; Translational Medicine; Ml-ops,,,"Machine Learning for Health (ML4H) has demonstrated efficacy in computer imaging and other self-contained digital workflows, but has failed to substantially impact routine clinical care. This is no longer because of poor adoption of Electronic Health Records Systems (EHRS), but because ML4H needs an infrastructure for development, deployment and evaluation within the healthcare institution. In this paper, we propose a design pattern called a Clinical Deployment Environment (CDE). We sketch the five pillars of the CDE: (1) real world development supported by live data where ML4H teams can iteratively build and test at the bedside (2) an ML-Ops platform that brings the rigour and standards of continuous deployment to ML4H (3) design and supervision by those with expertise in AI safety (4) the methods of implementation science that enable the algorithmic insights to influence the behaviour of clinicians and patients and (5) continuous evaluation that uses randomisation to avoid bias but in an agile manner. The CDE is intended to answer the same requirements that bio-medicine articulated in establishing the translational medicine domain. It envisions a transition from ""real-world"" data to ""real-world"" development.",,pdf:https://www.frontiersin.org/articles/10.3389/fdgth.2022.939292/pdf; doi:https://doi.org/10.3389/fdgth.2022.939292; html:https://europepmc.org/articles/PMC9437594; pdf:https://europepmc.org/articles/PMC9437594?pdf=render 34155917,https://doi.org/10.1161/jaha.120.020246,Antenatal Exposure to UV-B Radiation and Preeclampsia: A Retrospective Cohort Study.,"Hastie CE, Mackay DF, Clemens TL, Cherrie MPC, Megaw LJ, Smith GCS, Stock SJ, Dibben C, Pell JP.",,Journal of the American Heart Association,2021,2021-06-22,Y,UV light; Preeclampsia; Seasonal variations; Environmental Exposures,,,"Background Risk of preeclampsia varies by month of delivery. We tested whether this seasonal patterning may be mediated through maternal vitamin D concentration using antenatal exposure to UV-B radiation as an instrumental variable. Methods and Results Scottish maternity records were linked to antenatal UV-B exposure derived from satellites between 2000 and 2010. Logistic regression analyses were used to explore the association between UV-B and preeclampsia, adjusting for the potential confounding effects of month of conception, child's sex, gestation, parity, and mean monthly temperature. Of the 522 896 eligible singleton deliveries, 8689 (1.66%) mothers developed preeclampsia. Total antenatal UV-B exposure ranged from 43.18 to 101.11 kJ/m2 and was associated with reduced risk of preeclampsia with evidence of a dose-response relationship (highest quintile of exposure: adjusted odds ratio, 0.57; 95% CI, 0.44-0.72; P<0.001). Associations were demonstrated for UV-B exposure in all 3 trimesters. Conclusions The seasonal patterning of preeclampsia may be mediated through low maternal vitamin D concentration in winter resulting from low UV-B radiation. Interventional studies are required to determine whether vitamin D supplements or UV-B-emitting light boxes can reduce the seasonal patterning of preeclampsia.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/JAHA.120.020246; doi:https://doi.org/10.1161/JAHA.120.020246; html:https://europepmc.org/articles/PMC8403301; pdf:https://europepmc.org/articles/PMC8403301?pdf=render 32570434,https://doi.org/10.3233/shti200210,Using Unsupervised Learning to Identify Clinical Subtypes of Alzheimer's Disease in Electronic Health Records.,"Alexander N, Alexander DC, Barkhof F, Denaxas S.",,Studies in health technology and informatics,2020,2020-06-01,N,Phenotyping; Alzheimer’s disease; Machine Learning; Electronic Health Records,,,"Identifying subtypes of Alzheimer's Disease (AD) can lead towards the creation of personalized interventions and potentially improve outcomes. In this study, we use UK primary care electronic health records (EHR) from the CALIBER resource to identify and characterize clinically-meaningful clusters patients using unsupervised learning approaches of MCA and K-means. We discovered and characterized five clusters with different profiles (mental health, non-typical AD, typical AD, CVD and men with cancer). The mental health cluster had faster rate of progression than all the other clusters making it a target for future research and intervention. Our results demonstrate that unsupervised learning approaches can be utilized on EHR to identify subtypes of heterogeneous conditions.",,doi:https://doi.org/10.3233/SHTI200210 33559289,https://doi.org/10.1002/ejp.1750,The association between exposure to domestic abuse in women and the development of syndromes indicating central nervous system sensitization: A retrospective cohort study using UK primary care records.,"Chandan JS, Keerthy D, Gokhale KM, Bradbury-Jones C, Raza K, Bandyopadhyay S, Taylor J, Nirantharakumar K.",,"European journal of pain (London, England)",2021,2021-03-15,N,,,,"

Background

Domestic abuse is a global public health issue. The association between the development of central sensitivity syndromes (CSS) and previous exposure to domestic abuse has been poorly understood particularly within European populations.

Methods

A retrospective cohort study using the 'The Health Improvement Network,' (UK primary care medical records) between 1st January 1995-31st December 2018. 22,604 adult women exposed to domestic abuse were age matched to 44,671 unexposed women. The average age at cohort entry was 36 years and the median follow-up was 2.5 years. The outcomes of interest were the development of a variety of syndromes which demonstrate central nervous system sensitization. Fibromyalgia, chronic fatigue syndrome and temporomandibular joint disorder outcomes have been reported previously. Outcomes were adjusted for the presence of mental ill health.

Results

During the study period, women exposed to domestic abuse experienced an increased risk of developing chronic lower back pain (adjusted incidence rate ratio [aIRR] 2.28; 95% CI 1.85-2.80), chronic headaches (aIRR 3.15; 95% CI 1.07-9.23), irritable bowel syndrome (aIRR 1.41; 95% CI 1.25-1.60) and restless legs syndrome (aIRR 1.89; 95% CI 1.44-2.48). However, no positive association was seen with the development of interstitial cystitis (aIRR 0.52; 95% CI 0.14-1.93), vulvodynia (aIRR 0.42; 95% CI 0.14-1.25) and myofascial pain syndrome (aIRR 1.01; 95% CI 0.28-3.61).

Conclusion

This study demonstrates the need to consider a past history of domestic abuse in patients presenting with CSS; and also consider preventative approaches in mitigating the risk of developing CSS following exposure to domestic abuse.

Significance

Domestic abuse is a global public health issue, with a poorly understood relationship with the development of complex pain syndromes. Using a large UK primary care database, we were able to conduct the first global cohort study to explore this further. We found a strong pain morbidity burden associated with domestic abuse, suggesting the need for urgent public health intervention to not only prevent domestic abuse but also the associated negative pain consequences.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ejp.1750; doi:https://doi.org/10.1002/ejp.1750 -38597854,https://doi.org/10.1016/j.jcmg.2024.03.001,Noninvasive Techniques for Tracking Biological Aging of the Cardiovascular System: JACC Family Series.,"Raisi-Estabragh Z, Szabo L, Schuermans A, Salih AM, Chin CWL, Vágó H, Altmann A, Ng FS, Garg P, Pavanello S, Marwick TH, Petersen SE.",,JACC. Cardiovascular imaging,2024,2024-04-08,N,Molecular markers; Echocardiography; Cardiac Computed Tomography; Healthy Aging; Cardiac Magnetic Resonance; Multimodality Cardiovascular Imaging; Biological Heart Age,,,"Population aging is one of the most important demographic transformations of our time. Increasing the ""health span""-the proportion of life spent in good health-is a global priority. Biological aging comprises molecular and cellular modifications over many years, which culminate in gradual physiological decline across multiple organ systems and predispose to age-related illnesses. Cardiovascular disease is a major cause of ill health and premature death in older people. The rate at which biological aging occurs varies across individuals of the same age and is influenced by a wide range of genetic and environmental exposures. The authors review the hallmarks of biological cardiovascular aging and their capture using imaging and other noninvasive techniques and examine how this information may be used to understand aging trajectories, with the aim of guiding individual- and population-level interventions to promote healthy aging.",,doi:https://doi.org/10.1016/j.jcmg.2024.03.001 36960327,https://doi.org/10.2147/clep.s384605,Severe Mental Illness Among Adults with Atopic Eczema or Psoriasis: Population-Based Matched Cohort Studies within UK Primary Care.,"Adesanya EI, Henderson AD, Matthewman J, Bhate K, Hayes JF, Mulick A, Mathur R, Smith C, Carreira H, Rathod SD, Langan SM, Mansfield KE.",,Clinical epidemiology,2023,2023-03-17,Y,Psychology; epidemiology; Dermatology,,,"

Background

Existing research exploring associations between atopic eczema (AE) or psoriasis, and severe mental illness (SMI - ie, schizophrenia, bipolar disorder, other psychoses) is limited, with longitudinal evidence particularly scarce. Therefore, temporal directions of associations are unclear. We aimed to investigate associations between AE or psoriasis and incident SMI among adults.

Methods

We conducted matched cohort studies using primary care electronic health records (January 1997 to January 2020) from the UK Clinical Practice Research Datalink GOLD. We identified two cohorts: 1) adults (≥18 years) with and without AE and 2) adults with and without psoriasis. We matched (on age, sex, general practice) adults with AE or psoriasis with up to five adults without. We used Cox regression, stratified by matched set, to estimate hazard ratios (HRs) comparing incident SMI among adults with and without AE or psoriasis.

Results

We identified 1,023,232 adults with AE and 4,908,059 without, and 363,210 with psoriasis and 1,801,875 without. After adjusting for matching variables (age, sex, general practice) and potential confounders (deprivation, calendar period) both AE and psoriasis were associated with at least a 17% increased hazard of SMI (AE: HR=1.17,95% CI=1.12-1.22; psoriasis: HR=1.26,95% CI=1.18-1.35). After additionally adjusting for potential mediators (comorbidity burden, harmful alcohol use, smoking status, body mass index, and, in AE only, sleep problems and high-dose glucocorticoids), associations with SMI did not persist for AE (HR=0.98,95% CI=0.93-1.04), and were attenuated for psoriasis (HR=1.14,95% CI=1.05-1.23).

Conclusion

Our findings suggest adults with AE or psoriasis are at increased risk of SMI compared to matched comparators. After adjusting for potential mediators, associations with SMI did not persist for AE, and were attenuated for psoriasis, suggesting that the increased risk may be explained by mediating factors (eg, sleep problems). Our research highlights the importance of monitoring mental health in adults with AE or psoriasis.",,pdf:https://www.dovepress.com/getfile.php?fileID=88236; doi:https://doi.org/10.2147/CLEP.S384605; html:https://europepmc.org/articles/PMC10030004; pdf:https://europepmc.org/articles/PMC10030004?pdf=render -37751444,https://doi.org/10.1371/journal.pone.0290583,Long Covid symptoms and diagnosis in primary care: A cohort study using structured and unstructured data in The Health Improvement Network primary care database.,"Shah AD, Subramanian A, Lewis J, Dhalla S, Ford E, Haroon S, Kuan V, Nirantharakumar K.",,PloS one,2023,2023-09-26,Y,,,,"

Background

Long Covid is a widely recognised consequence of COVID-19 infection, but little is known about the burden of symptoms that patients present with in primary care, as these are typically recorded only in free text clinical notes.

Aims

To compare symptoms in patients with and without a history of COVID-19, and investigate symptoms associated with a Long Covid diagnosis.

Methods

We used primary care electronic health record data until the end of December 2020 from The Health Improvement Network (THIN), a Cegedim database. We included adults registered with participating practices in England, Scotland or Wales. We extracted information about 89 symptoms and 'Long Covid' diagnoses from free text using natural language processing. We calculated hazard ratios (adjusted for age, sex, baseline medical conditions and prior symptoms) for each symptom from 12 weeks after the COVID-19 diagnosis.

Results

We compared 11,015 patients with confirmed COVID-19 and 18,098 unexposed controls. Only 20% of symptom records were coded, with 80% in free text. A wide range of symptoms were associated with COVID-19 at least 12 weeks post-infection, with strongest associations for fatigue (adjusted hazard ratio (aHR) 3.46, 95% confidence interval (CI) 2.87, 4.17), shortness of breath (aHR 2.89, 95% CI 2.48, 3.36), palpitations (aHR 2.59, 95% CI 1.86, 3.60), and phlegm (aHR 2.43, 95% CI 1.65, 3.59). However, a limited subset of symptoms were recorded within 7 days prior to a Long Covid diagnosis in more than 20% of cases: shortness of breath, chest pain, pain, fatigue, cough, and anxiety / depression.

Conclusions

Numerous symptoms are reported to primary care at least 12 weeks after COVID-19 infection, but only a subset are commonly associated with a GP diagnosis of Long Covid.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0290583&type=printable; doi:https://doi.org/10.1371/journal.pone.0290583; html:https://europepmc.org/articles/PMC10521988; pdf:https://europepmc.org/articles/PMC10521988?pdf=render 32735830,https://doi.org/10.1016/s2352-3026(20)30228-3,Cardiovascular adverse events following treatment for non-Hodgkin lymphoma - Authors' reply.,"Linschoten M, Kamphuis JA, Asselbergs FW.",,The Lancet. Haematology,2020,2020-08-01,N,,,,,,doi:https://doi.org/10.1016/S2352-3026(20)30228-3 33615277,https://doi.org/10.1016/j.xpro.2021.100334,Massive expansion and cryopreservation of functional human induced pluripotent stem cell-derived cardiomyocytes.,"Maas RGC, Lee S, Harakalova M, Snijders Blok CJB, Goodyer WR, Hjortnaes J, Doevendans PAFM, Van Laake LW, van der Velden J, Asselbergs FW, Wu JC, Sluijter JPG, Wu SM, Buikema JW.",,STAR protocols,2021,2021-02-09,Y,Cell differentiation; Cell culture; Stem Cells,,,"Since the discovery of human induced pluripotent stem cells (hiPSCs), numerous strategies have been established to efficiently derive cardiomyocytes from hiPSCs (hiPSC-CMs). Here, we describe a cost-effective strategy for the subsequent massive expansion (>250-fold) of high-purity hiPSC-CMs relying on two aspects: removal of cell-cell contacts and small-molecule inhibition with CHIR99021. The protocol maintains CM functionality, allows cryopreservation, and the cells can be used in downstream assays such as disease modeling, drug and toxicity screening, and cell therapy. For complete details on the use and execution of this protocol, please refer to Buikema (2020).",,doi:https://doi.org/10.1016/j.xpro.2021.100334; doi:https://doi.org/10.1016/j.xpro.2021.100334; html:https://europepmc.org/articles/PMC7881265; pdf:https://europepmc.org/articles/PMC7881265?pdf=render +38597854,https://doi.org/10.1016/j.jcmg.2024.03.001,Noninvasive Techniques for Tracking Biological Aging of the Cardiovascular System: JACC Family Series.,"Raisi-Estabragh Z, Szabo L, Schuermans A, Salih AM, Chin CWL, Vágó H, Altmann A, Ng FS, Garg P, Pavanello S, Marwick TH, Petersen SE.",,JACC. Cardiovascular imaging,2024,2024-04-08,N,Molecular markers; Echocardiography; Cardiac Computed Tomography; Healthy Aging; Cardiac Magnetic Resonance; Multimodality Cardiovascular Imaging; Biological Heart Age,,,"Population aging is one of the most important demographic transformations of our time. Increasing the ""health span""-the proportion of life spent in good health-is a global priority. Biological aging comprises molecular and cellular modifications over many years, which culminate in gradual physiological decline across multiple organ systems and predispose to age-related illnesses. Cardiovascular disease is a major cause of ill health and premature death in older people. The rate at which biological aging occurs varies across individuals of the same age and is influenced by a wide range of genetic and environmental exposures. The authors review the hallmarks of biological cardiovascular aging and their capture using imaging and other noninvasive techniques and examine how this information may be used to understand aging trajectories, with the aim of guiding individual- and population-level interventions to promote healthy aging.",,doi:https://doi.org/10.1016/j.jcmg.2024.03.001 +37751444,https://doi.org/10.1371/journal.pone.0290583,Long Covid symptoms and diagnosis in primary care: A cohort study using structured and unstructured data in The Health Improvement Network primary care database.,"Shah AD, Subramanian A, Lewis J, Dhalla S, Ford E, Haroon S, Kuan V, Nirantharakumar K.",,PloS one,2023,2023-09-26,Y,,,,"

Background

Long Covid is a widely recognised consequence of COVID-19 infection, but little is known about the burden of symptoms that patients present with in primary care, as these are typically recorded only in free text clinical notes.

Aims

To compare symptoms in patients with and without a history of COVID-19, and investigate symptoms associated with a Long Covid diagnosis.

Methods

We used primary care electronic health record data until the end of December 2020 from The Health Improvement Network (THIN), a Cegedim database. We included adults registered with participating practices in England, Scotland or Wales. We extracted information about 89 symptoms and 'Long Covid' diagnoses from free text using natural language processing. We calculated hazard ratios (adjusted for age, sex, baseline medical conditions and prior symptoms) for each symptom from 12 weeks after the COVID-19 diagnosis.

Results

We compared 11,015 patients with confirmed COVID-19 and 18,098 unexposed controls. Only 20% of symptom records were coded, with 80% in free text. A wide range of symptoms were associated with COVID-19 at least 12 weeks post-infection, with strongest associations for fatigue (adjusted hazard ratio (aHR) 3.46, 95% confidence interval (CI) 2.87, 4.17), shortness of breath (aHR 2.89, 95% CI 2.48, 3.36), palpitations (aHR 2.59, 95% CI 1.86, 3.60), and phlegm (aHR 2.43, 95% CI 1.65, 3.59). However, a limited subset of symptoms were recorded within 7 days prior to a Long Covid diagnosis in more than 20% of cases: shortness of breath, chest pain, pain, fatigue, cough, and anxiety / depression.

Conclusions

Numerous symptoms are reported to primary care at least 12 weeks after COVID-19 infection, but only a subset are commonly associated with a GP diagnosis of Long Covid.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0290583&type=printable; doi:https://doi.org/10.1371/journal.pone.0290583; html:https://europepmc.org/articles/PMC10521988; pdf:https://europepmc.org/articles/PMC10521988?pdf=render 32023934,https://doi.org/10.3390/ijerph17030892,Identifying Homogeneous Patterns of Injury in Paediatric Trauma Patients to Improve Risk-Adjusted Models of Mortality and Functional Outcomes.,"Dipnall JF, Gabbe BJ, Teague WJ, Beck B.",,International journal of environmental research and public health,2020,2020-01-31,Y,"Trauma; Injury; Paediatric; Latent Class Analysis; Risk Adjustment; Mortality, Koschi, Classes",Improving Public Health,injuries and accidents,"Injury is a leading cause of morbidity and mortality in the paediatric population and exhibits complex injury patterns. This study aimed to identify homogeneous groups of paediatric major trauma patients based on their profile of injury for use in mortality and functional outcomes risk-adjusted models. Data were extracted from the population-based Victorian State Trauma Registry for patients aged 0-15 years, injured 2006-2016. Four Latent Class Analysis (LCA) models with/without covariates of age/sex tested up to six possible latent classes. Five risk-adjusted models of in-hospital mortality and 6-month functional outcomes incorporated a combination of Injury Severity Score (ISS), New ISS (NISS), and LCA classes. LCA models replicated the best log-likelihood and entropy > 0.8 for all models (N = 1281). Four latent injury classes were identified: isolated head; isolated abdominal organ; multi-trauma injuries, and other injuries. The best models, in terms of goodness of fit statistics and model diagnostics, included the LCA classes and NISS. The identification of isolated head, isolated abdominal, multi-trauma and other injuries as key latent paediatric injury classes highlights areas for emphasis in planning prevention initiatives and paediatric trauma system development. Future risk-adjusted paediatric injury models that include these injury classes with the NISS when evaluating mortality and functional outcomes is recommended.",,pdf:https://www.mdpi.com/1660-4601/17/3/892/pdf?version=1580475934; doi:https://doi.org/10.3390/ijerph17030892; html:https://europepmc.org/articles/PMC7037699; pdf:https://europepmc.org/articles/PMC7037699?pdf=render 35115301,https://doi.org/10.1136/bjophthalmol-2021-319641,Metformin and risk of age-related macular degeneration in individuals with type 2 diabetes: a retrospective cohort study.,"Gokhale KM, Adderley NJ, Subramanian A, Lee WH, Han D, Coker J, Braithwaite T, Denniston AK, Keane PA, Nirantharakumar K.",,The British journal of ophthalmology,2023,2022-02-03,N,Degeneration; epidemiology; Macula,,,"

Background

Age-related macular degeneration (AMD) in its late stages is a leading cause of sight loss in developed countries. Some previous studies have suggested that metformin may be associated with a reduced risk of developing AMD, but the evidence is inconclusive.

Aims

To explore the relationship between metformin use and development of AMD among patients with type 2 diabetes in the UK.

Methods

A large, population-based retrospective open cohort study with a time-dependent exposure design was carried out using IQVIA Medical Research Data, 1995-2019. Patients aged ≥40 with diagnosed type 2 diabetes were included.The exposed group was those prescribed metformin (with or without any other antidiabetic medications); the comparator (unexposed) group was those prescribed other antidiabetic medications only. The exposure status was treated as time varying, collected at 3-monthly time intervals.Extended Cox proportional hazards regression was used to calculate the adjusted HRs for development of the outcome, newly diagnosed AMD.

Results

A total of 173 689 patients, 57% men, mean (SD) age 62.8 (11.6) years, with incident type 2 diabetes and a record of one or more antidiabetic medications were included in the study. Median follow-up was 4.8 (IQR 2.3-8.3, range 0.5-23.8) years. 3111 (1.8%) patients developed AMD. The adjusted HR for diagnosis of AMD was 1.02 (95% CI 0.92 to 1.12) in patients prescribed metformin (with or without other antidiabetic medications) compared with those prescribed any other antidiabetic medication only.

Conclusion

We found no evidence that metformin was associated with risk of AMD in primary care patients requiring treatment for type 2 diabetes.",,pdf:https://discovery.ucl.ac.uk/10143945/1/Keane_T2DM%20metformin%20and%20risk%20of%20AMD%20BJO%2020220111%20clean.pdf; doi:https://doi.org/10.1136/bjophthalmol-2021-319641 37407123,https://doi.org/10.1016/j.jcmg.2023.01.016,Ischemic Heart Disease and Vascular Risk Factors Are Associated With Accelerated Brain Aging.,"Rauseo E, Salih A, Raisi-Estabragh Z, Aung N, Khanderia N, Slabaugh GG, Marshall CR, Neubauer S, Radeva P, Galazzo IB, Menegaz G, Petersen SE.",,JACC. Cardiovascular imaging,2023,2023-04-12,Y,brain aging; ischemic heart disease; Cognitive Decline; Vascular Risk Factors; Brain Health,,,"

Background

Ischemic heart disease (IHD) has been linked with poor brain outcomes. The brain magnetic resonance imaging-derived difference between predicted brain age and actual chronological age (brain-age delta in years, positive for accelerated brain aging) may serve as an effective means of communicating brain health to patients to promote healthier lifestyles.

Objectives

The authors investigated the impact of prevalent IHD on brain aging, potential underlying mechanisms, and its relationship with dementia risk, vascular risk factors, cardiovascular structure, and function.

Methods

Brain age was estimated in subjects with prevalent IHD (n = 1,341) using a Bayesian ridge regression model with 25 structural (volumetric) brain magnetic resonance imaging features and built using UK Biobank participants with no prevalent IHD (n = 35,237).

Results

Prevalent IHD was linked to significantly accelerated brain aging (P < 0.001) that was not fully mediated by microvascular injury. Brain aging (positive brain-age delta) was associated with increased risk of dementia (OR: 1.13 [95% CI: 1.04-1.22]; P = 0.002), vascular risk factors (such as diabetes), and high adiposity. In the absence of IHD, brain aging was also associated with cardiovascular structural and functional changes typically observed in aging hearts. However, such alterations were not linked with risk of dementia.

Conclusions

Prevalent IHD and coexisting vascular risk factors are associated with accelerated brain aging and risk of dementia. Positive brain-age delta representing accelerated brain aging may serve as an effective communication tool to show the impact of modifiable risk factors and disease supporting preventative strategies.",,doi:https://doi.org/10.1016/j.jcmg.2023.01.016; html:https://europepmc.org/articles/PMC10317841; pdf:https://europepmc.org/articles/PMC10317841?pdf=render 36456017,https://doi.org/10.1136/bmjopen-2022-066288,"Impact of the COVID-19 pandemic on timeliness and equity of measles, mumps and rubella vaccinations in North East London: a longitudinal study using electronic health records.","Firman N, Marszalek M, Gutierrez A, Homer K, Williams C, Harper G, Dostal I, Ahmed Z, Robson J, Dezateux C.",,BMJ open,2022,2022-12-01,Y,Public Health; Primary Care; Paediatric Infectious Disease & Immunisation; Covid-19,,,"

Objectives

To quantify the effect of the COVID-19 pandemic on the timeliness of, and geographical and sociodemographic inequalities in, receipt of first measles, mumps and rubella (MMR) vaccination.

Design

Longitudinal study using primary care electronic health records.

Setting

285 general practices in North East London.

Participants

Children born between 23 August 2017 and 22 September 2018 (pre-pandemic cohort) or between 23 March 2019 and 1 May 2020 (pandemic cohort).

Main outcome measure

Receipt of timely MMR vaccination between 12 and 18 months of age.

Methods

We used logistic regression to estimate the ORs (95% CIs) of receipt of a timely vaccination adjusting for sex, deprivation, ethnic background and Clinical Commissioning Group. We plotted choropleth maps of the proportion receiving timely vaccinations.

Results

Timely MMR receipt fell by 4.0% (95% CI: 3.4% to 4.6%) from 79.2% (78.8% to 79.6%) to 75.2% (74.7% to 75.7%) in the pre-pandemic (n=33 226; 51.3% boys) and pandemic (n=32 446; 51.4%) cohorts, respectively. After adjustment, timely vaccination was less likely in the pandemic cohort (0.79; 0.76 to 0.82), children from black (0.70; 0.65 to 0.76), mixed/other (0.77; 0.72 to 0.82) or with missing (0.77; 0.74 to 0.81) ethnic background, and more likely in girls (1.07; 1.03 to 1.11) and those from South Asian backgrounds (1.39; 1.30 to 1.48). Children living in the least deprived areas were more likely to receive a timely MMR (2.09; 1.78 to 2.46) but there was no interaction between cohorts and deprivation (Wald statistic: 3.44; p=0.49). The proportion of neighbourhoods where less than 60% of children received timely vaccination increased from 7.5% to 12.7% during the pandemic.

Conclusions

The COVID-19 pandemic was associated with a significant fall in timely MMR receipt and increased geographical clustering of measles susceptibility in an area of historically low and inequitable MMR coverage. Immediate action is needed to avert measles outbreaks and support primary care to deliver timely and equitable vaccinations.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/12/e066288.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-066288; html:https://europepmc.org/articles/PMC9723415; pdf:https://europepmc.org/articles/PMC9723415?pdf=render 36609282,https://doi.org/10.1186/s13063-022-06967-6,A comparison of covariate adjustment approaches under model misspecification in individually randomized trials.,"Tackney MS, Morris T, White I, Leyrat C, Diaz-Ordaz K, Williamson E.",,Trials,2023,2023-01-06,Y,Randomized controlled trials; Iptw; G-computation; Tmle; Covariate Adjustment; Ancova; Misspecification; Aiptw,,,"Adjustment for baseline covariates in randomized trials has been shown to lead to gains in power and can protect against chance imbalances in covariates. For continuous covariates, there is a risk that the the form of the relationship between the covariate and outcome is misspecified when taking an adjusted approach. Using a simulation study focusing on individually randomized trials with small sample sizes, we explore whether a range of adjustment methods are robust to misspecification, either in the covariate-outcome relationship or through an omitted covariate-treatment interaction. Specifically, we aim to identify potential settings where G-computation, inverse probability of treatment weighting (IPTW), augmented inverse probability of treatment weighting (AIPTW) and targeted maximum likelihood estimation (TMLE) offer improvement over the commonly used analysis of covariance (ANCOVA). Our simulations show that all adjustment methods are generally robust to model misspecification if adjusting for a few covariates, sample size is 100 or larger, and there are no covariate-treatment interactions. When there is a non-linear interaction of treatment with a skewed covariate and sample size is small, all adjustment methods can suffer from bias; however, methods that allow for interactions (such as G-computation with interaction and IPTW) show improved results compared to ANCOVA. When there are a high number of covariates to adjust for, ANCOVA retains good properties while other methods suffer from under- or over-coverage. An outstanding issue for G-computation, IPTW and AIPTW in small samples is that standard errors are underestimated; they should be used with caution without the availability of small-sample corrections, development of which is needed. These findings are relevant for covariate adjustment in interim analyses of larger trials.",,pdf:https://trialsjournal.biomedcentral.com/counter/pdf/10.1186/s13063-022-06967-6; doi:https://doi.org/10.1186/s13063-022-06967-6; html:https://europepmc.org/articles/PMC9817411; pdf:https://europepmc.org/articles/PMC9817411?pdf=render 36457326,https://doi.org/10.3389/fpubh.2022.1017337,Seroepidemiology of SARS-CoV-2 on a partially vaccinated island in Brazil: Determinants of infection and vaccine response.,"Cerbino-Neto J, Peres IT, Varela MC, Brandão LGP, de Matos JA, Pinto LF, da Costa MD, Garcia MHO, Soranz D, Maia MLS, Krieger MA, da Cunha RV, Camacho LAB, Ranzani O, Hamacher S, Bozza FA, Penna GO.",,Frontiers in public health,2022,2022-11-14,Y,Vaccine; Antibody response; risk factors; Seroepidemiologic Studies; Seropositivity; Covid-19,,,"

Background

A vaccination campaign targeted adults in response to the pandemic in the City of Rio de Janeiro.

Objective

We aimed to evaluate the seroprevalence of SARS-CoV-2 antibodies and identify factors associated with seropositivity on vaccinated and unvaccinated residents.

Methods

We performed a seroepidemiologic survey in all residents of Paquetá Island, a neighborhood of Rio de Janeiro city, during the COVID-19 vaccine roll-out. Serological tests were performed from June 16 to June 19, 2021, and adjusted seropositivity rates were estimated by age and epidemiological variables. Logistic regression models were used to estimate adjusted ORs for risk factors to SARS-CoV-2 seropositivity in non-vaccinated individuals, and potential determinants of the magnitude of antibody responses in the seropositive population.

Results

We included in the study 3,016 residents of Paquetá (83.5% of the island population). The crude seroprevalence of COVID-19 antibodies in our sample was 53.6% (95% CI = 51.0, 56.3). The risk factors for SARS-CoV-2 seropositivity in non-vaccinated individuals were history of confirmed previous COVID-19 infection (OR = 4.74; 95% CI = 3.3, 7.0), being a household contact of a case (OR = 1.93; 95% CI = 1.5, 2.6) and in-person learning (OR = 2.01; 95% CI = 1.4, 3.0). Potential determinants of the magnitude of antibody responses among the seropositive were hybrid immunity, the type of vaccine received, and time since the last vaccine dose. Being vaccinated with Pfizer or AstraZeneca (Beta = 2.2; 95% CI = 1.8, 2.6) determined higher antibody titers than those observed with CoronaVac (Beta = 1.2; 95% CI = 0.9, 1.5).

Conclusions

Our study highlights the impact of vaccination on COVID-19 collective immunity even in a highly affected population, showing the difference in antibody titers achieved with different vaccines and how they wane with time, reinforcing how these factors should be considered when estimating effectiveness of a vaccination program at any given time. We also found that hybrid immunity was superior to both infection-induced and vaccine-induced immunity alone, and online learning protected students from COVID-19 exposure.",,pdf:https://www.frontiersin.org/articles/10.3389/fpubh.2022.1017337/pdf; doi:https://doi.org/10.3389/fpubh.2022.1017337; html:https://europepmc.org/articles/PMC9706255; pdf:https://europepmc.org/articles/PMC9706255?pdf=render +31756303,https://doi.org/10.1161/circgen.119.002711,Genetic Determinants of Lipids and Cardiovascular Disease Outcomes: A Wide-Angled Mendelian Randomization Investigation.,"Allara E, Morani G, Carter P, Gkatzionis A, Zuber V, Foley CN, Rees JMB, Mason AM, Bell S, Gill D, Lindström S, Butterworth AS, Di Angelantonio E, Peters J, Burgess S, INVENT consortium.",,Circulation. Genomic and precision medicine,2019,2019-11-22,Y,Lipids; Aortic valve stenosis; epidemiology; Venous Thromboembolism; Mendelian Randomization,,,"

Background

Evidence from randomized trials has shown that therapies that lower LDL (low-density lipoprotein)-cholesterol and triglycerides reduce coronary artery disease (CAD) risk. However, there is still uncertainty about their effects on other cardiovascular outcomes. We therefore performed a systematic investigation of causal relationships between circulating lipids and cardiovascular outcomes using a Mendelian randomization approach.

Methods

In the primary analysis, we performed 2-sample multivariable Mendelian randomization using data from participants of European ancestry. We also conducted univariable analyses using inverse-variance weighted and robust methods, and gene-specific analyses using variants that can be considered as proxies for specific lipid-lowering medications. We obtained associations with lipid fractions from the Global Lipids Genetics Consortium, a meta-analysis of 188 577 participants, and genetic associations with cardiovascular outcomes from 367 703 participants in UK Biobank.

Results

For LDL-cholesterol, in addition to the expected positive associations with CAD risk (odds ratio [OR] per 1 SD increase, 1.45 [95% CI, 1.35-1.57]) and other atheromatous outcomes (ischemic cerebrovascular disease and peripheral vascular disease), we found independent associations of genetically predicted LDL-cholesterol with abdominal aortic aneurysm (OR, 1.75 [95% CI, 1.40-2.17]) and aortic valve stenosis (OR, 1.46 [95% CI, 1.25-1.70]). Genetically predicted triglyceride levels were positively associated with CAD (OR, 1.25 [95% CI, 1.12-1.40]), aortic valve stenosis (OR, 1.29 [95% CI, 1.04-1.61]), and hypertension (OR, 1.17 [95% CI, 1.07-1.27]), but inversely associated with venous thromboembolism (OR, 0.79 [95% CI, 0.67-0.93]) and hemorrhagic stroke (OR, 0.78 [95% CI, 0.62-0.98]). We also found positive associations of genetically predicted LDL-cholesterol and triglycerides with heart failure that appeared to be mediated by CAD.

Conclusions

Lowering LDL-cholesterol is likely to prevent abdominal aortic aneurysm and aortic stenosis, in addition to CAD and other atheromatous cardiovascular outcomes. Lowering triglycerides is likely to prevent CAD and aortic valve stenosis but may increase thromboembolic risk.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCGEN.119.002711; doi:https://doi.org/10.1161/CIRCGEN.119.002711; html:https://europepmc.org/articles/PMC6922071; pdf:https://europepmc.org/articles/PMC6922071?pdf=render 38246848,https://doi.org/10.1016/j.tim.2023.12.004,Harnessing human microbiomes for disease prediction.,"Liu Y, Fachrul M, Inouye M, Méric G.",,Trends in microbiology,2024,2024-01-20,N,Machine Learning; Gut Microbiota; Metagenomics; Microbiome; Disease Prediction,,,"The human microbiome has been increasingly recognized as having potential use for disease prediction. Predicting the risk, progression, and severity of diseases holds promise to transform clinical practice, empower patient decisions, and reduce the burden of various common diseases, as has been demonstrated for cardiovascular disease or breast cancer. Combining multiple modifiable and non-modifiable risk factors, including high-dimensional genomic data, has been traditionally favored, but few studies have incorporated the human microbiome into models for predicting the prospective risk of disease. Here, we review research into the use of the human microbiome for disease prediction with a particular focus on prospective studies as well as the modulation and engineering of the microbiome as a therapeutic strategy.",,doi:https://doi.org/10.1016/j.tim.2023.12.004 -36958365,https://doi.org/10.1016/s2352-3018(23)00028-0,Life expectancy after 2015 of adults with HIV on long-term antiretroviral therapy in Europe and North America: a collaborative analysis of cohort studies.,"Trickey A, Sabin CA, Burkholder G, Crane H, d'Arminio Monforte A, Egger M, Gill MJ, Grabar S, Guest JL, Jarrin I, Lampe FC, Obel N, Reyes JM, Stephan C, Sterling TR, Teira R, Touloumi G, Wasmuth JC, Wit F, Wittkop L, Zangerle R, Silverberg MJ, Justice A, Sterne JAC.",,The lancet. HIV,2023,2023-03-20,N,,,,"

Background

The life expectancy of people with HIV taking antiretroviral therapy (ART) has increased substantially over the past 25 years. Most previous studies of life expectancy were based on data from the first few years after starting ART, when mortality is highest. However, many people with HIV have been successfully treated with ART for many years, and up-to-date prognosis data are needed. We aimed to estimate life expectancy in adults with HIV on ART for at least 1 year in Europe and North America from 2015 onwards.

Methods

We used data for people with HIV taking ART from the Antiretroviral Therapy Cohort Collaboration and the UK Collaborative HIV Cohort Study. Included participants started ART between 1996 and 2014 and had been on ART for at least 1 year by 2015, or started ART between 2015 and 2019 and survived for at least 1 year; all participants were aged at least 16 years at ART initiation. We used Poisson models to estimate the associations between mortality and demographic and clinical characteristics, including CD4 cell count at the start of follow-up. We also estimated the remaining years of life left for people with HIV aged 40 years who were taking ART, and stratified these estimates by variables associated with mortality. These estimates were compared with estimates for years of life remaining in a corresponding multi-country general population.

Findings

Among 206 891 people with HIV included, 5780 deaths were recorded since 2015. We estimated that women with HIV at age 40 years had 35·8 years (95% CI 35·2-36·4) of life left if they started ART before 2015, and 39·0 years (38·5-39·5) left if they started ART after 2015. For men with HIV, the corresponding estimates were 34·5 years (33·8-35·2) and 37·0 (36·5-37·6). Women with CD4 counts of fewer than 49 cells per μL at the start of follow-up had an estimated 19·4 years (18·2-20·5) of life left at age 40 years if they started ART before 2015 and 24·9 years (23·9-25·9) left if they started ART after 2015. The corresponding estimates for men were 18·2 years (17·1-19·4) and 23·7 years (22·7-24·8). Women with CD4 counts of at least 500 cells per μL at the start of follow-up had an estimated 40·2 years (39·7-40·6) of life left at age 40 years if they started ART before 2015 and 42·0 years (41·7-42·3) left if they started ART after 2015. The corresponding estimates for men were 38·0 years (37·5-38·5) and 39·2 years (38·7-39·7).

Interpretation

For people with HIV on ART and with high CD4 cell counts who survived to 2015 or started ART after 2015, life expectancy was only a few years lower than that in the general population, irrespective of when ART was started. However, for people with low CD4 counts at the start of follow-up, life-expectancy estimates were substantially lower, emphasising the continuing importance of early diagnosis and sustained treatment of HIV.

Funding

US National Institute on Alcohol Abuse and Alcoholism and UK Medical Research Council.",,doi:https://doi.org/10.1016/s2352-3018(23)00028-0; doi:https://doi.org/10.1016/S2352-3018(23)00028-0; html:https://europepmc.org/articles/PMC10288029; pdf:https://europepmc.org/articles/PMC10288029?pdf=render; doi:https://doi.org/10.1016/s2352-3018(23)00028-0 34931349,https://doi.org/10.1111/bcp.15191,Dissecting the IL-6 pathway in cardiometabolic disease: A Mendelian randomization study on both IL6 and IL6R.,"Cupido AJ, Asselbergs FW, Natarajan P, CHARGE Inflammation Working Group, Ridker PM, Hovingh GK, Schmidt AF.",,British journal of clinical pharmacology,2022,2022-01-28,Y,IL-6; Cardiovascular disease; Trans-signalling; Classical Signalling,,,"

Aims

Chronic inflammation is a risk factor for cardiovascular disease (CVD). IL-6 signalling perturbation through IL-6 or IL-6R blockade may have potential benefit on cardiovascular risk. It is unknown whether targeting either IL-6 or IL-6 receptor may result in similar effects on CVD and adverse events. We compared the anticipated effects of targeting IL-6 and IL-6 receptor on cardiometabolic risk and potential side effects.

Methods

We constructed four instruments: two main instruments with genetic variants in the IL6 and IL6R loci weighted for their association with CRP, and two after firstly filtering variants for their association with IL-6 or IL-6R expression. Analyses were performed for coronary artery disease (CAD), ischemic stroke, atrial fibrillation (AF), heart failure, type 2 diabetes (T2D), rheumatoid arthritis (RA), infection endpoints, and quantitative haematological, metabolic and anthropometric parameters.

Results

A 1 mg/L lower CRP by the IL6 instrument was associated with lower CAD (odds ratio [OR] 0.86, 95% confidence interval [CI] 0.77;0.96), AF and T2D risk. A 1 mg/L lower CRP by the IL6R instrument was associated with lower CAD (OR 0.90, 95% CI 0.86;0.95), any stroke and ischemic stroke, AF, RA risk and higher pneumonia risk. The eQTL-filtered results were in concordance with the main results, but with wider confidence intervals.

Conclusions

IL-6 signalling perturbation by either IL6 or IL6R genetic instruments is associated with a similar risk reduction for multiple cardiometabolic diseases, suggesting that both IL-6 and IL-6R are potential therapeutic targets to lower CVD. Moreover, IL-6 rather than IL-6R inhibition might have a more favourable pneumonia risk.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/bcp.15191; doi:https://doi.org/10.1111/bcp.15191; html:https://europepmc.org/articles/PMC9303316; pdf:https://europepmc.org/articles/PMC9303316?pdf=render -31756303,https://doi.org/10.1161/circgen.119.002711,Genetic Determinants of Lipids and Cardiovascular Disease Outcomes: A Wide-Angled Mendelian Randomization Investigation.,"Allara E, Morani G, Carter P, Gkatzionis A, Zuber V, Foley CN, Rees JMB, Mason AM, Bell S, Gill D, Lindström S, Butterworth AS, Di Angelantonio E, Peters J, Burgess S, INVENT consortium.",,Circulation. Genomic and precision medicine,2019,2019-11-22,Y,Lipids; Aortic valve stenosis; epidemiology; Venous Thromboembolism; Mendelian Randomization,,,"

Background

Evidence from randomized trials has shown that therapies that lower LDL (low-density lipoprotein)-cholesterol and triglycerides reduce coronary artery disease (CAD) risk. However, there is still uncertainty about their effects on other cardiovascular outcomes. We therefore performed a systematic investigation of causal relationships between circulating lipids and cardiovascular outcomes using a Mendelian randomization approach.

Methods

In the primary analysis, we performed 2-sample multivariable Mendelian randomization using data from participants of European ancestry. We also conducted univariable analyses using inverse-variance weighted and robust methods, and gene-specific analyses using variants that can be considered as proxies for specific lipid-lowering medications. We obtained associations with lipid fractions from the Global Lipids Genetics Consortium, a meta-analysis of 188 577 participants, and genetic associations with cardiovascular outcomes from 367 703 participants in UK Biobank.

Results

For LDL-cholesterol, in addition to the expected positive associations with CAD risk (odds ratio [OR] per 1 SD increase, 1.45 [95% CI, 1.35-1.57]) and other atheromatous outcomes (ischemic cerebrovascular disease and peripheral vascular disease), we found independent associations of genetically predicted LDL-cholesterol with abdominal aortic aneurysm (OR, 1.75 [95% CI, 1.40-2.17]) and aortic valve stenosis (OR, 1.46 [95% CI, 1.25-1.70]). Genetically predicted triglyceride levels were positively associated with CAD (OR, 1.25 [95% CI, 1.12-1.40]), aortic valve stenosis (OR, 1.29 [95% CI, 1.04-1.61]), and hypertension (OR, 1.17 [95% CI, 1.07-1.27]), but inversely associated with venous thromboembolism (OR, 0.79 [95% CI, 0.67-0.93]) and hemorrhagic stroke (OR, 0.78 [95% CI, 0.62-0.98]). We also found positive associations of genetically predicted LDL-cholesterol and triglycerides with heart failure that appeared to be mediated by CAD.

Conclusions

Lowering LDL-cholesterol is likely to prevent abdominal aortic aneurysm and aortic stenosis, in addition to CAD and other atheromatous cardiovascular outcomes. Lowering triglycerides is likely to prevent CAD and aortic valve stenosis but may increase thromboembolic risk.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCGEN.119.002711; doi:https://doi.org/10.1161/CIRCGEN.119.002711; html:https://europepmc.org/articles/PMC6922071; pdf:https://europepmc.org/articles/PMC6922071?pdf=render +36958365,https://doi.org/10.1016/s2352-3018(23)00028-0,Life expectancy after 2015 of adults with HIV on long-term antiretroviral therapy in Europe and North America: a collaborative analysis of cohort studies.,"Trickey A, Sabin CA, Burkholder G, Crane H, d'Arminio Monforte A, Egger M, Gill MJ, Grabar S, Guest JL, Jarrin I, Lampe FC, Obel N, Reyes JM, Stephan C, Sterling TR, Teira R, Touloumi G, Wasmuth JC, Wit F, Wittkop L, Zangerle R, Silverberg MJ, Justice A, Sterne JAC.",,The lancet. HIV,2023,2023-03-20,N,,,,"

Background

The life expectancy of people with HIV taking antiretroviral therapy (ART) has increased substantially over the past 25 years. Most previous studies of life expectancy were based on data from the first few years after starting ART, when mortality is highest. However, many people with HIV have been successfully treated with ART for many years, and up-to-date prognosis data are needed. We aimed to estimate life expectancy in adults with HIV on ART for at least 1 year in Europe and North America from 2015 onwards.

Methods

We used data for people with HIV taking ART from the Antiretroviral Therapy Cohort Collaboration and the UK Collaborative HIV Cohort Study. Included participants started ART between 1996 and 2014 and had been on ART for at least 1 year by 2015, or started ART between 2015 and 2019 and survived for at least 1 year; all participants were aged at least 16 years at ART initiation. We used Poisson models to estimate the associations between mortality and demographic and clinical characteristics, including CD4 cell count at the start of follow-up. We also estimated the remaining years of life left for people with HIV aged 40 years who were taking ART, and stratified these estimates by variables associated with mortality. These estimates were compared with estimates for years of life remaining in a corresponding multi-country general population.

Findings

Among 206 891 people with HIV included, 5780 deaths were recorded since 2015. We estimated that women with HIV at age 40 years had 35·8 years (95% CI 35·2-36·4) of life left if they started ART before 2015, and 39·0 years (38·5-39·5) left if they started ART after 2015. For men with HIV, the corresponding estimates were 34·5 years (33·8-35·2) and 37·0 (36·5-37·6). Women with CD4 counts of fewer than 49 cells per μL at the start of follow-up had an estimated 19·4 years (18·2-20·5) of life left at age 40 years if they started ART before 2015 and 24·9 years (23·9-25·9) left if they started ART after 2015. The corresponding estimates for men were 18·2 years (17·1-19·4) and 23·7 years (22·7-24·8). Women with CD4 counts of at least 500 cells per μL at the start of follow-up had an estimated 40·2 years (39·7-40·6) of life left at age 40 years if they started ART before 2015 and 42·0 years (41·7-42·3) left if they started ART after 2015. The corresponding estimates for men were 38·0 years (37·5-38·5) and 39·2 years (38·7-39·7).

Interpretation

For people with HIV on ART and with high CD4 cell counts who survived to 2015 or started ART after 2015, life expectancy was only a few years lower than that in the general population, irrespective of when ART was started. However, for people with low CD4 counts at the start of follow-up, life-expectancy estimates were substantially lower, emphasising the continuing importance of early diagnosis and sustained treatment of HIV.

Funding

US National Institute on Alcohol Abuse and Alcoholism and UK Medical Research Council.",,doi:https://doi.org/10.1016/s2352-3018(23)00028-0; doi:https://doi.org/10.1016/S2352-3018(23)00028-0; html:https://europepmc.org/articles/PMC10288029; pdf:https://europepmc.org/articles/PMC10288029?pdf=render; doi:https://doi.org/10.1016/s2352-3018(23)00028-0 37671353,https://doi.org/10.23889/ijpds.v5i3.2133,Public Involvement & Engagement in health inequalities research on COVID-19 pandemic: a case study of CIDACS/FIOCRUZ BAHIA.,"Dos Anjos Fonseca A, Pimenta DM, de Almeida MRS, Lima RT, Barreto ML, Ichihara MYT.",,International journal of population data science,2020,2020-01-01,Y,Brazil; Pandemic; Policymakers; Social Inequalities; Public Engagement; Community Groups; Public Involvement,,,"

Introduction

Health inequalities in Brazil have deepened on Covid-19 pandemic, and the most vulnerable people were the more affected. A multidisciplinary team from Cidacs/Fiocruz Bahia developed a Social Disparities Index for Covid-19 (IDS-COVID-19) to support the evaluation of effects of health inequalities on the pandemic in Brazil. Public Involvement and Engagement were the pillars of this research because they allowed us to access first hand experiences about the social context in our country.

Objectives

This paper aims to describe our Public Involvement and Engagement experience by analysing our challenges, strategies, activities, results, and lessons learned during the construction of IDS-COVID-19.

Methods

The basis of the IDS-Covid-19 public engagement model was the participation of different social groups through methods and techniques that allow dialogue. Several activities and communication products supported the continuous interactions. Another guideline was the inclusion and the welcoming of participants from the beginning of the project to ensure that the participant's contributions could drive decision-making about the research.

Results

Participants made several contributions to the research as a new layer of information to the Index, and improvements were made to the interactive panel. They also compromised to support the dissemination and use of the product. Eight representatives of community groups and 29 policymakers participated in our engagement activities during the project. More than 500 people were in our open webinars. In addition, more than 140 news items about IDS-Covid-19 were published in national and international media.

Conclusions

We highlight as lessons learned the adaptation of some dissemination formats to the public, and the necessity of being flexible and accessible to participants. We strengthened the relationship with relevant stakeholders by exploring individual conversations by phone, WhatsApp, email, and interviews to produce a documentary that registered this whole experience. Cidacs/Fiocruz Bahia has also embedded public engagement and involvement in the study agenda.",,doi:https://doi.org/10.23889/ijpds.v5i3.2133; html:https://europepmc.org/articles/PMC10476697; pdf:https://europepmc.org/articles/PMC10476697?pdf=render 33653287,https://doi.org/10.1186/s12875-021-01384-1,"A cross-sectional study reporting concussion exposure, assessment and management in Western Australian general practice.","Thomas E, Chih H, Gabbe B, Fitzgerald M, Cowen G.",,BMC family practice,2021,2021-03-02,Y,,,,"

Background

General Practitioners (GPs) may be called upon to assess patients who have sustained a concussion despite limited information being available at this assessment. Information relating to how concussion is actually being assessed and managed in General Practice is scarce. This study aimed to identify characteristics of current Western Australian (WA) GP exposure to patients with concussion, factors associated with GPs' knowledge of concussion, confidence of GPs in diagnosing and managing patients with concussion, typical referral practices and familiarity of GPs with guidelines.

Methods

In this cross-sectional study, GPs in WA were recruited via the RACGP WA newsletter and shareGP and the consented GPs completed an electronic survey. Associations were performed using Chi-squared tests or Fisher's Exact test.

Results

Sixty-six GPs in WA responded to the survey (response rate = 1.7%). Demographics, usual practice, knowledge, confidence, identification of prolonged recovery as well as guideline and resource awareness of GPs who practised in regional and metropolitan areas were comparable (p > 0.05). Characteristics of GPs were similar between those who identified all symptoms of concussion and distractors correctly and those who did not (p > 0.05). However, 84% of the respondents who had never heard of concussion guidelines were less likely to answer all symptoms and distractors correctly (p = 0.039). Whilst 78% of the GPs who were confident in their diagnoses had heard of guidelines (p = 0.029), confidence in managing concussion was not significantly associated with GPs exposure to guidelines. It should be noted that none of the respondents correctly identified signs of concussion and excluded the distractors.

Conclusions

Knowledge surrounding concussion guidelines, diagnosis and management varied across GPs in WA. Promotion of available concussion guidelines may assist GPs who lack confidence in making a diagnosis. The lack of association between GPs exposure to guidelines and confidence managing concussion highlights that concussion management may be an area where GPs could benefit from additional education and support.",,pdf:https://bmcfampract.biomedcentral.com/track/pdf/10.1186/s12875-021-01384-1; doi:https://doi.org/10.1186/s12875-021-01384-1; html:https://europepmc.org/articles/PMC7927406; pdf:https://europepmc.org/articles/PMC7927406?pdf=render -38233595,https://doi.org/10.1038/s41588-023-01638-x,Inherited polygenic effects on common hematological traits influence clonal selection on JAK2V617F and the development of myeloproliferative neoplasms.,"Guo J, Walter K, Quiros PM, Gu M, Baxter EJ, Danesh J, Di Angelantonio E, Roberts D, Guglielmelli P, Harrison CN, Godfrey AL, Green AR, Vassiliou GS, Vuckovic D, Nangalia J, Soranzo N.",,Nature genetics,2024,2024-01-17,Y,,,,"Myeloproliferative neoplasms (MPNs) are chronic cancers characterized by overproduction of mature blood cells. Their causative somatic mutations, for example, JAK2V617F, are common in the population, yet only a minority of carriers develop MPN. Here we show that the inherited polygenic loci that underlie common hematological traits influence JAK2V617F clonal expansion. We identify polygenic risk scores (PGSs) for monocyte count and plateletcrit as new risk factors for JAK2V617F positivity. PGSs for several hematological traits influenced the risk of different MPN subtypes, with low PGSs for two platelet traits also showing protective effects in JAK2V617F carriers, making them two to three times less likely to have essential thrombocythemia than carriers with high PGSs. We observed that extreme hematological PGSs may contribute to an MPN diagnosis in the absence of somatic driver mutations. Our study showcases how polygenic backgrounds underlying common hematological traits influence both clonal selection on somatic mutations and the subsequent phenotype of cancer.",,pdf:https://www.nature.com/articles/s41588-023-01638-x.pdf; doi:https://doi.org/10.1038/s41588-023-01638-x; html:https://europepmc.org/articles/PMC10864174; pdf:https://europepmc.org/articles/PMC10864174?pdf=render 36732776,https://doi.org/10.1186/s13040-023-00321-5,LoFTK: a framework for fully automated calculation of predicted Loss-of-Function variants and genes.,"Alasiri A, Karczewski KJ, Cole B, Loza BL, Moore JH, van der Laan SW, Asselbergs FW, Keating BJ, van Setten J.",,BioData mining,2023,2023-02-02,Y,Human Genetic; Loss-of-function Variants; Compound Heterozygotes; Knockout Genes,,,"

Background

Loss-of-Function (LoF) variants in human genes are important due to their impact on clinical phenotypes and frequent occurrence in the genomes of healthy individuals. The association of LoF variants with complex diseases and traits may lead to the discovery and validation of novel therapeutic targets. Current approaches predict high-confidence LoF variants without identifying the specific genes or the number of copies they affect. Moreover, there is a lack of methods for detecting knockout genes caused by compound heterozygous (CH) LoF variants.

Results

We have developed the Loss-of-Function ToolKit (LoFTK), which allows efficient and automated prediction of LoF variants from genotyped, imputed and sequenced genomes. LoFTK enables the identification of genes that are inactive in one or two copies and provides summary statistics for downstream analyses. LoFTK can identify CH LoF variants, which result in LoF genes with two copies lost. Using data from parents and offspring we show that 96% of CH LoF genes predicted by LoFTK in the offspring have the respective alleles donated by each parent.

Conclusions

LoFTK is a command-line based tool that provides a reliable computational workflow for predicting LoF variants from genotyped and sequenced genomes, identifying genes that are inactive in 1 or 2 copies. LoFTK is an open software and is freely available to non-commercial users at https://github.com/CirculatoryHealth/LoFTK .",,pdf:https://biodatamining.biomedcentral.com/counter/pdf/10.1186/s13040-023-00321-5; doi:https://doi.org/10.1186/s13040-023-00321-5; html:https://europepmc.org/articles/PMC9893534; pdf:https://europepmc.org/articles/PMC9893534?pdf=render -38115598,https://doi.org/10.1089/neu.2023.0461,"The Australian Traumatic Brain Injury Initiative: Systematic Review and Consensus Process to Determine the Predictive Value of Demographic, Injury Event, and Social Characteristics on Outcomes for People With Moderate-Severe Traumatic Brain Injury.","Gabbe BJ, Keeves J, McKimmie A, Gadowski AM, Holland AJ, Semple BD, Young JT, Crowe L, Ownsworth T, Bagg MK, Antonic-Baker A, Hicks AJ, Hill R, Curtis K, Romero L, Ponsford JL, Lannin NA, O'Brien TJ, Cameron PA, Cooper DJ, Rushworth N, Fitzgerald M.",,Journal of neurotrauma,2024,2024-04-01,N,"Traumatic; Demography; Common Data Elements; Social Factors; Outcome Assessment, Health Care; Systematic Review [Publication Type]; Brain Injuries, Culture",,,"The objective of the Australian Traumatic Brain Injury (AUS-TBI) Initiative is to develop a data dictionary to inform data collection and facilitate prediction of outcomes of people who experience moderate-severe TBI in Australia. The aim of this systematic review was to summarize the evidence of the association between demographic, injury event, and social characteristics with outcomes, in people with moderate-severe TBI, to identify potentially predictive indicators. Standardized searches were implemented across bibliographic databases to March 31, 2022. English-language reports, excluding case series, which evaluated the association between demographic, injury event, and social characteristics, and any clinical outcome in at least 10 patients with moderate-severe TBI were included. Abstracts and full text records were independently screened by at least two reviewers in Covidence. A pre-defined algorithm was used to assign a judgement of predictive value to each observed association. The review findings were discussed with an expert panel to determine the feasibility of incorporation of routine measurement into standard care. The search strategy retrieved 16,685 records; 867 full-length records were screened, and 111 studies included. Twenty-two predictors of 32 different outcomes were identified; 7 were classified as high-level (age, sex, ethnicity, employment, insurance, education, and living situation at the time of injury). After discussion with an expert consensus group, 15 were recommended for inclusion in the data dictionary. This review identified numerous predictors capable of enabling early identification of those at risk for poor outcomes and improved personalization of care through inclusion in routine data collection.",,doi:https://doi.org/10.1089/neu.2023.0461 +38233595,https://doi.org/10.1038/s41588-023-01638-x,Inherited polygenic effects on common hematological traits influence clonal selection on JAK2V617F and the development of myeloproliferative neoplasms.,"Guo J, Walter K, Quiros PM, Gu M, Baxter EJ, Danesh J, Di Angelantonio E, Roberts D, Guglielmelli P, Harrison CN, Godfrey AL, Green AR, Vassiliou GS, Vuckovic D, Nangalia J, Soranzo N.",,Nature genetics,2024,2024-01-17,Y,,,,"Myeloproliferative neoplasms (MPNs) are chronic cancers characterized by overproduction of mature blood cells. Their causative somatic mutations, for example, JAK2V617F, are common in the population, yet only a minority of carriers develop MPN. Here we show that the inherited polygenic loci that underlie common hematological traits influence JAK2V617F clonal expansion. We identify polygenic risk scores (PGSs) for monocyte count and plateletcrit as new risk factors for JAK2V617F positivity. PGSs for several hematological traits influenced the risk of different MPN subtypes, with low PGSs for two platelet traits also showing protective effects in JAK2V617F carriers, making them two to three times less likely to have essential thrombocythemia than carriers with high PGSs. We observed that extreme hematological PGSs may contribute to an MPN diagnosis in the absence of somatic driver mutations. Our study showcases how polygenic backgrounds underlying common hematological traits influence both clonal selection on somatic mutations and the subsequent phenotype of cancer.",,pdf:https://www.nature.com/articles/s41588-023-01638-x.pdf; doi:https://doi.org/10.1038/s41588-023-01638-x; html:https://europepmc.org/articles/PMC10864174; pdf:https://europepmc.org/articles/PMC10864174?pdf=render 34982094,https://doi.org/10.1167/tvst.11.1.3,OCT Assisted Quantification of Vitreous Inflammation in Uveitis.,"Liu X, Kale AU, Ometto G, Montesano G, Sitch AJ, Capewell N, Radovanovic C, Bucknall N, Beare NAV, Moore DJ, Keane PA, Crabb DP, Denniston AK.",,Translational vision science & technology,2022,2022-01-01,Y,,,,"

Purpose

Vitreous haze (VH) is a key marker of inflammation in uveitis but limited by its subjectivity. Optical coherence tomography (OCT) has potential as an objective, noninvasive method for quantifying VH. We test the hypotheses that OCT can reliably quantify VH and the measurement is associated with slit-lamp based grading of VH.

Methods

In this prospective study, participants underwent three repeated OCT macular scans to evaluate the within-eye reliability of the OCT vitreous intensity (VI). Association between OCT VI and clinical findings (including VH grade, phakic status, visual acuity [VA], anterior chamber cells, and macular thickness) were assessed.

Results

One hundred nineteen participants were included (41 healthy participants, 32 patients with uveitis without VH, and 46 patients with uveitis with VH). Within-eye test reliability of OCT VI was high in healthy eyes and in all grades of VH (intraclass correlation coefficient [ICC] > 0.79). Average OCT VI was significantly different between healthy eyes and uveitic eyes without and uveitic eyes with VH, and was associated with increasing clinical VH grade (P < 0.05). OCT VI was significantly associated with VA, whereas clinical VH grading was not. Cataract was also associated with higher OCT VI (P = 0.03).

Conclusions

OCT VI is a fast, noninvasive, objective, and automated method for measuring vitreous inflammation. It is associated with clinician grading of vitreous inflammation and VA, however, it can be affected by media opacities.

Translational relevance

OCT imaging for quantifying vitreous inflammation shows high within-eye repeatability and is associated with clinical grading of vitreous haze. OCT measurements are also associated with visual acuity but may be affected by structures anterior to the acquisition window, such as lens opacity and other anterior segment changes.",,doi:https://doi.org/10.1167/tvst.11.1.3; doi:https://doi.org/10.1167/tvst.11.1.3; html:https://europepmc.org/articles/PMC8742534; pdf:https://europepmc.org/articles/PMC8742534?pdf=render +38115598,https://doi.org/10.1089/neu.2023.0461,"The Australian Traumatic Brain Injury Initiative: Systematic Review and Consensus Process to Determine the Predictive Value of Demographic, Injury Event, and Social Characteristics on Outcomes for People With Moderate-Severe Traumatic Brain Injury.","Gabbe BJ, Keeves J, McKimmie A, Gadowski AM, Holland AJ, Semple BD, Young JT, Crowe L, Ownsworth T, Bagg MK, Antonic-Baker A, Hicks AJ, Hill R, Curtis K, Romero L, Ponsford JL, Lannin NA, O'Brien TJ, Cameron PA, Cooper DJ, Rushworth N, Fitzgerald M.",,Journal of neurotrauma,2024,2024-04-01,N,"Traumatic; Demography; Common Data Elements; Social Factors; Outcome Assessment, Health Care; Systematic Review [Publication Type]; Brain Injuries, Culture",,,"The objective of the Australian Traumatic Brain Injury (AUS-TBI) Initiative is to develop a data dictionary to inform data collection and facilitate prediction of outcomes of people who experience moderate-severe TBI in Australia. The aim of this systematic review was to summarize the evidence of the association between demographic, injury event, and social characteristics with outcomes, in people with moderate-severe TBI, to identify potentially predictive indicators. Standardized searches were implemented across bibliographic databases to March 31, 2022. English-language reports, excluding case series, which evaluated the association between demographic, injury event, and social characteristics, and any clinical outcome in at least 10 patients with moderate-severe TBI were included. Abstracts and full text records were independently screened by at least two reviewers in Covidence. A pre-defined algorithm was used to assign a judgement of predictive value to each observed association. The review findings were discussed with an expert panel to determine the feasibility of incorporation of routine measurement into standard care. The search strategy retrieved 16,685 records; 867 full-length records were screened, and 111 studies included. Twenty-two predictors of 32 different outcomes were identified; 7 were classified as high-level (age, sex, ethnicity, employment, insurance, education, and living situation at the time of injury). After discussion with an expert consensus group, 15 were recommended for inclusion in the data dictionary. This review identified numerous predictors capable of enabling early identification of those at risk for poor outcomes and improved personalization of care through inclusion in routine data collection.",,doi:https://doi.org/10.1089/neu.2023.0461 35983770,https://doi.org/10.2807/1560-7917.es.2022.27.33.2100885,"Recording of 'COVID-19 vaccine declined': a cohort study on 57.9 million National Health Service patients' records in situ using OpenSAFELY, England, 8 December 2020 to 25 May 2021.","Curtis HJ, Inglesby P, MacKenna B, Croker R, Hulme WJ, Rentsch CT, Bhaskaran K, Mathur R, Morton CE, Bacon SC, Smith RM, Evans D, Mehrkar A, Tomlinson L, Walker AJ, Bates C, Hickman G, Ward T, Morley J, Cockburn J, Davy S, Williamson EJ, Eggo RM, Parry J, Hester F, Harper S, O'Hanlon S, Eavis A, Jarvis R, Avramov D, Griffiths P, Fowles A, Parkes N, Evans SJ, Douglas IJ, Smeeth L, Goldacre B.",,Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin,2022,2022-08-01,Y,Vaccination; Vaccine Hesitancy; Nhs England; Covid-19; Sars-cov-2,,,"BackgroundPriority patients in England were offered COVID-19 vaccination by mid-April 2021. Codes in clinical record systems can denote the vaccine being declined.AimWe describe records of COVID-19 vaccines being declined, according to clinical and demographic factors.MethodsWith the approval of NHS England, we conducted a retrospective cohort study between 8 December 2020 and 25 May 2021 with primary care records for 57.9 million patients using OpenSAFELY, a secure health analytics platform. COVID-19 vaccination priority patients were those aged ≥ 50 years or ≥ 16 years clinically extremely vulnerable (CEV) or 'at risk'. We describe the proportion recorded as declining vaccination for each group and stratified by clinical and demographic subgroups, subsequent vaccination and distribution of clinical code usage across general practices.ResultsOf 24.5 million priority patients, 663,033 (2.7%) had a decline recorded, while 2,155,076 (8.8%) had neither a vaccine nor decline recorded. Those recorded as declining, who were subsequently vaccinated (n = 125,587; 18.9%) were overrepresented in the South Asian population (32.3% vs 22.8% for other ethnicities aged ≥ 65 years). The proportion of declining unvaccinated patients was highest in CEV (3.3%), varied strongly with ethnicity (black 15.3%, South Asian 5.6%, white 1.5% for ≥ 80 years) and correlated positively with increasing deprivation.ConclusionsClinical codes indicative of COVID-19 vaccinations being declined are commonly used in England, but substantially more common among black and South Asian people, and in more deprived areas. Qualitative research is needed to determine typical reasons for recorded declines, including to what extent they reflect patients actively declining.",,pdf:https://www.eurosurveillance.org/deliver/fulltext/eurosurveillance/27/33/eurosurv-27-33-5.pdf?itemId=%2Fcontent%2F10.2807%2F1560-7917.ES.2022.27.33.2100885&mimeType=pdf&containerItemId=content/eurosurveillance; doi:https://doi.org/10.2807/1560-7917.ES.2022.27.33.2100885; html:https://europepmc.org/articles/PMC9389857 33354439,https://doi.org/10.1109/jtehm.2020.3040236,Modeling Large Sparse Data for Feature Selection: Hospital Admission Predictions of the Dementia Patients Using Primary Care Electronic Health Records.,"Tsang G, Zhou SM, Xie X.",,IEEE journal of translational engineering in health and medicine,2021,2020-11-24,Y,Dementia; risk factors; Hospitalization; Feature Selection; Machine Learning; Electronic Health Records; Deep Learning; Weight Regularization,,,"A growing elderly population suffering from incurable, chronic conditions such as dementia present a continual strain on medical services due to mental impairment paired with high comorbidity resulting in increased hospitalization risk. The identification of at risk individuals allows for preventative measures to alleviate said strain. Electronic health records provide opportunity for big data analysis to address such applications. Such data however, provides a challenging problem space for traditional statistics and machine learning due to high dimensionality and sparse data elements. This article proposes a novel machine learning methodology: entropy regularization with ensemble deep neural networks (ECNN), which simultaneously provides high predictive performance of hospitalization of patients with dementia whilst enabling an interpretable heuristic analysis of the model architecture, able to identify individual features of importance within a large feature domain space. Experimental results on health records containing 54,647 features were able to identify 10 event indicators within a patient timeline: a collection of diagnostic events, medication prescriptions and procedural events, the highest ranked being essential hypertension. The resulting subset was still able to provide a highly competitive hospitalization prediction (Accuracy: 0.759) as compared to the full feature domain (Accuracy: 0.755) or traditional feature selection techniques (Accuracy: 0.737), a significant reduction in feature size. The discovery and heuristic evidence of correlation provide evidence for further clinical study of said medical events as potential novel indicators. There also remains great potential for adaption of ECNN within other medical big data domains as a data mining tool for novel risk factor identification.",,pdf:https://ieeexplore.ieee.org/ielx7/6221039/9246949/09268962.pdf; doi:https://doi.org/10.1109/JTEHM.2020.3040236; html:https://europepmc.org/articles/PMC7737850; pdf:https://europepmc.org/articles/PMC7737850?pdf=render 33591566,https://doi.org/10.1007/s43441-021-00263-2,Advancing UK Regulatory Science Strategy in the Context of Global Regulation: a Stakeholder Survey.,"Cruz Rivera S, Torlinska B, Marston E, Denniston AK, Oliver K, Hoare S, Calvert MJ.",,Therapeutic innovation & regulatory science,2021,2021-02-16,Y,Regulatory Science; Health Products; Medicines And Devices,,,"

Background

The UK's transition from the European Union creates both an urgent need and key opportunity for the UK and its global collaborators to consider new approaches to the regulation of emerging technologies, underpinned by regulatory science. This survey aimed to identify the most accurate definition of regulatory science, to define strategic areas of the regulation of healthcare innovation which can be informed through regulatory science and to explore the training and infrastructure needed to advance UK and international regulatory science.

Methods

A survey was distributed to UK healthcare professionals, academics, patients, health technology assessment agencies, ethicists and trade associations, as well as international regulators, pharmaceutical companies and small or medium enterprises which have expertise in regulatory science and in developing or applying regulation in healthcare. Subsequently, a descriptive quantitative analyses of survey results and directed thematic analysis of free-text comments were applied.

Results

Priority areas for UK regulatory science identified by 145 participants included the following: flexibility: the capability of regulations to adapt to novel products and target patient outcomes; co-development: collaboration across sectors, e.g. patients, manufacturers, regulators, and educators working together to develop appropriate training for novel product deployment; responsiveness: the preparation of frameworks which enable timely innovation required by emerging events; speed: the rate at which new products can reach the market; reimbursement: developing effective tools to track and evaluate outcomes for ""pay for performance"" products; and education and professional development.

Conclusions

The UK has a time-critical opportunity to establish its national and international strategy for regulatory science leadership by harnessing broader academic input, developing strategic cross-sector collaborations, incorporating patients' experiences and perspectives, and investing in a skilled workforce.",,pdf:https://link.springer.com/content/pdf/10.1007/s43441-021-00263-2.pdf; doi:https://doi.org/10.1007/s43441-021-00263-2; html:https://europepmc.org/articles/PMC7885762; pdf:https://europepmc.org/articles/PMC7885762?pdf=render @@ -1675,8 +1675,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 37270201,https://doi.org/10.1136/heartjnl-2023-322616,Reliability of major bleeding events in UK routine data versus clinical trial adjudicated follow-up data.,"Harper C, Mafham M, Herrington W, Staplin N, Stevens W, Wallendszus K, Haynes R, Landray MJ, Parish S, Bowman L, Armitage J.",,Heart (British Cardiac Society),2023,2023-09-13,Y,"Atherosclerosis; Research Design; Electronic Health Records; Outcome Assessment, Health Care",,,"

Objective

To assess how reliable UK routine data are for ascertaining major bleeding events compared with adjudicated follow-up.

Methods

The ASCEND (A Study of Cardiovascular Events iN Diabetes) primary prevention trial randomised 15 480 UK people with diabetes to aspirin versus matching placebo. The primary safety outcome was major bleeding (including intracranial haemorrhage, sight-threatening eye bleeding, serious gastrointestinal bleeding and other major bleeding (epistaxis, haemoptysis, haematuria, vaginal and other bleeding)) ascertained by direct-participant mail-based follow-up, with >90% of outcomes undergoing adjudication. Nearly all participants were linked to routinely collected hospitalisation and death data (ie, routine data). An algorithm categorised bleeding events from routine data as major/minor. Kappa statistics were used to assess agreement between data sources, and randomised comparisons were re-run using routine data.

Results

When adjudicated follow-up and routine data were compared, there was agreement for 318 major bleeding events, with routine data identifying 281 additional-potential events, and not identifying 241 participant-reported events (kappa 0.53, 95% CI 0.49 to 0.57). Repeating ASCEND's randomised comparisons using routine data only found estimated relative and absolute effects of allocation to aspirin versus placebo on major bleeding similar to adjudicated follow-up (adjudicated follow-up: aspirin 314 (4.1%) vs placebo 245 (3.2%); rate ratio (RR) 1.29, 95% CI 1.09 to 1.52; absolute excess +6.3/5000 person-years (mean SE±2.1); vs routine data: 327 (4.2%) vs 272 (3.5%); RR 1.21, 95% CI 1.03 to 1.41; absolute excess +5.0/5000 (±2.2)).

Conclusions

Analyses of the ASCEND randomised trial found that major bleeding events ascertained via UK routine data sources provided relative and absolute treatment effects similar to adjudicated follow-up.

Trial registration number

ISRCTN60635500; NCT00135226.",,pdf:https://heart.bmj.com/content/heartjnl/early/2023/06/02/heartjnl-2023-322616.full.pdf; doi:https://doi.org/10.1136/heartjnl-2023-322616; html:https://europepmc.org/articles/PMC10511984; pdf:https://europepmc.org/articles/PMC10511984?pdf=render 34939832,https://doi.org/10.1308/rcsann.2021.0206,"Projections for primary hip and knee replacement surgery up to the year 2060: an analysis based on data from The National Joint Registry for England, Wales, Northern Ireland and the Isle of Man.","Matharu GS, Culliford DJ, Blom AW, Judge A.",,Annals of the Royal College of Surgeons of England,2022,2021-12-23,N,Total hip replacement; Total Knee Replacement; Demand; Future Numbers,,,"

Introduction

We estimated the number of primary total hip and knee replacements (THR and TKR) that will need to be performed up to the year 2060.

Methods

We used data from The National Joint Registry for England, Wales, Northern Ireland and the Isle of Man on the volume of primary THRs (n=94,936) and TKRs (n=100,547) performed in 2018. We projected future numbers of THR and TKR using a static estimated rate from 2018 applied to population growth forecast data from the UK Office for National Statistics up to 2060.

Results

By 2060, THR and TKR volume would increase from 2018 levels by an estimated 37.7% (n=130,766) and 36.6% (n=137,341), respectively. For both males and females demand for surgery was also higher for patients aged 70 and over, with older patients having the biggest relative increase in volume over time: 70-79 years (44.6% males, 41.2% females); 80-89 years (112.4% males, 85.6% females); 90 years and older (348.0% males, 198.2% females).

Conclusion

By 2060 demand for hip and knee joint replacement is estimated to increase by almost 40%. Demand will be greatest in older patients (70+ years), which will have significant implications for the health service requiring forward planning given that morbidity and resource use is higher in this population. These issues, coupled with two waves of COVID-19, will impact the ability of health services to deliver timely joint replacement to many patients for a number of years, requiring urgent planning.",,doi:https://doi.org/10.1308/rcsann.2021.0206; html:https://europepmc.org/articles/PMC9157920; pdf:https://europepmc.org/articles/PMC9157920?pdf=render; doi:https://doi.org/10.1308/rcsann.2021.0206 33174528,https://doi.org/10.3310/hta24570,Antimicrobial-impregnated central venous catheters for preventing neonatal bloodstream infection: the PREVAIL RCT.,"Gilbert R, Brown M, Faria R, Fraser C, Donohue C, Rainford N, Grosso A, Sinha AK, Dorling J, Gray J, Muller-Pebody B, Harron K, Moitt T, McGuire W, Bojke L, Gamble C, Oddie SJ.",,"Health technology assessment (Winchester, England)",2020,2020-11-01,Y,Infant; Newborn; Economic analysis; Central Venous Catheter; Bloodstream Infection; Randomised Controlled Trial; Generalisability; Antimicrobial-impregnated Catheter,,,"

Background

Clinical trials show that antimicrobial-impregnated central venous catheters reduce catheter-related bloodstream infection in adults and children receiving intensive care, but there is insufficient evidence for use in newborn babies.

Objectives

The objectives were (1) to determine clinical effectiveness by conducting a randomised controlled trial comparing antimicrobial-impregnated peripherally inserted central venous catheters with standard peripherally inserted central venous catheters for reducing bloodstream or cerebrospinal fluid infections (referred to as bloodstream infections); (2) to conduct an economic evaluation of the costs, cost-effectiveness and value of conducting additional research; and (3) to conduct a generalisability analysis of trial findings to neonatal care in the NHS.

Design

Three separate studies were undertaken, each addressing one of the three objectives. (1) This was a multicentre, open-label, pragmatic randomised controlled trial; (2) an analysis was undertaken of hospital care costs, lifetime cost-effectiveness and value of information from an NHS perspective; and (3) this was a retrospective cohort study of bloodstream infection rates in neonatal units in England.

Setting

The randomised controlled trial was conducted in 18 neonatal intensive care units in England.

Participants

Participants were babies who required a peripherally inserted central venous catheter (of 1 French gauge in size).

Interventions

The interventions were an antimicrobial-impregnated peripherally inserted central venous catheter (coated with rifampicin-miconazole) or a standard peripherally inserted central venous catheter, allocated randomly (1 : 1) using web randomisation.

Main outcome measure

Study 1 - time to first bloodstream infection, sampled between 24 hours after randomisation and 48 hours after peripherally inserted central venous catheter removal. Study 2 - cost-effectiveness of the antimicrobial-impregnated peripherally inserted central venous catheter compared with the standard peripherally inserted central venous catheters. Study 3 - risk-adjusted bloodstream rates in the trial compared with those in neonatal units in England. For study 3, the data used were as follows: (1) case report forms and linked death registrations; (2) case report forms and linked death registrations linked to administrative health records with 6-month follow-up; and (3) neonatal health records linked to infection surveillance data.

Results

Study 1, clinical effectiveness - 861 babies were randomised (antimicrobial-impregnated peripherally inserted central venous catheter, n = 430; standard peripherally inserted central venous catheter, n = 431). Bloodstream infections occurred in 46 babies (10.7%) randomised to antimicrobial-impregnated peripherally inserted central venous catheters and in 44 (10.2%) babies randomised to standard peripherally inserted central venous catheters. No difference in time to bloodstream infection was detected (hazard ratio 1.11, 95% confidence interval 0.73 to 1.67; p = 0.63). Secondary outcomes of rifampicin resistance in positive blood/cerebrospinal fluid cultures, mortality, clinical outcomes at neonatal unit discharge and time to peripherally inserted central venous catheter removal were similar in both groups. Rifampicin resistance in positive peripherally inserted central venous catheter tip cultures was higher in the antimicrobial-impregnated peripherally inserted central venous catheter group (relative risk 3.51, 95% confidence interval 1.16 to 10.57; p = 0.02) than in the standard peripherally inserted central venous catheter group. Adverse events were similar in both groups. Study 2, economic evaluation - the mean cost of babies' hospital care was £83,473. Antimicrobial-impregnated peripherally inserted central venous catheters were not cost-effective. Given the increased price, compared with standard peripherally inserted central venous catheters, the minimum reduction in risk of bloodstream infection for antimicrobial-impregnated peripherally inserted central venous catheters to be cost-effective was 3% and 15% for babies born at 23-27 and 28-32 weeks' gestation, respectively. Study 3, generalisability analysis - risk-adjusted bloodstream infection rates per 1000 peripherally inserted central venous catheter days were similar among babies in the trial and in all neonatal units. Of all bloodstream infections in babies receiving intensive or high-dependency care in neonatal units, 46% occurred during peripherally inserted central venous catheter days.

Limitations

The trial was open label as antimicrobial-impregnated and standard peripherally inserted central venous catheters are different colours. There was insufficient power to determine differences in rifampicin resistance.

Conclusions

No evidence of benefit or harm was found of peripherally inserted central venous catheters impregnated with rifampicin-miconazole during neonatal care. Interventions with small effects on bloodstream infections could be cost-effective over a child's life course. Findings were generalisable to neonatal units in England. Future research should focus on other types of antimicrobial impregnation of peripherally inserted central venous catheters and alternative approaches for preventing bloodstream infections in neonatal care.

Trial registration

Current Controlled Trials ISRCTN81931394.

Funding

This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 57. See the NIHR Journals Library website for further project information.",,pdf:https://njl-admin.nihr.ac.uk/document/download/2034745; html:http://europepmc.org/books/NBK563908; doi:https://doi.org/10.3310/hta24570 -37814896,https://doi.org/10.1161/circgen.123.004181,Cardiovascular Disease Knowledge Portal: A Community Resource for Cardiovascular Disease Research.,"Costanzo MC, Roselli C, Brandes M, Duby M, Hoang Q, Jang D, Koesterer R, Kudtarkar P, Moriondo A, Nguyen T, Ruebenacker O, Smadbeck P, Sun Y, Butterworth AS, Aragam KG, Lumbers RT, Khera AV, Lubitz SA, Ellinor PT, Gaulton KJ, Flannick J, Burtt NP.",,Circulation. Genomic and precision medicine,2023,2023-10-10,N,Cardiovascular diseases; Database; Phenotype; Myocardial infarction; Biomarkers; epigenomics,,,,,doi:https://doi.org/10.1161/CIRCGEN.123.004181 36814324,https://doi.org/10.1186/s13195-023-01184-y,"Investigating associations between blood metabolites, later life brain imaging measures, and genetic risk for Alzheimer's disease.","Green RE, Lord J, Scelsi MA, Xu J, Wong A, Naomi-James S, Handy A, Gilchrist L, Williams DM, Parker TD, Lane CA, Malone IB, Cash DM, Sudre CH, Coath W, Thomas DL, Keuss S, Dobson R, Legido-Quigley C, Fox NC, Schott JM, Richards M, Proitsi P, Insight 46 study team.",,Alzheimer's research & therapy,2023,2023-02-22,Y,Metabolites; Ageing; Brain imaging; Alzheimer’s disease; Dementia; Birth Cohort; Polygenic Scores; Weighted-gene Coexpression Network Analysis,,,"

Background

Identifying blood-based signatures of brain health and preclinical pathology may offer insights into early disease mechanisms and highlight avenues for intervention. Here, we systematically profiled associations between blood metabolites and whole-brain volume, hippocampal volume, and amyloid-β status among participants of Insight 46-the neuroscience sub-study of the National Survey of Health and Development (NSHD). We additionally explored whether key metabolites were associated with polygenic risk for Alzheimer's disease (AD).

Methods

Following quality control, levels of 1019 metabolites-detected with liquid chromatography-mass spectrometry-were available for 1740 participants at age 60-64. Metabolite data were subsequently clustered into modules of co-expressed metabolites using weighted coexpression network analysis. Accompanying MRI and amyloid-PET imaging data were present for 437 participants (age 69-71). Regression analyses tested relationships between metabolite measures-modules and hub metabolites-and imaging outcomes. Hub metabolites were defined as metabolites that were highly connected within significant (pFDR < 0.05) modules or were identified as a hub in a previous analysis on cognitive function in the same cohort. Regression models included adjustments for age, sex, APOE genotype, lipid medication use, childhood cognitive ability, and social factors. Finally, associations were tested between AD polygenic risk scores (PRS), including and excluding the APOE region, and metabolites and modules that significantly associated (pFDR < 0.05) with an imaging outcome (N = 1638).

Results

In the fully adjusted model, three lipid modules were associated with a brain volume measure (pFDR < 0.05): one enriched in sphingolipids (hippocampal volume: ß = 0.14, 95% CI = [0.055,0.23]), one in several fatty acid pathways (whole-brain volume: ß =  - 0.072, 95%CI = [- 0.12, - 0.026]), and another in diacylglycerols and phosphatidylethanolamines (whole-brain volume: ß =  - 0.066, 95% CI = [- 0.11, - 0.020]). Twenty-two hub metabolites were associated (pFDR < 0.05) with an imaging outcome (whole-brain volume: 22; hippocampal volume: 4). Some nominal associations were reported for amyloid-β, and with an AD PRS in our genetic analysis, but none survived multiple testing correction.

Conclusions

Our findings highlight key metabolites, with functions in membrane integrity and cell signalling, that associated with structural brain measures in later life. Future research should focus on replicating this work and interrogating causality.",,pdf:https://alzres.biomedcentral.com/counter/pdf/10.1186/s13195-023-01184-y; doi:https://doi.org/10.1186/s13195-023-01184-y; html:https://europepmc.org/articles/PMC9945600; pdf:https://europepmc.org/articles/PMC9945600?pdf=render +37814896,https://doi.org/10.1161/circgen.123.004181,Cardiovascular Disease Knowledge Portal: A Community Resource for Cardiovascular Disease Research.,"Costanzo MC, Roselli C, Brandes M, Duby M, Hoang Q, Jang D, Koesterer R, Kudtarkar P, Moriondo A, Nguyen T, Ruebenacker O, Smadbeck P, Sun Y, Butterworth AS, Aragam KG, Lumbers RT, Khera AV, Lubitz SA, Ellinor PT, Gaulton KJ, Flannick J, Burtt NP.",,Circulation. Genomic and precision medicine,2023,2023-10-10,N,Cardiovascular diseases; Database; Phenotype; Myocardial infarction; Biomarkers; epigenomics,,,,,doi:https://doi.org/10.1161/CIRCGEN.123.004181 38198570,https://doi.org/10.1126/scitranslmed.adf4428,Prospective study design and data analysis in UK Biobank.,"Allen NE, Lacey B, Lawlor DA, Pell JP, Gallacher J, Smeeth L, Elliott P, Matthews PM, Lyons RA, Whetton AD, Lucassen A, Hurles ME, Chapman M, Roddam AW, Fitzpatrick NK, Hansell AL, Hardy R, Marioni RE, O'Donnell VB, Williams J, Lindgren CM, Effingham M, Sellors J, Danesh J, Collins R.",,Science translational medicine,2024,2024-01-10,N,,,,"Population-based prospective studies, such as UK Biobank, are valuable for generating and testing hypotheses about the potential causes of human disease. We describe how UK Biobank's study design, data access policies, and approaches to statistical analysis can help to minimize error and improve the interpretability of research findings, with implications for other population-based prospective studies being established worldwide.",,pdf:https://www.pure.ed.ac.uk/ws/files/405264227/scitranslmed.adf4428.pdf; doi:https://doi.org/10.1126/scitranslmed.adf4428; html:https://europepmc.org/articles/PMC11127744; pdf:https://europepmc.org/articles/PMC11127744?pdf=render; doi:https://doi.org/10.1126/scitranslmed.adf4428 34750571,https://doi.org/10.1038/s42255-021-00478-5,Integrative analysis of the plasma proteome and polygenic risk of cardiometabolic diseases.,"Ritchie SC, Lambert SA, Arnold M, Teo SM, Lim S, Scepanovic P, Marten J, Zahid S, Chaffin M, Liu Y, Abraham G, Ouwehand WH, Roberts DJ, Watkins NA, Drew BG, Calkin AC, Di Angelantonio E, Soranzo N, Burgess S, Chapman M, Kathiresan S, Khera AV, Danesh J, Butterworth AS, Inouye M.",,Nature metabolism,2021,2021-11-08,Y,,,,"Cardiometabolic diseases are frequently polygenic in architecture, comprising a large number of risk alleles with small effects spread across the genome1-3. Polygenic scores (PGS) aggregate these into a metric representing an individual's genetic predisposition to disease. PGS have shown promise for early risk prediction4-7 and there is an open question as to whether PGS can also be used to understand disease biology8. Here, we demonstrate that cardiometabolic disease PGS can be used to elucidate the proteins underlying disease pathogenesis. In 3,087 healthy individuals, we found that PGS for coronary artery disease, type 2 diabetes, chronic kidney disease and ischaemic stroke are associated with the levels of 49 plasma proteins. Associations were polygenic in architecture, largely independent of cis and trans protein quantitative trait loci and present for proteins without quantitative trait loci. Over a follow-up of 7.7 years, 28 of these proteins associated with future myocardial infarction or type 2 diabetes events, 16 of which were mediators between polygenic risk and incident disease. Twelve of these were druggable targets with therapeutic potential. Our results demonstrate the potential for PGS to uncover causal disease biology and targets with therapeutic potential, including those that may be missed by approaches utilizing information at a single locus.",,pdf:https://www.nature.com/articles/s42255-021-00478-5.pdf; doi:https://doi.org/10.1038/s42255-021-00478-5; html:https://europepmc.org/articles/PMC8574944; pdf:https://europepmc.org/articles/PMC8574944?pdf=render 36774358,https://doi.org/10.1038/s41467-023-36439-7,Genomic and microenvironmental heterogeneity shaping epithelial-to-mesenchymal trajectories in cancer.,"Malagoli Tagliazucchi G, Wiecek AJ, Withnell E, Secrier M.",,Nature communications,2023,2023-02-11,Y,,,,"The epithelial to mesenchymal transition (EMT) is a key cellular process underlying cancer progression, with multiple intermediate states whose molecular hallmarks remain poorly characterised. To fill this gap, we present a method to robustly evaluate EMT transformation in individual tumours based on transcriptomic signals. We apply this approach to explore EMT trajectories in 7180 tumours of epithelial origin and identify three macro-states with prognostic and therapeutic value, attributable to epithelial, hybrid E/M and mesenchymal phenotypes. We show that the hybrid state is relatively stable and linked with increased aneuploidy. We further employ spatial transcriptomics and single cell datasets to explore the spatial heterogeneity of EMT transformation and distinct interaction patterns with cytotoxic, NK cells and fibroblasts in the tumour microenvironment. Additionally, we provide a catalogue of genomic events underlying distinct evolutionary constraints on EMT transformation. This study sheds light on the aetiology of distinct stages along the EMT trajectory, and highlights broader genomic and environmental hallmarks shaping the mesenchymal transformation of primary tumours.",,pdf:https://www.nature.com/articles/s41467-023-36439-7.pdf; doi:https://doi.org/10.1038/s41467-023-36439-7; html:https://europepmc.org/articles/PMC9922305; pdf:https://europepmc.org/articles/PMC9922305?pdf=render @@ -1707,16 +1707,16 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 35385889,https://doi.org/10.1515/dmpt-2021-0104,Prevalence of CYP2C19*2 carriers in Saudi ischemic stroke patients and the suitability of using genotyping to guide antiplatelet therapy in a university hospital setup.,"Al-Rubaish AM, Al-Muhanna FA, Alshehri AM, Alsulaiman AA, Alabdulali MM, Alkhamis F, Alamri AS, Alali RA, Akhtar MS, Cyrus C, Claassens DMF, Asselbergs FW, Al-Ali AK.",,Drug metabolism and personalized therapy,2021,2021-07-08,N,Genotyping; Stroke; aspirin; Clopidogrel; Cyp2c19*2,,,"

Objectives

To mitigate the incidence of recurrent stroke in patients, dual antiplatelet therapy comprising aspirin and clopidogrel is usually administered. Clopidogrel is a prodrug and its bioactivation is catalyzed by cytochrome P450 (CYP)2C19. The main objective of this work was to determine the prevalence of CYP2C19*2 carriers in Saudi ischemic stroke patients and assess the suitability of using genotyping to guide antiplatelet therapy in a university hospital setup.

Methods

This prospective (2018-2019) study was conducted on 256 patients (age 61 ± 12.5) clinically diagnosed with ischemic stroke who were genotyped using Spartan RX CYP2C19 assay.

Results

From the total patient group (256), upon admission, 210 patients were prescribed either aspirin, clopidogrel or dual antiplatelet therapy. Of the 27 patients with the CYP2C19*2 allele who were prescribed clopidogrel (18) or dual antiplatelet therapy (9), only 21 patients could be followed up for a period of six months post stroke event, in addition to 21 age- and sex-matched patients with the normal allele. The CYP2C19*2 allele carriers had a statistically significant increased risk of recurrent stroke compared to patients carrying the normal allele.

Conclusions

This study shows the suitability of using genotyping to guide antiplatelet therapy in ischemic stroke patients in a clinical setting.",,pdf:https://discovery.ucl.ac.uk/10135735/1/Asselbergs_10.1515_dmdi-2021-0104.pdf; doi:https://doi.org/10.1515/dmpt-2021-0104 34237806,https://doi.org/10.1515/dmdi-2021-0104,Prevalence of CYP2C19*2 carriers in Saudi ischemic stroke patients and the suitability of using genotyping to guide antiplatelet therapy in a university hospital setup.,"Al-Rubaish AM, Al-Muhanna FA, Alshehri AM, Alsulaiman AA, Alabdulali MM, Alkhamis F, Alamri AS, Alali RA, Akhtar MS, Cyrus C, Claassens DMF, Asselbergs FW, Al-Ali AK.",,Drug metabolism and personalized therapy,2021,2021-07-08,N,Genotyping; Stroke; aspirin; Clopidogrel; Cyp2c19*2,,,"

Objectives

To mitigate the incidence of recurrent stroke in patients, dual antiplatelet therapy comprising aspirin and clopidogrel is usually administered. Clopidogrel is a prodrug and its bioactivation is catalyzed by cytochrome P450 (CYP)2C19. The main objective of this work was to determine the prevalence of CYP2C19*2 carriers in Saudi ischemic stroke patients and assess the suitability of using genotyping to guide antiplatelet therapy in a university hospital setup.

Methods

This prospective (2018-2019) study was conducted on 256 patients (age 61 ± 12.5) clinically diagnosed with ischemic stroke who were genotyped using Spartan RX CYP2C19 assay.

Results

From the total patient group (256), upon admission, 210 patients were prescribed either aspirin, clopidogrel or dual antiplatelet therapy. Of the 27 patients with the CYP2C19*2 allele who were prescribed clopidogrel (18) or dual antiplatelet therapy (9), only 21 patients could be followed up for a period of six months post stroke event, in addition to 21 age- and sex-matched patients with the normal allele. The CYP2C19*2 allele carriers had a statistically significant increased risk of recurrent stroke compared to patients carrying the normal allele.

Conclusions

This study shows the suitability of using genotyping to guide antiplatelet therapy in ischemic stroke patients in a clinical setting.",,pdf:https://discovery.ucl.ac.uk/10135735/1/Asselbergs_10.1515_dmdi-2021-0104.pdf; doi:https://doi.org/10.1515/dmdi-2021-0104 32907797,https://doi.org/10.1136/bmj.m3210,Guidelines for clinical trial protocols for interventions involving artificial intelligence: the SPIRIT-AI Extension.,"Rivera SC, Liu X, Chan AW, Denniston AK, Calvert MJ, SPIRIT-AI and CONSORT-AI Working Group.",,BMJ (Clinical research ed.),2020,2020-09-09,Y,,,,"The SPIRIT 2013 (The Standard Protocol Items: Recommendations for Interventional Trials) statement aims to improve the completeness of clinical trial protocol reporting, by providing evidence-based recommendations for the minimum set of items to be addressed. This guidance has been instrumental in promoting transparent evaluation of new interventions. More recently, there is a growing recognition that interventions involving artificial intelligence need to undergo rigorous, prospective evaluation to demonstrate their impact on health outcomes.The SPIRIT-AI extension is a new reporting guideline for clinical trials protocols evaluating interventions with an AI component. It was developed in parallel with its companion statement for trial reports: CONSORT-AI. Both guidelines were developed using a staged consensus process, involving a literature review and expert consultation to generate 26 candidate items, which were consulted on by an international multi-stakeholder group in a 2-stage Delphi survey (103 stakeholders), agreed on in a consensus meeting (31 stakeholders) and refined through a checklist pilot (34 participants).The SPIRIT-AI extension includes 15 new items, which were considered sufficiently important for clinical trial protocols of AI interventions. These new items should be routinely reported in addition to the core SPIRIT 2013 items. SPIRIT-AI recommends that investigators provide clear descriptions of the AI intervention, including instructions and skills required for use, the setting in which the AI intervention will be integrated, considerations around the handling of input and output data, the human-AI interaction and analysis of error cases.SPIRIT-AI will help promote transparency and completeness for clinical trial protocols for AI interventions. Its use will assist editors and peer-reviewers, as well as the general readership, to understand, interpret and critically appraise the design and risk of bias for a planned clinical trial.",,pdf:https://www.bmj.com/content/bmj/370/bmj.m3210.full.pdf; doi:https://doi.org/10.1136/bmj.m3210; html:https://europepmc.org/articles/PMC7490785 -38115587,https://doi.org/10.1089/neu.2023.0464,The Australian Traumatic Brain Injury Initiative: Systematic Review of Predictive Value of Biological Markers for People With Moderate-Severe Traumatic Brain Injury.,"Bagg MK, Hellewell SC, Keeves J, Antonic-Baker A, McKimmie A, Hicks AJ, Gadowski A, Newcombe VFJ, Barlow KM, Balogh ZJ, Ross JP, Law M, Caeyenberghs K, Parizel PM, Thorne J, Papini M, Gill G, Jefferson A, Ponsford JL, Lannin NA, O'Brien TJ, Cameron PA, Cooper DJ, Rushworth N, Gabbe BJ, Fitzgerald M.",,Journal of neurotrauma,2024,2024-03-08,N,"Tomography, X-ray computed; Tissues; Biomarkers; Magnetic Resonance Imaging; Body Fluids; Common Data Elements; Brain Injuries, Traumatic; Systematic Review [Publication Type]",,,"The Australian Traumatic Brain Injury Initiative (AUS-TBI) aims to co-design a data resource to predict outcomes for people with moderate-severe traumatic brain injury (TBI) across Australia. Fundamental to this resource is the data dictionary, which is an ontology of data items. Here, we report the systematic review and consensus process for inclusion of biological markers in the data dictionary. Standardized database searches were implemented from inception through April 2022. English-language studies evaluating association between a fluid, tissue, or imaging marker and any clinical outcome in at least 10 patients with moderate-severe TBI were included. Records were screened using a prioritization algorithm and saturation threshold in Research Screener. Full-length records were then screened in Covidence. A pre-defined algorithm was used to assign a judgement of predictive value to each observed association, and high-value predictors were discussed in a consensus process. Searches retrieved 106,593 records; 1,417 full-length records were screened, resulting in 546 included records. Two hundred thirty-nine individual markers were extracted, evaluated against 101 outcomes. Forty-one markers were judged to be high-value predictors of 15 outcomes. Fluid markers retained following the consensus process included ubiquitin C-terminal hydrolase L1 (UCH-L1), S100, and glial fibrillary acidic protein (GFAP). Imaging markers included computed tomography (CT) scores (e.g., Marshall scores), pathological observations (e.g., hemorrhage, midline shift), and magnetic resonance imaging (MRI) classification (e.g., diffuse axonal injury). Clinical context and time of sampling of potential predictive indicators are important considerations for utility. This systematic review and consensus process has identified fluid and imaging biomarkers with high predictive value of clinical and long-term outcomes following moderate-severe TBI.",,doi:https://doi.org/10.1089/neu.2023.0464 32900377,https://doi.org/10.1186/s12916-020-01754-z,Going on up to the SPIRIT in AI: will new reporting guidelines for clinical trials of AI interventions improve their rigour?,"Wicks P, Liu X, Denniston AK.",,BMC medicine,2020,2020-09-09,Y,Artificial intelligence; Checklist; Clinical Trial; Machine Learning; Reporting Guidelines,,,,,pdf:https://bmcmedicine.biomedcentral.com/track/pdf/10.1186/s12916-020-01754-z; doi:https://doi.org/10.1186/s12916-020-01754-z; html:https://europepmc.org/articles/PMC7487816; pdf:https://europepmc.org/articles/PMC7487816?pdf=render +38115587,https://doi.org/10.1089/neu.2023.0464,The Australian Traumatic Brain Injury Initiative: Systematic Review of Predictive Value of Biological Markers for People With Moderate-Severe Traumatic Brain Injury.,"Bagg MK, Hellewell SC, Keeves J, Antonic-Baker A, McKimmie A, Hicks AJ, Gadowski A, Newcombe VFJ, Barlow KM, Balogh ZJ, Ross JP, Law M, Caeyenberghs K, Parizel PM, Thorne J, Papini M, Gill G, Jefferson A, Ponsford JL, Lannin NA, O'Brien TJ, Cameron PA, Cooper DJ, Rushworth N, Gabbe BJ, Fitzgerald M.",,Journal of neurotrauma,2024,2024-03-08,N,"Tomography, X-ray computed; Tissues; Biomarkers; Magnetic Resonance Imaging; Body Fluids; Common Data Elements; Brain Injuries, Traumatic; Systematic Review [Publication Type]",,,"The Australian Traumatic Brain Injury Initiative (AUS-TBI) aims to co-design a data resource to predict outcomes for people with moderate-severe traumatic brain injury (TBI) across Australia. Fundamental to this resource is the data dictionary, which is an ontology of data items. Here, we report the systematic review and consensus process for inclusion of biological markers in the data dictionary. Standardized database searches were implemented from inception through April 2022. English-language studies evaluating association between a fluid, tissue, or imaging marker and any clinical outcome in at least 10 patients with moderate-severe TBI were included. Records were screened using a prioritization algorithm and saturation threshold in Research Screener. Full-length records were then screened in Covidence. A pre-defined algorithm was used to assign a judgement of predictive value to each observed association, and high-value predictors were discussed in a consensus process. Searches retrieved 106,593 records; 1,417 full-length records were screened, resulting in 546 included records. Two hundred thirty-nine individual markers were extracted, evaluated against 101 outcomes. Forty-one markers were judged to be high-value predictors of 15 outcomes. Fluid markers retained following the consensus process included ubiquitin C-terminal hydrolase L1 (UCH-L1), S100, and glial fibrillary acidic protein (GFAP). Imaging markers included computed tomography (CT) scores (e.g., Marshall scores), pathological observations (e.g., hemorrhage, midline shift), and magnetic resonance imaging (MRI) classification (e.g., diffuse axonal injury). Clinical context and time of sampling of potential predictive indicators are important considerations for utility. This systematic review and consensus process has identified fluid and imaging biomarkers with high predictive value of clinical and long-term outcomes following moderate-severe TBI.",,doi:https://doi.org/10.1089/neu.2023.0464 34535985,https://doi.org/10.1002/hep4.1805,Genome-Wide Association Study of NAFLD Using Electronic Health Records.,"Fairfield CJ, Drake TM, Pius R, Bretherick AD, Campbell A, Clark DW, Fallowfield JA, Hayward C, Henderson NC, Joshi PK, Mills NL, Porteous DJ, Ramachandran P, Semple RK, Shaw CA, Sudlow CLM, Timmers PRHJ, Wilson JF, Wigmore SJ, Harrison EM, Spiliopoulou A.",,Hepatology communications,2022,2021-09-17,Y,,,,"Genome-wide association studies (GWAS) have identified several risk loci for nonalcoholic fatty liver disease (NAFLD). Previous studies have largely relied on small sample sizes and have assessed quantitative traits. We performed a case-control GWAS in the UK Biobank using recorded diagnosis of NAFLD based on diagnostic codes recommended in recent consensus guidelines. We performed a GWAS of 4,761 cases of NAFLD and 373,227 healthy controls without evidence of NAFLD. Sensitivity analyses were performed excluding other co-existing hepatic pathology, adjusting for body mass index (BMI) and adjusting for alcohol intake. A total of 9,723,654 variants were assessed by logistic regression adjusted for age, sex, genetic principal components, and genotyping batch. We performed a GWAS meta-analysis using available summary association statistics. Six risk loci were identified (P < 5*10-8 ) (apolipoprotein E [APOE], patatin-like phospholipase domain containing 3 [PNPLA3, transmembrane 6 superfamily member 2 [TM6SF2], glucokinase regulator [GCKR], mitochondrial amidoxime reducing component 1 [MARC1], and tribbles pseudokinase 1 [TRIB1]). All loci retained significance in sensitivity analyses without co-existent hepatic pathology and after adjustment for BMI. PNPLA3 and TM6SF2 remained significant after adjustment for alcohol (alcohol intake was known in only 158,388 individuals), with others demonstrating consistent direction and magnitude of effect. All six loci were significant on meta-analysis. Rs429358 (P = 2.17*10-11 ) is a missense variant within the APOE gene determining ϵ4 versus ϵ2/ϵ3 alleles. The ϵ4 allele of APOE offered protection against NAFLD (odds ratio for heterozygotes 0.84 [95% confidence interval 0.78-0.90] and homozygotes 0.64 [0.50-0.79]). Conclusion: This GWAS replicates six known NAFLD-susceptibility loci and confirms that the ϵ4 allele of APOE is associated with protection against NAFLD. The results are consistent with published GWAS using histological and radiological measures of NAFLD, confirming that NAFLD identified through diagnostic codes from consensus guidelines is a valid alternative to more invasive and costly approaches.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/hep4.1805; doi:https://doi.org/10.1002/hep4.1805; html:https://europepmc.org/articles/PMC8793997; pdf:https://europepmc.org/articles/PMC8793997?pdf=render 35861678,https://doi.org/10.2196/36989,Developing a Long COVID Phenotype for Postacute COVID-19 in a National Primary Care Sentinel Cohort: Observational Retrospective Database Analysis.,"Mayor N, Meza-Torres B, Okusi C, Delanerolle G, Chapman M, Wang W, Anand S, Feher M, Macartney J, Byford R, Joy M, Gatenby P, Curcin V, Greenhalgh T, Delaney B, de Lusignan S.",,JMIR public health and surveillance,2022,2022-08-11,Y,Phenotype; Surveillance; epidemiology; Public Health; Hospitalization; Social Class; Disease Management; General Practitioners; Ethnicity; Electronic Health Record; Medical Record Systems; Systematized Nomenclature Of Medicine; Computerized; Bioportal; Biomedical Ontologies; Data Accuracy; Digital Tool; Covid-19; Sars-cov-2; Long Covid; Postacute Covid-19 Syndrome; Data Extracts,,,"

Background

Following COVID-19, up to 40% of people have ongoing health problems, referred to as postacute COVID-19 or long COVID (LC). LC varies from a single persisting symptom to a complex multisystem disease. Research has flagged that this condition is underrecorded in primary care records, and seeks to better define its clinical characteristics and management. Phenotypes provide a standard method for case definition and identification from routine data and are usually machine-processable. An LC phenotype can underpin research into this condition.

Objective

This study aims to develop a phenotype for LC to inform the epidemiology and future research into this condition. We compared clinical symptoms in people with LC before and after their index infection, recorded from March 1, 2020, to April 1, 2021. We also compared people recorded as having acute infection with those with LC who were hospitalized and those who were not.

Methods

We used data from the Primary Care Sentinel Cohort (PCSC) of the Oxford Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) database. This network was recruited to be nationally representative of the English population. We developed an LC phenotype using our established 3-step ontological method: (1) ontological step (defining the reasoning process underpinning the phenotype, (2) coding step (exploring what clinical terms are available, and (3) logical extract model (testing performance). We created a version of this phenotype using Protégé in the ontology web language for BioPortal and using PhenoFlow. Next, we used the phenotype to compare people with LC (1) with regard to their symptoms in the year prior to acquiring COVID-19 and (2) with people with acute COVID-19. We also compared hospitalized people with LC with those not hospitalized. We compared sociodemographic details, comorbidities, and Office of National Statistics-defined LC symptoms between groups. We used descriptive statistics and logistic regression.

Results

The long-COVID phenotype differentiated people hospitalized with LC from people who were not and where no index infection was identified. The PCSC (N=7.4 million) includes 428,479 patients with acute COVID-19 diagnosis confirmed by a laboratory test and 10,772 patients with clinically diagnosed COVID-19. A total of 7471 (1.74%, 95% CI 1.70-1.78) people were coded as having LC, 1009 (13.5%, 95% CI 12.7-14.3) had a hospital admission related to acute COVID-19, and 6462 (86.5%, 95% CI 85.7-87.3) were not hospitalized, of whom 2728 (42.2%) had no COVID-19 index date recorded. In addition, 1009 (13.5%, 95% CI 12.73-14.28) people with LC were hospitalized compared to 17,993 (4.5%, 95% CI 4.48-4.61; P<.001) with uncomplicated COVID-19.

Conclusions

Our LC phenotype enables the identification of individuals with the condition in routine data sets, facilitating their comparison with unaffected people through retrospective research. This phenotype and study protocol to explore its face validity contributes to a better understanding of LC.",,pdf:https://publichealth.jmir.org/2022/8/e36989/PDF; doi:https://doi.org/10.2196/36989; html:https://europepmc.org/articles/PMC9374163 37494011,https://doi.org/10.1001/jamacardio.2023.2167,"Association of Longer Leukocyte Telomere Length With Cardiac Size, Function, and Heart Failure.","Aung N, Wang Q, van Duijvenboden S, Burns R, Stoma S, Raisi-Estabragh Z, Ahmet S, Allara E, Wood A, Di Angelantonio E, Danesh J, Munroe PB, Young A, Harvey NC, Codd V, Nelson CP, Petersen SE, Samani NJ.",,JAMA cardiology,2023,2023-09-01,Y,,,,"

Importance

Longer leukocyte telomere length (LTL) is associated with a lower risk of adverse cardiovascular outcomes. The extent to which variation in LTL is associated with intermediary cardiovascular phenotypes is unclear.

Objective

To evaluate the associations between LTL and a diverse set of cardiovascular imaging phenotypes.

Design, setting, and participants

This is a population-based cross-sectional study of UK Biobank participants recruited from 2006 to 2010. LTL was measured using a quantitative polymerase chain reaction method. Cardiovascular measurements were derived from cardiovascular magnetic resonance using machine learning. The median (IQR) duration of follow-up was 12.0 (11.3-12.7) years. The associations of LTL with imaging measurements and incident heart failure (HF) were evaluated by multivariable regression models. Genetic associations between LTL and significantly associated traits were investigated by mendelian randomization. Data were analyzed from January to May 2023.

Exposure

LTL.

Main outcomes and measures

Cardiovascular imaging traits and HF.

Results

Of 40 459 included participants, 19 529 (48.3%) were men, and the mean (SD) age was 55.1 (7.6) years. Longer LTL was independently associated with a pattern of positive cardiac remodeling (higher left ventricular mass, larger global ventricular size and volume, and higher ventricular and atrial stroke volumes) and a lower risk of incident HF (LTL fourth quartile vs first quartile: hazard ratio, 0.86; 95% CI, 0.81-0.91; P = 1.8 × 10-6). Mendelian randomization analysis suggested a potential causal association between LTL and left ventricular mass, global ventricular volume, and left ventricular stroke volume.

Conclusions and relevance

In this cross-sectional study, longer LTL was associated with a larger heart with better cardiac function in middle age, which could potentially explain the observed lower risk of incident HF.",,pdf:https://jamanetwork.com/journals/jamacardiology/articlepdf/2807386/jamacardiology_aung_2023_oi_230032_1689092909.06174.pdf; doi:https://doi.org/10.1001/jamacardio.2023.2167; html:https://europepmc.org/articles/PMC10372756 37201609,https://doi.org/10.1016/j.ijcard.2023.05.024,Identifying distinct clinical clusters in heart failure with mildly reduced ejection fraction.,"Meijs C, Brugts JJ, Lund LH, Linssen GCM, Rocca HB, Dahlström U, Vaartjes I, Koudstaal S, Asselbergs FW, Savarese G, Uijl A.",,International journal of cardiology,2023,2023-05-16,N,Heterogeneity; Clustering; Latent Class Analysis; Heart Failure With Mildly Reduced Ejection Fraction,,,"

Introduction

Heart failure (HF) is a heterogeneous syndrome, and the specific sub-category HF with mildly reduced ejection fraction (EF) range (HFmrEF; 41-49% EF) is only recently recognised as a distinct entity. Cluster analysis can characterise heterogeneous patient populations and could serve as a stratification tool in clinical trials and for prognostication. The aim of this study was to identify clusters in HFmrEF and compare cluster prognosis.

Methods and results

Latent class analysis to cluster HFmrEF patients based on their characteristics was performed in the Swedish HF registry (n = 7316). Identified clusters were validated in a Dutch cross-sectional HF registry-based dataset CHECK-HF (n = 1536). In Sweden, mortality and hospitalisation across the clusters were compared using a Cox proportional hazard model, with a Fine-Gray sub-distribution for competing risks and adjustment for age and sex. Six clusters were discovered with the following prevalence and hazard ratio with 95% confidence intervals (HR [95%CI]) vs. cluster 1: 1) low-comorbidity (17%, reference), 2) ischaemic-male (13%, HR 0.9 [95% CI 0.7-1.1]), 3) atrial fibrillation (20%, HR 1.5 [95% CI 1.2-1.9]), 4) device/wide QRS (9%, HR 2.7 [95% CI 2.2-3.4]), 5) metabolic (19%, HR 3.1 [95% CI 2.5-3.7]) and 6) cardio-renal phenotype (22%, HR 2.8 [95% CI 2.2-3.6]). The cluster model was robust between both datasets.

Conclusion

We found robust clusters with potential clinical meaning and differences in mortality and hospitalisation. Our clustering model could be valuable as a clinical differentiation support and prognostic tool in clinical trial design.",,pdf:http://www.internationaljournalofcardiology.com/article/S0167527323007180/pdf; doi:https://doi.org/10.1016/j.ijcard.2023.05.024 38351061,https://doi.org/10.1038/s41467-024-45419-4,Structural and mechanistic characterization of bifunctional heparan sulfate N-deacetylase-N-sulfotransferase 1.,"Mycroft-West CJ, Abdelkarim S, Duyvesteyn HME, Gandhi NS, Skidmore MA, Owens RJ, Wu L.",,Nature communications,2024,2024-02-13,Y,,,,"Heparan sulfate (HS) polysaccharides are major constituents of the extracellular matrix, which are involved in myriad structural and signaling processes. Mature HS polysaccharides contain complex, non-templated patterns of sulfation and epimerization, which mediate interactions with diverse protein partners. Complex HS modifications form around initial clusters of glucosamine-N-sulfate (GlcNS) on nascent polysaccharide chains, but the mechanistic basis underpinning incorporation of GlcNS itself into HS remains unclear. Here, we determine cryo-electron microscopy structures of human N-deacetylase-N-sulfotransferase (NDST)1, the bifunctional enzyme primarily responsible for initial GlcNS modification of HS. Our structures reveal the architecture of both NDST1 deacetylase and sulfotransferase catalytic domains, alongside a non-catalytic N-terminal domain. The two catalytic domains of NDST1 adopt a distinct back-to-back topology that limits direct cooperativity. Binding analyses, aided by activity-modulating nanobodies, suggest that anchoring of the substrate at the sulfotransferase domain initiates the NDST1 catalytic cycle, providing a plausible mechanism for cooperativity despite spatial domain separation. Our data shed light on key determinants of NDST1 activity, and describe tools to probe NDST1 function in vitro and in vivo.",,pdf:https://www.nature.com/articles/s41467-024-45419-4.pdf; doi:https://doi.org/10.1038/s41467-024-45419-4; html:https://europepmc.org/articles/PMC10864358; pdf:https://europepmc.org/articles/PMC10864358?pdf=render 36449515,https://doi.org/10.1371/journal.pcbi.1010726,Cluster detection with random neighbourhood covering: Application to invasive Group A Streptococcal disease.,"Cavallaro M, Coelho J, Ready D, Decraene V, Lamagni T, McCarthy ND, Todkill D, Keeling MJ.",,PLoS computational biology,2022,2022-11-30,Y,,,,"The rapid detection of outbreaks is a key step in the effective control and containment of infectious diseases. In particular, the identification of cases which might be epidemiologically linked is crucial in directing outbreak-containment efforts and shaping the intervention of public health authorities. Often this requires the detection of clusters of cases whose numbers exceed those expected by a background of sporadic cases. Quantifying exceedances rapidly is particularly challenging when only few cases are typically reported in a precise location and time. To address such important public health concerns, we present a general method which can detect spatio-temporal deviations from a Poisson point process and estimate the odds of an isolate being part of a cluster. This method can be applied to diseases where detailed geographical information is available. In addition, we propose an approach to explicitly take account of delays in microbial typing. As a case study, we considered invasive group A Streptococcus infection events as recorded and typed by Public Health England from 2015 to 2020.",,pdf:https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1010726&type=printable; doi:https://doi.org/10.1371/journal.pcbi.1010726; html:https://europepmc.org/articles/PMC9744322; pdf:https://europepmc.org/articles/PMC9744322?pdf=render -36512045,https://doi.org/10.1007/s00330-022-09323-z,Prediction of incident cardiovascular events using machine learning and CMR radiomics.,"Pujadas ER, Raisi-Estabragh Z, Szabo L, McCracken C, Morcillo CI, Campello VM, Martín-Isla C, Atehortua AM, Vago H, Merkely B, Maurovich-Horvat P, Harvey NC, Neubauer S, Petersen SE, Lekadir K.",,European radiology,2023,2022-12-13,Y,Atrial fibrillation; Heart Failure; Preventive Medicine; Machine Learning; Radiomics,,,"

Objectives

Evaluation of the feasibility of using cardiovascular magnetic resonance (CMR) radiomics in the prediction of incident atrial fibrillation (AF), heart failure (HF), myocardial infarction (MI), and stroke using machine learning techniques.

Methods

We identified participants from the UK Biobank who experienced incident AF, HF, MI, or stroke during the continuous longitudinal follow-up. The CMR indices and the vascular risk factors (VRFs) as well as the CMR images were obtained for each participant. Three-segmented regions of interest (ROIs) were computed: right ventricle cavity, left ventricle (LV) cavity, and LV myocardium in end-systole and end-diastole phases. Radiomics features were extracted from the 3D volumes of the ROIs. Seven integrative models were built for each incident cardiovascular disease (CVD) as an outcome. Each model was built with VRF, CMR indices, and radiomics features and a combination of them. Support vector machine was used for classification. To assess the model performance, the accuracy, sensitivity, specificity, and AUC were reported.

Results

AF prediction model using the VRF+CMR+Rad model (accuracy: 0.71, AUC 0.76) obtained the best result. However, the AUC was similar to the VRF+Rad model. HF showed the most significant improvement with the inclusion of CMR metrics (VRF+CMR+Rad: 0.79, AUC 0.84). Moreover, adding only the radiomics features to the VRF reached an almost similarly good performance (VRF+Rad: accuracy 0.77, AUC 0.83). Prediction models looking into incident MI and stroke reached slightly smaller improvement.

Conclusions

Radiomics features may provide incremental predictive value over VRF and CMR indices in the prediction of incident CVDs.

Key points

• Prediction of incident atrial fibrillation, heart failure, stroke, and myocardial infarction using machine learning techniques. • CMR radiomics, vascular risk factors, and standard CMR indices will be considered in the machine learning models. • The experiments show that radiomics features can provide incremental predictive value over VRF and CMR indices in the prediction of incident cardiovascular diseases.",,pdf:https://link.springer.com/content/pdf/10.1007/s00330-022-09323-z.pdf; doi:https://doi.org/10.1007/s00330-022-09323-z; html:https://europepmc.org/articles/PMC10121487; pdf:https://europepmc.org/articles/PMC10121487?pdf=render 30848519,https://doi.org/10.1111/dme.13945,Impact of glycaemic control on fracture risk in 5368 people with newly diagnosed Type 1 diabetes: a time-dependent analysis.,"Thayakaran R, Perrins M, Gokhale KM, Kumaran S, Narendran P, Price MJ, Nirantharakumar K, Toulis KA.",,Diabetic medicine : a journal of the British Diabetic Association,2019,2019-04-05,N,,,,"

Aims

To assess whether glycaemic control is associated with a lifelong increased risk of fracture in people with newly diagnosed Type 1 diabetes.

Methods

People with newly diagnosed Type 1 diabetes between 1 January 1995 and 10 May 2016 were identified in The Health Improvement Network database. Longitudinal HbA1c measurements from diagnosis to fracture or study end or loss to follow-up were collected. A Cox proportional hazards model with HbA1c included as a time-dependent variable was fitted to these data.

Results

Some 5368 people with newly diagnosed Type 1 diabetes were included. The estimated adjusted hazard ratio (aHR) for HbA1c was statistically significant [aHR 1.007; 95% confidence interval (CI) 1.002-1.011 (mmol/mol) and aHR 1.07; 95% CI 1.03-1.12 (%)]. An incremental higher risk of fracture was observed with increasing levels of HbA1c .

Conclusions

In people with newly diagnosed Type 1 diabetes, higher HbA1c is associated with an increased risk for fractures.",,doi:https://doi.org/10.1111/dme.13945 +36512045,https://doi.org/10.1007/s00330-022-09323-z,Prediction of incident cardiovascular events using machine learning and CMR radiomics.,"Pujadas ER, Raisi-Estabragh Z, Szabo L, McCracken C, Morcillo CI, Campello VM, Martín-Isla C, Atehortua AM, Vago H, Merkely B, Maurovich-Horvat P, Harvey NC, Neubauer S, Petersen SE, Lekadir K.",,European radiology,2023,2022-12-13,Y,Atrial fibrillation; Heart Failure; Preventive Medicine; Machine Learning; Radiomics,,,"

Objectives

Evaluation of the feasibility of using cardiovascular magnetic resonance (CMR) radiomics in the prediction of incident atrial fibrillation (AF), heart failure (HF), myocardial infarction (MI), and stroke using machine learning techniques.

Methods

We identified participants from the UK Biobank who experienced incident AF, HF, MI, or stroke during the continuous longitudinal follow-up. The CMR indices and the vascular risk factors (VRFs) as well as the CMR images were obtained for each participant. Three-segmented regions of interest (ROIs) were computed: right ventricle cavity, left ventricle (LV) cavity, and LV myocardium in end-systole and end-diastole phases. Radiomics features were extracted from the 3D volumes of the ROIs. Seven integrative models were built for each incident cardiovascular disease (CVD) as an outcome. Each model was built with VRF, CMR indices, and radiomics features and a combination of them. Support vector machine was used for classification. To assess the model performance, the accuracy, sensitivity, specificity, and AUC were reported.

Results

AF prediction model using the VRF+CMR+Rad model (accuracy: 0.71, AUC 0.76) obtained the best result. However, the AUC was similar to the VRF+Rad model. HF showed the most significant improvement with the inclusion of CMR metrics (VRF+CMR+Rad: 0.79, AUC 0.84). Moreover, adding only the radiomics features to the VRF reached an almost similarly good performance (VRF+Rad: accuracy 0.77, AUC 0.83). Prediction models looking into incident MI and stroke reached slightly smaller improvement.

Conclusions

Radiomics features may provide incremental predictive value over VRF and CMR indices in the prediction of incident CVDs.

Key points

• Prediction of incident atrial fibrillation, heart failure, stroke, and myocardial infarction using machine learning techniques. • CMR radiomics, vascular risk factors, and standard CMR indices will be considered in the machine learning models. • The experiments show that radiomics features can provide incremental predictive value over VRF and CMR indices in the prediction of incident cardiovascular diseases.",,pdf:https://link.springer.com/content/pdf/10.1007/s00330-022-09323-z.pdf; doi:https://doi.org/10.1007/s00330-022-09323-z; html:https://europepmc.org/articles/PMC10121487; pdf:https://europepmc.org/articles/PMC10121487?pdf=render 34596018,https://doi.org/10.2807/1560-7917.es.2021.26.39.2001440,"Strategies to reduce the risk of SARS-CoV-2 importation from international travellers: modelling estimations for the United Kingdom, July 2020.","Clifford S, Quilty BJ, Russell TW, Liu Y, Chan YD, Pearson CAB, Eggo RM, Endo A, CMMID COVID-19 Working Group, Flasche S, Edmunds WJ, Centre for Mathematical Modelling of Infectious Diseases (CMMID) COVID-19 Working Group.",,Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin,2021,2021-09-01,Y,Quarantine; Pcr Testing; Travel Screening; Covid-19; Sars-cov-2,,,"BackgroundTo mitigate SARS-CoV-2 transmission risks from international air travellers, many countries implemented a combination of up to 14 days of self-quarantine upon arrival plus PCR testing in the early stages of the COVID-19 pandemic in 2020.AimTo assess the effectiveness of quarantine and testing of international travellers to reduce risk of onward SARS-CoV-2 transmission into a destination country in the pre-COVID-19 vaccination era.MethodsWe used a simulation model of air travellers arriving in the United Kingdom from the European Union or the United States, incorporating timing of infection stages while varying quarantine duration and timing and number of PCR tests.ResultsQuarantine upon arrival with a PCR test on day 7 plus a 1-day delay for results can reduce the number of infectious arriving travellers released into the community by a median 94% (95% uncertainty interval (UI): 89-98) compared with a no quarantine/no test scenario. This reduction is similar to that achieved by a 14-day quarantine period (median > 99%; 95% UI: 98-100). Even shorter quarantine periods can prevent a substantial amount of transmission; all strategies in which travellers spend at least 5 days (mean incubation period) in quarantine and have at least one negative test before release are highly effective (median reduction 89%; 95% UI: 83-95)).ConclusionThe effect of different screening strategies impacts asymptomatic and symptomatic individuals differently. The choice of an optimal quarantine and testing strategy for unvaccinated air travellers may vary based on the number of possible imported infections relative to domestic incidence.",,pdf:https://www.eurosurveillance.org/deliver/fulltext/eurosurveillance/26/39/eurosurv-26-39-5.pdf?itemId=%2Fcontent%2F10.2807%2F1560-7917.ES.2021.26.39.2001440&mimeType=pdf&containerItemId=content/eurosurveillance; doi:https://doi.org/10.2807/1560-7917.ES.2021.26.39.2001440; html:https://europepmc.org/articles/PMC8485583; pdf:https://europepmc.org/articles/PMC8485583?pdf=render 34970633,https://doi.org/10.23889/ijpds.v6i1.1674,Evaluation of the ASSIGN open-source deterministic address-matching algorithm for allocating unique property reference numbers to general practitioner-recorded patient addresses.,"Harper G, Stables D, Simon P, Ahmed Z, Smith K, Robson J, Dezateux C.",,International journal of population data science,2021,2021-12-08,Y,Quality assurance; Data Linkage; Population Health; Electronic Health Record; Addresses; Place-based Health; Address-matching,,,"

Introduction

Linking places to people is a core element of the UK government's geospatial strategy. Matching patient addresses in electronic health records to their Unique Property Reference Numbers (UPRNs) enables spatial linkage for research, innovation and public benefit. Available algorithms are not transparent or evaluated for use with addresses recorded by health care providers.

Objectives

To describe and quality assure the open-source deterministic ASSIGN address-matching algorithm applied to general practitioner-recorded patient addresses.

Methods

Best practice standards were used to report the ASSIGN algorithm match rate, sensitivity and positive predictive value using gold-standard datasets from London and Wales. We applied the ASSIGN algorithm to the recorded addresses of a sample of 1,757,018 patients registered with all general practices in north east London. We examined bias in match results for the study population using multivariable analyses to estimate the likelihood of an address-matched UPRN by demographic, registration, and organisational variables.

Results

We found a 99.5% and 99.6% match rate with high sensitivity (0.999,0.998) and positive predictive value (0.996,0.998) for the Welsh and London gold standard datasets respectively, and a 98.6% match rate for the study population.The 1.4% of the study population without a UPRN match were more likely to have changed registered address in the last 12 months (match rate: 95.4%), be from a Chinese ethnic background (95.5%), or registered with a general practice using the SystmOne clinical record system (94.4%). Conversely, people registered for more than 6.5 years with their general practitioner were more likely to have a match (99.4%) than those with shorter registration durations.

Conclusions

ASSIGN is a highly accurate open-source address-matching algorithm with a high match rate and minimal biases when evaluated against a large sample of general practice-recorded patient addresses. ASSIGN has potential to be used in other address-based datasets including those with information relevant to the wider determinants of health.",,pdf:https://ijpds.org/article/download/1674/3300; doi:https://doi.org/10.23889/ijpds.v6i1.1674; html:https://europepmc.org/articles/PMC8678979; pdf:https://europepmc.org/articles/PMC8678979?pdf=render 32735547,https://doi.org/10.2196/20169,Can Robots Improve Testing Capacity for SARS-CoV-2?,"Cresswell K, Ramalingam S, Sheikh A.",,Journal of medical Internet research,2020,2020-08-12,Y,Virus; Infectious disease; Testing; Robotics; Pandemic; Covid-19; Sars-cov-2,,,"There is currently increasing interest internationally in deploying robotic applications for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing, as these can help to reduce the risk of transmission of the virus to health care staff and patients. We provide an overview of key recent developments in this area. We argue that, although there is some potential for deploying robots to help with SARS-CoV-2 testing, the potential of patient-facing applications is likely to be limited. This is due to the high costs associated with patient-facing functionality, and risks of potentially adverse impacts on health care staff work practices and patient interactions. In contrast, back-end laboratory-based robots dealing with sample extraction and amplification, that effectively integrate with established processes, software, and interfaces to process samples, are much more likely to result in safety and efficiency gains. Consideration should therefore be given to deploying these at scale.",,pdf:https://www.jmir.org/2020/8/e20169/PDF; doi:https://doi.org/10.2196/20169; html:https://europepmc.org/articles/PMC7450371 @@ -1731,19 +1731,19 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 34980174,https://doi.org/10.1186/s12967-021-03210-9,"Increased burden of cardiovascular disease in people with liver disease: unequal geographical variations, risk factors and excess years of life lost.","Chang WH, Mueller SH, Chung SC, Foster GR, Lai AG.",,Journal of translational medicine,2022,2022-01-03,Y,liver disease; Geographical variations; incidence; Cardiovascular Risk; Electronic Health Records; Years Of Life Lost,,,"

Background

People with liver disease are at increased risk of developing cardiovascular disease (CVD), however, there has yet been an investigation of incidence burden, risk, and premature mortality across a wide range of liver conditions and cardiovascular outcomes.

Methods

We employed population-wide electronic health records (EHRs; from 1998 to 2020) consisting of almost 4 million adults to assess regional variations in disease burden of five liver conditions, alcoholic liver disease (ALD), autoimmune liver disease, chronic hepatitis B infection (HBV), chronic hepatitis C infection (HCV) and NAFLD, in England. We analysed regional differences in incidence rates for 17 manifestations of CVD in people with or without liver disease. The associations between biomarkers and comorbidities and risk of CVD in patients with liver disease were estimated using Cox models. For each liver condition, we estimated excess years of life lost (YLL) attributable to CVD (i.e., difference in YLL between people with or without CVD).

Results

The age-standardised incidence rate for any liver disease was 114.5 per 100,000 person years. The highest incidence was observed in NAFLD (85.5), followed by ALD (24.7), HCV (6.0), HBV (4.1) and autoimmune liver disease (3.7). Regionally, the North West and North East regions consistently exhibited high incidence burden. Age-specific incidence rate analyses revealed that the peak incidence for liver disease of non-viral aetiology is reached in individuals aged 50-59 years. Patients with liver disease had a two-fold higher incidence burden of CVD (2634.6 per 100,000 persons) compared to individuals without liver disease (1339.7 per 100,000 persons). When comparing across liver diseases, atrial fibrillation was the most common initial CVD presentation while hypertrophic cardiomyopathy was the least common. We noted strong positive associations between body mass index and current smoking and risk of CVD. Patients who also had diabetes, hypertension, proteinuric kidney disease, chronic kidney disease, diverticular disease and gastro-oesophageal reflex disorders had a higher risk of CVD, as do patients with low albumin, raised C-reactive protein and raised International Normalized Ratio levels. All types of CVD were associated with shorter life expectancies. When evaluating excess YLLs by age of CVD onset and by liver disease type, differences in YLLs, when comparing across CVD types, were more pronounced at younger ages.

Conclusions

We developed a public online app ( https://lailab.shinyapps.io/cvd_in_liver_disease/ ) to showcase results interactively. We provide a blueprint that revealed previously underappreciated clinical factors related to the risk of CVD, which differed in the magnitude of effects across liver diseases. We found significant geographical variations in the burden of liver disease and CVD, highlighting the need to devise local solutions. Targeted policies and regional initiatives addressing underserved communities might help improve equity of access to CVD screening and treatment.",,pdf:https://translational-medicine.biomedcentral.com/counter/pdf/10.1186/s12967-021-03210-9; doi:https://doi.org/10.1186/s12967-021-03210-9; html:https://europepmc.org/articles/PMC8722174; pdf:https://europepmc.org/articles/PMC8722174?pdf=render 31312209,https://doi.org/10.3389/fgene.2019.00567,Use of Pharmacogenetic Drugs by the Dutch Population.,"Alshabeeb MA, Deneer VHM, Khan A, Asselbergs FW.",,Frontiers in genetics,2019,2019-07-02,Y,CYP2C19; CYP2D6; Pharmacogenetics; Adrs; Slco1b1; Preemptive Genetic Testing,Better Care,,"

Introduction

The Dutch Pharmacogenetics Working Group (DPWG) indicated a list of actionable genotypes that affect patients' response to more 50 drugs; these drugs which show variable effects based on patients' genetic traits were named as pharmacogenetics (PGX) drugs. Preemptive genetic testing before using these drugs may protect certain patients from serious adverse reactions and could help in avoiding treatment failures. The objectives of this study include identifying the rate of PGX drug usage among Dutch population, estimating the level of users who carry the actionable genotypes and determining the main genes involved in drug's effect variability.

Methods

Usage of PGX drugs over 2011-2017 by the insured population (an average of 11.4 million) in outpatient clinics in Netherlands was obtained from the publically available GIP databank. The data of 45 drugs were analyzed and their interactions with selected pharmacogenes were estimated. Frequency of actionable genotypes of 249 Dutch parents was obtained from the public database: Genome of Netherlands (GoNL), to identify the pattern of genetic characteristics of Dutch population.

Results

Over a 7 year period, 51.3 million exposures of patients to PGX drugs were reported with an average of 5.3 exposures per each drug user. One quarterof the exposures (12.4 million) are predicted to be experienced by individuals with actionable genotypes (risky exposures). Up to 60% of the risky exposures (around 7.5 million) were related to drugs metabolized by CYP2D6. SLCO1B1, and CYP2C19 were also identified among the top genes affecting response of drugs users (involved in about 22 and 12.4% of the risky exposures, respectively). Cardiovascular medications were the top prescribed PGX drug class (43%), followed by gastroenterology (29%) and psychiatry/neurology medications (15%). Women use more PGX drugs than men (55.8 vs. 44.2%, respectively) with the majority (84%) of users in both sexes are above 45 years.

Conclusion

PGX drugs are commonly used in Netherlands. Preemptive panel testing for CYP2D6, SLCO1B1, and CYP2C19 only could be useful to predict 95% of vulnerable patients' exposures to PGX drugs. Future studies to assess the economic impact of preemptive panel testing on patients of older age are suggested.",,pdf:https://www.frontiersin.org/articles/10.3389/fgene.2019.00567/pdf; doi:https://doi.org/10.3389/fgene.2019.00567; html:https://europepmc.org/articles/PMC6614185; pdf:https://europepmc.org/articles/PMC6614185?pdf=render 33933530,https://doi.org/10.1016/j.jinf.2021.04.027,Early observations on the impact of a healthcare worker COVID-19 vaccination programme at a major UK tertiary centre.,"Garvey MI, Wilkinson MAC, Holden E, Shields A, Robertson A, Richter A, Ball S.",,The Journal of infection,2021,2021-04-29,Y,Vaccination; Healthcare Workers; Lateral Flow; Covid-19,,,,,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8081749; doi:https://doi.org/10.1016/j.jinf.2021.04.027; html:https://europepmc.org/articles/PMC8081749; pdf:https://europepmc.org/articles/PMC8081749?pdf=render +30444743,https://doi.org/10.1097/ccm.0000000000003424,"Risk Factors for 1-Year Mortality and Hospital Utilization Patterns in Critical Care Survivors: A Retrospective, Observational, Population-Based Data Linkage Study.","Szakmany T, Walters AM, Pugh R, Battle C, Berridge DM, Lyons RA.",,Critical care medicine,2019,2019-01-01,N,,,,"

Objectives

Clear understanding of the long-term consequences of critical care survivorship is essential. We investigated the care process and individual factors associated with long-term mortality among ICU survivors and explored hospital use in this group.

Design

Population-based data linkage study using the Secure Anonymised Information Linkage databank.

Setting

All ICUs between 2006 and 2013 in Wales, United Kingdom.

Patients

We identified 40,631 patients discharged alive from Welsh adult ICUs.

Interventions

None.

Measurements and main results

Primary outcome was 365-day survival. The secondary outcomes were 30- and 90-day survival and hospital utilization in the 365 days following ICU discharge. Kaplan-Meier curves were plotted to compare survival rates. Cox proportional hazards regression models were used to determine risk factors of mortality. Seven-thousand eight-hundred eighty-three patients (19.4%) died during the 1-year follow-up period. In the multivariable Cox regression analysis, advanced age and comorbidities were significant determinants of long-term mortality. Expedited discharge due to ICU bed shortage was associated with higher risk. The rate of hospitalization in the year prior to the critical care admission was 28 hospitalized days/1,000 d; post critical care was 88 hospitalized days/1,000 d for those who were still alive; and 57 hospitalized days/1,000 d and 412 hospitalized days/1,000 d for those who died by the end of the study, respectively.

Conclusions

One in five ICU survivors die within 1 year, with advanced age and comorbidity being significant predictors of outcome, leading to high resource use. Care process factors indicating high system stress were associated with increased risk. More detailed understanding is needed on the effects of the potentially modifiable factors to optimize service delivery and improve long-term outcomes of the critically ill.",,pdf:https://europepmc.org/articles/pmc6330072?pdf=render; doi:https://doi.org/10.1097/CCM.0000000000003424; html:https://europepmc.org/articles/PMC6330072; pdf:https://europepmc.org/articles/PMC6330072?pdf=render; doi:https://doi.org/10.1097/ccm.0000000000003424 34040552,https://doi.org/10.3389/fpsyt.2021.627996,Optimising a Simple Fully Convolutional Network for Accurate Brain Age Prediction in the PAC 2019 Challenge.,"Gong W, Beckmann CF, Vedaldi A, Smith SM, Peng H.",,Frontiers in psychiatry,2021,2021-05-10,Y,Brain imaging; Predictive Analysis; Big Data; Deep Learning; Convolution Neural Network; Brain Age Prediction,,,"Brain age prediction from brain MRI scans not only helps improve brain ageing modelling generally, but also provides benchmarks for predictive analysis methods. Brain-age delta, which is the difference between a subject's predicted age and true age, has become a meaningful biomarker for the health of the brain. Here, we report the details of our brain age prediction models and results in the Predictive Analysis Challenge 2019. The aim of the challenge was to use T1-weighted brain MRIs to predict a subject's age in multicentre datasets. We apply a lightweight deep convolutional neural network architecture, Simple Fully Convolutional Neural Network (SFCN), and combined several techniques including data augmentation, transfer learning, model ensemble, and bias correction for brain age prediction. The model achieved first place in both of the two objectives in the PAC 2019 brain age prediction challenge: Mean absolute error (MAE) = 2.90 years without bias removal (Second Place = 3.09 yrs; Third Place = 3.33 yrs), and MAE = 2.95 years with bias removal, leading by a large margin (Second Place = 3.80 yrs; Third Place = 3.92 yrs).",,pdf:https://www.frontiersin.org/articles/10.3389/fpsyt.2021.627996/pdf; doi:https://doi.org/10.3389/fpsyt.2021.627996; html:https://europepmc.org/articles/PMC8141616; pdf:https://europepmc.org/articles/PMC8141616?pdf=render 33824163,https://doi.org/10.3399/bjgp20x714161,Post-bariatric surgery nutritional follow-up in primary care: a population-based cohort study.,"Parretti HM, Subramanian A, Adderley NJ, Abbott S, Tahrani AA, Nirantharakumar K.",,The British journal of general practice : the journal of the Royal College of General Practitioners,2021,2021-05-27,Y,Nutrition; Followup; Cohort studies; General Practice; Bariatric Surgery; The Health Improvement Network,,,"

Background

Bariatric surgery is the most effective treatment for severe obesity. However, without recommended follow-up it has long-term risks.

Aim

To investigate whether nutritional and weight monitoring in primary care meets current clinical guidance, after patients are discharged from specialist bariatric care.

Design and setting

Retrospective cohort study in primary care practices contributing to IQVIA Medical Research Data in the UK (1 January 2000 to 17 January 2018).

Method

Participants were adults who had had bariatric surgery with a minimum of 3 years' follow-up post-surgery, as this study focused on patients discharged from specialist care (at 2 years post-surgery). Outcomes were the annual proportion of patients from 2 years post-surgery with a record of recommended nutritional screening blood tests, weight measurement, and prescription of nutritional supplements, and the proportions with nutritional deficiencies based on blood tests.

Results

A total of 3137 participants were included in the study, and median follow-up post-surgery was 5.7 (4.2-7.6) years. Between 45% and 59% of these patients had an annual weight measurement. The greatest proportions of patients with a record of annual nutritional blood tests were for tests routinely conducted in primary care, for example, recorded haemoglobin measurement varied between 44.9% (n = 629/1400) and 61.2% (n = 653/1067). Annual proportions of blood tests specific to bariatric surgery were low, for example, recorded copper measurement varied between 1.2% (n = 10/818) and 1.5% (n = 16/1067) where recommended. Results indicated that the most common deficiency was anaemia. Annual proportions of patients with prescriptions for recommended nutritional supplements were low.

Conclusion

This study suggests that patients who have bariatric surgery are not receiving the recommended nutritional monitoring after discharge from specialist care. GPs and patients should be supported to engage with follow-up care. Future research should aim to understand the reasons underpinning these findings.",,pdf:https://bjgp.org/content/bjgp/71/707/e441.full.pdf; doi:https://doi.org/10.3399/bjgp20X714161; html:https://europepmc.org/articles/PMC8041293; pdf:https://europepmc.org/articles/PMC8041293?pdf=render -30444743,https://doi.org/10.1097/ccm.0000000000003424,"Risk Factors for 1-Year Mortality and Hospital Utilization Patterns in Critical Care Survivors: A Retrospective, Observational, Population-Based Data Linkage Study.","Szakmany T, Walters AM, Pugh R, Battle C, Berridge DM, Lyons RA.",,Critical care medicine,2019,2019-01-01,N,,,,"

Objectives

Clear understanding of the long-term consequences of critical care survivorship is essential. We investigated the care process and individual factors associated with long-term mortality among ICU survivors and explored hospital use in this group.

Design

Population-based data linkage study using the Secure Anonymised Information Linkage databank.

Setting

All ICUs between 2006 and 2013 in Wales, United Kingdom.

Patients

We identified 40,631 patients discharged alive from Welsh adult ICUs.

Interventions

None.

Measurements and main results

Primary outcome was 365-day survival. The secondary outcomes were 30- and 90-day survival and hospital utilization in the 365 days following ICU discharge. Kaplan-Meier curves were plotted to compare survival rates. Cox proportional hazards regression models were used to determine risk factors of mortality. Seven-thousand eight-hundred eighty-three patients (19.4%) died during the 1-year follow-up period. In the multivariable Cox regression analysis, advanced age and comorbidities were significant determinants of long-term mortality. Expedited discharge due to ICU bed shortage was associated with higher risk. The rate of hospitalization in the year prior to the critical care admission was 28 hospitalized days/1,000 d; post critical care was 88 hospitalized days/1,000 d for those who were still alive; and 57 hospitalized days/1,000 d and 412 hospitalized days/1,000 d for those who died by the end of the study, respectively.

Conclusions

One in five ICU survivors die within 1 year, with advanced age and comorbidity being significant predictors of outcome, leading to high resource use. Care process factors indicating high system stress were associated with increased risk. More detailed understanding is needed on the effects of the potentially modifiable factors to optimize service delivery and improve long-term outcomes of the critically ill.",,pdf:https://europepmc.org/articles/pmc6330072?pdf=render; doi:https://doi.org/10.1097/CCM.0000000000003424; html:https://europepmc.org/articles/PMC6330072; pdf:https://europepmc.org/articles/PMC6330072?pdf=render; doi:https://doi.org/10.1097/ccm.0000000000003424 -38082486,https://doi.org/10.1681/asn.0000000000000271,"Effects of Empagliflozin on Fluid Overload, Weight, and Blood Pressure in CKD.","Mayne KJ, Staplin N, Keane DF, Wanner C, Brenner S, Cejka V, Stegbauer J, Judge PK, Preiss D, Emberson J, Trinca D, Dayanandan R, Lee R, Nolan J, Omata A, Green JB, Cherney DZI, Hooi LS, Pontremoli R, Tuttle KR, Lees JS, Mark PB, Davies SJ, Hauske SJ, Steubl D, Brückmann M, Landray MJ, Baigent C, Haynes R, Herrington WG, EMPA-KIDNEY Collaborative Group.",,Journal of the American Society of Nephrology : JASN,2024,2023-12-12,Y,,,,"

Significance statement

SGLT2 inhibitors reduce risk of kidney progression, AKI, and cardiovascular disease, but the mechanisms of benefit are incompletely understood. Bioimpedance spectroscopy can estimate body water and fat mass. One quarter of the EMPA-KIDNEY bioimpedance substudy CKD population had clinically significant levels of bioimpedance-derived ""Fluid Overload"" at recruitment. Empagliflozin induced a prompt and sustained reduction in ""Fluid Overload,"" irrespective of sex, diabetes, and baseline N-terminal pro B-type natriuretic peptide or eGFR. No significant effect on bioimpedance-derived fat mass was observed. The effects of SGLT2 inhibitors on body water may be one of the contributing mechanisms by which they mediate effects on cardiovascular risk.

Background

CKD is associated with fluid excess that can be estimated by bioimpedance spectroscopy. We aimed to assess effects of sodium glucose co-transporter 2 inhibition on bioimpedance-derived ""Fluid Overload"" and adiposity in a CKD population.

Methods

EMPA-KIDNEY was a double-blind placebo-controlled trial of empagliflozin 10 mg once daily in patients with CKD at risk of progression. In a substudy, bioimpedance measurements were added to the main trial procedures at randomization and at 2- and 18-month follow-up visits. The substudy's primary outcome was the study-average difference in absolute ""Fluid Overload"" (an estimate of excess extracellular water) analyzed using a mixed model repeated measures approach.

Results

The 660 substudy participants were broadly representative of the 6609-participant trial population. Substudy mean baseline absolute ""Fluid Overload"" was 0.4±1.7 L. Compared with placebo, the overall mean absolute ""Fluid Overload"" difference among those allocated empagliflozin was -0.24 L (95% confidence interval [CI], -0.38 to -0.11), with similar sized differences at 2 and 18 months, and in prespecified subgroups. Total body water differences comprised between-group differences in extracellular water of -0.49 L (95% CI, -0.69 to -0.30, including the -0.24 L ""Fluid Overload"" difference) and a -0.30 L (95% CI, -0.57 to -0.03) difference in intracellular water. There was no significant effect of empagliflozin on bioimpedance-derived adipose tissue mass (-0.28 kg [95% CI, -1.41 to 0.85]). The between-group difference in weight was -0.7 kg (95% CI, -1.3 to -0.1).

Conclusions

In a broad range of patients with CKD, empagliflozin resulted in a sustained reduction in a bioimpedance-derived estimate of fluid overload, with no statistically significant effect on fat mass.

Trial registration

Clinicaltrials.gov: NCT03594110 ; EuDRACT: 2017-002971-24 ( https://eudract.ema.europa.eu/ ).",,doi:https://doi.org/10.1681/ASN.0000000000000271; html:https://europepmc.org/articles/PMC7615589; pdf:https://europepmc.org/articles/PMC7615589?pdf=render 33036417,https://doi.org/10.3390/ijerph17197320,"Prognostic Role of Demographic, Injury and Claim Factors in Disabling Pain and Mental Health Conditions 12 Months after Compensable Injury.","Nguyen TL, Baker KS, Ioannou L, Hassani-Mahmooei B, Gibson SJ, Collie A, Ponsford J, Cameron PA, Gabbe BJ, Giummarra MJ.",,International journal of environmental research and public health,2020,2020-10-07,Y,Injury; Pain; Compensation; Mental health; Insurance; Disability; Traumatic Injury,,,"Identifying who might develop disabling pain or poor mental health after injury is a high priority so that healthcare providers can provide targeted preventive interventions. This retrospective cohort study aimed to identify predictors of disabling pain or probable mental health conditions at 12 months post-injury. Participants were recruited 12-months after admission to a major trauma service for a compensable transport or workplace injury (n = 157). Injury, compensation claim, health services and medication information were obtained from the Victorian Orthopaedic Trauma Outcome Registry, Victorian State Trauma Registry and Compensation Research Database. Participants completed questionnaires about pain, and mental health (anxiety, depression, posttraumatic stress disorder) at 12 months post-injury. One third had disabling pain, one third had at least one probable mental health condition and more than one in five had both disabling pain and a mental health condition at 12 months post-injury. Multivariable logistic regression found mental health treatment 3-6 months post-injury, persistent work disability and opioid use at 6-12 months predicted disabling pain at 12 months post-injury. The presence of opioid use at 3-6 months, work disability and psychotropic medications at 6-12 months predicted a mental health condition at 12 months post-injury. These factors could be used to identify at risk of developing disabling pain who could benefit from timely interventions to better manage both pain and mental health post-injury. Implications for healthcare and compensation system are discussed.",,pdf:https://www.mdpi.com/1660-4601/17/19/7320/pdf?version=1602228180; doi:https://doi.org/10.3390/ijerph17197320; html:https://europepmc.org/articles/PMC7579145; pdf:https://europepmc.org/articles/PMC7579145?pdf=render +38082486,https://doi.org/10.1681/asn.0000000000000271,"Effects of Empagliflozin on Fluid Overload, Weight, and Blood Pressure in CKD.","Mayne KJ, Staplin N, Keane DF, Wanner C, Brenner S, Cejka V, Stegbauer J, Judge PK, Preiss D, Emberson J, Trinca D, Dayanandan R, Lee R, Nolan J, Omata A, Green JB, Cherney DZI, Hooi LS, Pontremoli R, Tuttle KR, Lees JS, Mark PB, Davies SJ, Hauske SJ, Steubl D, Brückmann M, Landray MJ, Baigent C, Haynes R, Herrington WG, EMPA-KIDNEY Collaborative Group.",,Journal of the American Society of Nephrology : JASN,2024,2023-12-12,Y,,,,"

Significance statement

SGLT2 inhibitors reduce risk of kidney progression, AKI, and cardiovascular disease, but the mechanisms of benefit are incompletely understood. Bioimpedance spectroscopy can estimate body water and fat mass. One quarter of the EMPA-KIDNEY bioimpedance substudy CKD population had clinically significant levels of bioimpedance-derived ""Fluid Overload"" at recruitment. Empagliflozin induced a prompt and sustained reduction in ""Fluid Overload,"" irrespective of sex, diabetes, and baseline N-terminal pro B-type natriuretic peptide or eGFR. No significant effect on bioimpedance-derived fat mass was observed. The effects of SGLT2 inhibitors on body water may be one of the contributing mechanisms by which they mediate effects on cardiovascular risk.

Background

CKD is associated with fluid excess that can be estimated by bioimpedance spectroscopy. We aimed to assess effects of sodium glucose co-transporter 2 inhibition on bioimpedance-derived ""Fluid Overload"" and adiposity in a CKD population.

Methods

EMPA-KIDNEY was a double-blind placebo-controlled trial of empagliflozin 10 mg once daily in patients with CKD at risk of progression. In a substudy, bioimpedance measurements were added to the main trial procedures at randomization and at 2- and 18-month follow-up visits. The substudy's primary outcome was the study-average difference in absolute ""Fluid Overload"" (an estimate of excess extracellular water) analyzed using a mixed model repeated measures approach.

Results

The 660 substudy participants were broadly representative of the 6609-participant trial population. Substudy mean baseline absolute ""Fluid Overload"" was 0.4±1.7 L. Compared with placebo, the overall mean absolute ""Fluid Overload"" difference among those allocated empagliflozin was -0.24 L (95% confidence interval [CI], -0.38 to -0.11), with similar sized differences at 2 and 18 months, and in prespecified subgroups. Total body water differences comprised between-group differences in extracellular water of -0.49 L (95% CI, -0.69 to -0.30, including the -0.24 L ""Fluid Overload"" difference) and a -0.30 L (95% CI, -0.57 to -0.03) difference in intracellular water. There was no significant effect of empagliflozin on bioimpedance-derived adipose tissue mass (-0.28 kg [95% CI, -1.41 to 0.85]). The between-group difference in weight was -0.7 kg (95% CI, -1.3 to -0.1).

Conclusions

In a broad range of patients with CKD, empagliflozin resulted in a sustained reduction in a bioimpedance-derived estimate of fluid overload, with no statistically significant effect on fat mass.

Trial registration

Clinicaltrials.gov: NCT03594110 ; EuDRACT: 2017-002971-24 ( https://eudract.ema.europa.eu/ ).",,doi:https://doi.org/10.1681/ASN.0000000000000271; html:https://europepmc.org/articles/PMC7615589; pdf:https://europepmc.org/articles/PMC7615589?pdf=render 33605084,https://doi.org/10.1111/jcmm.16388,P62-positive aggregates are homogenously distributed in the myocardium and associated with the type of mutation in genetic cardiomyopathy.,"van der Klooster ZJ, Sepehrkhouy S, Dooijes D, Te Rijdt WP, Schuiringa FSAM, Lingeman J, van Tintelen JP, Harakalova M, Goldschmeding R, Suurmeijer AJH, Asselbergs FW, Vink A.",,Journal of cellular and molecular medicine,2021,2021-02-18,Y,Histology; Pathology; Senescence; Genetic; Cardiomyopathy; Autophagy; P62; Phospholamban; Desminopathy; Sequestosome-1,,,"Genetic cardiomyopathy is caused by mutations in various genes. The accumulation of potentially proteotoxic mutant protein aggregates due to insufficient autophagy is a possible mechanism of disease development. The objective of this study was to investigate the distribution in the myocardium of such aggregates in relation to specific pathogenic genetic mutations in cardiomyopathy hearts. Hearts from 32 genetic cardiomyopathy patients, 4 non-genetic cardiomyopathy patients and 5 controls were studied. Microscopic slices from an entire midventricular heart slice were stained for p62 (sequestosome-1, marker for aggregated proteins destined for autophagy). The percentage of cardiomyocytes with p62 accumulation was higher in cardiomyopathy hearts (median 3.3%) than in healthy controls (0.3%; P < .0001). p62 accumulation was highest in the desmin (15.6%) and phospholamban (7.2%) groups. P62 accumulation was homogeneously distributed in the myocardium. Fibrosis was not associated with p62 accumulation in subgroup analysis of phospholamban hearts. In conclusion, accumulation of p62-positive protein aggregates is homogeneously distributed in the myocardium independently of fibrosis distribution and associated with desmin and phospholamban cardiomyopathy. Proteotoxic protein accumulation is a diffuse process in the myocardium while a more localized second hit, such as local strain during exercise, might determine whether this leads to regional myocyte decay.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/jcmm.16388; doi:https://doi.org/10.1111/jcmm.16388; html:https://europepmc.org/articles/PMC7957157; pdf:https://europepmc.org/articles/PMC7957157?pdf=render 34906385,https://doi.org/10.1016/j.burns.2021.07.025,Re: Re: Driving improved burns care and patient outcomes through clinical registry data: A review of quality indicators in the burns registry of Australia and New Zealand.,"Cleland H, Tracy LM, Singer Y, Wood F, Gong J, Cameron P, Gabbe BJ.",,Burns : journal of the International Society for Burn Injuries,2022,2021-08-12,N,,,,,,doi:https://doi.org/10.1016/j.burns.2021.07.025 -37817277,https://doi.org/10.1186/s13063-023-07656-8,"e-Consent in UK academic-led clinical trials: current practice, challenges and the need for more evidence.","Mitchell EJ, Appelbe D, Bravery A, Culliford L, Evans H, Farrin AJ, Gillies K, Hood K, Love SB, Sydes MR, Williamson PR, Wakefield N, as part of the e-Consent collaborative group.",,Trials,2023,2023-10-10,Y,Consent; Clinical Trial; E-consent,,,"

Background

During the COVID-19 pandemic, in-person healthcare visits were reduced. Consequently, trial teams needed to consider implementing remote methods for conducting clinical trials, including e-Consent. Although some clinical trials may have implemented e-Consent prior to the pandemic, anecdotes of uptake for this method increased within academic-led trials. When the increased use of this process emerged, representatives from several large academic clinical trial groups within the UK collaborated to discuss ways in which trialists can learn from one another when implementing e-Consent.

Methods

A survey of UKCRC-registered Clinical Trials Units (CTUs) was undertaken in April-June 2021 to understand the implementation of and their views on the use of e-Consent and experiences from the perspectives of systems programmers and quality assurance staff on the use of e-Consent. CTUs not using e-Consent were asked to provide any reasons/barriers (including no suitable trials) and any plans for implementing it in the future. Two events for trialists and patient and public involvement (PPI) representatives were then held to disseminate findings, foster discussion, share experiences and aid in the identification of areas that the academic CTU community felt required more research.

Results

Thirty-four (64%) of 53 CTUs responded to the survey, with good geographical representation across the UK. Twenty-one (62%) of the responding CTUs had implemented e-Consent in at least one of their trials, across different types of trials, including CTIMPs (Clinical Trial of Investigational Medicinal Product), ATIMPs (Advanced Therapy Medicinal Products) and non-CTIMPs. One hundred ninety-seven participants attended the two workshops for wide-ranging discussions.

Conclusion

e-Consent is increasingly used in academic-led trials, yet uncertainties remain amongst trialists, patients and members of the public. Uncertainties include a lack of formal, practical guidance and a lack of evidence to demonstrate optimal or appropriate methods to use. We strongly encourage trialists to continue to share their own experiences of the implementation of e-Consent.",,doi:https://doi.org/10.1186/s13063-023-07656-8; html:https://europepmc.org/articles/PMC10565982; pdf:https://europepmc.org/articles/PMC10565982?pdf=render 31481394,https://doi.org/10.1136/bmj.l4892,"Thyroid replacement therapy, thyroid stimulating hormone concentrations, and long term health outcomes in patients with hypothyroidism: longitudinal study.","Thayakaran R, Adderley NJ, Sainsbury C, Torlinska B, Boelaert K, Šumilo D, Price M, Thomas GN, Toulis KA, Nirantharakumar K.",,BMJ (Clinical research ed.),2019,2019-09-03,Y,,Understanding the Causes of Disease,,"

Objective

To explore whether thyroid stimulating hormone (TSH) concentration in patients with a diagnosis of hypothyroidism is associated with increased all cause mortality and a higher risk of cardiovascular disease and fractures.

Design

Retrospective cohort study.

Setting

The Health Improvement Network (THIN), a database of electronic patient records from UK primary care.

Participants

Adult patients with incident hypothyroidism from 1 January 1995 to 31 December 2017.

Exposure

TSH concentration in patients with hypothyroidism.

Main outcome measures

Ischaemic heart disease, heart failure, stroke/transient ischaemic attack, atrial fibrillation, any fractures, fragility fractures, and mortality. Longitudinal TSH measurements from diagnosis to outcomes, study end, or loss to follow-up were collected. An extended Cox proportional hazards model with TSH considered as a time varying covariate was fitted for each outcome.

Results

162 369 patients with hypothyroidism and 863 072 TSH measurements were included in the analysis. Compared with the reference TSH category (2-2.5 mIU/L), risk of ischaemic heart disease and heart failure increased at high TSH concentrations (>10 mIU/L) (hazard ratio 1.18 (95% confidence interval 1.02 to 1.38; P=0.03) and 1.42 (1.21 to 1.67; P<0.001), respectively). A protective effect for heart failure was seen at low TSH concentrations (hazard ratio 0.79 (0.64 to 0.99; P=0.04) for TSH <0.1 mIU/L and 0.76 (0.62 to 0.92; P=0.006) for 0.1-0.4 mIU/L). Increased mortality was observed in both the lowest and highest TSH categories (hazard ratio 1.18 (1.08 to 1.28; P<0.001), 1.29 (1.22 to 1.36; P<0.001), and 2.21 (2.07 to 2.36; P<0.001) for TSH <0.1 mIU/L, 4-10 mIU/L, and >10 mIU/L. An increase in the risk of fragility fractures was observed in patients in the highest TSH category (>10 mIU/L) (hazard ratio 1.15 (1.01 to 1.31; P=0.03)).

Conclusions

In patients with a diagnosis of hypothyroidism, no evidence was found to suggest a clinically meaningful difference in the pattern of long term health outcomes (all cause mortality, atrial fibrillation, ischaemic heart disease, heart failure, stroke/transient ischaemic attack, fractures) when TSH concentrations were within recommended normal limits. Evidence was found for adverse health outcomes when TSH concentration is outside this range, particularly above the upper reference value.",,pdf:https://www.bmj.com/content/bmj/366/bmj.l4892.full.pdf; doi:https://doi.org/10.1136/bmj.l4892; html:https://europepmc.org/articles/PMC6719286 +37817277,https://doi.org/10.1186/s13063-023-07656-8,"e-Consent in UK academic-led clinical trials: current practice, challenges and the need for more evidence.","Mitchell EJ, Appelbe D, Bravery A, Culliford L, Evans H, Farrin AJ, Gillies K, Hood K, Love SB, Sydes MR, Williamson PR, Wakefield N, as part of the e-Consent collaborative group.",,Trials,2023,2023-10-10,Y,Consent; Clinical Trial; E-consent,,,"

Background

During the COVID-19 pandemic, in-person healthcare visits were reduced. Consequently, trial teams needed to consider implementing remote methods for conducting clinical trials, including e-Consent. Although some clinical trials may have implemented e-Consent prior to the pandemic, anecdotes of uptake for this method increased within academic-led trials. When the increased use of this process emerged, representatives from several large academic clinical trial groups within the UK collaborated to discuss ways in which trialists can learn from one another when implementing e-Consent.

Methods

A survey of UKCRC-registered Clinical Trials Units (CTUs) was undertaken in April-June 2021 to understand the implementation of and their views on the use of e-Consent and experiences from the perspectives of systems programmers and quality assurance staff on the use of e-Consent. CTUs not using e-Consent were asked to provide any reasons/barriers (including no suitable trials) and any plans for implementing it in the future. Two events for trialists and patient and public involvement (PPI) representatives were then held to disseminate findings, foster discussion, share experiences and aid in the identification of areas that the academic CTU community felt required more research.

Results

Thirty-four (64%) of 53 CTUs responded to the survey, with good geographical representation across the UK. Twenty-one (62%) of the responding CTUs had implemented e-Consent in at least one of their trials, across different types of trials, including CTIMPs (Clinical Trial of Investigational Medicinal Product), ATIMPs (Advanced Therapy Medicinal Products) and non-CTIMPs. One hundred ninety-seven participants attended the two workshops for wide-ranging discussions.

Conclusion

e-Consent is increasingly used in academic-led trials, yet uncertainties remain amongst trialists, patients and members of the public. Uncertainties include a lack of formal, practical guidance and a lack of evidence to demonstrate optimal or appropriate methods to use. We strongly encourage trialists to continue to share their own experiences of the implementation of e-Consent.",,doi:https://doi.org/10.1186/s13063-023-07656-8; html:https://europepmc.org/articles/PMC10565982; pdf:https://europepmc.org/articles/PMC10565982?pdf=render 31964672,https://doi.org/10.1136/bmjopen-2019-033318,"Educational differentials in key domains of physical activity by ethnicity, age and sex: a cross-sectional study of over 40 000 participants in the UK household longitudinal study (2013-2015).","Fluharty ME, Pinto Pereira SM, Benzeval M, Hamer M, Jefferis B, Griffiths LJ, Cooper R, Bann D.",,BMJ open,2020,2020-01-20,Y,epidemiology; Physical Activity; Health Disparities,Improving Public Health,,"

Objectives

To assess whether educational differentials in three key physical activity (PA) domains vary by age, sex and ethnicity.

Design

National cross-sectional survey.

Setting

UK.

Participants

Altogether 40 270 participants, aged 20 years and over, from the UK Household Longitudinal Study with information on education, PA and demographics collected in 2013-2015.

Outcome measures

Participation in active travel (AT), occupational activity (OA) and leisure time physical activity (LTPA) at the time of assessment.

Results

Lower educational attainment was associated with higher AT and OA, but lower weekly LTPA activity; these associations were modified by sex, ethnicity and age. Education-related differences in AT were larger for women-the difference in predicted probability of activity between the highest and the lowest education groups was -10% in women (95% CI: -11.9% to 7.9%) and -3% in men (-4.8% to -0.4%). Education-related differences in OA were larger among men -35% (-36.9% to -32.4%) than women -17% (-19.4% to -15.0%). Finally, education-related differences in moderate-to-vigorous LTPA varied by ethnicity; for example, differences were 17% (16.2% to 18.7%) for white individuals compared with 6% (0.6% to 11.6%) for black individuals.

Conclusions

Educational differences in PA vary by domain and are modified by age, sex and ethnicity. A better understanding of physically inactive subgroups may aid development of interventions to both increase activity levels and reduce health inequalities.","This study which includes over 40 thousant adults in the UK, aims to assess whether there are links between different levels of physical activity and educational achievements. It found that lower educational achievement was associated with higher travel and work related physical activity, but not leisure time activity. They found this difference to be larger in men than in women, and also in white compared to black individuals.",pdf:https://bmjopen.bmj.com/content/bmjopen/10/1/e033318.full.pdf; doi:https://doi.org/10.1136/bmjopen-2019-033318; html:https://europepmc.org/articles/PMC7045199; pdf:https://europepmc.org/articles/PMC7045199?pdf=render 36330526,https://doi.org/10.3389/fimmu.2022.1032331,Levels of soluble complement regulators predict severity of COVID-19 symptoms.,"Tierney AL, Alali WM, Scott T, Rees-Unwin KS, CITIID-NIHR BioResource COVID-19 Collaboration, Clark SJ, Unwin RD.",,Frontiers in immunology,2022,2022-10-18,Y,Complement; Mass spectrometry; Biomarkers; Factor H; Factor H-related Proteins; Covid-19; Sars-cov-2,,,"The SARS-CoV-2 virus continues to cause significant morbidity and mortality worldwide from COVID-19. One of the major challenges of patient management is the broad range of symptoms observed. While the majority of individuals experience relatively mild disease, a significant minority of patients require hospitalisation, with COVID-19 still proving fatal for some. As such, there remains a desperate need to better understand what drives this severe disease, both in terms of the underlying biology, but also to potentially predict at diagnosis which patients are likely to require further interventions, thus enabling better outcomes for both patients and healthcare systems. Several lines of evidence have pointed to dysregulation of the complement cascade as a major factor in severe COVID-19 outcomes. How this is underpinned mechanistically is not known. Here, we have focussed on the role of the soluble complement regulators Complement Factor H (FH), its splice variant Factor H-like 1 (FHL-1) and five Factor H-Related proteins (FHR1-5). Using a targeted mass spectrometry approach, we quantified these proteins in a cohort of 188 plasma samples from controls and SARS-CoV-2 patients taken at diagnosis. This analysis revealed significant elevations in all FHR proteins, but not FH, in patients with more severe disease, particularly FHR2 and FHR5 (FHR2: 1.97-fold, p<0.0001; FHR5: 2.4-fold, p<0.0001). Furthermore, for a subset of 77 SARS-CoV-2 +ve patients we also analysed time course samples taken approximately 28 days post-diagnosis. Here, we see complement regulator levels drop in all individuals with asymptomatic or mild disease, but regulators remain high in those with more severe outcomes, with elevations in FHR2 over baseline levels in this group. These data support the hypothesis that elevation of circulating levels of the FHR family of proteins could predict disease severity in COVID-19 patients, and that the duration of elevation (or lack of immune activation resolution) may be partly responsible for driving poor outcomes in COVID-19.",,pdf:https://www.frontiersin.org/articles/10.3389/fimmu.2022.1032331/pdf; doi:https://doi.org/10.3389/fimmu.2022.1032331; html:https://europepmc.org/articles/PMC9624227; pdf:https://europepmc.org/articles/PMC9624227?pdf=render -37339333,https://doi.org/10.1002/jia2.26104,"COVID-19 among adults living with HIV: correlates of mortality among public sector healthcare users in Western Cape, South Africa.","Kassanjee R, Davies MA, Ngwenya O, Osei-Yeboah R, Jacobs T, Morden E, Timmerman V, Britz S, Mendelson M, Taljaard J, Riou J, Boulle A, Tiffin N, Zinyakatira N.",,Journal of the International AIDS Society,2023,2023-06-01,Y,Mortality; HIV; South Africa; Cd4 Count; Covid-19; Sars-cov-2,,,"

Introduction

While a large proportion of people with HIV (PWH) have experienced SARS-CoV-2 infections, there is uncertainty about the role of HIV disease severity on COVID-19 outcomes, especially in lower-income settings. We studied the association of mortality with characteristics of HIV severity and management, and vaccination, among adult PWH.

Methods

We analysed observational cohort data on all PWH aged ≥15 years experiencing a diagnosed SARS-CoV-2 infection (until March 2022), who accessed public sector healthcare in the Western Cape province of South Africa. Logistic regression was used to study the association of mortality with evidence of antiretroviral therapy (ART) collection, time since first HIV evidence, CD4 cell count, viral load (among those with evidence of ART collection) and COVID-19 vaccination, adjusting for demographic characteristics, comorbidities, admission pressure, location and time period.

Results

Mortality occurred in 5.7% (95% CI: 5.3,6.0) of 17,831 first-diagnosed infections. Higher mortality was associated with lower recent CD4, no evidence of ART collection, high or unknown recent viral load and recent first HIV evidence, differentially by age. Vaccination was protective. The burden of comorbidities was high, and tuberculosis (especially more recent episodes of tuberculosis), chronic kidney disease, diabetes and hypertension were associated with higher mortality, more strongly in younger adults.

Conclusions

Mortality was strongly associated with suboptimal HIV control, and the prevalence of these risk factors increased in later COVID-19 waves. It remains a public health priority to ensure PWH are on suppressive ART and vaccinated, and manage any disruptions in care that occurred during the pandemic. The diagnosis and management of comorbidities, including for tuberculosis, should be optimized.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/jia2.26104; doi:https://doi.org/10.1002/jia2.26104; html:https://europepmc.org/articles/PMC10281639; pdf:https://europepmc.org/articles/PMC10281639?pdf=render 32401709,https://doi.org/10.1016/s2468-2667(20)30112-2,COVID-19: a public health approach to manage domestic violence is needed.,"Chandan JS, Taylor J, Bradbury-Jones C, Nirantharakumar K, Kane E, Bandyopadhyay S.",,The Lancet. Public health,2020,2020-05-10,Y,,,,,Chandan et al. comment on the effect the covid pandemic may have on domestic violence and propose surveillance for domestic violence is needed. ,pdf:http://www.thelancet.com/article/S2468266720301122/pdf; doi:https://doi.org/10.1016/S2468-2667(20)30112-2; html:https://europepmc.org/articles/PMC7252171; pdf:https://europepmc.org/articles/PMC7252171?pdf=render +37339333,https://doi.org/10.1002/jia2.26104,"COVID-19 among adults living with HIV: correlates of mortality among public sector healthcare users in Western Cape, South Africa.","Kassanjee R, Davies MA, Ngwenya O, Osei-Yeboah R, Jacobs T, Morden E, Timmerman V, Britz S, Mendelson M, Taljaard J, Riou J, Boulle A, Tiffin N, Zinyakatira N.",,Journal of the International AIDS Society,2023,2023-06-01,Y,Mortality; HIV; South Africa; Cd4 Count; Covid-19; Sars-cov-2,,,"

Introduction

While a large proportion of people with HIV (PWH) have experienced SARS-CoV-2 infections, there is uncertainty about the role of HIV disease severity on COVID-19 outcomes, especially in lower-income settings. We studied the association of mortality with characteristics of HIV severity and management, and vaccination, among adult PWH.

Methods

We analysed observational cohort data on all PWH aged ≥15 years experiencing a diagnosed SARS-CoV-2 infection (until March 2022), who accessed public sector healthcare in the Western Cape province of South Africa. Logistic regression was used to study the association of mortality with evidence of antiretroviral therapy (ART) collection, time since first HIV evidence, CD4 cell count, viral load (among those with evidence of ART collection) and COVID-19 vaccination, adjusting for demographic characteristics, comorbidities, admission pressure, location and time period.

Results

Mortality occurred in 5.7% (95% CI: 5.3,6.0) of 17,831 first-diagnosed infections. Higher mortality was associated with lower recent CD4, no evidence of ART collection, high or unknown recent viral load and recent first HIV evidence, differentially by age. Vaccination was protective. The burden of comorbidities was high, and tuberculosis (especially more recent episodes of tuberculosis), chronic kidney disease, diabetes and hypertension were associated with higher mortality, more strongly in younger adults.

Conclusions

Mortality was strongly associated with suboptimal HIV control, and the prevalence of these risk factors increased in later COVID-19 waves. It remains a public health priority to ensure PWH are on suppressive ART and vaccinated, and manage any disruptions in care that occurred during the pandemic. The diagnosis and management of comorbidities, including for tuberculosis, should be optimized.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/jia2.26104; doi:https://doi.org/10.1002/jia2.26104; html:https://europepmc.org/articles/PMC10281639; pdf:https://europepmc.org/articles/PMC10281639?pdf=render 36482104,https://doi.org/10.1038/s41591-022-02100-x,Association of wearable device-measured vigorous intermittent lifestyle physical activity with mortality.,"Stamatakis E, Ahmadi MN, Gill JMR, Thøgersen-Ntoumani C, Gibala MJ, Doherty A, Hamer M.",,Nature medicine,2022,2022-12-08,Y,,,,"Wearable devices can capture unexplored movement patterns such as brief bursts of vigorous intermittent lifestyle physical activity (VILPA) that is embedded into everyday life, rather than being done as leisure time exercise. Here, we examined the association of VILPA with all-cause, cardiovascular disease (CVD) and cancer mortality in 25,241 nonexercisers (mean age 61.8 years, 14,178 women/11,063 men) in the UK Biobank. Over an average follow-up of 6.9 years, during which 852 deaths occurred, VILPA was inversely associated with all three of these outcomes in a near-linear fashion. Compared with participants who engaged in no VILPA, participants who engaged in VILPA at the sample median VILPA frequency of 3 length-standardized bouts per day (lasting 1 or 2 min each) showed a 38%-40% reduction in all-cause and cancer mortality risk and a 48%-49% reduction in CVD mortality risk. Moreover, the sample median VILPA duration of 4.4 min per day was associated with a 26%-30% reduction in all-cause and cancer mortality risk and a 32%-34% reduction in CVD mortality risk. We obtained similar results when repeating the above analyses for vigorous physical activity (VPA) in 62,344 UK Biobank participants who exercised (1,552 deaths, 35,290 women/27,054 men). These results indicate that small amounts of vigorous nonexercise physical activity are associated with substantially lower mortality. VILPA in nonexercisers appears to elicit similar effects to VPA in exercisers, suggesting that VILPA may be a suitable physical activity target, especially in people not able or willing to exercise.",,pdf:https://www.nature.com/articles/s41591-022-02100-x.pdf; doi:https://doi.org/10.1038/s41591-022-02100-x; html:https://europepmc.org/articles/PMC9800274; pdf:https://europepmc.org/articles/PMC9800274?pdf=render 37348789,https://doi.org/10.1016/j.jhep.2023.05.046,Liver disease is a significant risk factor for cardiovascular outcomes - A UK Biobank study.,"Roca-Fernandez A, Banerjee R, Thomaides-Brears H, Telford A, Sanyal A, Neubauer S, Nichols TE, Raman B, McCracken C, Petersen SE, Ntusi NA, Cuthbertson DJ, Lai M, Dennis A, Banerjee A.",,Journal of hepatology,2023,2023-06-20,N,Cardiac; MRI; Imaging; Hepatic; Heart Failure; liver disease; Cvd; Nafld; Atrial Fibrilliation,,,"

Background & aims

Chronic liver disease (CLD) is associated with increased cardiovascular disease (CVD) risk. We investigated whether early signs of liver disease (measured by iron-corrected T1-mapping [cT1]) were associated with an increased risk of major CVD events.

Methods

Liver disease activity (cT1) and fat (proton density fat fraction [PDFF]) were measured using LiverMultiScan® between January 2016 and February 2020 in the UK Biobank imaging sub-study. Using multivariable Cox regression, we explored associations between liver cT1 (MRI) and primary CVD (coronary artery disease, atrial fibrillation [AF], embolism/vascular events, heart failure [HF] and stroke), and CVD hospitalisation and all-cause mortality. Liver blood biomarkers, general metabolism biomarkers, and demographics were also included. Subgroup analysis was conducted in those without metabolic syndrome (defined as at least three of: a large waist, high triglycerides, low high-density lipoprotein cholesterol, increased systolic blood pressure, or elevated haemoglobin A1c).

Results

A total of 33,616 participants (mean age 65 years, mean BMI 26 kg/m2, mean haemoglobin A1c 35 mmol/mol) had complete MRI liver data with linked clinical outcomes (median time to major CVD event onset: 1.4 years [range: 0.002-5.1]; follow-up: 2.5 years [range: 1.1-5.2]). Liver disease activity (cT1), but not liver fat (PDFF), was associated with higher risk of any major CVD event (hazard ratio 1.14; 95% CI 1.03-1.26; p = 0.008), AF (1.30; 1.12-1.51; p <0.001); HF (1.30; 1.09-1.56; p= 0.004); CVD hospitalisation (1.27; 1.18-1.37; p <0.001) and all-cause mortality (1.19; 1.02-1.38; p = 0.026). FIB-4 index was associated with HF (1.06; 1.01-1.10; p = 0.007). Risk of CVD hospitalisation was independently associated with cT1 in individuals without metabolic syndrome (1.26; 1.13-1.4; p <0.001).

Conclusion

Liver disease activity, by cT1, was independently associated with a higher risk of incident CVD and all-cause mortality, independent of pre-existing metabolic syndrome, liver fibrosis or fat.

Impact and implications

Chronic liver disease (CLD) is associated with a twofold greater incidence of cardiovascular disease. Our work shows that early liver disease on iron-corrected T1 mapping was associated with a higher risk of major cardiovascular disease (14%), cardiovascular disease hospitalisation (27%) and all-cause mortality (19%). These findings highlight the prognostic relevance of a comprehensive evaluation of liver health in populations at risk of CVD and/or CLD, even in the absence of clinical manifestations or metabolic syndrome, when there is an opportunity to modify/address risk factors and prevent disease progression. As such, they are relevant to patients, carers, clinicians, and policymakers.",,pdf:http://www.journal-of-hepatology.eu/article/S0168827823004208/pdf; doi:https://doi.org/10.1016/j.jhep.2023.05.046 35244709,https://doi.org/10.1093/europace/euac022,Impact of oral anticoagulation on the association between frailty and clinical outcomes in people with atrial fibrillation: nationwide primary care records on treatment analysis.,"Wilkinson C, Wu J, Clegg A, Nadarajah R, Rockwood K, Todd O, Gale CP.",,"Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology",2022,2022-07-01,Y,Bleeding; Atrial fibrillation; Stroke; Frailty; Outcome; Oral Anticoagulation; Oral Anticoagulation Prescription,,,"

Aims

People with atrial fibrillation (AF) frequently live with frailty, which increases the risk of mortality and stroke. This study reports the association between oral anticoagulation (OAC) and outcomes for people with frailty, and whether there is overall net benefit from treatment in people with AF.

Methods and results

Retrospective open cohort electronic records study. Frailty was identified using the electronic frailty index. Primary care electronic health records of 89 996 adults with AF and CHA2DS2-Vasc score of ≥2 were linked with secondary care and mortality data in the Clinical Practice Research Database (CPRD) from 1 January 1998 to 30 November 2018. The primary outcome was a composite of death, stroke, systemic embolism, or major bleeding. Secondary outcomes were stroke, major bleeding, all-cause mortality, transient ischaemic attack, and falls. Of 89 996 participants, 71 256 (79.2%) were living with frailty. The prescription of OAC increased with degree of frailty. For patients not prescribed OAC, rates of the primary outcome increased alongside frailty category. Prescription of OAC was associated with a reduction in the primary outcome for each frailty category [adjusted hazard ratio, 95% confidence interval, no OAC as reference; fit: vitamin K antagonist (VKA) 0.69, 0.64-0.75, direct oral anticoagulant (DOAC) 0.42, 0.33-0.53; mild frailty: VKA 0.52, 0.50-0.54, DOAC 0.57, 0.52-0.63; moderate: VKA 0.54, 0.52-0.56, DOAC 0.57, 0.52-0.63; severe: VKA 0.48, 0.45-0.51, DOAC 0.58, 0.52-0.65], with cumulative incidence function effects greater for DOAC than VKA.

Conclusion

Frailty among people with AF is common. The OAC was associated with a reduction in the primary endpoint across all degrees of frailty.",,doi:https://doi.org/10.1093/europace/euac022; doi:https://doi.org/10.1093/europace/euac022; html:https://europepmc.org/articles/PMC9326851; pdf:https://europepmc.org/articles/PMC9326851?pdf=render @@ -1752,9 +1752,9 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 34930919,https://doi.org/10.1038/s41467-021-26280-1,Finding genetically-supported drug targets for Parkinson's disease using Mendelian randomization of the druggable genome.,"Storm CS, Kia DA, Almramhi MM, Bandres-Ciga S, Finan C, International Parkinson’s Disease Genomics Consortium (IPDGC), Hingorani AD, Wood NW.",,Nature communications,2021,2021-12-20,Y,,,,"Parkinson's disease is a neurodegenerative movement disorder that currently has no disease-modifying treatment, partly owing to inefficiencies in drug target identification and validation. We use Mendelian randomization to investigate over 3,000 genes that encode druggable proteins and predict their efficacy as drug targets for Parkinson's disease. We use expression and protein quantitative trait loci to mimic exposure to medications, and we examine the causal effect on Parkinson's disease risk (in two large cohorts), age at onset and progression. We propose 23 drug-targeting mechanisms for Parkinson's disease, including four possible drug repurposing opportunities and two drugs which may increase Parkinson's disease risk. Of these, we put forward six drug targets with the strongest Mendelian randomization evidence. There is remarkably little overlap between our drug targets to reduce Parkinson's disease risk versus progression, suggesting different molecular mechanisms. Drugs with genetic support are considerably more likely to succeed in clinical trials, and we provide compelling genetic evidence and an analysis pipeline to prioritise Parkinson's disease drug development.",,pdf:https://www.nature.com/articles/s41467-021-26280-1.pdf; doi:https://doi.org/10.1038/s41467-021-26280-1; html:https://europepmc.org/articles/PMC8688480; pdf:https://europepmc.org/articles/PMC8688480?pdf=render 35967893,https://doi.org/10.1080/20008066.2022.2105577,Factors influencing the mental health of an ethnically diverse healthcare workforce during COVID-19: a qualitative study in the United Kingdom.,"Qureshi I, Gogoi M, Al-Oraibi A, Wobi F, Chaloner J, Gray L, Guyatt AL, Hassan O, Nellums LB, Pareek M, UK-REACH Collaborative Group.",,European journal of psychotraumatology,2022,2022-08-09,Y,Stress; Trauma; Anxiety; Mental health; Workforce; Healthcare; Ethnic Minority; Covid-19,,,"Background: Healthcare workers (HCWs) have been reported to be experiencing a deterioration in their mental health due to COVID-19. In addition, ethnic minority populations in the United Kingdom are disproportionately affected by COVID-19. It is imperative that HCWs are appropriately supported and protected from mental harm during the pandemic. Our research aims to add to the evidence base by providing greater insight into the lived experience of HCWs from diverse ethnic backgrounds during the pandemic that had an impact on their mental health. Methods: We undertook a qualitative work package as part of the United Kingdom Research study into Ethnicity And COVID-19 outcomes among Healthcare workers (UK-REACH). As part of the qualitative research, we carried out 16 focus groups with a total of 61 HCWs between December 2020 and July 2021. The aim of the study was to explore topics such as their experiences, fears and concerns, while working during the pandemic. The purposive sample included ancillary healthcare workers, doctors, nurses, midwives and allied health professionals from diverse ethnic backgrounds to ensure inclusion of underrepresented and disproportionately impacted individuals. We conducted discussions using Microsoft Teams. Recordings were transcribed and thematically analysed. Results: Several factors were identified which impacted on the mental health of HCWs during this period including anxiety (due to inconsistent protocols and policy); fear (of infection); trauma (due to increased exposure to severe illness and death); guilt (of potentially infecting loved ones); and stress (due to longer working hours and increased workload). Conclusion: COVID-19 has affected the mental health of HCWs. We identified a number of factors which may be contributing to a deterioration in mental health for participants from diverse ethnic backgrounds. Healthcare organisations should consider developing strategies to counter the negative impact of these factors, including recommendations made by HCWs themselves.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9364733; doi:https://doi.org/10.1080/20008066.2022.2105577; html:https://europepmc.org/articles/PMC9364733; pdf:https://europepmc.org/articles/PMC9364733?pdf=render 38429458,https://doi.org/10.1038/s41590-024-01754-8,Iron dysregulation and inflammatory stress erythropoiesis associates with long-term outcome of COVID-19.,"Hanson AL, Mulè MP, Ruffieux H, Mescia F, Bergamaschi L, Pelly VS, Turner L, Kotagiri P, Cambridge Institute of Therapeutic Immunology and Infectious Disease–National Institute for Health Research (CITIID–NIHR) COVID BioResource Collaboration, Göttgens B, Hess C, Gleadall N, Bradley JR, Nathan JA, Lyons PA, Drakesmith H, Smith KGC.",,Nature immunology,2024,2024-03-01,Y,,,,"Persistent symptoms following SARS-CoV-2 infection are increasingly reported, although the drivers of post-acute sequelae (PASC) of COVID-19 are unclear. Here we assessed 214 individuals infected with SARS-CoV-2, with varying disease severity, for one year from COVID-19 symptom onset to determine the early correlates of PASC. A multivariate signature detected beyond two weeks of disease, encompassing unresolving inflammation, anemia, low serum iron, altered iron-homeostasis gene expression and emerging stress erythropoiesis; differentiated those who reported PASC months later, irrespective of COVID-19 severity. A whole-blood heme-metabolism signature, enriched in hospitalized patients at month 1-3 post onset, coincided with pronounced iron-deficient reticulocytosis. Lymphopenia and low numbers of dendritic cells persisted in those with PASC, and single-cell analysis reported iron maldistribution, suggesting monocyte iron loading and increased iron demand in proliferating lymphocytes. Thus, defects in iron homeostasis, dysregulated erythropoiesis and immune dysfunction due to COVID-19 possibly contribute to inefficient oxygen transport, inflammatory disequilibrium and persisting symptomatology, and may be therapeutically tractable.",,doi:https://doi.org/10.1038/s41590-024-01754-8; doi:https://doi.org/10.1038/s41590-024-01754-8; html:https://europepmc.org/articles/PMC10907301; pdf:https://europepmc.org/articles/PMC10907301?pdf=render +31220083,https://doi.org/10.1371/journal.pmed.1002833,Associations of genetically determined iron status across the phenome: A mendelian randomization study.,"Gill D, Benyamin B, Moore LSP, Monori G, Zhou A, Koskeridis F, Evangelou E, Laffan M, Walker AP, Tsilidis KK, Dehghan A, Elliott P, Hyppönen E, Tzoulaki I.",,PLoS medicine,2019,2019-06-20,Y,,Understanding the Causes of Disease,,"

Background

Iron is integral to many physiological processes, and variations in its levels, even within the normal range, can have implications for health. The objective of this study was to explore the broad clinical effects of varying iron status.

Methods and findings

Genome-wide association study (GWAS) summary data obtained from 48,972 European individuals (55% female) across 19 cohorts in the Genetics of Iron Status Consortium were used to identify 3 genetic variants (rs1800562 and rs1799945 in the hemochromatosis gene [HFE] and rs855791 in the transmembrane protease serine 6 gene [TMPRSS6]) that associate with increased serum iron, ferritin, and transferrin saturation and decreased transferrin levels, thus serving as instruments for systemic iron status. Phenome-wide association study (PheWAS) of these instruments was performed on 424,439 European individuals (54% female) in the UK Biobank who were aged 40-69 years when recruited from 2006 to 2010, with their genetic data linked to Hospital Episode Statistics (HES) from April, 1995 to March, 2016. Two-sample summary data mendelian randomization (MR) analysis was performed to investigate the effect of varying iron status on outcomes across the human phenome. MR-PheWAS analysis for the 3 iron status genetic instruments was performed separately and then pooled by meta-analysis. Correction was made for testing of multiple correlated phenotypes using a 5% false discovery rate (FDR) threshold. Heterogeneity between MR estimates for different instruments was used to indicate possible bias due to effects of the genetic variants through pathways unrelated to iron status. There were 904 distinct phenotypes included in the MR-PheWAS analyses. After correcting for multiple testing, the 3 genetic instruments for systemic iron status demonstrated consistent evidence of a causal effect of higher iron status on decreasing risk of traits related to anemia (iron deficiency anemia: odds ratio [OR] scaled to a standard deviation [SD] increase in genetically determined serum iron levels 0.72, 95% confidence interval [CI] 0.64-0.81, P = 4 × 10-8) and hypercholesterolemia (hypercholesterolemia: OR 0.88, 95% CI 0.83-0.93, P = 2 × 10-5) and increasing risk of traits related to infection of the skin and related structures (cellulitis and abscess of the leg: OR 1.25, 95% CI 1.10-1.42, P = 6 × 10-4). The main limitations of this study relate to possible bias from pleiotropic effects of the considered genetic variants and misclassification of diagnoses in the HES data. Furthermore, this work only investigated participants with European ancestry, and the findings may not be applicable to other ethnic groups.

Conclusions

Our findings offer novel, to our knowledge, insight into previously unreported effects of iron status, highlighting a potential protective effect of higher iron status on hypercholesterolemia and a detrimental role on risk of skin and skin structure infections. Given the modifiable and variable nature of iron status, these findings warrant further investigation.",,doi:https://doi.org/10.1371/journal.pmed.1002833; doi:https://doi.org/10.1371/journal.pmed.1002833; html:https://europepmc.org/articles/PMC6586257; pdf:https://europepmc.org/articles/PMC6586257?pdf=render 38594327,https://doi.org/10.1038/s41698-024-00580-3,Image-based consensus molecular subtyping in rectal cancer biopsies and response to neoadjuvant chemoradiotherapy.,"Lafarge MW, Domingo E, Sirinukunwattana K, Wood R, Samuel L, Murray G, Richman SD, Blake A, Sebag-Montefiore D, Gollins S, Klieser E, Neureiter D, Huemer F, Greil R, Dunne P, Quirke P, Weiss L, Rittscher J, Maughan T, Koelzer VH.",,NPJ precision oncology,2024,2024-04-09,Y,,,,"The development of deep learning (DL) models to predict the consensus molecular subtypes (CMS) from histopathology images (imCMS) is a promising and cost-effective strategy to support patient stratification. Here, we investigate whether imCMS calls generated from whole slide histopathology images (WSIs) of rectal cancer (RC) pre-treatment biopsies are associated with pathological complete response (pCR) to neoadjuvant long course chemoradiotherapy (LCRT) with single agent fluoropyrimidine. DL models were trained to classify WSIs of colorectal cancers stained with hematoxylin and eosin into one of the four CMS classes using a multi-centric dataset of resection and biopsy specimens (n = 1057 WSIs) with paired transcriptional data. Classifiers were tested on a held out RC biopsy cohort (ARISTOTLE) and correlated with pCR to LCRT in an independent dataset merging two RC cohorts (ARISTOTLE, n = 114 and SALZBURG, n = 55 patients). DL models predicted CMS with high classification performance in multiple comparative analyses. In the independent cohorts (ARISTOTLE, SALZBURG), cases with WSIs classified as imCMS1 had a significantly higher likelihood of achieving pCR (OR = 2.69, 95% CI 1.01-7.17, p = 0.048). Conversely, imCMS4 was associated with lack of pCR (OR = 0.25, 95% CI 0.07-0.88, p = 0.031). Classification maps demonstrated pathologist-interpretable associations with high stromal content in imCMS4 cases, associated with poor outcome. No significant association was found in imCMS2 or imCMS3. imCMS classification of pre-treatment biopsies is a fast and inexpensive solution to identify patient groups that could benefit from neoadjuvant LCRT. The significant associations between imCMS1/imCMS4 with pCR suggest the existence of predictive morphological features that could enhance standard pathological assessment.",,pdf:https://www.nature.com/articles/s41698-024-00580-3.pdf; doi:https://doi.org/10.1038/s41698-024-00580-3; html:https://europepmc.org/articles/PMC11003957; pdf:https://europepmc.org/articles/PMC11003957?pdf=render 35639667,https://doi.org/10.1093/eurheartj/ehac238,Critical appraisal of artificial intelligence-based prediction models for cardiovascular disease.,"van Smeden M, Heinze G, Van Calster B, Asselbergs FW, Vardas PE, Bruining N, de Jaegere P, Moore JH, Denaxas S, Boulesteix AL, Moons KGM.",,European heart journal,2022,2022-08-01,Y,Prediction; Artificial intelligence; Diagnosis; Prognosis; Machine Learning; Digital Health,,,"The medical field has seen a rapid increase in the development of artificial intelligence (AI)-based prediction models. With the introduction of such AI-based prediction model tools and software in cardiovascular patient care, the cardiovascular researcher and healthcare professional are challenged to understand the opportunities as well as the limitations of the AI-based predictions. In this article, we present 12 critical questions for cardiovascular health professionals to ask when confronted with an AI-based prediction model. We aim to support medical professionals to distinguish the AI-based prediction models that can add value to patient care from the AI that does not.",,pdf:https://academic.oup.com/eurheartj/article-pdf/43/31/2921/45333809/ehac238.pdf; doi:https://doi.org/10.1093/eurheartj/ehac238; html:https://europepmc.org/articles/PMC9443991; pdf:https://europepmc.org/articles/PMC9443991?pdf=render -31220083,https://doi.org/10.1371/journal.pmed.1002833,Associations of genetically determined iron status across the phenome: A mendelian randomization study.,"Gill D, Benyamin B, Moore LSP, Monori G, Zhou A, Koskeridis F, Evangelou E, Laffan M, Walker AP, Tsilidis KK, Dehghan A, Elliott P, Hyppönen E, Tzoulaki I.",,PLoS medicine,2019,2019-06-20,Y,,Understanding the Causes of Disease,,"

Background

Iron is integral to many physiological processes, and variations in its levels, even within the normal range, can have implications for health. The objective of this study was to explore the broad clinical effects of varying iron status.

Methods and findings

Genome-wide association study (GWAS) summary data obtained from 48,972 European individuals (55% female) across 19 cohorts in the Genetics of Iron Status Consortium were used to identify 3 genetic variants (rs1800562 and rs1799945 in the hemochromatosis gene [HFE] and rs855791 in the transmembrane protease serine 6 gene [TMPRSS6]) that associate with increased serum iron, ferritin, and transferrin saturation and decreased transferrin levels, thus serving as instruments for systemic iron status. Phenome-wide association study (PheWAS) of these instruments was performed on 424,439 European individuals (54% female) in the UK Biobank who were aged 40-69 years when recruited from 2006 to 2010, with their genetic data linked to Hospital Episode Statistics (HES) from April, 1995 to March, 2016. Two-sample summary data mendelian randomization (MR) analysis was performed to investigate the effect of varying iron status on outcomes across the human phenome. MR-PheWAS analysis for the 3 iron status genetic instruments was performed separately and then pooled by meta-analysis. Correction was made for testing of multiple correlated phenotypes using a 5% false discovery rate (FDR) threshold. Heterogeneity between MR estimates for different instruments was used to indicate possible bias due to effects of the genetic variants through pathways unrelated to iron status. There were 904 distinct phenotypes included in the MR-PheWAS analyses. After correcting for multiple testing, the 3 genetic instruments for systemic iron status demonstrated consistent evidence of a causal effect of higher iron status on decreasing risk of traits related to anemia (iron deficiency anemia: odds ratio [OR] scaled to a standard deviation [SD] increase in genetically determined serum iron levels 0.72, 95% confidence interval [CI] 0.64-0.81, P = 4 × 10-8) and hypercholesterolemia (hypercholesterolemia: OR 0.88, 95% CI 0.83-0.93, P = 2 × 10-5) and increasing risk of traits related to infection of the skin and related structures (cellulitis and abscess of the leg: OR 1.25, 95% CI 1.10-1.42, P = 6 × 10-4). The main limitations of this study relate to possible bias from pleiotropic effects of the considered genetic variants and misclassification of diagnoses in the HES data. Furthermore, this work only investigated participants with European ancestry, and the findings may not be applicable to other ethnic groups.

Conclusions

Our findings offer novel, to our knowledge, insight into previously unreported effects of iron status, highlighting a potential protective effect of higher iron status on hypercholesterolemia and a detrimental role on risk of skin and skin structure infections. Given the modifiable and variable nature of iron status, these findings warrant further investigation.",,doi:https://doi.org/10.1371/journal.pmed.1002833; doi:https://doi.org/10.1371/journal.pmed.1002833; html:https://europepmc.org/articles/PMC6586257; pdf:https://europepmc.org/articles/PMC6586257?pdf=render 31242963,https://doi.org/10.1016/j.vaccine.2019.06.019,An online decision tree for vaccine efficacy trial design during infectious disease epidemics: The InterVax-Tool.,"Bellan SE, Eggo RM, Gsell PS, Kucharski AJ, Dean NE, Donohue R, Zook M, Edmunds WJ, Odhiambo F, Longini IM, Brisson M, Mahon BE, Henao-Restrepo AM.",,Vaccine,2019,2019-06-24,Y,Vaccines; Decision support system; epidemics; Outbreaks; Emerging Infectious Diseases; Phase Iii Trial; Scientific Communication; Public Health Emergency; Vaccine Trial Design,"Applied Analytics, Better Care, Better, Faster and More Efficient Clinical Trials",,"

Background

Licensed vaccines are urgently needed for emerging infectious diseases, but the nature of these epidemics causes challenges for the design of phase III trials to evaluate vaccine efficacy. Designing and executing rigorous, fast, and ethical, vaccine efficacy trials is difficult, and the decisions and limitations in the design of these trials encompass epidemiological, logistical, regulatory, statistical, and ethical dimensions.

Results

Trial design decisions are complex and interrelated, but current guidance documents do not lend themselves to efficient decision-making. We created InterVax-Tool (http://vaxeval.com), an online, interactive decision-support tool, to help diverse stakeholders navigate the decisions in the design of phase III vaccine trials. InterVax-Tool offers high-level visual and interactive assistance through a set of four decision trees, guiding users through selection of the: (1) Primary Endpoint, (2) Target Population, (3) Randomization Scheme, and, (4) Comparator. We provide guidance on how key considerations - grouped as Epidemiological, Vaccine-related, Infrastructural, or Sociocultural - inform each decision in the trial design process.

Conclusions

InterVax-Tool facilitates structured, transparent, and collaborative discussion of trial design, while recording the decision-making process. Users can save and share their decisions, which is useful both for comparing proposed trial designs, and for justifying particular design choices. Here, we describe the goals and features of InterVax-Tool as well as its application to the design of a Zika vaccine efficacy trial.",,doi:https://doi.org/10.1016/j.vaccine.2019.06.019; doi:https://doi.org/10.1016/j.vaccine.2019.06.019; html:https://europepmc.org/articles/PMC6620503 38352035,https://doi.org/10.26633/rpsp.2024.13,[Reporting guidelines for clinical trial reports for interventions involving artificial intelligence: the CONSORT-AI extensionDiretrizes para relatórios de ensaios clínicos com intervenções que utilizam inteligência artificial: a extensão CONSORT-AI].,"Liu X, Cruz Rivera S, Moher D, Calvert MJ, Denniston AK, Grupo de Trabajo SPIRIT-AI y CONSORT-AI, GRUPO DE DIRECCIÓN SPIRIT-AI Y CONSORT-AI , Grupo de Consenso SPIRIT-AI y CONSORT-AI .",,Revista panamericana de salud publica = Pan American journal of public health,2024,2023-02-12,Y,,,,"The CONSORT 2010 statement provides minimum guidelines for reporting randomized trials. Its widespread use has been instrumental in ensuring transparency in the evaluation of new interventions. More recently, there has been a growing recognition that interventions involving artificial intelligence (AI) need to undergo rigorous, prospective evaluation to demonstrate impact on health outcomes. The CONSORT-AI (Consolidated Standards of Reporting Trials-Artificial Intelligence) extension is a new reporting guideline for clinical trials evaluating interventions with an AI component. It was developed in parallel with its companion statement for clinical trial protocols: SPIRIT-AI (Standard Protocol Items: Recommendations for Interventional Trials-Artificial Intelligence). Both guidelines were developed through a staged consensus process involving literature review and expert consultation to generate 29 candidate items, which were assessed by an international multi-stakeholder group in a two-stage Delphi survey (103 stakeholders), agreed upon in a two-day consensus meeting (31 stakeholders) and refined through a checklist pilot (34 participants). The CONSORT-AI extension includes 14 new items that were considered sufficiently important for AI interventions that they should be routinely reported in addition to the core CONSORT 2010 items. CONSORT-AI recommends that investigators provide clear descriptions of the AI intervention, including instructions and skills required for use, the setting in which the AI intervention is integrated, the handling of inputs and outputs of the AI intervention, the human-AI interaction and provision of an analysis of error cases. CONSORT-AI will help promote transparency and completeness in reporting clinical trials for AI interventions. It will assist editors and peer reviewers, as well as the general readership, to understand, interpret and critically appraise the quality of clinical trial design and risk of bias in the reported outcomes.",,pdf:https://iris.paho.org/bitstream/10665.2/59257/5/v48e132024.pdf; doi:https://doi.org/10.26633/RPSP.2024.13; html:https://europepmc.org/articles/PMC10863743; pdf:https://europepmc.org/articles/PMC10863743?pdf=render 35641524,https://doi.org/10.1038/s41533-022-00280-0,Development and validation of a multivariable mortality risk prediction model for COPD in primary care.,"Shah SA, Nwaru BI, Sheikh A, Simpson CR, Kotz D.",,NPJ primary care respiratory medicine,2022,2022-05-31,Y,,,,"Risk stratification of chronic obstructive pulmonary disease (COPD) patients is important to enable targeted management. Existing disease severity classification systems, such as GOLD staging, do not take co-morbidities into account despite their high prevalence in COPD patients. We sought to develop and validate a prognostic model to predict 10-year mortality in patients with diagnosed COPD. We constructed a longitudinal cohort of 37,485 COPD patients (149,196 person-years) from a UK-wide primary care database. The risk factors included in the model pertained to demographic and behavioural characteristics, co-morbidities, and COPD severity. The outcome of interest was all-cause mortality. We fitted an extended Cox-regression model to estimate hazard ratios (HR) with 95% confidence intervals (CI), used machine learning-based data modelling approaches including k-fold cross-validation to validate the prognostic model, and assessed model fitting and discrimination. The inter-quartile ranges of the three metrics on the validation set suggested good performance: 0.90-1.06 for model fit, 0.80-0.83 for Harrel's c-index, and 0.40-0.46 for Royston and Saurebrei's [Formula: see text] with a strong overlap of these metrics on the training dataset. According to the validated prognostic model, the two most important risk factors of mortality were heart failure (HR 1.92; 95% CI 1.87-1.96) and current smoking (HR 1.68; 95% CI 1.66-1.71). We have developed and validated a national, population-based prognostic model to predict 10-year mortality of patients diagnosed with COPD. This model could be used to detect high-risk patients and modify risk factors such as optimising heart failure management and offering effective smoking cessation interventions.",,pdf:https://www.nature.com/articles/s41533-022-00280-0.pdf; doi:https://doi.org/10.1038/s41533-022-00280-0; html:https://europepmc.org/articles/PMC9156666; pdf:https://europepmc.org/articles/PMC9156666?pdf=render @@ -1765,24 +1765,24 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 35869125,https://doi.org/10.1038/s41598-022-16375-0,Minimising multi-centre radiomics variability through image normalisation: a pilot study.,"Campello VM, Martín-Isla C, Izquierdo C, Guala A, Palomares JFR, Viladés D, Descalzo ML, Karakas M, Çavuş E, Raisi-Estabragh Z, Petersen SE, Escalera S, Seguí S, Lekadir K.",,Scientific reports,2022,2022-07-22,Y,,,,"Radiomics is an emerging technique for the quantification of imaging data that has recently shown great promise for deeper phenotyping of cardiovascular disease. Thus far, the technique has been mostly applied in single-centre studies. However, one of the main difficulties in multi-centre imaging studies is the inherent variability of image characteristics due to centre differences. In this paper, a comprehensive analysis of radiomics variability under several image- and feature-based normalisation techniques was conducted using a multi-centre cardiovascular magnetic resonance dataset. 218 subjects divided into healthy (n = 112) and hypertrophic cardiomyopathy (n = 106, HCM) groups from five different centres were considered. First and second order texture radiomic features were extracted from three regions of interest, namely the left and right ventricular cavities and the left ventricular myocardium. Two methods were used to assess features' variability. First, feature distributions were compared across centres to obtain a distribution similarity index. Second, two classification tasks were proposed to assess: (1) the amount of centre-related information encoded in normalised features (centre identification) and (2) the generalisation ability for a classification model when trained on these features (healthy versus HCM classification). The results showed that the feature-based harmonisation technique ComBat is able to remove the variability introduced by centre information from radiomic features, at the expense of slightly degrading classification performance. Piecewise linear histogram matching normalisation gave features with greater generalisation ability for classification ( balanced accuracy in between 0.78 ± 0.08 and 0.79 ± 0.09). Models trained with features from images without normalisation showed the worst performance overall ( balanced accuracy in between 0.45 ± 0.28 and 0.60 ± 0.22). In conclusion, centre-related information removal did not imply good generalisation ability for classification.",,pdf:https://www.nature.com/articles/s41598-022-16375-0.pdf; doi:https://doi.org/10.1038/s41598-022-16375-0; html:https://europepmc.org/articles/PMC9307565; pdf:https://europepmc.org/articles/PMC9307565?pdf=render 34236053,https://doi.org/10.1172/jci.insight.149446,Combining multiomics and drug perturbation profiles to identify muscle-specific treatments for spinal muscular atrophy.,"Meijboom KE, Volpato V, Monzón-Sandoval J, Hoolachan JM, Hammond SM, Abendroth F, de Jong OG, Hazell G, Ahlskog N, Wood MJ, Webber C, Bowerman M.",,JCI insight,2021,2021-07-08,Y,Bioinformatics; Drug therapy; Neuroscience; Genetic diseases; Muscle Biology,,,"Spinal muscular atrophy (SMA) is a neuromuscular disorder caused by loss of survival motor neuron (SMN) protein. While SMN restoration therapies are beneficial, they are not a cure. We aimed to identify potentially novel treatments to alleviate muscle pathology combining transcriptomics, proteomics, and perturbational data sets. This revealed potential drug candidates for repurposing in SMA. One of the candidates, harmine, was further investigated in cell and animal models, improving multiple disease phenotypes, including lifespan, weight, and key molecular networks in skeletal muscle. Our work highlights the potential of multiple and parallel data-driven approaches for the development of potentially novel treatments for use in combination with SMN restoration therapies.",,pdf:http://insight.jci.org/articles/view/149446/files/pdf; doi:https://doi.org/10.1172/jci.insight.149446; html:https://europepmc.org/articles/PMC8410072; pdf:https://europepmc.org/articles/PMC8410072?pdf=render 36947103,https://doi.org/10.1093/molbev/msad070,An Assessment of Quaternary Structure Functionality in Homomer Protein Complexes.,"Abrusán G, Foguet C.",,Molecular biology and evolution,2023,2023-04-01,Y,Protein complexes; Coevolution; Neutral evolution; Ligand binding; Homomers,,,"It has been recently suggested that a significant fraction of homomer protein-protein interfaces evolve neutrally, without contributing to function, due to a hydrophobic bias in missense mutations. However, the fraction of such gratuitous complexes is currently unknown. Here, we quantified the fraction of homodimers where multimerization is unlikely to contribute to their biochemical function. We show that: 1) ligand binding-site structure predicts whether a homomer is functional or not; the vast majority of homodimers with multichain binding-sites (MBS) are likely to be functional, while in homodimers with single-chain binding-sites (SBS) and small to medium interfaces, quaternary structure is unlikely to be functional in a significant fraction-35%, even up to 42%-of complexes; 2) the hydrophobicity of interfaces changes little with the strength of selection, and the amino acid composition of interfaces is shaped by the ""hydrophobic ratchet"" in both types, but they are not in a strict equilibrium with mutations; particularly cysteines are much more abundant in mutations than in interfaces or surfaces; 3) in MBS homomers, the interfaces are conserved, while in a high fraction of SBS homomers, the interface is not more conserved than the solvent-accessible surface; and 4) MBS homomer interfaces coevolve more strongly with ligand binding sites than the interfaces of SBS homomers, and MBS complexes have higher capacity to transfer information from ligands across the interfaces than SBS homomers, explaining the enrichment of allostery in the former.",,pdf:https://academic.oup.com/mbe/advance-article-pdf/doi/10.1093/molbev/msad070/49594873/msad070.pdf; doi:https://doi.org/10.1093/molbev/msad070; html:https://europepmc.org/articles/PMC10118308; pdf:https://europepmc.org/articles/PMC10118308?pdf=render -37699620,https://doi.org/10.1136/bmjopen-2023-074626,Development of the TrAnsparent ReportinG of observational studies Emulating a Target trial (TARGET) guideline.,"Hansford HJ, Cashin AG, Jones MD, Swanson SA, Islam N, Dahabreh IJ, Dickerman BA, Egger M, Garcia-Albeniz X, Golub RM, Lodi S, Moreno-Betancur M, Pearson SA, Schneeweiss S, Sterne J, Sharp MK, Stuart EA, Hernan MA, Lee H, McAuley JH.",,BMJ open,2023,2023-09-12,Y,Retrospective studies; epidemiology; Statistics & Research Methods,,,"

Background

Observational studies are increasingly used to inform health decision-making when randomised trials are not feasible, ethical or timely. The target trial approach provides a framework to help minimise common biases in observational studies that aim to estimate the causal effect of interventions. Incomplete reporting of studies using the target trial framework limits the ability for clinicians, researchers, patients and other decision-makers to appraise, synthesise and interpret findings to inform clinical and public health practice and policy. This paper describes the methods that we will use to develop the TrAnsparent ReportinG of observational studies Emulating a Target trial (TARGET) reporting guideline.

Methods/design

The TARGET reporting guideline will be developed in five stages following recommended guidance. The first stage will identify target trial reporting practices by systematically reviewing published studies that explicitly emulated a target trial. The second stage will identify and refine items to be considered for inclusion in the TARGET guideline by consulting content experts using sequential online surveys. The third stage will prioritise and consolidate key items to be included in the TARGET guideline at an in-person consensus meeting of TARGET investigators. The fourth stage will produce and pilot-test both the TARGET guideline and explanation and elaboration document with relevant stakeholders. The fifth stage will disseminate the TARGET guideline and resources via journals, conferences and courses.

Ethics and dissemination

Ethical approval for the survey has been attained (HC220536). The TARGET guideline will be disseminated widely in partnership with stakeholders to maximise adoption and improve reporting of these studies.",,doi:https://doi.org/10.1136/bmjopen-2023-074626; html:https://europepmc.org/articles/PMC10503363; pdf:https://europepmc.org/articles/PMC10503363?pdf=render 32679111,https://doi.org/10.1016/s0140-6736(20)31356-8,COVID-19 pandemic and admission rates for and management of acute coronary syndromes in England.,"Mafham MM, Spata E, Goldacre R, Gair D, Curnow P, Bray M, Hollings S, Roebuck C, Gale CP, Mamas MA, Deanfield JE, de Belder MA, Luescher TF, Denwood T, Landray MJ, Emberson JR, Collins R, Morris EJA, Casadei B, Baigent C.",,"Lancet (London, England)",2020,2020-07-14,Y,,,,"

Background

Several countries affected by the COVID-19 pandemic have reported a substantial drop in the number of patients attending the emergency department with acute coronary syndromes and a reduced number of cardiac procedures. We aimed to understand the scale, nature, and duration of changes to admissions for different types of acute coronary syndrome in England and to evaluate whether in-hospital management of patients has been affected as a result of the COVID-19 pandemic.

Methods

We analysed data on hospital admissions in England for types of acute coronary syndrome from Jan 1, 2019, to May 24, 2020, that were recorded in the Secondary Uses Service Admitted Patient Care database. Admissions were classified as ST-elevation myocardial infarction (STEMI), non-STEMI (NSTEMI), myocardial infarction of unknown type, or other acute coronary syndromes (including unstable angina). We identified revascularisation procedures undertaken during these admissions (ie, coronary angiography without percutaneous coronary intervention [PCI], PCI, and coronary artery bypass graft surgery). We calculated the numbers of weekly admissions and procedures undertaken; percentage reductions in weekly admissions and across subgroups were also calculated, with 95% CIs.

Findings

Hospital admissions for acute coronary syndrome declined from mid-February, 2020, falling from a 2019 baseline rate of 3017 admissions per week to 1813 per week by the end of March, 2020, a reduction of 40% (95% CI 37-43). This decline was partly reversed during April and May, 2020, such that by the last week of May, 2020, there were 2522 admissions, representing a 16% (95% CI 13-20) reduction from baseline. During the period of declining admissions, there were reductions in the numbers of admissions for all types of acute coronary syndrome, including both STEMI and NSTEMI, but relative and absolute reductions were larger for NSTEMI, with 1267 admissions per week in 2019 and 733 per week by the end of March, 2020, a percent reduction of 42% (95% CI 38-46). In parallel, reductions were recorded in the number of PCI procedures for patients with both STEMI (438 PCI procedures per week in 2019 vs 346 by the end of March, 2020; percent reduction 21%, 95% CI 12-29) and NSTEMI (383 PCI procedures per week in 2019 vs 240 by the end of March, 2020; percent reduction 37%, 29-45). The median length of stay among patients with acute coronary syndrome fell from 4 days (IQR 2-9) in 2019 to 3 days (1-5) by the end of March, 2020.

Interpretation

Compared with the weekly average in 2019, there was a substantial reduction in the weekly numbers of patients with acute coronary syndrome who were admitted to hospital in England by the end of March, 2020, which had been partly reversed by the end of May, 2020. The reduced number of admissions during this period is likely to have resulted in increases in out-of-hospital deaths and long-term complications of myocardial infarction and missed opportunities to offer secondary prevention treatment for patients with coronary heart disease. The full extent of the effect of COVID-19 on the management of patients with acute coronary syndrome will continue to be assessed by updating these analyses.

Funding

UK Medical Research Council, British Heart Foundation, Public Health England, Health Data Research UK, and the National Institute for Health Research Oxford Biomedical Research Centre.",,doi:https://doi.org/10.1016/s0140-6736(20)31356-8; doi:https://doi.org/10.1016/S0140-6736(20)31356-8; html:https://europepmc.org/articles/PMC7429983; pdf:https://europepmc.org/articles/PMC7429983?pdf=render +37699620,https://doi.org/10.1136/bmjopen-2023-074626,Development of the TrAnsparent ReportinG of observational studies Emulating a Target trial (TARGET) guideline.,"Hansford HJ, Cashin AG, Jones MD, Swanson SA, Islam N, Dahabreh IJ, Dickerman BA, Egger M, Garcia-Albeniz X, Golub RM, Lodi S, Moreno-Betancur M, Pearson SA, Schneeweiss S, Sterne J, Sharp MK, Stuart EA, Hernan MA, Lee H, McAuley JH.",,BMJ open,2023,2023-09-12,Y,Retrospective studies; epidemiology; Statistics & Research Methods,,,"

Background

Observational studies are increasingly used to inform health decision-making when randomised trials are not feasible, ethical or timely. The target trial approach provides a framework to help minimise common biases in observational studies that aim to estimate the causal effect of interventions. Incomplete reporting of studies using the target trial framework limits the ability for clinicians, researchers, patients and other decision-makers to appraise, synthesise and interpret findings to inform clinical and public health practice and policy. This paper describes the methods that we will use to develop the TrAnsparent ReportinG of observational studies Emulating a Target trial (TARGET) reporting guideline.

Methods/design

The TARGET reporting guideline will be developed in five stages following recommended guidance. The first stage will identify target trial reporting practices by systematically reviewing published studies that explicitly emulated a target trial. The second stage will identify and refine items to be considered for inclusion in the TARGET guideline by consulting content experts using sequential online surveys. The third stage will prioritise and consolidate key items to be included in the TARGET guideline at an in-person consensus meeting of TARGET investigators. The fourth stage will produce and pilot-test both the TARGET guideline and explanation and elaboration document with relevant stakeholders. The fifth stage will disseminate the TARGET guideline and resources via journals, conferences and courses.

Ethics and dissemination

Ethical approval for the survey has been attained (HC220536). The TARGET guideline will be disseminated widely in partnership with stakeholders to maximise adoption and improve reporting of these studies.",,doi:https://doi.org/10.1136/bmjopen-2023-074626; html:https://europepmc.org/articles/PMC10503363; pdf:https://europepmc.org/articles/PMC10503363?pdf=render 35047183,https://doi.org/10.7189/jogh.11.01011,The COVID-19 pandemic in children and young people during 2020-2021: A complex discussion on vaccination.,"Rudan I, Adeloye D, Katikireddi V, Murray J, Simpson C, Shah SA, Robertson C, Sheikh A, EAVE II collaboration.",,Journal of global health,2021,2021-12-25,Y,,,,,,doi:https://doi.org/10.7189/jogh.11.01011; doi:https://doi.org/10.7189/jogh.11.01011; html:https://europepmc.org/articles/PMC8763337; pdf:https://europepmc.org/articles/PMC8763337?pdf=render 35047182,https://doi.org/10.7189/jogh.11.01010,"The COVID-19 pandemic in children and young people during 2020-2021: Learning about clinical presentation, patterns of spread, viral load, diagnosis and treatment.","Rudan I, Adeloye D, Katikireddi SV, Murray J, Simpson C, Shah SA, Robertson C, Sheikh A, EAVE II collaboration.",,Journal of global health,2021,2021-12-25,Y,,,,,,doi:https://doi.org/10.7189/jogh.11.01010; doi:https://doi.org/10.7189/jogh.11.01010; html:https://europepmc.org/articles/PMC8763336; pdf:https://europepmc.org/articles/PMC8763336?pdf=render 32935062,https://doi.org/10.23889/ijpds.v5i2.1383,Prospective data linkage to facilitate COVID-19 trials - A call to action.,"Paprica PA, Sydes MR, McGrail KM, Morris AD, Schull MJ, Walker R.",,International journal of population data science,2020,2020-08-11,Y,,,,,,pdf:https://ijpds.org/article/download/1383/2566; doi:https://doi.org/10.23889/ijpds.v5i2.1383; html:https://europepmc.org/articles/PMC7473253; pdf:https://europepmc.org/articles/PMC7473253?pdf=render -38280393,https://doi.org/10.1016/s2352-3018(23)00272-2,Longitudinal trends in causes of death among adults with HIV on antiretroviral therapy in Europe and North America from 1996 to 2020: a collaboration of cohort studies.,"Trickey A, McGinnis K, Gill MJ, Abgrall S, Berenguer J, Wyen C, Hessamfar M, Reiss P, Kusejko K, Silverberg MJ, Imaz A, Teira R, d'Arminio Monforte A, Zangerle R, Guest JL, Papastamopoulos V, Crane H, Sterling TR, Grabar S, Ingle SM, Sterne JAC.",,The lancet. HIV,2024,2024-01-24,N,,,,"

Background

Mortality rates among people with HIV have fallen since 1996 following the widespread availability of effective antiretroviral therapy (ART). Patterns of cause-specific mortality are evolving as the population with HIV ages. We aimed to investigate longitudinal trends in cause-specific mortality among people with HIV starting ART in Europe and North America.

Methods

In this collaborative observational cohort study, we used data from 17 European and North American HIV cohorts contributing data to the Antiretroviral Therapy Cohort Collaboration. We included data for people with HIV who started ART between 1996 and 2020 at the age of 16 years or older. Causes of death were classified into a single cause by both a clinician and an algorithm if International Classification of Diseases, Ninth Revision or Tenth Revision data were available, or independently by two clinicians. Disagreements were resolved through panel discussion. We used Poisson models to compare cause-specific mortality rates during the calendar periods 1996-99, 2000-03, 2004-07, 2008-11, 2012-15, and 2016-20, adjusted for time-updated age, CD4 count, and whether the individual was ART-naive at the start of each period.

Findings

Among 189 301 people with HIV included in this study, 16 832 (8·9%) deaths were recorded during 1 519 200 person-years of follow-up. 13 180 (78·3%) deaths were classified by cause: the most common causes were AIDS (4203 deaths; 25·0%), non-AIDS non-hepatitis malignancy (2311; 13·7%), and cardiovascular or heart-related (1403; 8·3%) mortality. The proportion of deaths due to AIDS declined from 49% during 1996-99 to 16% during 2016-20. Rates of all-cause mortality per 1000 person-years decreased from 16·8 deaths (95% CI 15·4-18·4) during 1996-99 to 7·9 deaths (7·6-8·2) during 2016-20. Rates of all-cause mortality declined with time: the average adjusted mortality rate ratio per calendar period was 0·85 (95% CI 0·84-0·86). Rates of cause-specific mortality also declined: the most pronounced reduction was for AIDS-related mortality (0·81; 0·79-0·83). There were also reductions in rates of cardiovascular-related (0·83, 0·79-0·87), liver-related (0·88, 0·84-0·93), non-AIDS infection-related (0·91, 0·86-0·96), non-AIDS-non-hepatocellular carcinoma malignancy-related (0·94, 0·90-0·97), and suicide or accident-related mortality (0·89, 0·82-0·95). Mortality rates among people who acquired HIV through injecting drug use increased in women (1·07, 1·00-1·14) and decreased slightly in men (0·96, 0·93-0·99).

Interpretation

Reductions of most major causes of death, particularly AIDS-related deaths among people with HIV on ART, were not seen for all subgroups. Interventions targeted at high-risk groups, substance use, and comorbidities might further increase life expectancy in people with HIV towards that in the general population.

Funding

US National Institute on Alcohol Abuse and Alcoholism.",,doi:https://doi.org/10.1016/S2352-3018(23)00272-2 32909959,https://doi.org/10.1136/bmj.m3164,Reporting guidelines for clinical trial reports for interventions involving artificial intelligence: the CONSORT-AI Extension.,"Liu X, Rivera SC, Moher D, Calvert MJ, Denniston AK, SPIRIT-AI and CONSORT-AI Working Group.",,BMJ (Clinical research ed.),2020,2020-09-09,Y,,,,"The CONSORT 2010 (Consolidated Standards of Reporting Trials) statement provides minimum guidelines for reporting randomised trials. Its widespread use has been instrumental in ensuring transparency when evaluating new interventions. More recently, there has been a growing recognition that interventions involving artificial intelligence (AI) need to undergo rigorous, prospective evaluation to demonstrate impact on health outcomes.The CONSORT-AI extension is a new reporting guideline for clinical trials evaluating interventions with an AI component. It was developed in parallel with its companion statement for clinical trial protocols: SPIRIT-AI. Both guidelines were developed through a staged consensus process, involving a literature review and expert consultation to generate 29 candidate items, which were assessed by an international multi-stakeholder group in a two-stage Delphi survey (103 stakeholders), agreed on in a two-day consensus meeting (31 stakeholders) and refined through a checklist pilot (34 participants).The CONSORT-AI extension includes 14 new items, which were considered sufficiently important for AI interventions, that they should be routinely reported in addition to the core CONSORT 2010 items. CONSORT-AI recommends that investigators provide clear descriptions of the AI intervention, including instructions and skills required for use, the setting in which the AI intervention is integrated, the handling of inputs and outputs of the AI intervention, the human-AI interaction and providing analysis of error cases.CONSORT-AI will help promote transparency and completeness in reporting clinical trials for AI interventions. It will assist editors and peer-reviewers, as well as the general readership, to understand, interpret and critically appraise the quality of clinical trial design and risk of bias in the reported outcomes.",,pdf:https://www.bmj.com/content/bmj/370/bmj.m3164.full.pdf; doi:https://doi.org/10.1136/bmj.m3164; html:https://europepmc.org/articles/PMC7490784 36343994,https://doi.org/10.1136/bmjopen-2022-063159,"Demographic, behavioural and occupational risk factors associated with SARS-CoV-2 infection in UK healthcare workers: a retrospective observational study.","Cooper DJ, Lear S, Sithole N, Shaw A, Stark H, Ferris M, CITIID-NIHR BioResource COVID-19 collaboration consortium, Bradley J, Maxwell P, Goodfellow I, Weekes MP, Seaman S, Baker S.",,BMJ open,2022,2022-11-07,Y,Infection control; epidemiology; Public Health; Covid-19,,,"

Objective

Healthcare workers (HCWs) are at higher risk of SARS-CoV-2 infection than the general population. This group is pivotal to healthcare system resilience during the COVID-19, and future, pandemics. We investigated demographic, social, behavioural and occupational risk factors for SARS-CoV-2 infection among HCWs.

Design/setting/participants

HCWs enrolled in a large-scale sero-epidemiological study at a UK university teaching hospital were sent questionnaires spanning a 5-month period from March to July 2020. In a retrospective observational cohort study, univariate logistic regression was used to assess factors associated with SARS-CoV-2 infection. A Least Absolute Shrinkage Selection Operator regression model was used to identify variables to include in a multivariate logistic regression model.

Results

Among 2258 HCWs, highest ORs associated with SARS-CoV-2 antibody seropositivity on multivariate analysis were having a household member previously testing positive for SARS-CoV-2 antibodies (OR 6.94 (95% CI 4.15 to 11.6); p<0.0001) and being of black ethnicity (6.21 (95% CI 2.69 to 14.3); p<0.0001). Occupational factors associated with a higher risk of seropositivity included working as a physiotherapist (OR 2.78 (95% CI 1.21 to 6.36); p=0.015) and working predominantly in acute medicine (OR 2.72 (95% CI 1.57 to 4.69); p<0.0001) or medical subspecialties (not including infectious diseases) (OR 2.33 (95% CI 1.4 to 3.88); p=0.001). Reporting that adequate personal protective equipment (PPE) was 'rarely' available had an OR of 2.83 (95% CI 1.29 to 6.25; p=0.01). Reporting attending a handover where social distancing was not possible had an OR of 1.39 (95% CI 1.02 to 1.9; p=0.038).

Conclusions

The emergence of SARS-CoV-2 variants and potential vaccine escape continue to threaten stability of healthcare systems worldwide, and sustained vigilance against HCW infection remains a priority. Enhanced risk assessments should be considered for HCWs of black ethnicity, physiotherapists and those working in acute medicine or medical subspecialties. Workplace risk reduction measures include ongoing access to high-quality PPE and effective social distancing measures.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/11/e063159.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-063159; html:https://europepmc.org/articles/PMC9644078; pdf:https://europepmc.org/articles/PMC9644078?pdf=render +38280393,https://doi.org/10.1016/s2352-3018(23)00272-2,Longitudinal trends in causes of death among adults with HIV on antiretroviral therapy in Europe and North America from 1996 to 2020: a collaboration of cohort studies.,"Trickey A, McGinnis K, Gill MJ, Abgrall S, Berenguer J, Wyen C, Hessamfar M, Reiss P, Kusejko K, Silverberg MJ, Imaz A, Teira R, d'Arminio Monforte A, Zangerle R, Guest JL, Papastamopoulos V, Crane H, Sterling TR, Grabar S, Ingle SM, Sterne JAC.",,The lancet. HIV,2024,2024-01-24,N,,,,"

Background

Mortality rates among people with HIV have fallen since 1996 following the widespread availability of effective antiretroviral therapy (ART). Patterns of cause-specific mortality are evolving as the population with HIV ages. We aimed to investigate longitudinal trends in cause-specific mortality among people with HIV starting ART in Europe and North America.

Methods

In this collaborative observational cohort study, we used data from 17 European and North American HIV cohorts contributing data to the Antiretroviral Therapy Cohort Collaboration. We included data for people with HIV who started ART between 1996 and 2020 at the age of 16 years or older. Causes of death were classified into a single cause by both a clinician and an algorithm if International Classification of Diseases, Ninth Revision or Tenth Revision data were available, or independently by two clinicians. Disagreements were resolved through panel discussion. We used Poisson models to compare cause-specific mortality rates during the calendar periods 1996-99, 2000-03, 2004-07, 2008-11, 2012-15, and 2016-20, adjusted for time-updated age, CD4 count, and whether the individual was ART-naive at the start of each period.

Findings

Among 189 301 people with HIV included in this study, 16 832 (8·9%) deaths were recorded during 1 519 200 person-years of follow-up. 13 180 (78·3%) deaths were classified by cause: the most common causes were AIDS (4203 deaths; 25·0%), non-AIDS non-hepatitis malignancy (2311; 13·7%), and cardiovascular or heart-related (1403; 8·3%) mortality. The proportion of deaths due to AIDS declined from 49% during 1996-99 to 16% during 2016-20. Rates of all-cause mortality per 1000 person-years decreased from 16·8 deaths (95% CI 15·4-18·4) during 1996-99 to 7·9 deaths (7·6-8·2) during 2016-20. Rates of all-cause mortality declined with time: the average adjusted mortality rate ratio per calendar period was 0·85 (95% CI 0·84-0·86). Rates of cause-specific mortality also declined: the most pronounced reduction was for AIDS-related mortality (0·81; 0·79-0·83). There were also reductions in rates of cardiovascular-related (0·83, 0·79-0·87), liver-related (0·88, 0·84-0·93), non-AIDS infection-related (0·91, 0·86-0·96), non-AIDS-non-hepatocellular carcinoma malignancy-related (0·94, 0·90-0·97), and suicide or accident-related mortality (0·89, 0·82-0·95). Mortality rates among people who acquired HIV through injecting drug use increased in women (1·07, 1·00-1·14) and decreased slightly in men (0·96, 0·93-0·99).

Interpretation

Reductions of most major causes of death, particularly AIDS-related deaths among people with HIV on ART, were not seen for all subgroups. Interventions targeted at high-risk groups, substance use, and comorbidities might further increase life expectancy in people with HIV towards that in the general population.

Funding

US National Institute on Alcohol Abuse and Alcoholism.",,doi:https://doi.org/10.1016/S2352-3018(23)00272-2 32371477,https://doi.org/10.1126/science.abc0473,Rapid implementation of mobile technology for real-time epidemiology of COVID-19.,"Drew DA, Nguyen LH, Steves CJ, Menni C, Freydin M, Varsavsky T, Sudre CH, Cardoso MJ, Ourselin S, Wolf J, Spector TD, Chan AT, COPE Consortium.",,"Science (New York, N.Y.)",2020,2020-05-05,Y,,,,"The rapid pace of the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents challenges to the robust collection of population-scale data to address this global health crisis. We established the COronavirus Pandemic Epidemiology (COPE) Consortium to unite scientists with expertise in big data research and epidemiology to develop the COVID Symptom Study, previously known as the COVID Symptom Tracker, mobile application. This application-which offers data on risk factors, predictive symptoms, clinical outcomes, and geographical hotspots-was launched in the United Kingdom on 24 March 2020 and the United States on 29 March 2020 and has garnered more than 2.8 million users as of 2 May 2020. Our initiative offers a proof of concept for the repurposing of existing approaches to enable rapidly scalable epidemiologic data collection and analysis, which is critical for a data-driven response to this public health challenge.","Drew et al. decribe the use of a smart-phone App to track Covid-19 symptoms reported by users to track, in real time, information on newly infected individuals. It has been launched in the UK and US and has 2.8 million users and is used to rapidly identify emerging hot spots for infection.",pdf:https://www.science.org/cms/asset/fb31d61b-4be3-483a-b040-2ee970dfb432/pap.pdf; doi:https://doi.org/10.1126/science.abc0473; html:https://europepmc.org/articles/PMC7200009; pdf:https://europepmc.org/articles/PMC7200009?pdf=render 36351458,https://doi.org/10.1016/s0140-6736(22)02074-8,Impact of diabetes on the effects of sodium glucose co-transporter-2 inhibitors on kidney outcomes: collaborative meta-analysis of large placebo-controlled trials.,"Nuffield Department of Population Health Renal Studies Group, SGLT2 inhibitor Meta-Analysis Cardio-Renal Trialists' Consortium.",,"Lancet (London, England)",2022,2022-11-06,Y,,,,"

Background

Large trials have shown that sodium glucose co-transporter-2 (SGLT2) inhibitors reduce the risk of adverse kidney and cardiovascular outcomes in patients with heart failure or chronic kidney disease, or with type 2 diabetes and high risk of atherosclerotic cardiovascular disease. None of the trials recruiting patients with and without diabetes were designed to assess outcomes separately in patients without diabetes.

Methods

We did a systematic review and meta-analysis of SGLT2 inhibitor trials. We searched the MEDLINE and Embase databases for trials published from database inception to Sept 5, 2022. SGLT2 inhibitor trials that were double-blind, placebo-controlled, performed in adults (age ≥18 years), large (≥500 participants per group), and at least 6 months in duration were included. Summary-level data used for analysis were extracted from published reports or provided by trial investigators, and inverse-variance-weighted meta-analyses were conducted to estimate treatment effects. The main efficacy outcomes were kidney disease progression (standardised to a definition of a sustained ≥50% decrease in estimated glomerular filtration rate [eGFR] from randomisation, a sustained low eGFR, end-stage kidney disease, or death from kidney failure), acute kidney injury, and a composite of cardiovascular death or hospitalisation for heart failure. Other outcomes were death from cardiovascular and non-cardiovascular disease considered separately, and the main safety outcomes were ketoacidosis and lower limb amputation. This study is registered with PROSPERO, CRD42022351618.

Findings

We identified 13 trials involving 90 413 participants. After exclusion of four participants with uncertain diabetes status, we analysed 90 409 participants (74 804 [82·7%] participants with diabetes [>99% with type 2 diabetes] and 15 605 [17·3%] without diabetes; trial-level mean baseline eGFR range 37-85 mL/min per 1·73 m2). Compared with placebo, allocation to an SGLT2 inhibitor reduced the risk of kidney disease progression by 37% (relative risk [RR] 0·63, 95% CI 0·58-0·69) with similar RRs in patients with and without diabetes. In the four chronic kidney disease trials, RRs were similar irrespective of primary kidney diagnosis. SGLT2 inhibitors reduced the risk of acute kidney injury by 23% (0·77, 0·70-0·84) and the risk of cardiovascular death or hospitalisation for heart failure by 23% (0·77, 0·74-0·81), again with similar effects in those with and without diabetes. SGLT2 inhibitors also reduced the risk of cardiovascular death (0·86, 0·81-0·92) but did not significantly reduce the risk of non-cardiovascular death (0·94, 0·88-1·02). For these mortality outcomes, RRs were similar in patients with and without diabetes. For all outcomes, results were broadly similar irrespective of trial mean baseline eGFR. Based on estimates of absolute effects, the absolute benefits of SGLT2 inhibition outweighed any serious hazards of ketoacidosis or amputation.

Interpretation

In addition to the established cardiovascular benefits of SGLT2 inhibitors, the randomised data support their use for modifying risk of kidney disease progression and acute kidney injury, not only in patients with type 2 diabetes at high cardiovascular risk, but also in patients with chronic kidney disease or heart failure irrespective of diabetes status, primary kidney disease, or kidney function.

Funding

UK Medical Research Council and Kidney Research UK.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7613836; doi:https://doi.org/10.1016/S0140-6736(22)02074-8; html:https://europepmc.org/articles/PMC7613836 37755828,https://doi.org/10.1001/jamanetworkopen.2023.36023,Reporting of Observational Studies Explicitly Aiming to Emulate Randomized Trials: A Systematic Review.,"Hansford HJ, Cashin AG, Jones MD, Swanson SA, Islam N, Douglas SRG, Rizzo RRN, Devonshire JJ, Williams SA, Dahabreh IJ, Dickerman BA, Egger M, Garcia-Albeniz X, Golub RM, Lodi S, Moreno-Betancur M, Pearson SA, Schneeweiss S, Sterne JAC, Sharp MK, Stuart EA, Hernán MA, Lee H, McAuley JH.",,JAMA network open,2023,2023-09-05,Y,,,,"

Importance

Observational (nonexperimental) studies that aim to emulate a randomized trial (ie, the target trial) are increasingly informing medical and policy decision-making, but it is unclear how these studies are reported in the literature. Consistent reporting is essential for quality appraisal, evidence synthesis, and translation of evidence to policy and practice.

Objective

To assess the reporting of observational studies that explicitly aimed to emulate a target trial.

Evidence review

We searched Medline, Embase, PsycINFO, and Web of Science for observational studies published between March 2012 and October 2022 that explicitly aimed to emulate a target trial of a health or medical intervention. Two reviewers double-screened and -extracted data on study characteristics, key predefined components of the target trial protocol and its emulation (eligibility criteria, treatment strategies, treatment assignment, outcome[s], follow-up, causal contrast[s], and analysis plan), and other items related to the target trial emulation.

Findings

A total of 200 studies that explicitly aimed to emulate a target trial were included. These studies included 26 subfields of medicine, and 168 (84%) were published from January 2020 to October 2022. The aim to emulate a target trial was explicit in 70 study titles (35%). Forty-three studies (22%) reported use of a published reporting guideline (eg, Strengthening the Reporting of Observational Studies in Epidemiology). Eighty-five studies (43%) did not describe all key items of how the target trial was emulated and 113 (57%) did not describe the protocol of the target trial and its emulation.

Conclusion and relevance

In this systematic review of 200 studies that explicitly aimed to emulate a target trial, reporting of how the target trial was emulated was inconsistent. A reporting guideline for studies explicitly aiming to emulate a target trial may improve the reporting of the target trial protocols and other aspects of these emulation attempts.",,pdf:https://jamanetwork.com/journals/jamanetworkopen/articlepdf/2809945/hansford_2023_oi_231035_1695236241.69575.pdf; doi:https://doi.org/10.1001/jamanetworkopen.2023.36023; html:https://europepmc.org/articles/PMC10534275 35410184,https://doi.org/10.1186/s12889-022-13069-0,The local burden of disease during the first wave of the COVID-19 epidemic in England: estimation using different data sources from changing surveillance practices.,"Nightingale ES, Abbott S, Russell TW, CMMID Covid-19 Working Group, Lowe R, Medley GF, Brady OJ.",,BMC public health,2022,2022-04-11,Y,,,,"

Background

The COVID-19 epidemic has differentially impacted communities across England, with regional variation in rates of confirmed cases, hospitalisations and deaths. Measurement of this burden changed substantially over the first months, as surveillance was expanded to accommodate the escalating epidemic. Laboratory confirmation was initially restricted to clinical need (""pillar 1"") before expanding to community-wide symptomatics (""pillar 2""). This study aimed to ascertain whether inconsistent measurement of case data resulting from varying testing coverage could be reconciled by drawing inference from COVID-19-related deaths.

Methods

We fit a Bayesian spatio-temporal model to weekly COVID-19-related deaths per local authority (LTLA) throughout the first wave (1 January 2020-30 June 2020), adjusting for the local epidemic timing and the age, deprivation and ethnic composition of its population. We combined predictions from this model with case data under community-wide, symptomatic testing and infection prevalence estimates from the ONS infection survey, to infer the likely trajectory of infections implied by the deaths in each LTLA.

Results

A model including temporally- and spatially-correlated random effects was found to best accommodate the observed variation in COVID-19-related deaths, after accounting for local population characteristics. Predicted case counts under community-wide symptomatic testing suggest a total of 275,000-420,000 cases over the first wave - a median of over 100,000 additional to the total confirmed in practice under varying testing coverage. This translates to a peak incidence of around 200,000 total infections per week across England. The extent to which estimated total infections are reflected in confirmed case counts was found to vary substantially across LTLAs, ranging from 7% in Leicester to 96% in Gloucester with a median of 23%.

Conclusions

Limitations in testing capacity biased the observed trajectory of COVID-19 infections throughout the first wave. Basing inference on COVID-19-related mortality and higher-coverage testing later in the time period, we could explore the extent of this bias more explicitly. Evidence points towards substantial under-representation of initial growth and peak magnitude of infections nationally, to which different parts of the country contribute unequally.",,pdf:https://bmcpublichealth.biomedcentral.com/track/pdf/10.1186/s12889-022-13069-0; doi:https://doi.org/10.1186/s12889-022-13069-0; html:https://europepmc.org/articles/PMC8996221; pdf:https://europepmc.org/articles/PMC8996221?pdf=render -33048945,https://doi.org/10.1371/journal.pmed.1003290,Neurodevelopmental multimorbidity and educational outcomes of Scottish schoolchildren: A population-based record linkage cohort study.,"Fleming M, Salim EE, Mackay DF, Henderson A, Kinnear D, Clark D, King A, McLay JS, Cooper SA, Pell JP.",,PLoS medicine,2020,2020-10-13,Y,,,,"

Background

Neurodevelopmental conditions commonly coexist in children, but compared to adults, childhood multimorbidity attracts less attention in research and clinical practice. We previously reported that children treated for attention deficit hyperactivity disorder (ADHD) and depression have more school absences and exclusions, additional support needs, poorer attainment, and increased unemployment. They are also more likely to have coexisting conditions, including autism and intellectual disability. We investigated prevalence of neurodevelopmental multimorbidity (≥2 conditions) among Scottish schoolchildren and their educational outcomes compared to peers.

Methods and findings

We retrospectively linked 6 Scotland-wide databases to analyse 766,244 children (390,290 [50.9%] boys; 375,954 [49.1%] girls) aged 4 to 19 years (mean = 10.9) attending Scottish schools between 2009 and 2013. Children were distributed across all deprivation quintiles (most to least deprived: 22.7%, 20.1%, 19.3%, 19.5%, 18.4%). The majority (96.2%) were white ethnicity. We ascertained autism spectrum disorder (ASD) and intellectual disabilities from records of additional support needs and ADHD and depression through relevant encashed prescriptions. We identified neurodevelopmental multimorbidity (≥2 of these conditions) in 4,789 (0.6%) children, with ASD and intellectual disability the most common combination. On adjusting for sociodemographic (sex, age, ethnicity, deprivation) and maternity (maternal age, maternal smoking, sex-gestation-specific birth weight centile, gestational age, 5-minute Apgar score, mode of delivery, parity) factors, multimorbidity was associated with increased school absenteeism and exclusion, unemployment, and poorer exam attainment. Significant dose relationships were evident between number of conditions (0, 1, ≥2) and the last 3 outcomes. Compared to children with no conditions, children with 1 condition, and children with 2 or more conditions, had more absenteeism (1 condition adjusted incidence rate ratio [IRR] 1.28, 95% CI 1.27-1.30, p < 0.001 and 2 or more conditions adjusted IRR 1.23, 95% CI 1.20-1.28, p < 0.001), greater exclusion (adjusted IRR 2.37, 95% CI 2.25-2.48, p < 0.001 and adjusted IRR 3.04, 95% CI 2.74-3.38, p < 0.001), poorer attainment (adjusted odds ratio [OR] 3.92, 95% CI 3.63-4.23, p < 0.001 and adjusted OR 12.07, 95% CI 9.15-15.94, p < 0.001), and increased unemployment (adjusted OR 1.57, 95% CI 1.49-1.66, p < 0.001 and adjusted OR 2.11, 95% CI 1.83-2.45, p < 0.001). Associations remained after further adjustment for comorbid physical conditions and additional support needs. Coexisting depression was the strongest driver of absenteeism and coexisting ADHD the strongest driver of exclusion. Absence of formal primary care diagnoses was a limitation since ascertaining depression and ADHD from prescriptions omitted affected children receiving alternative or no treatment and some antidepressants can be prescribed for other indications.

Conclusions

Structuring clinical practice and training around single conditions may disadvantage children with neurodevelopmental multimorbidity, who we observed had significantly poorer educational outcomes compared to children with 1 condition and no conditions.",,pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1003290&type=printable; doi:https://doi.org/10.1371/journal.pmed.1003290; html:https://europepmc.org/articles/PMC7553326; pdf:https://europepmc.org/articles/PMC7553326?pdf=render 30993728,https://doi.org/10.1111/cen.13990,Risk of incident circulatory disease in patients treated for differentiated thyroid carcinoma with no history of cardiovascular disease.,"Toulis KA, Viola D, Gkoutos G, Keerthy D, Boelaert K, Nirantharakumar K.",,Clinical endocrinology,2019,2019-05-17,N,Atrial fibrillation; Cardiovascular events; Thyroid cancer; Differentiated Thyroid Carcinoma,,,"

Context

The incidence of differentiated thyroid cancer (DTC) is increasing, yet the prognosis is favourable and long-term survival is expected. Exogenous TSH suppression has been used for many years to prevent DTC recurrence and may be associated with increased risks of circulatory diseases.

Design

Risks of circulatory disease in patients treated for DTC were compared to randomly matched patients without DTC (controls) up to a 1:5 ratio using age, sex, body mass index (BMI) and smoking as the matching parameters in a population-based, open cohort study using The Health Improvement Network.

Patients

A total of 3009 patients treated for DTC with no pre-existing cardiovascular disease were identified and matched to 11 303 controls, followed up to median of 5 years.

Results

A total of 1259 incident circulatory events were recorded during the observation period. No difference in the risk of ischaemic heart disease (IHD) (adjusted hazards ratio [aHR]: 1.04, 95% CI: 0.80-1.36) or heart failure (HF) (aHR: 1.27, 95% CI: 0.89-1.81) was detected. The risk of atrial fibrillation (AF) and stroke was significantly higher in patients with DTC (aHR: 1.71, 95% CI: 1.36-2.15 and aHR: 1.34, 95% CI: 1.05-1.72, respectively). In a sensitivity analysis limited to newly diagnosed patients with DTC, only the risk of AF was consistently elevated (aHR: 1.86, 95% CI: 1.33-2.60).

Conclusions

The increased risk of AF in patients who have undergone treatment for DTC but without pre-existing CVD may warrant periodic screening for this arrhythmia. Whereas no evidence of increased risk of IHD or HF was observed, the increased risk of stroke/TIA warrants further investigation.",,doi:https://doi.org/10.1111/cen.13990 +33048945,https://doi.org/10.1371/journal.pmed.1003290,Neurodevelopmental multimorbidity and educational outcomes of Scottish schoolchildren: A population-based record linkage cohort study.,"Fleming M, Salim EE, Mackay DF, Henderson A, Kinnear D, Clark D, King A, McLay JS, Cooper SA, Pell JP.",,PLoS medicine,2020,2020-10-13,Y,,,,"

Background

Neurodevelopmental conditions commonly coexist in children, but compared to adults, childhood multimorbidity attracts less attention in research and clinical practice. We previously reported that children treated for attention deficit hyperactivity disorder (ADHD) and depression have more school absences and exclusions, additional support needs, poorer attainment, and increased unemployment. They are also more likely to have coexisting conditions, including autism and intellectual disability. We investigated prevalence of neurodevelopmental multimorbidity (≥2 conditions) among Scottish schoolchildren and their educational outcomes compared to peers.

Methods and findings

We retrospectively linked 6 Scotland-wide databases to analyse 766,244 children (390,290 [50.9%] boys; 375,954 [49.1%] girls) aged 4 to 19 years (mean = 10.9) attending Scottish schools between 2009 and 2013. Children were distributed across all deprivation quintiles (most to least deprived: 22.7%, 20.1%, 19.3%, 19.5%, 18.4%). The majority (96.2%) were white ethnicity. We ascertained autism spectrum disorder (ASD) and intellectual disabilities from records of additional support needs and ADHD and depression through relevant encashed prescriptions. We identified neurodevelopmental multimorbidity (≥2 of these conditions) in 4,789 (0.6%) children, with ASD and intellectual disability the most common combination. On adjusting for sociodemographic (sex, age, ethnicity, deprivation) and maternity (maternal age, maternal smoking, sex-gestation-specific birth weight centile, gestational age, 5-minute Apgar score, mode of delivery, parity) factors, multimorbidity was associated with increased school absenteeism and exclusion, unemployment, and poorer exam attainment. Significant dose relationships were evident between number of conditions (0, 1, ≥2) and the last 3 outcomes. Compared to children with no conditions, children with 1 condition, and children with 2 or more conditions, had more absenteeism (1 condition adjusted incidence rate ratio [IRR] 1.28, 95% CI 1.27-1.30, p < 0.001 and 2 or more conditions adjusted IRR 1.23, 95% CI 1.20-1.28, p < 0.001), greater exclusion (adjusted IRR 2.37, 95% CI 2.25-2.48, p < 0.001 and adjusted IRR 3.04, 95% CI 2.74-3.38, p < 0.001), poorer attainment (adjusted odds ratio [OR] 3.92, 95% CI 3.63-4.23, p < 0.001 and adjusted OR 12.07, 95% CI 9.15-15.94, p < 0.001), and increased unemployment (adjusted OR 1.57, 95% CI 1.49-1.66, p < 0.001 and adjusted OR 2.11, 95% CI 1.83-2.45, p < 0.001). Associations remained after further adjustment for comorbid physical conditions and additional support needs. Coexisting depression was the strongest driver of absenteeism and coexisting ADHD the strongest driver of exclusion. Absence of formal primary care diagnoses was a limitation since ascertaining depression and ADHD from prescriptions omitted affected children receiving alternative or no treatment and some antidepressants can be prescribed for other indications.

Conclusions

Structuring clinical practice and training around single conditions may disadvantage children with neurodevelopmental multimorbidity, who we observed had significantly poorer educational outcomes compared to children with 1 condition and no conditions.",,pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1003290&type=printable; doi:https://doi.org/10.1371/journal.pmed.1003290; html:https://europepmc.org/articles/PMC7553326; pdf:https://europepmc.org/articles/PMC7553326?pdf=render 33306713,https://doi.org/10.1371/journal.pone.0243383,"Health, educational and employment outcomes among children treated for a skin disorder: Scotland-wide retrospective record linkage cohort study of 766,244 children.","Fleming M, McLay JS, Clark D, King A, Mackay DF, Pell JP.",,PloS one,2020,2020-12-11,Y,,,,"

Background

To compare health, educational and employment outcomes of schoolchildren receiving medication for a skin disorder with peers.

Methods

This retrospective population cohort study linked eight Scotland-wide databases, covering dispensed prescriptions, hospital admissions, maternity records, death certificates, annual pupil census, school examinations, school absences/exclusions and unemployment to investigate educational (absence, exclusion, special educational need, academic attainment), employment, and health (admissions and mortality) outcomes of 766,244 children attending local authority run primary, secondary and special schools in Scotland between 2009 and 2013.

Results

After adjusting for sociodemographic and maternity confounders the 130,087 (17.0%) children treated for a skin disorder had increased hospitalisation, particularly within one year of commencing treatment (IRR 1.38, 95% CI 1.35-1.41, p<0.001) and mortality (HR 1.50, 95% CI 1.18-1.90, p<0.001). They had greater special educational need (OR 1.19, 95% CI 1.17-1.21, p<0.001) and more frequent absences from school (IRR 1.07, 95% CI 1.06-1.08, p<0.001) but did not exhibit poorer exam attainment or increased post-school unemployment. The associations remained after further adjustment for comorbid chronic conditions.

Conclusions

Despite increased hospitalisation, school absenteeism, and special educational need, children treated for a skin disorder did not have poorer exam attainment or employment outcomes. Whilst findings relating to educational and employment outcomes are reassuring, the association with increased risk of mortality is alarming and merits further investigation.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0243383&type=printable; doi:https://doi.org/10.1371/journal.pone.0243383; html:https://europepmc.org/articles/PMC7732076; pdf:https://europepmc.org/articles/PMC7732076?pdf=render 36093379,https://doi.org/10.1016/j.isci.2022.105079,Epidemiologic information discovery from open-access COVID-19 case reports via pretrained language model.,"Wang Z, Liu XF, Du Z, Wang L, Wu Y, Holme P, Lachmann M, Lin H, Wong ZSY, Xu XK, Sun Y.",,iScience,2022,2022-09-05,Y,Artificial intelligence; Virology; Machine Learning; Health Sciences,,,"Although open-access data are increasingly common and useful to epidemiological research, the curation of such datasets is resource-intensive and time-consuming. Despite the existence of a major source of COVID-19 data, the regularly disclosed case reports were often written in natural language with an unstructured format. Here, we propose a computational framework that can automatically extract epidemiological information from open-access COVID-19 case reports. We develop this framework by coupling a language model developed using deep neural networks with training samples compiled using an optimized data annotation strategy. When applied to the COVID-19 case reports collected from mainland China, our framework outperforms all other state-of-the-art deep learning models. The information extracted from our approach is highly consistent with that obtained from the gold-standard manual coding, with a matching rate of 80%. To disseminate our algorithm, we provide an open-access online platform that is able to estimate key epidemiological statistics in real time, with much less effort for data curation.",,pdf:http://www.cell.com/article/S2589004222013517/pdf; doi:https://doi.org/10.1016/j.isci.2022.105079; html:https://europepmc.org/articles/PMC9441477; pdf:https://europepmc.org/articles/PMC9441477?pdf=render -37719788,https://doi.org/10.1093/noajnl/vdad096,Development of a core outcome set for use in adult primary glioma phase III interventional trials: A mixed methods study.,"Retzer A, Baddeley E, Sivell S, Scott H, Nelson A, Bulbeck H, Seddon K, Grant R, Adams R, Watts C, Aiyegbusi OL, Kearns P, Rivera SC, Dirven L, Calvert M, Byrne A.",,Neuro-oncology advances,2023,2023-01-01,Y,trials; Outcomes; Neuro-oncology; Delphi; Primary Glioma,,,"

Background

Glioma interventional studies should collect data aligned with patient priorities, enabling treatment benefit assessment and informed decision-making. This requires effective data synthesis and meta-analyses, underpinned by consistent trial outcome measurement, analysis, and reporting. Development of a core outcome set (COS) may contribute to a solution.

Methods

A 5-stage process was used to develop a COS for glioma trials from the UK perspective. Outcome lists were generated in stages 1: a trial registry review and systematic review of qualitative studies and 2: interviews with glioma patients and caregivers. In stage 3, the outcome lists were de-duplicated with accessible terminology, in stage 4 outcomes were rated via a 2-round Delphi process, and stage 5 comprised a consensus meeting to finalize the COS. Patient-reportable COS outcomes were identified.

Results

In Delphi round 1, 96 participants rated 35 outcomes identified in stages 1 and 2, to which a further 10 were added. Participants (77/96) rated the resulting 45 outcomes in round 2. Of these, 22 outcomes met a priori threshold for inclusion in the COS. After further review, a COS consisting of 19 outcomes grouped into 7 outcome domains (survival, adverse events, activities of daily living, health-related quality of life, seizure activity, cognitive function, and physical function) was finalized by 13 participants at the consensus meeting.

Conclusions

A COS for glioma trials was developed, comprising 7 outcome domains. Additional research will identify appropriate measurement tools and further validate this COS.",,pdf:https://academic.oup.com/noa/advance-article-pdf/doi/10.1093/noajnl/vdad096/51026152/vdad096.pdf; doi:https://doi.org/10.1093/noajnl/vdad096; html:https://europepmc.org/articles/PMC10503650; pdf:https://europepmc.org/articles/PMC10503650?pdf=render 34112101,https://doi.org/10.1186/s12872-021-02020-7,Routine clinical care data from thirteen cardiac outpatient clinics: design of the Cardiology Centers of the Netherlands (CCN) database.,"Bots SH, Siegersma KR, Onland-Moret NC, Asselbergs FW, Somsen GA, Tulevski II, den Ruijter HM, Hofstra L.",,BMC cardiovascular disorders,2021,2021-06-10,Y,Prevention; Big Data; Cardiovascular Care; Clinical Care Data,,,"

Background

Despite the increasing availability of clinical data due to the digitalisation of healthcare systems, data often remain inaccessible due to the diversity of data collection systems. In the Netherlands, Cardiology Centers of the Netherlands (CCN) introduced ""one-stop shop"" diagnostic clinics for patients suspected of cardiac disease by their general practitioner. All CCN clinics use the same data collection system and standardised protocol, creating a large regular care database. This database can be used to describe referral practices, evaluate risk factors for cardiovascular disease (CVD) in important patient subgroups, and develop prediction models for use in daily care.

Construction and content

The current database contains data on all patients who underwent a cardiac workup in one of the 13 CCN clinics between 2007 and February 2018 (n = 109,151, 51.9% women). Data were pseudonymised and contain information on anthropometrics, cardiac symptoms, risk factors, comorbidities, cardiovascular and family history, standard blood laboratory measurements, transthoracic echocardiography, electrocardiography in rest and during exercise, and medication use. Clinical follow-up is based on medical need and consisted of either a repeat visit at CCN (43.8%) or referral for an external procedure in a hospital (16.5%). Passive follow-up via linkage to national mortality registers is available for 95% of the database.

Utility and discussion

The CCN database provides a strong base for research into historically underrepresented patient groups due to the large number of patients and the lack of in- and exclusion criteria. It also enables the development of artificial intelligence-based decision support tools. Its contemporary nature allows for comparison of daily care with the current guidelines and protocols. Missing data is an inherent limitation, as the cardiologist could deviate from standardised protocols when clinically indicated.

Conclusion

The CCN database offers the opportunity to conduct research in a unique population referred from the general practitioner to the cardiologist for diagnostic workup. This, in combination with its large size, the representation of historically underrepresented patient groups and contemporary nature makes it a valuable tool for expanding our knowledge of cardiovascular diseases.

Trial registration

Not applicable.",,pdf:https://bmccardiovascdisord.biomedcentral.com/counter/pdf/10.1186/s12872-021-02020-7; doi:https://doi.org/10.1186/s12872-021-02020-7; html:https://europepmc.org/articles/PMC8191101; pdf:https://europepmc.org/articles/PMC8191101?pdf=render +37719788,https://doi.org/10.1093/noajnl/vdad096,Development of a core outcome set for use in adult primary glioma phase III interventional trials: A mixed methods study.,"Retzer A, Baddeley E, Sivell S, Scott H, Nelson A, Bulbeck H, Seddon K, Grant R, Adams R, Watts C, Aiyegbusi OL, Kearns P, Rivera SC, Dirven L, Calvert M, Byrne A.",,Neuro-oncology advances,2023,2023-01-01,Y,trials; Outcomes; Neuro-oncology; Delphi; Primary Glioma,,,"

Background

Glioma interventional studies should collect data aligned with patient priorities, enabling treatment benefit assessment and informed decision-making. This requires effective data synthesis and meta-analyses, underpinned by consistent trial outcome measurement, analysis, and reporting. Development of a core outcome set (COS) may contribute to a solution.

Methods

A 5-stage process was used to develop a COS for glioma trials from the UK perspective. Outcome lists were generated in stages 1: a trial registry review and systematic review of qualitative studies and 2: interviews with glioma patients and caregivers. In stage 3, the outcome lists were de-duplicated with accessible terminology, in stage 4 outcomes were rated via a 2-round Delphi process, and stage 5 comprised a consensus meeting to finalize the COS. Patient-reportable COS outcomes were identified.

Results

In Delphi round 1, 96 participants rated 35 outcomes identified in stages 1 and 2, to which a further 10 were added. Participants (77/96) rated the resulting 45 outcomes in round 2. Of these, 22 outcomes met a priori threshold for inclusion in the COS. After further review, a COS consisting of 19 outcomes grouped into 7 outcome domains (survival, adverse events, activities of daily living, health-related quality of life, seizure activity, cognitive function, and physical function) was finalized by 13 participants at the consensus meeting.

Conclusions

A COS for glioma trials was developed, comprising 7 outcome domains. Additional research will identify appropriate measurement tools and further validate this COS.",,pdf:https://academic.oup.com/noa/advance-article-pdf/doi/10.1093/noajnl/vdad096/51026152/vdad096.pdf; doi:https://doi.org/10.1093/noajnl/vdad096; html:https://europepmc.org/articles/PMC10503650; pdf:https://europepmc.org/articles/PMC10503650?pdf=render 35210596,https://doi.org/10.1038/s41591-022-01736-z,Modeling comparative cost-effectiveness of SARS-CoV-2 vaccine dose fractionation in India.,"Du Z, Wang L, Pandey A, Lim WW, Chinazzi M, Piontti APY, Lau EHY, Wu P, Malani A, Cobey S, Cowling BJ.",,Nature medicine,2022,2022-02-24,Y,,,,"Given global Coronavirus Disease 2019 (COVID-19) vaccine shortages and inequity of vaccine distributions, fractionation of vaccine doses might be an effective strategy for reducing public health and economic burden, notwithstanding the emergence of new variants of concern. In this study, we developed a multi-scale model incorporating population-level transmission and individual-level vaccination to estimate the costs of hospitalization and vaccination and the economic benefits of reducing COVID-19 deaths due to dose-fractionation strategies in India. We used large-scale survey data of the willingness to pay together with data of vaccine and hospital admission costs to build the model. We found that fractional doses of vaccines could be an economically viable vaccination strategy compared to alternatives of either full-dose vaccination or no vaccination. Dose-sparing strategies could save a large number of lives, even with the emergence of new variants with higher transmissibility.",,pdf:https://www.nature.com/articles/s41591-022-01736-z.pdf; doi:https://doi.org/10.1038/s41591-022-01736-z; html:https://europepmc.org/articles/PMC9117137; pdf:https://europepmc.org/articles/PMC9117137?pdf=render 32692755,https://doi.org/10.1371/journal.pone.0236193,A genetic model of ivabradine recapitulates results from randomized clinical trials.,"Legault MA, Sandoval J, Provost S, Barhdadi A, Lemieux Perreault LP, Shah S, Lumbers RT, de Denus S, Tyl B, Tardif JC, Dubé MP.",,PloS one,2020,2020-07-21,Y,,,,"

Background

Naturally occurring human genetic variants provide a valuable tool to identify drug targets and guide drug prioritization and clinical trial design. Ivabradine is a heart rate lowering drug with protective effects on heart failure despite increasing the risk of atrial fibrillation. In patients with coronary artery disease without heart failure, the drug does not protect against major cardiovascular adverse events prompting questions about the ability of genetics to have predicted those effects. This study evaluates the effect of a variant in HCN4, ivabradine's drug target, on safety and efficacy endpoints.

Methods

We used genetic association testing and Mendelian randomization to predict the effect of ivabradine and heart rate lowering on cardiovascular outcomes.

Results

Using data from the UK Biobank and large GWAS consortia, we evaluated the effect of a heart rate-reducing genetic variant at the HCN4 locus encoding ivabradine's drug target. These genetic association analyses showed increases in risk for atrial fibrillation (OR 1.09, 95% CI: 1.06-1.13, P = 9.3 ×10-9) in the UK Biobank. In a cause-specific competing risk model to account for the increased risk of atrial fibrillation, the HCN4 variant reduced incident heart failure in participants that did not develop atrial fibrillation (HR 0.90, 95% CI: 0.83-0.98, P = 0.013). In contrast, the same heart rate reducing HCN4 variant did not prevent a composite endpoint of myocardial infarction or cardiovascular death (OR 0.99, 95% CI: 0.93-1.04, P = 0.61).

Conclusion

Genetic modelling of ivabradine recapitulates its benefits in heart failure, promotion of atrial fibrillation, and neutral effect on myocardial infarction.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0236193&type=printable; doi:https://doi.org/10.1371/journal.pone.0236193; html:https://europepmc.org/articles/PMC7373274; pdf:https://europepmc.org/articles/PMC7373274?pdf=render 30120083,https://doi.org/10.1016/j.ebiom.2018.08.004,"Genome-Wide Association Study of Circadian Rhythmicity in 71,500 UK Biobank Participants and Polygenic Association with Mood Instability.","Ferguson A, Lyall LM, Ward J, Strawbridge RJ, Cullen B, Graham N, Niedzwiedz CL, Johnston KJA, MacKay D, Biello SM, Pell JP, Cavanagh J, McIntosh AM, Doherty A, Bailey MES, Lyall DM, Wyse CA, Smith DJ.",,EBioMedicine,2018,2018-08-14,Y,Mood Instability; Gwas; Polygenic Risk Score; Circadian Rhythmicity; Relative Amplitude,Understanding the Causes of Disease,,"

Background

Circadian rhythms are fundamental to health and are particularly important for mental wellbeing. Disrupted rhythms of rest and activity are recognised as risk factors for major depressive disorder and bipolar disorder.

Methods

We conducted a genome-wide association study (GWAS) of low relative amplitude (RA), an objective measure of rest-activity cycles derived from the accelerometer data of 71,500 UK Biobank participants. Polygenic risk scores (PRS) for low RA were used to investigate potential associations with psychiatric phenotypes.

Outcomes

Two independent genetic loci were associated with low RA, within genomic regions for Neurofascin (NFASC) and Solute Carrier Family 25 Member 17 (SLC25A17). A secondary GWAS of RA as a continuous measure identified a locus within Meis Homeobox 1 (MEIS1). There were no significant genetic correlations between low RA and any of the psychiatric phenotypes assessed. However, PRS for low RA was significantly associated with mood instability across multiple PRS thresholds (at PRS threshold 0·05: OR = 1·02, 95% CI = 1·01-1·02, p = 9·6 × 10-5), and with major depressive disorder (at PRS threshold 0·1: OR = 1·03, 95% CI = 1·01-1·05, p = 0·025) and neuroticism (at PRS threshold 0·5: Beta = 0·02, 95% CI = 0·007-0·04, p = 0·021).

Interpretation

Overall, our findings contribute new knowledge on the complex genetic architecture of circadian rhythmicity and suggest a putative biological link between disrupted circadian function and mood disorder phenotypes, particularly mood instability, but also major depressive disorder and neuroticism.

Funding

Medical Research Council (MR/K501335/1).",,pdf:http://www.thelancet.com/article/S2352396418302925/pdf; doi:https://doi.org/10.1016/j.ebiom.2018.08.004; html:https://europepmc.org/articles/PMC6154782; pdf:https://europepmc.org/articles/PMC6154782?pdf=render @@ -1804,11 +1804,11 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 32704413,https://doi.org/10.1167/tvst.9.2.7,A Clinician's Guide to Artificial Intelligence: How to Critically Appraise Machine Learning Studies.,"Faes L, Liu X, Wagner SK, Fu DJ, Balaskas K, Sim DA, Bachmann LM, Keane PA, Denniston AK.",,Translational vision science & technology,2020,2020-02-12,Y,Artificial intelligence; Critical Appraisal; Machine Learning,,,"In recent years, there has been considerable interest in the prospect of machine learning models demonstrating expert-level diagnosis in multiple disease contexts. However, there is concern that the excitement around this field may be associated with inadequate scrutiny of methodology and insufficient adoption of scientific good practice in the studies involving artificial intelligence in health care. This article aims to empower clinicians and researchers to critically appraise studies of clinical applications of machine learning, through: (1) introducing basic machine learning concepts and nomenclature; (2) outlining key applicable principles of evidence-based medicine; and (3) highlighting some of the potential pitfalls in the design and reporting of these studies.",,pdf:https://tvst.arvojournals.org/arvo/content_public/journal/tvst/938366/i2164-2591-9-2-7_1597165820.03912.pdf; doi:https://doi.org/10.1167/tvst.9.2.7; html:https://europepmc.org/articles/PMC7346877; pdf:https://europepmc.org/articles/PMC7346877?pdf=render 36215124,https://doi.org/10.1161/circgen.121.003598,Gene Sequencing Identifies Perturbation in Nitric Oxide Signaling as a Nonlipid Molecular Subtype of Coronary Artery Disease.,"Khera AV, Wang M, Chaffin M, Emdin CA, Samani NJ, Schunkert H, Watkins H, McPherson R, Erdmann J, Elosua R, Boerwinkle E, Ardissino D, Butterworth AS, Di Angelantonio E, Naheed A, Danesh J, Chowdhury R, Krumholz HM, Sheu WH, Rich SS, Rotter JI, Chen YI, Gabriel S, Lander ES, Saleheen D, Kathiresan S.",,Circulation. Genomic and precision medicine,2022,2022-10-10,N,Atherosclerosis; coronary artery disease; Genetic Association Studies; Nitric Oxide Synthase Type Iii; Precision Medicine,,,"

Background

A key goal of precision medicine is to disaggregate common, complex diseases into discrete molecular subtypes. Rare coding variants in the low-density lipoprotein receptor gene (LDLR) are identified in 1% to 2% of coronary artery disease (CAD) patients, defining a molecular subtype with risk driven by hypercholesterolemia.

Methods

To search for additional subtypes, we compared the frequency of rare, predicted loss-of-function and damaging missense variants aggregated within a given gene in 41 081 CAD cases versus 217 115 controls.

Results

Rare variants in LDLR were most strongly associated with CAD, present in 1% of cases and associated with 4.4-fold increased CAD risk. A second subtype was characterized by variants in endothelial nitric oxide synthase gene (NOS3), a key enzyme regulating vascular tone, endothelial function, and platelet aggregation. A rare predicted loss-of-function or damaging missense variants in NOS3 was present in 0.6% of cases and associated with 2.42-fold increased risk of CAD (95% CI, 1.80-3.26; P=5.50×10-9). These variants were associated with higher systolic blood pressure (+3.25 mm Hg; [95% CI, 1.86-4.65]; P=5.00×10-6) and increased risk of hypertension (adjusted odds ratio 1.31; [95% CI, 1.14-1.51]; P=2.00×10-4) but not circulating cholesterol concentrations, suggesting that, beyond lipid pathways, nitric oxide synthesis is a key nonlipid driver of CAD risk.

Conclusions

Beyond LDLR, we identified an additional nonlipid molecular subtype of CAD characterized by rare variants in the NOS3 gene.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCGEN.121.003598; doi:https://doi.org/10.1161/CIRCGEN.121.003598; html:https://europepmc.org/articles/PMC9771961; pdf:https://europepmc.org/articles/PMC9771961?pdf=render; doi:https://doi.org/10.1161/circgen.121.003598 32781946,https://doi.org/10.1098/rspb.2020.1405,Key questions for modelling COVID-19 exit strategies.,"Thompson RN, Hollingsworth TD, Isham V, Arribas-Bel D, Ashby B, Britton T, Challenor P, Chappell LHK, Clapham H, Cunniffe NJ, Dawid AP, Donnelly CA, Eggo RM, Funk S, Gilbert N, Glendinning P, Gog JR, Hart WS, Heesterbeek H, House T, Keeling M, Kiss IZ, Kretzschmar ME, Lloyd AL, McBryde ES, McCaw JM, McKinley TJ, Miller JC, Morris M, O'Neill PD, Parag KV, Pearson CAB, Pellis L, Pulliam JRC, Ross JV, Tomba GS, Silverman BW, Struchiner CJ, Tildesley MJ, Trapman P, Webb CR, Mollison D, Restif O.",,Proceedings. Biological sciences,2020,2020-08-12,Y,Uncertainty; Mathematical Modelling; Epidemic Control; Exit Strategy; Covid-19; Sars-cov-2,,,"Combinations of intense non-pharmaceutical interventions (lockdowns) were introduced worldwide to reduce SARS-CoV-2 transmission. Many governments have begun to implement exit strategies that relax restrictions while attempting to control the risk of a surge in cases. Mathematical modelling has played a central role in guiding interventions, but the challenge of designing optimal exit strategies in the face of ongoing transmission is unprecedented. Here, we report discussions from the Isaac Newton Institute 'Models for an exit strategy' workshop (11-15 May 2020). A diverse community of modellers who are providing evidence to governments worldwide were asked to identify the main questions that, if answered, would allow for more accurate predictions of the effects of different exit strategies. Based on these questions, we propose a roadmap to facilitate the development of reliable models to guide exit strategies. This roadmap requires a global collaborative effort from the scientific community and policymakers, and has three parts: (i) improve estimation of key epidemiological parameters; (ii) understand sources of heterogeneity in populations; and (iii) focus on requirements for data collection, particularly in low-to-middle-income countries. This will provide important information for planning exit strategies that balance socio-economic benefits with public health.",,doi:https://doi.org/10.1098/rspb.2020.1405; doi:https://doi.org/10.1098/rspb.2020.1405; html:https://europepmc.org/articles/PMC7575516; pdf:https://europepmc.org/articles/PMC7575516?pdf=render -37025302,https://doi.org/10.1093/jacamr/dlad039,Inclusion of minor alleles improves catalogue-based prediction of fluoroquinolone resistance in Mycobacterium tuberculosis.,"Brankin AE, Fowler PW.",,JAC-antimicrobial resistance,2023,2023-04-04,Y,,,,"

Objectives

Fluoroquinolone resistance poses a threat to the successful treatment of tuberculosis. WGS, and the subsequent detection of catalogued resistance-associated mutations, offers an attractive solution to fluoroquinolone susceptibility testing but sensitivities are often less than 90%. We hypothesize that this is partly because the bioinformatic pipelines used usually mask the recognition of minor alleles that have been implicated in fluoroquinolone resistance.

Methods

We analysed the Comprehensive Resistance Prediction for Tuberculosis: an International Consortium (CRyPTIC) dataset of globally diverse WGS Mycobacterium tuberculosis isolates, with matched MICs for two fluoroquinolone drugs and allowed putative minor alleles to contribute to resistance prediction.

Results

Detecting minor alleles increased the sensitivity of WGS for moxifloxacin resistance prediction from 85.4% to 94.0%, without significantly reducing specificity. We also found no correlation between the proportion of an M. tuberculosis population containing a resistance-conferring allele and the magnitude of resistance.

Conclusions

Together our results highlight the importance of detecting minor resistance-conferring alleles when using WGS, or indeed any sequencing-based approach, to diagnose fluoroquinolone resistance.",,pdf:https://academic.oup.com/jacamr/article-pdf/5/2/dlad039/49747584/dlad039.pdf; doi:https://doi.org/10.1093/jacamr/dlad039; html:https://europepmc.org/articles/PMC10072237; pdf:https://europepmc.org/articles/PMC10072237?pdf=render -36423925,https://doi.org/10.1136/thorax-2022-219591,Rebound in asthma exacerbations following relaxation of COVID-19 restrictions: a longitudinal population-based study (COVIDENCE UK).,"Tydeman F, Pfeffer PE, Vivaldi G, Holt H, Talaei M, Jolliffe D, Davies G, Lyons RA, Griffiths C, Kee F, Sheikh A, Shaheen SO, Martineau AR.",,Thorax,2023,2022-11-23,Y,Asthma; Covid-19,,,"

Background

The imposition of restrictions on social mixing early in the COVID-19 pandemic was followed by a reduction in asthma exacerbations in multiple settings internationally. Temporal trends in social mixing, incident acute respiratory infections (ARI) and asthma exacerbations following relaxation of COVID-19 restrictions have not yet been described.

Methods

We conducted a population-based longitudinal study in 2312 UK adults with asthma between November 2020 and April 2022. Details of face covering use, social mixing, incident ARI and severe asthma exacerbations were collected via monthly online questionnaires. Temporal changes in these parameters were visualised using Poisson generalised additive models. Multilevel logistic regression was used to test for associations between incident ARI and risk of asthma exacerbations, adjusting for potential confounders.

Results

Relaxation of COVID-19 restrictions from April 2021 coincided with reduced face covering use (p<0.001), increased frequency of indoor visits to public places and other households (p<0.001) and rising incidence of COVID-19 (p<0.001), non-COVID-19 ARI (p<0.001) and severe asthma exacerbations (p=0.007). Incident non-COVID-19 ARI associated independently with increased risk of asthma exacerbation (adjusted OR 5.75, 95% CI 4.75 to 6.97) as did incident COVID-19, both prior to emergence of the omicron variant of SARS-CoV-2 (5.89, 3.45 to 10.04) and subsequently (5.69, 3.89 to 8.31).

Conclusions

Relaxation of COVID-19 restrictions coincided with decreased face covering use, increased social mixing and a rebound in ARI and asthma exacerbations. Associations between incident ARI and risk of severe asthma exacerbation were similar for non-COVID-19 ARI and COVID-19, both before and after emergence of the SARS-CoV-2 omicron variant.

Study registration number

NCT04330599.",,pdf:https://thorax.bmj.com/content/thoraxjnl/early/2022/12/29/thorax-2022-219591.full.pdf; doi:https://doi.org/10.1136/thorax-2022-219591; html:https://europepmc.org/articles/PMC10359556; pdf:https://europepmc.org/articles/PMC10359556?pdf=render 35165324,https://doi.org/10.1038/s41598-022-06315-3,Improving robustness of automatic cardiac function quantification from cine magnetic resonance imaging using synthetic image data.,"Gheorghiță BA, Itu LM, Sharma P, Suciu C, Wetzl J, Geppert C, Ali MAA, Lee AM, Piechnik SK, Neubauer S, Petersen SE, Schulz-Menger J, Chițiboi T.",,Scientific reports,2022,2022-02-14,Y,,,,"Although having been the subject of intense research over the years, cardiac function quantification from MRI is still not a fully automatic process in the clinical practice. This is partly due to the shortage of training data covering all relevant cardiovascular disease phenotypes. We propose to synthetically generate short axis CINE MRI using a generative adversarial model to expand the available data sets that consist of predominantly healthy subjects to include more cases with reduced ejection fraction. We introduce a deep learning convolutional neural network (CNN) to predict the end-diastolic volume, end-systolic volume, and implicitly the ejection fraction from cardiac MRI without explicit segmentation. The left ventricle volume predictions were compared to the ground truth values, showing superior accuracy compared to state-of-the-art segmentation methods. We show that using synthetic data generated for pre-training a CNN significantly improves the prediction compared to only using the limited amount of available data, when the training set is imbalanced.",,pdf:https://www.nature.com/articles/s41598-022-06315-3.pdf; doi:https://doi.org/10.1038/s41598-022-06315-3; html:https://europepmc.org/articles/PMC8844403; pdf:https://europepmc.org/articles/PMC8844403?pdf=render -37865101,https://doi.org/10.1016/s2213-8587(23)00253-x,"Empagliflozin in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial.",RECOVERY Collaborative Group.,,The lancet. Diabetes & endocrinology,2023,2023-10-18,Y,,,,"

Background

Empagliflozin has been proposed as a treatment for COVID-19 on the basis of its anti-inflammatory, metabolic, and haemodynamic effects. The RECOVERY trial aimed to assess its safety and efficacy in patients admitted to hospital with COVID-19.

Methods

In the randomised, controlled, open-label RECOVERY trial, several possible treatments are compared with usual care in patients hospitalised with COVID-19. In this analysis, we assess eligible and consenting adults who were randomly allocated in a 1:1 ratio to either usual standard of care alone or usual standard of care plus oral empagliflozin 10 mg once daily for 28 days or until discharge (whichever came first) using web-based simple (unstratified) randomisation with allocation concealment. The primary outcome was 28-day mortality; secondary outcomes were duration of hospitalisation and (among participants not on invasive mechanical ventilation at baseline) the composite of invasive mechanical ventilation or death. On March 3, 2023 the independent data monitoring committee recommended that the investigators review the data and recruitment was consequently stopped on March 7, 2023. The ongoing RECOVERY trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936).

Findings

Between July 28, 2021 and March 6, 2023, 4271 patients were randomly allocated to receive either empagliflozin (2113 patients) or usual care alone (2158 patients). Primary and secondary outcome data were known for greater than 99% of randomly assigned patients. Overall, 289 (14%) of 2113 patients allocated to empagliflozin and 307 (14%) of 2158 patients allocated to usual care died within 28 days (rate ratio 0·96 [95% CI 0·82-1·13]; p=0·64). There was no evidence of significant differences in duration of hospitalisation (median 8 days for both groups) or the proportion of patients discharged from hospital alive within 28 days (1678 [79%] in the empagliflozin group vs 1677 [78%] in the usual care group; rate ratio 1·03 [95% CI 0·96-1·10]; p=0·44). Among those not on invasive mechanical ventilation at baseline, there was no evidence of a significant difference in the proportion meeting the composite endpoint of invasive mechanical ventilation or death (338 [16%] of 2084 vs 371 [17%] of 2143; risk ratio 0·95 [95% CI 0·84-1·08]; p=0·44). Two serious adverse events believed to be related to empagliflozin were reported: both were ketosis without acidosis.

Interpretation

In adults hospitalised with COVID-19, empagliflozin was not associated with reductions in 28-day mortality, duration of hospital stay, or risk of progressing to invasive mechanical ventilation or death so is not indicated for the treatment of such patients unless there is an established indication due to a different condition such as diabetes.

Funding

UK Research and Innovation (Medical Research Council) and National Institute of Health Research (MC_PC_19056), and Wellcome Trust (222406/Z/20/Z).

Translations

For the Nepali, Hindi, Indonesian (Bahasa) and Vietnamese translations of the abstract see Supplementary Materials section.",,doi:https://doi.org/10.1016/S2213-8587(23)00253-X; html:https://europepmc.org/articles/PMC10957483; pdf:https://europepmc.org/articles/PMC10957483?pdf=render +36423925,https://doi.org/10.1136/thorax-2022-219591,Rebound in asthma exacerbations following relaxation of COVID-19 restrictions: a longitudinal population-based study (COVIDENCE UK).,"Tydeman F, Pfeffer PE, Vivaldi G, Holt H, Talaei M, Jolliffe D, Davies G, Lyons RA, Griffiths C, Kee F, Sheikh A, Shaheen SO, Martineau AR.",,Thorax,2023,2022-11-23,Y,Asthma; Covid-19,,,"

Background

The imposition of restrictions on social mixing early in the COVID-19 pandemic was followed by a reduction in asthma exacerbations in multiple settings internationally. Temporal trends in social mixing, incident acute respiratory infections (ARI) and asthma exacerbations following relaxation of COVID-19 restrictions have not yet been described.

Methods

We conducted a population-based longitudinal study in 2312 UK adults with asthma between November 2020 and April 2022. Details of face covering use, social mixing, incident ARI and severe asthma exacerbations were collected via monthly online questionnaires. Temporal changes in these parameters were visualised using Poisson generalised additive models. Multilevel logistic regression was used to test for associations between incident ARI and risk of asthma exacerbations, adjusting for potential confounders.

Results

Relaxation of COVID-19 restrictions from April 2021 coincided with reduced face covering use (p<0.001), increased frequency of indoor visits to public places and other households (p<0.001) and rising incidence of COVID-19 (p<0.001), non-COVID-19 ARI (p<0.001) and severe asthma exacerbations (p=0.007). Incident non-COVID-19 ARI associated independently with increased risk of asthma exacerbation (adjusted OR 5.75, 95% CI 4.75 to 6.97) as did incident COVID-19, both prior to emergence of the omicron variant of SARS-CoV-2 (5.89, 3.45 to 10.04) and subsequently (5.69, 3.89 to 8.31).

Conclusions

Relaxation of COVID-19 restrictions coincided with decreased face covering use, increased social mixing and a rebound in ARI and asthma exacerbations. Associations between incident ARI and risk of severe asthma exacerbation were similar for non-COVID-19 ARI and COVID-19, both before and after emergence of the SARS-CoV-2 omicron variant.

Study registration number

NCT04330599.",,pdf:https://thorax.bmj.com/content/thoraxjnl/early/2022/12/29/thorax-2022-219591.full.pdf; doi:https://doi.org/10.1136/thorax-2022-219591; html:https://europepmc.org/articles/PMC10359556; pdf:https://europepmc.org/articles/PMC10359556?pdf=render +37025302,https://doi.org/10.1093/jacamr/dlad039,Inclusion of minor alleles improves catalogue-based prediction of fluoroquinolone resistance in Mycobacterium tuberculosis.,"Brankin AE, Fowler PW.",,JAC-antimicrobial resistance,2023,2023-04-04,Y,,,,"

Objectives

Fluoroquinolone resistance poses a threat to the successful treatment of tuberculosis. WGS, and the subsequent detection of catalogued resistance-associated mutations, offers an attractive solution to fluoroquinolone susceptibility testing but sensitivities are often less than 90%. We hypothesize that this is partly because the bioinformatic pipelines used usually mask the recognition of minor alleles that have been implicated in fluoroquinolone resistance.

Methods

We analysed the Comprehensive Resistance Prediction for Tuberculosis: an International Consortium (CRyPTIC) dataset of globally diverse WGS Mycobacterium tuberculosis isolates, with matched MICs for two fluoroquinolone drugs and allowed putative minor alleles to contribute to resistance prediction.

Results

Detecting minor alleles increased the sensitivity of WGS for moxifloxacin resistance prediction from 85.4% to 94.0%, without significantly reducing specificity. We also found no correlation between the proportion of an M. tuberculosis population containing a resistance-conferring allele and the magnitude of resistance.

Conclusions

Together our results highlight the importance of detecting minor resistance-conferring alleles when using WGS, or indeed any sequencing-based approach, to diagnose fluoroquinolone resistance.",,pdf:https://academic.oup.com/jacamr/article-pdf/5/2/dlad039/49747584/dlad039.pdf; doi:https://doi.org/10.1093/jacamr/dlad039; html:https://europepmc.org/articles/PMC10072237; pdf:https://europepmc.org/articles/PMC10072237?pdf=render 32637892,https://doi.org/10.1016/j.eclinm.2020.100392,The association between exposure to childhood maltreatment and the subsequent development of functional somatic and visceral pain syndromes.,"Chandan JS, Keerthy D, Zemedikun DT, Okoth K, Gokhale KM, Raza K, Bandyopadhyay S, Taylor J, Nirantharakumar K.",,EClinicalMedicine,2020,2020-06-06,Y,epidemiology; Primary Care; Childhood Maltreatment; Central Sensitivity Syndromes,,,"

Background

Childhood maltreatment is a global public health issue linked to a vast mortality and morbidity burden. This study builds on current literature to explore the risk of developing central sensitivity syndromes (CSS) (consisting of somatic and visceral pain syndromes) subsequent to childhood maltreatment exposure.

Methods

A retrospective population based open cohort study using the UK primary care database, 'The Health Improvement Network,' between 1st January 1995-31st December 2018. 80,657 adult patients who had experienced childhood maltreatment or maltreatment related concerns (exposed patients) were matched to 161,314 unexposed patients by age and sex. Outcomes of interest were the development of CSS: either somatic (Fibromyalgia, chronic fatigue syndrome, temporomandibular joint disorder, chronic lower back pain, chronic headache, myofascial pain syndrome and restless leg syndrome) or visceral (Interstitial cystitis, vulvodynia, chronic prostatitis and irritable bowel syndrome) in nature. Effect sizes are presented as adjusted incidence rate ratios (aIRR) with confidence intervals (CI). Models were adjusted for the following covariates at cohort entry: age, sex, deprivation, anxiety, depression and serious mental ill health.

Results

The average age at cohort entry was 23.4 years and the median follow was 2.2 years. There was an increased risk of developing fibromyalgia (aIRR 2.06; 95% CI 1.71-2.48), chronic fatigue syndrome (1.47; 1.08-2.00), chronic lower back pain (1.99; 1.68-2.35), restless leg syndrome (1.82; 1.41-2.35) and irritable bowel syndrome (1.15; 1.08-1.22) when compared to the unexposed group, whereas no statistical association was seen with the development of temporomandibular joint disorder (1.00; 0.88-1.13), chronic headache (1.04; 0.59-1.86), interstitial cystitis (1.19; 0.51-2.74), vulvodynia (0.65; 0.34-1.26), chronic prostatitis (0.34; 0.07-1.77) and myofascial pain syndrome (0.88; 0.36-2.14). Outcome numbers were low, most likely, due to the rarity of visceral conditions (aside from irritable bowel syndrome). The association between a history of childhood maltreatment and CSS were mainly observed in somatic CSS.

Interpretation

The debilitating effects of CSS carry a substantial physical, psychological and economic burden to both the individuals who are diagnosed with them and the health services who serve them. Primary prevention approaches targeting childhood maltreatment as well as secondary preventative approaches should be considered to minimise the associated burden of CSS.",,pdf:http://www.thelancet.com/article/S258953702030136X/pdf; doi:https://doi.org/10.1016/j.eclinm.2020.100392; html:https://europepmc.org/articles/PMC7329705; pdf:https://europepmc.org/articles/PMC7329705?pdf=render +37865101,https://doi.org/10.1016/s2213-8587(23)00253-x,"Empagliflozin in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial.",RECOVERY Collaborative Group.,,The lancet. Diabetes & endocrinology,2023,2023-10-18,Y,,,,"

Background

Empagliflozin has been proposed as a treatment for COVID-19 on the basis of its anti-inflammatory, metabolic, and haemodynamic effects. The RECOVERY trial aimed to assess its safety and efficacy in patients admitted to hospital with COVID-19.

Methods

In the randomised, controlled, open-label RECOVERY trial, several possible treatments are compared with usual care in patients hospitalised with COVID-19. In this analysis, we assess eligible and consenting adults who were randomly allocated in a 1:1 ratio to either usual standard of care alone or usual standard of care plus oral empagliflozin 10 mg once daily for 28 days or until discharge (whichever came first) using web-based simple (unstratified) randomisation with allocation concealment. The primary outcome was 28-day mortality; secondary outcomes were duration of hospitalisation and (among participants not on invasive mechanical ventilation at baseline) the composite of invasive mechanical ventilation or death. On March 3, 2023 the independent data monitoring committee recommended that the investigators review the data and recruitment was consequently stopped on March 7, 2023. The ongoing RECOVERY trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936).

Findings

Between July 28, 2021 and March 6, 2023, 4271 patients were randomly allocated to receive either empagliflozin (2113 patients) or usual care alone (2158 patients). Primary and secondary outcome data were known for greater than 99% of randomly assigned patients. Overall, 289 (14%) of 2113 patients allocated to empagliflozin and 307 (14%) of 2158 patients allocated to usual care died within 28 days (rate ratio 0·96 [95% CI 0·82-1·13]; p=0·64). There was no evidence of significant differences in duration of hospitalisation (median 8 days for both groups) or the proportion of patients discharged from hospital alive within 28 days (1678 [79%] in the empagliflozin group vs 1677 [78%] in the usual care group; rate ratio 1·03 [95% CI 0·96-1·10]; p=0·44). Among those not on invasive mechanical ventilation at baseline, there was no evidence of a significant difference in the proportion meeting the composite endpoint of invasive mechanical ventilation or death (338 [16%] of 2084 vs 371 [17%] of 2143; risk ratio 0·95 [95% CI 0·84-1·08]; p=0·44). Two serious adverse events believed to be related to empagliflozin were reported: both were ketosis without acidosis.

Interpretation

In adults hospitalised with COVID-19, empagliflozin was not associated with reductions in 28-day mortality, duration of hospital stay, or risk of progressing to invasive mechanical ventilation or death so is not indicated for the treatment of such patients unless there is an established indication due to a different condition such as diabetes.

Funding

UK Research and Innovation (Medical Research Council) and National Institute of Health Research (MC_PC_19056), and Wellcome Trust (222406/Z/20/Z).

Translations

For the Nepali, Hindi, Indonesian (Bahasa) and Vietnamese translations of the abstract see Supplementary Materials section.",,doi:https://doi.org/10.1016/S2213-8587(23)00253-X; html:https://europepmc.org/articles/PMC10957483; pdf:https://europepmc.org/articles/PMC10957483?pdf=render 32170038,https://doi.org/10.1136/heartjnl-2019-316088,Cardiovascular risk factors and the risk of major adverse limb events in patients with symptomatic cardiovascular disease.,"Hageman SHJ, de Borst GJ, Dorresteijn JAN, Bots ML, Westerink J, Asselbergs FW, Visseren FLJ, UCC-SMART Study Group.",,Heart (British Cardiac Society),2020,2020-03-13,N,Hypertension; Smoking Cessation; Peripheral Vascular Disease; Cardiac Risk Factors And Prevention; Lipoproteins And Hyperlipidaemia,,,"

Aim

To determine the relationship between non-high-density lipoprotein cholesterol (non-HDL-c), systolic blood pressure (SBP) and smoking and the risk of major adverse limb events (MALE) and the combination with major adverse cardiovascular events (MALE/MACE) in patients with symptomatic vascular disease.

Methods

Patients with symptomatic vascular disease from the Utrecht Cardiovascular Cohort - Secondary Manifestations of ARTerial disease (1996-2017) study were included. The effects of non-HDL-c, SBP and smoking on the risk of MALE were analysed with Cox proportional hazard models stratified for presence of peripheral artery disease (PAD). MALE was defined as major amputation, peripheral revascularisation or thrombolysis in the lower limb.

Results

In 8139 patients (median follow-up 7.8 years, IQR 4.0-11.8), 577 MALE (8.7 per 1000 person-years) and 1933 MALE/MACE were observed (29.1 per 1000 person-years). In patients with PAD there was no relation between non-HDL-c and MALE, and in patients with coronary artery disease (CAD), cerebrovascular disease (CVD) or abdominal aortic aneurysm (AAA) the risk of MALE was higher per 1 mmol/L non-HDL-c (HR 1.14, 95% CI 1.01 to 1.29). Per 10 mm Hg SBP, the risk of MALE was higher in patients with PAD (HR 1.06, 95% CI 1.01 to 1.12) and in patients with CVD/CAD/AAA (HR 1.15, 95% CI 1.08 to 1.22). The risk of MALE was higher in smokers with PAD (HR 1.45, 95% CI 0.97 to 2.14) and CAD/CVD/AAA (HR 7.08, 95% CI 3.99 to 12.57).

Conclusions

The risk of MALE and MALE/MACE in patients with symptomatic vascular disease differs according to vascular disease location and is associated with non-HDL-c, SBP and smoking. These findings confirm the importance of MALE as an outcome and underline the importance of risk factor management in patients with vascular disease.",,pdf:https://discovery.ucl.ac.uk/10096914/1/Hageman_Manuscript_MALE_20200211_clean.pdf; doi:https://doi.org/10.1136/heartjnl-2019-316088 31363735,https://doi.org/10.1093/hmg/ddz187,Towards clinical utility of polygenic risk scores.,"Lambert SA, Abraham G, Inouye M.",,Human molecular genetics,2019,2019-11-01,N,,,,"Prediction of disease risk is an essential part of preventative medicine, often guiding clinical management. Risk prediction typically includes risk factors such as age, sex, family history of disease and lifestyle (e.g. smoking status); however, in recent years, there has been increasing interest to include genomic information into risk models. Polygenic risk scores (PRS) aggregate the effects of many genetic variants across the human genome into a single score and have recently been shown to have predictive value for multiple common diseases. In this review, we summarize the potential use cases for seven common diseases (breast cancer, prostate cancer, coronary artery disease, obesity, type 1 diabetes, type 2 diabetes and Alzheimer's disease) where PRS has or could have clinical utility. PRS analysis for these diseases frequently revolved around (i) risk prediction performance of a PRS alone and in combination with other non-genetic risk factors, (ii) estimation of lifetime risk trajectories, (iii) the independent information of PRS and family history of disease or monogenic mutations and (iv) estimation of the value of adding a PRS to specific clinical risk prediction scenarios. We summarize open questions regarding PRS usability, ancestry bias and transferability, emphasizing the need for the next wave of studies to focus on the implementation and health-economic value of PRS testing. In conclusion, it is becoming clear that PRS have value in disease risk prediction and there are multiple areas where this may have clinical utility.",,pdf:https://academic.oup.com/hmg/article-pdf/28/R2/R133/31081033/ddz187.pdf; doi:https://doi.org/10.1093/hmg/ddz187 30537243,https://doi.org/10.1002/ejhf.1370,"Can advanced analytics fix modern medicine's problem of uncertainty, imprecision, and inaccuracy?","Ahmad T, Freeman JV, Asselbergs FW.",,European journal of heart failure,2019,2018-12-10,N,,,,,,doi:https://doi.org/10.1002/ejhf.1370 @@ -1833,24 +1833,24 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 34347787,https://doi.org/10.1371/journal.pone.0253809,Developing a Natural Language Processing tool to identify perinatal self-harm in electronic healthcare records.,"Ayre K, Bittar A, Kam J, Verma S, Howard LM, Dutta R.",,PloS one,2021,2021-08-04,Y,,,,"

Background

Self-harm occurring within pregnancy and the postnatal year (""perinatal self-harm"") is a clinically important yet under-researched topic. Current research likely under-estimates prevalence due to methodological limitations. Electronic healthcare records (EHRs) provide a source of clinically rich data on perinatal self-harm.

Aims

(1) To create a Natural Language Processing (NLP) tool that can, with acceptable precision and recall, identify mentions of acts of perinatal self-harm within EHRs. (2) To use this tool to identify service-users who have self-harmed perinatally, based on their EHRs.

Methods

We used the Clinical Record Interactive Search system to extract de-identified EHRs of secondary mental healthcare service-users at South London and Maudsley NHS Foundation Trust. We developed a tool that applied several layers of linguistic processing based on the spaCy NLP library for Python. We evaluated mention-level performance in the following domains: span, status, temporality and polarity. Evaluation was done against a manually coded reference standard. Mention-level performance was reported as precision, recall, F-score and Cohen's kappa for each domain. Performance was also assessed at 'service-user' level and explored whether a heuristic rule improved this. We report per-class statistics for service-user performance, as well as likelihood ratios and post-test probabilities.

Results

Mention-level performance: micro-averaged F-score, precision and recall for span, polarity and temporality >0.8. Kappa for status 0.68, temporality 0.62, polarity 0.91. Service-user level performance with heuristic: F-score, precision, recall of minority class 0.69, macro-averaged F-score 0.81, positive LR 9.4 (4.8-19), post-test probability 69.0% (53-82%). Considering the task difficulty, the tool performs well, although temporality was the attribute with the lowest level of annotator agreement.

Conclusions

It is feasible to develop an NLP tool that identifies, with acceptable validity, mentions of perinatal self-harm within EHRs, although with limitations regarding temporality. Using a heuristic rule, it can also function at a service-user-level.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0253809&type=printable; doi:https://doi.org/10.1371/journal.pone.0253809; html:https://europepmc.org/articles/PMC8336818; pdf:https://europepmc.org/articles/PMC8336818?pdf=render 31234639,https://doi.org/10.1161/circulationaha.118.038814,Use of Genetic Variants Related to Antihypertensive Drugs to Inform on Efficacy and Side Effects.,"Gill D, Georgakis MK, Koskeridis F, Jiang L, Feng Q, Wei WQ, Theodoratou E, Elliott P, Denny JC, Malik R, Evangelou E, Dehghan A, Dichgans M, Tzoulaki I.",,Circulation,2019,2019-06-25,Y,Antihypertensive drugs; Mendelian Randomization Analysis,"Better Care, The Human Phenome",,"

Background

Drug effects can be investigated through natural variation in the genes for their protein targets. The present study aimed to use this approach to explore the potential side effects and repurposing potential of antihypertensive drugs, which are among the most commonly used medications worldwide.

Methods

Genetic proxies for the effect of antihypertensive drug classes were identified as variants in the genes for the corresponding targets that associated with systolic blood pressure at genome-wide significance. Mendelian randomization estimates for drug effects on coronary heart disease and stroke risk were compared with randomized, controlled trial results. A phenome-wide association study in the UK Biobank was performed to identify potential side effects and repurposing opportunities, with findings investigated in the Vanderbilt University biobank (BioVU) and in observational analysis of the UK Biobank.

Results

Suitable genetic proxies for angiotensin-converting enzyme inhibitors, β-blockers, and calcium channel blockers (CCBs) were identified. Mendelian randomization estimates for their effect on coronary heart disease and stroke risk, respectively, were comparable to results from randomized, controlled trials against placebo. A phenome-wide association study in the UK Biobank identified an association of the CCB standardized genetic risk score with increased risk of diverticulosis (odds ratio, 1.02 per standard deviation increase; 95% CI, 1.01-1.04), with a consistent estimate found in BioVU (odds ratio, 1.01; 95% CI, 1.00-1.02). Cox regression analysis of drug use in the UK Biobank suggested that this association was specific to nondihydropyridine CCBs (hazard ratio 1.49 considering thiazide diuretic agents as a comparator; 95% CI, 1.04-2.14) but not dihydropyridine CCBs (hazard ratio, 1.04; 95% CI, 0.83-1.32).

Conclusions

Genetic variants can be used to explore the efficacy and side effects of antihypertensive medications. The identified potential effect of nondihydropyridine CCBs on diverticulosis risk could have clinical implications and warrants further investigation.",,doi:https://doi.org/10.1161/circulationaha.118.038814; doi:https://doi.org/10.1161/CIRCULATIONAHA.118.038814; html:https://europepmc.org/articles/PMC6687408; pdf:https://europepmc.org/articles/PMC6687408?pdf=render 37538810,https://doi.org/10.1016/j.ekir.2023.05.008,Impact of outcome adjudication in kidney disease trials: observations from the Study of Heart and Renal Protection (SHARP).,"Herrington WG, Harper C, Staplin N, Haynes R, Emberson J, Reith C, Hooi LS, Levin A, Wanner C, Baigent C, Landray M, SHARP Collaborative Group.",,Kidney international reports,2023,2023-08-01,Y,Transplantation; Dialysis; Chronic Kidney Disease; Clinical Trials; Adjudication,,,"

Introduction

We aimed to assess opportunities for trial streamlining and the scientific impact of adjudication on kidney and cardiovascular outcomes in CKD.

Methods

We analysed the effects of adjudication of ~2100 maintenance kidney replacement therapy (KRT) and ~1300 major atherosclerotic events (MAEs) recorded in SHARP. We first compared outcome classification before versus after adjudication, and then re-ran randomised comparisons using pre-adjudicated follow-up data.

Results

For maintenance KRT, adjudication had little impact with only 1% of events being refuted (28/2115). Consequently, randomised comparisons using pre-adjudication reports found almost identical results (pre-adjudication: simvastatin/ezetimibe 1038 vs placebo 1077; risk ratio [RR] 0.95, 95%CI 0.88-1.04; post-adjudicated: 1057 vs 1084; RR=0.97, 95%CI 0.89-1.05). For MAEs, about one-quarter of patient reports were refuted (324/1275 [25%]), and reviewing 3538 other potential vascular events and death reports identified only 194 additional MAEs. Nevertheless, randomised analyses using SHARP's pre-adjudicated data alone found similar results to analyses based on adjudicated outcomes (pre-adjudication: 573 vs 702; RR=0.80, 95%CI 0.72-0.89; adjudicated: 526 vs 619; RR=0.83, 95%CI 0.74- 0.94), and also suggested refuted MAEs were likely to represent atherosclerotic disease (RR for refuted MAEs=0.80, 95%CI 0.65-1.00).

Conclusions

These analyses provide three key insights. First, they provide a rationale for nephrology trials not to adjudicate maintenance KRT. Secondly, when an event that mimics an atherosclerotic outcome is not expected to be influenced by the treatment under study (e.g. heart failure), the aim of adjudicating atherosclerotic outcomes should be to remove such events. Lastly, restrictive definitions for the remaining suspected atherosclerotic outcomes may reduce statistical power.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7614871; doi:https://doi.org/10.1016/j.ekir.2023.05.008; html:https://europepmc.org/articles/PMC7614871; pdf:https://europepmc.org/articles/PMC7614871?pdf=render -38553074,https://doi.org/10.1136/bmjopen-2024-085392,Protocol for a mixed-methods study to develop and feasibility test a digital system for the capture of patient-reported outcomes (PROs) in patients receiving chimeric antigen receptor T-cell (CAR-T) therapies (the PRO-CAR-T study).,"Hughes SE, McMullan C, Aiyegbusi OL, Shaw K, Kinsella F, Ferguson P, Khatsuria F, Burns D, Pyatt L, Ansell J, Chakera E, Richardson-Abraham J, Denniston AK, Davies EH, Craddock C, Calvert M.",,BMJ open,2024,2024-03-29,Y,Gene therapy; Quality of life; Haematology; Patient-centered Care; Ehealth; Patient Reported Outcome Measures,,,"

Introduction

Chimeric antigen receptor (CAR) T-cell therapies are novel, potentially curative therapies for haematological malignancies. CAR T-cell therapies are associated with severe toxicities, meaning patients require monitoring during acute and postacute treatment phases. Electronic patient-reported outcomes (ePROs), self-reports of health status provided via online questionnaires, can complement clinician observation with potential to improve patient outcomes. This study will develop and evaluate feasibility of a new ePRO system for CAR-T patients in routine care.

Methods and analysis

Multiphase, mixed-methods study involving multiple stakeholder groups (patients, family members, carers, clinicians, academics/researchers and policy-makers). The intervention development phase comprises a Delphi study to select PRO measures for the digital system, a codesign workshop and consensus meetings to establish thresholds for notifications to the clinical team if a patient reports severe symptoms or side effects. Usability testing will evaluate how users interact with the digital system and, lastly, we will evaluate ePRO system feasibility with 30 CAR-T patients (adults aged 18+ years) when used in addition to usual care. Feasibility study participants will use the ePRO system to submit self-reports of symptoms, treatment tolerability and quality of life at specific time points. The CAR-T clinical team will respond to system notifications triggered by patients' submitted responses with actions in line with standard clinical practice. Feasibility measures will be collected at prespecified time points following CAR T-cell infusion. A qualitative substudy involving patients and clinical team members will explore acceptability of the ePRO system.

Ethics and dissemination

Favourable ethical opinion was granted by the Health and Social Care Research Ethics Committee B(HSC REC B) (ref: 23/NI/0104) on 28 September 2023. Findings will be submitted for publication in high-quality, peer-reviewed journals. Summaries of results, codeveloped with the Blood and Transplant Research Unit Patient and Public Involvement and Engagement group, will be disseminated to all interested groups.

Trial registration number

ISCTRN11232653.",,pdf:https://bmjopen.bmj.com/content/bmjopen/14/3/e085392.full.pdf; doi:https://doi.org/10.1136/bmjopen-2024-085392; html:https://europepmc.org/articles/PMC10982800; pdf:https://europepmc.org/articles/PMC10982800?pdf=render 36936592,https://doi.org/10.1136/bmjmed-2022-000151,Covid-19 variants of concern and pregnancy.,"Stock SJ, Harmer C, Calvert C.",,BMJ medicine,2022,2022-03-02,Y,Pregnancy complications; Covid-19,,,,,pdf:https://bmjmedicine.bmj.com/content/bmjmed/1/1/e000151.full.pdf; doi:https://doi.org/10.1136/bmjmed-2022-000151; html:https://europepmc.org/articles/PMC9951363; pdf:https://europepmc.org/articles/PMC9951363?pdf=render +38553074,https://doi.org/10.1136/bmjopen-2024-085392,Protocol for a mixed-methods study to develop and feasibility test a digital system for the capture of patient-reported outcomes (PROs) in patients receiving chimeric antigen receptor T-cell (CAR-T) therapies (the PRO-CAR-T study).,"Hughes SE, McMullan C, Aiyegbusi OL, Shaw K, Kinsella F, Ferguson P, Khatsuria F, Burns D, Pyatt L, Ansell J, Chakera E, Richardson-Abraham J, Denniston AK, Davies EH, Craddock C, Calvert M.",,BMJ open,2024,2024-03-29,Y,Gene therapy; Quality of life; Haematology; Patient-centered Care; Ehealth; Patient Reported Outcome Measures,,,"

Introduction

Chimeric antigen receptor (CAR) T-cell therapies are novel, potentially curative therapies for haematological malignancies. CAR T-cell therapies are associated with severe toxicities, meaning patients require monitoring during acute and postacute treatment phases. Electronic patient-reported outcomes (ePROs), self-reports of health status provided via online questionnaires, can complement clinician observation with potential to improve patient outcomes. This study will develop and evaluate feasibility of a new ePRO system for CAR-T patients in routine care.

Methods and analysis

Multiphase, mixed-methods study involving multiple stakeholder groups (patients, family members, carers, clinicians, academics/researchers and policy-makers). The intervention development phase comprises a Delphi study to select PRO measures for the digital system, a codesign workshop and consensus meetings to establish thresholds for notifications to the clinical team if a patient reports severe symptoms or side effects. Usability testing will evaluate how users interact with the digital system and, lastly, we will evaluate ePRO system feasibility with 30 CAR-T patients (adults aged 18+ years) when used in addition to usual care. Feasibility study participants will use the ePRO system to submit self-reports of symptoms, treatment tolerability and quality of life at specific time points. The CAR-T clinical team will respond to system notifications triggered by patients' submitted responses with actions in line with standard clinical practice. Feasibility measures will be collected at prespecified time points following CAR T-cell infusion. A qualitative substudy involving patients and clinical team members will explore acceptability of the ePRO system.

Ethics and dissemination

Favourable ethical opinion was granted by the Health and Social Care Research Ethics Committee B(HSC REC B) (ref: 23/NI/0104) on 28 September 2023. Findings will be submitted for publication in high-quality, peer-reviewed journals. Summaries of results, codeveloped with the Blood and Transplant Research Unit Patient and Public Involvement and Engagement group, will be disseminated to all interested groups.

Trial registration number

ISCTRN11232653.",,pdf:https://bmjopen.bmj.com/content/bmjopen/14/3/e085392.full.pdf; doi:https://doi.org/10.1136/bmjopen-2024-085392; html:https://europepmc.org/articles/PMC10982800; pdf:https://europepmc.org/articles/PMC10982800?pdf=render 36058413,https://doi.org/10.1016/j.jinf.2022.08.030,A prospective study of risk factors associated with seroprevalence of SARS-CoV-2 antibodies in healthcare workers at a large UK teaching hospital.,"Cooper DJ, Lear S, Watson L, Shaw A, Ferris M, Doffinger R, Bousfield R, Sharrocks K, Weekes MP, Warne B, Sparkes D, Jones NK, Rivett L, Routledge M, Chaudhry A, Dempsey K, Matson M, Lakha A, Gathercole G, O'Connor O, Wilson E, Shahzad O, Toms K, Thompson R, Halsall I, Halsall D, Houghton S, Papadia S, Kingston N, Stirrups KE, Graves B, Townsend P, Walker N, Stark H, CITIID-NIHR BioResource COVID-19 Collaboration, De Angelis D, Seaman S, Dougan G, Bradley JR, Török ME, Goodfellow I, Baker S.",,The Journal of infection,2022,2022-09-02,Y,Healthcare Workers; Sero-epidemiology; Risk Factor Analysis; Covid-19; Sars-cov-2,,,"

Objectives

To describe the risk factors for SARS-CoV-2 infection in UK healthcare workers (HCWs).

Methods

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

Results

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

Conclusions

Risk of SARS-CoV-2 infection amongst HCWs is highly heterogeneous and influenced by COVID-19 working location, role, age and ethnicity. Increased risk amongst BAME staff cannot be accounted for solely by occupational factors.",,pdf:https://www.repository.cam.ac.uk/bitstream/1810/341240/2/1-s2.0-S016344532200514X-main.pdf; doi:https://doi.org/10.1016/j.jinf.2022.08.030; html:https://europepmc.org/articles/PMC9436870; pdf:https://europepmc.org/articles/PMC9436870?pdf=render 35803473,https://doi.org/10.1016/j.neuroimage.2022.119452,Identifying microstructural changes in diffusion MRI; How to circumvent parameter degeneracy.,"Rafipoor H, Zheng YQ, Griffanti L, Jbabdi S, Cottaar M.",,NeuroImage,2022,2022-07-05,Y,,,,"Biophysical models that attempt to infer real-world quantities from data usually have many free parameters. This over-parameterisation can result in degeneracies in model inversion and render parameter estimation ill-posed. However, in many applications, we are not interested in quantifying the parameters per se, but rather in identifying changes in parameters between experimental conditions (e.g. patients vs controls). Here we present a Bayesian framework to make inference on changes in the parameters of biophysical models even when model inversion is degenerate, which we refer to as Bayesian EstimatioN of CHange (BENCH). We infer the parameter changes in two steps; First, we train models that can estimate the pattern of change in the measurements given any hypothetical direction of change in the parameters using simulations. Next, for any pair of real data sets, we use these pre-trained models to estimate the probability that an observed difference in the data can be explained by each model of change. BENCH is applicable to any type of data and models and particularly useful for biophysical models with parameter degeneracies, where we can assume the change is sparse. In this paper, we apply the approach in the context of microstructural modelling of diffusion MRI data, where the models are usually over-parameterised and not invertible without injecting strong assumptions. Using simulations, we show that in the context of the standard model of white matter our approach is able to identify changes in microstructural parameters from conventional multi-shell diffusion MRI data. We also apply our approach to a subset of subjects from the UK-Biobank Imaging to identify the dominant standard model parameter change in areas of white matter hyperintensities under the assumption that the standard model holds in white matter hyperintensities.",,doi:https://doi.org/10.1016/j.neuroimage.2022.119452; doi:https://doi.org/10.1016/j.neuroimage.2022.119452; html:https://europepmc.org/articles/PMC10933779; pdf:https://europepmc.org/articles/PMC10933779?pdf=render 34345870,https://doi.org/10.1016/j.bbih.2021.100286,The effects of genotype on inflammatory response in hippocampal progenitor cells: A computational approach.,"Lee H, Metz A, McDiarmid A, Palmos A, Lee SH, Curtis CJ, Patel H, Newhouse SJ, Thuret S.",,"Brain, behavior, & immunity - health",2021,2021-08-01,Y,Hippocampus; Neurogenesis; Inflammation; Neural stem cells; in vitro model; single nucleotide polymorphisms SNP; Eqtl; Gene Variants,,,"Cell culture models are valuable tools to study biological mechanisms underlying health and disease in a controlled environment. Although their genotype influences their phenotype, subtle genetic variations in cell lines are rarely characterised and taken into account for in vitro studies. To investigate how the genetic makeup of a cell line might affect the cellular response to inflammation, we characterised the single nucleotide variants (SNPs) relevant to inflammation-related genes in an established hippocampal progenitor cell line (HPC0A07/03C) that is frequently used as an in vitro model for hippocampal neurogenesis (HN). SNPs were identified using a genotyping array, and genes associated with chronic inflammatory and neuroinflammatory response gene ontology terms were retrieved using the AmiGO application. SNPs associated with these genes were then extracted from the genotyping dataset, for which a literature search was conducted, yielding relevant research articles for a total of 17 SNPs. Of these variants, 10 were found to potentially affect hippocampal neurogenesis whereby a majority (n=7) is likely to reduce neurogenesis under inflammatory conditions. Taken together, the existing literature seems to suggest that all stages of hippocampal neurogenesis could be negatively affected due to the genetic makeup in HPC0A07/03C cells under inflammation. Additional experiments will be needed to validate these specific findings in a laboratory setting. However, this computational approach already confirms that in vitro studies in general should control for cell lines subtle genetic variations which could mask or exacerbate findings.",,doi:https://doi.org/10.1016/j.bbih.2021.100286; doi:https://doi.org/10.1016/j.bbih.2021.100286; html:https://europepmc.org/articles/PMC8261829; pdf:https://europepmc.org/articles/PMC8261829?pdf=render -36335192,https://doi.org/10.1038/s41598-022-22218-9,"Genetic insights into smoking behaviours in 10,558 men of African ancestry from continental Africa and the UK.","Piga NN, Boua PR, Soremekun C, Shrine N, Coley K, Brandenburg JT, Tobin MD, Ramsay M, Fatumo S, Choudhury A, Batini C.",,Scientific reports,2022,2022-11-05,Y,,,,"Smoking is a leading risk factor for many of the top ten causes of death worldwide. Of the 1.3 billion smokers globally, 80% live in low- and middle-income countries, where the number of deaths due to tobacco use is expected to double in the next decade according to the World Health Organization. Genetic studies have helped to identify biological pathways for smoking behaviours, but have mostly focussed on individuals of European ancestry or living in either North America or Europe. We performed a genome-wide association study of two smoking behaviour traits in 10,558 men of African ancestry living in five African countries and the UK. Eight independent variants were associated with either smoking initiation or cessation at P-value < 5 × 10-6, four being monomorphic or rare in European populations. Gene prioritisation strategy highlighted five genes, including SEMA6D, previously described as associated with several smoking behaviour traits. These results confirm the importance of analysing underrepresented populations in genetic epidemiology, and the urgent need for larger genomic studies to boost discovery power to better understand smoking behaviours, as well as many other traits.",,pdf:https://www.nature.com/articles/s41598-022-22218-9.pdf; doi:https://doi.org/10.1038/s41598-022-22218-9; html:https://europepmc.org/articles/PMC9637114; pdf:https://europepmc.org/articles/PMC9637114?pdf=render 35212847,https://doi.org/10.1007/s00455-022-10425-5,Identifying Dysphagia and Demographic Associations in Older Adults Using Electronic Health Records: A National Longitudinal Observational Study in Wales (United Kingdom) 2008-2018.,"Hollinghurst J, Smithard DG.",,Dysphagia,2022,2022-02-25,Y,Prevalence; Frailty; epidemiology; Old Age; Dysphagia; Deprivation,,,"Dysphagia is increasingly being recognised as a geriatric syndrome (giant). There is limited research on the prevalence of dysphagia using electronic health records. To investigate associations between dysphagia, as recorded in electronic health records and age, frailty using the electronic frailty index, gender and deprivation (Welsh index of multiple deprivation). A Cross-sectional longitudinal cohort study in over 400,000 older adults was undertaken (65 +) in Wales (United Kingdom) per year from 2008 to 2018. We used the secure anonymised information linkage databank to identify dysphagia diagnoses in primary and secondary care. We used chi-squared tests and multivariate logistic regression to investigate associations between dysphagia diagnosis and age, frailty (using the electronic Frailty index), gender and deprivation. Data indicated < 1% of individuals were recorded as having a dysphagia diagnosis per year. We found dysphagia to be statistically significantly associated with older age, more severe frailty and individuals from more deprived areas. Multivariate analyses indicated increased odds ratios [OR (95% confidence intervals)] for a dysphagia diagnosis with increased age [reference 65-74: aged 75-84 OR 1.09 (1.07, 1.12), 85 + OR 1.23 (1.20, 1.27)], frailty (reference fit: mild frailty 2.45 (2.38, 2.53), moderate frailty 4.64 (4.49, 4.79) and severe frailty 7.87 (7.55, 8.21)] and individuals from most deprived areas [reference 5. Least deprived, 1. Most deprived: 1.10 (1.06, 1.14)]. The study has identified that prevalence of diagnosed dysphagia is lower than previously reported. This study has confirmed the association of dysphagia with increasing age and frailty. A previously unreported association with deprivation has been identified. Deprivation is a multifactorial problem that is known to affect health outcomes, and the association with dysphagia should not be a surprise. Research in to this relationship is indicated.",,pdf:https://link.springer.com/content/pdf/10.1007/s00455-022-10425-5.pdf; doi:https://doi.org/10.1007/s00455-022-10425-5; html:https://europepmc.org/articles/PMC9643178; pdf:https://europepmc.org/articles/PMC9643178?pdf=render +36335192,https://doi.org/10.1038/s41598-022-22218-9,"Genetic insights into smoking behaviours in 10,558 men of African ancestry from continental Africa and the UK.","Piga NN, Boua PR, Soremekun C, Shrine N, Coley K, Brandenburg JT, Tobin MD, Ramsay M, Fatumo S, Choudhury A, Batini C.",,Scientific reports,2022,2022-11-05,Y,,,,"Smoking is a leading risk factor for many of the top ten causes of death worldwide. Of the 1.3 billion smokers globally, 80% live in low- and middle-income countries, where the number of deaths due to tobacco use is expected to double in the next decade according to the World Health Organization. Genetic studies have helped to identify biological pathways for smoking behaviours, but have mostly focussed on individuals of European ancestry or living in either North America or Europe. We performed a genome-wide association study of two smoking behaviour traits in 10,558 men of African ancestry living in five African countries and the UK. Eight independent variants were associated with either smoking initiation or cessation at P-value < 5 × 10-6, four being monomorphic or rare in European populations. Gene prioritisation strategy highlighted five genes, including SEMA6D, previously described as associated with several smoking behaviour traits. These results confirm the importance of analysing underrepresented populations in genetic epidemiology, and the urgent need for larger genomic studies to boost discovery power to better understand smoking behaviours, as well as many other traits.",,pdf:https://www.nature.com/articles/s41598-022-22218-9.pdf; doi:https://doi.org/10.1038/s41598-022-22218-9; html:https://europepmc.org/articles/PMC9637114; pdf:https://europepmc.org/articles/PMC9637114?pdf=render 37981722,https://doi.org/10.1093/aje/kwad232,Inconsistency in UK Biobank Event Definitions From Different Data Sources and Its Impact on Bias and Generalizability: A Case Study of Venous Thromboembolism.,"Bassett E, Broadbent J, Gill D, Burgess S, Mason AM.",,American journal of epidemiology,2024,2024-05-01,Y,Pulmonary embolism; Bias; Deep vein thrombosis; Venous Thromboembolism; Generalizability; Uk Biobank; Sociodemographic Characteristics; Representativeness; Event Definition,,,"The UK Biobank study contains several sources of diagnostic data, including hospital inpatient data and data on self-reported conditions for approximately 500,000 participants and primary-care data for approximately 177,000 participants (35%). Epidemiologic investigations require a primary disease definition, but whether to combine data sources to maximize statistical power or focus on only 1 source to ensure a consistent outcome is not clear. The consistency of disease definitions was investigated for venous thromboembolism (VTE) by evaluating overlap when defining cases from 3 sources: hospital inpatient data, primary-care reports, and self-reported questionnaires. VTE cases showed little overlap between data sources, with only 6% of reported events for persons with primary-care data being identified by all 3 sources (hospital, primary-care, and self-reports), while 71% appeared in only 1 source. Deep vein thrombosis-only events represented 68% of self-reported VTE cases and 36% of hospital-reported VTE cases, while pulmonary embolism-only events represented 20% of self-reported VTE cases and 50% of hospital-reported VTE cases. Additionally, different distributions of sociodemographic characteristics were observed; for example, patients in 46% of hospital-reported VTE cases were female, compared with 58% of self-reported VTE cases. These results illustrate how seemingly neutral decisions taken to improve data quality can affect the representativeness of a data set.",,pdf:https://academic.oup.com/aje/advance-article-pdf/doi/10.1093/aje/kwad232/53485177/kwad232.pdf; doi:https://doi.org/10.1093/aje/kwad232; html:https://europepmc.org/articles/PMC11074710; pdf:https://europepmc.org/articles/PMC11074710?pdf=render 34791170,https://doi.org/10.1093/eurheartj/ehab759,A sex-specific prediction model is not enough to achieve equality for women in preventative cardiovascular medicine.,"Kimenai DM, Shah ASV, Mills NL.",,European heart journal,2022,2022-01-01,Y,,,,,,pdf:https://academic.oup.com/eurheartj/article-pdf/43/3/239/42296399/ehab759.pdf; doi:https://doi.org/10.1093/eurheartj/ehab759; html:https://europepmc.org/articles/PMC8790764; pdf:https://europepmc.org/articles/PMC8790764?pdf=render 34062542,https://doi.org/10.1159/000517521,Structural Endpoints and Outcome Measures in Uveitis.,"Wintergerst MWM, Liu X, Terheyden JH, Pohlmann D, Li JQ, Montesano G, Ometto G, Holz FG, Crabb DP, Pleyer U, Heinz C, Denniston AK, Finger RP.",,Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde,2021,2021-06-01,N,Biomarker; Uveitis; Outcome; Outcome Measure; Endpoint; Imaging Biomarker; Inflammatory Eye Diseases; Instrument-based Measure,,,"Most uveitis entities are rare diseases but, taken together, are responsible for 5-10% of worldwide visual impairment which largely affects persons of working age. As with many rare diseases, there is a lack of high-level evidence regarding its clinical management, partly due to a dearth of reliable and objective quantitative endpoints for clinical trials. This review provides an overview of available structural outcome measures for uveitis disease activity and damage in an anatomical order from the anterior to the posterior segment of the eye. While there is a multitude of available structural outcome measures, not all might qualify as endpoints for clinical uveitis trials, and thorough testing of applicability is warranted. Furthermore, a consensus on endpoint definition, standardization, and ""core outcomes"" is required. As stipulated by regulatory agencies, endpoints should be precisely defined, clinically important, internally consistent, reliable, responsive to treatment, and relevant for the respective subtype of uveitis. Out of all modalities used for assessment of the reviewed structural outcome measures, optical coherence tomography, color fundus photography, fundus autofluorescence, and fluorescein/indocyanine green angiography represent current ""core modalities"" for reliable and objective quantification of uveitis outcome measures, based on their practical availability and the evidence provided so far.",,pdf:https://www.karger.com/Article/Pdf/517521; doi:https://doi.org/10.1159/000517521 -37474660,https://doi.org/10.1038/s41591-023-02445-x,Considerations for patient and public involvement and engagement in health research.,"Aiyegbusi OL, McMullan C, Hughes SE, Turner GM, Subramanian A, Hotham R, Davies EH, Frost C, Alder Y, Agyen L, Buckland L, Camaradou J, Chong A, Jeyes F, Kumar S, Matthews KL, Moore P, Ormerod J, Price G, Saint-Cricq M, Stanton D, Walker A, Haroon S, Denniston AK, Calvert MJ, TLC Study Group.",,Nature medicine,2023,2023-07-20,N,,,,"Patient and public involvement and engagement (PPIE) can provide valuable insights into the experiences of those living with and affected by a disease or health condition. Inclusive collaboration between patients, the public and researchers can lead to productive relationships, ensuring that health research addresses patient needs. Guidelines are available to support effective PPIE; however, evaluation of the impact of PPIE strategies in health research is limited. In this Review, we evaluate the impact of PPIE in the 'Therapies for Long COVID in non-hospitalised individuals' (TLC) Study, using a combination of group discussions and interviews with patient partners and researchers. We identify areas of good practice and reflect on areas for improvement. Using these insights and the results of a survey, we synthesize two checklists of considerations for PPIE, and we propose that research teams use these checklists to optimize the impact of PPIE for both patients and researchers in future studies.",,doi:https://doi.org/10.1038/s41591-023-02445-x 35434685,https://doi.org/10.1016/j.lanepe.2022.100381,Dosing interval strategies for two-dose COVID-19 vaccination in 13 middle-income countries of Europe: Health impact modelling and benefit-risk analysis.,"Liu Y, Pearson CAB, Sandmann FG, Barnard RC, Kim JH, CMMID COVID-19 Working Group, Flasche S, Jit M, Abbas K.",,The Lancet regional health. Europe,2022,2022-04-11,Y,"Quantitative Methods; Mathematical Modelling; Public Health Intervention; Vaccine Policy; Ve, Vaccine Efficacy; Covid-19; Sars-cov-2; Voc, Variant Of Concern; Mic, Middle Income Country; Aefi, Adverse Events Following Immunisation",,,"

Background

In settings where the COVID-19 vaccine supply is constrained, extending the intervals between the first and second doses of the COVID-19 vaccine may allow more people receive their first doses earlier. Our aim is to estimate the health impact of COVID-19 vaccination alongside benefit-risk assessment of different dosing intervals in 13 middle-income countries (MICs) of Europe.

Methods

We fitted a dynamic transmission model to country-level daily reported COVID-19 mortality in 13 MICs in Europe (Albania, Armenia, Azerbaijan, Belarus, Bosnia and Herzegovina, Bulgaria, Georgia, Republic of Moldova, Russian Federation, Serbia, North Macedonia, Turkey, and Ukraine). A vaccine product with characteristics similar to those of the Oxford/AstraZeneca COVID-19 (AZD1222) vaccine was used in the base case scenario and was complemented by sensitivity analyses around efficacies similar to other COVID-19 vaccines. Both fixed dosing intervals at 4, 8, 12, 16, and 20 weeks and dose-specific intervals that prioritise specific doses for certain age groups were tested. Optimal intervals minimise COVID-19 mortality between March 2021 and December 2022. We incorporated the emergence of variants of concern (VOCs) into the model and conducted a benefit-risk assessment to quantify the tradeoff between health benefits versus adverse events following immunisation.

Findings

In all countries modelled, optimal strategies are those that prioritise the first doses among older adults (60+ years) or adults (20+ years), which lead to dosing intervals longer than six months. In comparison, a four-week fixed dosing interval may incur 10.1% [range: 4.3% - 19.0%; n = 13 (countries)] more deaths. The rapid waning of the immunity induced by the first dose (i.e. with means ranging 60-120 days as opposed to 360 days in the base case) resulted in shorter optimal dosing intervals of 8-20 weeks. Benefit-risk ratios were the highest for fixed dosing intervals of 8-12 weeks.

Interpretation

We infer that longer dosing intervals of over six months could reduce COVID-19 mortality in MICs of Europe. Certain parameters, such as rapid waning of first-dose induced immunity and increased immune escape through the emergence of VOCs, could significantly shorten the optimal dosing intervals.

Funding

World Health Organization.",,doi:https://doi.org/10.1016/j.lanepe.2022.100381; doi:https://doi.org/10.1016/j.lanepe.2022.100381; html:https://europepmc.org/articles/PMC8996067; pdf:https://europepmc.org/articles/PMC8996067?pdf=render +37474660,https://doi.org/10.1038/s41591-023-02445-x,Considerations for patient and public involvement and engagement in health research.,"Aiyegbusi OL, McMullan C, Hughes SE, Turner GM, Subramanian A, Hotham R, Davies EH, Frost C, Alder Y, Agyen L, Buckland L, Camaradou J, Chong A, Jeyes F, Kumar S, Matthews KL, Moore P, Ormerod J, Price G, Saint-Cricq M, Stanton D, Walker A, Haroon S, Denniston AK, Calvert MJ, TLC Study Group.",,Nature medicine,2023,2023-07-20,N,,,,"Patient and public involvement and engagement (PPIE) can provide valuable insights into the experiences of those living with and affected by a disease or health condition. Inclusive collaboration between patients, the public and researchers can lead to productive relationships, ensuring that health research addresses patient needs. Guidelines are available to support effective PPIE; however, evaluation of the impact of PPIE strategies in health research is limited. In this Review, we evaluate the impact of PPIE in the 'Therapies for Long COVID in non-hospitalised individuals' (TLC) Study, using a combination of group discussions and interviews with patient partners and researchers. We identify areas of good practice and reflect on areas for improvement. Using these insights and the results of a survey, we synthesize two checklists of considerations for PPIE, and we propose that research teams use these checklists to optimize the impact of PPIE for both patients and researchers in future studies.",,doi:https://doi.org/10.1038/s41591-023-02445-x 37730620,https://doi.org/10.1186/s13643-023-02333-y,What is known about what works in community-involved decision-making relating to urban green and blue spaces? A realist review protocol.,"Rahtz E, Bell SL, Nurse A, Wheeler BW, Guell C, Elliott LR, Thompson CW, McDougall CW, Lovell R.",,Systematic reviews,2023,2023-09-20,Y,,,,"

Background

There is now a relatively well-established evidence base suggesting that greener living environments and time spent in urban green and blue spaces (UGBS) can be beneficial for human health and wellbeing. However, benefits are not universal and there remain widespread social inequalities in access to such resources and experiences, particularly along axes of class, race, ethnicity, age and disability, and in relation to efforts to increase the availability and accessibility of such spaces. These injustices often relate to distributive, procedural and recognition-based processes. There is growing interest in how to ensure that efforts to increase access to or use of UGBS (whether through infrastructural or social programmes) result in equitable outcomes whilst minimising potential for exacerbating existing inequalities and injustices. Community engagement is considered an important step towards more inclusive UGBS decision-making, from planning and design to management and maintenance processes. It is thought to contribute to better and more widely trusted decisions, enhanced democracy, community satisfaction, civic interest and feelings of green space ownership, and greater longevity of UGBS projects. However, uneven representation and barriers to participation can create imbalances and undermine these benefits.

Methods

An iterative, multi-stage realist-inspired review will be conducted to ask what works, in what context and in what ways relating to the meaningful involvement of communities in UGBS decision-making, focusing on the skills, capacities and capabilities of different stakeholders and the role of contexts and processes. 'Effectiveness' (or what works) will be understood as a multifaceted outcome, encompassing both the processes and results of community engagement efforts. Following a scoping stage to identify initial programme theory, inclusion/exclusion criteria and derive search terms, relevant databases and grey literature will be searched to identify interdisciplinary literature in two phases. The first phase will be used to further develop programme theories, which will be articulated as 'if then' statements. The second phase searches will be used to identify sources to further explore and evidence the programme and formal theory. We will assess all includable evidence for conceptual richness, prioritising more conceptually rich sources if needed.

Discussion

The realist synthesis will explore the key context, mechanism and outcome configurations that appear to explain if and how different approaches to community-involved UGBS decision-making are or are not effective. We will consider factors such as different conceptualisations of community, and if and how they have been involved in UGBS decision-making; the types of tools and approaches used; and the socio-cultural and political or governance structures within which decision-making takes place.",,pdf:https://systematicreviewsjournal.biomedcentral.com/counter/pdf/10.1186/s13643-023-02333-y; doi:https://doi.org/10.1186/s13643-023-02333-y; html:https://europepmc.org/articles/PMC10512649; pdf:https://europepmc.org/articles/PMC10512649?pdf=render 30102210,https://doi.org/10.1016/s1470-2045(18)30425-x,A roadmap for restoring trust in Big Data.,"Lawler M, Morris AD, Sullivan R, Birney E, Middleton A, Makaroff L, Knoppers BM, Horgan D, Eggermont A.",,The Lancet. Oncology,2018,2018-08-01,N,,,,,,doi:https://doi.org/10.1016/S1470-2045(18)30425-X 33453763,https://doi.org/10.1016/s2468-1253(21)00005-4,Impact of the COVID-19 pandemic on the detection and management of colorectal cancer in England: a population-based study.,"Morris EJA, Goldacre R, Spata E, Mafham M, Finan PJ, Shelton J, Richards M, Spencer K, Emberson J, Hollings S, Curnow P, Gair D, Sebag-Montefiore D, Cunningham C, Rutter MD, Nicholson BD, Rashbass J, Landray M, Collins R, Casadei B, Baigent C.",,The lancet. Gastroenterology & hepatology,2021,2021-01-15,Y,,,,"

Background

There are concerns that the COVID-19 pandemic has had a negative effect on cancer care but there is little direct evidence to quantify any effect. This study aims to investigate the impact of the COVID-19 pandemic on the detection and management of colorectal cancer in England.

Methods

Data were extracted from four population-based datasets spanning NHS England (the National Cancer Cancer Waiting Time Monitoring, Monthly Diagnostic, Secondary Uses Service Admitted Patient Care and the National Radiotherapy datasets) for all referrals, colonoscopies, surgical procedures, and courses of rectal radiotherapy from Jan 1, 2019, to Oct 31, 2020, related to colorectal cancer in England. Differences in patterns of care were investigated between 2019 and 2020. Percentage reductions in monthly numbers and proportions were calculated.

Findings

As compared to the monthly average in 2019, in April, 2020, there was a 63% (95% CI 53-71) reduction (from 36 274 to 13 440) in the monthly number of 2-week referrals for suspected cancer and a 92% (95% CI 89-95) reduction in the number of colonoscopies (from 46 441 to 3484). Numbers had just recovered by October, 2020. This resulted in a 22% (95% CI 8-34) relative reduction in the number of cases referred for treatment (from a monthly average of 2781 in 2019 to 2158 referrals in April, 2020). By October, 2020, the monthly rate had returned to 2019 levels but did not exceed it, suggesting that, from April to October, 2020, over 3500 fewer people had been diagnosed and treated for colorectal cancer in England than would have been expected. There was also a 31% (95% CI 19-42) relative reduction in the numbers receiving surgery in April, 2020, and a lower proportion of laparoscopic and a greater proportion of stoma-forming procedures, relative to the monthly average in 2019. By October, 2020, laparoscopic surgery and stoma rates were similar to 2019 levels. For rectal cancer, there was a 44% (95% CI 17-76) relative increase in the use of neoadjuvant radiotherapy in April, 2020, relative to the monthly average in 2019, due to greater use of short-course regimens. Although in June, 2020, there was a drop in the use of short-course regimens, rates remained above 2019 levels until October, 2020.

Interpretation

The COVID-19 pandemic has led to a sustained reduction in the number of people referred, diagnosed, and treated for colorectal cancer. By October, 2020, achievement of care pathway targets had returned to 2019 levels, albeit with smaller volumes of patients and with modifications to usual practice. As pressure grows in the NHS due to the second wave of COVID-19, urgent action is needed to address the growing burden of undetected and untreated colorectal cancer in England.

Funding

Cancer Research UK, the Medical Research Council, Public Health England, Health Data Research UK, NHS Digital, and the National Institute for Health Research Oxford Biomedical Research Centre.",,pdf:http://www.thelancet.com/article/S2468125321000054/pdf; doi:https://doi.org/10.1016/S2468-1253(21)00005-4; html:https://europepmc.org/articles/PMC7808901; pdf:https://europepmc.org/articles/PMC7808901?pdf=render -37872160,https://doi.org/10.1038/s41467-023-42284-5,"Genome-wide association study of thyroid-stimulating hormone highlights new genes, pathways and associations with thyroid disease.","Williams AT, Chen J, Coley K, Batini C, Izquierdo A, Packer R, Abner E, Kanoni S, Shepherd DJ, Free RC, Hollox EJ, Brunskill NJ, Ntalla I, Reeve N, Brightling CE, Venn L, Adams E, Bee C, Wallace SE, Pareek M, Hansell AL, Esko T, Estonian Biobank Research Team, Stow D, Jacobs BM, van Heel DA, Genes & Health Research Team, Hennah W, Rao BS, Dudbridge F, Wain LV, Shrine N, Tobin MD, John C.",,Nature communications,2023,2023-10-23,Y,,,,"Thyroid hormones play a critical role in regulation of multiple physiological functions and thyroid dysfunction is associated with substantial morbidity. Here, we use electronic health records to undertake a genome-wide association study of thyroid-stimulating hormone (TSH) levels, with a total sample size of 247,107. We identify 158 novel genetic associations, more than doubling the number of known associations with TSH, and implicate 112 putative causal genes, of which 76 are not previously implicated. A polygenic score for TSH is associated with TSH levels in African, South Asian, East Asian, Middle Eastern and admixed American ancestries, and associated with hypothyroidism and other thyroid disease in South Asians. In Europeans, the TSH polygenic score is associated with thyroid disease, including thyroid cancer and age-of-onset of hypothyroidism and hyperthyroidism. We develop pathway-specific genetic risk scores for TSH levels and use these in phenome-wide association studies to identify potential consequences of pathway perturbation. Together, these findings demonstrate the potential utility of genetic associations to inform future therapeutics and risk prediction for thyroid diseases.",,pdf:https://www.nature.com/articles/s41467-023-42284-5.pdf; doi:https://doi.org/10.1038/s41467-023-42284-5; html:https://europepmc.org/articles/PMC10593800; pdf:https://europepmc.org/articles/PMC10593800?pdf=render 32619549,https://doi.org/10.1016/j.cels.2020.05.012,Ultra-High-Throughput Clinical Proteomics Reveals Classifiers of COVID-19 Infection.,"Messner CB, Demichev V, Wendisch D, Michalick L, White M, Freiwald A, Textoris-Taube K, Vernardis SI, Egger AS, Kreidl M, Ludwig D, Kilian C, Agostini F, Zelezniak A, Thibeault C, Pfeiffer M, Hippenstiel S, Hocke A, von Kalle C, Campbell A, Hayward C, Porteous DJ, Marioni RE, Langenberg C, Lilley KS, Kuebler WM, Mülleder M, Drosten C, Suttorp N, Witzenrath M, Kurth F, Sander LE, Ralser M.",,Cell systems,2020,2020-06-02,Y,Mass spectrometry; High-throughput Proteomics; Swath-ms; Antiviral Immune Response; Clinical Classifiers; Covid-19 Infection,,,"The COVID-19 pandemic is an unprecedented global challenge, and point-of-care diagnostic classifiers are urgently required. Here, we present a platform for ultra-high-throughput serum and plasma proteomics that builds on ISO13485 standardization to facilitate simple implementation in regulated clinical laboratories. Our low-cost workflow handles up to 180 samples per day, enables high precision quantification, and reduces batch effects for large-scale and longitudinal studies. We use our platform on samples collected from a cohort of early hospitalized cases of the SARS-CoV-2 pandemic and identify 27 potential biomarkers that are differentially expressed depending on the WHO severity grade of COVID-19. They include complement factors, the coagulation system, inflammation modulators, and pro-inflammatory factors upstream and downstream of interleukin 6. All protocols and software for implementing our approach are freely available. In total, this work supports the development of routine proteomic assays to aid clinical decision making and generate hypotheses about potential COVID-19 therapeutic targets.",,pdf:http://www.cell.com/article/S2405471220301976/pdf; doi:https://doi.org/10.1016/j.cels.2020.05.012; html:https://europepmc.org/articles/PMC7264033 32212911,https://doi.org/10.1161/jaha.119.013684,Prognostic significance of troponin level in 3121 patients presenting with atrial fibrillation (The NIHR Health Informatics Collaborative TROP-AF study).,"Kaura A, Arnold AD, Panoulas V, Glampson B, Davies J, Mulla A, Woods K, Omigie J, Shah AD, Channon KM, Weber JN, Thursz MR, Elliott P, Hemingway H, Williams B, Asselbergs FW, O'Sullivan M, Lord GM, Melikian N, Lefroy DC, Francis DP, Shah AM, Kharbanda R, Perera D, Patel RS, Mayet J.",,Journal of the American Heart Association,2020,2020-03-26,Y,Troponin; Mortality; Atrial fibrillation; coronary artery disease; angiography,,,"Background Patients presenting with atrial fibrillation (AF) often undergo a blood test to measure troponin, but interpretation of the result is impeded by uncertainty about its clinical importance. We investigated the relationship between troponin level, coronary angiography, and all-cause mortality in real-world patients presenting with AF. Methods and Results We used National Institute of Health Research Health Informatics Collaborative data to identify patients admitted between 2010 and 2017 at 5 tertiary centers in the United Kingdom with a primary diagnosis of AF. Peak troponin results were scaled as multiples of the upper limit of normal. A total of 3121 patients were included in the analysis. Over a median follow-up of 1462 (interquartile range, 929-1975) days, there were 586 deaths (18.8%). The adjusted hazard ratio for mortality associated with a positive troponin (value above upper limit of normal) was 1.20 (95% CI, 1.01-1.43; P<0.05). Higher troponin levels were associated with higher risk of mortality, reaching a maximum hazard ratio of 2.6 (95% CI, 1.9-3.4) at ≈250 multiples of the upper limit of normal. There was an exponential relationship between higher troponin levels and increased odds of coronary angiography. The mortality risk was 36% lower in patients undergoing coronary angiography than in those who did not (adjusted hazard ratio, 0.61; 95% CI, 0.42-0.89; P=0.01). Conclusions Increased troponin was associated with increased risk of mortality in patients presenting with AF. The lower hazard ratio in patients undergoing invasive management raises the possibility that the clinical importance of troponin release in AF may be mediated by coronary artery disease, which may be responsive to revascularization.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/JAHA.119.013684; doi:https://doi.org/10.1161/JAHA.119.013684; html:https://europepmc.org/articles/PMC7428631; pdf:https://europepmc.org/articles/PMC7428631?pdf=render +37872160,https://doi.org/10.1038/s41467-023-42284-5,"Genome-wide association study of thyroid-stimulating hormone highlights new genes, pathways and associations with thyroid disease.","Williams AT, Chen J, Coley K, Batini C, Izquierdo A, Packer R, Abner E, Kanoni S, Shepherd DJ, Free RC, Hollox EJ, Brunskill NJ, Ntalla I, Reeve N, Brightling CE, Venn L, Adams E, Bee C, Wallace SE, Pareek M, Hansell AL, Esko T, Estonian Biobank Research Team, Stow D, Jacobs BM, van Heel DA, Genes & Health Research Team, Hennah W, Rao BS, Dudbridge F, Wain LV, Shrine N, Tobin MD, John C.",,Nature communications,2023,2023-10-23,Y,,,,"Thyroid hormones play a critical role in regulation of multiple physiological functions and thyroid dysfunction is associated with substantial morbidity. Here, we use electronic health records to undertake a genome-wide association study of thyroid-stimulating hormone (TSH) levels, with a total sample size of 247,107. We identify 158 novel genetic associations, more than doubling the number of known associations with TSH, and implicate 112 putative causal genes, of which 76 are not previously implicated. A polygenic score for TSH is associated with TSH levels in African, South Asian, East Asian, Middle Eastern and admixed American ancestries, and associated with hypothyroidism and other thyroid disease in South Asians. In Europeans, the TSH polygenic score is associated with thyroid disease, including thyroid cancer and age-of-onset of hypothyroidism and hyperthyroidism. We develop pathway-specific genetic risk scores for TSH levels and use these in phenome-wide association studies to identify potential consequences of pathway perturbation. Together, these findings demonstrate the potential utility of genetic associations to inform future therapeutics and risk prediction for thyroid diseases.",,pdf:https://www.nature.com/articles/s41467-023-42284-5.pdf; doi:https://doi.org/10.1038/s41467-023-42284-5; html:https://europepmc.org/articles/PMC10593800; pdf:https://europepmc.org/articles/PMC10593800?pdf=render 33928785,https://doi.org/10.1161/circulationaha.120.049844,Unfolded Protein Response as a Compensatory Mechanism and Potential Therapeutic Target in PLN R14del Cardiomyopathy.,"Feyen DAM, Perea-Gil I, Maas RGC, Harakalova M, Gavidia AA, Arthur Ataam J, Wu TH, Vink A, Pei J, Vadgama N, Suurmeijer AJ, Te Rijdt WP, Vu M, Amatya PL, Prado M, Zhang Y, Dunkenberger L, Sluijter JPG, Sallam K, Asselbergs FW, Mercola M, Karakikes I.",,Circulation,2021,2021-04-30,N,"Unfolded protein response; Models, Biological; Induced Pluripotent Stem Cells; Phospholamban; Cardiomyopathy, Dilated; Sequence Analysis, Rna",,,"

Background

Phospholamban (PLN) is a critical regulator of calcium cycling and contractility in the heart. The loss of arginine at position 14 in PLN (R14del) is associated with dilated cardiomyopathy with a high prevalence of ventricular arrhythmias. How the R14 deletion causes dilated cardiomyopathy is poorly understood, and there are no disease-specific therapies.

Methods

We used single-cell RNA sequencing to uncover PLN R14del disease mechanisms in human induced pluripotent stem cells (hiPSC-CMs). We used both 2-dimensional and 3-dimensional functional contractility assays to evaluate the impact of modulating disease-relevant pathways in PLN R14del hiPSC-CMs.

Results

Modeling of the PLN R14del cardiomyopathy with isogenic pairs of hiPSC-CMs recapitulated the contractile deficit associated with the disease in vitro. Single-cell RNA sequencing revealed the induction of the unfolded protein response (UPR) pathway in PLN R14del compared with isogenic control hiPSC-CMs. The activation of UPR was also evident in the hearts from PLN R14del patients. Silencing of each of the 3 main UPR signaling branches (IRE1, ATF6, or PERK) by siRNA exacerbated the contractile dysfunction of PLN R14del hiPSC-CMs. We explored the therapeutic potential of activating the UPR with a small molecule activator, BiP (binding immunoglobulin protein) inducer X. PLN R14del hiPSC-CMs treated with BiP protein inducer X showed a dose-dependent amelioration of the contractility deficit in both 2-dimensional cultures and 3-dimensional engineered heart tissues without affecting calcium homeostasis.

Conclusions

Together, these findings suggest that the UPR exerts a protective effect in the setting of PLN R14del cardiomyopathy and that modulation of the UPR might be exploited therapeutically.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCULATIONAHA.120.049844; doi:https://doi.org/10.1161/CIRCULATIONAHA.120.049844; html:https://europepmc.org/articles/PMC8667423; pdf:https://europepmc.org/articles/PMC8667423?pdf=render; doi:https://doi.org/10.1161/circulationaha.120.049844 31657946,https://doi.org/10.1164/rccm.201903-0673oc,Long-Term Outcomes after Severe Traumatic Brain Injury in Older Adults. A Registry-based Cohort Study.,"Maiden MJ, Cameron PA, Rosenfeld JV, Cooper DJ, McLellan S, Gabbe BJ.",,American journal of respiratory and critical care medicine,2020,2020-01-01,N,Elderly; Brain trauma; Functional Performance; Critical Care Outcomes,,,"Rationale: Older adults (≥65 yr old) account for an increasing proportion of patients with severe traumatic brain injury (TBI), yet clinical trials and outcome studies contain relatively few of these patients.Objectives: To determine functional status 6 months after severe TBI in older adults, changes in this status over 2 years, and outcome covariates.Methods: This was a registry-based cohort study of older adults who were admitted to hospitals in Victoria, Australia, between 2007 and 2016 with severe TBI. Functional status was assessed with Glasgow Outcome Scale Extended (GOSE) 6, 12, and 24 months after injury. Cohort subgroups were defined by admission to an ICU. Features associated with functional outcome were assessed from the ICU subgroup.Measurements and Main Results: The study included 540 older adults who had been hospitalized with severe TBI over the 10-year period; 428 (79%) patients died in hospital, and 456 (84%) died 6 months after injury. There were 277 patients who had not been admitted to an ICU; at 6 months, 268 (97%) had died, 8 (3%) were dependent (GOSE 2-4), and 1 (0.4%) was functionally independent (GOSE 5-8). There were 263 patients who had been admitted to an ICU; at 6 months, 188 (73%) had died, 39 (15%) were dependent, and 32 (12%) were functionally independent. These proportions did not change over longer follow-up. The only clinical features associated with a lower rate of functional independence were Injury Severity Score ≥25 (adjusted odds ratio, 0.24 [95% confidence interval, 0.09-0.67]; P = 0.007) and older age groups (P = 0.017).Conclusions: Severe TBI in older adults is a condition with very high mortality, and few recover to functional independence.",,doi:https://doi.org/10.1164/rccm.201903-0673OC 35568032,https://doi.org/10.1016/j.ajhg.2022.04.009,Whole-exome sequencing identifies rare genetic variants associated with human plasma metabolites.,"Bomba L, Walter K, Guo Q, Surendran P, Kundu K, Nongmaithem S, Karim MA, Stewart ID, Langenberg C, Danesh J, Di Angelantonio E, Roberts DJ, Ouwehand WH, INTERVAL study, Dunham I, Butterworth AS, Soranzo N.",,American journal of human genetics,2022,2022-05-13,Y,Sequencing; Proteomics; drug targets; Metabolomics; Endophenotypes; Loss-of-function; Metabolon; Wgs; Wes; Rare Genetic Variant,,,"Metabolite levels measured in the human population are endophenotypes for biological processes. We combined sequencing data for 3,924 (whole-exome sequencing, WES, discovery) and 2,805 (whole-genome sequencing, WGS, replication) donors from a prospective cohort of blood donors in England. We used multiple approaches to select and aggregate rare genetic variants (minor allele frequency [MAF] < 0.1%) in protein-coding regions and tested their associations with 995 metabolites measured in plasma by using ultra-high-performance liquid chromatography-tandem mass spectrometry. We identified 40 novel associations implicating rare coding variants (27 genes and 38 metabolites), of which 28 (15 genes and 28 metabolites) were replicated. We developed algorithms to prioritize putative driver variants at each locus and used mediation and Mendelian randomization analyses to test directionality at associations of metabolite and protein levels at the ACY1 locus. Overall, 66% of reported associations implicate gene targets of approved drugs or bioactive drug-like compounds, contributing to drug targets' validating efforts.",,pdf:https://www.repository.cam.ac.uk/bitstream/1810/337646/3/1-s2.0-S0002929722001574-main.pdf; doi:https://doi.org/10.1016/j.ajhg.2022.04.009; html:https://europepmc.org/articles/PMC9247822; pdf:https://europepmc.org/articles/PMC9247822?pdf=render @@ -1865,26 +1865,26 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 35386996,https://doi.org/10.3389/falgy.2021.677677,Purinergic Receptors in the Airways: Potential Therapeutic Targets for Asthma?,"Thompson RJ, Sayers I, Kuokkanen K, Hall IP.",,Frontiers in allergy,2021,2021-05-31,Y,Lung; Bioinformatics; Asthma; airway; Gene Expression; purinergic receptor; Purinergic Signaling,,,"Extracellular ATP functions as a signaling messenger through its actions on purinergic receptors, and is known to be involved in numerous physiological and pathophysiological processes throughout the body, including in the lungs and airways. Consequently, purinergic receptors are considered to be promising therapeutic targets for many respiratory diseases, including asthma. This review explores how online bioinformatics resources combined with recently generated datasets can be utilized to investigate purinergic receptor gene expression in tissues and cell types of interest in respiratory disease to identify potential therapeutic targets, which can then be investigated further. These approaches show that different purinergic receptors are expressed at different levels in lung tissue, and that purinergic receptors tend to be expressed at higher levels in immune cells and at more moderate levels in airway structural cells. Notably, P2RX1, P2RX4, P2RX7, P2RY1, P2RY11, and P2RY14 were revealed as the most highly expressed purinergic receptors in lung tissue, therefore suggesting that these receptors have good potential as therapeutic targets for asthma and other respiratory diseases.",,pdf:https://www.frontiersin.org/articles/10.3389/falgy.2021.677677/pdf; doi:https://doi.org/10.3389/falgy.2021.677677; html:https://europepmc.org/articles/PMC8974712; pdf:https://europepmc.org/articles/PMC8974712?pdf=render 33043790,https://doi.org/10.1177/0141076820961776,Advancing UK regulatory science and innovation in healthcare.,"Calvert MJ, Marston E, Samuels M, Rivera SC, Torlinska B, Oliver K, Denniston AK, Hoare S.",,Journal of the Royal Society of Medicine,2021,2020-10-12,Y,,,,,,pdf:https://journals.sagepub.com/doi/pdf/10.1177/0141076820961776; doi:https://doi.org/10.1177/0141076820961776; html:https://europepmc.org/articles/PMC7809339; pdf:https://europepmc.org/articles/PMC7809339?pdf=render 35099396,https://doi.org/10.2196/21341,"Collaborative Research and Development of a Novel, Patient-Centered Digital Platform (MyEyeSite) for Rare Inherited Retinal Disease Data: Acceptability and Feasibility Study.","Gilbert RM, Sumodhee D, Pontikos N, Hollyhead C, Patrick A, Scarles S, Van Der Smissen S, Young RM, Nettleton N, Webster AR, Cammack J.",,JMIR formative research,2022,2022-01-31,Y,Genetics; Mobile phone; Ophthalmology; Rare Diseases; Digital Health; Gdpr; Eye Data; Inherited Retinal Diseases (Ird); Myeyesite; Subject Access Request (Sar),,,"

Background

Inherited retinal diseases (IRDs) are a leading cause of blindness in children and working age adults in the United Kingdom and other countries, with an appreciable socioeconomic impact. However, by definition, IRD data are individually rare, and as a result, this patient group has been underserved by research. Researchers need larger amounts of these rare data to make progress in this field, for example, through the development of gene therapies. The challenge has been how to find and make these data available to researchers in the most productive way. MyEyeSite is a research collaboration aiming to design and develop a digital platform (the MyEyeSite platform) for people with rare IRDs that will enable patients, doctors, and researchers to aggregate and share specialist eye health data. A crucial component of this platform is the MyEyeSite patient application, which will provide the means for patients with IRD to interact with the system and, in particular, to collate, manage, and share their personal specialist IRD data both for research and their own health care.

Objective

This study aims to test the acceptability and feasibility of the MyEyeSite platform in the target IRD population through a collaborative patient-centered study.

Methods

Qualitative data were generated through focus groups and workshops, and quantitative data were obtained through a survey of patients with IRD. Participants were recruited through clinics at Moorfields Eye Hospital National Health Service (NHS) Foundation Trust and the National Institute for Health Research (NIHR) Moorfields Biomedical Research Centre through their patient and public involvement databases.

Results

Our IRD focus group sample (n=50) highlighted the following themes: frustration with the current system regarding data sharing within the United Kingdom's NHS; positive expectations of the potential benefits of the MyEyeSite patient application, resulting from increased access to this specialized data; and concerns regarding data security, including potentially unethical use of the data outside the NHS. Of the surveyed 80 participants, 68 (85%) were motivated to have a more active role in their eye care and share their data for research purposes using a secure technology, such as a web application or mobile app.

Conclusions

This study demonstrates that patients with IRD are highly motivated to be actively involved in managing their own data for research and their own eye care. It demonstrates the feasibility of involving patients with IRD in the detailed design of the MyEyeSite platform exemplar, with input from the patient with IRD workshops playing a key role in determining both the functionality and accessibility of the designs and prototypes. The development of a user-centered technological solution to the problem of rare health data has the potential to benefit not only the patient with IRD community but also others with rare diseases.",,pdf:https://formative.jmir.org/2022/1/e21341/PDF; doi:https://doi.org/10.2196/21341; html:https://europepmc.org/articles/PMC8845013; pdf:https://europepmc.org/articles/PMC8845013?pdf=render -35861818,https://doi.org/10.1161/jaha.121.025473,Interatrial Block Predicts Life-Threatening Arrhythmias in Dilated Cardiomyopathy.,"Henkens MTHM, López Martínez H, Weerts J, Sammani A, Raafs AG, Verdonschot JAJ, van de Leur RR, Sikking MA, Stroeks S, van Empel VPM, Brunner-La Rocca HP, van Stipdonk AMW, Farmakis D, Hazebroek MR, Vernooy K, Bayés-de-Luna A, Asselbergs FW, Bayés-Genís A, Heymans SRB.",,Journal of the American Heart Association,2022,2022-07-15,Y,Electrocardiography; Dilated cardiomyopathy; Sudden Cardiac Death; Interatrial Block; Non‐ischemic Cardiomyopathy; Life‐threatening Arrhythmias,,,"Background Interatrial block (IAB) has been associated with supraventricular arrhythmias and stroke, and even with sudden cardiac death in the general population. Whether IAB is associated with life-threatening arrhythmias (LTA) and sudden cardiac death in dilated cardiomyopathy (DCM) remains unknown. This study aimed to determine the association between IAB and LTA in ambulant patients with DCM. Methods and Results A derivation cohort (Maastricht Dilated Cardiomyopathy Registry; N=469) and an external validation cohort (Utrecht Cardiomyopathy Cohort; N=321) were used for this study. The presence of IAB (P-wave duration>120 milliseconds) or atrial fibrillation (AF) was determined using digital calipers by physicians blinded to the study data. In the derivation cohort, IAB and AF were present in 291 (62%) and 70 (15%) patients with DCM, respectively. LTA (defined as sudden cardiac death, justified shock from implantable cardioverter-defibrillator or anti-tachypacing, or hemodynamic unstable ventricular fibrillation/tachycardia) occurred in 49 patients (3 with no IAB, 35 with IAB, and 11 patients with AF, respectively; median follow-up, 4.4 years [2.1; 7.4]). The LTA-free survival distribution significantly differed between IAB or AF versus no IAB (both P<0.01), but not between IAB versus AF (P=0.999). This association remained statistically significant in the multivariable model (IAB: HR, 4.8 (1.4-16.1), P=0.013; AF: HR, 6.4 (1.7-24.0), P=0.007). In the external validation cohort, the survival distribution was also significantly worse for IAB or AF versus no IAB (P=0.037; P=0.005), but not for IAB versus AF (P=0.836). Conclusions IAB is an easy to assess, widely applicable marker associated with LTA in DCM. IAB and AF seem to confer similar risk of LTA. Further research on IAB in DCM, and on the management of IAB in DCM is warranted.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/JAHA.121.025473; doi:https://doi.org/10.1161/JAHA.121.025473; html:https://europepmc.org/articles/PMC9707810; pdf:https://europepmc.org/articles/PMC9707810?pdf=render 33184391,https://doi.org/10.1038/s41598-020-76816-6,Prediction of vascular aging based on smartphone acquired PPG signals.,"Dall'Olio L, Curti N, Remondini D, Safi Harb Y, Asselbergs FW, Castellani G, Uh HW.",,Scientific reports,2020,2020-11-12,Y,,,,"Photoplethysmography (PPG) measured by smartphone has the potential for a large scale, non-invasive, and easy-to-use screening tool. Vascular aging is linked to increased arterial stiffness, which can be measured by PPG. We investigate the feasibility of using PPG to predict healthy vascular aging (HVA) based on two approaches: machine learning (ML) and deep learning (DL). We performed data preprocessing, including detrending, demodulating, and denoising on the raw PPG signals. For ML, ridge penalized regression has been applied to 38 features extracted from PPG, whereas for DL several convolutional neural networks (CNNs) have been applied to the whole PPG signals as input. The analysis has been conducted using the crowd-sourced Heart for Heart data. The prediction performance of ML using two features (AUC of 94.7%) - the a wave of the second derivative PPG and tpr, including four covariates, sex, height, weight, and smoking - was similar to that of the best performing CNN, 12-layer ResNet (AUC of 95.3%). Without having the heavy computational cost of DL, ML might be advantageous in finding potential biomarkers for HVA prediction. The whole workflow of the procedure is clearly described, and open software has been made available to facilitate replication of the results.",,pdf:https://www.nature.com/articles/s41598-020-76816-6.pdf; doi:https://doi.org/10.1038/s41598-020-76816-6; html:https://europepmc.org/articles/PMC7661535; pdf:https://europepmc.org/articles/PMC7661535?pdf=render +35861818,https://doi.org/10.1161/jaha.121.025473,Interatrial Block Predicts Life-Threatening Arrhythmias in Dilated Cardiomyopathy.,"Henkens MTHM, López Martínez H, Weerts J, Sammani A, Raafs AG, Verdonschot JAJ, van de Leur RR, Sikking MA, Stroeks S, van Empel VPM, Brunner-La Rocca HP, van Stipdonk AMW, Farmakis D, Hazebroek MR, Vernooy K, Bayés-de-Luna A, Asselbergs FW, Bayés-Genís A, Heymans SRB.",,Journal of the American Heart Association,2022,2022-07-15,Y,Electrocardiography; Dilated cardiomyopathy; Sudden Cardiac Death; Interatrial Block; Non‐ischemic Cardiomyopathy; Life‐threatening Arrhythmias,,,"Background Interatrial block (IAB) has been associated with supraventricular arrhythmias and stroke, and even with sudden cardiac death in the general population. Whether IAB is associated with life-threatening arrhythmias (LTA) and sudden cardiac death in dilated cardiomyopathy (DCM) remains unknown. This study aimed to determine the association between IAB and LTA in ambulant patients with DCM. Methods and Results A derivation cohort (Maastricht Dilated Cardiomyopathy Registry; N=469) and an external validation cohort (Utrecht Cardiomyopathy Cohort; N=321) were used for this study. The presence of IAB (P-wave duration>120 milliseconds) or atrial fibrillation (AF) was determined using digital calipers by physicians blinded to the study data. In the derivation cohort, IAB and AF were present in 291 (62%) and 70 (15%) patients with DCM, respectively. LTA (defined as sudden cardiac death, justified shock from implantable cardioverter-defibrillator or anti-tachypacing, or hemodynamic unstable ventricular fibrillation/tachycardia) occurred in 49 patients (3 with no IAB, 35 with IAB, and 11 patients with AF, respectively; median follow-up, 4.4 years [2.1; 7.4]). The LTA-free survival distribution significantly differed between IAB or AF versus no IAB (both P<0.01), but not between IAB versus AF (P=0.999). This association remained statistically significant in the multivariable model (IAB: HR, 4.8 (1.4-16.1), P=0.013; AF: HR, 6.4 (1.7-24.0), P=0.007). In the external validation cohort, the survival distribution was also significantly worse for IAB or AF versus no IAB (P=0.037; P=0.005), but not for IAB versus AF (P=0.836). Conclusions IAB is an easy to assess, widely applicable marker associated with LTA in DCM. IAB and AF seem to confer similar risk of LTA. Further research on IAB in DCM, and on the management of IAB in DCM is warranted.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/JAHA.121.025473; doi:https://doi.org/10.1161/JAHA.121.025473; html:https://europepmc.org/articles/PMC9707810; pdf:https://europepmc.org/articles/PMC9707810?pdf=render 36688706,https://doi.org/10.1093/rheumatology/kead038,Classification of patients with osteoarthritis through clusters of comorbidities using 633 330 individuals from Spain.,"Pineda-Moncusí M, Dernie F, Dell'Isola A, Kamps A, Runhaar J, Swain S, Zhang W, Englund M, Pitsillidou I, Strauss VY, Robinson DE, Prieto-Alhambra D, Khalid S.",,"Rheumatology (Oxford, England)",2023,2023-11-01,Y,Clustering; epidemiology; Comorbidities; Oa,,,"

Objectives

To explore clustering of comorbidities among patients with a new diagnosis of OA and estimate the 10-year mortality risk for each identified cluster.

Methods

This is a population-based cohort study of individuals with first incident diagnosis of OA of the hip, knee, ankle/foot, wrist/hand or 'unspecified' site between 2006 and 2020, using SIDIAP (a primary care database representative of Catalonia, Spain). At the time of OA diagnosis, conditions associated with OA in the literature that were found in ≥1% of the individuals (n = 35) were fitted into two cluster algorithms, k-means and latent class analysis. Models were assessed using a range of internal and external evaluation procedures. Mortality risk of the obtained clusters was assessed by survival analysis using Cox proportional hazards.

Results

We identified 633 330 patients with a diagnosis of OA. Our proposed best solution used latent class analysis to identify four clusters: 'low-morbidity' (relatively low number of comorbidities), 'back/neck pain plus mental health', 'metabolic syndrome' and 'multimorbidity' (higher prevalence of all studied comorbidities). Compared with the 'low-morbidity' cluster, the 'multimorbidity' cluster had the highest risk of 10-year mortality (adjusted hazard ratio [HR]: 2.19 [95% CI: 2.15, 2.23]), followed by the 'metabolic syndrome' cluster (adjusted HR: 1.24 [95% CI: 1.22, 1.27]) and the 'back/neck pain plus mental health' cluster (adjusted HR: 1.12 [95% CI: 1.09, 1.15]).

Conclusion

Patients with a new diagnosis of OA can be clustered into groups based on their comorbidity profile, with significant differences in 10-year mortality risk. Further research is required to understand the interplay between OA and particular comorbidity groups, and the clinical significance of such results.",,pdf:https://academic.oup.com/rheumatology/advance-article-pdf/doi/10.1093/rheumatology/kead038/49101708/kead038.pdf; doi:https://doi.org/10.1093/rheumatology/kead038; html:https://europepmc.org/articles/PMC10629784; pdf:https://europepmc.org/articles/PMC10629784?pdf=render 38296965,https://doi.org/10.1038/s41467-023-43644-x,"Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial.","RECOVERY Collaborative Group, Horby PW, Peto L, Staplin N, Campbell M, Pessoa-Amorim G, Mafham M, Emberson JR, Stewart R, Prudon B, Uriel A, Green CA, Dhasmana DJ, Malein F, Majumdar J, Collini P, Shurmer J, Yates B, Baillie JK, Buch MH, Day J, Faust SN, Jaki T, Jeffery K, Juszczak E, Knight M, Lim WS, Montgomery A, Mumford A, Rowan K, Thwaites G, Haynes R, Landray MJ.",,Nature communications,2024,2024-01-31,Y,,,,"Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome.",,pdf:https://www.nature.com/articles/s41467-023-43644-x.pdf; doi:https://doi.org/10.1038/s41467-023-43644-x; html:https://europepmc.org/articles/PMC10831058; pdf:https://europepmc.org/articles/PMC10831058?pdf=render 33724919,https://doi.org/10.2196/26627,Artificial Intelligence-Enabled Analysis of Public Attitudes on Facebook and Twitter Toward COVID-19 Vaccines in the United Kingdom and the United States: Observational Study.,"Hussain A, Tahir A, Hussain Z, Sheikh Z, Gogate M, Dashtipour K, Ali A, Sheikh A.",,Journal of medical Internet research,2021,2021-04-05,Y,Artificial intelligence; Vaccination; Public Health; Health Informatics; Natural Language Processing; Facebook; Social Media; Twitter; Sentiment Analysis; Infodemiology; Deep Learning; Covid-19,,,"

Background

Global efforts toward the development and deployment of a vaccine for COVID-19 are rapidly advancing. To achieve herd immunity, widespread administration of vaccines is required, which necessitates significant cooperation from the general public. As such, it is crucial that governments and public health agencies understand public sentiments toward vaccines, which can help guide educational campaigns and other targeted policy interventions.

Objective

The aim of this study was to develop and apply an artificial intelligence-based approach to analyze public sentiments on social media in the United Kingdom and the United States toward COVID-19 vaccines to better understand the public attitude and concerns regarding COVID-19 vaccines.

Methods

Over 300,000 social media posts related to COVID-19 vaccines were extracted, including 23,571 Facebook posts from the United Kingdom and 144,864 from the United States, along with 40,268 tweets from the United Kingdom and 98,385 from the United States from March 1 to November 22, 2020. We used natural language processing and deep learning-based techniques to predict average sentiments, sentiment trends, and topics of discussion. These factors were analyzed longitudinally and geospatially, and manual reading of randomly selected posts on points of interest helped identify underlying themes and validated insights from the analysis.

Results

Overall averaged positive, negative, and neutral sentiments were at 58%, 22%, and 17% in the United Kingdom, compared to 56%, 24%, and 18% in the United States, respectively. Public optimism over vaccine development, effectiveness, and trials as well as concerns over their safety, economic viability, and corporation control were identified. We compared our findings to those of nationwide surveys in both countries and found them to correlate broadly.

Conclusions

Artificial intelligence-enabled social media analysis should be considered for adoption by institutions and governments alongside surveys and other conventional methods of assessing public attitude. Such analyses could enable real-time assessment, at scale, of public confidence and trust in COVID-19 vaccines, help address the concerns of vaccine sceptics, and help develop more effective policies and communication strategies to maximize uptake.",,pdf:https://www.jmir.org/2021/4/e26627/PDF; doi:https://doi.org/10.2196/26627; html:https://europepmc.org/articles/PMC8023383 -37391266,https://doi.org/10.1016/s2589-7500(23)00087-0,Wearable technology and the cardiovascular system: the future of patient assessment.,"Williams GJ, Al-Baraikan A, Rademakers FE, Ciravegna F, van de Vosse FN, Lawrie A, Rothman A, Ashley EA, Wilkins MR, Lawford PV, Omholt SW, Wisløff U, Hose DR, Chico TJA, Gunn JP, Morris PD.",,The Lancet. Digital health,2023,2023-07-01,N,,,,"The past decade has seen a dramatic rise in consumer technologies able to monitor a variety of cardiovascular parameters. Such devices initially recorded markers of exercise, but now include physiological and health-care focused measurements. The public are keen to adopt these devices in the belief that they are useful to identify and monitor cardiovascular disease. Clinicians are therefore often presented with health app data accompanied by a diverse range of concerns and queries. Herein, we assess whether these devices are accurate, their outputs validated, and whether they are suitable for professionals to make management decisions. We review underpinning methods and technologies and explore the evidence supporting the use of these devices as diagnostic and monitoring tools in hypertension, arrhythmia, heart failure, coronary artery disease, pulmonary hypertension, and valvular heart disease. Used correctly, they might improve health care and support research.",,pdf:http://www.thelancet.com/article/S2589750023000870/pdf; doi:https://doi.org/10.1016/S2589-7500(23)00087-0 -37096818,https://doi.org/10.1093/ehjacc/zuad042,"Serially measured high-sensitivity cardiac troponin T, N-terminal-pro-B-type natriuretic peptide, high-sensitivity C-reactive protein, and growth differentiation factor 15 for risk assessment after acute coronary syndrome: the BIOMArCS cohort.","Gürgöze MT, Akkerhuis KM, Oemrawsingh RM, Umans VAWM, Kietselaer B, Schotborgh CE, Ronner E, Lenderink T, Aksoy I, van der Harst P, Asselbergs FW, Maas AC, Oude Ophuis AJ, Krenning B, de Winter RJ, The SHK, Wardeh AJ, Hermans WRM, Cramer GE, van Gorp I, de Rijke YB, van Schaik RHN, Boersma E.",,European heart journal. Acute cardiovascular care,2023,2023-07-01,Y,Prognosis; Biomarkers; acute coronary syndrome; risk assessment; Repeated Measurements,,,"

Aims

Evidence regarding the role of serial measurements of biomarkers for risk assessment in post-acute coronary syndrome (ACS) patients is limited. The aim was to explore the prognostic value of four, serially measured biomarkers in a large, real-world cohort of post-ACS patients.

Methods and results

BIOMArCS is a prospective, multi-centre, observational study in 844 post-ACS patients in whom 12 218 blood samples (median 17 per patient) were obtained during 1-year follow-up. The longitudinal patterns of high-sensitivity cardiac troponin T (hs-cTnT), N-terminal-pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein (hs-CRP), and growth differentiation factor 15 (GDF-15) were analysed in relation to the primary endpoint (PE) of cardiovascular mortality and recurrent ACS using multivariable joint models. Median age was 63 years, 78% were men and the PE was reached by 45 patients. The average biomarker levels were systematically higher in PE compared with PE-free patients. After adjustment for 6-month post-discharge Global Registry of Acute Coronary Events score, 1 standard deviation increase in log[hs-cTnT] was associated with a 61% increased risk of the PE [hazard ratio (HR) 1.61, 95% confidence interval (CI) 1.02-2.44, P = 0.045], while for log[GDF-15] this was 81% (HR 1.81, 95% CI 1.28-2.70, P = 0.001). These associations remained significant after multivariable adjustment, while NT-proBNP and hs-CRP were not. Furthermore, GDF-15 level showed an increasing trend prior to the PE (Structured Graphical Abstract).

Conclusion

Longitudinally measured hs-cTnT and GDF-15 concentrations provide prognostic value in the risk assessment of clinically stabilized patients post-ACS.

Clinical trial registration

The Netherlands Trial Register. Currently available at URL https://trialsearch.who.int/; Unique Identifiers: NTR1698 and NTR1106.",,pdf:https://academic.oup.com/ehjacc/advance-article-pdf/doi/10.1093/ehjacc/zuad042/50087609/zuad042.pdf; doi:https://doi.org/10.1093/ehjacc/zuad042; html:https://europepmc.org/articles/PMC10328437; pdf:https://europepmc.org/articles/PMC10328437?pdf=render 32685697,https://doi.org/10.12688/wellcomeopenres.15788.1,The contribution of pre-symptomatic infection to the transmission dynamics of COVID-2019.,"Liu Y, Centre for Mathematical Modelling of Infectious Diseases nCoV Working Group, Funk S, Flasche S.",,Wellcome open research,2020,2020-04-01,Y,Incubation period; Serial Interval; Covid-19; Pre-symptomatic Transmission,,,"Background: Pre-symptomatic transmission can be a key determinant of the effectiveness of containment and mitigation strategies for infectious diseases, particularly if interventions rely on syndromic case finding. For COVID-19, infections in the absence of apparent symptoms have been reported frequently alongside circumstantial evidence for asymptomatic or pre-symptomatic transmission. We estimated the potential contribution of pre-symptomatic cases to COVID-19 transmission. Methods: Using the probability for symptom onset on a given day inferred from the incubation period, we attributed the serial interval reported from Shenzen, China, into likely pre-symptomatic and symptomatic transmission. We used the serial interval derived for cases isolated more than 6 days after symptom onset as the no active case finding scenario and the unrestricted serial interval as the active case finding scenario. We reported the estimate assuming no correlation between the incubation period and the serial interval alongside a range indicating alternative assumptions of positive and negative correlation. Results: We estimated that 23% (range accounting for correlation: 12 - 28%) of transmissions in Shenzen may have originated from pre-symptomatic infections. Through accelerated case isolation following symptom onset, this percentage increased to 46% (21 - 46%), implying that about 35% of secondary infections among symptomatic cases have been prevented. These results were robust to using reported incubation periods and serial intervals from other settings. Conclusions: Pre-symptomatic transmission may be essential to consider for containment and mitigation strategies for COVID-19.",,pdf:https://wellcomeopenresearch.org/articles/5-58/v1/pdf; doi:https://doi.org/10.12688/wellcomeopenres.15788.1; html:https://europepmc.org/articles/PMC7324944; pdf:https://europepmc.org/articles/PMC7324944?pdf=render 33825703,https://doi.org/10.1107/s2059798321000826,Vagabond: bond-based parametrization reduces overfitting for refinement of proteins.,Ginn HM.,,"Acta crystallographica. Section D, Structural biology",2021,2021-03-30,Y,Models; X-ray diffraction; Protein Flexibility; Bonds; Refinement Software,,,"Structural biology methods have delivered over 150 000 high-resolution structures of macromolecules, which have fundamentally altered our understanding of biology and our approach to developing new medicines. However, the description of molecular flexibility is instrinsically flawed and in almost all cases, regardless of the experimental method used for structure determination, there remains a strong overfitting bias during molecular model building and refinement. In the worst case this can lead to wholly incorrect structures and thus incorrect biological interpretations. Here, by reparametrizing the description of these complex structures in terms of bonds rather than atomic positions, and by modelling flexibility using a deterministic ensemble of structures, it is demonstrated that structures can be described using fewer parameters than in conventional refinement. The current implementation, applied to X-ray diffraction data, significantly reduces the extent of overfitting, allowing the experimental data to reveal more biological information in electron-density maps.",,pdf:https://journals.iucr.org/d/issues/2021/04/00/qj5007/qj5007.pdf; doi:https://doi.org/10.1107/S2059798321000826; html:https://europepmc.org/articles/PMC8025884; pdf:https://europepmc.org/articles/PMC8025884?pdf=render 32255392,https://doi.org/10.1080/09273948.2019.1709650,Non-invasive Instrument-Based Tests for Quantifying Anterior Chamber Flare in Uveitis: A Systematic Review.,"Liu X, McNally TW, Beese S, Downie LE, Solebo AL, Faes L, Husain S, Keane PA, Moore DJ, Denniston AK.",,Ocular immunology and inflammation,2021,2020-04-07,N,"Diagnostic test; Systematic review; Uveitis; optical coherence tomography; Laser Flare Photometry; Anterior Chamber Flare; Tyndall Effect; Aqueous Humor, Aqueous Humour; Aqueous Protein Concentration",,,"Purpose: Anterior chamber (AC) flare is a key sign for anterior uveitis. New instrument-based techniques for measuring AC flare can offer automation and objectivity. This review aims to identify objective instrument-based measures for AC flare.Methods: In this systematic review, we identified studies reporting correlation between instrument-based tests versus clinician AC flare grading, and/or aqueous protein concentration, as well as test reliability.Results: Four index tests were identified in 11 studies: laser-flare photometry (LFP), optical coherence tomography, ocular flare analysis meter (OFAM) and the double-pass technique. The correlation between LFP and clinician grading was 0.40-0.93 and 0.87-0.94 for LFP and protein concentration. The double-pass technique showed no correlation with clinician grading and insufficient information was available for OFAM.Conclusion: LFP shows moderate to strong correlation with clinician grading and aqueous protein concentration. LFP could be a superior reference test compared to clinician AC flare grading for validating new index tests.",,pdf:https://discovery.ucl.ac.uk/10097154/3/Solebo_Liu%20AC%20Flare%20SR%20290919.pdf; doi:https://doi.org/10.1080/09273948.2019.1709650 -33782080,https://doi.org/10.1136/thoraxjnl-2020-216512,Impact of COVID-19 national lockdown on asthma exacerbations: interrupted time-series analysis of English primary care data.,"Shah SA, Quint JK, Nwaru BI, Sheikh A.",,Thorax,2021,2021-03-29,Y,Asthma; Asthma Epidemiology; Covid-19,,,"

Background

The impact of COVID-19 and ensuing national lockdown on asthma exacerbations is unclear.

Methods

We conducted an interrupted time-series (lockdown on 23 March 2020 as point of interruption) analysis in asthma cohort identified using a validated algorithm from a national-level primary care database, the Optimum Patient Care Database. We derived asthma exacerbation rates for every week and compared exacerbation rates in the period: January to August 2020 with a pre-COVID-19 period and January to August 2016-2019. Exacerbations were defined as asthma-related hospital attendance/admission (including accident and emergency visit), or an acute course of oral corticosteroids with evidence of respiratory review, as recorded in primary care. We used a generalised least squares modelling approach and stratified the analyses by age, sex, English region and healthcare setting.

Results

From a database of 9 949 387 patients, there were 100 165 patients with asthma who experienced at least one exacerbation during 2016-2020. Of 278 996 exacerbation episodes, 49 938 (17.9%) required hospital visit. Comparing pre-lockdown to post-lockdown period, we observed a statistically significant reduction in the level (-0.196 episodes per person-year; p<0.001; almost 20 episodes for every 100 patients with asthma per year) of exacerbation rates across all patients. The reductions in level in stratified analyses were: 0.005-0.244 (healthcare setting, only those without hospital attendance/admission were significant), 0.210-0.277 (sex), 0.159-0.367 (age), 0.068-0.590 (region).

Conclusions

There has been a significant reduction in attendance to primary care for asthma exacerbations during the pandemic. This reduction was observed in all age groups, both sexes and across most regions in England.",,pdf:https://thorax.bmj.com/content/thoraxjnl/76/9/860.full.pdf; doi:https://doi.org/10.1136/thoraxjnl-2020-216512; html:https://europepmc.org/articles/PMC8011425; pdf:https://europepmc.org/articles/PMC8011425?pdf=render +37391266,https://doi.org/10.1016/s2589-7500(23)00087-0,Wearable technology and the cardiovascular system: the future of patient assessment.,"Williams GJ, Al-Baraikan A, Rademakers FE, Ciravegna F, van de Vosse FN, Lawrie A, Rothman A, Ashley EA, Wilkins MR, Lawford PV, Omholt SW, Wisløff U, Hose DR, Chico TJA, Gunn JP, Morris PD.",,The Lancet. Digital health,2023,2023-07-01,N,,,,"The past decade has seen a dramatic rise in consumer technologies able to monitor a variety of cardiovascular parameters. Such devices initially recorded markers of exercise, but now include physiological and health-care focused measurements. The public are keen to adopt these devices in the belief that they are useful to identify and monitor cardiovascular disease. Clinicians are therefore often presented with health app data accompanied by a diverse range of concerns and queries. Herein, we assess whether these devices are accurate, their outputs validated, and whether they are suitable for professionals to make management decisions. We review underpinning methods and technologies and explore the evidence supporting the use of these devices as diagnostic and monitoring tools in hypertension, arrhythmia, heart failure, coronary artery disease, pulmonary hypertension, and valvular heart disease. Used correctly, they might improve health care and support research.",,pdf:http://www.thelancet.com/article/S2589750023000870/pdf; doi:https://doi.org/10.1016/S2589-7500(23)00087-0 +37096818,https://doi.org/10.1093/ehjacc/zuad042,"Serially measured high-sensitivity cardiac troponin T, N-terminal-pro-B-type natriuretic peptide, high-sensitivity C-reactive protein, and growth differentiation factor 15 for risk assessment after acute coronary syndrome: the BIOMArCS cohort.","Gürgöze MT, Akkerhuis KM, Oemrawsingh RM, Umans VAWM, Kietselaer B, Schotborgh CE, Ronner E, Lenderink T, Aksoy I, van der Harst P, Asselbergs FW, Maas AC, Oude Ophuis AJ, Krenning B, de Winter RJ, The SHK, Wardeh AJ, Hermans WRM, Cramer GE, van Gorp I, de Rijke YB, van Schaik RHN, Boersma E.",,European heart journal. Acute cardiovascular care,2023,2023-07-01,Y,Prognosis; Biomarkers; acute coronary syndrome; risk assessment; Repeated Measurements,,,"

Aims

Evidence regarding the role of serial measurements of biomarkers for risk assessment in post-acute coronary syndrome (ACS) patients is limited. The aim was to explore the prognostic value of four, serially measured biomarkers in a large, real-world cohort of post-ACS patients.

Methods and results

BIOMArCS is a prospective, multi-centre, observational study in 844 post-ACS patients in whom 12 218 blood samples (median 17 per patient) were obtained during 1-year follow-up. The longitudinal patterns of high-sensitivity cardiac troponin T (hs-cTnT), N-terminal-pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein (hs-CRP), and growth differentiation factor 15 (GDF-15) were analysed in relation to the primary endpoint (PE) of cardiovascular mortality and recurrent ACS using multivariable joint models. Median age was 63 years, 78% were men and the PE was reached by 45 patients. The average biomarker levels were systematically higher in PE compared with PE-free patients. After adjustment for 6-month post-discharge Global Registry of Acute Coronary Events score, 1 standard deviation increase in log[hs-cTnT] was associated with a 61% increased risk of the PE [hazard ratio (HR) 1.61, 95% confidence interval (CI) 1.02-2.44, P = 0.045], while for log[GDF-15] this was 81% (HR 1.81, 95% CI 1.28-2.70, P = 0.001). These associations remained significant after multivariable adjustment, while NT-proBNP and hs-CRP were not. Furthermore, GDF-15 level showed an increasing trend prior to the PE (Structured Graphical Abstract).

Conclusion

Longitudinally measured hs-cTnT and GDF-15 concentrations provide prognostic value in the risk assessment of clinically stabilized patients post-ACS.

Clinical trial registration

The Netherlands Trial Register. Currently available at URL https://trialsearch.who.int/; Unique Identifiers: NTR1698 and NTR1106.",,pdf:https://academic.oup.com/ehjacc/advance-article-pdf/doi/10.1093/ehjacc/zuad042/50087609/zuad042.pdf; doi:https://doi.org/10.1093/ehjacc/zuad042; html:https://europepmc.org/articles/PMC10328437; pdf:https://europepmc.org/articles/PMC10328437?pdf=render 31145509,https://doi.org/10.1002/gepi.22215,A comparison of two workflows for regulome and transcriptome-based prioritization of genetic variants associated with myocardial mass.,"Manduchi E, Hemerich D, van Setten J, Tragante V, Harakalova M, Pei J, Williams SM, van der Harst P, Asselbergs FW, Moore JH.",,Genetic epidemiology,2019,2019-05-30,N,Functional genomics; Gwas; left ventricular mass; Snp Preselection,,,"A typical task arising from main effect analyses in a Genome Wide Association Study (GWAS) is to identify single nucleotide polymorphisms (SNPs), in linkage disequilibrium with the observed signals, that are likely causal variants and the affected genes. The affected genes may not be those closest to associating SNPs. Functional genomics data from relevant tissues are believed to be helpful in selecting likely causal SNPs and interpreting implicated biological mechanisms, ultimately facilitating prevention and treatment in the case of a disease trait. These data are typically used post GWAS analyses to fine-map the statistically significant signals identified agnostically by testing all SNPs and applying a multiple testing correction. The number of tested SNPs is typically in the millions, so the multiple testing burden is high. Motivated by this, in this study we investigated an alternative workflow, which consists in utilizing the available functional genomics data as a first step to reduce the number of SNPs tested for association. We analyzed GWAS on electrocardiographic QRS duration using these two workflows. The alternative workflow identified more SNPs, including some residing in loci not discovered with the typical workflow. Moreover, the latter are corroborated by other reports on QRS duration. This indicates the potential value of incorporating functional genomics information at the onset in GWAS analyses.",,pdf:https://pure.rug.nl/ws/files/89611268/Manduchi_et_al_2019_Genetic_Epidemiology.pdf; doi:https://doi.org/10.1002/gepi.22215; html:https://europepmc.org/articles/PMC6687530; pdf:https://europepmc.org/articles/PMC6687530?pdf=render; doi:https://doi.org/10.1002/gepi.22215 -36357634,https://doi.org/10.1007/s00467-022-05789-7,Shared genetic risk across different presentations of gene test-negative idiopathic nephrotic syndrome.,"Downie ML, Gupta S, Chan MMY, Sadeghi-Alavijeh O, Cao J, Parekh RS, Diz CB, Bierzynska A, Levine AP, Pepper RJ, Stanescu H, Saleem MA, Kleta R, Bockenhauer D, Koziell AB, Gale DP.",,"Pediatric nephrology (Berlin, Germany)",2023,2022-11-10,Y,Paediatrics; Minimal Change Disease; Focal Segmental Glomerulosclerosis; Monogenic; Genetic Risk Score; Steroid-resistant Nephrotic Syndrome; Steroid-sensitive Nephrotic Syndrome,,,"

Background

Idiop athic nephrotic syndrome (INS) is classified in children according to response to initial corticosteroid therapy into steroid-sensitive (SSNS) and steroid-resistant nephrotic syndrome (SRNS), and in adults according to histology into minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS). However, there is well-recognised phenotypic overlap between these entities. Genome-wide association studies (GWAS) have shown a strong association between SSNS and variation at HLA, suggesting an underlying immunological basis. We sought to determine whether a risk score generated from genetic variants associated with SSNS could be used to gain insight into the pathophysiology of INS presenting in other ways.

Methods

We developed an SSNS genetic risk score (SSNS-GRS) from the five variants independently associated with childhood SSNS in a previous European GWAS. We quantified SSNS-GRS in independent cohorts of European individuals with childhood SSNS, non-monogenic SRNS, MCD, and FSGS, and contrasted them with SSNS-GRS quantified in individuals with monogenic SRNS, membranous nephropathy (a different immune-mediated disease-causing nephrotic syndrome), and healthy controls.

Results

The SSNS-GRS was significantly elevated in cohorts with SSNS, non-monogenic SRNS, MCD, and FSGS compared to healthy participants and those with membranous nephropathy. The SSNS-GRS in all cohorts with non-monogenic INS were also significantly elevated compared to those with monogenic SRNS.

Conclusions

The shared genetic risk factors among patients with different presentations of INS strongly suggests a shared autoimmune pathogenesis when monogenic causes are excluded. Use of the SSNS-GRS, in addition to testing for monogenic causes, may help to classify patients presenting with INS. A higher resolution version of the Graphical abstract is available as Supplementary information.",,pdf:https://link.springer.com/content/pdf/10.1007/s00467-022-05789-7.pdf; doi:https://doi.org/10.1007/s00467-022-05789-7; html:https://europepmc.org/articles/PMC10154254; pdf:https://europepmc.org/articles/PMC10154254?pdf=render +33782080,https://doi.org/10.1136/thoraxjnl-2020-216512,Impact of COVID-19 national lockdown on asthma exacerbations: interrupted time-series analysis of English primary care data.,"Shah SA, Quint JK, Nwaru BI, Sheikh A.",,Thorax,2021,2021-03-29,Y,Asthma; Asthma Epidemiology; Covid-19,,,"

Background

The impact of COVID-19 and ensuing national lockdown on asthma exacerbations is unclear.

Methods

We conducted an interrupted time-series (lockdown on 23 March 2020 as point of interruption) analysis in asthma cohort identified using a validated algorithm from a national-level primary care database, the Optimum Patient Care Database. We derived asthma exacerbation rates for every week and compared exacerbation rates in the period: January to August 2020 with a pre-COVID-19 period and January to August 2016-2019. Exacerbations were defined as asthma-related hospital attendance/admission (including accident and emergency visit), or an acute course of oral corticosteroids with evidence of respiratory review, as recorded in primary care. We used a generalised least squares modelling approach and stratified the analyses by age, sex, English region and healthcare setting.

Results

From a database of 9 949 387 patients, there were 100 165 patients with asthma who experienced at least one exacerbation during 2016-2020. Of 278 996 exacerbation episodes, 49 938 (17.9%) required hospital visit. Comparing pre-lockdown to post-lockdown period, we observed a statistically significant reduction in the level (-0.196 episodes per person-year; p<0.001; almost 20 episodes for every 100 patients with asthma per year) of exacerbation rates across all patients. The reductions in level in stratified analyses were: 0.005-0.244 (healthcare setting, only those without hospital attendance/admission were significant), 0.210-0.277 (sex), 0.159-0.367 (age), 0.068-0.590 (region).

Conclusions

There has been a significant reduction in attendance to primary care for asthma exacerbations during the pandemic. This reduction was observed in all age groups, both sexes and across most regions in England.",,pdf:https://thorax.bmj.com/content/thoraxjnl/76/9/860.full.pdf; doi:https://doi.org/10.1136/thoraxjnl-2020-216512; html:https://europepmc.org/articles/PMC8011425; pdf:https://europepmc.org/articles/PMC8011425?pdf=render 33560344,https://doi.org/10.1210/clinem/dgab067,Association of Metformin with Susceptibility to COVID-19 in People with Type 2 Diabetes.,"Wang J, Cooper JM, Gokhale K, Acosta-Mena D, Dhalla S, Byne N, Chandan JS, Anand A, Okoth K, Subramanian A, Bangash MN, Jackson T, Zemedikun D, Taverner T, Hanif W, Ghosh S, Narendran P, Toulis KA, Tahrani AA, Surenthirakumaran R, Adderley NJ, Haroon S, Khunti K, Sainsbury C, Thomas GN, Nirantharakumar K.",,The Journal of clinical endocrinology and metabolism,2021,2021-04-01,Y,Type 2 diabetes mellitus; Metformin; Covid-19; Sars-cov-2 Infection,,,"

Objective

Diabetes has emerged as an important risk factor for mortality from COVID-19. Metformin, the most commonly prescribed glucose-lowering agent, has been proposed to influence susceptibility to and outcomes of COVID-19 via multiple mechanisms. We investigated whether, in patients with diabetes, metformin is associated with susceptibility to COVID-19 and its outcomes.

Research design and methods

We performed a propensity score-matched cohort study with active comparators using a large UK primary care dataset. Adults with type 2 diabetes patients and a current prescription for metformin and other glucose-lowering agents (MF+) were compared to those with a current prescription for glucose-lowering agents that did not include metformin (MF-). Outcomes were confirmed COVID-19, suspected/confirmed COVID-19, and associated mortality. A negative control outcome analysis (back pain) was also performed.

Results

There were 29 558 and 10 271 patients in the MF+ and MF- groups, respectively, who met the inclusion criteria. In the propensity score-matched analysis, the adjusted hazard ratios for suspected/confirmed COVID-19, confirmed COVID-19, and COVID-19-related mortality were 0.85 (95% CI 0.67, 1.08), 0.80 (95% CI 0.49, 1.30), and 0.87 (95% CI 0.34, 2.20) respectively. The negative outcome control analysis did not suggest unobserved confounding.

Conclusion

Current prescription of metformin was not associated with the risk of COVID-19 or COVID-19-related mortality. It is safe to continue prescribing metformin to improve glycemic control in patients with.",,pdf:https://academic.oup.com/jcem/article-pdf/106/5/1255/41848481/dgab067.pdf; doi:https://doi.org/10.1210/clinem/dgab067; html:https://europepmc.org/articles/PMC7928949 -36210800,https://doi.org/10.1038/s43856-022-00189-2,Feasibility and ethics of using data from the Scottish newborn blood spot archive for research.,"Cunningham-Burley S, McCartney DL, Campbell A, Flaig R, Orange CEL, Porteous C, Aitken M, Mulholland C, Davidson S, McCafferty SM, Murphy L, Wrobel N, McCafferty S, Wallace K, StClair D, Kerr S, Hayward C, McIntosh AM, Sudlow C, Marioni RE, Pell J, Miedzybrodzka Z, Porteous DJ.",,Communications medicine,2022,2022-10-06,Y,epigenomics; epidemiology,,,"

Background

Newborn heel prick blood spots are routinely used to screen for inborn errors of metabolism and life-limiting inherited disorders. The potential value of secondary data from newborn blood spot archives merits ethical consideration and assessment of feasibility for public benefit. Early life exposures and behaviours set health trajectories in childhood and later life. The newborn blood spot is potentially well placed to create an unbiased and cost-effective population-level retrospective birth cohort study. Scotland has retained newborn blood spots for all children born since 1965, around 3 million in total. However, a moratorium on research access is currently in place, pending public consultation.

Methods

We conducted a Citizens' Jury as a first step to explore whether research use of newborn blood spots was in the public interest. We also assessed the feasibility and value of extracting research data from dried blood spots for predictive medicine.

Results

Jurors delivered an agreed verdict that conditional research access to the newborn blood spots was in the public interest. The Chief Medical Officer for Scotland authorised restricted lifting of the current research moratorium to allow a feasibility study. Newborn blood spots from consented Generation Scotland volunteers were retrieved and their potential for both epidemiological and biological research demonstrated.

Conclusions

Through the Citizens' Jury, we have begun to identify under what conditions, if any, should researchers in Scotland be granted access to the archive. Through the feasibility study, we have demonstrated the potential value of research access for health data science and predictive medicine.",,pdf:https://www.nature.com/articles/s43856-022-00189-2.pdf; doi:https://doi.org/10.1038/s43856-022-00189-2; html:https://europepmc.org/articles/PMC9537278; pdf:https://europepmc.org/articles/PMC9537278?pdf=render +36357634,https://doi.org/10.1007/s00467-022-05789-7,Shared genetic risk across different presentations of gene test-negative idiopathic nephrotic syndrome.,"Downie ML, Gupta S, Chan MMY, Sadeghi-Alavijeh O, Cao J, Parekh RS, Diz CB, Bierzynska A, Levine AP, Pepper RJ, Stanescu H, Saleem MA, Kleta R, Bockenhauer D, Koziell AB, Gale DP.",,"Pediatric nephrology (Berlin, Germany)",2023,2022-11-10,Y,Paediatrics; Minimal Change Disease; Focal Segmental Glomerulosclerosis; Monogenic; Genetic Risk Score; Steroid-resistant Nephrotic Syndrome; Steroid-sensitive Nephrotic Syndrome,,,"

Background

Idiop athic nephrotic syndrome (INS) is classified in children according to response to initial corticosteroid therapy into steroid-sensitive (SSNS) and steroid-resistant nephrotic syndrome (SRNS), and in adults according to histology into minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS). However, there is well-recognised phenotypic overlap between these entities. Genome-wide association studies (GWAS) have shown a strong association between SSNS and variation at HLA, suggesting an underlying immunological basis. We sought to determine whether a risk score generated from genetic variants associated with SSNS could be used to gain insight into the pathophysiology of INS presenting in other ways.

Methods

We developed an SSNS genetic risk score (SSNS-GRS) from the five variants independently associated with childhood SSNS in a previous European GWAS. We quantified SSNS-GRS in independent cohorts of European individuals with childhood SSNS, non-monogenic SRNS, MCD, and FSGS, and contrasted them with SSNS-GRS quantified in individuals with monogenic SRNS, membranous nephropathy (a different immune-mediated disease-causing nephrotic syndrome), and healthy controls.

Results

The SSNS-GRS was significantly elevated in cohorts with SSNS, non-monogenic SRNS, MCD, and FSGS compared to healthy participants and those with membranous nephropathy. The SSNS-GRS in all cohorts with non-monogenic INS were also significantly elevated compared to those with monogenic SRNS.

Conclusions

The shared genetic risk factors among patients with different presentations of INS strongly suggests a shared autoimmune pathogenesis when monogenic causes are excluded. Use of the SSNS-GRS, in addition to testing for monogenic causes, may help to classify patients presenting with INS. A higher resolution version of the Graphical abstract is available as Supplementary information.",,pdf:https://link.springer.com/content/pdf/10.1007/s00467-022-05789-7.pdf; doi:https://doi.org/10.1007/s00467-022-05789-7; html:https://europepmc.org/articles/PMC10154254; pdf:https://europepmc.org/articles/PMC10154254?pdf=render 31055854,https://doi.org/10.5694/mja2.50143,"Traumatic spinal cord injury in Victoria, 2007-2016.","Beck B, Cameron PA, Braaf S, Nunn A, Fitzgerald MC, Judson RT, Teague WJ, Lennox A, Middleton JW, Harrison JE, Gabbe BJ.",,The Medical journal of Australia,2019,2019-05-01,N,"Spinal cord injuries; epidemiology; Traumatology; Trauma, Nervous System",,,"

Objective

To investigate trends in the incidence and causes of traumatic spinal cord injury (TSCI) in Victoria over a 10-year period.

Design, setting, participants

Retrospective cohort study: analysis of Victorian State Trauma Registry (VSTR) data for people who sustained TSCIs during 2007-2016.

Main outcomes and measures

Temporal trends in population-based incidence rates of TSCI (injury to the spinal cord with an Abbreviated Injury Scale [AIS] score of 4 or more).

Results

There were 706 cases of TSCI, most the result of transport events (269 cases, 38%) or low falls (197 cases, 28%). The overall crude incidence of TSCI was 1.26 cases per 100 000 population (95% CI, 1.17-1.36 per 100 000 population), and did not change over the study period (incidence rate ratio [IRR], 1.01; 95% CI, 0.99-1.04). However, the incidence of TSCI resulting from low falls increased by 9% per year (95% CI, 4-15%). The proportion of TSCI cases classified as incomplete tetraplegia increased from 41% in 2007 to 55% in 2016 (P < 0.001). Overall in-hospital mortality was 15% (104 deaths), and was highest among people aged 65 years or more (31%, 70 deaths).

Conclusions

Given the devastating consequences of TSCI, improved primary prevention strategies are needed, particularly as the incidence of TSCI did not decline over the study period. The epidemiologic profile of TSCI has shifted, with an increasing number of TSCI events in older adults. This change has implications for prevention, acute and post-discharge care, and support.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.5694/mja2.50143; doi:https://doi.org/10.5694/mja2.50143 +36210800,https://doi.org/10.1038/s43856-022-00189-2,Feasibility and ethics of using data from the Scottish newborn blood spot archive for research.,"Cunningham-Burley S, McCartney DL, Campbell A, Flaig R, Orange CEL, Porteous C, Aitken M, Mulholland C, Davidson S, McCafferty SM, Murphy L, Wrobel N, McCafferty S, Wallace K, StClair D, Kerr S, Hayward C, McIntosh AM, Sudlow C, Marioni RE, Pell J, Miedzybrodzka Z, Porteous DJ.",,Communications medicine,2022,2022-10-06,Y,epigenomics; epidemiology,,,"

Background

Newborn heel prick blood spots are routinely used to screen for inborn errors of metabolism and life-limiting inherited disorders. The potential value of secondary data from newborn blood spot archives merits ethical consideration and assessment of feasibility for public benefit. Early life exposures and behaviours set health trajectories in childhood and later life. The newborn blood spot is potentially well placed to create an unbiased and cost-effective population-level retrospective birth cohort study. Scotland has retained newborn blood spots for all children born since 1965, around 3 million in total. However, a moratorium on research access is currently in place, pending public consultation.

Methods

We conducted a Citizens' Jury as a first step to explore whether research use of newborn blood spots was in the public interest. We also assessed the feasibility and value of extracting research data from dried blood spots for predictive medicine.

Results

Jurors delivered an agreed verdict that conditional research access to the newborn blood spots was in the public interest. The Chief Medical Officer for Scotland authorised restricted lifting of the current research moratorium to allow a feasibility study. Newborn blood spots from consented Generation Scotland volunteers were retrieved and their potential for both epidemiological and biological research demonstrated.

Conclusions

Through the Citizens' Jury, we have begun to identify under what conditions, if any, should researchers in Scotland be granted access to the archive. Through the feasibility study, we have demonstrated the potential value of research access for health data science and predictive medicine.",,pdf:https://www.nature.com/articles/s43856-022-00189-2.pdf; doi:https://doi.org/10.1038/s43856-022-00189-2; html:https://europepmc.org/articles/PMC9537278; pdf:https://europepmc.org/articles/PMC9537278?pdf=render 35238940,https://doi.org/10.1093/ndt/gfac040,"Design, recruitment, and baseline characteristics of the EMPA-KIDNEY trial.",EMPA-KIDNEY Collaborative Group.,,"Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association",2022,2022-06-01,Y,"Cardiovascular disease; Empagliflozin; Sodium-glucose Co-transporter 2 Inhibitor; Ckd, Clinical Trial",,,"

Background

The effects of the sodium-glucose co-transporter 2 inhibitor empagliflozin on renal and cardiovascular disease have not been tested in a dedicated population of people with chronic kidney disease (CKD).

Methods

The EMPA-KIDNEY trial is an international randomized, double-blind, placebo-controlled trial assessing whether empagliflozin 10 mg daily decreases the risk of kidney disease progression or cardiovascular death in people with CKD. People with or without diabetes mellitus (DM) were eligible provided they had an estimated glomerular filtration rate (eGFR) ≥20 but <45 mL/min/1.73 m2 or an eGFR ≥45 but <90 mL/min/1.73 m2 with a urinary albumin:creatinine ratio (uACR) ≥200 mg/g. The trial design is streamlined, as extra work for collaborating sites is kept to a minimum and only essential information is collected.

Results

Between 15 May 2019 and 16 April 2021, 6609 people from eight countries in Europe, North America and East Asia were randomized. The mean age at randomization was 63.8 years [standard deviation (SD) 13.9)], 2192 (33%) were female and 3570 (54%) had no prior history of DM. The mean eGFR was 37.5 mL/min/1.73 m2 (SD 14.8), including 5185 (78%) with an eGFR <45 mL/min/1.73 m2. The median uACR was 412 mg/g) (quartile 1-quartile 3 94-1190), with a uACR <300 mg/g in 3194 (48%). The causes of kidney disease included diabetic kidney disease [n = 2057 (31%)], glomerular disease [n = 1669 (25%)], hypertensive/renovascular disease [n = 1445 (22%)], other [n = 808 (12%)] and unknown causes [n = 630 (10%)].

Conclusions

EMPA-KIDNEY will evaluate the efficacy and safety of empagliflozin in a widely generalizable population of people with CKD at risk of kidney disease progression. Results are anticipated in 2022.",,pdf:https://academic.oup.com/ndt/article-pdf/37/7/1317/44138360/gfac040.pdf; doi:https://doi.org/10.1093/ndt/gfac040; html:https://europepmc.org/articles/PMC9217655; pdf:https://europepmc.org/articles/PMC9217655?pdf=render 37338017,https://doi.org/10.1111/jvh.13863,Contribution of alcohol use in HIV/hepatitis C virus co-infection to all-cause and cause-specific mortality: A collaboration of cohort studies.,"Trickey A, Ingle SM, Boyd A, Gill MJ, Grabar S, Jarrin I, Obel N, Touloumi G, Zangerle R, Rauch A, Rentsch CT, Satre DD, Silverberg MJ, Bonnet F, Guest J, Burkholder G, Crane H, Teira R, Berenguer J, Wyen C, Abgrall S, Hessamfar M, Reiss P, d'Arminio Monforte A, McGinnis KA, Sterne JAC, Wittkop L, Antiretroviral Therapy Cohort Collaboration.",,Journal of viral hepatitis,2023,2023-06-20,Y,Mortality; Alcohol; Hepatitis C virus; HIV; Cohort; Cause-specific,,,"Among persons with HIV (PWH), higher alcohol use and having hepatitis C virus (HCV) are separately associated with increased morbidity and mortality. We investigated whether the association between alcohol use and mortality among PWH is modified by HCV. Data were combined from European and North American cohorts of adult PWH who started antiretroviral therapy (ART). Self-reported alcohol use data, collected in diverse ways between cohorts, were converted to grams/day. Eligible PWH started ART during 2001-2017 and were followed from ART initiation for mortality. Interactions between the associations of baseline alcohol use (0, 0.1-20.0, >20.0 g/day) and HCV status were assessed using multivariable Cox models. Of 58,769 PWH, 29,711 (51%), 23,974 (41%) and 5084 (9%) self-reported alcohol use of 0 g/day, 0.1-20.0 g/day, and > 20.0 g/day, respectively, and 4799 (8%) had HCV at baseline. There were 844 deaths in 37,729 person-years and 2755 deaths in 443,121 person-years among those with and without HCV, respectively. Among PWH without HCV, adjusted hazard ratios (aHRs) for mortality were 1.18 (95% CI: 1.08-1.29) for 0.0 g/day and 1.84 (1.62-2.09) for >20.0 g/day compared with 0.1-20.0 g/day. This J-shaped pattern was absent among those with HCV: aHRs were 1.00 (0.86-1.17) for 0.0 g/day and 1.64 (1.33-2.02) for >20.0 g/day compared with 0.1-20.0 g/day (interaction p < .001). Among PWH without HCV, mortality was higher in both non-drinkers and heavy drinkers compared with moderate alcohol drinkers. Among those with HCV, mortality was higher in heavy drinkers but not non-drinkers, potentially due to differing reasons for not drinking (e.g. illness) between those with and without HCV.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/jvh.13863; doi:https://doi.org/10.1111/jvh.13863; html:https://europepmc.org/articles/PMC10526649; pdf:https://europepmc.org/articles/PMC10526649?pdf=render -36256701,https://doi.org/10.1093/eurjcn/zvac098,Bed rest duration and complications after transfemoral cardiac catheterization: a network meta-analysis.,"Busca E, Airoldi C, Bertoncini F, Buratti G, Casarotto R, Gaboardi S, Faggiano F, Barisone M, White IR, Allara E, Dal Molin A.",,European journal of cardiovascular nursing,2023,2023-07-01,Y,Cardiac catheterization; Percutaneous coronary intervention; Systematic review; Network Meta-analysis; Femoral Access,,,"

Aims

To assess the effects of bed rest duration on short-term complications following transfemoral catheterization.

Methods and results

A systematic search was carried out in MEDLINE, Embase, CINAHL, Cochrane Database of Systematic Reviews, Scopus, SciELO and in five registries of grey literature. Randomized controlled trials and quasi-experimental studies comparing different durations of bed rest after transfemoral catheterization were included. Primary outcomes were haematoma and bleeding near the access site. Secondary outcomes were arteriovenous fistula, pseudoaneurysm, back pain, general patient discomfort and urinary discomfort. Study findings were summarized using a network meta-analysis (NMA). Twenty-eight studies and 9217 participants were included (mean age 60.4 years). In NMA, bed rest duration was not consistently associated with either primary outcome, and this was confirmed in sensitivity analyses. There was no evidence of associations with secondary outcomes, except for two effects related to back pain. A bed rest duration of 2-2.9 h was associated with lower risk of back pain [risk ratio (RR) 0.33, 95% confidence interval (CI) 0.17-0.62] and a duration over 12 h with greater risk of back pain (RR 1.94, 95% CI 1.16-3.24), when compared with the 4-5.9 h interval. Post hoc analysis revealed an increased risk of back pain per hour of bed rest (RR 1.08, 95% CI 1.04-1.11).

Conclusion

A short bed rest was not associated with complications in patients undergoing transfemoral catheterization; the greater the duration of bed rest, the more likely the patients were to experience back pain. Ambulation as early as 2 h after transfemoral catheterization can be safely implemented.

Registration

PROSPERO: CRD42014014222.",,pdf:https://academic.oup.com/eurjcn/advance-article-pdf/doi/10.1093/eurjcn/zvac098/47022353/zvac098.pdf; doi:https://doi.org/10.1093/eurjcn/zvac098; html:https://europepmc.org/articles/PMC10353909; pdf:https://europepmc.org/articles/PMC10353909?pdf=render 33323251,https://doi.org/10.1016/s2589-7500(19)30123-2,A comparison of deep learning performance against health-care professionals in detecting diseases from medical imaging: a systematic review and meta-analysis.,"Liu X, Faes L, Kale AU, Wagner SK, Fu DJ, Bruynseels A, Mahendiran T, Moraes G, Shamdas M, Kern C, Ledsam JR, Schmid MK, Balaskas K, Topol EJ, Bachmann LM, Keane PA, Denniston AK.",,The Lancet. Digital health,2019,2019-09-25,N,,,,"

Background

Deep learning offers considerable promise for medical diagnostics. We aimed to evaluate the diagnostic accuracy of deep learning algorithms versus health-care professionals in classifying diseases using medical imaging.

Methods

In this systematic review and meta-analysis, we searched Ovid-MEDLINE, Embase, Science Citation Index, and Conference Proceedings Citation Index for studies published from Jan 1, 2012, to June 6, 2019. Studies comparing the diagnostic performance of deep learning models and health-care professionals based on medical imaging, for any disease, were included. We excluded studies that used medical waveform data graphics material or investigated the accuracy of image segmentation rather than disease classification. We extracted binary diagnostic accuracy data and constructed contingency tables to derive the outcomes of interest: sensitivity and specificity. Studies undertaking an out-of-sample external validation were included in a meta-analysis, using a unified hierarchical model. This study is registered with PROSPERO, CRD42018091176.

Findings

Our search identified 31 587 studies, of which 82 (describing 147 patient cohorts) were included. 69 studies provided enough data to construct contingency tables, enabling calculation of test accuracy, with sensitivity ranging from 9·7% to 100·0% (mean 79·1%, SD 0·2) and specificity ranging from 38·9% to 100·0% (mean 88·3%, SD 0·1). An out-of-sample external validation was done in 25 studies, of which 14 made the comparison between deep learning models and health-care professionals in the same sample. Comparison of the performance between health-care professionals in these 14 studies, when restricting the analysis to the contingency table for each study reporting the highest accuracy, found a pooled sensitivity of 87·0% (95% CI 83·0-90·2) for deep learning models and 86·4% (79·9-91·0) for health-care professionals, and a pooled specificity of 92·5% (95% CI 85·1-96·4) for deep learning models and 90·5% (80·6-95·7) for health-care professionals.

Interpretation

Our review found the diagnostic performance of deep learning models to be equivalent to that of health-care professionals. However, a major finding of the review is that few studies presented externally validated results or compared the performance of deep learning models and health-care professionals using the same sample. Additionally, poor reporting is prevalent in deep learning studies, which limits reliable interpretation of the reported diagnostic accuracy. New reporting standards that address specific challenges of deep learning could improve future studies, enabling greater confidence in the results of future evaluations of this promising technology.

Funding

None.",,pdf:http://www.thelancet.com/article/S2589750019301232/pdf; doi:https://doi.org/10.1016/S2589-7500(19)30123-2 +36256701,https://doi.org/10.1093/eurjcn/zvac098,Bed rest duration and complications after transfemoral cardiac catheterization: a network meta-analysis.,"Busca E, Airoldi C, Bertoncini F, Buratti G, Casarotto R, Gaboardi S, Faggiano F, Barisone M, White IR, Allara E, Dal Molin A.",,European journal of cardiovascular nursing,2023,2023-07-01,Y,Cardiac catheterization; Percutaneous coronary intervention; Systematic review; Network Meta-analysis; Femoral Access,,,"

Aims

To assess the effects of bed rest duration on short-term complications following transfemoral catheterization.

Methods and results

A systematic search was carried out in MEDLINE, Embase, CINAHL, Cochrane Database of Systematic Reviews, Scopus, SciELO and in five registries of grey literature. Randomized controlled trials and quasi-experimental studies comparing different durations of bed rest after transfemoral catheterization were included. Primary outcomes were haematoma and bleeding near the access site. Secondary outcomes were arteriovenous fistula, pseudoaneurysm, back pain, general patient discomfort and urinary discomfort. Study findings were summarized using a network meta-analysis (NMA). Twenty-eight studies and 9217 participants were included (mean age 60.4 years). In NMA, bed rest duration was not consistently associated with either primary outcome, and this was confirmed in sensitivity analyses. There was no evidence of associations with secondary outcomes, except for two effects related to back pain. A bed rest duration of 2-2.9 h was associated with lower risk of back pain [risk ratio (RR) 0.33, 95% confidence interval (CI) 0.17-0.62] and a duration over 12 h with greater risk of back pain (RR 1.94, 95% CI 1.16-3.24), when compared with the 4-5.9 h interval. Post hoc analysis revealed an increased risk of back pain per hour of bed rest (RR 1.08, 95% CI 1.04-1.11).

Conclusion

A short bed rest was not associated with complications in patients undergoing transfemoral catheterization; the greater the duration of bed rest, the more likely the patients were to experience back pain. Ambulation as early as 2 h after transfemoral catheterization can be safely implemented.

Registration

PROSPERO: CRD42014014222.",,pdf:https://academic.oup.com/eurjcn/advance-article-pdf/doi/10.1093/eurjcn/zvac098/47022353/zvac098.pdf; doi:https://doi.org/10.1093/eurjcn/zvac098; html:https://europepmc.org/articles/PMC10353909; pdf:https://europepmc.org/articles/PMC10353909?pdf=render 36048760,https://doi.org/10.1371/journal.pgen.1010294,Neurocognitive trajectory and proteomic signature of inherited risk for Alzheimer's disease.,"Paranjpe MD, Chaffin M, Zahid S, Ritchie S, Rotter JI, Rich SS, Gerszten R, Guo X, Heckbert S, Tracy R, Danesh J, Lander ES, Inouye M, Kathiresan S, Butterworth AS, Khera AV.",,PLoS genetics,2022,2022-09-01,Y,,,,"For Alzheimer's disease-a leading cause of dementia and global morbidity-improved identification of presymptomatic high-risk individuals and identification of new circulating biomarkers are key public health needs. Here, we tested the hypothesis that a polygenic predictor of risk for Alzheimer's disease would identify a subset of the population with increased risk of clinically diagnosed dementia, subclinical neurocognitive dysfunction, and a differing circulating proteomic profile. Using summary association statistics from a recent genome-wide association study, we first developed a polygenic predictor of Alzheimer's disease comprised of 7.1 million common DNA variants. We noted a 7.3-fold (95% CI 4.8 to 11.0; p < 0.001) gradient in risk across deciles of the score among 288,289 middle-aged participants of the UK Biobank study. In cross-sectional analyses stratified by age, minimal differences in risk of Alzheimer's disease and performance on a digit recall test were present according to polygenic score decile at age 50 years, but significant gradients emerged by age 65. Similarly, among 30,541 participants of the Mass General Brigham Biobank, we again noted no significant differences in Alzheimer's disease diagnosis at younger ages across deciles of the score, but for those over 65 years we noted an odds ratio of 2.0 (95% CI 1.3 to 3.2; p = 0.002) in the top versus bottom decile of the polygenic score. To understand the proteomic signature of inherited risk, we performed aptamer-based profiling in 636 blood donors (mean age 43 years) with very high or low polygenic scores. In addition to the well-known apolipoprotein E biomarker, this analysis identified 27 additional proteins, several of which have known roles related to disease pathogenesis. Differences in protein concentrations were consistent even among the youngest subset of blood donors (mean age 33 years). Of these 28 proteins, 7 of the 8 proteins with concentrations available were similarly associated with the polygenic score in participants of the Multi-Ethnic Study of Atherosclerosis. These data highlight the potential for a DNA-based score to identify high-risk individuals during the prolonged presymptomatic phase of Alzheimer's disease and to enable biomarker discovery based on profiling of young individuals in the extremes of the score distribution.",,pdf:https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1010294&type=printable; doi:https://doi.org/10.1371/journal.pgen.1010294; html:https://europepmc.org/articles/PMC9436054; pdf:https://europepmc.org/articles/PMC9436054?pdf=render 35184736,https://doi.org/10.1186/s12916-022-02271-x,Comparative assessment of methods for short-term forecasts of COVID-19 hospital admissions in England at the local level.,"Meakin S, Abbott S, Bosse N, Munday J, Gruson H, Hellewell J, Sherratt K, CMMID COVID-19 Working Group, Funk S.",,BMC medicine,2022,2022-02-21,Y,Forecasting; Infectious disease; outbreak; Real-time; Ensemble; Healthcare Demand; Covid-19,,,"

Background

Forecasting healthcare demand is essential in epidemic settings, both to inform situational awareness and facilitate resource planning. Ideally, forecasts should be robust across time and locations. During the COVID-19 pandemic in England, it is an ongoing concern that demand for hospital care for COVID-19 patients in England will exceed available resources.

Methods

We made weekly forecasts of daily COVID-19 hospital admissions for National Health Service (NHS) Trusts in England between August 2020 and April 2021 using three disease-agnostic forecasting models: a mean ensemble of autoregressive time series models, a linear regression model with 7-day-lagged local cases as a predictor, and a scaled convolution of local cases and a delay distribution. We compared their point and probabilistic accuracy to a mean-ensemble of them all and to a simple baseline model of no change from the last day of admissions. We measured predictive performance using the weighted interval score (WIS) and considered how this changed in different scenarios (the length of the predictive horizon, the date on which the forecast was made, and by location), as well as how much admissions forecasts improved when future cases were known.

Results

All models outperformed the baseline in the majority of scenarios. Forecasting accuracy varied by forecast date and location, depending on the trajectory of the outbreak, and all individual models had instances where they were the top- or bottom-ranked model. Forecasts produced by the mean-ensemble were both the most accurate and most consistently accurate forecasts amongst all the models considered. Forecasting accuracy was improved when using future observed, rather than forecast, cases, especially at longer forecast horizons.

Conclusions

Assuming no change in current admissions is rarely better than including at least a trend. Using confirmed COVID-19 cases as a predictor can improve admissions forecasts in some scenarios, but this is variable and depends on the ability to make consistently good case forecasts. However, ensemble forecasts can make forecasts that make consistently more accurate forecasts across time and locations. Given minimal requirements on data and computation, our admissions forecasting ensemble could be used to anticipate healthcare needs in future epidemic or pandemic settings.",,pdf:https://bmcmedicine.biomedcentral.com/track/pdf/10.1186/s12916-022-02271-x; doi:https://doi.org/10.1186/s12916-022-02271-x; html:https://europepmc.org/articles/PMC8858706; pdf:https://europepmc.org/articles/PMC8858706?pdf=render 32623924,https://doi.org/10.1161/hypertensionaha.119.14302,Estimated 24-Hour Urinary Sodium Excretion and Incident Cardiovascular Disease and Mortality Among 398 628 Individuals in UK Biobank.,"Elliott P, Muller DC, Schneider-Luftman D, Pazoki R, Evangelou E, Dehghan A, Neal B, Tzoulaki I.",,"Hypertension (Dallas, Tex. : 1979)",2020,2020-07-06,N,Cardiovascular diseases; Mortality; Blood pressure; risk,,,"We report on an analysis to explore the association between estimated 24-hour urinary sodium excretion (surrogate for sodium intake) and incident cardiovascular disease (CVD) and mortality. Data were obtained from 398 628 UK Biobank prospective cohort study participants (40-69 years) recruited between 2006 and 2010, with no history of CVD, renal disease, diabetes mellitus or cancer, and cardiovascular events and mortality recorded during follow-up. Hazard ratios between 24-hour sodium excretion were estimated from spot urinary sodium concentrations across incident CVD and its components and all-cause and cause-specific mortality. In restricted cubic splines analyses, there was little evidence for an association between estimated 24-hour sodium excretion and CVD, coronary heart disease, or stroke; hazard ratios for CVD (95% CIs) for the 15th and 85th percentiles (2.5 and 4.2 g/day, respectively) compared with the 50th percentile of estimated sodium excretion (3.2 g/day) were 1.05 (1.01-1.10) and 0.96 (0.92-1.00), respectively. An inverse association was observed with heart failure, but that was no longer apparent in sensitivity analysis. A J-shaped association was observed between estimated sodium excretion and mortality. Our findings do not support a J-shaped association of estimated sodium excretion with CVD, although such an association was apparent for all-cause and cause-specific mortality across a wide range of diseases. Reasons for these differences are unclear; methodological limitations, including the use of estimating equations based on spot urinary data, need to be considered in interpreting our findings.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/HYPERTENSIONAHA.119.14302; doi:https://doi.org/10.1161/HYPERTENSIONAHA.119.14302 @@ -1900,8 +1900,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 31653530,https://doi.org/10.1016/j.echo.2019.08.015,A Practical Guide to Assess the Reproducibility of Echocardiographic Measurements.,"Bunting KV, Steeds RP, Slater K, Rogers JK, Gkoutos GV, Kotecha D.",,Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography,2019,2019-10-22,N,Reproducibility; Echocardiography; Repeatability; reliability,,,"Echocardiography plays an essential role in the diagnosis and assessment of cardiovascular disease. Measurements derived from echocardiography are also used to determine the severity of disease, its progression over time, and to aid in the choice of optimal therapy. It is therefore clinically important that echocardiographic measurements be reproducible, repeatable, and reliable. There are a variety of statistical tests available to assess these parameters, and in this article the authors summarize those available for use by echocardiographers to improve their clinical practice. Correlation coefficients, linear regression, Bland-Altman plots, and the coefficient of variation are explored, along with their limitations. The authors also provide an online tool for the easy calculation of these statistics in the clinical environment (www.birmingham.ac.uk/echo). Quantifying and enhancing the reproducibility of echocardiography has important potential to improve the value of echocardiography as the basis for good clinical decision-making.",,pdf:http://www.onlinejase.com/article/S0894731719309460/pdf; doi:https://doi.org/10.1016/j.echo.2019.08.015 34396248,https://doi.org/10.1016/j.jaccao.2020.07.001,Prediction of Lifetime and 10-Year Risk of Cancer in Individual Patients With Established Cardiovascular Disease.,"van 't Klooster CC, Ridker PM, Cook NR, Aerts JGJV, Westerink J, Asselbergs FW, van der Graaf Y, Visseren FLJ, UCC-SMART Study Group.",,JACC. CardioOncology,2020,2020-08-28,Y,"Lung cancer; Colorectal Cancer; Risk Prediction; Crp, C-reactive Protein; Sd, Standard Deviation; Cvd, Cardiovascular Disease; Ci, Confidence Interval; Aic, Akaike’s Information Criterion",,,"

Background

Cardiovascular disease (CVD) and cancer share many common risk factors; patients with CVD also may be at risk of developing cancer.

Objectives

The aim of this study was to derive and externally validate prediction models for the estimation of lifetime and 10-year risk for total, colorectal, and lung cancer in patients with established CVD.

Methods

Data from patients with established CVD from the UCC-SMART cohort (N = 7,280) were used for model development, and from the CANTOS trial (N = 9,322) for model validation. Predictors were selected based on previously published cancer risk scores, clinical availability, and presence in the derivation dataset. Fine and Gray competing risk-adjusted lifetime models were developed for the outcomes total, colorectal, and lung cancer.

Results

Selected predictors were age, sex, smoking, weight, height, alcohol use, antiplatelet use, diabetes, and C-reactive protein. External calibration for the 4-year risk of lung, colorectal, and total cancer was reasonable in our models, as was discrimination with C-statistics of 0.74, 0.64, and 0.63, respectively. Median predicted lifetime and 10-year risks in CANTOS were 26% (range 1% to 52%) and 13% (range 1% to 31%) for total cancer; 4% (range 0% to 13%) and 2% (range 0% to 6%) for colorectal cancer; and 5% (range 0% to 37%) and 2% (range 0% to 24%) for lung cancer.

Conclusions

Lifetime and 10-year risk of total, colorectal, and lung cancer can be estimated reasonably well in patients with established CVD with readily available clinical predictors. With additional study, these tools could be used in clinical practice to further aid in the emphasis of healthy lifestyle changes and to guide thresholds for targeted diagnostics and screening.",,doi:https://doi.org/10.1016/j.jaccao.2020.07.001; doi:https://doi.org/10.1016/j.jaccao.2020.07.001; html:https://europepmc.org/articles/PMC8352343; pdf:https://europepmc.org/articles/PMC8352343?pdf=render 31492797,https://doi.org/10.1136/bmjopen-2019-032165,Evaluation of the impact of the GRACE risk score on the management and outcome of patients hospitalised with non-ST elevation acute coronary syndrome in the UK: protocol of the UKGRIS cluster-randomised registry-based trial.,"Everett CC, Fox KA, Reynolds C, Fernandez C, Sharples L, Stocken DD, Carruthers K, Hemingway H, Yan AT, Goodman SG, Brieger D, Chew DP, Gale CP.",,BMJ open,2019,2019-09-05,Y,Risk stratification; acute coronary syndrome; Grace; Nsteacs; Cluster Randomised Trial; Guideline-indicated Treatment,"Better, Faster and More Efficient Clinical Trials",,"

Introduction

For non-ST-segment elevation acute coronary syndrome (NSTEACS) there is a gap between the use of class I guideline recommended therapies and clinical practice. The Global Registry of Acute Coronary Events (GRACE) risk score is recommended in international guidelines for the risk stratification of NSTEACS, but its impact on adherence to guideline-indicated treatments and reducing adverse clinical outcomes is unknown. The objective of the UK GRACE Risk Score Intervention Study (UKGRIS) trial is to assess the effectiveness of the GRACE risk score tool and associated treatment recommendations on the use of guideline-indicated care and clinical outcomes.

Methods and analysis

The UKGRIS, a parallel-group cluster randomised registry-based controlled trial, will allocate hospitals in a 1:1 ratio to manage NSTEACS by standard care or according to the GRACE risk score and associated international guidelines. UKGRIS will recruit a minimum of 3000 patients from at least 30 English National Health Service hospitals and collect healthcare data from national electronic health records. The co-primary endpoints are the use of guideline-indicated therapies, and the composite of cardiovascular death, non-fatal myocardial infarction, new onset heart failure hospitalisation or cardiovascular readmission at 12 months. Secondary endpoints include duration of inpatient hospital stay over 12 months, EQ-5D-5L responses and utilities, unscheduled revascularisation and the components of the composite endpoint over 12 months follow-up.

Ethics and dissemination

The study has ethical approval (North East - Tyne & Wear South Research Ethics Committee reference: 14/NE/1180). Findings will be announced at relevant conferences and published in peer-reviewed journals in line with the funder's open access policy.

Trial registration number

ISRCTN29731761; Pre-results.",,pdf:https://bmjopen.bmj.com/content/bmjopen/9/9/e032165.full.pdf; doi:https://doi.org/10.1136/bmjopen-2019-032165; html:https://europepmc.org/articles/PMC6731819; pdf:https://europepmc.org/articles/PMC6731819?pdf=render -37104291,https://doi.org/10.1371/journal.pmed.1004221,A nutritional biomarker score of the Mediterranean diet and incident type 2 diabetes: Integrated analysis of data from the MedLey randomised controlled trial and the EPIC-InterAct case-cohort study.,"Sobiecki JG, Imamura F, Davis CR, Sharp SJ, Koulman A, Hodgson JM, Guevara M, Schulze MB, Zheng JS, Agnoli C, Bonet C, Colorado-Yohar SM, Fagherazzi G, Franks PW, Gundersen TE, Jannasch F, Kaaks R, Katzke V, Molina-Montes E, Nilsson PM, Palli D, Panico S, Papier K, Rolandsson O, Sacerdote C, Tjønneland A, Tong TYN, van der Schouw YT, Danesh J, Butterworth AS, Riboli E, Murphy KJ, Wareham NJ, Forouhi NG.",,PLoS medicine,2023,2023-04-27,Y,,,,"

Background

Self-reported adherence to the Mediterranean diet has been modestly inversely associated with incidence of type 2 diabetes (T2D) in cohort studies. There is uncertainty about the validity and magnitude of this association due to subjective reporting of diet. The association has not been evaluated using an objectively measured biomarker of the Mediterranean diet.

Methods and findings

We derived a biomarker score based on 5 circulating carotenoids and 24 fatty acids that discriminated between the Mediterranean or habitual diet arms of a parallel design, 6-month partial-feeding randomised controlled trial (RCT) conducted between 2013 and 2014, the MedLey trial (128 participants out of 166 randomised). We applied this biomarker score in an observational study, the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study, to assess the association of the score with T2D incidence over an average of 9.7 years of follow-up since the baseline (1991 to 1998). We included 22,202 participants, of whom 9,453 were T2D cases, with relevant biomarkers from an original case-cohort of 27,779 participants sampled from a cohort of 340,234 people. As a secondary measure of the Mediterranean diet, we used a score estimated from dietary-self report. Within the trial, the biomarker score discriminated well between the 2 arms; the cross-validated C-statistic was 0.88 (95% confidence interval (CI) 0.82 to 0.94). The score was inversely associated with incident T2D in EPIC-InterAct: the hazard ratio (HR) per standard deviation of the score was 0.71 (95% CI: 0.65 to 0.77) following adjustment for sociodemographic, lifestyle and medical factors, and adiposity. In comparison, the HR per standard deviation of the self-reported Mediterranean diet was 0.90 (95% CI: 0.86 to 0.95). Assuming the score was causally associated with T2D, higher adherence to the Mediterranean diet in Western European adults by 10 percentiles of the score was estimated to reduce the incidence of T2D by 11% (95% CI: 7% to 14%). The study limitations included potential measurement error in nutritional biomarkers, unclear specificity of the biomarker score to the Mediterranean diet, and possible residual confounding.

Conclusions

These findings suggest that objectively assessed adherence to the Mediterranean diet is associated with lower risk of T2D and that even modestly higher adherence may have the potential to reduce the population burden of T2D meaningfully.

Trial registration

Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12613000602729 https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=363860.",,pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1004221&type=printable; doi:https://doi.org/10.1371/journal.pmed.1004221; html:https://europepmc.org/articles/PMC10138823; pdf:https://europepmc.org/articles/PMC10138823?pdf=render 34661196,https://doi.org/10.1093/ehjopen/oeab019,Pericoronary and periaortic adipose tissue density are associated with inflammatory disease activity in Takayasu arteritis and atherosclerosis.,"Wall C, Huang Y, Le EPV, Ćorović A, Uy CP, Gopalan D, Ma C, Manavaki R, Fryer TD, Aloj L, Graves MJ, Tombetti E, Ariff B, Bambrough P, Hoole SP, Rusk RA, Jayne DR, Dweck MR, Newby D, Fayad ZA, Bennett MR, Peters JE, Slomka P, Dey D, Mason JC, Rudd JHF, Tarkin JM.",,European heart journal open,2021,2021-08-06,Y,coronary artery disease; Takayasu Arteritis; Pericoronary Adipose Tissue Density,,,"

Aims

To examine pericoronary adipose tissue (PCAT) and periaortic adipose tissue (PAAT) density on coronary computed tomography angiography for assessing arterial inflammation in Takayasu arteritis (TAK) and atherosclerosis.

Methods and results

PCAT and PAAT density was measured in coronary (n = 1016) and aortic (n = 108) segments from 108 subjects [TAK + coronary artery disease (CAD), n = 36; TAK, n = 18; atherosclerotic CAD, n = 32; matched controls, n = 22]. Median PCAT and PAAT densities varied between groups (mPCAT: P < 0.0001; PAAT: P = 0.0002). PCAT density was 7.01 ± standard error of the mean (SEM) 1.78 Hounsfield Unit (HU) higher in coronary segments from TAK + CAD patients than stable CAD patients (P = 0.0002), and 8.20 ± SEM 2.04 HU higher in TAK patients without CAD than controls (P = 0.0001). mPCAT density was correlated with Indian Takayasu Clinical Activity Score (r = 0.43, P = 0.001) and C-reactive protein (r = 0.41, P < 0.0001) and was higher in active vs. inactive TAK (P = 0.002). mPCAT density above -74 HU had 100% sensitivity and 95% specificity for differentiating active TAK from controls [area under the curve = 0.99 (95% confidence interval 0.97-1)]. The association of PCAT density and coronary arterial inflammation measured by 68Ga-DOTATATE positron emission tomography (PET) equated to an increase of 2.44 ± SEM 0.77 HU in PCAT density for each unit increase in 68Ga-DOTATATE maximum tissue-to-blood ratio (P = 0.002). These findings remained in multivariable sensitivity analyses adjusted for potential confounders.

Conclusions

PCAT and PAAT density are higher in TAK than atherosclerotic CAD or controls and are associated with clinical, biochemical, and PET markers of inflammation. Owing to excellent diagnostic accuracy, PCAT density could be useful as a clinical adjunct for assessing disease activity in TAK.",,pdf:https://academic.oup.com/ehjopen/article-pdf/1/2/oeab019/41727950/oeab019.pdf; doi:https://doi.org/10.1093/ehjopen/oeab019; html:https://europepmc.org/articles/PMC8508012; pdf:https://europepmc.org/articles/PMC8508012?pdf=render +37104291,https://doi.org/10.1371/journal.pmed.1004221,A nutritional biomarker score of the Mediterranean diet and incident type 2 diabetes: Integrated analysis of data from the MedLey randomised controlled trial and the EPIC-InterAct case-cohort study.,"Sobiecki JG, Imamura F, Davis CR, Sharp SJ, Koulman A, Hodgson JM, Guevara M, Schulze MB, Zheng JS, Agnoli C, Bonet C, Colorado-Yohar SM, Fagherazzi G, Franks PW, Gundersen TE, Jannasch F, Kaaks R, Katzke V, Molina-Montes E, Nilsson PM, Palli D, Panico S, Papier K, Rolandsson O, Sacerdote C, Tjønneland A, Tong TYN, van der Schouw YT, Danesh J, Butterworth AS, Riboli E, Murphy KJ, Wareham NJ, Forouhi NG.",,PLoS medicine,2023,2023-04-27,Y,,,,"

Background

Self-reported adherence to the Mediterranean diet has been modestly inversely associated with incidence of type 2 diabetes (T2D) in cohort studies. There is uncertainty about the validity and magnitude of this association due to subjective reporting of diet. The association has not been evaluated using an objectively measured biomarker of the Mediterranean diet.

Methods and findings

We derived a biomarker score based on 5 circulating carotenoids and 24 fatty acids that discriminated between the Mediterranean or habitual diet arms of a parallel design, 6-month partial-feeding randomised controlled trial (RCT) conducted between 2013 and 2014, the MedLey trial (128 participants out of 166 randomised). We applied this biomarker score in an observational study, the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study, to assess the association of the score with T2D incidence over an average of 9.7 years of follow-up since the baseline (1991 to 1998). We included 22,202 participants, of whom 9,453 were T2D cases, with relevant biomarkers from an original case-cohort of 27,779 participants sampled from a cohort of 340,234 people. As a secondary measure of the Mediterranean diet, we used a score estimated from dietary-self report. Within the trial, the biomarker score discriminated well between the 2 arms; the cross-validated C-statistic was 0.88 (95% confidence interval (CI) 0.82 to 0.94). The score was inversely associated with incident T2D in EPIC-InterAct: the hazard ratio (HR) per standard deviation of the score was 0.71 (95% CI: 0.65 to 0.77) following adjustment for sociodemographic, lifestyle and medical factors, and adiposity. In comparison, the HR per standard deviation of the self-reported Mediterranean diet was 0.90 (95% CI: 0.86 to 0.95). Assuming the score was causally associated with T2D, higher adherence to the Mediterranean diet in Western European adults by 10 percentiles of the score was estimated to reduce the incidence of T2D by 11% (95% CI: 7% to 14%). The study limitations included potential measurement error in nutritional biomarkers, unclear specificity of the biomarker score to the Mediterranean diet, and possible residual confounding.

Conclusions

These findings suggest that objectively assessed adherence to the Mediterranean diet is associated with lower risk of T2D and that even modestly higher adherence may have the potential to reduce the population burden of T2D meaningfully.

Trial registration

Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12613000602729 https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=363860.",,pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1004221&type=printable; doi:https://doi.org/10.1371/journal.pmed.1004221; html:https://europepmc.org/articles/PMC10138823; pdf:https://europepmc.org/articles/PMC10138823?pdf=render 34632432,https://doi.org/10.1016/s2666-5247(21)00128-2,Epidemiology of Mycobacterium abscessus in England: an observational study.,"Lipworth S, Hough N, Weston N, Muller-Pebody B, Phin N, Myers R, Chapman S, Flight W, Alexander E, Smith EG, Robinson E, Peto TEA, Crook DW, Walker AS, Hopkins S, Eyre DW, Walker TM.",,The Lancet. Microbe,2021,2021-10-01,Y,,,,"

Background

Mycobacterium abscessus has emerged as a significant clinical concern following reports that it is readily transmissible in health-care settings between patients with cystic fibrosis. We linked routinely collected whole-genome sequencing and health-care usage data with the aim of investigating the extent to which such transmission explains acquisition in patients with and without cystic fibrosis in England.

Methods

In this retrospective observational study, we analysed consecutive M abscessus whole-genome sequencing data from England (beginning of February, 2015, to Nov 14, 2019) to identify genomically similar isolates. Linkage to a national health-care usage database was used to investigate possible contacts between patients. Multivariable regression analysis was done to investigate factors associated with acquisition of a genomically clustered strain (genomic distance <25 single nucleotide polymorphisms [SNPs]).

Findings

2297 isolates from 906 patients underwent whole-genome sequencing as part of the routine Public Health England diagnostic service. Of 14 genomic clusters containing isolates from ten or more patients, all but one contained patients with cystic fibrosis and patients without cystic fibrosis. Patients with cystic fibrosis were equally likely to have clustered isolates (258 [60%] of 431 patients) as those without cystic fibrosis (322 [63%] of 513 patients; p=0·38). High-density phylogenetic clusters were randomly distributed over a wide geographical area. Most isolates with a closest genetic neighbour consistent with potential transmission had no identifiable relevant epidemiological contacts. Having a clustered isolate was independently associated with increasing age (adjusted odds ratio 1·14 per 10 years, 95% CI 1·04-1·26), but not time spent as an hospital inpatient or outpatient. We identified two sibling pairs with cystic fibrosis with genetically highly divergent isolates and one pair with closely related isolates, and 25 uninfected presumed household contacts with cystic fibrosis.

Interpretation

Previously identified widely disseminated dominant clones of M abscessus are not restricted to patients with cystic fibrosis and occur in other chronic respiratory diseases. Although our analysis showed a small number of cases where person-to-person transmission could not be excluded, it did not support this being a major mechanism for M abscessus dissemination at a national level in England. Overall, these data should reassure patients and clinicians that the risk of acquisition from other patients in health-care settings is relatively low and motivate future research efforts to focus on identifying routes of acquisition outside of the cystic fibrosis health-care-associated niche.

Funding

The National Institute for Health Research, Health Data Research UK, The Wellcome Trust, The Medical Research Council, and Public Health England.",,pdf:http://www.thelancet.com/article/S2666524721001282/pdf; doi:https://doi.org/10.1016/S2666-5247(21)00128-2; html:https://europepmc.org/articles/PMC8481905 32294163,https://doi.org/10.1093/europace/euaa039,Diagnosing arrhythmogenic right ventricular cardiomyopathy by 2010 Task Force Criteria: clinical performance and simplified practical implementation.,"Bosman LP, Cadrin-Tourigny J, Bourfiss M, Aliyari Ghasabeh M, Sharma A, Tichnell C, Roudijk RW, Murray B, Tandri H, Khairy P, Kamel IR, Zimmerman SL, Reitsma JB, Asselbergs FW, van Tintelen JP, van der Heijden JF, Hauer RNW, Calkins H, James CA, Te Riele ASJM.",,"Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology",2020,2020-05-01,Y,Diagnosis; Cardiomyopathy; ventricular arrhythmia; Arrhythmogenic Right Ventricular Cardiomyopathy,,,"

Aims

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is diagnosed by a complex set of clinical tests as per 2010 Task Force Criteria (TFC). Avoiding misdiagnosis is crucial to prevent sudden cardiac death as well as unnecessary implantable cardioverter-defibrillator implantations. This study aims to validate the overall performance of the TFC in a real-world cohort of patients referred for ARVC evaluation.

Methods and results

We included patients consecutively referred to our centres for ARVC evaluation. Patients were diagnosed by consensus of three independent clinical experts. Using this as a reference standard, diagnostic performance was measured for each individual criterion as well as the overall TFC classification. Of 407 evaluated patients (age 38 ± 17 years, 51% male), the expert panel diagnosed 66 (16%) with ARVC. The clinically observed TFC was false negative in 7/66 (11%) patients and false positive in 10/69 (14%) patients. Idiopathic outflow tract ventricular tachycardia was the most common alternative diagnosis. While the TFC performed well overall (sensitivity and specificity 92%), signal-averaged electrocardiogram (SAECG, P = 0.43), and several family history criteria (P ≥ 0.17) failed to discriminate. Eliminating these criteria reduced false positives without increasing false negatives (net reclassification improvement 4.3%, P = 0.019). Furthermore, all ARVC patients met at least one electrocardiogram (ECG) or arrhythmia criterion (sensitivity 100%).

Conclusion

The TFC perform well but are complex and can lead to misdiagnosis. Simplification by eliminating SAECG and several family history criteria improves diagnostic accuracy. Arrhythmogenic right ventricular cardiomyopathy can be ruled out using ECG and arrhythmia criteria alone, hence these tests may serve as a first-line screening strategy among at-risk individuals.",,pdf:https://academic.oup.com/europace/article-pdf/22/5/787/33178222/euaa039.pdf; doi:https://doi.org/10.1093/europace/euaa039; html:https://europepmc.org/articles/PMC7203633; pdf:https://europepmc.org/articles/PMC7203633?pdf=render 35189884,https://doi.org/10.1186/s12913-022-07607-0,Factors influencing follow-up care post-TIA and minor stroke: a qualitative study using the theoretical domains framework.,"Turner GM, Aquino MRJV, Atkins L, Foy R, Mant J, Calvert M.",,BMC health services research,2022,2022-02-21,Y,Follow-up; Transient Ischaemic Attack; Tia; Minor Stroke; Theoretical Domains Framework,,,"

Background

Follow-up care after transient ischaemic attack (TIA) and minor stroke has been found to be sub-optimal, with individuals often feeling abandoned. We aimed to explore factors influencing holistic follow-up care after TIA and minor stroke.

Methods

Qualitative semi-structured interviews with 24 healthcare providers (HCPs): 5 stroke doctors, 4 nurses, 9 allied health professionals and 6 general practitioners. Participants were recruited from three TIA clinics, seven general practices and one community care trust in the West Midlands, England. Interview transcripts were deductively coded using the Theoretical Domains Framework and themes were generated from coded data.

Results

There was no clear pathway for supporting people with TIA or minor stroke after rapid specialist review in hospital; consequently, these patients had limited access to HCPs from all settings ('Environmental context and resources'). There was lack of understanding of potential needs post-TIA/minor stroke, in particular residual problems such as anxiety/fatigue ('Knowledge'). Identification and management of needs was largely influenced by HCPs' perceived role, professional training ('Social professional role and identity') and time constraints ('Environmental context and resources'). Follow-up was often passive - with onerous on patients to seek support - and predominantly focused on acute medical management ('Intentions'/'Goal').

Conclusions

Follow-up care post-TIA/minor stroke is currently sub-optimal. Through identifying factors which influence follow-up, we can inform guidelines and practical strategies to improve holistic healthcare.",,pdf:https://bmchealthservres.biomedcentral.com/track/pdf/10.1186/s12913-022-07607-0; doi:https://doi.org/10.1186/s12913-022-07607-0; html:https://europepmc.org/articles/PMC8859903; pdf:https://europepmc.org/articles/PMC8859903?pdf=render @@ -1914,8 +1914,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 32222069,https://doi.org/10.1111/bjd.19052,Risk of hospitalization and death due to infection in people with psoriasis: a population-based cohort study using the Clinical Practice Research Datalink.,"Yiu ZZN, Parisi R, Lunt M, Warren RB, Griffiths CEM, Langan SM, Ashcroft DM.",,The British journal of dermatology,2021,2020-05-12,N,,,,"

Background

Psoriasis is associated with risk factors for serious infections, but the independent relationship between psoriasis and serious infection is as yet unclear.

Objectives

To determine whether people with psoriasis have a higher risk of hospitalization due to any infection, respiratory infections, soft-tissue and skin infections, or a higher risk of death due to infection.

Methods

We conducted a cohort study of people (≥ 18 years) with psoriasis using the UK Clinical Practice Research Datalink (CPRD GOLD) linked to Hospital Episode Statistics (HES) and Office for National Statistics (ONS) mortality records between 1 April 2003 and 31 December 2016, and matched with up to six comparators on age, sex and general practice. Hospitalization was ascertained from HES records; death was ascertained from ONS mortality records. Stratified Cox proportional hazard models were estimated, with stepwise adjustment in different models for potential confounders or mediators between psoriasis and serious infection.

Results

There were 69 315 people with psoriasis and 338 620 comparators who were followed up for a median (interquartile range) of 4·9 (5·9) and 5·1 (6·3) years, respectively. People with psoriasis had a higher incidence rate of serious infection [20·5 per 1000 person-years, 95% confidence interval (CI) 20·0-21·0, n = 7631] compared with those without psoriasis (16·1 per 1000 person-years, 95% CI 15·9-16·3, n = 30 761). The fully adjusted hazard ratio for the association between psoriasis and serious infection was 1·36 (95% CI 1·31-1·40), with similar results across the other outcomes.

Conclusions

Psoriasis is associated with a small increase in the risk of serious infection. Further research is needed to understand how psoriasis predisposes to a higher risk of infection.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/bjd.19052; doi:https://doi.org/10.1111/bjd.19052 33090454,https://doi.org/10.1111/bjd.19597,Atopic eczema and obesity: a population-based study.,"Ascott A, Mansfield KE, Schonmann Y, Mulick A, Abuabara K, Roberts A, Smeeth L, Langan SM.",,The British journal of dermatology,2021,2020-12-01,N,,,,"

Background

Atopic eczema is a common chronic inflammatory skin disease. Research suggests an association between atopic eczema and obesity, with inconsistent evidence from European populations.

Objectives

To explore the association between diagnosed atopic eczema and being overweight or obese, and whether increased atopic eczema severity was associated with higher body mass index.

Methods

We undertook a cross-sectional analysis within a cohort of adults (matched by age, sex and general practice) with and without a diagnosis of atopic eczema. We used primary care (Clinical Practice Research Datalink Gold) and linked hospital admissions data (1998-2016). We used conditional logistic regression to compare the odds of being overweight or obese (adjusting for confounders and potential mediators) in those with atopic eczema (mild, moderate and severe, and all eczema) vs. those without.

Results

We identified 441 746 people with atopic eczema, matched to 1 849 722 without. People with atopic eczema had slightly higher odds of being overweight or obese vs. those without [odds ratio (OR) 1·08, 95% confidence interval (CI) 1·07-1·09] after adjusting for age, asthma and socioeconomic deprivation. Adjusting for potential mediators (high-dose glucocorticoids, harmful alcohol use, anxiety, depression, smoking) had a minimal impact on effect estimates (OR 1·07, 95% CI 1·06-1·08). We saw no evidence that odds of being overweight or obese increased with increasing atopic eczema severity, and there was no association in people with severe eczema.

Conclusions

We found evidence of a small overall association between atopic eczema and being overweight or obese. However, there was no association with obesity among those with the most severe eczema. Our findings are largely reassuring for this prevalent patient group who may already have an increased risk of cardiovascular disease.",,pdf:https://researchonline.lshtm.ac.uk/id/eprint/4658151/1/Ascott-etal-2020_Atopic_eczema_and-obesity.pdf; doi:https://doi.org/10.1111/bjd.19597 33637859,https://doi.org/10.1038/s41746-021-00404-9,Automatic multilabel detection of ICD10 codes in Dutch cardiology discharge letters using neural networks.,"Sammani A, Bagheri A, van der Heijden PGM, Te Riele ASJM, Baas AF, Oosters CAJ, Oberski D, Asselbergs FW.",,NPJ digital medicine,2021,2021-02-26,Y,,,,"Standard reference terminology of diagnoses and risk factors is crucial for billing, epidemiological studies, and inter/intranational comparisons of diseases. The International Classification of Disease (ICD) is a standardized and widely used method, but the manual classification is an enormously time-consuming endeavor. Natural language processing together with machine learning allows automated structuring of diagnoses using ICD-10 codes, but the limited performance of machine learning models, the necessity of gigantic datasets, and poor reliability of terminal parts of these codes restricted clinical usability. We aimed to create a high performing pipeline for automated classification of reliable ICD-10 codes in the free medical text in cardiology. We focussed on frequently used and well-defined three- and four-digit ICD-10 codes that still have enough granularity to be clinically relevant such as atrial fibrillation (I48), acute myocardial infarction (I21), or dilated cardiomyopathy (I42.0). Our pipeline uses a deep neural network known as a Bidirectional Gated Recurrent Unit Neural Network and was trained and tested with 5548 discharge letters and validated in 5089 discharge and procedural letters. As in clinical practice discharge letters may be labeled with more than one code, we assessed the single- and multilabel performance of main diagnoses and cardiovascular risk factors. We investigated using both the entire body of text and only the summary paragraph, supplemented by age and sex. Given the privacy-sensitive information included in discharge letters, we added a de-identification step. The performance was high, with F1 scores of 0.76-0.99 for three-character and 0.87-0.98 for four-character ICD-10 codes, and was best when using complete discharge letters. Adding variables age/sex did not affect results. For model interpretability, word coefficients were provided and qualitative assessment of classification was manually performed. Because of its high performance, this pipeline can be useful to decrease the administrative burden of classifying discharge diagnoses and may serve as a scaffold for reimbursement and research applications.",,pdf:https://www.nature.com/articles/s41746-021-00404-9.pdf; doi:https://doi.org/10.1038/s41746-021-00404-9; html:https://europepmc.org/articles/PMC7910461; pdf:https://europepmc.org/articles/PMC7910461?pdf=render -33941991,https://doi.org/10.1016/j.rse.2021.112339,"Multimodal deep learning from satellite and street-level imagery for measuring income, overcrowding, and environmental deprivation in urban areas.","Suel E, Bhatt S, Brauer M, Flaxman S, Ezzati M.",,Remote sensing of environment,2021,2021-05-01,Y,Segmentation; Satellite Images; Convolutional Neural Networks; Street-Level Images; Urban Measurements,,,"Data collected at large scale and low cost (e.g. satellite and street level imagery) have the potential to substantially improve resolution, spatial coverage, and temporal frequency of measurement of urban inequalities. Multiple types of data from different sources are often available for a given geographic area. Yet, most studies utilize a single type of input data when making measurements due to methodological difficulties in their joint use. We propose two deep learning-based methods for jointly utilizing satellite and street level imagery for measuring urban inequalities. We use London as a case study for three selected outputs, each measured in decile classes: income, overcrowding, and environmental deprivation. We compare the performances of our proposed multimodal models to corresponding unimodal ones using mean absolute error (MAE). First, satellite tiles are appended to street level imagery to enhance predictions at locations where street images are available leading to improvements in accuracy by 20, 10, and 9% in units of decile classes for income, overcrowding, and living environment. The second approach, novel to the best of our knowledge, uses a U-Net architecture to make predictions for all grid cells in a city at high spatial resolution (e.g. for 3 m × 3 m pixels in London in our experiments). It can utilize city wide availability of satellite images as well as more sparse information from street-level images where they are available leading to improvements in accuracy by 6, 10, and 11%. We also show examples of prediction maps from both approaches to visually highlight performance differences.",,doi:https://doi.org/10.1016/j.rse.2021.112339; doi:https://doi.org/10.1016/j.rse.2021.112339; html:https://europepmc.org/articles/PMC7985619; pdf:https://europepmc.org/articles/PMC7985619?pdf=render 33493433,https://doi.org/10.1016/s1470-2045(20)30743-9,"The impact of the COVID-19 pandemic on radiotherapy services in England, UK: a population-based study.","Spencer K, Jones CM, Girdler R, Roe C, Sharpe M, Lawton S, Miller L, Lewis P, Evans M, Sebag-Montefiore D, Roques T, Smittenaar R, Morris E.",,The Lancet. Oncology,2021,2021-01-22,Y,,,,"

Background

The indirect impact of the COVID-19 pandemic on cancer outcomes is of increasing concern. However, the extent to which key treatment modalities have been affected is unclear. We aimed to assess the impact of the pandemic on radiotherapy activity in England.

Methods

In this population-based study, data relating to all radiotherapy delivered for cancer in the English NHS, between Feb 4, 2019, and June 28, 2020, were extracted from the National Radiotherapy Dataset. Changes in mean weekly radiotherapy courses, attendances (reflecting fractions), and fractionation patterns following the start of the UK lockdown were compared with corresponding months in 2019 overall, for specific diagnoses, and across age groups. The significance of changes in radiotherapy activity during lockdown was examined using interrupted time-series (ITS) analysis.

Findings

In 2020, mean weekly radiotherapy courses fell by 19·9% in April, 6·2% in May, and 11·6% in June compared with corresponding months in 2019. A relatively greater fall was observed for attendances (29·1% in April, 31·4% in May, and 31·5% in June). These changes were significant on ITS analysis (p<0·0001). A greater reduction in treatment courses between 2019 and 2020 was seen for patients aged 70 years or older compared with those aged younger than 70 years (34·4% vs 7·3% in April). By diagnosis, the largest reduction from 2019 to 2020 in treatment courses was for prostate cancer (77·0% in April) and non-melanoma skin cancer (72·4% in April). Conversely, radiotherapy courses in April, 2020, compared with April, 2019, increased by 41·2% in oesophageal cancer, 64·2% in bladder cancer, and 36·3% in rectal cancer. Increased use of ultra-hypofractionated (26 Gy in five fractions) breast radiotherapy as a percentage of all courses (0·2% in April, 2019, to 60·6% in April, 2020; ITS p<0·0001) contributed to the substantial reduction in attendances.

Interpretation

Radiotherapy activity fell significantly, but use of hypofractionated regimens rapidly increased in the English NHS during the first peak of the COVID-19 pandemic. An increase in treatments for some cancers suggests that radiotherapy compensated for reduced surgical activity. These data will assist health-care providers in understanding the indirect consequences of the pandemic and the role of radiotherapy services in minimising these consequences.

Funding

None.",,pdf:http://www.thelancet.com/article/S1470204520307439/pdf; doi:https://doi.org/10.1016/S1470-2045(20)30743-9; html:https://europepmc.org/articles/PMC7825861; pdf:https://europepmc.org/articles/PMC7825861?pdf=render +33941991,https://doi.org/10.1016/j.rse.2021.112339,"Multimodal deep learning from satellite and street-level imagery for measuring income, overcrowding, and environmental deprivation in urban areas.","Suel E, Bhatt S, Brauer M, Flaxman S, Ezzati M.",,Remote sensing of environment,2021,2021-05-01,Y,Segmentation; Satellite Images; Convolutional Neural Networks; Street-Level Images; Urban Measurements,,,"Data collected at large scale and low cost (e.g. satellite and street level imagery) have the potential to substantially improve resolution, spatial coverage, and temporal frequency of measurement of urban inequalities. Multiple types of data from different sources are often available for a given geographic area. Yet, most studies utilize a single type of input data when making measurements due to methodological difficulties in their joint use. We propose two deep learning-based methods for jointly utilizing satellite and street level imagery for measuring urban inequalities. We use London as a case study for three selected outputs, each measured in decile classes: income, overcrowding, and environmental deprivation. We compare the performances of our proposed multimodal models to corresponding unimodal ones using mean absolute error (MAE). First, satellite tiles are appended to street level imagery to enhance predictions at locations where street images are available leading to improvements in accuracy by 20, 10, and 9% in units of decile classes for income, overcrowding, and living environment. The second approach, novel to the best of our knowledge, uses a U-Net architecture to make predictions for all grid cells in a city at high spatial resolution (e.g. for 3 m × 3 m pixels in London in our experiments). It can utilize city wide availability of satellite images as well as more sparse information from street-level images where they are available leading to improvements in accuracy by 6, 10, and 11%. We also show examples of prediction maps from both approaches to visually highlight performance differences.",,doi:https://doi.org/10.1016/j.rse.2021.112339; doi:https://doi.org/10.1016/j.rse.2021.112339; html:https://europepmc.org/articles/PMC7985619; pdf:https://europepmc.org/articles/PMC7985619?pdf=render 35144751,https://doi.org/10.1016/j.jacc.2021.11.045,Echocardiographic Deformation Imaging for Early Detection of Genetic Cardiomyopathies: JACC Review Topic of the Week.,"Taha K, Kirkels FP, Teske AJ, Asselbergs FW, van Tintelen JP, Doevendans PA, Kutty S, Haugaa KH, Cramer MJ.",,Journal of the American College of Cardiology,2022,2022-02-01,N,Early Detection; Speckle Tracking; Family Screening; Deformation Imaging; Genetic Cardiomyopathy,,,"Clinical screening of the relatives of patients with genetic cardiomyopathies is challenging, as they often lack detectable cardiac abnormalities at presentation. Life-threatening adverse events can already occur in these early stages of disease, so sensitive tools to reveal the earliest signs of disease are needed. The utility of echocardiographic deformation imaging for early detection has been explored for this population in multiple studies but has not been broadly implemented in clinical practice. The authors discuss contemporary evidence on the utility of deformation imaging in relatives of patients with genetic cardiomyopathies. The available body of data shows that deformation imaging reveals early disease-specific abnormalities in dilated cardiomyopathy, hypertrophic cardiomyopathy, and arrhythmogenic cardiomyopathy. Deformation imaging seems promising to enhance the screening and follow-up protocols in relatives, and the authors propose measures to accelerate its implementation in clinical care.",,doi:https://doi.org/10.1016/j.jacc.2021.11.045; doi:https://doi.org/10.1016/j.jacc.2021.11.045 34468736,https://doi.org/10.1093/europace/euab162,Comparing clinical performance of current implantable cardioverter-defibrillator implantation recommendations in arrhythmogenic right ventricular cardiomyopathy.,"Bosman LP, Bosman LP, Nielsen Gerlach CL, Cadrin-Tourigny J, Orgeron G, Tichnell C, Murray B, Bourfiss M, van der Heijden JF, Yap SC, Zeppenfeld K, van den Berg MP, Wilde AAM, Asselbergs FW, Tandri H, Calkins H, van Tintelen JP, James CA, Te Riele ASJM.",,"Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology",2022,2022-02-01,Y,Prognosis; Risk stratification; Ventricular Arrhythmias; Implantable Cardioverter-defibrillator; Arrhythmogenic Right Ventricular Cardiomyopathy,,,"

Aims

Arrhythmogenic right ventricular cardiomyopathy (ARVC) patients have an increased risk of ventricular arrhythmias (VA). Four implantable cardioverter-defibrillator (ICD) recommendation algorithms are available The International Task Force Consensus ('ITFC'), an ITFC modification by Orgeron et al. ('mITFC'), the AHA/HRS/ACC guideline for VA management ('AHA'), and the HRS expert consensus statement ('HRS'). This study aims to validate and compare the performance of these algorithms in ARVC.

Methods and results

We classified 617 definite ARVC patients (38.5 ± 15.1 years, 52.4% male, 39.2% prior sustained VA) according to four algorithms. Clinical performance was evaluated by sensitivity, specificity, ROC-analysis, and decision curve analysis for any sustained VA and for fast VA (>250 b.p.m.). During 6.4 [2.8-11.5] years follow-up, 282 (45.7%) patients experienced any sustained VA, and 63 (10.2%) fast VA. For any sustained VA, ITFC and mITFC provide higher sensitivity than AHA and HRS (94.0-97.8% vs. 76.7-83.5%), but lower specificity (15.9-32.0% vs. 42.7%-60.1%). Similarly, for fast VA, ITFC and mITFC provide higher sensitivity than AHA and HRS (95.2-97.1% vs. 76.7-78.4%) but lower specificity (42.7-43.1 vs. 76.7-78.4%). Decision curve analysis showed ITFC and mITFC to be superior for a 5-year sustained VA risk ICD indication threshold between 5-25% or 2-9% for fast VA.

Conclusion

The ITFC and mITFC provide the highest protection rates, whereas AHA and HRS decrease unnecessary ICD placements. ITFC or mITFC should be used if we consider the 5-year threshold for ICD indication to lie within 5-25% for sustained VA or 2-9% for fast VA. These data will inform decision-making for ICD placement in ARVC.",,pdf:https://academic.oup.com/europace/article-pdf/24/2/296/42370389/euab162.pdf; doi:https://doi.org/10.1093/europace/euab162; html:https://europepmc.org/articles/PMC8824519; pdf:https://europepmc.org/articles/PMC8824519?pdf=render 33246414,https://doi.org/10.1186/s12874-020-01163-z,Patient-specific record linkage between emergency department and hospital admission data for a cohort of people who inject drugs: methodological considerations for frequent presenters.,"Di Rico R, Nambiar D, Gabbe B, Stoové M, Dietze P.",,BMC medical research methodology,2020,2020-11-27,Y,Methods; Australia; Data Linkage; Record Linkage; Administrative Data; People Who Inject Drugs; Patient Pathways; Frequent Presenters; Vaed; Vemd,,,"

Background

People who inject drugs (PWID) have been identified as frequent users of emergency department (ED) and hospital inpatient services. The specific challenges of record linkage in cohorts with numerous administrative health records occurring in close proximity are not well understood. Here, we present a method for patient-specific record linkage of ED and hospital admission data for a cohort of PWID.

Methods

Data from 688 PWID were linked to two state-wide administrative health databases identifying all ED visits and hospital admissions for the cohort between January 2008 and June 2013. We linked patient-specific ED and hospital admissions data, using administrative date-time timestamps and pre-specified linkage criteria, to identify hospital admissions stemming from ED presentations for a given individual. The ability of standalone databases to identify linked ED visits or hospital admissions was examined.

Results

There were 3459 ED visits and 1877 hospital admissions identified during the study period. Thirty-four percent of ED visits were linked to hospital admissions. Most links had hospital admission timestamps in-between or identical to their ED visit timestamps (n = 1035, 87%). Allowing 24-h between ED visits and hospital admissions captured more linked records, but increased manual inspection requirements. In linked records (n = 1190), the ED 'departure status' variable correctly reflected subsequent hospital admission in only 68% of cases. The hospital 'admission type' variable was non-specific in identifying if a preceding ED visit had occurred.

Conclusions

Linking ED visits with subsequent hospital admissions in PWID requires access to date and time variables for accurate temporal sorting, especially for same-day presentations. Selecting time-windows to capture linked records requires discretion. Researchers risk under-ascertainment of hospital admissions if using ED data alone.",,pdf:https://bmcmedresmethodol.biomedcentral.com/track/pdf/10.1186/s12874-020-01163-z; doi:https://doi.org/10.1186/s12874-020-01163-z; html:https://europepmc.org/articles/PMC7694355; pdf:https://europepmc.org/articles/PMC7694355?pdf=render @@ -1933,18 +1933,18 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 34563860,https://doi.org/10.1016/j.media.2021.102228,Shape registration with learned deformations for 3D shape reconstruction from sparse and incomplete point clouds.,"Chen X, Ravikumar N, Xia Y, Attar R, Diaz-Pinto A, Piechnik SK, Neubauer S, Petersen SE, Frangi AF.",,Medical image analysis,2021,2021-09-09,N,Deep Learning; Graph Convolutional Network; Cardiac Mesh Reconstruction; Cardiac Surface Reconstruction; Contours To Mesh Reconstruction,,,"Shape reconstruction from sparse point clouds/images is a challenging and relevant task required for a variety of applications in computer vision and medical image analysis (e.g. surgical navigation, cardiac motion analysis, augmented/virtual reality systems). A subset of such methods, viz. 3D shape reconstruction from 2D contours, is especially relevant for computer-aided diagnosis and intervention applications involving meshes derived from multiple 2D image slices, views or projections. We propose a deep learning architecture, coined Mesh Reconstruction Network (MR-Net), which tackles this problem. MR-Net enables accurate 3D mesh reconstruction in real-time despite missing data and with sparse annotations. Using 3D cardiac shape reconstruction from 2D contours defined on short-axis cardiac magnetic resonance image slices as an exemplar, we demonstrate that our approach consistently outperforms state-of-the-art techniques for shape reconstruction from unstructured point clouds. Our approach can reconstruct 3D cardiac meshes to within 2.5-mm point-to-point error, concerning the ground-truth data (the original image spatial resolution is ∼1.8×1.8×10mm3). We further evaluate the robustness of the proposed approach to incomplete data, and contours estimated using an automatic segmentation algorithm. MR-Net is generic and could reconstruct shapes of other organs, making it compelling as a tool for various applications in medical image analysis.",,doi:https://doi.org/10.1016/j.media.2021.102228; doi:https://doi.org/10.1016/j.media.2021.102228 32564639,https://doi.org/10.1177/0300060520931298,Mortality statistics in England and Wales: the SARS-CoV-2 paradox.,"Harrison G, Newport D, Robbins T, Arvanitis TN, Stein A.",,The Journal of international medical research,2020,2020-06-01,Y,Respiratory disease; United Kingdom; Mortality Rate; Paradox; Covid-19; Sars-cov-2,,,"

Objective

To analyse mortality statistics in the United Kingdom during the initial phases of the severe acute respiratory coronavirus 2 (SARS-CoV-2) pandemic and to understand the impact of the pandemic on national mortality.

Methods

Retrospective review of weekly national mortality statistics in the United Kingdom over the past 5 years, including subgroup analysis of respiratory mortality rates.

Results

During the early phases of the SARS-CoV-2 pandemic in the first months of 2020, there were consistently fewer deaths per week compared with the preceding 5 years. This pattern was not observed at any other time within the past 5 years. We have termed this phenomenon the ""SARS-CoV-2 paradox."" We postulate potential explanations for this seeming paradox and explore the implications of these data.

Conclusions

Paradoxically, but potentially importantly, lower rather than higher weekly mortality rates were observed during the early stages of the SARS-CoV-2 pandemic. This paradox may have implications for current and future healthcare utilisation. A rebound increase in non-SARS-CoV-2 mortality later this year might coincide with the peak of SARS-CoV-2 admissions and mortality.",,doi:https://doi.org/10.1177/0300060520931298; doi:https://doi.org/10.1177/0300060520931298; html:https://europepmc.org/articles/PMC7307394; pdf:https://europepmc.org/articles/PMC7307394?pdf=render 33414548,https://doi.org/10.1038/s41588-020-00751-5,A cross-platform approach identifies genetic regulators of human metabolism and health.,"Lotta LA, Pietzner M, Stewart ID, Wittemans LBL, Li C, Bonelli R, Raffler J, Biggs EK, Oliver-Williams C, Auyeung VPW, Luan J, Wheeler E, Paige E, Surendran P, Michelotti GA, Scott RA, Burgess S, Zuber V, Sanderson E, Koulman A, Imamura F, Forouhi NG, Khaw KT, MacTel Consortium, Griffin JL, Wood AM, Kastenmüller G, Danesh J, Butterworth AS, Gribble FM, Reimann F, Bahlo M, Fauman E, Wareham NJ, Langenberg C.",,Nature genetics,2021,2021-01-07,N,,,,"In cross-platform analyses of 174 metabolites, we identify 499 associations (P < 4.9 × 10-10) characterized by pleiotropy, allelic heterogeneity, large and nonlinear effects and enrichment for nonsynonymous variation. We identify a signal at GLP2R (p.Asp470Asn) shared among higher citrulline levels, body mass index, fasting glucose-dependent insulinotropic peptide and type 2 diabetes, with β-arrestin signaling as the underlying mechanism. Genetically higher serine levels are shown to reduce the likelihood (by 95%) and predict development of macular telangiectasia type 2, a rare degenerative retinal disease. Integration of genomic and small molecule data across platforms enables the discovery of regulators of human metabolism and translation into clinical insights.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7612925; doi:https://doi.org/10.1038/s41588-020-00751-5; html:https://europepmc.org/articles/PMC7612925; pdf:https://europepmc.org/articles/PMC7612925?pdf=render; doi:https://doi.org/10.1038/s41588-020-00751-5 -38388497,https://doi.org/10.1038/s41467-024-45355-3,Concordance of randomised controlled trials for artificial intelligence interventions with the CONSORT-AI reporting guidelines.,"Martindale APL, Ng B, Ngai V, Kale AU, Ferrante di Ruffano L, Golub RM, Collins GS, Moher D, McCradden MD, Oakden-Rayner L, Rivera SC, Calvert M, Kelly CJ, Lee CS, Yau C, Chan AW, Keane PA, Beam AL, Denniston AK, Liu X.",,Nature communications,2024,2024-02-22,Y,,,,"The Consolidated Standards of Reporting Trials extension for Artificial Intelligence interventions (CONSORT-AI) was published in September 2020. Since its publication, several randomised controlled trials (RCTs) of AI interventions have been published but their completeness and transparency of reporting is unknown. This systematic review assesses the completeness of reporting of AI RCTs following publication of CONSORT-AI and provides a comprehensive summary of RCTs published in recent years. 65 RCTs were identified, mostly conducted in China (37%) and USA (18%). Median concordance with CONSORT-AI reporting was 90% (IQR 77-94%), although only 10 RCTs explicitly reported its use. Several items were consistently under-reported, including algorithm version, accessibility of the AI intervention or code, and references to a study protocol. Only 3 of 52 included journals explicitly endorsed or mandated CONSORT-AI. Despite a generally high concordance amongst recent AI RCTs, some AI-specific considerations remain systematically poorly reported. Further encouragement of CONSORT-AI adoption by journals and funders may enable more complete adoption of the full CONSORT-AI guidelines.",,pdf:https://www.nature.com/articles/s41467-024-45355-3.pdf; doi:https://doi.org/10.1038/s41467-024-45355-3; html:https://europepmc.org/articles/PMC10883966; pdf:https://europepmc.org/articles/PMC10883966?pdf=render 33391794,https://doi.org/10.1098/rsos.200958,"ACE inhibition and cardiometabolic risk factors, lung ACE2 and TMPRSS2 gene expression, and plasma ACE2 levels: a Mendelian randomization study.","Gill D, Arvanitis M, Carter P, Hernández Cordero AI, Jo B, Karhunen V, Larsson SC, Li X, Lockhart SM, Mason A, Pashos E, Saha A, Tan VY, Zuber V, Bossé Y, Fahle S, Hao K, Jiang T, Joubert P, Lunt AC, Ouwehand WH, Roberts DJ, Timens W, van den Berge M, Watkins NA, Battle A, Butterworth AS, Danesh J, Di Angelantonio E, Engelhardt BE, Peters JE, Sin DD, Burgess S.",,Royal Society open science,2020,2020-11-18,Y,Genetic epidemiology; Angiotensin-converting enzyme inhibitors; Mendelian Randomization; Covid-19,,,"Angiotensin-converting enzyme 2 (ACE2) and serine protease TMPRSS2 have been implicated in cell entry for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19). The expression of ACE2 and TMPRSS2 in the lung epithelium might have implications for the risk of SARS-CoV-2 infection and severity of COVID-19. We use human genetic variants that proxy angiotensin-converting enzyme (ACE) inhibitor drug effects and cardiovascular risk factors to investigate whether these exposures affect lung ACE2 and TMPRSS2 gene expression and circulating ACE2 levels. We observed no consistent evidence of an association of genetically predicted serum ACE levels with any of our outcomes. There was weak evidence for an association of genetically predicted serum ACE levels with ACE2 gene expression in the Lung eQTL Consortium (p = 0.014), but this finding did not replicate. There was evidence of a positive association of genetic liability to type 2 diabetes mellitus with lung ACE2 gene expression in the Gene-Tissue Expression (GTEx) study (p = 4 × 10-4) and with circulating plasma ACE2 levels in the INTERVAL study (p = 0.03), but not with lung ACE2 expression in the Lung eQTL Consortium study (p = 0.68). There were no associations of genetically proxied liability to the other cardiometabolic traits with any outcome. This study does not provide consistent evidence to support an effect of serum ACE levels (as a proxy for ACE inhibitors) or cardiometabolic risk factors on lung ACE2 and TMPRSS2 expression or plasma ACE2 levels.",,pdf:https://royalsocietypublishing.org/doi/pdf/10.1098/rsos.200958; doi:https://doi.org/10.1098/rsos.200958; html:https://europepmc.org/articles/PMC7735342; pdf:https://europepmc.org/articles/PMC7735342?pdf=render +38388497,https://doi.org/10.1038/s41467-024-45355-3,Concordance of randomised controlled trials for artificial intelligence interventions with the CONSORT-AI reporting guidelines.,"Martindale APL, Ng B, Ngai V, Kale AU, Ferrante di Ruffano L, Golub RM, Collins GS, Moher D, McCradden MD, Oakden-Rayner L, Rivera SC, Calvert M, Kelly CJ, Lee CS, Yau C, Chan AW, Keane PA, Beam AL, Denniston AK, Liu X.",,Nature communications,2024,2024-02-22,Y,,,,"The Consolidated Standards of Reporting Trials extension for Artificial Intelligence interventions (CONSORT-AI) was published in September 2020. Since its publication, several randomised controlled trials (RCTs) of AI interventions have been published but their completeness and transparency of reporting is unknown. This systematic review assesses the completeness of reporting of AI RCTs following publication of CONSORT-AI and provides a comprehensive summary of RCTs published in recent years. 65 RCTs were identified, mostly conducted in China (37%) and USA (18%). Median concordance with CONSORT-AI reporting was 90% (IQR 77-94%), although only 10 RCTs explicitly reported its use. Several items were consistently under-reported, including algorithm version, accessibility of the AI intervention or code, and references to a study protocol. Only 3 of 52 included journals explicitly endorsed or mandated CONSORT-AI. Despite a generally high concordance amongst recent AI RCTs, some AI-specific considerations remain systematically poorly reported. Further encouragement of CONSORT-AI adoption by journals and funders may enable more complete adoption of the full CONSORT-AI guidelines.",,pdf:https://www.nature.com/articles/s41467-024-45355-3.pdf; doi:https://doi.org/10.1038/s41467-024-45355-3; html:https://europepmc.org/articles/PMC10883966; pdf:https://europepmc.org/articles/PMC10883966?pdf=render 32040531,https://doi.org/10.1371/journal.pone.0228940,Risk assessment for hospital admission in patients with COPD; a multi-centre UK prospective observational study.,"Fermont JM, Bolton CE, Fisk M, Mohan D, Macnee W, Cockcroft JR, McEniery C, Fuld J, Cheriyan J, Tal-Singer R, Wilkinson IB, Wood AM, Polkey MI, Müllerova H.",,PloS one,2020,2020-02-10,Y,,Better Care,,"In chronic obstructive pulmonary disease (COPD), acute exacerbation of COPD requiring hospital admission is associated with mortality and healthcare costs. The ERICA study assessed multiple clinical measures in people with COPD, including the short physical performance battery (SPPB), a simple test of physical function with 3 components (gait speed, balance and sit-to-stand). We tested the hypothesis that SPPB score would relate to risk of hospital admissions and length of hospital stay. Data were analysed from 714 of the total 729 participants (434 men and 280 women) with COPD. Data from this prospective observational longitudinal study were obtained from 4 secondary and 1 tertiary centres from England, Scotland, and Wales. The main outcome measures were to estimate the risk of hospitalisation with acute exacerbation of COPD (AECOPD and length of hospital stay derived from hospital episode statistics (HES). In total, 291 of 714 individuals experienced 762 hospitalised AECOPD during five-year follow up. Poorer performance of SPPB was associated with both higher rate (IRR 1.08 per 1 point decrease, 95% CI 1.01 to 1.14) and increased length of stay (IRR 1.18 per 1 point decrease, 95% CI 1.10 to 1.27) for hospitalised AECOPD. For the individual sit-to-stand component of the SPPB, the association was even stronger (IRR 1.14, 95% CI 1.02 to 1.26 for rate and IRR 1.32, 95% CI 1.16 to 1.49 for length of stay for hospitalised AECOPD). The SPPB, and in particular the sit-to-stand component can both evaluate the risk of H-AECOPD and length of hospital stay in COPD. The SPPB can aid in clinical decision making and when prioritising healthcare resources.","This article looks at risk assessment for hospital admission in patients with Chronic Obstructive Pulmonary Disease (COPD), which is a group of lung conditions that make it difficult to empty air out of the lungs. The objective of the risk assessment was to eventually aid in clinical decision making and prioritising healthcare resources.",pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0228940&type=printable; doi:https://doi.org/10.1371/journal.pone.0228940; html:https://europepmc.org/articles/PMC7010290; pdf:https://europepmc.org/articles/PMC7010290?pdf=render 34459239,https://doi.org/10.1161/jaha.120.021115,Factor V Leiden and the Risk of Bleeding in Patients With Acute Coronary Syndromes Treated With Antiplatelet Therapy: Pooled Analysis of 3 Randomized Clinical Trials.,"Mahmoodi BK, Eriksson N, Ross S, Claassens DMF, Asselbergs FW, Meijer K, Siegbahn A, James S, Pare G, Wallentin L, Ten Berg JM.",,Journal of the American Heart Association,2021,2021-08-28,Y,Bleeding; acute coronary syndrome; Factor V Leiden; Antiplatelet Therapy,,,"Background Whether factor V Leiden is associated with lower bleeding risk in patients with acute coronary syndromes using (dual) antiplatelet therapy has yet to be investigated. Methods and Results We pooled data from 3 randomized clinical trials, conducted in patients with acute coronary syndromes, with adjudicated bleeding outcomes. Cox regression models were used to obtain overall and cause-specific hazard ratios (HRs) to account for competing risk of atherothrombotic outcomes (ie, composite of ischemic stroke, myocardial infarction, and cardiovascular death) in each study. Estimates from the individual studies were pooled using fixed effect meta-analysis. The 3 studies combined included 17 623 patients of whom 969 (5.5%) were either heterozygous or homozygous (n=23) carriers of factor V Leiden. During 1 year of follow-up, a total of 1289 (7.3%) patients developed major (n=559) or minor bleeding. Factor V Leiden was associated with a lower risk of combined major and minor bleeding (adjusted cause-specific HR, 0.75; 95% CI, 0.56-1.00; P=0.046; I2=0%) but a comparable risk of major bleeding (adjusted cause-specific HR, 0.93; 95% CI, 0.62-1.39; P=0.73; I2=0%). Adjusted pooled cause-specific HRs for the association of factor V Leiden with atherothrombotic events alone and in combination with bleeding events were 0.75 (95% CI, 0.55-1.02; P=0.06; I2=0%) and 0.75 (95% CI, 0.61-0.92; P=0.007; I2=0%), respectively. Conclusions Given that the lower risk of bleeding conferred by factor V Leiden was not counterbalanced by a higher risk of atherothrombotic events, these findings warrant future assessment for personalized medicine such as selecting patients for extended or intensive antiplatelet therapy.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/JAHA.120.021115; doi:https://doi.org/10.1161/JAHA.120.021115; html:https://europepmc.org/articles/PMC8649290; pdf:https://europepmc.org/articles/PMC8649290?pdf=render -37808344,https://doi.org/10.1016/j.jacadv.2023.100573,CYP2C19 Genotype Prevalence and Association With Recurrent Myocardial Infarction in British-South Asians Treated With Clopidogrel.,"Magavern EF, Jacobs B, Warren H, Finocchiaro G, Finer S, van Heel DA, Genes & Health Research Team, Smedley D, Caulfield MJ.",,JACC. Advances,2023,2023-09-01,Y,Pharmacogenomics; ischemic heart disease; Pharmacotherapy; Preventive Cardiology,,,"

Background

Cytochrome P450 family 2 subfamily C member 19 (CYP2C19) is a hepatic enzyme involved in the metabolism of clopidogrel from a prodrug to its active metabolite. Prior studies of genetic polymorphisms in CYP2C19 and their relationship with clinical efficacy have not included South Asian populations.

Objectives

The objective of this study was to assess prevalence of common CYP2C19 genotype polymorphisms in a British-South Asian population and correlate these with recurrent myocardial infarction risk in participants prescribed clopidogrel.

Methods

The Genes & Health cohort of British Bangladeshi and Pakistani ancestry participants were studied. CYP2C19 diplotypes were assessed using array data. Multivariable logistic regression was used to test for association between genetically inferred CYP2C19 metabolizer status and recurrent myocardial infarction, controlling for known cardiovascular disease risk factors, percutaneous coronary intervention, age, sex, and population stratification.

Results

Genes & Health cohort participants (N = 44,396) have a high prevalence (57%) of intermediate or poor CYP2C19 metabolizers, with at least 1 loss-of-function CYP2C19 allele. The prevalence of poor metabolizers carrying 2 CYP2C19 loss-of-function alleles is 13%, which is higher than that in previously studied European (2.4%) and Central/South Asian populations (8.2%). Sixty-nine percent of the cohort who were diagnosed with an acute myocardial infarction were prescribed clopidogrel. Poor metabolizers were significantly more likely to have a recurrent myocardial infarction (OR: 3.1; P = 0.019).

Conclusions

A pharmacogenomic-driven approach to clopidogrel prescribing has the potential to impact significantly on clinical management and outcomes in individuals of Bangladeshi and Pakistani ancestry.",,doi:https://doi.org/10.1016/j.jacadv.2023.100573; html:https://europepmc.org/articles/PMC10550831; pdf:https://europepmc.org/articles/PMC10550831?pdf=render 33947203,https://doi.org/10.1161/circulationaha.120.053033,Evidence-Based Assessment of Genes in Dilated Cardiomyopathy.,"Jordan E, Peterson L, Ai T, Asatryan B, Bronicki L, Brown E, Celeghin R, Edwards M, Fan J, Ingles J, James CA, Jarinova O, Johnson R, Judge DP, Lahrouchi N, Lekanne Deprez RH, Lumbers RT, Mazzarotto F, Medeiros Domingo A, Miller RL, Morales A, Murray B, Peters S, Pilichou K, Protonotarios A, Semsarian C, Shah P, Syrris P, Thaxton C, van Tintelen JP, Walsh R, Wang J, Ware J, Hershberger RE.",,Circulation,2021,2021-05-05,Y,Genetics; Cardiomyopathy,,,"

Background

Each of the cardiomyopathies, classically categorized as hypertrophic cardiomyopathy, dilated cardiomyopathy (DCM), and arrhythmogenic right ventricular cardiomyopathy, has a signature genetic theme. Hypertrophic cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy are largely understood as genetic diseases of sarcomere or desmosome proteins, respectively. In contrast, >250 genes spanning >10 gene ontologies have been implicated in DCM, representing a complex and diverse genetic architecture. To clarify this, a systematic curation of evidence to establish the relationship of genes with DCM was conducted.

Methods

An international panel with clinical and scientific expertise in DCM genetics evaluated evidence supporting monogenic relationships of genes with idiopathic DCM. The panel used the Clinical Genome Resource semiquantitative gene-disease clinical validity classification framework with modifications for DCM genetics to classify genes into categories on the basis of the strength of currently available evidence. Representation of DCM genes on clinically available genetic testing panels was evaluated.

Results

Fifty-one genes with human genetic evidence were curated. Twelve genes (23%) from 8 gene ontologies were classified as having definitive (BAG3, DES, FLNC, LMNA, MYH7, PLN, RBM20, SCN5A, TNNC1, TNNT2, TTN) or strong (DSP) evidence. Seven genes (14%; ACTC1, ACTN2, JPH2, NEXN, TNNI3, TPM1, VCL) including 2 additional ontologies were classified as moderate evidence; these genes are likely to emerge as strong or definitive with additional evidence. Of these 19 genes, 6 were similarly classified for hypertrophic cardiomyopathy and 3 for arrhythmogenic right ventricular cardiomyopathy. Of the remaining 32 genes (63%), 25 (49%) had limited evidence, 4 (8%) were disputed, 2 (4%) had no disease relationship, and 1 (2%) was supported by animal model data only. Of the 16 evaluated clinical genetic testing panels, most definitive genes were included, but panels also included numerous genes with minimal human evidence.

Conclusions

In the curation of 51 genes, 19 had high evidence (12 definitive/strong, 7 moderate). It is notable that these 19 genes explain only a minority of cases, leaving the remainder of DCM genetic architecture incompletely addressed. Clinical genetic testing panels include most high-evidence genes; however, genes lacking robust evidence are also commonly included. We recommend that high-evidence DCM genes be used for clinical practice and that caution be exercised in the interpretation of variants in variable-evidence DCM genes.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCULATIONAHA.120.053033; doi:https://doi.org/10.1161/CIRCULATIONAHA.120.053033; html:https://europepmc.org/articles/PMC8247549; pdf:https://europepmc.org/articles/PMC8247549?pdf=render +37808344,https://doi.org/10.1016/j.jacadv.2023.100573,CYP2C19 Genotype Prevalence and Association With Recurrent Myocardial Infarction in British-South Asians Treated With Clopidogrel.,"Magavern EF, Jacobs B, Warren H, Finocchiaro G, Finer S, van Heel DA, Genes & Health Research Team, Smedley D, Caulfield MJ.",,JACC. Advances,2023,2023-09-01,Y,Pharmacogenomics; ischemic heart disease; Pharmacotherapy; Preventive Cardiology,,,"

Background

Cytochrome P450 family 2 subfamily C member 19 (CYP2C19) is a hepatic enzyme involved in the metabolism of clopidogrel from a prodrug to its active metabolite. Prior studies of genetic polymorphisms in CYP2C19 and their relationship with clinical efficacy have not included South Asian populations.

Objectives

The objective of this study was to assess prevalence of common CYP2C19 genotype polymorphisms in a British-South Asian population and correlate these with recurrent myocardial infarction risk in participants prescribed clopidogrel.

Methods

The Genes & Health cohort of British Bangladeshi and Pakistani ancestry participants were studied. CYP2C19 diplotypes were assessed using array data. Multivariable logistic regression was used to test for association between genetically inferred CYP2C19 metabolizer status and recurrent myocardial infarction, controlling for known cardiovascular disease risk factors, percutaneous coronary intervention, age, sex, and population stratification.

Results

Genes & Health cohort participants (N = 44,396) have a high prevalence (57%) of intermediate or poor CYP2C19 metabolizers, with at least 1 loss-of-function CYP2C19 allele. The prevalence of poor metabolizers carrying 2 CYP2C19 loss-of-function alleles is 13%, which is higher than that in previously studied European (2.4%) and Central/South Asian populations (8.2%). Sixty-nine percent of the cohort who were diagnosed with an acute myocardial infarction were prescribed clopidogrel. Poor metabolizers were significantly more likely to have a recurrent myocardial infarction (OR: 3.1; P = 0.019).

Conclusions

A pharmacogenomic-driven approach to clopidogrel prescribing has the potential to impact significantly on clinical management and outcomes in individuals of Bangladeshi and Pakistani ancestry.",,doi:https://doi.org/10.1016/j.jacadv.2023.100573; html:https://europepmc.org/articles/PMC10550831; pdf:https://europepmc.org/articles/PMC10550831?pdf=render 34053260,https://doi.org/10.1098/rstb.2020.0283,Exploring surveillance data biases when estimating the reproduction number: with insights into subpopulation transmission of COVID-19 in England.,"Sherratt K, Abbott S, Meakin SR, Hellewell J, Munday JD, Bosse N, CMMID COVID-19 Working Group, Jit M, Funk S.",,"Philosophical transactions of the Royal Society of London. Series B, Biological sciences",2021,2021-05-31,Y,Transmission; Surveillance; Bias; Covid-19; Sars-cov-2; Time-varying Reproduction Number,,,"The time-varying reproduction number (Rt: the average number of secondary infections caused by each infected person) may be used to assess changes in transmission potential during an epidemic. While new infections are not usually observed directly, they can be estimated from data. However, data may be delayed and potentially biased. We investigated the sensitivity of Rt estimates to different data sources representing COVID-19 in England, and we explored how this sensitivity could track epidemic dynamics in population sub-groups. We sourced public data on test-positive cases, hospital admissions and deaths with confirmed COVID-19 in seven regions of England over March through August 2020. We estimated Rt using a model that mapped unobserved infections to each data source. We then compared differences in Rt with the demographic and social context of surveillance data over time. Our estimates of transmission potential varied for each data source, with the relative inconsistency of estimates varying across regions and over time. Rt estimates based on hospital admissions and deaths were more spatio-temporally synchronous than when compared to estimates from all test positives. We found these differences may be linked to biased representations of subpopulations in each data source. These included spatially clustered testing, and where outbreaks in hospitals, care homes, and young age groups reflected the link between age and severity of the disease. We highlight that policy makers could better target interventions by considering the source populations of Rt estimates. Further work should clarify the best way to combine and interpret Rt estimates from different data sources based on the desired use. This article is part of the theme issue 'Modelling that shaped the early COVID-19 pandemic response in the UK'.",,doi:https://doi.org/10.1098/rstb.2020.0283; doi:https://doi.org/10.1098/rstb.2020.0283; html:https://europepmc.org/articles/PMC8165604; pdf:https://europepmc.org/articles/PMC8165604?pdf=render 38347162,https://doi.org/10.1038/s42003-024-05840-3,Genomic attributes of airway commensal bacteria and mucosa.,"Cuthbertson L, Löber U, Ish-Horowicz JS, McBrien CN, Churchward C, Parker JC, Olanipekun MT, Burke C, McGowan A, Davies GA, Lewis KE, Hopkin JM, Chung KF, O'Carroll O, Faul J, Creaser-Thomas J, Andrews M, Ghosal R, Piatek S, Willis-Owen SAG, Bartolomaeus TUP, Birkner T, Dwyer S, Kumar N, Turek EM, William Musk A, Hui J, Hunter M, James A, Dumas ME, Filippi S, Cox MJ, Lawley TD, Forslund SK, Moffatt MF, Cookson WOC.",,Communications biology,2024,2024-02-12,Y,,,,"Microbial communities at the airway mucosal barrier are conserved and highly ordered, in likelihood reflecting co-evolution with human host factors. Freed of selection to digest nutrients, the airway microbiome underpins cognate management of mucosal immunity and pathogen resistance. We show here the initial results of systematic culture and whole-genome sequencing of the thoracic airway bacteria, identifying 52 novel species amongst 126 organisms that constitute 75% of commensals typically present in heathy individuals. Clinically relevant genes encode antimicrobial synthesis, adhesion and biofilm formation, immune modulation, iron utilisation, nitrous oxide (NO) metabolism and sphingolipid signalling. Using whole-genome content we identify dysbiotic features that may influence asthma and chronic obstructive pulmonary disease. We match isolate gene content to transcripts and metabolites expressed late in airway epithelial differentiation, identifying pathways to sustain host interactions with microbiota. Our results provide a systematic basis for decrypting interactions between commensals, pathogens, and mucosa in lung diseases of global significance.",,doi:https://doi.org/10.1038/s42003-024-05840-3; html:https://europepmc.org/articles/PMC10861553; pdf:https://europepmc.org/articles/PMC10861553?pdf=render 35520099,https://doi.org/10.23889/ijpds.v6i1.1718,"What makes administrative data ""research-ready""? A systematic review and thematic analysis of published literature.","Grath-Lone LM, Jay MA, Blackburn R, Gordon E, Zylbersztejn A, Wiljaars L, Gilbert R.",,International journal of population data science,2022,2022-04-27,Y,Systematic review; Administrative Data; Thematic Analysis; Research-ready,,,"

Introduction

Administrative data are a valuable research resource, but are under-utilised in the UK due to governance, technical and other barriers (e.g., the time and effort taken to gain secure data access). In recent years, there has been considerable government investment in making administrative data ""research-ready"", but there is no definition of what this term means. A common understanding of what constitutes research-ready administrative data is needed to establish clear principles and frameworks for their development and the realisation of their full research potential.

Objective

To define the characteristics of research-ready administrative data based on a systematic review and synthesis of existing literature.

Methods

On 29th June 2021, we systematically searched seven electronic databases for (1) peer-reviewed literature (2) related to research-ready administrative data (3) written in the English language. Following supplementary searches and snowball screening, we conducted a thematic analysis of the identified relevant literature.

Results

Overall, we screened 2,375 records and identified 38 relevant studies published between 2012 and 2021. Most related to administrative data from the UK and US and particularly to health data. The term research-ready was used inconsistently in the literature and there was some conflation with the concept of data being ready for statistical analysis. From the thematic analysis, we identified five defining characteristics of research-ready administrative data: (a) accessible, (b) broad, (c) curated, (d) documented and (e) enhanced for research purposes.

Conclusions

Our proposed characteristics of research-ready administrative data could act as a starting point to help data owners and researchers develop common principles and standards. In the more immediate term, the proposed characteristics are a useful framework for cataloguing existing research-ready administrative databases and relevant resources that can support their development.",,doi:https://doi.org/10.23889/ijpds.v6i1.1718; html:https://europepmc.org/articles/PMC9052961; pdf:https://europepmc.org/articles/PMC9052961?pdf=render -38381822,https://doi.org/10.1126/sciadv.adi9379,"Spontaneous, persistent, T cell-dependent IFN-γ release in patients who progress to Long Covid.","Krishna BA, Lim EY, Metaxaki M, Jackson S, Mactavous L, NIHR BioResource, Lyons PA, Doffinger R, Bradley JR, Smith KGC, Sinclair J, Matheson NJ, Lehner PJ, Sithole N, Wills MR.",,Science advances,2024,2024-02-21,Y,,,,"After acute infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a proportion of patients experience persistent symptoms beyond 12 weeks, termed Long Covid. Understanding the mechanisms that cause this debilitating disease and identifying biomarkers for diagnostic, therapeutic, and monitoring purposes are urgently required. We detected persistently high levels of interferon-γ (IFN-γ) from peripheral blood mononuclear cells of patients with Long Covid using highly sensitive FluoroSpot assays. This IFN-γ release was seen in the absence of ex vivo peptide stimulation and remains persistently elevated in patients with Long Covid, unlike the resolution seen in patients recovering from acute SARS-CoV-2 infection. The IFN-γ release was CD8+ T cell-mediated and dependent on antigen presentation by CD14+ cells. Longitudinal follow-up of our study cohort showed that symptom improvement and resolution correlated with a decrease in IFN-γ production to baseline levels. Our study highlights a potential mechanism underlying Long Covid, enabling the search for biomarkers and therapeutics in patients with Long Covid.",,pdf:https://www.science.org/doi/pdf/10.1126/sciadv.adi9379?download=true; doi:https://doi.org/10.1126/sciadv.adi9379; html:https://europepmc.org/articles/PMC10881041; pdf:https://europepmc.org/articles/PMC10881041?pdf=render 35751107,https://doi.org/10.1186/s13059-022-02702-1,Epigenomic analysis reveals a dynamic and context-specific macrophage enhancer landscape associated with innate immune activation and tolerance.,"Zhang P, Amarasinghe HE, Whalley JP, Tay C, Fang H, Migliorini G, Brown AC, Allcock A, Scozzafava G, Rath P, Davies B, Knight JC.",,Genome biology,2022,2022-06-24,Y,,,,"

Background

Chromatin states and enhancers associate gene expression, cell identity and disease. Here, we systematically delineate the acute innate immune response to endotoxin in terms of human macrophage enhancer activity and contrast with endotoxin tolerance, profiling the coding and non-coding transcriptome, chromatin accessibility and epigenetic modifications.

Results

We describe the spectrum of enhancers under acute and tolerance conditions and the regulatory networks between these enhancers and biological processes including gene expression, splicing regulation, transcription factor binding and enhancer RNA signatures. We demonstrate that the vast majority of differentially regulated enhancers on acute stimulation are subject to tolerance and that expression quantitative trait loci, disease-risk variants and eRNAs are enriched in these regulatory regions and related to context-specific gene expression. We find enrichment for context-specific eQTL involving endotoxin response and specific infections and delineate specific differential regions informative for GWAS variants in inflammatory bowel disease and multiple sclerosis, together with a context-specific enhancer involving a bacterial infection eQTL for KLF4. We show enrichment in differential enhancers for tolerance involving transcription factors NFκB-p65, STATs and IRFs and prioritize putative causal genes directly linking genetic variants and disease risk enhancers. We further delineate similarities and differences in epigenetic landscape between stem cell-derived macrophages and primary cells and characterize the context-specific enhancer activities for key innate immune response genes KLF4, SLAMF1 and IL2RA.

Conclusions

Our study demonstrates the importance of context-specific macrophage enhancers in gene regulation and utility for interpreting disease associations, providing a roadmap to link genetic variants with molecular and cellular functions.",,pdf:https://genomebiology.biomedcentral.com/counter/pdf/10.1186/s13059-022-02702-1; doi:https://doi.org/10.1186/s13059-022-02702-1; html:https://europepmc.org/articles/PMC9229144; pdf:https://europepmc.org/articles/PMC9229144?pdf=render 35913736,https://doi.org/10.1093/ehjqcco/qcac045,Impact of cancer diagnosis on distribution and trends of cardiovascular hospitalizations in the USA between 2004 and 2017.,"Kobo O, Raisi-Estabragh Z, Gevaert S, Rana JS, Van Spall HGC, Roguin A, Petersen SE, Ky B, Mamas MA.",,European heart journal. Quality of care & clinical outcomes,2022,2022-10-01,N,Prognosis; trends; Cardio- Oncology,,,"

Background and aims

There is limited data on temporal trends of cardiovascular hospitalizations and outcomes amongst cancer patients. We describe the distribution, trends of admissions, and in-hospital mortality associated with key cardiovascular diseases among cancer patients in the USA between 2004 and 2017.

Methods

Using the Nationwide Inpatient Sample we, identified admissions with five cardiovascular diseases of interest: acute myocardial infarction (AMI), pulmonary embolism (PE), ischaemic stroke, heart failure, atrial fibrillation (AF) or atrial flutter, and intracranial haemorrhage. Patients were stratified by cancer status and type. We estimated crude annual rates of hospitalizations and annual in-hospital all-cause mortality rates.

Results

From >42.5 million hospitalizations with a primary cardiovascular diagnosis, 1.9 million (4.5%) had a concurrent record of cancer. Between 2004 and 2017, cardiovascular admission rates increased by 23.2% in patients with cancer, whilst decreasing by 10.9% in patients without cancer. The admission rate increased among cancer patients across all admission causes and cancer types except prostate cancer. Patients with haematological (9.7-13.5), lung (7.4-8.9), and GI cancer (4.6-6.3) had the highest crude rates of cardiovascular hospitalizations per 100 000 US population. Heart failure was the most common reason for cardiovascular admission in patients across all cancer types, except GI cancer (crude admission rates of 13.6-16.6 per 100 000 US population for patients with cancer).

Conclusions

In contrast to declining trends in patients without cancer, primary cardiovascular admissions in patients with cancer is increasing. The highest admission rates are in patients with haematological cancer, and the most common cause of admission is heart failure.",,pdf:https://biblio.ugent.be/publication/01GTEZMFA3PQ4FR2HWVVMJE1PP/file/01GTEZP5YQ68PC7TFPP52TS6QR.pdf; doi:https://doi.org/10.1093/ehjqcco/qcac045; html:https://europepmc.org/articles/PMC9603542; pdf:https://europepmc.org/articles/PMC9603542?pdf=render; doi:https://doi.org/10.1093/ehjqcco/qcac045 +38381822,https://doi.org/10.1126/sciadv.adi9379,"Spontaneous, persistent, T cell-dependent IFN-γ release in patients who progress to Long Covid.","Krishna BA, Lim EY, Metaxaki M, Jackson S, Mactavous L, NIHR BioResource, Lyons PA, Doffinger R, Bradley JR, Smith KGC, Sinclair J, Matheson NJ, Lehner PJ, Sithole N, Wills MR.",,Science advances,2024,2024-02-21,Y,,,,"After acute infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a proportion of patients experience persistent symptoms beyond 12 weeks, termed Long Covid. Understanding the mechanisms that cause this debilitating disease and identifying biomarkers for diagnostic, therapeutic, and monitoring purposes are urgently required. We detected persistently high levels of interferon-γ (IFN-γ) from peripheral blood mononuclear cells of patients with Long Covid using highly sensitive FluoroSpot assays. This IFN-γ release was seen in the absence of ex vivo peptide stimulation and remains persistently elevated in patients with Long Covid, unlike the resolution seen in patients recovering from acute SARS-CoV-2 infection. The IFN-γ release was CD8+ T cell-mediated and dependent on antigen presentation by CD14+ cells. Longitudinal follow-up of our study cohort showed that symptom improvement and resolution correlated with a decrease in IFN-γ production to baseline levels. Our study highlights a potential mechanism underlying Long Covid, enabling the search for biomarkers and therapeutics in patients with Long Covid.",,pdf:https://www.science.org/doi/pdf/10.1126/sciadv.adi9379?download=true; doi:https://doi.org/10.1126/sciadv.adi9379; html:https://europepmc.org/articles/PMC10881041; pdf:https://europepmc.org/articles/PMC10881041?pdf=render 34870142,https://doi.org/10.1016/j.infpip.2021.100192,"Effectiveness of infection prevention and control interventions, excluding personal protective equipment, to prevent nosocomial transmission of SARS-CoV-2: a systematic review and call for action.","Jafari Y, Yin M, Lim C, Pople D, Evans S, Stimson J, Pham TM, LSHTM CMMID COVID-19 working group, Read JM, Robotham JV, Cooper BS, Knight GM.",,Infection prevention in practice,2022,2021-11-29,Y,,,,"Many infection prevention and control (IPC) interventions have been adopted by hospitals to limit nosocomial transmission of SARS-CoV-2. The aim of this systematic review is to identify evidence on the effectiveness of these interventions. We conducted a literature search of five databases (OVID MEDLINE, Embase, CENTRAL, COVID-19 Portfolio (pre-print), Web of Science). SWIFT ActiveScreener software was used to screen English titles and abstracts published between 1st January 2020 and 6th April 2021. Intervention studies, defined by Cochrane Effective Practice and Organisation of Care, that evaluated IPC interventions with an outcome of SARS-CoV-2 infection in either patients or healthcare workers were included. Personal protective equipment (PPE) was excluded as this intervention had been previously reviewed. Risks of bias were assessed using the Cochrane tool for randomised trials (RoB2) and non-randomized studies of interventions (ROBINS-I). From 23,156 screened articles, we identified seven articles that met the inclusion criteria, all of which evaluated interventions to prevent infections in healthcare workers and the majority of which were focused on effectiveness of prophylaxes. Due to heterogeneity in interventions, we did not conduct a meta-analysis. All agents used for prophylaxes have little to no evidence of effectiveness against SARS-CoV-2 infections. We did not find any studies evaluating the effectiveness of interventions including but not limited to screening, isolation and improved ventilation. There is limited evidence from interventional studies, excluding PPE, evaluating IPC measures for SARS-CoV-2. This review calls for urgent action to implement such studies to inform policies to protect our most vulnerable populations and healthcare workers.",,doi:https://doi.org/10.1016/j.infpip.2021.100192; doi:https://doi.org/10.1016/j.infpip.2021.100192; html:https://europepmc.org/articles/PMC8628369; pdf:https://europepmc.org/articles/PMC8628369?pdf=render 36446465,https://doi.org/10.1136/bmjopen-2022-065142,"Prevalence, pathophysiology, prediction and health-related quality of life of long COVID: study protocol of the longitudinal multiple cohort CORona Follow Up (CORFU) study.","Ghossein-Doha C, Wintjens MSJN, Janssen EBNJ, Klein D, Heemskerk SCM, Asselbergs FW, Birnie E, Bonsel GJ, van Bussel BCT, Cals JWL, Ten Cate H, Haagsma J, Hemmen B, van der Horst ICC, Kietselaer BLJH, Klok FA, de Kruif MD, Linschoten M, van Santen S, Vernooy K, Willems LH, Westerborg R, Warle M, van Kuijk SMJ.",,BMJ open,2022,2022-11-29,Y,epidemiology; Public Health; Protocols & Guidelines; Covid-19,,,"

Introduction

The variety, time patterns and long-term prognosis of persistent COVID-19 symptoms (long COVID-19) in patients who suffered from mild to severe acute COVID-19 are incompletely understood. Cohort studies will be combined to describe the prevalence of long COVID-19 symptoms, and to explore the pathophysiological mechanisms and impact on health-related quality of life. A prediction model for long COVID-19 will be developed and internally validated to guide care in future patients.

Methods and analysis

Data from seven COVID-19 cohorts will be aggregated in the longitudinal multiple cohort CORona Follow Up (CORFU) study. CORFU includes Dutch patients who suffered from COVID-19 at home, were hospitalised without or with intensive care unit treatment, needed inpatient or outpatient rehabilitation and controls who did not suffer from COVID-19. Individual cohort study designs were aligned and follow-up has been synchronised. Cohort participants will be followed up for a maximum of 24 months after acute infection. Next to the clinical characteristics measured in individual cohorts, the CORFU questionnaire on long COVID-19 outcomes and determinants will be administered digitally at 3, 6, 12, 18 and 24 months after the infection. The primary outcome is the prevalence of long COVID-19 symptoms up to 2 years after acute infection. Secondary outcomes are health-related quality of life (eg, EQ-5D), physical functioning, and the prevalence of thromboembolic complications, respiratory complications, cardiovascular diseases and endothelial dysfunction. A prediction model and a patient platform prototype will be developed.

Ethics and dissemination

Approval was obtained from the medical research ethics committee of Maastricht University Medical Center+ and Maastricht University (METC 2021-2990) and local committees of the participating cohorts. The project is supported by ZonMW and EuroQol Research Foundation. Results will be published in open access peer-reviewed scientific journals and presented at (inter)national conferences.

Trial registration number

NCT05240742.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/11/e065142.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-065142; html:https://europepmc.org/articles/PMC9709810; pdf:https://europepmc.org/articles/PMC9709810?pdf=render 33713332,https://doi.org/10.1007/s40620-021-00996-1,End-stage kidney disease in patients with clinically manifest vascular disease; incidence and risk factors: results from the UCC-SMART cohort study.,"Østergaard HB, Westerink J, Verhaar MC, Bots ML, Asselbergs FW, de Borst GJ, Kappelle LJ, Visseren FLJ, van der Leeuw J, UCC-SMART studygroup.",,Journal of nephrology,2021,2021-03-13,Y,Cardiovascular disease; incidence; End-stage Kidney Disease; Modifiable Risk Factors,,,"

Background

Patients with cardiovascular disease (CVD) are at increased risk of end-stage kidney disease (ESKD). Insights into the incidence and role of modifiable risk factors for end-stage kidney disease may provide means for prevention in patients with cardiovascular disease.

Methods

We included 8402 patients with stable cardiovascular disease. Incidence rates (IRs) for end-stage kidney disease were determined stratified according to vascular disease location. Cox proportional hazard models were used to assess the risk of end-stage kidney disease for the different determinants.

Results

Sixty-five events were observed with a median follow-up of 8.6 years. The overall incidence rate of end-stage kidney disease was 0.9/1000 person-years. Patients with polyvascular disease had the highest incidence rate (1.8/1000 person-years). Smoking (Hazard ratio (HR) 1.87; 95% CI 1.10-3.19), type 2 diabetes (HR 1.81; 95% CI 1.05-3.14), higher systolic blood pressure (HR 1.37; 95% CI 1.24-1.52/10 mmHg), lower estimated glomerular filtration rate (eGFR) (HR 2.86; 95% CI 2.44-3.23/10 mL/min/1.73 m2) and higher urine albumin/creatinine ratio (uACR) (HR 1.19; 95% CI 1.15-1.23/10 mg/mmol) were independently associated with elevated risk of end-stage kidney disease. Body mass index (BMI), waist circumference, non-HDL-cholesterol and exercise were not independently associated with risk of end-stage kidney disease.

Conclusions

Incidence of end-stage kidney disease in patients with cardiovascular disease varies according to vascular disease location. Several modifiable risk factors for end-stage kidney disease were identified in patients with cardiovascular disease. These findings highlight the potential of risk factor management in patients with manifest cardiovascular disease.",,pdf:https://link.springer.com/content/pdf/10.1007/s40620-021-00996-1.pdf; doi:https://doi.org/10.1007/s40620-021-00996-1; html:https://europepmc.org/articles/PMC8494654; pdf:https://europepmc.org/articles/PMC8494654?pdf=render @@ -1978,14 +1978,14 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 34991479,https://doi.org/10.1186/s12877-021-02684-y,The dynamics of frailty development and progression in older adults in primary care in England (2006-2017): a retrospective cohort profile.,"Fogg C, Fraser SDS, Roderick P, de Lusignan S, Clegg A, Brailsford S, Barkham A, Patel HP, Windle V, Harris S, Zhu S, England T, Evenden D, Lambert F, Walsh B, Frailty Dynamics study team.",,BMC geriatrics,2022,2022-01-06,Y,Adults; Frailty; Cohort study; Primary Care; Service Use; Electronic Health Records; Trajectories; Computer Simulation Modelling,,,"

Background

Frailty is a common condition in older adults and has a major impact on patient outcomes and service use. Information on the prevalence in middle-aged adults and the patterns of progression of frailty at an individual and population level is scarce. To address this, a cohort was defined from a large primary care database in England to describe the epidemiology of frailty and understand the dynamics of frailty within individuals and across the population. This article describes the structure of the dataset, cohort characteristics and planned analyses.

Methods

Retrospective cohort study using electronic health records. Participants were aged ≥50 years registered in practices contributing to the Oxford Royal College of General Practitioners Research and Surveillance Centre between 2006 to 2017. Data include GP practice details, patient sociodemographic and clinical characteristics, twice-yearly electronic Frailty Index (eFI), deaths, medication use and primary and secondary care health service use. Participants in each cohort year by age group, GP and patient characteristics at cohort entry are described.

Results

The cohort includes 2,177,656 patients, contributing 15,552,946 person-years, registered at 419 primary care practices in England. The mean age was 61 years, 52.1% of the cohort was female, and 77.6% lived in urban environments. Frailty increased with age, affecting 10% of adults aged 50-64 and 43.7% of adults aged ≥65. The prevalence of long-term conditions and specific frailty deficits increased with age, as did the eFI and the severity of frailty categories.

Conclusion

A comprehensive understanding of frailty dynamics will inform predictions of current and future care needs to facilitate timely planning of appropriate interventions, service configurations and workforce requirements. Analysis of this large, nationally representative cohort including participants aged ≥50 will capture earlier transitions to frailty and enable a detailed understanding of progression and impact. These results will inform novel simulation models which predict future health and service needs of older people living with frailty.

Study registration

Registered on www.clinicaltrials.gov October 25th 2019, NCT04139278 .",,pdf:https://bmcgeriatr.biomedcentral.com/counter/pdf/10.1186/s12877-021-02684-y; doi:https://doi.org/10.1186/s12877-021-02684-y; html:https://europepmc.org/articles/PMC8740419; pdf:https://europepmc.org/articles/PMC8740419?pdf=render 32285648,https://doi.org/10.1002/ehf2.12689,Predicting sustained ventricular arrhythmias in dilated cardiomyopathy: a meta-analysis and systematic review.,"Sammani A, Kayvanpour E, Bosman LP, Sedaghat-Hamedani F, Proctor T, Gi WT, Broezel A, Jensen K, Katus HA, Te Riele ASJM, Meder B, Asselbergs FW.",,ESC heart failure,2020,2020-04-14,Y,Prognosis; Dilated cardiomyopathy; risk; Sudden Cardiac Death; Implantable Cardiac-defibrillator,,,"

Aims

Patients with non-ischaemic dilated cardiomyopathy (DCM) are at increased risk of sudden cardiac death. Identification of patients that may benefit from implantable cardioverter-defibrillator implantation remains challenging. In this study, we aimed to determine predictors of sustained ventricular arrhythmias in patients with DCM.

Methods and results

We searched MEDLINE/Embase for studies describing predictors of sustained ventricular arrhythmias in patients with DCM. Quality and bias were assessed using the Quality in Prognostic Studies tool, articles with high risk of bias in ≥2 areas were excluded. Unadjusted hazard ratios (HRs) of uniformly defined predictors were pooled, while all other predictors were evaluated in a systematic review. We included 55 studies (11 451 patients and 3.7 ± 2.3 years follow-up). Crude annual event rate was 4.5%. Younger age [HR 0.82; 95% CI (0.74-1.00)], hypertension [HR 1.95; 95% CI (1.26-3.00)], prior sustained ventricular arrhythmia [HR 4.15; 95% CI (1.32-13.02)], left ventricular ejection fraction on ultrasound [HR 1.45; 95% CI (1.19-1.78)], left ventricular dilatation (HR 1.10), and presence of late gadolinium enhancement [HR 5.55; 95% CI (4.02-7.67)] were associated with arrhythmic outcome in pooled analyses. Prior non-sustained ventricular arrhythmia and several genotypes [mutations in Phospholamban (PLN), Lamin A/C (LMNA), and Filamin-C (FLNC)] were associated with arrhythmic outcome in non-pooled analyses. Quality of evidence was moderate, and heterogeneity among studies was moderate to high.

Conclusions

In patients with DCM, the annual event rate of sustained ventricular arrhythmias is approximately 4.5%. This risk is considerably higher in younger patients with hypertension, prior (non-)sustained ventricular arrhythmia, decreased left ventricular ejection fraction, left ventricular dilatation, late gadolinium enhancement, and genetic mutations (PLN, LMNA, and FLNC). These results may help determine appropriate candidates for implantable cardioverter-defibrillator implantation.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ehf2.12689; doi:https://doi.org/10.1002/ehf2.12689; html:https://europepmc.org/articles/PMC7373946; pdf:https://europepmc.org/articles/PMC7373946?pdf=render 37006331,https://doi.org/10.1093/braincomms/fcad041,Polygenic risk score prediction of multiple sclerosis in individuals of South Asian ancestry.,"Breedon JR, Marshall CR, Giovannoni G, van Heel DA, Genes & Health Research Team , Dobson R, Jacobs BM.",,Brain communications,2023,2023-02-22,Y,Genetics; Multiple sclerosis; Ethnicity,,,"Polygenic risk scores aggregate an individual's burden of risk alleles to estimate the overall genetic risk for a specific trait or disease. Polygenic risk scores derived from genome-wide association studies of European populations perform poorly for other ancestral groups. Given the potential for future clinical utility, underperformance of polygenic risk scores in South Asian populations has the potential to reinforce health inequalities. To determine whether European-derived polygenic risk scores underperform at multiple sclerosis prediction in a South Asian-ancestry population compared with a European-ancestry cohort, we used data from two longitudinal genetic cohort studies: Genes & Health (2015-present), a study of ∼50 000 British-Bangladeshi and British-Pakistani individuals, and UK Biobank (2006-present), which is comprised of ∼500 000 predominantly White British individuals. We compared individuals with and without multiple sclerosis in both studies (Genes & Health: N Cases = 42, N Control = 40 490; UK Biobank: N Cases = 2091, N Control = 374 866). Polygenic risk scores were calculated using clumping and thresholding with risk allele effect sizes obtained from the largest multiple sclerosis genome-wide association study to date. Scores were calculated with and without the major histocompatibility complex region, the most influential locus in determining multiple sclerosis risk. Polygenic risk score prediction was evaluated using Nagelkerke's pseudo-R 2 metric adjusted for case ascertainment, age, sex and the first four genetic principal components. We found that, as expected, European-derived polygenic risk scores perform poorly in the Genes & Health cohort, explaining 1.1% (including the major histocompatibility complex) and 1.5% (excluding the major histocompatibility complex) of disease risk. In contrast, multiple sclerosis polygenic risk scores explained 4.8% (including the major histocompatibility complex) and 2.8% (excluding the major histocompatibility complex) of disease risk in European-ancestry UK Biobank participants. These findings suggest that polygenic risk score prediction of multiple sclerosis based on European genome-wide association study results is less accurate in a South Asian population. Genetic studies of ancestrally diverse populations are required to ensure that polygenic risk scores can be useful across ancestries.",,pdf:https://academic.oup.com/braincomms/article-pdf/5/2/fcad041/49521070/fcad041.pdf; doi:https://doi.org/10.1093/braincomms/fcad041; html:https://europepmc.org/articles/PMC10053643; pdf:https://europepmc.org/articles/PMC10053643?pdf=render -36998408,https://doi.org/10.3389/fmicb.2023.1070340,A longitudinal study reveals persistence of antimicrobial resistance on livestock farms is not due to antimicrobial usage alone.,"Smith RP, May HE, AbuOun M, Stubberfield E, Gilson D, Chau KK, Crook DW, Shaw LP, Read DS, Stoesser N, Vilar MJ, Anjum MF.",,Frontiers in microbiology,2023,2023-03-14,Y,Sheep; Cattle; Pigs; Antimicrobial resistance; Longitudinal; Antimicrobial Usage,,,"

Introduction

There are concerns that antimicrobial usage (AMU) is driving an increase in multi-drug resistant (MDR) bacteria so treatment of microbial infections is becoming harder in humans and animals. The aim of this study was to evaluate factors, including usage, that affect antimicrobial resistance (AMR) on farm over time.

Methods

A population of 14 cattle, sheep and pig farms within a defined area of England were sampled three times over a year to collect data on AMR in faecal Enterobacterales flora; AMU; and husbandry or management practices. Ten pooled samples were collected at each visit, with each comprising of 10 pinches of fresh faeces. Up to 14 isolates per visit were whole genome sequenced to determine presence of AMR genes.

Results

Sheep farms had very low AMU in comparison to the other species and very few sheep isolates were genotypically resistant at any time point. AMR genes were detected persistently across pig farms at all visits, even on farms with low AMU, whereas AMR bacteria was consistently lower on cattle farms than pigs, even for those with comparably high AMU. MDR bacteria was also more commonly detected on pig farms than any other livestock species.

Discussion

The results may be explained by a complex combination of factors on pig farms including historic AMU; co-selection of AMR bacteria; variation in amounts of antimicrobials used between visits; potential persistence in environmental reservoirs of AMR bacteria; or importation of pigs with AMR microbiota from supplying farms. Pig farms may also be at increased risk of AMR due to the greater use of oral routes of group antimicrobial treatment, which were less targeted than cattle treatments; the latter mostly administered to individual animals. Also, farms which exhibited either increasing or decreasing trends of AMR across the study did not have corresponding trends in their AMU. Therefore, our results suggest that factors other than AMU on individual farms are important for persistence of AMR bacteria on farms, which may be operating at the farm and livestock species level.",,pdf:https://www.frontiersin.org/articles/10.3389/fmicb.2023.1070340/pdf; doi:https://doi.org/10.3389/fmicb.2023.1070340; html:https://europepmc.org/articles/PMC10043416; pdf:https://europepmc.org/articles/PMC10043416?pdf=render 33325834,https://doi.org/10.2196/23530,Cystic Fibrosis Point of Personalized Detection (CFPOPD): An Interactive Web Application.,"Wolfe C, Pestian T, Gecili E, Su W, Keogh RH, Pestian JP, Seid M, Diggle PJ, Ziady A, Clancy JP, Grossoehme DH, Szczesniak RD, Brokamp C.",,JMIR medical informatics,2020,2020-12-16,Y,Chronic disease; Clinical Decision Support; Medical Monitoring; Clinical Decision Rules; Application Programming Interface,,,"

Background

Despite steady gains in life expectancy, individuals with cystic fibrosis (CF) lung disease still experience rapid pulmonary decline throughout their clinical course, which can ultimately end in respiratory failure. Point-of-care tools for accurate and timely information regarding the risk of rapid decline is essential for clinical decision support.

Objective

This study aims to translate a novel algorithm for earlier, more accurate prediction of rapid lung function decline in patients with CF into an interactive web-based application that can be integrated within electronic health record systems, via collaborative development with clinicians.

Methods

Longitudinal clinical history, lung function measurements, and time-invariant characteristics were obtained for 30,879 patients with CF who were followed in the US Cystic Fibrosis Foundation Patient Registry (2003-2015). We iteratively developed the application using the R Shiny framework and by conducting a qualitative study with care provider focus groups (N=17).

Results

A clinical conceptual model and 4 themes were identified through coded feedback from application users: (1) ambiguity in rapid decline, (2) clinical utility, (3) clinical significance, and (4) specific suggested revisions. These themes were used to revise our application to the currently released version, available online for exploration. This study has advanced the application's potential prognostic utility for monitoring individuals with CF lung disease. Further application development will incorporate additional clinical characteristics requested by the users and also a more modular layout that can be useful for care provider and family interactions.

Conclusions

Our framework for creating an interactive and visual analytics platform enables generalized development of applications to synthesize, model, and translate electronic health data, thereby enhancing clinical decision support and improving care and health outcomes for chronic diseases and disorders. A prospective implementation study is necessary to evaluate this tool's effectiveness regarding increased communication, enhanced shared decision-making, and improved clinical outcomes for patients with CF.",,pdf:https://medinform.jmir.org/2020/12/e23530/PDF; doi:https://doi.org/10.2196/23530; html:https://europepmc.org/articles/PMC7773511 32951912,https://doi.org/10.1016/j.jhep.2020.08.030,"Corrigendum to: ""Genome-wide and Mendelian randomisation studies of liver MRI yield insights into the pathogenesis of steatohepatitis"" [J Hepatol (2020) 241-251].","Parisinos CA, Wilman HR, Thomas EL, Kelly M, Nicholls RC, McGonigle J, Neubauer S, Hingorani AD, Patel RS, Hemingway H, Bell JD, Banerjee R, Yaghootkar H.",,Journal of hepatology,2020,2020-09-18,Y,,,,,,pdf:http://www.journal-of-hepatology.eu/article/S0168827820336035/pdf; doi:https://doi.org/10.1016/j.jhep.2020.08.030; html:https://europepmc.org/articles/PMC8055539; pdf:https://europepmc.org/articles/PMC8055539?pdf=render +36998408,https://doi.org/10.3389/fmicb.2023.1070340,A longitudinal study reveals persistence of antimicrobial resistance on livestock farms is not due to antimicrobial usage alone.,"Smith RP, May HE, AbuOun M, Stubberfield E, Gilson D, Chau KK, Crook DW, Shaw LP, Read DS, Stoesser N, Vilar MJ, Anjum MF.",,Frontiers in microbiology,2023,2023-03-14,Y,Sheep; Cattle; Pigs; Antimicrobial resistance; Longitudinal; Antimicrobial Usage,,,"

Introduction

There are concerns that antimicrobial usage (AMU) is driving an increase in multi-drug resistant (MDR) bacteria so treatment of microbial infections is becoming harder in humans and animals. The aim of this study was to evaluate factors, including usage, that affect antimicrobial resistance (AMR) on farm over time.

Methods

A population of 14 cattle, sheep and pig farms within a defined area of England were sampled three times over a year to collect data on AMR in faecal Enterobacterales flora; AMU; and husbandry or management practices. Ten pooled samples were collected at each visit, with each comprising of 10 pinches of fresh faeces. Up to 14 isolates per visit were whole genome sequenced to determine presence of AMR genes.

Results

Sheep farms had very low AMU in comparison to the other species and very few sheep isolates were genotypically resistant at any time point. AMR genes were detected persistently across pig farms at all visits, even on farms with low AMU, whereas AMR bacteria was consistently lower on cattle farms than pigs, even for those with comparably high AMU. MDR bacteria was also more commonly detected on pig farms than any other livestock species.

Discussion

The results may be explained by a complex combination of factors on pig farms including historic AMU; co-selection of AMR bacteria; variation in amounts of antimicrobials used between visits; potential persistence in environmental reservoirs of AMR bacteria; or importation of pigs with AMR microbiota from supplying farms. Pig farms may also be at increased risk of AMR due to the greater use of oral routes of group antimicrobial treatment, which were less targeted than cattle treatments; the latter mostly administered to individual animals. Also, farms which exhibited either increasing or decreasing trends of AMR across the study did not have corresponding trends in their AMU. Therefore, our results suggest that factors other than AMU on individual farms are important for persistence of AMR bacteria on farms, which may be operating at the farm and livestock species level.",,pdf:https://www.frontiersin.org/articles/10.3389/fmicb.2023.1070340/pdf; doi:https://doi.org/10.3389/fmicb.2023.1070340; html:https://europepmc.org/articles/PMC10043416; pdf:https://europepmc.org/articles/PMC10043416?pdf=render +30649175,https://doi.org/10.1001/jamacardio.2018.4537,Cardiovascular Risk Factors Associated With Venous Thromboembolism.,"Gregson J, Kaptoge S, Bolton T, Pennells L, Willeit P, Burgess S, Bell S, Sweeting M, Rimm EB, Kabrhel C, Zöller B, Assmann G, Gudnason V, Folsom AR, Arndt V, Fletcher A, Norman PE, Nordestgaard BG, Kitamura A, Mahmoodi BK, Whincup PH, Knuiman M, Salomaa V, Meisinger C, Koenig W, Kavousi M, Völzke H, Cooper JA, Ninomiya T, Casiglia E, Rodriguez B, Ben-Shlomo Y, Després JP, Simons L, Barrett-Connor E, Björkelund C, Notdurfter M, Kromhout D, Price J, Sutherland SE, Sundström J, Kauhanen J, Gallacher J, Beulens JWJ, Dankner R, Cooper C, Giampaoli S, Deen JF, Gómez de la Cámara A, Kuller LH, Rosengren A, Svensson PJ, Nagel D, Crespo CJ, Brenner H, Albertorio-Diaz JR, Atkins R, Brunner EJ, Shipley M, Njølstad I, Lawlor DA, van der Schouw YT, Selmer RM, Trevisan M, Verschuren WMM, Greenland P, Wassertheil-Smoller S, Lowe GDO, Wood AM, Butterworth AS, Thompson SG, Danesh J, Di Angelantonio E, Meade T, Emerging Risk Factors Collaboration.",,JAMA cardiology,2019,2019-02-01,Y,,Understanding the Causes of Disease,,"

Importance

It is uncertain to what extent established cardiovascular risk factors are associated with venous thromboembolism (VTE).

Objective

To estimate the associations of major cardiovascular risk factors with VTE, ie, deep vein thrombosis and pulmonary embolism.

Design, setting, and participants

This study included individual participant data mostly from essentially population-based cohort studies from the Emerging Risk Factors Collaboration (ERFC; 731 728 participants; 75 cohorts; years of baseline surveys, February 1960 to June 2008; latest date of follow-up, December 2015) and the UK Biobank (421 537 participants; years of baseline surveys, March 2006 to September 2010; latest date of follow-up, February 2016). Participants without cardiovascular disease at baseline were included. Data were analyzed from June 2017 to September 2018.

Exposures

A panel of several established cardiovascular risk factors.

Main outcomes and measures

Hazard ratios (HRs) per 1-SD higher usual risk factor levels (or presence/absence). Incident fatal outcomes in ERFC (VTE, 1041; coronary heart disease [CHD], 25 131) and incident fatal/nonfatal outcomes in UK Biobank (VTE, 2321; CHD, 3385). Hazard ratios were adjusted for age, sex, smoking status, diabetes, and body mass index (BMI).

Results

Of the 731 728 participants from the ERFC, 403 396 (55.1%) were female, and the mean (SD) age at the time of the survey was 51.9 (9.0) years; of the 421 537 participants from the UK Biobank, 233 699 (55.4%) were female, and the mean (SD) age at the time of the survey was 56.4 (8.1) years. Risk factors for VTE included older age (ERFC: HR per decade, 2.67; 95% CI, 2.45-2.91; UK Biobank: HR, 1.81; 95% CI, 1.71-1.92), current smoking (ERFC: HR, 1.38; 95% CI, 1.20-1.58; UK Biobank: HR, 1.23; 95% CI, 1.08-1.40), and BMI (ERFC: HR per 1-SD higher BMI, 1.43; 95% CI, 1.35-1.50; UK Biobank: HR, 1.37; 95% CI, 1.32-1.41). For these factors, there were similar HRs for pulmonary embolism and deep vein thrombosis in UK Biobank (except adiposity was more strongly associated with pulmonary embolism) and similar HRs for unprovoked vs provoked VTE. Apart from adiposity, these risk factors were less strongly associated with VTE than CHD. There were inconsistent associations of VTEs with diabetes and blood pressure across ERFC and UK Biobank, and there was limited ability to study lipid and inflammation markers.

Conclusions and relevance

Older age, smoking, and adiposity were consistently associated with higher VTE risk.",,pdf:https://pdxscholar.library.pdx.edu/cgi/viewcontent.cgi?article=1451&context=sph_facpub; doi:https://doi.org/10.1001/jamacardio.2018.4537; html:https://europepmc.org/articles/PMC6386140 34965929,https://doi.org/10.1136/bmj-2021-065834,GP consultation rates for sequelae after acute covid-19 in patients managed in the community or hospital in the UK: population based study.,"Whittaker HR, Gulea C, Koteci A, Kallis C, Morgan AD, Iwundu C, Weeks M, Gupta R, Quint JK.",,BMJ (Clinical research ed.),2021,2021-12-29,Y,,,,"

Objectives

To describe the rates for consulting a general practitioner (GP) for sequelae after acute covid-19 in patients admitted to hospital with covid-19 and those managed in the community, and to determine how the rates change over time for patients in the community and after vaccination for covid-19.

Design

Population based study.

Setting

1392 general practices in England contributing to the Clinical Practice Research Datalink Aurum database.

Participants

456 002 patients with a diagnosis of covid-19 between 1 August 2020 and 14 February 2021 (44.7% men; median age 61 years), admitted to hospital within two weeks of diagnosis or managed in the community, and followed-up for a maximum of 9.2 months. A negative control group included individuals without covid-19 (n=38 511) and patients with influenza before the pandemic (n=21 803).

Main outcome measures

Comparison of rates for consulting a GP for new symptoms, diseases, prescriptions, and healthcare use in individuals admitted to hospital and those managed in the community, separately, before and after covid-19 infection, using Cox regression and negative binomial regression for healthcare use. The analysis was repeated for the negative control and influenza cohorts. In individuals in the community, outcomes were also described over time after a diagnosis of covid-19, and compared before and after vaccination for individuals who were symptomatic after covid-19 infection, using negative binomial regression.

Results

Relative to the negative control and influenza cohorts, patients in the community (n=437 943) had significantly higher GP consultation rates for multiple sequelae, and the most common were loss of smell or taste, or both (adjusted hazard ratio 5.28, 95% confidence interval 3.89 to 7.17, P<0.001); venous thromboembolism (3.35, 2.87 to 3.91, P<0.001); lung fibrosis (2.41, 1.37 to 4.25, P=0.002), and muscle pain (1.89, 1.63 to 2.20, P<0.001); and also for healthcare use after a diagnosis of covid-19 compared with 12 months before infection. For absolute proportions, the most common outcomes ≥4 weeks after a covid-19 diagnosis in patients in the community were joint pain (2.5%), anxiety (1.2%), and prescriptions for non-steroidal anti-inflammatory drugs (1.2%). Patients admitted to hospital (n=18 059) also had significantly higher GP consultation rates for multiple sequelae, most commonly for venous thromboembolism (16.21, 11.28 to 23.31, P<0.001), nausea (4.64, 2.24 to 9.21, P<0.001), prescriptions for paracetamol (3.68, 2.86 to 4.74, P<0.001), renal failure (3.42, 2.67 to 4.38, P<0.001), and healthcare use after a covid-19 diagnosis compared with 12 months before infection. For absolute proportions, the most common outcomes ≥4 weeks after a covid-19 diagnosis in patients admitted to hospital were venous thromboembolism (3.5%), joint pain (2.7%), and breathlessness (2.8%). In patients in the community, anxiety and depression, abdominal pain, diarrhoea, general pain, nausea, chest tightness, and tinnitus persisted throughout follow-up. GP consultation rates were reduced for all symptoms, prescriptions, and healthcare use, except for neuropathic pain, cognitive impairment, strong opiates, and paracetamol use in patients in the community after the first vaccination dose for covid-19 relative to before vaccination. GP consultation rates were also reduced for ischaemic heart disease, asthma, and gastro-oesophageal disease.

Conclusions

GP consultation rates for sequelae after acute covid-19 infection differed between patients with covid-19 who were admitted to hospital and those managed in the community. For individuals in the community, rates of some sequelae decreased over time but those for others, such as anxiety and depression, persisted. Rates of some outcomes decreased after vaccination in this group.",,pdf:https://www.bmj.com/content/bmj/375/bmj-2021-065834.full.pdf; doi:https://doi.org/10.1136/bmj-2021-065834; html:https://europepmc.org/articles/PMC8715128; pdf:https://europepmc.org/articles/PMC8715128?pdf=render 37208429,https://doi.org/10.1038/s41598-023-33391-w,Rare variant contribution to cholestatic liver disease in a South Asian population in the United Kingdom.,"Zöllner J, Finer S, Linton KJ, Genes and Health Research Team, van Heel DA, Williamson C, Dixon PH.",,Scientific reports,2023,2023-05-19,Y,,,,"This study assessed the contribution of five genes previously known to be involved in cholestatic liver disease in British Bangladeshi and Pakistani people. Five genes (ABCB4, ABCB11, ATP8B1, NR1H4, TJP2) were interrogated by exome sequencing data of 5236 volunteers. Included were non-synonymous or loss of function (LoF) variants with a minor allele frequency < 5%. Variants were filtered, and annotated to perform rare variant burden analysis, protein structure, and modelling analysis in-silico. Out of 314 non-synonymous variants, 180 fulfilled the inclusion criteria and were mostly heterozygous unless specified. 90 were novel and of those variants, 22 were considered likely pathogenic and 9 pathogenic. We identified variants in volunteers with gallstone disease (n = 31), intrahepatic cholestasis of pregnancy (ICP, n = 16), cholangiocarcinoma and cirrhosis (n = 2). Fourteen novel LoF variants were identified: 7 frameshift, 5 introduction of premature stop codon and 2 splice acceptor variants. The rare variant burden was significantly increased in ABCB11. Protein modelling demonstrated variants that appeared to likely cause significant structural alterations. This study highlights the significant genetic burden contributing to cholestatic liver disease. Novel likely pathogenic and pathogenic variants were identified addressing the underrepresentation of diverse ancestry groups in genomic research.",,doi:https://doi.org/10.1038/s41598-023-33391-w; doi:https://doi.org/10.1038/s41598-023-33391-w; html:https://europepmc.org/articles/PMC10199085; pdf:https://europepmc.org/articles/PMC10199085?pdf=render -30649175,https://doi.org/10.1001/jamacardio.2018.4537,Cardiovascular Risk Factors Associated With Venous Thromboembolism.,"Gregson J, Kaptoge S, Bolton T, Pennells L, Willeit P, Burgess S, Bell S, Sweeting M, Rimm EB, Kabrhel C, Zöller B, Assmann G, Gudnason V, Folsom AR, Arndt V, Fletcher A, Norman PE, Nordestgaard BG, Kitamura A, Mahmoodi BK, Whincup PH, Knuiman M, Salomaa V, Meisinger C, Koenig W, Kavousi M, Völzke H, Cooper JA, Ninomiya T, Casiglia E, Rodriguez B, Ben-Shlomo Y, Després JP, Simons L, Barrett-Connor E, Björkelund C, Notdurfter M, Kromhout D, Price J, Sutherland SE, Sundström J, Kauhanen J, Gallacher J, Beulens JWJ, Dankner R, Cooper C, Giampaoli S, Deen JF, Gómez de la Cámara A, Kuller LH, Rosengren A, Svensson PJ, Nagel D, Crespo CJ, Brenner H, Albertorio-Diaz JR, Atkins R, Brunner EJ, Shipley M, Njølstad I, Lawlor DA, van der Schouw YT, Selmer RM, Trevisan M, Verschuren WMM, Greenland P, Wassertheil-Smoller S, Lowe GDO, Wood AM, Butterworth AS, Thompson SG, Danesh J, Di Angelantonio E, Meade T, Emerging Risk Factors Collaboration.",,JAMA cardiology,2019,2019-02-01,Y,,Understanding the Causes of Disease,,"

Importance

It is uncertain to what extent established cardiovascular risk factors are associated with venous thromboembolism (VTE).

Objective

To estimate the associations of major cardiovascular risk factors with VTE, ie, deep vein thrombosis and pulmonary embolism.

Design, setting, and participants

This study included individual participant data mostly from essentially population-based cohort studies from the Emerging Risk Factors Collaboration (ERFC; 731 728 participants; 75 cohorts; years of baseline surveys, February 1960 to June 2008; latest date of follow-up, December 2015) and the UK Biobank (421 537 participants; years of baseline surveys, March 2006 to September 2010; latest date of follow-up, February 2016). Participants without cardiovascular disease at baseline were included. Data were analyzed from June 2017 to September 2018.

Exposures

A panel of several established cardiovascular risk factors.

Main outcomes and measures

Hazard ratios (HRs) per 1-SD higher usual risk factor levels (or presence/absence). Incident fatal outcomes in ERFC (VTE, 1041; coronary heart disease [CHD], 25 131) and incident fatal/nonfatal outcomes in UK Biobank (VTE, 2321; CHD, 3385). Hazard ratios were adjusted for age, sex, smoking status, diabetes, and body mass index (BMI).

Results

Of the 731 728 participants from the ERFC, 403 396 (55.1%) were female, and the mean (SD) age at the time of the survey was 51.9 (9.0) years; of the 421 537 participants from the UK Biobank, 233 699 (55.4%) were female, and the mean (SD) age at the time of the survey was 56.4 (8.1) years. Risk factors for VTE included older age (ERFC: HR per decade, 2.67; 95% CI, 2.45-2.91; UK Biobank: HR, 1.81; 95% CI, 1.71-1.92), current smoking (ERFC: HR, 1.38; 95% CI, 1.20-1.58; UK Biobank: HR, 1.23; 95% CI, 1.08-1.40), and BMI (ERFC: HR per 1-SD higher BMI, 1.43; 95% CI, 1.35-1.50; UK Biobank: HR, 1.37; 95% CI, 1.32-1.41). For these factors, there were similar HRs for pulmonary embolism and deep vein thrombosis in UK Biobank (except adiposity was more strongly associated with pulmonary embolism) and similar HRs for unprovoked vs provoked VTE. Apart from adiposity, these risk factors were less strongly associated with VTE than CHD. There were inconsistent associations of VTEs with diabetes and blood pressure across ERFC and UK Biobank, and there was limited ability to study lipid and inflammation markers.

Conclusions and relevance

Older age, smoking, and adiposity were consistently associated with higher VTE risk.",,pdf:https://pdxscholar.library.pdx.edu/cgi/viewcontent.cgi?article=1451&context=sph_facpub; doi:https://doi.org/10.1001/jamacardio.2018.4537; html:https://europepmc.org/articles/PMC6386140 -37647632,https://doi.org/10.1182/blood.2023020118,The effects of pathogenic and likely pathogenic variants for inherited hemostasis disorders in 140 214 UK Biobank participants.,"Stefanucci L, Collins J, Sims MC, Barrio-Hernandez I, Sun L, Burren OS, Perfetto L, Bender I, Callahan TJ, Fleming K, Guerrero JA, Hermjakob H, Martin MJ, Stephenson J, Paneerselvam K, Petrovski S, Porras P, Robinson PN, Wang Q, Watkins X, Frontini M, Laskowski RA, Beltrao P, Di Angelantonio E, Gomez K, Laffan M, Ouwehand WH, Mumford AD, Freson K, Carss K, Downes K, Gleadall N, Megy K, Bruford E, Vuckovic D.",,Blood,2023,2023-12-01,Y,,,,"Rare genetic diseases affect millions, and identifying causal DNA variants is essential for patient care. Therefore, it is imperative to estimate the effect of each independent variant and improve their pathogenicity classification. Our study of 140 214 unrelated UK Biobank (UKB) participants found that each of them carries a median of 7 variants previously reported as pathogenic or likely pathogenic. We focused on 967 diagnostic-grade gene (DGG) variants for rare bleeding, thrombotic, and platelet disorders (BTPDs) observed in 12 367 UKB participants. By association analysis, for a subset of these variants, we estimated effect sizes for platelet count and volume, and odds ratios for bleeding and thrombosis. Variants causal of some autosomal recessive platelet disorders revealed phenotypic consequences in carriers. Loss-of-function variants in MPL, which cause chronic amegakaryocytic thrombocytopenia if biallelic, were unexpectedly associated with increased platelet counts in carriers. We also demonstrated that common variants identified by genome-wide association studies (GWAS) for platelet count or thrombosis risk may influence the penetrance of rare variants in BTPD DGGs on their associated hemostasis disorders. Network-propagation analysis applied to an interactome of 18 410 nodes and 571 917 edges showed that GWAS variants with large effect sizes are enriched in DGGs and their first-order interactors. Finally, we illustrate the modifying effect of polygenic scores for platelet count and thrombosis risk on disease severity in participants carrying rare variants in TUBB1 or PROC and PROS1, respectively. Our findings demonstrate the power of association analyses using large population datasets in improving pathogenicity classifications of rare variants.",,doi:https://doi.org/10.1182/blood.2023020118; html:https://europepmc.org/articles/PMC10733830 32680743,https://doi.org/10.1016/j.jphys.2020.06.008,"Adaptation, self-motivation and support services are key to physical activity participation three to five years after major trauma: a qualitative study.","Ekegren CL, Braaf S, Ameratunga S, Ponsford J, Nunn A, Cameron P, Lyons RA, Gabbe BJ.",,Journal of physiotherapy,2020,2020-07-14,N,Trauma; Recovery; Exercise; wounds and injuries; Sedentary Lifestyle,,,"

Questions

What are the perceived long-term impacts of major trauma on physical activity participation over time? What factors influence physical activity participation in people recovering from major trauma?

Design

Longitudinal qualitative study.

Participants

Sixty-six people aged ≥ 16 years with non-neurological major trauma.

Methods

Participants were interviewed 3 years (n = 66), 4 years (n = 63) and 5 years (n = 57) after their injury. A thematic analysis was performed.

Results

Despite wanting to be physically active, many participants experienced significant, long-term physical activity restriction after their injury, which persisted over time. Restrictions were often related to a fear of re-injury or of exacerbating pain and fatigue levels. These restrictions were a source of distress and frustration for many participants, given the perceived impacts on their social life, family roles and enjoyment of life. Participants were also concerned about weight gain, health decline and reduced physical fitness. Participants valued the support of insurers and specialised services in facilitating access to modified activities, such as clinical Pilates and hydrotherapy. Many participants also recognised the importance of adaptation, goal-setting, self-motivation and determination to be physically active despite limitations.

Conclusion

People recovering from major trauma experienced significant and persistent physical activity restriction after their injury. Given the high prevalence of activity restrictions, distress and health concerns that were reported, there is an urgent need to develop and evaluate support strategies to improve physical activity participation in this group.",,doi:https://doi.org/10.1016/j.jphys.2020.06.008; doi:https://doi.org/10.1016/j.jphys.2020.06.008 +37647632,https://doi.org/10.1182/blood.2023020118,The effects of pathogenic and likely pathogenic variants for inherited hemostasis disorders in 140 214 UK Biobank participants.,"Stefanucci L, Collins J, Sims MC, Barrio-Hernandez I, Sun L, Burren OS, Perfetto L, Bender I, Callahan TJ, Fleming K, Guerrero JA, Hermjakob H, Martin MJ, Stephenson J, Paneerselvam K, Petrovski S, Porras P, Robinson PN, Wang Q, Watkins X, Frontini M, Laskowski RA, Beltrao P, Di Angelantonio E, Gomez K, Laffan M, Ouwehand WH, Mumford AD, Freson K, Carss K, Downes K, Gleadall N, Megy K, Bruford E, Vuckovic D.",,Blood,2023,2023-12-01,Y,,,,"Rare genetic diseases affect millions, and identifying causal DNA variants is essential for patient care. Therefore, it is imperative to estimate the effect of each independent variant and improve their pathogenicity classification. Our study of 140 214 unrelated UK Biobank (UKB) participants found that each of them carries a median of 7 variants previously reported as pathogenic or likely pathogenic. We focused on 967 diagnostic-grade gene (DGG) variants for rare bleeding, thrombotic, and platelet disorders (BTPDs) observed in 12 367 UKB participants. By association analysis, for a subset of these variants, we estimated effect sizes for platelet count and volume, and odds ratios for bleeding and thrombosis. Variants causal of some autosomal recessive platelet disorders revealed phenotypic consequences in carriers. Loss-of-function variants in MPL, which cause chronic amegakaryocytic thrombocytopenia if biallelic, were unexpectedly associated with increased platelet counts in carriers. We also demonstrated that common variants identified by genome-wide association studies (GWAS) for platelet count or thrombosis risk may influence the penetrance of rare variants in BTPD DGGs on their associated hemostasis disorders. Network-propagation analysis applied to an interactome of 18 410 nodes and 571 917 edges showed that GWAS variants with large effect sizes are enriched in DGGs and their first-order interactors. Finally, we illustrate the modifying effect of polygenic scores for platelet count and thrombosis risk on disease severity in participants carrying rare variants in TUBB1 or PROC and PROS1, respectively. Our findings demonstrate the power of association analyses using large population datasets in improving pathogenicity classifications of rare variants.",,doi:https://doi.org/10.1182/blood.2023020118; html:https://europepmc.org/articles/PMC10733830 35849350,https://doi.org/10.1093/nar/gkac612,Whole-genome long-read TAPS deciphers DNA methylation patterns at base resolution using PacBio SMRT sequencing technology.,"Chen J, Cheng J, Chen X, Inoue M, Liu Y, Song CX.",,Nucleic acids research,2022,2022-10-01,Y,,,,"Long-read sequencing provides valuable information on difficult-to-map genomic regions, which can complement short-read sequencing to improve genome assembly, yet limited methods are available to accurately detect DNA methylation over long distances at a whole-genome scale. By combining our recently developed TET-assisted pyridine borane sequencing (TAPS) method, which enables direct detection of 5-methylcytosine and 5-hydroxymethylcytosine, with PacBio single-molecule real-time sequencing, we present here whole-genome long-read TAPS (wglrTAPS). To evaluate the performance of wglrTAPS, we applied it to mouse embryonic stem cells as a proof of concept, and an N50 read length of 3.5 kb is achieved. By sequencing wglrTAPS to 8.2× depth, we discovered a significant proportion of CpG sites that were not covered in previous 27.5× short-read TAPS. Our results demonstrate that wglrTAPS facilitates methylation profiling on problematic genomic regions with repetitive elements or structural variations, and also in an allelic manner, all of which are extremely difficult for short-read sequencing methods to resolve. This method therefore enhances applications of third-generation sequencing technologies for DNA epigenetics.",,pdf:https://academic.oup.com/nar/article-pdf/50/18/e104/46501243/gkac612.pdf; doi:https://doi.org/10.1093/nar/gkac612; html:https://europepmc.org/articles/PMC9561279; pdf:https://europepmc.org/articles/PMC9561279?pdf=render 35188939,https://doi.org/10.1097/pts.0000000000000867,Optimizing Hospital Electronic Prescribing Systems: A Systematic Scoping Review.,"Williams J, Malden S, Heeney C, Bouamrane M, Holder M, Perera U, Bates DW, Sheikh A.",,Journal of patient safety,2022,2022-03-01,Y,,,,"

Objective

Considerable international investment in hospital electronic prescribing (ePrescribing) systems has been made, but despite this, it is proving difficult for most organizations to realize safety, quality, and efficiency gains in prescribing. The objective of this work was to develop policy-relevant insights into the optimization of hospital ePrescribing systems to maximize the benefits and minimize the risks of these expensive digital health infrastructures.

Methods

We undertook a systematic scoping review of the literature by searching MEDLINE, Embase, and CINAHL databases. We searched for primary studies reporting on ePrescribing optimization strategies and independently screened and abstracted data until saturation was achieved. Findings were theoretically and thematically synthesized taking a medicine life-cycle perspective, incorporating consultative phases with domain experts.

Results

We identified 23,609 potentially eligible studies from which 1367 satisfied our inclusion criteria. Thematic synthesis was conducted on a data set of 76 studies, of which 48 were based in the United States. Key approaches to optimization included the following: stakeholder engagement, system or process redesign, technological innovations, and education and training packages. Single-component interventions (n = 26) described technological optimization strategies focusing on a single, specific step in the prescribing process. Multicomponent interventions (n = 50) used a combination of optimization strategies, typically targeting multiple steps in the medicines management process.

Discussion

We identified numerous optimization strategies for enhancing the performance of ePrescribing systems. Key considerations for ePrescribing optimization include meaningful stakeholder engagement to reconceptualize the service delivery model and implementing technological innovations with supporting training packages to simultaneously impact on different facets of the medicines management process.",,html:https://journals.lww.com/journalpatientsafety/Fulltext/2022/03000/Optimizing_Hospital_Electronic_Prescribing.36.aspx; doi:https://doi.org/10.1097/PTS.0000000000000867; html:https://europepmc.org/articles/PMC8855945; pdf:https://europepmc.org/articles/PMC8855945?pdf=render 30887727,https://doi.org/10.1002/ppul.24314,Physical activity among children with asthma: Cross-sectional analysis in the UK millennium cohort.,"Pike KC, Griffiths LJ, Dezateux C, Pearce A.",,Pediatric pulmonology,2019,2019-03-18,Y,Children; Cohort study; epidemiology; Physical Activity; Asthma And Early Wheeze,Improving Public Health,,"

Background

Although beneficial for health and well-being, most children do not achieve recommended levels of physical activity. Evidence for children with asthma is mixed, with symptom severity rarely considered. This paper aimed to address this gap.

Methods

We analyzed cross-sectional associations between physical activity and parent-reported asthma symptoms and severity for 6497 UK Millennium Cohort Study 7-year-old participants (3321, [49%] girls). Primary outcomes were daily moderate-to-vigorous physical activity (MVPA, minutes) and proportion of children achieving recommended minimum daily levels of 60 minutes of MVPA. Daily steps, sedentary time, and total activity counts per minute (cpm) were recorded, as were parent-reported asthma symptoms, medications, and recent hospital admissions. Associations were investigated using quantile (continuous outcomes) and Poisson (binary outcomes) regression, adjusting for demographic, socioeconomic, health, and environmental factors.

Results

Neither asthma status nor severity was associated with MVPA; children recently hospitalized for asthma were less likely to achieve recommended daily MVPA (risk ratio [95% confidence interval [CI]]: 0.67 [0.44, 1.03]). Recent wheeze, current asthma, and severe asthma symptoms were associated with fewer sedentary hours (difference in medians [95% CI]: -0.18 [-0.27, -0.08]; -0.14 [-0.24, -0.05]; -0.15, [-0.28, -0.02], respectively) and hospital admission with lower total activity (-48 cpm [-68, -28]).

Conclusion

Children with asthma are as physically active as their asthma-free counterparts, while those recently hospitalized for asthma are less active. Qualitative studies are needed to understand the perceptions of children and families about physical activity following hospital admission and to inform support and advice needed to maintain active lifestyles for children with asthma.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ppul.24314; doi:https://doi.org/10.1002/ppul.24314; html:https://europepmc.org/articles/PMC6617805; pdf:https://europepmc.org/articles/PMC6617805?pdf=render @@ -1995,8 +1995,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 38548763,https://doi.org/10.1038/s41467-024-46982-6,The SARS-CoV-2 neutralizing antibody response to SD1 and its evasion by BA.2.86.,"Zhou D, Supasa P, Liu C, Dijokaite-Guraliuc A, Duyvesteyn HME, Selvaraj M, Mentzer AJ, Das R, Dejnirattisai W, Temperton N, Klenerman P, Dunachie SJ, Fry EE, Mongkolsapaya J, Ren J, Stuart DI, Screaton GR.",,Nature communications,2024,2024-03-28,Y,,,,"Under pressure from neutralising antibodies induced by vaccination or infection the SARS-CoV-2 spike gene has become a hotspot for evolutionary change, leading to the failure of all mAbs developed for clinical use. Most potent antibodies bind to the receptor binding domain which has become heavily mutated. Here we study responses to a conserved epitope in sub-domain-1 (SD1) of spike which have become more prominent because of mutational escape from antibodies directed to the receptor binding domain. Some SD1 reactive mAbs show potent and broad neutralization of SARS-CoV-2 variants. We structurally map the dominant SD1 epitope and provide a mechanism of action by blocking interaction with ACE2. Mutations in SD1 have not been sustained to date, but one, E554K, leads to escape from mAbs. This mutation has now emerged in several sublineages including BA.2.86, reflecting selection pressure on the virus exerted by the increasing prominence of the anti-SD1 response.",,pdf:https://www.nature.com/articles/s41467-024-46982-6.pdf; doi:https://doi.org/10.1038/s41467-024-46982-6; html:https://europepmc.org/articles/PMC10978878; pdf:https://europepmc.org/articles/PMC10978878?pdf=render 36168404,https://doi.org/10.1016/j.lanepe.2022.100501,Risk factors for SARS-CoV-2 infection after primary vaccination with ChAdOx1 nCoV-19 or BNT162b2 and after booster vaccination with BNT162b2 or mRNA-1273: A population-based cohort study (COVIDENCE UK).,"Vivaldi G, Jolliffe DA, Holt H, Tydeman F, Talaei M, Davies GA, Lyons RA, Griffiths CJ, Kee F, Sheikh A, Shaheen SO, Martineau AR.",,The Lancet regional health. Europe,2022,2022-09-23,Y,Vaccination; Breakthrough Infection; Chadox1; Sars-cov-2; Mrna-1273; Bnt162b2,,,"

Background

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

Methods

This prospective, population-based, UK study in adults (≥16 years) vaccinated against SARS-CoV-2 assessed risk of breakthrough SARS-CoV-2 infection up to February, 2022, for participants who completed a primary vaccination course (ChAdOx1 nCoV-19 or BNT162b2) and those who received a booster dose (BNT162b2 or mRNA-1273). Cox regression models explored associations between sociodemographic, behavioural, clinical, pharmacological, and nutritional factors and test-positive breakthrough infection, adjusted for local weekly SARS-CoV-2 incidence.

Findings

1051 (7·1%) of 14 713 post-primary participants and 1009 (9·5%) of 10 665 post-booster participants reported breakthrough infection, over a median follow-up of 203 days (IQR 195-216) and 85 days (66-103), respectively. Primary vaccination with ChAdOx1 (vs BNT162b2) was associated with higher risk of infection in both post-primary analysis (adjusted hazard ratio 1·63, 95% CI 1·41-1·88) and after an mRNA-1273 booster (1·26 [1·00-1·57] vs BNT162b2 primary and booster). Lower risk of infection was associated with older age (post-primary: 0·97 [0·96-0·97] per year; post-booster: 0·97 [0·97-0·98]), whereas higher risk of infection was associated with lower educational attainment (post-primary: 1·78 [1·44-2·20] for primary/secondary vs postgraduate; post-booster: 1·46 [1·16-1·83]) and at least three weekly visits to indoor public places (post-primary: 1·36 [1·13-1·63] vs none; post-booster: 1·29 [1·07-1·56]).

Interpretation

Vaccine type, socioeconomic status, age, and behaviours affect risk of breakthrough infection after primary and booster vaccinations.

Funding

Barts Charity, UK Research and Innovation Industrial Strategy Challenge Fund.",,doi:https://doi.org/10.1016/j.lanepe.2022.100501; doi:https://doi.org/10.1016/j.lanepe.2022.100501; html:https://europepmc.org/articles/PMC9499825; pdf:https://europepmc.org/articles/PMC9499825?pdf=render 33025017,https://doi.org/10.1093/schbul/sbaa126,Using Natural Language Processing on Electronic Health Records to Enhance Detection and Prediction of Psychosis Risk.,"Irving J, Patel R, Oliver D, Colling C, Pritchard M, Broadbent M, Baldwin H, Stahl D, Stewart R, Fusar-Poli P.",,Schizophrenia bulletin,2021,2021-03-01,N,Prediction; Prevention; Psychosis; Machine Learning; Electronic Health Records; Natural Language Processing,,,"

Background

Using novel data mining methods such as natural language processing (NLP) on electronic health records (EHRs) for screening and detecting individuals at risk for psychosis.

Method

The study included all patients receiving a first index diagnosis of nonorganic and nonpsychotic mental disorder within the South London and Maudsley (SLaM) NHS Foundation Trust between January 1, 2008, and July 28, 2018. Least Absolute Shrinkage and Selection Operator (LASSO)-regularized Cox regression was used to refine and externally validate a refined version of a five-item individualized, transdiagnostic, clinically based risk calculator previously developed (Harrell's C = 0.79) and piloted for implementation. The refined version included 14 additional NLP-predictors: tearfulness, poor appetite, weight loss, insomnia, cannabis, cocaine, guilt, irritability, delusions, hopelessness, disturbed sleep, poor insight, agitation, and paranoia.

Results

A total of 92 151 patients with a first index diagnosis of nonorganic and nonpsychotic mental disorder within the SLaM Trust were included in the derivation (n = 28 297) or external validation (n = 63 854) data sets. Mean age was 33.6 years, 50.7% were women, and 67.0% were of white race/ethnicity. Mean follow-up was 1590 days. The overall 6-year risk of psychosis in secondary mental health care was 3.4 (95% CI, 3.3-3.6). External validation indicated strong performance on unseen data (Harrell's C 0.85, 95% CI 0.84-0.86), an increase of 0.06 from the original model.

Conclusions

Using NLP on EHRs can considerably enhance the prognostic accuracy of psychosis risk calculators. This can help identify patients at risk of psychosis who require assessment and specialized care, facilitating earlier detection and potentially improving patient outcomes.",,pdf:https://academic.oup.com/schizophreniabulletin/article-pdf/47/2/405/36620462/sbaa126.pdf; doi:https://doi.org/10.1093/schbul/sbaa126; html:https://europepmc.org/articles/PMC7965059; pdf:https://europepmc.org/articles/PMC7965059?pdf=render; doi:https://doi.org/10.1093/schbul/sbaa126 -33185016,https://doi.org/10.1002/art.41593,Nonsteroidal Antiinflammatory Drugs and Susceptibility to COVID-19.,"Chandan JS, Zemedikun DT, Thayakaran R, Byne N, Dhalla S, Acosta-Mena D, Gokhale KM, Thomas T, Sainsbury C, Subramanian A, Cooper J, Anand A, Okoth KO, Wang J, Adderley NJ, Taverner T, Denniston AK, Lord J, Thomas GN, Buckley CD, Raza K, Bhala N, Nirantharakumar K, Haroon S.",,"Arthritis & rheumatology (Hoboken, N.J.)",2021,2021-05-01,Y,,,,"

Objective

To identify whether active use of nonsteroidal antiinflammatory drugs (NSAIDs) increases susceptibility to developing suspected or confirmed coronavirus disease 2019 (COVID-19) compared to the use of other common analgesics.

Methods

We performed a propensity score-matched cohort study with active comparators, using a large UK primary care data set. The cohort consisted of adult patients age ≥18 years with osteoarthritis (OA) who were followed up from January 30 to July 31, 2020. Patients prescribed an NSAID (excluding topical preparations) were compared to those prescribed either co-codamol (paracetamol and codeine) or co-dydramol (paracetamol and dihydrocodeine). A total of 13,202 patients prescribed NSAIDs were identified, compared to 12,457 patients prescribed the comparator drugs. The primary outcome measure was the documentation of suspected or confirmed COVID-19, and the secondary outcome measure was all-cause mortality.

Results

During follow-up, the incidence rates of suspected/confirmed COVID-19 were 15.4 and 19.9 per 1,000 person-years in the NSAID-exposed group and comparator group, respectively. Adjusted hazard ratios for suspected or confirmed COVID-19 among the unmatched and propensity score-matched OA cohorts, using data from clinical consultations in primary care settings, were 0.82 (95% confidence interval [95% CI] 0.62-1.10) and 0.79 (95% CI 0.57-1.11), respectively, and adjusted hazard ratios for the risk of all-cause mortality were 0.97 (95% CI 0.75-1.27) and 0.85 (95% CI 0.61-1.20), respectively. There was no effect modification by age or sex.

Conclusion

No increase in the risk of suspected or confirmed COVID-19 or mortality was observed among patients with OA in a primary care setting who were prescribed NSAIDs as compared to those who received comparator drugs. These results are reassuring and suggest that in the absence of acute illness, NSAIDs can be safely prescribed during the ongoing pandemic.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/art.41593; doi:https://doi.org/10.1002/art.41593; html:https://europepmc.org/articles/PMC8252419; pdf:https://europepmc.org/articles/PMC8252419?pdf=render 31780306,https://doi.org/10.1016/s2215-0366(19)30298-6,Pharmacoepidemiology research: delivering evidence about drug safety and effectiveness in mental health.,"Davis KAS, Farooq S, Hayes JF, John A, Lee W, MacCabe JH, McIntosh A, Osborn DPJ, Stewart RJ, Woelbert E.",,The lancet. Psychiatry,2020,2019-11-25,N,,,,"Research that provides an evidence base for the pharmacotherapy of people with mental disorders is needed. The abundance of digital data has facilitated pharmacoepidemiology and, in particular, observational research on the effectiveness of real-world medication. Advantages of pharmacoepidemiological research are the availability of large patient samples, and coverage of under-researched subpopulations in their naturalistic conditions. Such research is also cheaper and quicker to do than randomised controlled trials, meaning that issues regarding generic medication, stopping medication (deprescribing), and long-term outcomes are more likely to be addressed. Pharmacoepidemiological methods can also be extended to pharmacovigilance and to aid the development of new purposes for existing drugs. Drawbacks of observational pharmacoepidemiological studies come from the non-randomised nature of treatment selection, leading to confounding by indication. Potential methods for managing this drawback include active comparison groups, within-individual designs, and propensity scoring. Many of the more rigorous pharmacoepidemiology studies have been strengthened through multiple analytical approaches triangulated to improve confidence in inferred causal relationships. With developments in data resources and analytical techniques, it is encouraging that guidelines are beginning to include evidence from robust observational pharmacoepidemiological studies alongside randomised controlled trials. Collaboration between guideline writers and researchers involved in pharmacoepidemiology could help researchers to answer the questions that are important to policy makers and ensure that results are integrated into the evidence base. Further development of statistical and data science techniques, alongside public engagement and capacity building (data resources and researcher base), will be necessary to take full advantage of future opportunities.",,html:https://eprints.keele.ac.uk/6650/1/Pharamcoepidemiology%20Lancet%20Psych%202019%20submitted%20version.docx; doi:https://doi.org/10.1016/S2215-0366(19)30298-6 +33185016,https://doi.org/10.1002/art.41593,Nonsteroidal Antiinflammatory Drugs and Susceptibility to COVID-19.,"Chandan JS, Zemedikun DT, Thayakaran R, Byne N, Dhalla S, Acosta-Mena D, Gokhale KM, Thomas T, Sainsbury C, Subramanian A, Cooper J, Anand A, Okoth KO, Wang J, Adderley NJ, Taverner T, Denniston AK, Lord J, Thomas GN, Buckley CD, Raza K, Bhala N, Nirantharakumar K, Haroon S.",,"Arthritis & rheumatology (Hoboken, N.J.)",2021,2021-05-01,Y,,,,"

Objective

To identify whether active use of nonsteroidal antiinflammatory drugs (NSAIDs) increases susceptibility to developing suspected or confirmed coronavirus disease 2019 (COVID-19) compared to the use of other common analgesics.

Methods

We performed a propensity score-matched cohort study with active comparators, using a large UK primary care data set. The cohort consisted of adult patients age ≥18 years with osteoarthritis (OA) who were followed up from January 30 to July 31, 2020. Patients prescribed an NSAID (excluding topical preparations) were compared to those prescribed either co-codamol (paracetamol and codeine) or co-dydramol (paracetamol and dihydrocodeine). A total of 13,202 patients prescribed NSAIDs were identified, compared to 12,457 patients prescribed the comparator drugs. The primary outcome measure was the documentation of suspected or confirmed COVID-19, and the secondary outcome measure was all-cause mortality.

Results

During follow-up, the incidence rates of suspected/confirmed COVID-19 were 15.4 and 19.9 per 1,000 person-years in the NSAID-exposed group and comparator group, respectively. Adjusted hazard ratios for suspected or confirmed COVID-19 among the unmatched and propensity score-matched OA cohorts, using data from clinical consultations in primary care settings, were 0.82 (95% confidence interval [95% CI] 0.62-1.10) and 0.79 (95% CI 0.57-1.11), respectively, and adjusted hazard ratios for the risk of all-cause mortality were 0.97 (95% CI 0.75-1.27) and 0.85 (95% CI 0.61-1.20), respectively. There was no effect modification by age or sex.

Conclusion

No increase in the risk of suspected or confirmed COVID-19 or mortality was observed among patients with OA in a primary care setting who were prescribed NSAIDs as compared to those who received comparator drugs. These results are reassuring and suggest that in the absence of acute illness, NSAIDs can be safely prescribed during the ongoing pandemic.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/art.41593; doi:https://doi.org/10.1002/art.41593; html:https://europepmc.org/articles/PMC8252419; pdf:https://europepmc.org/articles/PMC8252419?pdf=render 35068290,https://doi.org/10.1080/09537104.2021.2003317,Higher body mass index raises immature platelet count: potential contribution to obesity-related thrombosis.,"Goudswaard LJ, Corbin LJ, Burley KL, Mumford A, Akbari P, Soranzo N, Butterworth AS, Watkins NA, Pournaras DJ, Harris J, Timpson NJ, Hers I.",,Platelets,2022,2022-01-24,N,Obesity; Aggregation; epidemiology; Mendelian Randomization; Immature Platelets,,,"Higher body mass index (BMI) is a risk factor for thrombosis. Platelets are essential for hemostasis but contribute to thrombosis when activated pathologically. We hypothesized that higher BMI leads to changes in platelet characteristics, thereby increasing thrombotic risk. The effect of BMI on platelet traits (measured by Sysmex) was explored in 33 388 UK blood donors (INTERVAL study). Linear regression showed that higher BMI was positively associated with greater plateletcrit (PCT), platelet count (PLT), immature platelet count (IPC), and side fluorescence (SFL, a measure of mRNA content used to derive IPC). Mendelian randomization (MR), applied to estimate a causal effect with BMI proxied by a genetic risk score, provided causal estimates for a positive effect of BMI on both SFL and IPC, but there was little evidence for a causal effect of BMI on PCT or PLT. Follow-up analyses explored the functional relevance of platelet characteristics in a pre-operative cardiac cohort (COPTIC). Linear regression provided observational evidence for a positive association between IPC and agonist-induced whole blood platelet aggregation. Results indicate that higher BMI raises the number of immature platelets, which is associated with greater whole blood platelet aggregation in a cardiac cohort. Higher IPC could therefore contribute to obesity-related thrombosis.",,doi:https://doi.org/10.1080/09537104.2021.2003317; doi:https://doi.org/10.1080/09537104.2021.2003317 31163036,https://doi.org/10.1371/journal.pone.0217158,Differences in the epidemiology of out-of-hospital and in-hospital trauma deaths.,"Beck B, Smith K, Mercier E, Gabbe B, Bassed R, Mitra B, Teague W, Siedenburg J, McLellan S, Cameron P.",,PloS one,2019,2019-06-04,Y,,Improving Public Health,,"

Background

Trauma is a leading cause of mortality. Holistic views of trauma systems consider injury as a public health problem that requires efforts in primary, secondary and tertiary prevention. However, the performance of trauma systems is commonly judged on the in-hospital mortality rate. Such a focus misses opportunities to consider all deaths within a population, to understand differences in in-hospital and out-of-hospital trauma deaths and to inform population-level injury prevention efforts. The aim of this study was to provide an epidemiological overview of out-of-hospital and in-hospital trauma deaths in a geographically-defined area over a 10-year period.

Methods

We performed a population-based review of out-of-hospital and in-hospital trauma deaths over the period of 01 July 2006 to 30 June 2016 in Victoria, Australia, using data from the National Coronial Information System and the Victorian State Trauma Registry. Temporal trends in population-based incidence rates were evaluated.

Results

Over the study period, there were 11,246 trauma deaths, of which 71% were out-of-hospital deaths. Out-of-hospital trauma deaths commonly resulted from intentional self-harm events (50%) and transport events (35%), while in-hospital trauma deaths commonly resulted from low falls (≤1 metre) (50%). The incidence of overall trauma deaths did not change over the study period (incidence rate ratio 0.998; 95%CI: 0.991, 1.004; P = 0.56).

Conclusions

Out-of-hospital deaths accounted for most trauma deaths. Given the notable differences between out-of-hospital and in-hospital trauma deaths, monitoring of all trauma deaths is necessary to inform injury prevention activities and to reduce trauma mortality. The absence of a change in the incidence of both out-of-hospital and in-hospital trauma deaths demonstrates the need for enhanced activities across all aspects of injury prevention.",,doi:https://doi.org/10.1371/journal.pone.0217158; doi:https://doi.org/10.1371/journal.pone.0217158; html:https://europepmc.org/articles/PMC6548370; pdf:https://europepmc.org/articles/PMC6548370?pdf=render 31196949,https://doi.org/10.1183/13993003.02309-2018,Educational and health outcomes of children treated for asthma: Scotland-wide record linkage study of 683 716 children.,"Fleming M, Fitton CA, Steiner MFC, McLay JS, Clark D, King A, Mackay DF, Pell JP.",,The European respiratory journal,2019,2019-09-05,Y,,Improving Public Health,,"

Background

The global prevalence of childhood asthma is increasing. The condition impacts physical and psychosocial morbidity; therefore, wide-ranging effects on health and education outcomes are plausible.

Methods

Linkage of eight Scotland-wide databases, covering dispensed prescriptions, hospital admissions, maternity records, death certificates, annual pupil census, examinations, school absences/exclusions and unemployment, provided data on 683 716 children attending Scottish schools between 2009 and 2013. We compared schoolchildren on medication for asthma with peers, adjusting for sociodemographic, maternity and comorbidity confounders, and explored effect modifiers and mediators.

Results

The 45 900 (6.0%) children treated for asthma had an increased risk of hospitalisation, particularly within the first year of treatment (incidence rate ratio 1.98, 95% CI 1.93-2.04), and increased mortality (HR 1.77, 95% CI 1.30-2.40). They were more likely to have special educational need for mental (OR 1.76, 95% CI 1.49-2.08) and physical (OR 2.76, 95% CI 2.57-2.95) health reasons, and performed worse in school exams (OR 1.11, 95% CI 1.06-1.16). Higher absenteeism (incidence rate ratio 1.25, 95% CI 1.24-1.26) partially explained their poorer attainment.

Conclusions

Children with treated asthma have poorer education and health outcomes than their peers. Educational interventions that mitigate the adverse effects of absenteeism should be considered.",,pdf:https://erj.ersjournals.com/content/erj/54/3/1802309.full.pdf; doi:https://doi.org/10.1183/13993003.02309-2018; html:https://europepmc.org/articles/PMC6727030; pdf:https://europepmc.org/articles/PMC6727030?pdf=render @@ -2019,18 +2019,18 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 33905882,https://doi.org/10.1016/j.media.2021.102050,Phenotype discovery from population brain imaging.,"Gong W, Beckmann CF, Smith SM.",,Medical image analysis,2021,2021-03-31,Y,Neuroimaging; Uk Biobank; Behaviour Prediction; Multimodal Independent Component Analysis; Phenotype Discovery,,,"Neuroimaging allows for the non-invasive study of the brain in rich detail. Data-driven discovery of patterns of population variability in the brain has the potential to be extremely valuable for early disease diagnosis and understanding the brain. The resulting patterns can be used as imaging-derived phenotypes (IDPs), and may complement existing expert-curated IDPs. However, population datasets, comprising many different structural and functional imaging modalities from thousands of subjects, provide a computational challenge not previously addressed. Here, for the first time, a multimodal independent component analysis approach is presented that is scalable for data fusion of voxel-level neuroimaging data in the full UK Biobank (UKB) dataset, that will soon reach 100,000 imaged subjects. This new computational approach can estimate modes of population variability that enhance the ability to predict thousands of phenotypic and behavioural variables using data from UKB and the Human Connectome Project. A high-dimensional decomposition achieved improved predictive power compared with widely-used analysis strategies, single-modality decompositions and existing IDPs. In UKB data (14,503 subjects with 47 different data modalities), many interpretable associations with non-imaging phenotypes were identified, including multimodal spatial maps related to fluid intelligence, handedness and disease, in some cases where IDP-based approaches failed.",,doi:https://doi.org/10.1016/j.media.2021.102050; doi:https://doi.org/10.1016/j.media.2021.102050; html:https://europepmc.org/articles/PMC8850869; pdf:https://europepmc.org/articles/PMC8850869?pdf=render 33299071,https://doi.org/10.1038/s41746-020-00357-5,Belief of having had unconfirmed Covid-19 infection reduces willingness to participate in app-based contact tracing.,"Bachtiger P, Adamson A, Quint JK, Peters NS.",,NPJ digital medicine,2020,2020-11-06,Y,,,,"Contact tracing and lockdown are health policies being used worldwide to combat the coronavirus (COVID-19). The UK National Health Service (NHS) Track and Trace Service has plans for a nationwide app that notifies the need for self-isolation to those in contact with a person testing positive for COVID-19. To be successful, such an app will require high uptake, the determinants and willingness for which are unclear but essential to understand for effective public health benefit. The objective of this study was to measure the determinants of willingness to participate in an NHS app-based contact-tracing programme using a questionnaire within the Care Information Exchange (CIE)-the largest patient-facing electronic health record in the NHS. Among 47,708 registered NHS users of the CIE, 27% completed a questionnaire asking about willingness to participate in app-based contact tracing, understanding of government advice, mental and physical wellbeing and their healthcare utilisation-related or not to COVID-19. Descriptive statistics are reported alongside univariate and multivariable logistic regression models, with positive or negative responses to a question on app-based contact tracing as the dependent variable. 26.1% of all CIE participants were included in the analysis (N = 12,434, 43.0% male, mean age 55.2). 60.3% of respondents were willing to participate in app-based contact tracing. Out of those who responded 'no', 67.2% stated that this was due to privacy concerns. In univariate analysis, worsening mood, fear and anxiety in relation to changes in government rules around lockdown were associated with lower willingness to participate. Multivariable analysis showed that difficulty understanding government rules was associated with a decreased inclination to download the app, with those scoring 1-2 and 3-4 in their understanding of the new government rules being 45% and 27% less inclined to download the contact-tracing app, respectively; when compared to those who rated their understanding as 5-6/10 (OR for 1-2/10 = 0.57 [CI 0.48-0.67]; OR for 3-4/10 = 0.744 [CI 0.64-0.87]), whereas scores of 7-8 and 9-10 showed a 43% and 31% respective increase. Those reporting an unconfirmed belief of having previously had and recovered from COVID-19 were 27% less likely to be willing to download the app; belief of previous recovery from COVID-19 infection OR 0.727 [0.585-0.908]). In this large UK-wide questionnaire of wellbeing in lockdown, a willingness for app-based contact tracing over an appropriate age range is 60%-close to the estimated 56% population uptake, and substantially less than the smartphone-user uptake considered necessary for an app-based contact tracing to be an effective intervention to help suppress an epidemic. Difficulty comprehending government advice and uncertainty of diagnosis, based on a public health policy of not testing to confirm self-reported COVID-19 infection during lockdown, therefore reduce willingness to adopt a government contact-tracing app to a level below the threshold for effectiveness as a tool to suppress an epidemic.",,pdf:https://www.nature.com/articles/s41746-020-00357-5.pdf; doi:https://doi.org/10.1038/s41746-020-00357-5; html:https://europepmc.org/articles/PMC7648058; pdf:https://europepmc.org/articles/PMC7648058?pdf=render 35482474,https://doi.org/10.1111/bjd.21627,Biomarkers of disease progression in people with psoriasis: a scoping review.,"Ramessur R, Corbett M, Marshall D, Acencio ML, Barbosa IA, Dand N, Di Meglio P, Haddad S, Jensen AHM, Koopmann W, Mahil SK, Ostaszewski M, Rahmatulla S, Rastrick J, Saklatvala J, Weidinger S, Wright K, Eyerich K, Ndlovu M, Barker JN, Skov L, Conrad C, Smith CH, BIOMAP consortium.",,The British journal of dermatology,2022,2022-07-11,Y,,,,"

Background

Identification of those at risk of more severe psoriasis and/or associated morbidities offers opportunity for early intervention, reduced disease burden and more cost-effective healthcare. Prognostic biomarkers of disease progression have thus been the focus of intense research, but none are part of routine practice.

Objectives

To identify and catalogue candidate biomarkers of disease progression in psoriasis for the translational research community.

Methods

A systematic search of CENTRAL, Embase, LILACS and MEDLINE was performed for relevant articles published between 1990 and December 2021. Eligibility criteria were studies involving patients with psoriasis (any age, n ≥ 50) reporting biomarkers associated with disease progression. The main outcomes were any measure of skin severity or any prespecified psoriasis comorbidity. Data were extracted by one reviewer and checked by a second; studies meeting minimal quality criteria (longitudinal design and/or use of methods to control for confounding) were formally assessed for bias. Candidate biomarkers were identified by an expert multistakeholder group using a majority voting consensus exercise, and mapped to relevant cellular and molecular pathways.

Results

Of 181 included studies, most investigated genomic or proteomic biomarkers associated with disease severity (n = 145) or psoriatic arthritis (n = 30). Methodological and reporting limitations compromised interpretation of findings, most notably a lack of longitudinal studies, and inadequate control for key prognostic factors. The following candidate biomarkers with future potential utility were identified for predicting disease severity: LCE3D, interleukin (IL)23R, IL23A, NFKBIL1 loci, HLA-C*06:02 (genomic), IL-17A, IgG aHDL, GlycA, I-FABP and kallikrein 8 (proteomic), tyramine (metabolomic); psoriatic arthritis: HLA-C*06:02, HLA-B*27, HLA-B*38, HLA-B*08, and variation at the IL23R and IL13 loci (genomic); IL-17A, CXCL10, Mac-2 binding protein, integrin b5, matrix metalloproteinase-3 and macrophage-colony stimulating factor (proteomic) and tyramine and mucic acid (metabolomic); and type 2 diabetes mellitus: variation in IL12B and IL23R loci (genomic). No biomarkers were supported by sufficient evidence for clinical use without further validation.

Conclusions

This review provides a comprehensive catalogue of investigated biomarkers of disease progression in psoriasis. Future studies must address the common methodological limitations identified herein to expedite discovery and validation of biomarkers for clinical use. What is already known about this topic? The current treatment paradigm in psoriasis is reactive. There is a need to develop effective risk-stratified management approaches that can proactively attenuate the substantial burden of disease. Prognostic biomarkers of disease progression have therefore been the focus of intense research. What does this study add? This review is the first to scope, collate and catalogue research investigating biomarkers of disease progression in psoriasis. The review identifies potentially promising candidate biomarkers for further investigation and highlights common important limitations that should be considered when designing and conducting future studies in this area.",,pdf:https://kclpure.kcl.ac.uk/ws/files/177671246/Br_J_Dermatol_2022_Ramessur_Biomarkers_of_disease_progression_in_people_with_psoriasis_a_scoping_review.pdf; doi:https://doi.org/10.1111/bjd.21627; html:https://europepmc.org/articles/PMC9796834; pdf:https://europepmc.org/articles/PMC9796834?pdf=render -37789377,https://doi.org/10.1186/s12943-023-01863-2,Spatial transcriptomic analysis of virtual prostate biopsy reveals confounding effect of tissue heterogeneity on genomic signatures.,"Figiel S, Yin W, Doultsinos D, Erickson A, Poulose N, Singh R, Magnussen A, Anbarasan T, Teague R, He M, Lundeberg J, Loda M, Verrill C, Colling R, Gill PS, Bryant RJ, Hamdy FC, Woodcock DJ, Mills IG, Cussenot O, Lamb AD.",,Molecular cancer,2023,2023-10-03,Y,prostate cancer; Virtual Biopsy; Spatial Transcriptomics; Prognostic Genetic Signatures,,,"Genetic signatures have added a molecular dimension to prognostics and therapeutic decision-making. However, tumour heterogeneity in prostate cancer and current sampling methods could confound accurate assessment. Based on previously published spatial transcriptomic data from multifocal prostate cancer, we created virtual biopsy models that mimic conventional biopsy placement and core size. We then analysed the gene expression of different prognostic signatures (OncotypeDx®, Decipher®, Prostadiag®) using a step-wise approach with increasing resolution from pseudo-bulk analysis of the whole biopsy, to differentiation by tissue subtype (benign, stroma, tumour), followed by distinct tumour grade and finally clonal resolution. The gene expression profile of virtual tumour biopsies revealed clear differences between grade groups and tumour clones, compared to a benign control, which were not reflected in bulk analyses. This suggests that bulk analyses of whole biopsies or tumour-only areas, as used in clinical practice, may provide an inaccurate assessment of gene profiles. The type of tissue, the grade of the tumour and the clonal composition all influence the gene expression in a biopsy. Clinical decision making based on biopsy genomics should be made with caution while we await more precise targeting and cost-effective spatial analyses.",,pdf:https://molecular-cancer.biomedcentral.com/counter/pdf/10.1186/s12943-023-01863-2; doi:https://doi.org/10.1186/s12943-023-01863-2; html:https://europepmc.org/articles/PMC10546768; pdf:https://europepmc.org/articles/PMC10546768?pdf=render 31588514,https://doi.org/10.1093/ptj/pzz151,Physical Activity and Sedentary Behavior 6 Months After Musculoskeletal Trauma: What Factors Predict Recovery?,"Ekegren CL, Climie RE, Simpson PM, Owen N, Dunstan DW, Veitch W, Gabbe BJ.",,Physical therapy,2020,2020-02-01,N,,,,"

Background

Physical activity is increasingly recognized as an important marker of functional recovery following fracture.

Objective

The objectives of this study were to measure sedentary behavior and physical activity 2 weeks and 6 months following fracture and to determine associated demographic and injury factors.

Design

This was an observational study.

Methods

Two weeks and 6 months following fracture, 83 adults who were 18 to 69 years old and had upper limb (UL) or lower limb (LL) fractures wore an accelerometer and an inclinometer for 10 days. We calculated sitting time, steps, moderate-intensity physical activity (MPA), and vigorous-intensity physical activity and conducted linear mixed-effects multivariable regression analyses to determine factors associated with temporal changes in activity.

Results

At 6 months versus 2 weeks after fracture, participants sat less, took more steps, and engaged in more MPA. Participants with LL fractures sat 2 hours more, took 66% fewer steps, and engaged in 77% less MPA than participants with UL fractures. Greater reductions in sitting time were observed for participants in the youngest age group and with LL fractures, participants with high preinjury activity, and participants who were overweight or obese. For steps, greater improvement was observed for participants in the youngest and middle-aged groups and those with LL fractures. For MPA, greater improvement was observed for middle-aged participants and those with LL fractures.

Limitations

Although this study was sufficiently powered for the analysis of major categories, a convenience sample that may not be representative of all people with musculoskeletal trauma was used.

Conclusions

Working-age adults with LL fractures had lower levels of physical activity 6 months after fracture than those with UL fractures. Older adults showed less improvement over time, suggesting that they are an important target group for interventions aimed at regaining preinjury activity levels.",,pdf:https://academic.oup.com/ptj/article-pdf/100/2/332/32901113/pzz151.pdf; doi:https://doi.org/10.1093/ptj/pzz151 +37789377,https://doi.org/10.1186/s12943-023-01863-2,Spatial transcriptomic analysis of virtual prostate biopsy reveals confounding effect of tissue heterogeneity on genomic signatures.,"Figiel S, Yin W, Doultsinos D, Erickson A, Poulose N, Singh R, Magnussen A, Anbarasan T, Teague R, He M, Lundeberg J, Loda M, Verrill C, Colling R, Gill PS, Bryant RJ, Hamdy FC, Woodcock DJ, Mills IG, Cussenot O, Lamb AD.",,Molecular cancer,2023,2023-10-03,Y,prostate cancer; Virtual Biopsy; Spatial Transcriptomics; Prognostic Genetic Signatures,,,"Genetic signatures have added a molecular dimension to prognostics and therapeutic decision-making. However, tumour heterogeneity in prostate cancer and current sampling methods could confound accurate assessment. Based on previously published spatial transcriptomic data from multifocal prostate cancer, we created virtual biopsy models that mimic conventional biopsy placement and core size. We then analysed the gene expression of different prognostic signatures (OncotypeDx®, Decipher®, Prostadiag®) using a step-wise approach with increasing resolution from pseudo-bulk analysis of the whole biopsy, to differentiation by tissue subtype (benign, stroma, tumour), followed by distinct tumour grade and finally clonal resolution. The gene expression profile of virtual tumour biopsies revealed clear differences between grade groups and tumour clones, compared to a benign control, which were not reflected in bulk analyses. This suggests that bulk analyses of whole biopsies or tumour-only areas, as used in clinical practice, may provide an inaccurate assessment of gene profiles. The type of tissue, the grade of the tumour and the clonal composition all influence the gene expression in a biopsy. Clinical decision making based on biopsy genomics should be made with caution while we await more precise targeting and cost-effective spatial analyses.",,pdf:https://molecular-cancer.biomedcentral.com/counter/pdf/10.1186/s12943-023-01863-2; doi:https://doi.org/10.1186/s12943-023-01863-2; html:https://europepmc.org/articles/PMC10546768; pdf:https://europepmc.org/articles/PMC10546768?pdf=render 34173574,https://doi.org/10.1016/j.puhip.2020.100039,Schools and COVID-19: Reopening Pandora's box?,"Ziauddeen N, Woods-Townsend K, Saxena S, Gilbert R, Alwan NA.",,"Public health in practice (Oxford, England)",2020,2020-11-01,Y,Safety; Covid-19; School Re-Opening,,,"Schools in countries across the world are reopening as lockdown to slow progression of COVID-19 is eased. The UK government ordered school closures in England from March 20, 2020, later than the rest of Europe. A temporary and limited return for some year groups was trialled from June 2020. Teachers, school governors, the public and doctors have openly challenged the decision. The UK government has struggled to provide enough detailed information to convince the public, teachers and health practitioners, that effective systems for protection, including test, trace and isolate, are in place to prevent and manage outbreaks in schools. Risks of infection on reopening to children, staff and families must be weighed against the harms of closure to children's education and social development. The potential consequences, if the re-opening of schools is managed badly, is subsequent waves of COVID-19 infection leading to more deaths, further school closures and prolonged restrictions, losing any ground gained thus far. This article weighs the evidence for risks and benefits of reopening schools during the pandemic.",,doi:https://doi.org/10.1016/j.puhip.2020.100039; doi:https://doi.org/10.1016/j.puhip.2020.100039; html:https://europepmc.org/articles/PMC7486860; pdf:https://europepmc.org/articles/PMC7486860?pdf=render -34767555,https://doi.org/10.1371/journal.pmed.1003832,Educational and health outcomes of schoolchildren in local authority care in Scotland: A retrospective record linkage study.,"Fleming M, McLay JS, Clark D, King A, Mackay DF, Minnis H, Pell JP.",,PLoS medicine,2021,2021-11-12,Y,,,,"

Background

Looked after children are defined as children who are in the care of their local authority. Previous studies have reported that looked after children have poorer mental and physical health, increased behavioural problems, and increased self-harm and mortality compared to peers. They also experience poorer educational outcomes, yet population-wide research into the latter is lacking, particularly in the United Kingdom. Education and health share a bidirectional relationship; therefore, it is important to dually investigate both outcomes. Our study aimed to compare educational and health outcomes for looked after children with peers, adjusting for sociodemographic, maternity, and comorbidity confounders.

Methods and findings

Linkage of 9 Scotland-wide databases, covering dispensed prescriptions, hospital admissions, maternity records, death certificates, annual pupil census, examinations, school absences/exclusions, unemployment, and looked after children provided retrospective data on 715,111 children attending Scottish schools between 2009 and 2012 (13,898 [1.9%] looked after). Compared to peers, 13,898 (1.9%) looked after children were more likely to be absent (adjusted incidence rate ratio [AIRR] 1.27, 95% confidence interval [CI] 1.24 to 1.30) and excluded (AIRR 4.09, 95% CI 3.86 to 4.33) from school, have special educational need (SEN; adjusted odds ratio [AOR] 3.48, 95% CI 3.35 to 3.62) and neurodevelopmental multimorbidity (AOR 2.45, 95% CI 2.34 to 2.57), achieve the lowest level of academic attainment (AOR 5.92, 95% CI 5.17 to 6.78), and be unemployed after leaving school (AOR 2.12, 95% CI 1.96 to 2.29). They were more likely to require treatment for epilepsy (AOR 1.50, 95% CI 1.27 to 1.78), attention deficit hyperactivity disorder (ADHD; AOR 3.01, 95% CI 2.76 to 3.27), and depression (AOR 1.90, 95% CI 1.62 to 2.22), be hospitalised overall (adjusted hazard ratio [AHR] 1.23, 95% CI 1.19 to 1.28) for injury (AHR 1.80, 95% CI 1.69 to 1.91) and self-harm (AHR 5.19, 95% CI 4.66 to 5.78), and die prematurely (AHR 3.21, 95% CI 2.16 to 4.77). Compared to children looked after at home, children looked after away from home had less absenteeism (AIRR 0.35, 95% CI 0.33 to 0.36), less exclusion (AIRR 0.63, 95% CI 0.56 to 0.71), less unemployment (AOR 0.53, 95% CI 0.46 to 0.62), and better attainment (AIRR 0.31, 95% CI 0.23 to 0.40). Therefore, among those in care, being cared for away from home appeared to be a protective factor resulting in better educational outcomes. The main limitations of this study were lack of data on local authority care preschool or before 2009, total time spent in care, and age of first contact with social care.

Conclusions

Looked after children had poorer health and educational outcomes than peers independent of increased neurodevelopmental conditions and SEN. Further work is required to understand whether poorer outcomes relate to reasons for entering care, including maltreatment and adverse childhood events, neurodevelopmental vulnerabilities, or characteristics of the care system.",,pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1003832&type=printable; doi:https://doi.org/10.1371/journal.pmed.1003832; html:https://europepmc.org/articles/PMC8589203; pdf:https://europepmc.org/articles/PMC8589203?pdf=render 31101093,https://doi.org/10.1186/s12889-019-6888-9,Educational and health outcomes of children and adolescents receiving antiepileptic medication: Scotland-wide record linkage study of 766 244 schoolchildren.,"Fleming M, Fitton CA, Steiner MFC, McLay JS, Clark D, King A, Mackay DF, Pell JP.",,BMC public health,2019,2019-05-17,Y,Epilepsy; Health; Prescribing; Educational Outcomes; Record Linkage; Population Cohort,Improving Public Health,,"

Background

Childhood epilepsy can adversely affect education and employment in addition to health. Previous studies are small or highly selective producing conflicting results. This retrospective cohort study aims to compare educational and health outcomes of children receiving antiepileptic medication versus peers.

Methods

Record linkage of Scotland-wide databases covering dispensed prescriptions, acute and psychiatric hospitalisations, maternity records, deaths, annual pupil census, school absences/exclusions, special educational needs, school examinations, and (un)employment provided data on 766,244 children attending Scottish schools between 2009 and 2013. Outcomes were adjusted for sociodemographic and maternity confounders and comorbid conditions.

Results

Compared with peers, children on antiepileptic medication were more likely to experience school absence (Incidence Rate Ratio [IRR] 1.43, 95% CI: 1.38, 1.48), special educational needs (Odds ratio [OR] 9.60, 95% CI: 9.02, 10.23), achieve the lowest level of attainment (OR 3.43, 95% CI: 2.74, 4.29) be unemployed (OR 1.82, 95% CI: 1.60, 2.07), be admitted to hospital (Hazard Ratio [HR] 3.56, 95% CI: 3.42, 3.70), and die (HR 22.02, 95% CI: 17.00, 28.53). Absenteeism partly explained poorer attainment and higher unemployment. Girls and younger children on antiepileptic medication had higher risk of poor outcomes.

Conclusions

Children on antiepileptic medication fare worse than peers across educational and health outcomes. In order to reduce school absenteeism and mitigate its effects, children with epilepsy should receive integrated care from a multidisciplinary team that spans education and healthcare.",,pdf:https://bmcpublichealth.biomedcentral.com/track/pdf/10.1186/s12889-019-6888-9; doi:https://doi.org/10.1186/s12889-019-6888-9; html:https://europepmc.org/articles/PMC6525436; pdf:https://europepmc.org/articles/PMC6525436?pdf=render +34767555,https://doi.org/10.1371/journal.pmed.1003832,Educational and health outcomes of schoolchildren in local authority care in Scotland: A retrospective record linkage study.,"Fleming M, McLay JS, Clark D, King A, Mackay DF, Minnis H, Pell JP.",,PLoS medicine,2021,2021-11-12,Y,,,,"

Background

Looked after children are defined as children who are in the care of their local authority. Previous studies have reported that looked after children have poorer mental and physical health, increased behavioural problems, and increased self-harm and mortality compared to peers. They also experience poorer educational outcomes, yet population-wide research into the latter is lacking, particularly in the United Kingdom. Education and health share a bidirectional relationship; therefore, it is important to dually investigate both outcomes. Our study aimed to compare educational and health outcomes for looked after children with peers, adjusting for sociodemographic, maternity, and comorbidity confounders.

Methods and findings

Linkage of 9 Scotland-wide databases, covering dispensed prescriptions, hospital admissions, maternity records, death certificates, annual pupil census, examinations, school absences/exclusions, unemployment, and looked after children provided retrospective data on 715,111 children attending Scottish schools between 2009 and 2012 (13,898 [1.9%] looked after). Compared to peers, 13,898 (1.9%) looked after children were more likely to be absent (adjusted incidence rate ratio [AIRR] 1.27, 95% confidence interval [CI] 1.24 to 1.30) and excluded (AIRR 4.09, 95% CI 3.86 to 4.33) from school, have special educational need (SEN; adjusted odds ratio [AOR] 3.48, 95% CI 3.35 to 3.62) and neurodevelopmental multimorbidity (AOR 2.45, 95% CI 2.34 to 2.57), achieve the lowest level of academic attainment (AOR 5.92, 95% CI 5.17 to 6.78), and be unemployed after leaving school (AOR 2.12, 95% CI 1.96 to 2.29). They were more likely to require treatment for epilepsy (AOR 1.50, 95% CI 1.27 to 1.78), attention deficit hyperactivity disorder (ADHD; AOR 3.01, 95% CI 2.76 to 3.27), and depression (AOR 1.90, 95% CI 1.62 to 2.22), be hospitalised overall (adjusted hazard ratio [AHR] 1.23, 95% CI 1.19 to 1.28) for injury (AHR 1.80, 95% CI 1.69 to 1.91) and self-harm (AHR 5.19, 95% CI 4.66 to 5.78), and die prematurely (AHR 3.21, 95% CI 2.16 to 4.77). Compared to children looked after at home, children looked after away from home had less absenteeism (AIRR 0.35, 95% CI 0.33 to 0.36), less exclusion (AIRR 0.63, 95% CI 0.56 to 0.71), less unemployment (AOR 0.53, 95% CI 0.46 to 0.62), and better attainment (AIRR 0.31, 95% CI 0.23 to 0.40). Therefore, among those in care, being cared for away from home appeared to be a protective factor resulting in better educational outcomes. The main limitations of this study were lack of data on local authority care preschool or before 2009, total time spent in care, and age of first contact with social care.

Conclusions

Looked after children had poorer health and educational outcomes than peers independent of increased neurodevelopmental conditions and SEN. Further work is required to understand whether poorer outcomes relate to reasons for entering care, including maltreatment and adverse childhood events, neurodevelopmental vulnerabilities, or characteristics of the care system.",,pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1003832&type=printable; doi:https://doi.org/10.1371/journal.pmed.1003832; html:https://europepmc.org/articles/PMC8589203; pdf:https://europepmc.org/articles/PMC8589203?pdf=render 35331425,https://doi.org/10.1016/j.jacep.2021.09.001,Clinical Characteristics and Follow-Up of Pediatric-Onset Arrhythmogenic Right Ventricular Cardiomyopathy.,"Roudijk RW, Verheul L, Bosman LP, Bourfiss M, Breur JMPJ, Slieker MG, Blank AC, Dooijes D, van der Heijden JF, van den Heuvel F, Clur SA, Udink Ten Cate FEA, van den Berg MP, Wilde AAM, Asselbergs FW, Peter van Tintelen J, Te Riele ASJM.",,JACC. Clinical electrophysiology,2022,2021-12-22,N,Genetics; Ventricular tachycardia; Heart Failure; Sudden Cardiac Death; Arrhythmogenic Right Ventricular Cardiomyopathy; Pediatric-onset; Cascade Screening,,,"

Objectives

The goal of this study was to describe characteristics, cascade screening results, and predictors of adverse outcome in pediatric-onset arrhythmogenic right ventricular cardiomyopathy (ARVC).

Background

Although ARVC is increasingly recognized in children, pediatric ARVC cohorts remain underrepresented in the literature.

Methods

This study included 12 probands with pediatric-onset ARVC (aged <18 years at diagnosis) and 68 pediatric relatives (aged <18 years at first evaluation) referred for cascade screening. ARVC diagnosis was based on 2010 Task Force Criteria. Clinical presentation, diagnostic testing, and outcomes (sustained ventricular tachycardia [VT]; heart failure) were ascertained. Predictors of adverse outcome were determined by using univariable logistic regression.

Results

Pediatric-onset ARVC was diagnosed in 12 probands and 12 (18%) relatives at a median age of 16.6 years (interquartile range: 13.8-17.4 years), whereas 12 (18%) relatives reached ARVC diagnosis as adults (median age, 22.0 years; interquartile range: 20.0-26.7 years). Sudden cardiac death/arrest was the first disease manifestation in 3 (25%) probands and 3 (4%) relatives. In patients without ARVC diagnosis at presentation (n = 61), electrocardiogram and Holter monitoring abnormalities occurred before development of imaging Task Force Criteria (7.3 ± 5.0 years vs 8.4 ± 5.0 years). Clinical course was characterized by sustained VT (91%) and heart failure (36%) in probands, which were rare in relatives (2% and 0%, respectively). Male sex (P < 0.01), T-wave inversion V1-V3 (P < 0.01), premature ventricular complexes/runs (P ≤ 0.01), and decrease in biventricular ejection fraction (P ≤ 0.01) were associated with VT occurrence.

Conclusions

Pediatric ARVC carries high arrhythmic risk, especially in probands. Disease progression is particularly observed on electrocardiogram or Holter monitoring. Arrhythmic events are associated with male sex, T-wave inversions, premature ventricular complexes/runs, and reduced biventricular ejection fraction.",,doi:https://doi.org/10.1016/j.jacep.2021.09.001; doi:https://doi.org/10.1016/j.jacep.2021.09.001 32303767,https://doi.org/10.1093/schbul/sbaa040,Real-World Clinical Outcomes Two Years After Transition to Psychosis in Individuals at Clinical High Risk: Electronic Health Record Cohort Study.,"Fusar-Poli P, De Micheli A, Patel R, Signorini L, Miah S, Spencer T, McGuire P.",,Schizophrenia bulletin,2020,2020-09-01,N,Neuroscience; Psychosis; Neuroimaging,,,"The objective of this study is to describe the 2-year real-world clinical outcomes after transition to psychosis in patients at clinical high-risk. The study used the clinical electronic health record cohort study including all patients receiving a first index primary diagnosis of nonorganic International Classification of Diseases (ICD)-10 psychotic disorder within the early psychosis pathway in the South London and Maudsley (SLaM) National Health Service (NHS) Trust from 2001 to 2017. Outcomes encompassed: cumulative probability (at 3, 6, 12, and 24 months) of receiving a first (1) treatment with antipsychotic, (2) informal admission, (3) compulsory admission, and (4) treatment with clozapine and (5) numbers of days spent in hospital (at 12 and 24 months) in patients transitioning to psychosis from clinical high-risk services (Outreach and Support in south London; OASIS) compared to other first-episode groups. Analyses included logistic and 0-inflated negative binomial regressions. In the study, 1561 patients were included; those who had initially been managed by OASIS and had subsequently transitioned to a first episode of psychosis (n = 130) were more likely to receive antipsychotic medication (at 3, 6, and 24 months; all P < .023), to be admitted informally (at all timepoints, all P < .004) and on a compulsory basis (at all timepoints, all P < .013), and to have spent more time in hospital (all timepoints, all P < .007) than first-episode patients who were already psychotic when seen by the OASIS service (n = 310), or presented to early intervention services (n = 1121). The likelihood of receiving clozapine was similar across all groups (at 12/24 months, all P < .101). Transition to psychosis from a clinical high-risk state is associated with severe real-world clinical outcomes. Prevention of transition to psychosis should remain a core target of future research. The study protocol was registered on www.researchregistry.com; researchregistry5039).",,pdf:https://academic.oup.com/schizophreniabulletin/article-pdf/46/5/1114/33777256/sbaa040.pdf; doi:https://doi.org/10.1093/schbul/sbaa040; html:https://europepmc.org/articles/PMC7505186; pdf:https://europepmc.org/articles/PMC7505186?pdf=render; doi:https://doi.org/10.1093/schbul/sbaa040 35094586,https://doi.org/10.1177/17407745221077691,The PROTEUS-Trials Consortium: Optimizing the use of patient-reported outcomes in clinical trials.,"Snyder C, Crossnohere N, King M, Reeve BB, Bottomley A, Calvert M, Thorner E, Wu AW, Brundage M, PROTEUS-Trials Consortium.",,"Clinical trials (London, England)",2022,2022-01-31,Y,Clinical Trials; Protocols; Data Visualization; Patient-reported Outcomes; Reporting Methods; Measure Selection,,,"

Background

The assessment of patient-reported outcomes in clinical trials has enormous potential to promote patient-centred care, but for this potential to be realized, the patient-reported outcomes must be captured effectively and communicated clearly. Over the past decade, methodologic tools have been developed to inform the design, analysis, reporting, and interpretation of patient-reported outcome data from clinical trials. We formed the PROTEUS-Trials Consortium (Patient-Reported Outcomes Tools: Engaging Users and Stakeholders) to disseminate and implement these methodologic tools.

Methods

PROTEUS-Trials are engaging with patient, clinician, research, and regulatory stakeholders from 27 organizations in the United States, Canada, Australia, the United Kingdom, and Europe to develop both organization-specific and cross-cutting strategies for implementing and disseminating the methodologic tools. Guided by the Knowledge-to-Action framework, we conducted consortium-wide webinars and meetings, as well as individual calls with participating organizations, to develop a workplan, which we are currently executing.

Results

Six methodologic tools serve as the foundation for PROTEUS-Trials dissemination and implementation efforts: the Standard Protocol Items: Recommendations for Interventional Trials-patient-reported outcome extension for writing protocols with patient-reported outcomes, the International Society for Quality of Life Research Minimum Standards for selecting a patient-reported outcome measure, Setting International Standards in Analysing Patient-Reported Outcomes and Quality of Life Endpoints Data Consortium recommendations for patient-reported outcome data analysis, the Consolidated Standards for Reporting of Trials-patient-reported outcome extension for reporting clinical trials with patient-reported outcomes, recommendations for the graphic display of patient-reported outcome data, and a Clinician's Checklist for reading and using an article about patient-reported outcomes. The PROTEUS-Trials website (www.TheProteusConsortium.org) serves as a central repository for the methodologic tools and associated resources. To date, we have developed (1) a roadmap to visually display where each of the six methodologic tools applies along the clinical trial trajectory, (2) web tutorials that provide guidance on the methodologic tools at different levels of detail, (3) checklists to provide brief summaries of each tool's recommendations, (4) a handbook to provide a self-guided approach to learning about the tools and recommendations, and (5) publications that address key topics related to patient-reported outcomes in clinical trials. We are also conducting organization-specific activities, including meetings, presentations, workshops, and webinars to publicize the existence of the methodologic tools and the PROTEUS-Trials resources. Work to develop communications strategies to ensure that PROTEUS-Trials reach key audiences with relevant information about patient-reported outcomes in clinical trials and PROTEUS-Trials is ongoing.

Discussion

The PROTEUS-Trials Consortium aims to help researchers generate patient-reported outcome data from clinical trials to (1) enable investigators, regulators, and policy-makers to take the patient perspective into account when conducting research and making decisions; (2) help patients understand treatment options and make treatment decisions; and (3) inform clinicians' discussions with patients regarding treatment options. In these ways, the PROTEUS Consortium promotes patient-centred research and care.",,pdf:http://pure-oai.bham.ac.uk/ws/files/160459757/17407745221077691.pdf; doi:https://doi.org/10.1177/17407745221077691; html:https://europepmc.org/articles/PMC9203669; pdf:https://europepmc.org/articles/PMC9203669?pdf=render 37575973,https://doi.org/10.2147/clep.s417176,Anxiety and Depression in People with Eczema or Psoriasis: A Comparison of Associations in UK Biobank and Linked Primary Care Data.,"Matthewman J, Mansfield KE, Hayes JF, Adesanya EI, Smith CH, Roberts A, Langan SM, Henderson AD.",,Clinical epidemiology,2023,2023-08-07,Y,Depression; Psoriasis; Anxiety; Eczema; Cross-sectional study; Data Linkage; Electronic Health Records; Ascertainment; Uk Biobank,,,"

Introduction

Previous research has shown associations between eczema and psoriasis and anxiety and depression. We investigated whether associations are consistent across different settings of ascertainment for depression and anxiety, including interview and survey responses from UK Biobank (a large longitudinal cohort recruiting individuals aged 40-69 years between 2006-2010), and linked primary care data, with the aim of drawing more reliable conclusions through triangulation.

Methods

In cross-sectional studies, we estimated associations between eczema or psoriasis and anxiety or depression, defining anxiety or depression as 1) self-reported previous diagnosis at UK Biobank recruitment interview; 2) PHQ-9/GAD-7 score indicating depression or anxiety from a UK Biobank mental health follow-up survey in 2016; and 3) diagnosis in linked primary care electronic health record data.

Results

We analysed 230,047 people with linked Biobank and primary care data. We found poor agreement between the data sources for eczema, psoriasis, anxiety, and depression. Eg, 9474 had a previous eczema diagnosis in primary care data, 4069 self-reported previous eczema diagnosis at the UK biobank interview, and 1536 had eczema in both data sources (for depression 40,455; 13,320; and 9588 respectively). Having eczema or psoriasis (recorded in primary care or baseline interview) was associated with higher odds of anxiety and depression. Eg, the adjusted odds ratio for depression comparing those with eczema to those without was greater than 1 when defining the outcome from 1) the recruitment interview (1.36, 95% confidence interval 1.27-1.45); 2) the follow-up survey (1.24, 1.09-1.39), and 3) primary care records (1.56, 1.50-1.62).

Discussion

Our findings support increased prevalence of mental illness in people with psoriasis and eczema across multiple data sources, which should be considered in planning of mental health services. However, we found poor agreement in disease ascertainment between settings, with implications for data interpretation in electronic health records.",,pdf:https://www.dovepress.com/getfile.php?fileID=91773; doi:https://doi.org/10.2147/CLEP.S417176; html:https://europepmc.org/articles/PMC10421744; pdf:https://europepmc.org/articles/PMC10421744?pdf=render 35991675,https://doi.org/10.1016/j.lana.2022.100335,Primary healthcare protects vulnerable populations from inequity in COVID-19 vaccination: An ecological analysis of nationwide data from Brazil.,"Bastos LSL, Aguilar S, Rache B, Maçaira P, Baião F, Cerbino-Neto J, Rocha R, Hamacher S, Ranzani OT, Bozza FA.",,Lancet regional health. Americas,2022,2022-08-17,Y,Vaccine; Socioeconomic Factors; Human Development; Primary Healthcare; Low-and-middle-income Countries; Covid19,,,"

Background

There is limited information on the inequity of access to vaccination in low-and-middle-income countries during the COVID-19 pandemic. Here, we described the progression of the Brazilian immunisation program for COVID-19, and the association of socioeconomic development with vaccination rates, considering the potential protective effect of primary health care coverage.

Methods

We performed an ecological analysis of COVID-19 immunisation data from the Brazilian National Immunization Program from January 17 to August 31, 2021. We analysed the dynamics of vaccine coverage in the adult population of 5,570 Brazilian municipalities. We estimated the association of human development index (HDI) levels (low, medium, and high) with age-sex standardised first dose coverage using a multivariable negative binomial regression model. We evaluated the interaction between the HDI and primary health care coverage. Finally, we compared the adjusted monthly progression of vaccination rates, hospital admission and in-hospital death rates among HDI levels.

Findings

From January 17 to August 31, 2021, 202,427,355 COVID-19 vaccine doses were administered in Brazil. By the end of the period, 64·2% of adults had first and 31·4% second doses, with more than 90% of those aged ≥60 years with primary scheme completed. Four distinct vaccine platforms were used in the country, ChAdOx1-S/nCoV-19, Sinovac-CoronaVac, BNT162b2, Ad26.COV2.S, composing 44·8%, 33·2%, 19·6%, and 2·4% of total doses, respectively. First dose coverage differed between municipalities with high, medium, and low HDI (Median [interquartile range] 72 [66, 79], 68 [61, 75] and 63 [55, 70] doses per 100 people, respectively). Municipalities with low (Rate Ratio [RR, 95% confidence interval]: 0·87 [0·85-0·88]) and medium (RR [95% CI]: 0·94 [0·93-0·95]) development were independently associated with lower vaccination rates compared to those with high HDI. Primary health care coverage modified the association of HDI and vaccination rate, improving vaccination rates in those municipalities of low HDI and high primary health care coverage. Low HDI municipalities presented a delayed decrease in adjusted in-hospital death rates by first dose coverage compared to high HDI locations.

Interpretation

In Brazil, socioeconomic disparities negatively impacted the first dose vaccination rate. However, the primary health care mitigated these disparities, suggesting that the primary health care coverage guarantees more equitable access to vaccines in vulnerable locations.

Funding

This work is part of the Grand Challenges ICODA pilot initiative, delivered by Health Data Research UK and funded by the Bill & Melinda Gates Foundation and the Minderoo Foundation. This study was supported by the National Council for Scientific and Technological Development (CNPq), the Coordination for the Improvement of Higher Education Personnel (CAPES) - Finance Code 001, Carlos Chagas Filho Foundation for Research Support of the State of Rio de Janeiro (FAPERJ) and the Pontifical Catholic University of Rio de Janeiro.",,doi:https://doi.org/10.1016/j.lana.2022.100335; doi:https://doi.org/10.1016/j.lana.2022.100335; html:https://europepmc.org/articles/PMC9381845; pdf:https://europepmc.org/articles/PMC9381845?pdf=render -34091032,https://doi.org/10.1016/j.neuroimage.2021.118235,Subspace-constrained approaches to low-rank fMRI acceleration.,"Mason HT, Graedel NN, Miller KL, Chiew M.",,NeuroImage,2021,2021-06-03,Y,fMRI; Tikhonov regularization; Acceleration; temporal resolution; Low Rank; Temporal Smoothing; K-t Faster; Low Resolution Priors,,,"Acceleration methods in fMRI aim to reconstruct high fidelity images from under-sampled k-space, allowing fMRI datasets to achieve higher temporal resolution, reduced physiological noise aliasing, and increased statistical degrees of freedom. While low levels of acceleration are typically part of standard fMRI protocols through parallel imaging, there exists the potential for approaches that allow much greater acceleration. One such existing approach is k-t FASTER, which exploits the inherent low-rank nature of fMRI. In this paper, we present a reformulated version of k-t FASTER which includes additional L2 constraints within a low-rank framework. We evaluated the effect of three different constraints against existing low-rank approaches to fMRI reconstruction: Tikhonov constraints, low-resolution priors, and temporal subspace smoothness. The different approaches are separately tested for robustness to under-sampling and thermal noise levels, in both retrospectively and prospectively-undersampled finger-tapping task fMRI data. Reconstruction quality is evaluated by accurate reconstruction of low-rank subspaces and activation maps. The use of L2 constraints was found to achieve consistently improved results, producing high fidelity reconstructions of statistical parameter maps at higher acceleration factors and lower SNR values than existing methods, but at a cost of longer computation time. In particular, the Tikhonov constraint proved very robust across all tested datasets, and the temporal subspace smoothness constraint provided the best reconstruction scores in the prospectively-undersampled dataset. These results demonstrate that regularized low-rank reconstruction of fMRI data can recover functional information at high acceleration factors without the use of any model-based spatial constraints.",,doi:https://doi.org/10.1016/j.neuroimage.2021.118235; doi:https://doi.org/10.1016/j.neuroimage.2021.118235; html:https://europepmc.org/articles/PMC7611820; pdf:https://europepmc.org/articles/PMC7611820?pdf=render 30382236,https://doi.org/10.1038/s41433-018-0229-6,The diagnostic accuracy of OCT angiography in naive and treated neovascular age-related macular degeneration: a review.,"Perrott-Reynolds R, Cann R, Cronbach N, Neo YN, Ho V, McNally O, Madi HA, Cochran C, Chakravarthy U.",,"Eye (London, England)",2019,2018-10-31,N,,,,"Optical coherence tomography angiography (OCTA) is a non-invasive retinal imaging innovation that has been gaining popularity for the evaluation of the retinal vasculature. Of clinical importance is its current use either as an alternative or in conjunction with conventional dye-based angiography in neovascular age-related macular degeneration. OCTA is not without limitations and these include image artefact, a relatively small field of view and failure of the segmentation algorithms, which can confound the interpretation of findings. While there are numerous publications on OCTA in neovascular AMD, few have examined the diagnostic accuracy of this new technology compared with the accepted gold standard of fundus fluorescein angiography (FFA). In this review, we summarise the literature on the clinical application of OCTA in nAMD. In particular, we have reviewed the published articles that have reported the sensitivity and specificity of OCTA in the diagnosis of nAMD, and those that have described and or correlated the morphological findings and compared them to dye-based angiography.",Perrott et al. reviewed strengths and limitations of an eye (retinal) imagining method for diagnosis of a condition affecting the central part of the retina (the macula). This degenerative condition may result in loss of central vision in older adults. Perrott et al. concluded that diagnostic accuracy depends on both method and equipment. ,pdf:https://www.nature.com/articles/s41433-018-0229-6.pdf; doi:https://doi.org/10.1038/s41433-018-0229-6; html:https://europepmc.org/articles/PMC6367454; pdf:https://europepmc.org/articles/PMC6367454?pdf=render; doi:https://doi.org/10.1038/s41433-018-0229-6 +34091032,https://doi.org/10.1016/j.neuroimage.2021.118235,Subspace-constrained approaches to low-rank fMRI acceleration.,"Mason HT, Graedel NN, Miller KL, Chiew M.",,NeuroImage,2021,2021-06-03,Y,fMRI; Tikhonov regularization; Acceleration; temporal resolution; Low Rank; Temporal Smoothing; K-t Faster; Low Resolution Priors,,,"Acceleration methods in fMRI aim to reconstruct high fidelity images from under-sampled k-space, allowing fMRI datasets to achieve higher temporal resolution, reduced physiological noise aliasing, and increased statistical degrees of freedom. While low levels of acceleration are typically part of standard fMRI protocols through parallel imaging, there exists the potential for approaches that allow much greater acceleration. One such existing approach is k-t FASTER, which exploits the inherent low-rank nature of fMRI. In this paper, we present a reformulated version of k-t FASTER which includes additional L2 constraints within a low-rank framework. We evaluated the effect of three different constraints against existing low-rank approaches to fMRI reconstruction: Tikhonov constraints, low-resolution priors, and temporal subspace smoothness. The different approaches are separately tested for robustness to under-sampling and thermal noise levels, in both retrospectively and prospectively-undersampled finger-tapping task fMRI data. Reconstruction quality is evaluated by accurate reconstruction of low-rank subspaces and activation maps. The use of L2 constraints was found to achieve consistently improved results, producing high fidelity reconstructions of statistical parameter maps at higher acceleration factors and lower SNR values than existing methods, but at a cost of longer computation time. In particular, the Tikhonov constraint proved very robust across all tested datasets, and the temporal subspace smoothness constraint provided the best reconstruction scores in the prospectively-undersampled dataset. These results demonstrate that regularized low-rank reconstruction of fMRI data can recover functional information at high acceleration factors without the use of any model-based spatial constraints.",,doi:https://doi.org/10.1016/j.neuroimage.2021.118235; doi:https://doi.org/10.1016/j.neuroimage.2021.118235; html:https://europepmc.org/articles/PMC7611820; pdf:https://europepmc.org/articles/PMC7611820?pdf=render 37770476,https://doi.org/10.1038/s41467-023-41249-y,Genome-wide association studies and cross-population meta-analyses investigating short and long sleep duration.,"Austin-Zimmerman I, Levey DF, Giannakopoulou O, Deak JD, Galimberti M, Adhikari K, Zhou H, Denaxas S, Irizar H, Kuchenbaecker K, McQuillin A, Million Veteran Program, Concato J, Buysse DJ, Gaziano JM, Gottlieb DJ, Polimanti R, Stein MB, Bramon E, Gelernter J.",,Nature communications,2023,2023-09-28,Y,,,,"Sleep duration has been linked to a wide range of negative health outcomes and to reduced life expectancy. We present genome-wide association studies of short ( ≤ 5 h) and long ( ≥ 10 h) sleep duration in adults of European (N = 445,966), African (N = 27,785), East Asian (N = 3141), and admixed-American (N = 16,250) ancestry from UK Biobank and the Million Veteran Programme. In a cross-population meta-analysis, we identify 84 independent loci for short sleep and 1 for long sleep. We estimate SNP-based heritability for both sleep traits in each ancestry based on population derived linkage disequilibrium (LD) scores using cov-LDSC. We identify positive genetic correlation between short and long sleep traits (rg = 0.16 ± 0.04; p = 0.0002), as well as similar patterns of genetic correlation with other psychiatric and cardiometabolic phenotypes. Mendelian randomisation reveals a directional causal relationship between short sleep and depression, and a bidirectional causal relationship between long sleep and depression.",,pdf:https://www.nature.com/articles/s41467-023-41249-y.pdf; doi:https://doi.org/10.1038/s41467-023-41249-y; html:https://europepmc.org/articles/PMC10539313; pdf:https://europepmc.org/articles/PMC10539313?pdf=render 36717723,https://doi.org/10.1038/s41590-022-01380-2,A patient-centric modeling framework captures recovery from SARS-CoV-2 infection.,"Ruffieux H, Hanson AL, Lodge S, Lawler NG, Whiley L, Gray N, Nolan TH, Bergamaschi L, Mescia F, Turner L, de Sa A, Pelly VS, Cambridge Institute of Therapeutic Immunology and Infectious Disease-National Institute of Health Research (CITIID-NIHR) BioResource COVID-19 Collaboration, Kotagiri P, Kingston N, Bradley JR, Holmes E, Wist J, Nicholson JK, Lyons PA, Smith KGC, Richardson S, Bantug GR, Hess C.",,Nature immunology,2023,2023-01-30,Y,,,,"The biology driving individual patient responses to severe acute respiratory syndrome coronavirus 2 infection remains ill understood. Here, we developed a patient-centric framework leveraging detailed longitudinal phenotyping data and covering a year after disease onset, from 215 infected individuals with differing disease severities. Our analyses revealed distinct 'systemic recovery' profiles, with specific progression and resolution of the inflammatory, immune cell, metabolic and clinical responses. In particular, we found a strong inter-patient and intra-patient temporal covariation of innate immune cell numbers, kynurenine metabolites and lipid metabolites, which highlighted candidate immunologic and metabolic pathways influencing the restoration of homeostasis, the risk of death and that of long COVID. Based on these data, we identified a composite signature predictive of systemic recovery, using a joint model on cellular and molecular parameters measured soon after disease onset. New predictions can be generated using the online tool http://shiny.mrc-bsu.cam.ac.uk/apps/covid-19-systemic-recovery-prediction-app , designed to test our findings prospectively.",,pdf:https://www.nature.com/articles/s41590-022-01380-2.pdf; doi:https://doi.org/10.1038/s41590-022-01380-2; html:https://europepmc.org/articles/PMC9892000; pdf:https://europepmc.org/articles/PMC9892000?pdf=render 37542272,https://doi.org/10.1186/s12916-023-02948-x,Common mental health disorders in adults with inflammatory skin conditions: nationwide population-based matched cohort studies in the UK.,"Henderson AD, Adesanya E, Mulick A, Matthewman J, Vu N, Davies F, Smith CH, Hayes J, Mansfield KE, Langan SM.",,BMC medicine,2023,2023-08-04,Y,Depression; Anxiety; Skin Disease; Electronic Health Records,,,"

Background

Psoriasis and atopic eczema are common inflammatory skin diseases. Existing research has identified increased risks of common mental disorders (anxiety, depression) in people with eczema and psoriasis; however, explanations for the associations remain unclear. We aimed to establish the risk factors for mental illness in those with eczema or psoriasis and identify the population groups most at risk.

Methods

We used routinely collected data from the UK Clinical Practice Research Datalink (CPRD) GOLD. Adults registered with a general practice in CPRD (1997-2019) were eligible for inclusion. Individuals with eczema/psoriasis were matched (age, sex, practice) to up to five adults without eczema/psoriasis. We used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for hazards of anxiety or depression in people with eczema/psoriasis compared to people without. We adjusted for known confounders (deprivation, asthma [eczema], psoriatic arthritis [psoriasis], Charlson comorbidity index, calendar period) and potential mediators (harmful alcohol use, body mass index [BMI], smoking status, and, in eczema only, sleep quality [insomnia diagnoses, specific sleep problem medications] and high-dose oral glucocorticoids).

Results

We identified two cohorts with and without eczema (1,032,782, matched to 4,990,125 without), and with and without psoriasis (366,884, matched to 1,834,330 without). Sleep quality was imbalanced in the eczema cohorts, twice as many people with eczema had evidence of poor sleep at baseline than those without eczema, including over 20% of those with severe eczema. After adjusting for potential confounders and mediators, eczema and psoriasis were associated with anxiety (adjusted HR [95% CI]: eczema 1.14 [1.13-1.16], psoriasis 1.17 [1.15-1.19]) and depression (adjusted HR [95% CI]: eczema 1.11 [1.1-1.12], psoriasis 1.21 [1.19-1.22]). However, we found evidence that these increased hazards are unlikely to be constant over time and were especially high 1-year after study entry.

Conclusions

Atopic eczema and psoriasis are associated with increased incidence of anxiety and depression in adults. These associations may be mediated through known modifiable risk factors, especially sleep quality in people with eczema. Our findings highlight potential opportunities for the prevention of anxiety and depression in people with eczema/psoriasis through treatment of modifiable risk factors and enhanced eczema/psoriasis management.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-023-02948-x; doi:https://doi.org/10.1186/s12916-023-02948-x; html:https://europepmc.org/articles/PMC10403838; pdf:https://europepmc.org/articles/PMC10403838?pdf=render @@ -2041,12 +2041,12 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 33737684,https://doi.org/10.1038/s41598-021-85877-0,"Proteomic blood profiling in mild, severe and critical COVID-19 patients.","Patel H, Ashton NJ, Dobson RJB, Andersson LM, Yilmaz A, Blennow K, Gisslen M, Zetterberg H.",,Scientific reports,2021,2021-03-18,Y,,,,"The recent SARS-CoV-2 pandemic manifests itself as a mild respiratory tract infection in most individuals, leading to COVID-19 disease. However, in some infected individuals, this can progress to severe pneumonia and acute respiratory distress syndrome (ARDS), leading to multi-organ failure and death. This study explores the proteomic differences between mild, severe, and critical COVID-19 positive patients to further understand the disease progression, identify proteins associated with disease severity, and identify potential therapeutic targets. Blood protein profiling was performed on 59 COVID-19 mild (n = 26), severe (n = 9) or critical (n = 24) cases and 28 controls using the OLINK inflammation, autoimmune, cardiovascular and neurology panels. Differential expression analysis was performed within and between disease groups to generate nine different analyses. From the 368 proteins measured per individual, more than 75% were observed to be significantly perturbed in COVID-19 cases. Six proteins (IL6, CKAP4, Gal-9, IL-1ra, LILRB4 and PD-L1) were identified to be associated with disease severity. The results have been made readily available through an interactive web-based application for instant data exploration and visualization, and can be accessed at https://phidatalab-shiny.rosalind.kcl.ac.uk/COVID19/ . Our results demonstrate that dynamic changes in blood proteins associated with disease severity can potentially be used as early biomarkers to monitor disease severity in COVID-19 and serve as potential therapeutic targets.",,pdf:https://www.nature.com/articles/s41598-021-85877-0.pdf; doi:https://doi.org/10.1038/s41598-021-85877-0; html:https://europepmc.org/articles/PMC7973581; pdf:https://europepmc.org/articles/PMC7973581?pdf=render 37723491,https://doi.org/10.1186/s13073-023-01221-3,Identification of novel genetic risk factors of dilated cardiomyopathy: from canine to human.,"Niskanen JE, Ohlsson Å, Ljungvall I, Drögemüller M, Ernst RF, Dooijes D, van Deutekom HWM, van Tintelen JP, Snijders Blok CJB, van Vugt M, van Setten J, Asselbergs FW, Petrič AD, Salonen M, Hundi S, Hörtenhuber M, DoGA consortium, Kere J, Pyle WG, Donner J, Postma AV, Leeb T, Andersson G, Hytönen MK, Häggström J, Wiberg M, Friederich J, Eberhard J, Harakalova M, van Steenbeek FG, Wess G, Lohi H.",,Genome medicine,2023,2023-09-18,Y,Genetics; Cardiac; Arrhythmia; Cardiology; Gwas; Transcriptomics; Complex Trait; Companion Animal,,,"

Background

Dilated cardiomyopathy (DCM) is a life-threatening heart disease and a common cause of heart failure due to systolic dysfunction and subsequent left or biventricular dilatation. A significant number of cases have a genetic etiology; however, as a complex disease, the exact genetic risk factors are largely unknown, and many patients remain without a molecular diagnosis.

Methods

We performed GWAS followed by whole-genome, transcriptome, and immunohistochemical analyses in a spontaneously occurring canine model of DCM. Canine gene discovery was followed up in three human DCM cohorts.

Results

Our results revealed two independent additive loci associated with the typical DCM phenotype comprising left ventricular systolic dysfunction and dilatation. We highlight two novel candidate genes, RNF207 and PRKAA2, known for their involvement in cardiac action potentials, energy homeostasis, and morphology. We further illustrate the distinct genetic etiologies underlying the typical DCM phenotype and ventricular premature contractions. Finally, we followed up on the canine discoveries in human DCM patients and discovered candidate variants in our two novel genes.

Conclusions

Collectively, our study yields insight into the molecular pathophysiology of DCM and provides a large animal model for preclinical studies.",,pdf:https://genomemedicine.biomedcentral.com/counter/pdf/10.1186/s13073-023-01221-3; doi:https://doi.org/10.1186/s13073-023-01221-3; html:https://europepmc.org/articles/PMC10506233; pdf:https://europepmc.org/articles/PMC10506233?pdf=render 32402553,https://doi.org/10.1016/j.ophtha.2020.03.029,"Visual Field Outcomes from the Multicenter, Randomized Controlled Laser in Glaucoma and Ocular Hypertension Trial (LiGHT).","Wright DM, Konstantakopoulou E, Montesano G, Nathwani N, Garg A, Garway-Heath D, Crabb DP, Gazzard G, Laser in Glaucoma and Ocular Hypertension Trial (LiGHT) Study Group, Adeleke M, Ambler G, Barton K, Bourne R, Broadway D, Bunce C, Buszewicz M, Crabb D, Davis A, Garg A, Garway-Heath D, Gazzard G, Hornan D, Hunter R, Jayaram H, Jiang Y, Konstantakopoulou E, Lim S, Liput J, Manners T, Montesano G, Morris S, Nathwani N, Ometto G, Rubin G, Strouthidis N, Vickerstaff V, Wilson S, Wormald R, Wright D, Zhu H.",,Ophthalmology,2020,2020-04-03,N,,,,"

Purpose

To compare visual field outcomes of ocular hypertensive and glaucoma patients treated first with medical therapy with those treated first with selective laser trabeculoplasty (SLT).

Design

Secondary analysis of patients from the Laser in Glaucoma and Ocular Hypertension study, a multicenter randomized controlled trial.

Participants

Three hundred forty-four patients (588 eyes) treated first with medical therapy and 344 patients (590 eyes) treated first with SLT.

Methods

Visual fields (VFs) were measured using standard automated perimetry and arranged in series (median length and duration, 9 VFs over 48 months). Hierarchical linear models were used to estimate pointwise VF progression rates, which were then averaged to produce a global progression estimate for each eye. Proportions of points and patients in each treatment group with fast (<-1 dB/year) or moderate (<-0.5 dB/year) progression were compared using log-binomial regression.

Main outcome measures

Pointwise and global progression rates of total deviation (TD) and pattern deviation (PD).

Results

A greater proportion of eyes underwent moderate or fast TD progression in the medical therapy group compared with the SLT group (26.2% vs. 16.9%; risk ratio [RR], 1.55; 95% confidence interval [CI], 1.23-1.93; P < 0.001). A similar pattern was observed for pointwise rates (medical therapy, 26.1% vs. SLT, 19.0%; RR, 1.37; 95% CI, 1.33-1.42; P < 0.001). A greater proportion of pointwise PD rates were categorized as moderate or fast in the medical therapy group (medical therapy, 11.5% vs. SLT, 8.3%; RR, 1.39; 95% CI, 1.32-1.46; P < 0.001). No statistical difference was found in the proportion of eyes that underwent moderate or fast PD progression (medical therapy, 9.9% vs. SLT, 7.1%; RR, 1.39; 95% CI, 0.95, 2.03; P = 0.0928).

Conclusions

A slightly larger proportion of ocular hypertensive and glaucoma patients treated first with medical therapy underwent rapid VF progression compared with those treated first with SLT.",,pdf:https://openaccess.city.ac.uk/id/eprint/24492/1/Wright%20Crabb%20et%20al%20Ophthalmology%202020.pdf; doi:https://doi.org/10.1016/j.ophtha.2020.03.029 -33782396,https://doi.org/10.1038/s41467-021-22213-0,Implications of the school-household network structure on SARS-CoV-2 transmission under school reopening strategies in England.,"Munday JD, Sherratt K, Meakin S, Endo A, Pearson CAB, Hellewell J, Abbott S, Bosse NI, CMMID COVID-19 Working Group, Atkins KE, Wallinga J, Edmunds WJ, van Hoek AJ, Funk S.",,Nature communications,2021,2021-03-29,Y,,,,"In early 2020 many countries closed schools to mitigate the spread of SARS-CoV-2. Since then, governments have sought to relax the closures, engendering a need to understand associated risks. Using address records, we construct a network of schools in England connected through pupils who share households. We evaluate the risk of transmission between schools under different reopening scenarios. We show that whilst reopening select year-groups causes low risk of large-scale transmission, reopening secondary schools could result in outbreaks affecting up to 2.5 million households if unmitigated, highlighting the importance of careful monitoring and within-school infection control to avoid further school closures or other restrictions.",,pdf:https://www.nature.com/articles/s41467-021-22213-0.pdf; doi:https://doi.org/10.1038/s41467-021-22213-0; html:https://europepmc.org/articles/PMC8007691; pdf:https://europepmc.org/articles/PMC8007691?pdf=render 29780001,https://doi.org/10.1016/s2352-3026(18)30053-x,Automated typing of red blood cell and platelet antigens: a whole-genome sequencing study.,"Lane WJ, Westhoff CM, Gleadall NS, Aguad M, Smeland-Wagman R, Vege S, Simmons DP, Mah HH, Lebo MS, Walter K, Soranzo N, Di Angelantonio E, Danesh J, Roberts DJ, Watkins NA, Ouwehand WH, Butterworth AS, Kaufman RM, Rehm HL, Silberstein LE, Green RC, MedSeq Project.",,The Lancet. Haematology,2018,2018-05-17,N,,The Human Phenome,,"

Background

There are more than 300 known red blood cell (RBC) antigens and 33 platelet antigens that differ between individuals. Sensitisation to antigens is a serious complication that can occur in prenatal medicine and after blood transfusion, particularly for patients who require multiple transfusions. Although pre-transfusion compatibility testing largely relies on serological methods, reagents are not available for many antigens. Methods based on single-nucleotide polymorphism (SNP) arrays have been used, but typing for ABO and Rh-the most important blood groups-cannot be done with SNP typing alone. We aimed to develop a novel method based on whole-genome sequencing to identify RBC and platelet antigens.

Methods

This whole-genome sequencing study is a subanalysis of data from patients in the whole-genome sequencing arm of the MedSeq Project randomised controlled trial (NCT01736566) with no measured patient outcomes. We created a database of molecular changes in RBC and platelet antigens and developed an automated antigen-typing algorithm based on whole-genome sequencing (bloodTyper). This algorithm was iteratively improved to address cis-trans haplotype ambiguities and homologous gene alignments. Whole-genome sequencing data from 110 MedSeq participants (30 × depth) were used to initially validate bloodTyper through comparison with conventional serology and SNP methods for typing of 38 RBC antigens in 12 blood-group systems and 22 human platelet antigens. bloodTyper was further validated with whole-genome sequencing data from 200 INTERVAL trial participants (15 × depth) with serological comparisons.

Findings

We iteratively improved bloodTyper by comparing its typing results with conventional serological and SNP typing in three rounds of testing. The initial whole-genome sequencing typing algorithm was 99·5% concordant across the first 20 MedSeq genomes. Addressing discordances led to development of an improved algorithm that was 99·8% concordant for the remaining 90 MedSeq genomes. Additional modifications led to the final algorithm, which was 99·2% concordant across 200 INTERVAL genomes (or 99·9% after adjustment for the lower depth of coverage).

Interpretation

By enabling more precise antigen-matching of patients with blood donors, antigen typing based on whole-genome sequencing provides a novel approach to improve transfusion outcomes with the potential to transform the practice of transfusion medicine.

Funding

National Human Genome Research Institute, Doris Duke Charitable Foundation, National Health Service Blood and Transplant, National Institute for Health Research, and Wellcome Trust.",,pdf:http://www.thelancet.com/article/S235230261830053X/pdf; doi:https://doi.org/10.1016/S2352-3026(18)30053-X; html:https://europepmc.org/articles/PMC6438177; pdf:https://europepmc.org/articles/PMC6438177?pdf=render; doi:https://doi.org/10.1016/s2352-3026(18)30053-x +33782396,https://doi.org/10.1038/s41467-021-22213-0,Implications of the school-household network structure on SARS-CoV-2 transmission under school reopening strategies in England.,"Munday JD, Sherratt K, Meakin S, Endo A, Pearson CAB, Hellewell J, Abbott S, Bosse NI, CMMID COVID-19 Working Group, Atkins KE, Wallinga J, Edmunds WJ, van Hoek AJ, Funk S.",,Nature communications,2021,2021-03-29,Y,,,,"In early 2020 many countries closed schools to mitigate the spread of SARS-CoV-2. Since then, governments have sought to relax the closures, engendering a need to understand associated risks. Using address records, we construct a network of schools in England connected through pupils who share households. We evaluate the risk of transmission between schools under different reopening scenarios. We show that whilst reopening select year-groups causes low risk of large-scale transmission, reopening secondary schools could result in outbreaks affecting up to 2.5 million households if unmitigated, highlighting the importance of careful monitoring and within-school infection control to avoid further school closures or other restrictions.",,pdf:https://www.nature.com/articles/s41467-021-22213-0.pdf; doi:https://doi.org/10.1038/s41467-021-22213-0; html:https://europepmc.org/articles/PMC8007691; pdf:https://europepmc.org/articles/PMC8007691?pdf=render 30351417,https://doi.org/10.1093/bioinformatics/bty837,pJRES Binning Algorithm (JBA): a new method to facilitate the recovery of metabolic information from pJRES 1H NMR spectra.,"Rodriguez-Martinez A, Ayala R, Posma JM, Harvey N, Jiménez B, Sonomura K, Sato TA, Matsuda F, Zalloua P, Gauguier D, Nicholson JK, Dumas ME.",,"Bioinformatics (Oxford, England)",2019,2019-06-01,Y,,Applied Analytics,,"

Motivation

Data processing is a key bottleneck for 1H NMR-based metabolic profiling of complex biological mixtures, such as biofluids. These spectra typically contain several thousands of signals, corresponding to possibly few hundreds of metabolites. A number of binning-based methods have been proposed to reduce the dimensionality of 1 D 1H NMR datasets, including statistical recoupling of variables (SRV). Here, we introduce a new binning method, named JBA (""pJRES Binning Algorithm""), which aims to extend the applicability of SRV to pJRES spectra.

Results

The performance of JBA is comprehensively evaluated using 617 plasma 1H NMR spectra from the FGENTCARD cohort. The results presented here show that JBA exhibits higher sensitivity than SRV to detect peaks from low-abundance metabolites. In addition, JBA allows a more efficient removal of spectral variables corresponding to pure electronic noise, and this has a positive impact on multivariate model building.

Availability and implementation

The algorithm is implemented using the MWASTools R/Bioconductor package.

Supplementary information

Supplementary data are available at Bioinformatics online.",,pdf:https://academic.oup.com/bioinformatics/article-pdf/35/11/1916/28759353/bty837.pdf; doi:https://doi.org/10.1093/bioinformatics/bty837; html:https://europepmc.org/articles/PMC6546129; pdf:https://europepmc.org/articles/PMC6546129?pdf=render 31848017,https://doi.org/10.1016/j.injury.2019.12.016,Pre-injury health status of major trauma patients with orthopaedic injuries.,"Gelaw AY, Gabbe BJ, Simpson PM, Ekegren CL.",,Injury,2020,2019-12-10,N,Trauma; Injury; Quality of life; Health Status; Orthopaedic; Pre-injury,,,"

Background

Pre-injury health status is an important determining factor of long-term outcomes after orthopaedic major trauma. Determining pre-injury health status of major trauma patients with orthopaedic injuries is also important for evaluating the change from pre to post-injury health status.

Objectives

Describe pre-injury health statuses reported at three different time points (6, 12 and 24 months) after injury and compare these with Australian normative values; determine the agreement between pre-injury health status collected at multiple time points post-injury; and identify factors associated with reporting better pre-injury health status.

Materials and methods

A registry-based cohort study was conducted. Major trauma patients with orthopaedic injuries captured by the Victorian State Trauma Registry with a date of injury from January 2009 to December 2016 were included. Pre-injury health status (measured using the EuroQol-Visual Analogue Scale (EQ-VAS)), reported 6, 12 and 24 months post-injury, was compared against Australian population normative values. The Bland-Altman method of comparison was used to determine the agreement between pre-injury EQ-VAS scores reported 6 to 12 and 6 to 24 months post-injury. Mixed effects ordinal logistic regression was used to determine factors associated with reporting better pre-injury health status.

Results

A total of 3,371 patients were eligible for the study. The median (IQR) pre-injury EQ-VAS score reported 6, 12 and 24 months post-injury was 90 (85-100) out of 100. Participants' pre-injury EQ-VAS scores reported 6, 12 and 24 months post-injury were significantly higher than Australian population normative values. Pre-injury EQ-VAS scores reported 6 months post-injury agreed with pre-injury EQ-VAS scores reported 12 and 24 months post-injury. A significant association exists between pre-injury health status and age, comorbidities, injury characteristics, socioeconomic status and pre-injury work status.

Conclusions

People with orthopaedic major trauma have better pre-injury health compared to the general Australian population. Therefore, population-specific values should be used as baseline measures to evaluate orthopaedic trauma outcomes. Pre-injury health status values reported at three different post-injury time points were comparable. If conducting a retrospective pre-injury health evaluation, researchers need be aware of factors that influence self-reporting of pre-injury health status and the response shift that may happen due to encountering injury.",,doi:https://doi.org/10.1016/j.injury.2019.12.016 -34708157,https://doi.org/10.12688/wellcomeopenres.16701.3,Estimating the duration of seropositivity of human seasonal coronaviruses using seroprevalence studies.,"Rees EM, Waterlow NR, Centre for the Mathematical Modelling of Infectious Diseases COVID-19 Working Group, Lowe R, Kucharski AJ.",,Wellcome open research,2021,2021-12-21,Y,Catalytic model; Seroprevalence; Waning Immunity; Seasonal Coronavirus,,,"Background: The duration of immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still uncertain, but it is of key clinical and epidemiological importance. Seasonal human coronaviruses (HCoV) have been circulating for longer and, therefore, may offer insights into the long-term dynamics of reinfection for such viruses. Methods: Combining historical seroprevalence data from five studies covering the four circulating HCoVs with an age-structured reverse catalytic model, we estimated the likely duration of seropositivity following seroconversion. Results: We estimated that antibody persistence lasted between 0.9 (95% Credible interval: 0.6 - 1.6) and 3.8 (95% CrI: 2.0 - 7.4) years. Furthermore, we found the force of infection in older children and adults (those over 8.5 [95% CrI: 7.5 - 9.9] years) to be higher compared with young children in the majority of studies. Conclusions: These estimates of endemic HCoV dynamics could provide an indication of the future long-term infection and reinfection patterns of SARS-CoV-2.",,doi:https://doi.org/10.12688/wellcomeopenres.16701.3; html:https://europepmc.org/articles/PMC8517721; pdf:https://europepmc.org/articles/PMC8517721?pdf=render 33550229,https://doi.org/10.1136/bmjopen-2020-040167,Assessing public support for extending smoke-free policies beyond enclosed public places and workplaces: protocol for a systematic review and meta-analysis.,"Boderie NW, Mölenberg FJ, Sheikh A, Bramer WM, Burdorf A, van Lenthe FJ, Been JV.",,BMJ open,2021,2021-02-05,Y,Tobacco smoke pollution; Attitude; Smoke-free Policy,,,"

Introduction

Smoke-free enclosed public environments are effective in reducing exposure to secondhand smoke and yield major public health benefits. Building on this, many countries are now implementing smoke-free policies regulating smoking beyond enclosed public places and workplaces. In order to successfully implement such 'novel smoke-free policies', public support is essential. We aim to provide the first comprehensive systematic review and meta-analysis assessing levels and determinants of public support for novel smoke-free policies.

Methods and analysis

The primary objective of this review is to summarise the level of public support for novel smoke-free policies. Eight online databases (Embase.com, Medline ALL Ovid, Web of Science Core Collection, WHO Library Database, Latin American and Caribbean Health Sciences Literature, Scientific Online Library Online, PsychINFO and Google Scholar) will be searched from 1 January 2004 by two independent researchers with no language restrictions. The initial search was performed on 15 April 2020 and will be updated prior to finalisation of the report. Studies are eligible if assessing support for novel smoke-free policies in the general population (age ≥16 years) and have a sample size of n≥400. Studies funded by the tobacco industry or evaluating support among groups with vested interest are excluded. The primary outcome is proportion of public support for smoke-free policies, subdivided according to the spaces covered: (1) indoor private spaces (eg, cars) (2) indoor semiprivate spaces (eg, multi-unit housing) (3) outdoor (semi)private spaces (eg, courtyards) (4) non-hospitality outdoor public spaces (eg, parks, hospital grounds, playgrounds) and (5) hospitality outdoor public spaces (eg, restaurant terraces). The secondary objective is to identify determinants associated with public support on three levels: (1) within-study determinants (eg, smoking status) (2) between-study determinants (eg, survey year) and (3) context-specific determinants (eg, social norms). Risk of bias will be assessed using the Mixed Methods Appraisal Tool and a sensitivity analysis will be performed excluding studies at high risk of bias.

Ethics and dissemination

No formal ethical approval is required. Findings will be disseminated to academics, policymakers and the general public.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/2/e040167.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-040167; html:https://europepmc.org/articles/PMC7925902; pdf:https://europepmc.org/articles/PMC7925902?pdf=render +34708157,https://doi.org/10.12688/wellcomeopenres.16701.3,Estimating the duration of seropositivity of human seasonal coronaviruses using seroprevalence studies.,"Rees EM, Waterlow NR, Centre for the Mathematical Modelling of Infectious Diseases COVID-19 Working Group, Lowe R, Kucharski AJ.",,Wellcome open research,2021,2021-12-21,Y,Catalytic model; Seroprevalence; Waning Immunity; Seasonal Coronavirus,,,"Background: The duration of immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still uncertain, but it is of key clinical and epidemiological importance. Seasonal human coronaviruses (HCoV) have been circulating for longer and, therefore, may offer insights into the long-term dynamics of reinfection for such viruses. Methods: Combining historical seroprevalence data from five studies covering the four circulating HCoVs with an age-structured reverse catalytic model, we estimated the likely duration of seropositivity following seroconversion. Results: We estimated that antibody persistence lasted between 0.9 (95% Credible interval: 0.6 - 1.6) and 3.8 (95% CrI: 2.0 - 7.4) years. Furthermore, we found the force of infection in older children and adults (those over 8.5 [95% CrI: 7.5 - 9.9] years) to be higher compared with young children in the majority of studies. Conclusions: These estimates of endemic HCoV dynamics could provide an indication of the future long-term infection and reinfection patterns of SARS-CoV-2.",,doi:https://doi.org/10.12688/wellcomeopenres.16701.3; html:https://europepmc.org/articles/PMC8517721; pdf:https://europepmc.org/articles/PMC8517721?pdf=render 35507331,https://doi.org/10.1002/art.42154,Comparative Genetic Analysis of Psoriatic Arthritis and Psoriasis for the Discovery of Genetic Risk Factors and Risk Prediction Modeling.,"Soomro M, Stadler M, Dand N, Bluett J, Jadon D, Jalali-Najafabadi F, Duckworth M, Ho P, Marzo-Ortega H, Helliwell PS, Ryan AW, Kane D, Korendowych E, Simpson MA, Packham J, McManus R, Gabay C, Lamacchia C, Nissen MJ, Brown MA, Verstappen SMM, Van Staa T, Barker JN, Smith CH, BADBIR Study Group, BSTOP study group, FitzGerald O, McHugh N, Warren RB, Bowes J, Barton A.",,"Arthritis & rheumatology (Hoboken, N.J.)",2022,2022-08-04,Y,,,,"

Objectives

Psoriatic arthritis (PsA) has a strong genetic component, and the identification of genetic risk factors could help identify the ~30% of psoriasis patients at high risk of developing PsA. Our objectives were to identify genetic risk factors and pathways that differentiate PsA from cutaneous-only psoriasis (PsC) and to evaluate the performance of PsA risk prediction models.

Methods

Genome-wide meta-analyses were conducted separately for 5,065 patients with PsA and 21,286 healthy controls and separately for 4,340 patients with PsA and 6,431 patients with PsC. The heritability of PsA was calculated as a single-nucleotide polymorphism (SNP)-based heritability estimate (h2 SNP ) and biologic pathways that differentiate PsA from PsC were identified using Priority Index software. The generalizability of previously published PsA risk prediction pipelines was explored, and a risk prediction model was developed with external validation.

Results

We identified a novel genome-wide significant susceptibility locus for the development of PsA on chromosome 22q11 (rs5754467; P = 1.61 × 10-9 ), and key pathways that differentiate PsA from PsC, including NF-κB signaling (adjusted P = 1.4 × 10-45 ) and Wnt signaling (adjusted P = 9.5 × 10-58 ). The heritability of PsA in this cohort was found to be moderate (h2 SNP  = 0.63), which was similar to the heritability of PsC (h2 SNP  = 0.61). We observed modest performance of published classification pipelines (maximum area under the curve 0.61), with similar performance of a risk model derived using the current data.

Conclusion

Key biologic pathways associated with the development of PsA were identified, but the investigation of risk classification revealed modest utility in the available data sets, possibly because many of the PsC patients included in the present study were receiving treatments that are also effective in PsA. Future predictive models of PsA should be tested in PsC patients recruited from primary care.",,pdf:https://eprints.whiterose.ac.uk/191095/1/Arthritis%20%20%20Rheumatology%20-%202022%20-%20Soomro%20-%20Comparative%20Genetic%20Analysis%20of%20Psoriatic%20Arthritis%20and%20Psoriasis%20for%20the.pdf; doi:https://doi.org/10.1002/art.42154; html:https://europepmc.org/articles/PMC9539852; pdf:https://europepmc.org/articles/PMC9539852?pdf=render 35606928,https://doi.org/10.1111/bjd.21677,Biomarkers of systemic treatment response in people with psoriasis: a scoping review.,"Corbett M, Ramessur R, Marshall D, Acencio ML, Ostaszewski M, Barbosa IA, Dand N, Di Meglio P, Haddad S, Jensen AHM, Koopmann W, Mahil SK, Rahmatulla S, Rastrick J, Saklatvala J, Weidinger S, Wright K, Eyerich K, Barker JN, Ndlovu M, Conrad C, Skov L, Smith CH, BIOMAP consortium.",,The British journal of dermatology,2022,2022-07-20,Y,,,,"

Background

Responses to the systemic treatments commonly used to treat psoriasis vary. Biomarkers that accurately predict effectiveness and safety would enable targeted treatment selection, improved patient outcomes and more cost-effective healthcare.

Objectives

To perform a scoping review to identify and catalogue candidate biomarkers of systemic treatment response in psoriasis for the translational research community.

Methods

A systematic search of CENTRAL, Embase, LILACS and MEDLINE was performed for relevant articles published between 1990 and December 2021. Eligibility criteria were studies involving patients with psoriasis (any age, n ≥ 50) reporting biomarkers associated with systemic treatment response. The main outcomes were any measure of systemic treatment efficacy or safety. Data were extracted by one reviewer and checked by a second; studies meeting minimal quality criteria (use of methods to control for confounding) were formally assessed for bias. Candidate biomarkers were identified by an expert multistakeholder group using a majority voting consensus exercise and mapped to relevant cellular and molecular pathways.

Results

Of 71 included studies (67 studying effectiveness outcomes and eight safety outcomes; four studied both), most reported genomic or proteomic biomarkers associated with response to biologics (48 studies). Methodological or reporting limitations frequently compromised the interpretation of findings, including inadequate control for key covariates, lack of adjustment for multiple testing, and selective outcome reporting. We identified candidate biomarkers of efficacy to tumour necrosis factor inhibitors [variation in CARD14, CDKAL1, IL1B, IL12B and IL17RA loci, and lipopolysaccharide-induced phosphorylation of nuclear factor (NF)-κB in type 2 dendritic cells] and ustekinumab (HLA-C*06:02 and variation in an IL1B locus). None were supported by sufficient evidence for clinical use without further validation studies. Candidate biomarkers were found to be involved in the immune cellular crosstalk implicated in psoriasis pathogenesis, most notably antigen presentation, T helper (Th)17 cell differentiation, positive regulation of NF-κB, and Th17 cell activation.

Conclusions

This comprehensive catalogue provides a key resource for researchers and reveals a diverse range of biomarker types and outcomes in the included studies. The candidate biomarkers identified require further evaluation in methodologically robust studies to establish potential clinical utility. Future studies should aim to address the common methodological limitations highlighted in this review to expedite discovery and validation of biomarkers for clinical use. What is already known about this topic? Responses to the systemic treatments commonly used to treat psoriasis vary. Biomarkers that accurately predict effectiveness and safety would enable targeted treatment selection, improved patient outcomes and more cost-effective healthcare. What does this study add? This review provides a comprehensive catalogue of investigated biomarkers of systemic treatment response in psoriasis. A diverse range of biomarker types and outcomes was found in the included studies, serving as a key resource for the translational research community.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9796396; doi:https://doi.org/10.1111/bjd.21677; html:https://europepmc.org/articles/PMC9796396; pdf:https://europepmc.org/articles/PMC9796396?pdf=render 34139154,https://doi.org/10.1016/j.cels.2021.05.005,A time-resolved proteomic and prognostic map of COVID-19.,"Demichev V, Tober-Lau P, Lemke O, Nazarenko T, Thibeault C, Whitwell H, Röhl A, Freiwald A, Szyrwiel L, Ludwig D, Correia-Melo C, Aulakh SK, Helbig ET, Stubbemann P, Lippert LJ, Grüning NM, Blyuss O, Vernardis S, White M, Messner CB, Joannidis M, Sonnweber T, Klein SJ, Pizzini A, Wohlfarter Y, Sahanic S, Hilbe R, Schaefer B, Wagner S, Mittermaier M, Machleidt F, Garcia C, Ruwwe-Glösenkamp C, Lingscheid T, Bosquillon de Jarcy L, Stegemann MS, Pfeiffer M, Jürgens L, Denker S, Zickler D, Enghard P, Zelezniak A, Campbell A, Hayward C, Porteous DJ, Marioni RE, Uhrig A, Müller-Redetzky H, Zoller H, Löffler-Ragg J, Keller MA, Tancevski I, Timms JF, Zaikin A, Hippenstiel S, Ramharter M, Witzenrath M, Suttorp N, Lilley K, Mülleder M, Sander LE, PA-COVID-19 Study group, Ralser M, Kurth F.",,Cell systems,2021,2021-06-14,Y,Proteomics; Biomarkers; Physiological parameters; Machine Learning; Disease Prognosis; Clinical Disease Progression; Covid-19; Longitudinal Profiling; Patient Trajectories,,,"COVID-19 is highly variable in its clinical presentation, ranging from asymptomatic infection to severe organ damage and death. We characterized the time-dependent progression of the disease in 139 COVID-19 inpatients by measuring 86 accredited diagnostic parameters, such as blood cell counts and enzyme activities, as well as untargeted plasma proteomes at 687 sampling points. We report an initial spike in a systemic inflammatory response, which is gradually alleviated and followed by a protein signature indicative of tissue repair, metabolic reconstitution, and immunomodulation. We identify prognostic marker signatures for devising risk-adapted treatment strategies and use machine learning to classify therapeutic needs. We show that the machine learning models based on the proteome are transferable to an independent cohort. Our study presents a map linking routinely used clinical diagnostic parameters to plasma proteomes and their dynamics in an infectious disease.",,pdf:http://www.cell.com/article/S2405471221001605/pdf; doi:https://doi.org/10.1016/j.cels.2021.05.005; html:https://europepmc.org/articles/PMC8201874 @@ -2066,9 +2066,9 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 34725404,https://doi.org/10.1038/s41598-021-00748-y,Probabilistic modelling of effects of antibiotics and calendar time on transmission of healthcare-associated infection.,"Laager M, Cooper BS, Eyre DW, CDC Modeling Infectious Diseases in Healthcare Program (MInD-Healthcare).",,Scientific reports,2021,2021-11-01,Y,,,,"Healthcare-associated infection and antimicrobial resistance are major concerns. However, the extent to which antibiotic exposure affects transmission and detection of infections such as MRSA is unclear. Additionally, temporal trends are typically reported in terms of changes in incidence, rather than analysing underling transmission processes. We present a data-augmented Markov chain Monte Carlo approach for inferring changing transmission parameters over time, screening test sensitivity, and the effect of antibiotics on detection and transmission. We expand a basic model to allow use of typing information when inferring sources of infections. Using simulated data, we show that the algorithms are accurate, well-calibrated and able to identify antibiotic effects in sufficiently large datasets. We apply the models to study MRSA transmission in an intensive care unit in Oxford, UK with 7924 admissions over 10 years. We find that falls in MRSA incidence over time were associated with decreases in both the number of patients admitted to the ICU colonised with MRSA and in transmission rates. In our inference model, the data were not informative about the effect of antibiotics on risk of transmission or acquisition of MRSA, a consequence of the limited number of possible transmission events in the data. Our approach has potential to be applied to a range of healthcare-associated infections and settings and could be applied to study the impact of other potential risk factors for transmission. Evidence generated could be used to direct infection control interventions.",,pdf:https://www.nature.com/articles/s41598-021-00748-y.pdf; doi:https://doi.org/10.1038/s41598-021-00748-y; html:https://europepmc.org/articles/PMC8560804; pdf:https://europepmc.org/articles/PMC8560804?pdf=render 35505938,https://doi.org/10.1016/j.eclinm.2022.101417,Multivariate profile and acute-phase correlates of cognitive deficits in a COVID-19 hospitalised cohort.,"Hampshire A, Chatfield DA, MPhil AM, Jolly A, Trender W, Hellyer PJ, Giovane MD, Newcombe VFJ, Outtrim JG, Warne B, Bhatti J, Pointon L, Elmer A, Sithole N, Bradley J, Kingston N, Sawcer SJ, Bullmore ET, Rowe JB, Menon DK, Cambridge NeuroCOVID Group, the NIHR COVID-19 BioResource, and Cambridge NIHR Clinical Research Facility.",,EClinicalMedicine,2022,2022-04-28,Y,Memory; Cognition; Attention; Planning; Cognitive Assessment; Reasoning; Covid-19,,,"

Background

Preliminary evidence has highlighted a possible association between severe COVID-19 and persistent cognitive deficits. Further research is required to confirm this association, determine whether cognitive deficits relate to clinical features from the acute phase or to mental health status at the point of assessment, and quantify rate of recovery.

Methods

46 individuals who received critical care for COVID-19 at Addenbrooke's hospital between 10th March 2020 and 31st July 2020 (16 mechanically ventilated) underwent detailed computerised cognitive assessment alongside scales measuring anxiety, depression and post-traumatic stress disorder under supervised conditions at a mean follow up of 6.0 (± 2.1) months following acute illness. Patient and matched control (N = 460) performances were transformed into standard deviation from expected scores, accounting for age and demographic factors using N = 66,008 normative datasets. Global accuracy and response time composites were calculated (G_SScore & G_RT). Linear modelling predicted composite score deficits from acute severity, mental-health status at assessment, and time from hospital admission. The pattern of deficits across tasks was qualitatively compared with normal age-related decline, and early-stage dementia.

Findings

COVID-19 survivors were less accurate (G_SScore=-0.53SDs) and slower (G_RT=+0.89SDs) in their responses than expected compared to their matched controls. Acute illness, but not chronic mental health, significantly predicted cognitive deviation from expected scores (G_SScore (p=​​0.0037) and G_RT (p = 0.0366)). The most prominent task associations with COVID-19 were for higher cognition and processing speed, which was qualitatively distinct from the profiles of normal ageing and dementia and similar in magnitude to the effects of ageing between 50 and 70 years of age. A trend towards reduced deficits with time from illness (r∼=0.15) did not reach statistical significance.

Interpretation

Cognitive deficits after severe COVID-19 relate most strongly to acute illness severity, persist long into the chronic phase, and recover slowly if at all, with a characteristic profile highlighting higher cognitive functions and processing speed.

Funding

This work was funded by the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre (BRC), NIHR Cambridge Clinical Research Facility (BRC-1215-20014), the Addenbrooke's Charities Trust and NIHR COVID-19 BioResource RG9402. AH is funded by the UK Dementia Research Institute Care Research and Technology Centre and Imperial College London Biomedical Research Centre. ETB and DKM are supported by NIHR Senior Investigator awards. JBR is supported by the Wellcome Trust (220258) and Medical Research Council (SUAG/051 G101400). VFJN is funded by an Academy of Medical Sciences/ The Health Foundation Clinician Scientist Fellowship. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care.",,pdf:http://www.thelancet.com/article/S258953702200147X/pdf; doi:https://doi.org/10.1016/j.eclinm.2022.101417; html:https://europepmc.org/articles/PMC9048584; pdf:https://europepmc.org/articles/PMC9048584?pdf=render 33829489,https://doi.org/10.1111/bjd.20140,Defining trajectories of response in patients with psoriasis treated with biologic therapies.,"Geifman N, Azadbakht N, Zeng J, Wilkinson T, Dand N, Buchan I, Stocken D, Di Meglio P, Warren RB, Barker JN, Reynolds NJ, Barnes MR, Smith CH, Griffiths CEM, Peek N, BADBIR Study Group, on behalf of the PSORT Consortium.",,The British journal of dermatology,2021,2021-06-04,N,,,,"

Background

The effectiveness and cost-effectiveness of biologic therapies for psoriasis are significantly compromised by variable treatment responses. Thus, more precise management of psoriasis is needed.

Objectives

To identify subgroups of patients with psoriasis treated with biologic therapies, based on changes in their disease activity over time, that may better inform patient management.

Methods

We applied latent class mixed modelling to identify trajectory-based patient subgroups from longitudinal, routine clinical data on disease severity, as measured by the Psoriasis Area and Severity Index (PASI), from 3546 patients in the British Association of Dermatologists Biologics and Immunomodulators Register, as well as in an independent cohort of 2889 patients pooled across four clinical trials.

Results

We discovered four discrete classes of global response trajectories, each characterized in terms of time to response, size of effect and relapse. Each class was associated with differing clinical characteristics, e.g. body mass index, baseline PASI and prevalence of different manifestations. The results were verified in a second cohort of clinical trial participants, where similar trajectories following the initiation of biologic therapy were identified. Further, we found differential associations of the genetic marker HLA-C*06:02 between our registry-identified trajectories.

Conclusions

These subgroups, defined by change in disease over time, may be indicative of distinct endotypes driven by different biological mechanisms and may help inform the management of patients with psoriasis. Future work will aim to further delineate these mechanisms by extensively characterizing the subgroups with additional molecular and pharmacological data.",,doi:https://doi.org/10.1111/bjd.20140 -35710247,https://doi.org/10.1136/bmjopen-2021-060280,Structured follow-up pathway to support people after transient ischaemic attack and minor stroke (SUPPORT TIA): protocol for a feasibility study and process evaluation.,"Turner GM, Jones R, Collis P, Patel S, Jowett S, Tearne S, Foy R, Atkins L, Mant J, Calvert M.",,BMJ open,2022,2022-06-16,Y,Qualitative Research; Rehabilitation Medicine; Stroke Medicine; Protocols & Guidelines; Organisation Of Health Services; Depression & Mood Disorders,,,"

Introduction

People who experience transient ischaemic attack (TIA) and minor stroke have limited follow-up despite rapid specialist review in hospital. This means they often have unmet needs and feel abandoned following discharge. Care needs after TIA/minor stroke include information provision (diagnosis and stroke risk), stroke prevention (medication and lifestyle change) and holistic care (residual problems and return to work or usual activities). This protocol describes a feasibility study and process evaluation of an intervention to support people after TIA/minor stroke. The study aims to assess the feasibility and acceptability of (1) the intervention and (2) the trial procedures for a future randomised controlled trial of this intervention.

Methods and analysis

This is a multicentre, randomised (1:1) feasibility study with a mixed-methods process evaluation. Sixty participants will be recruited from TIA clinics or stroke wards at three hospital sites (England). Intervention arm participants will be offered a nurse or allied health professional-led follow-up appointment 4 weeks after TIA/minor stroke. The multifaceted intervention includes: a needs checklist, action plan, resources to support management of needs, a general practitioner letter and training to deliver the intervention. Control arm participants will receive usual care. Follow-up will be self-completed questionnaires (12 weeks and 24 weeks) and a clinic appointment (24 weeks). Follow-up questionnaires will measure anxiety, depression, fatigue, health related quality of life, self-efficacy and medication adherence. The clinic appointment will collect body mass index, blood pressure, cholesterol and medication. Assessment of feasibility and acceptability will include quantitative process variables (such as recruitment and questionnaire response rates), structured observations of study processes, and interviews with a subsample of participants and clinical staff.

Ethics and dissemination

Favourable ethical opinion was gained from the Wales Research Ethics Committee (REC) 1 (23 February 2021, REC reference: 21/WA/0036). Study results will be published in peer-reviewed journals and presented at conferences. A lay summary and dissemination strategy will be codesigned with consumers. The lay summary and journal publication will be distributed on social media.

Trial registration number

ISRCTN39864003.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/6/e060280.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-060280; html:https://europepmc.org/articles/PMC9207897; pdf:https://europepmc.org/articles/PMC9207897?pdf=render 33742045,https://doi.org/10.1038/s41598-021-85354-8,Short and long-read genome sequencing methodologies for somatic variant detection; genomic analysis of a patient with diffuse large B-cell lymphoma.,"Roberts HE, Lopopolo M, Pagnamenta AT, Sharma E, Parkes D, Lonie L, Freeman C, Knight SJL, Lunter G, Dreau H, Lockstone H, Taylor JC, Schuh A, Bowden R, Buck D.",,Scientific reports,2021,2021-03-19,Y,,,,"Recent advances in throughput and accuracy mean that the Oxford Nanopore Technologies PromethION platform is a now a viable solution for genome sequencing. Much of the validation of bioinformatic tools for this long-read data has focussed on calling germline variants (including structural variants). Somatic variants are outnumbered many-fold by germline variants and their detection is further complicated by the effects of tumour purity/subclonality. Here, we evaluate the extent to which Nanopore sequencing enables detection and analysis of somatic variation. We do this through sequencing tumour and germline genomes for a patient with diffuse B-cell lymphoma and comparing results with 150 bp short-read sequencing of the same samples. Calling germline single nucleotide variants (SNVs) from specific chromosomes of the long-read data achieved good specificity and sensitivity. However, results of somatic SNV calling highlight the need for the development of specialised joint calling algorithms. We find the comparative genome-wide performance of different tools varies significantly between structural variant types, and suggest long reads are especially advantageous for calling large somatic deletions and duplications. Finally, we highlight the utility of long reads for phasing clinically relevant variants, confirming that a somatic 1.6 Mb deletion and a p.(Arg249Met) mutation involving TP53 are oriented in trans.",,pdf:https://www.nature.com/articles/s41598-021-85354-8.pdf; doi:https://doi.org/10.1038/s41598-021-85354-8; html:https://europepmc.org/articles/PMC7979876; pdf:https://europepmc.org/articles/PMC7979876?pdf=render 32247823,https://doi.org/10.1016/j.jhep.2020.03.032,Genome-wide and Mendelian randomisation studies of liver MRI yield insights into the pathogenesis of steatohepatitis.,"Parisinos CA, Wilman HR, Thomas EL, Kelly M, Nicholls RC, McGonigle J, Neubauer S, Hingorani AD, Patel RS, Hemingway H, Bell JD, Banerjee R, Yaghootkar H.",,Journal of hepatology,2020,2020-04-02,Y,metabolic syndrome; Magnetic Resonance Imaging; fibrosis; Transaminases; Genome-wide Association Study; Steatohepatitis; Ct1,Understanding the Causes of Disease,oral and gastrointestinal,"

Background & aims

MRI-based corrected T1 (cT1) is a non-invasive method to grade the severity of steatohepatitis and liver fibrosis. We aimed to identify genetic variants influencing liver cT1 and use genetics to understand mechanisms underlying liver fibroinflammatory disease and its link with other metabolic traits and diseases.

Methods

First, we performed a genome-wide association study (GWAS) in 14,440 Europeans, with liver cT1 measures, from the UK Biobank. Second, we explored the effects of the cT1 variants on liver blood tests, and a range of metabolic traits and diseases. Third, we used Mendelian randomisation to test the causal effects of 24 predominantly metabolic traits on liver cT1 measures.

Results

We identified 6 independent genetic variants associated with liver cT1 that reached the GWAS significance threshold (p <5×10-8). Four of the variants (rs759359281 in SLC30A10, rs13107325 in SLC39A8, rs58542926 in TM6SF2, rs738409 in PNPLA3) were also associated with elevated aminotransferases and had variable effects on liver fat and other metabolic traits. Insulin resistance, type 2 diabetes, non-alcoholic fatty liver and body mass index were causally associated with elevated cT1, whilst favourable adiposity (instrumented by variants associated with higher adiposity but lower risk of cardiometabolic disease and lower liver fat) was found to be protective.

Conclusion

The association between 2 metal ion transporters and cT1 indicates an important new mechanism in steatohepatitis. Future studies are needed to determine whether interventions targeting the identified transporters might prevent liver disease in at-risk individuals.

Lay summary

We estimated levels of liver inflammation and scarring based on magnetic resonance imaging of 14,440 UK Biobank participants. We performed a genetic study and identified variations in 6 genes associated with levels of liver inflammation and scarring. Participants with variations in 4 of these genes also had higher levels of markers of liver cell injury in blood samples, further validating their role in liver health. Two identified genes are involved in the transport of metal ions in our body. Further investigation of these variations may lead to better detection, assessment, and/or treatment of liver inflammation and scarring.",,pdf:http://www.journal-of-hepatology.eu/article/S016882782030194X/pdf; doi:https://doi.org/10.1016/j.jhep.2020.03.032; html:https://europepmc.org/articles/PMC7372222; pdf:https://europepmc.org/articles/PMC7372222?pdf=render +35710247,https://doi.org/10.1136/bmjopen-2021-060280,Structured follow-up pathway to support people after transient ischaemic attack and minor stroke (SUPPORT TIA): protocol for a feasibility study and process evaluation.,"Turner GM, Jones R, Collis P, Patel S, Jowett S, Tearne S, Foy R, Atkins L, Mant J, Calvert M.",,BMJ open,2022,2022-06-16,Y,Qualitative Research; Rehabilitation Medicine; Stroke Medicine; Protocols & Guidelines; Organisation Of Health Services; Depression & Mood Disorders,,,"

Introduction

People who experience transient ischaemic attack (TIA) and minor stroke have limited follow-up despite rapid specialist review in hospital. This means they often have unmet needs and feel abandoned following discharge. Care needs after TIA/minor stroke include information provision (diagnosis and stroke risk), stroke prevention (medication and lifestyle change) and holistic care (residual problems and return to work or usual activities). This protocol describes a feasibility study and process evaluation of an intervention to support people after TIA/minor stroke. The study aims to assess the feasibility and acceptability of (1) the intervention and (2) the trial procedures for a future randomised controlled trial of this intervention.

Methods and analysis

This is a multicentre, randomised (1:1) feasibility study with a mixed-methods process evaluation. Sixty participants will be recruited from TIA clinics or stroke wards at three hospital sites (England). Intervention arm participants will be offered a nurse or allied health professional-led follow-up appointment 4 weeks after TIA/minor stroke. The multifaceted intervention includes: a needs checklist, action plan, resources to support management of needs, a general practitioner letter and training to deliver the intervention. Control arm participants will receive usual care. Follow-up will be self-completed questionnaires (12 weeks and 24 weeks) and a clinic appointment (24 weeks). Follow-up questionnaires will measure anxiety, depression, fatigue, health related quality of life, self-efficacy and medication adherence. The clinic appointment will collect body mass index, blood pressure, cholesterol and medication. Assessment of feasibility and acceptability will include quantitative process variables (such as recruitment and questionnaire response rates), structured observations of study processes, and interviews with a subsample of participants and clinical staff.

Ethics and dissemination

Favourable ethical opinion was gained from the Wales Research Ethics Committee (REC) 1 (23 February 2021, REC reference: 21/WA/0036). Study results will be published in peer-reviewed journals and presented at conferences. A lay summary and dissemination strategy will be codesigned with consumers. The lay summary and journal publication will be distributed on social media.

Trial registration number

ISRCTN39864003.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/6/e060280.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-060280; html:https://europepmc.org/articles/PMC9207897; pdf:https://europepmc.org/articles/PMC9207897?pdf=render 33480434,https://doi.org/10.1093/pubmed/fdaa267,"Complex differences in infection rates between ethnic groups in Scotland: a retrospective, national census-linked cohort study of 1.65 million cases.","Gruer LD, Cézard GI, Wallace LA, Hutchinson SJ, Douglas AF, Buchanan D, Katikireddi SV, Millard AD, Goldberg DJ, Sheikh A, Bhopal RS.",,"Journal of public health (Oxford, England)",2022,2022-03-01,Y,Infectious disease; epidemiology; Ethnicity,,,"

Background

Ethnicity can influence susceptibility to infection, as COVID-19 has shown. Few countries have systematically investigated ethnic variations in infection.

Methods

We linked the Scotland 2001 Census, including ethnic group, to national databases of hospitalizations/deaths and serological diagnoses of bloodborne viruses for 2001-2013. We calculated age-adjusted rate ratios (RRs) in 12 ethnic groups for all infections combined, 15 infection categories, and human immunodeficiency virus (HIV), hepatitis B (HBV) and hepatitis C (HCV) viruses.

Results

We analysed over 1.65 million infection-related hospitalisations/deaths. Compared with White Scottish, RRs for all infections combined were 0.8 or lower for Other White British, Other White and Chinese males and females, and 1.2-1.4 for Pakistani and African males and females. Adjustment for socioeconomic status or birthplace had little effect. RRs for specific infection categories followed similar patterns with striking exceptions. For HIV, RRs were 136 in African females and 14 in males; for HBV, 125 in Chinese females and 59 in males, 55 in African females and 24 in males; and for HCV, 2.3-3.1 in Pakistanis and Africans.

Conclusions

Ethnic differences were found in overall rates and many infection categories, suggesting multiple causative pathways. We recommend census linkage as a powerful method for studying the disproportionate impact of COVID-19.",,pdf:https://academic.oup.com/jpubhealth/advance-article-pdf/doi/10.1093/pubmed/fdaa267/36684631/fdaa267.pdf; doi:https://doi.org/10.1093/pubmed/fdaa267; html:https://europepmc.org/articles/PMC7928762; pdf:https://europepmc.org/articles/PMC7928762?pdf=render 36470992,https://doi.org/10.1038/s41375-022-01773-0,Continuous Indexing of Fibrosis (CIF): improving the assessment and classification of MPN patients.,"Ryou H, Sirinukunwattana K, Aberdeen A, Grindstaff G, Stolz BJ, Byrne H, Harrington HA, Sousos N, Godfrey AL, Harrison CN, Psaila B, Mead AJ, Rees G, Turner GDH, Rittscher J, Royston D.",,Leukemia,2023,2022-12-05,Y,,,,"The grading of fibrosis in myeloproliferative neoplasms (MPN) is an important component of disease classification, prognostication and monitoring. However, current fibrosis grading systems are only semi-quantitative and fail to fully capture sample heterogeneity. To improve the quantitation of reticulin fibrosis, we developed a machine learning approach using bone marrow trephine (BMT) samples (n = 107) from patients diagnosed with MPN or a reactive marrow. The resulting Continuous Indexing of Fibrosis (CIF) enhances the detection and monitoring of fibrosis within BMTs, and aids MPN subtyping. When combined with megakaryocyte feature analysis, CIF discriminates between the frequently challenging differential diagnosis of essential thrombocythemia (ET) and pre-fibrotic myelofibrosis with high predictive accuracy [area under the curve = 0.94]. CIF also shows promise in the identification of MPN patients at risk of disease progression; analysis of samples from 35 patients diagnosed with ET and enrolled in the Primary Thrombocythemia-1 trial identified features predictive of post-ET myelofibrosis (area under the curve = 0.77). In addition to these clinical applications, automated analysis of fibrosis has clear potential to further refine disease classification boundaries and inform future studies of the micro-environmental factors driving disease initiation and progression in MPN and other stem cell disorders.",,pdf:https://www.nature.com/articles/s41375-022-01773-0.pdf; doi:https://doi.org/10.1038/s41375-022-01773-0; html:https://europepmc.org/articles/PMC9898027; pdf:https://europepmc.org/articles/PMC9898027?pdf=render 32678323,https://doi.org/10.1038/s41366-020-0642-3,"Cross-sectional associations between central and general adiposity with albuminuria: observations from 400,000 people in UK Biobank.","Zhu P, Lewington S, Haynes R, Emberson J, Landray MJ, Cherney D, Woodward M, Baigent C, Herrington WG, Staplin N.",,International journal of obesity (2005),2020,2020-07-16,Y,,,,"

Background

Whether measures of central adiposity are more or less strongly associated with risk of albuminuria than body mass index (BMI), and by how much diabetes/levels of glycosylated haemoglobin (HbA1c) explain or modify these associations, is uncertain.

Methods

Ordinal logistic regression was used to estimate associations between values of central adiposity (waist-to-hip ratio) and, separately, general adiposity (BMI) with categories of urinary albumin-to-creatinine ratio (uACR) in 408,527 UK Biobank participants. Separate central and general adiposity-based models were initially adjusted for potential confounders and measurement error, then sequentially, models were mutually adjusted (e.g. waist-to-hip ratio adjusted for BMI, and vice versa), and finally they were adjusted for potential mediators.

Results

Levels of albuminuria were generally low: 20,425 (5%) had a uACR ≥3 mg/mmol. After adjustment for confounders and measurement error, each 0.06 higher waist-to-hip ratio was associated with a 55% (95%CI 53-57%) increase in the odds of being in a higher uACR category. After adjustment for baseline BMI, this association was reduced to 32% (30-34%). Each 5 kg/m2 higher BMI was associated with a 47% (46-49%) increase in the odds of being in a higher uACR category. Adjustment for baseline waist-to-hip ratio reduced this association to 35% (33-37%). Those with higher HbA1c were at progressively higher odds of albuminuria, but positive associations between both waist-to-hip ratio and BMI were apparent irrespective of HbA1c. Altogether, about 40% of central adiposity associations appeared to be mediated by diabetes, vascular disease and blood pressure.

Conclusions

Conventional epidemiological approaches suggest that higher waist-to-hip ratio and BMI are independently positively associated with albuminuria. Adiposity-albuminuria associations appear strong among people with normal HbA1c, as well as people with pre-diabetes or diabetes.",,pdf:https://www.nature.com/articles/s41366-020-0642-3.pdf; doi:https://doi.org/10.1038/s41366-020-0642-3; html:https://europepmc.org/articles/PMC7577847; pdf:https://europepmc.org/articles/PMC7577847?pdf=render @@ -2081,17 +2081,17 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 32808938,https://doi.org/10.2196/17022,Technological Capabilities to Assess Digital Excellence in Hospitals in High Performing Health Care Systems: International eDelphi Exercise.,"Krasuska M, Williams R, Sheikh A, Franklin BD, Heeney C, Lane W, Mozaffar H, Mason K, Eason S, Hinder S, Dunscombe R, Potts HWW, Cresswell K.",,Journal of medical Internet research,2020,2020-08-18,Y,"Delphi Technique; Digital Maturity; Digital Excellence; Hospitals, Ehealth",,,"

Background

Hospitals worldwide are developing ambitious digital transformation programs as part of broader efforts to create digitally advanced health care systems. However, there is as yet no consensus on how best to characterize and assess digital excellence in hospitals.

Objective

Our aim was to develop an international agreement on a defined set of technological capabilities to assess digital excellence in hospitals.

Methods

We conducted a two-stage international modified electronic Delphi (eDelphi) consensus-building exercise, which included a qualitative analysis of free-text responses. In total, 31 international health informatics experts participated, representing clinical, academic, public, and vendor organizations.

Results

We identified 35 technological capabilities that indicate digital excellence in hospitals. These are divided into two categories: (a) capabilities within a hospital (n=20) and (b) capabilities enabling communication with other parts of the health and social care system, and with patients and carers (n=15). The analysis of free-text responses pointed to the importance of nontechnological aspects of digitally enabled change, including social and organizational factors. Examples included an institutional culture characterized by a willingness to transform established ways of working and openness to risk-taking. The availability of a range of skills within digitization teams, including technological, project management and business expertise, and availability of resources to support hospital staff, were also highlighted.

Conclusions

We have identified a set of criteria for assessing digital excellence in hospitals. Our findings highlight the need to broaden the focus from technical functionalities to wider digital transformation capabilities.",,pdf:https://www.jmir.org/2020/8/e17022/PDF; doi:https://doi.org/10.2196/17022; html:https://europepmc.org/articles/PMC7463397 33341984,https://doi.org/10.1111/tme.12750,Comparison of four methods to measure haemoglobin concentrations in whole blood donors (COMPARE): A diagnostic accuracy study.,"Bell S, Sweeting M, Ramond A, Chung R, Kaptoge S, Walker M, Bolton T, Sambrook J, Moore C, McMahon A, Fahle S, Cullen D, Mehenny S, Wood AM, Armitage J, Ouwehand WH, Miflin G, Roberts DJ, Danesh J, Di Angelantonio E, COMPARE Study Group.",,"Transfusion medicine (Oxford, England)",2021,2020-12-20,Y,Hemocue; Gravimetry; Whole Blood Donor; Haemoglobin Screening; Inappropriate Bleeding; Inappropriate Deferral; Non-invasive Haemoglobin Measurement,,,"

Objective

To compare four haemoglobin measurement methods in whole blood donors.

Background

To safeguard donors, blood services measure haemoglobin concentration in advance of each donation. NHS Blood and Transplant's (NHSBT) customary method have been capillary gravimetry (copper sulphate), followed by venous spectrophotometry (HemoCue) for donors failing gravimetry. However, NHSBT's customary method results in 10% of donors being inappropriately bled (ie, with haemoglobin values below the regulatory threshold).

Methods

We compared the following four methods in 21 840 blood donors (aged ≥18 years) recruited from 10 NHSBT centres in England, with the Sysmex XN-2000 haematology analyser, the reference standard: (1) NHSBT's customary method; (2) ""post donation"" approach, that is, estimating current haemoglobin concentration from that measured by a haematology analyser at a donor's most recent prior donation; (3) ""portable haemoglobinometry"" (using capillary HemoCue); (4) non-invasive spectrometry (using MBR Haemospect or Orsense NMB200). We assessed sensitivity; specificity; proportion who would have been inappropriately bled, or rejected from donation (""deferred"") incorrectly; and test preference.

Results

Compared with the reference standard, the methods ranged in test sensitivity from 17.0% (MBR Haemospect) to 79.0% (portable haemoglobinometry) in men, and from 19.0% (MBR Haemospect) to 82.8% (portable haemoglobinometry) in women. For specificity, the methods ranged from 87.2% (MBR Haemospect) to 99.9% (NHSBT's customary method) in men, and from 74.1% (Orsense NMB200) to 99.8% (NHSBT's customary method) in women. The proportion of donors who would have been inappropriately bled ranged from 2.2% in men for portable haemoglobinometry to 18.9% in women for MBR Haemospect. The proportion of donors who would have been deferred incorrectly with haemoglobin concentration above the minimum threshold ranged from 0.1% in men for NHSBT's customary method to 20.3% in women for OrSense. Most donors preferred non-invasive spectrometry.

Conclusion

In the largest study reporting head-to-head comparisons of four methods to measure haemoglobin prior to blood donation, our results support replacement of NHSBT's customary method with portable haemoglobinometry.",,pdf:https://www.repository.cam.ac.uk/bitstream/1810/315673/1/tme.12750.pdf; doi:https://doi.org/10.1111/tme.12750; html:https://europepmc.org/articles/PMC8048787; pdf:https://europepmc.org/articles/PMC8048787?pdf=render 31134468,https://doi.org/10.1007/s12471-019-1288-4,UNRAVEL: big data analytics research data platform to improve care of patients with cardiomyopathies using routine electronic health records and standardised biobanking.,"Sammani A, Jansen M, Linschoten M, Bagheri A, de Jonge N, Kirkels H, van Laake LW, Vink A, van Tintelen JP, Dooijes D, Te Riele ASJM, Harakalova M, Baas AF, Asselbergs FW.",,Netherlands heart journal : monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation,2019,2019-09-01,Y,Cardiomyopathy; Electronic Health Record; Biobanking; Big Data Analytics; Machine learning; Research Data Platform,,,"

Introduction

Despite major advances in our understanding of genetic cardiomyopathies, they remain the leading cause of premature sudden cardiac death and end-stage heart failure in persons under the age of 60 years. Integrated research databases based on a large number of patients may provide a scaffold for future research. Using routine electronic health records and standardised biobanking, big data analysis on a larger number of patients and investigations are possible. In this article, we describe the UNRAVEL research data platform embedded in routine practice to facilitate research in genetic cardiomyopathies.

Design

Eligible participants with proven or suspected cardiac disease and their relatives are asked for permission to use their data and to draw blood for biobanking. Routinely collected clinical data are included in a research database by weekly extraction. A text-mining tool has been developed to enrich UNRAVEL with unstructured data in clinical notes.

Preliminary results

Thus far, 828 individuals with a median age of 57 years have been included, 58% of whom are male. All data are captured in a temporal sequence amounting to a total of 18,565 electrocardiograms, 3619 echocardiograms, data from over 20,000 radiological examinations and 650,000 individual laboratory measurements.

Conclusion

Integration of routine electronic health care in a research data platform allows efficient data collection, including all investigations in chronological sequence. Trials embedded in the electronic health record are now possible, providing cost-effective ways to answer clinical questions. We explicitly welcome national and international collaboration and have provided our protocols and other materials on www.unravelrdp.nl .",,pdf:https://link.springer.com/content/pdf/10.1007/s12471-019-1288-4.pdf; doi:https://doi.org/10.1007/s12471-019-1288-4; html:https://europepmc.org/articles/PMC6712144; pdf:https://europepmc.org/articles/PMC6712144?pdf=render -36401199,https://doi.org/10.1186/s12888-022-04275-6,Patient characteristics associated with retrospectively self-reported treatment outcomes following psychological therapy for anxiety or depressive disorders - a cohort of GLAD study participants.,"Rayner C, Coleman JRI, Skelton M, Armour C, Bradley J, Buckman JEJ, Davies MR, Hirsch CR, Hotopf M, Hübel C, Jones IR, Kalsi G, Kingston N, Krebs G, Lin Y, Monssen D, McIntosh AM, Mundy JR, Peel AJ, Rimes KA, Rogers HC, Smith DJ, Ter Kuile AR, Thompson KN, Veale D, Wingrove J, Walters JTR, Breen G, Eley TC.",,BMC psychiatry,2022,2022-11-18,Y,Counselling; Cognitive Behavioral Therapy; Minimal Phenotyping,,,"

Background

Progress towards stratified care for anxiety and depression will require the identification of new predictors. We collected data on retrospectively self-reported therapeutic outcomes in adults who received psychological therapy in the UK in the past ten years. We aimed to replicate factors associated with traditional treatment outcome measures from the literature.

Methods

Participants were from the Genetic Links to Anxiety and Depression (GLAD) Study, a UK-based volunteer cohort study. We investigated associations between retrospectively self-reported outcomes following therapy, on a five-point scale (global rating of change; GRC) and a range of sociodemographic, clinical and therapy-related factors, using ordinal logistic regression models (n = 2890).

Results

Four factors were associated with therapy outcomes (adjusted odds ratios, OR). One sociodemographic factor, having university-level education, was associated with favourable outcomes (OR = 1.37, 95%CI: 1.18, 1.59). Two clinical factors, greater number of reported episodes of illness (OR = 0.95, 95%CI: 0.92, 0.97) and higher levels of personality disorder symptoms (OR = 0.89, 95%CI: 0.87, 0.91), were associated with less favourable outcomes. Finally, reported regular use of additional therapeutic activities was associated with favourable outcomes (OR = 1.39, 95%CI: 1.19, 1.63). There were no statistically significant differences between fully adjusted multivariable and unadjusted univariable odds ratios.

Conclusion

Therapy outcome data can be collected quickly and inexpensively using retrospectively self-reported measures in large observational cohorts. Retrospectively self-reported therapy outcomes were associated with four factors previously reported in the literature. Similar data collected in larger observational cohorts may enable detection of novel associations with therapy outcomes, to generate new hypotheses, which can be followed up in prospective studies.",,pdf:https://bmcpsychiatry.biomedcentral.com/counter/pdf/10.1186/s12888-022-04275-6; doi:https://doi.org/10.1186/s12888-022-04275-6; html:https://europepmc.org/articles/PMC9675224; pdf:https://europepmc.org/articles/PMC9675224?pdf=render 32479194,https://doi.org/10.1161/circulationaha.120.045826,"Lipoprotein(a) in Alzheimer, Atherosclerotic, Cerebrovascular, Thrombotic, and Valvular Disease: Mendelian Randomization Investigation.","Larsson SC, Gill D, Mason AM, Jiang T, Bäck M, Butterworth AS, Burgess S.",,Circulation,2020,2020-06-01,N,Atherosclerosis; Lipoprotein(a); Alzheimer disease; Stroke; Heart valve diseases; Mendelian Randomization Analysis,,,,,pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCULATIONAHA.120.045826; doi:https://doi.org/10.1161/CIRCULATIONAHA.120.045826; html:https://europepmc.org/articles/PMC7614586; pdf:https://europepmc.org/articles/PMC7614586?pdf=render; doi:https://doi.org/10.1161/circulationaha.120.045826 -35614427,https://doi.org/10.1186/s12889-022-13457-6,"The association between childhood hearing loss and self-reported peer victimisation, depressive symptoms, and self-harm: longitudinal analyses of a prospective, nationally representative cohort study.","Butcher E, Cortina-Borja M, Dezateux C, Knowles R.",,BMC public health,2022,2022-05-25,Y,Child; Hearing loss; Cohort studies; Mental health; Self-harm; Depressive Symptoms; Peer Victimisation,,,"

Background

Childhood hearing loss (HL) predicts poor mental health and is associated with a higher risk of communication difficulties. The relationship of childhood HL with specific types of poor mental health (such as depressive symptoms or self-harm) and peer victimisation remains unclear.

Methods

We analysed data from the Millennium Cohort Study (MCS), a prospective observational cohort study of children living in the UK at age 9 months and born between 2000 to 2002. Data were available on the children and their families at ages 9 months, then at 3, 5, 7, 11, and 14 years. Participants were 10,858 singleton children with self-reported data on peer victimisation, depressive symptoms, and self-harm at age 14 years. Multivariable logistic regression models were fitted to estimate odds ratios (OR) for HL with peer victimisation, depressive symptoms, and self-harm. HL presence was examined in terms of any HL between ages 9 months and 14 years, as well as by HL trajectory type (defined by onset and persistence). Analyses were adjusted for potential sources of confounding, survey design, and attrition at age 14 years. Interactions between sex and HL were examined in each model and multiple imputation procedures used to address missing data.

Results

Children with any HL had increased odds of depressive symptoms (OR: 1.32, 95% CI: 1.09-1.60), self-harm (1.41, 1.12-1.78) and, in girls only, peer victimisation (girls: 1.81, 1.29-2.55; boys: 1.05, 0.73-1.51), compared to those without HL. HL with later age at onset and persistence to age 14 years was the only trajectory associated with all outcomes.

Conclusions

Childhood HL may predict peer victimisation (in girls), depressive symptoms, and self-harm. Further research is needed to identify HL trajectories and methods to facilitate good mental health in children with HL.",,pdf:https://bmcpublichealth.biomedcentral.com/counter/pdf/10.1186/s12889-022-13457-6; doi:https://doi.org/10.1186/s12889-022-13457-6; html:https://europepmc.org/articles/PMC9131522; pdf:https://europepmc.org/articles/PMC9131522?pdf=render +36401199,https://doi.org/10.1186/s12888-022-04275-6,Patient characteristics associated with retrospectively self-reported treatment outcomes following psychological therapy for anxiety or depressive disorders - a cohort of GLAD study participants.,"Rayner C, Coleman JRI, Skelton M, Armour C, Bradley J, Buckman JEJ, Davies MR, Hirsch CR, Hotopf M, Hübel C, Jones IR, Kalsi G, Kingston N, Krebs G, Lin Y, Monssen D, McIntosh AM, Mundy JR, Peel AJ, Rimes KA, Rogers HC, Smith DJ, Ter Kuile AR, Thompson KN, Veale D, Wingrove J, Walters JTR, Breen G, Eley TC.",,BMC psychiatry,2022,2022-11-18,Y,Counselling; Cognitive Behavioral Therapy; Minimal Phenotyping,,,"

Background

Progress towards stratified care for anxiety and depression will require the identification of new predictors. We collected data on retrospectively self-reported therapeutic outcomes in adults who received psychological therapy in the UK in the past ten years. We aimed to replicate factors associated with traditional treatment outcome measures from the literature.

Methods

Participants were from the Genetic Links to Anxiety and Depression (GLAD) Study, a UK-based volunteer cohort study. We investigated associations between retrospectively self-reported outcomes following therapy, on a five-point scale (global rating of change; GRC) and a range of sociodemographic, clinical and therapy-related factors, using ordinal logistic regression models (n = 2890).

Results

Four factors were associated with therapy outcomes (adjusted odds ratios, OR). One sociodemographic factor, having university-level education, was associated with favourable outcomes (OR = 1.37, 95%CI: 1.18, 1.59). Two clinical factors, greater number of reported episodes of illness (OR = 0.95, 95%CI: 0.92, 0.97) and higher levels of personality disorder symptoms (OR = 0.89, 95%CI: 0.87, 0.91), were associated with less favourable outcomes. Finally, reported regular use of additional therapeutic activities was associated with favourable outcomes (OR = 1.39, 95%CI: 1.19, 1.63). There were no statistically significant differences between fully adjusted multivariable and unadjusted univariable odds ratios.

Conclusion

Therapy outcome data can be collected quickly and inexpensively using retrospectively self-reported measures in large observational cohorts. Retrospectively self-reported therapy outcomes were associated with four factors previously reported in the literature. Similar data collected in larger observational cohorts may enable detection of novel associations with therapy outcomes, to generate new hypotheses, which can be followed up in prospective studies.",,pdf:https://bmcpsychiatry.biomedcentral.com/counter/pdf/10.1186/s12888-022-04275-6; doi:https://doi.org/10.1186/s12888-022-04275-6; html:https://europepmc.org/articles/PMC9675224; pdf:https://europepmc.org/articles/PMC9675224?pdf=render 30949070,https://doi.org/10.3389/fpsyt.2019.00109,Real World Implementation of a Transdiagnostic Risk Calculator for the Automatic Detection of Individuals at Risk of Psychosis in Clinical Routine: Study Protocol.,"Fusar-Poli P, Oliver D, Spada G, Patel R, Stewart R, Dobson R, McGuire P.",,Frontiers in psychiatry,2019,2019-03-13,Y,Schizophrenia; Prevention; risk; Psychosis; Transdiagnostic,"Applied Analytics, Better Care",,"Background: Primary indicated prevention in individuals at-risk for psychosis has the potential to improve the outcomes of this disorder. The ability to detect the majority of at-risk individuals is the main barrier toward extending benefits for the lives of many adolescents and young adults. Current detection strategies are highly inefficient. Only 5% (standalone specialized early detection services) to 12% (youth mental health services) of individuals who will develop a first psychotic disorder can be detected at the time of their at-risk stage. To overcome these challenges a pragmatic, clinically-based, individualized, transdiagnostic risk calculator has been developed to detect individuals at-risk of psychosis in secondary mental health care at scale. This calculator has been externally validated and has demonstrated good prognostic performance. However, it is not known whether it can be used in the real world clinical routine. For example, clinicians may not be willing to adhere to the recommendations made by the transdiagnostic risk calculator. Implementation studies are needed to address pragmatic challenges relating to the real world use of the transdiagnostic risk calculator. The aim of the current study is to provide in-vitro and in-vivo feasibility data to support the implementation of the transdiagnostic risk calculator in clinical routine. Method: This is a study which comprises of two subsequent phases: an in-vitro phase of 1 month and an in-vivo phase of 11 months. The in-vitro phase aims at developing and integrating the transdiagnostic risk calculator in the local electronic health register (primary outcome). The in-vivo phase aims at addressing the clinicians' adherence to the recommendations made by the transdiagnostic risk calculator (primary outcome) and other secondary feasibility parameters that are necessary to estimate the resources needed for its implementation. Discussion: This is the first implementation study for risk prediction models in individuals at-risk for psychosis. Ultimately, successful implementation is the true measure of a prediction model's utility. Therefore, the overall translational deliverable of the current study would be to extend the benefits of primary indicated prevention and improve outcomes of first episode psychosis. This may produce significant social benefits for many adolescents and young adults and their families.",,pdf:https://www.frontiersin.org/articles/10.3389/fpsyt.2019.00109/pdf; doi:https://doi.org/10.3389/fpsyt.2019.00109; html:https://europepmc.org/articles/PMC6436079; pdf:https://europepmc.org/articles/PMC6436079?pdf=render +35614427,https://doi.org/10.1186/s12889-022-13457-6,"The association between childhood hearing loss and self-reported peer victimisation, depressive symptoms, and self-harm: longitudinal analyses of a prospective, nationally representative cohort study.","Butcher E, Cortina-Borja M, Dezateux C, Knowles R.",,BMC public health,2022,2022-05-25,Y,Child; Hearing loss; Cohort studies; Mental health; Self-harm; Depressive Symptoms; Peer Victimisation,,,"

Background

Childhood hearing loss (HL) predicts poor mental health and is associated with a higher risk of communication difficulties. The relationship of childhood HL with specific types of poor mental health (such as depressive symptoms or self-harm) and peer victimisation remains unclear.

Methods

We analysed data from the Millennium Cohort Study (MCS), a prospective observational cohort study of children living in the UK at age 9 months and born between 2000 to 2002. Data were available on the children and their families at ages 9 months, then at 3, 5, 7, 11, and 14 years. Participants were 10,858 singleton children with self-reported data on peer victimisation, depressive symptoms, and self-harm at age 14 years. Multivariable logistic regression models were fitted to estimate odds ratios (OR) for HL with peer victimisation, depressive symptoms, and self-harm. HL presence was examined in terms of any HL between ages 9 months and 14 years, as well as by HL trajectory type (defined by onset and persistence). Analyses were adjusted for potential sources of confounding, survey design, and attrition at age 14 years. Interactions between sex and HL were examined in each model and multiple imputation procedures used to address missing data.

Results

Children with any HL had increased odds of depressive symptoms (OR: 1.32, 95% CI: 1.09-1.60), self-harm (1.41, 1.12-1.78) and, in girls only, peer victimisation (girls: 1.81, 1.29-2.55; boys: 1.05, 0.73-1.51), compared to those without HL. HL with later age at onset and persistence to age 14 years was the only trajectory associated with all outcomes.

Conclusions

Childhood HL may predict peer victimisation (in girls), depressive symptoms, and self-harm. Further research is needed to identify HL trajectories and methods to facilitate good mental health in children with HL.",,pdf:https://bmcpublichealth.biomedcentral.com/counter/pdf/10.1186/s12889-022-13457-6; doi:https://doi.org/10.1186/s12889-022-13457-6; html:https://europepmc.org/articles/PMC9131522; pdf:https://europepmc.org/articles/PMC9131522?pdf=render 31040096,https://doi.org/10.1016/s2352-4642(19)30114-2,"Antimicrobial-impregnated central venous catheters for prevention of neonatal bloodstream infection (PREVAIL): an open-label, parallel-group, pragmatic, randomised controlled trial.","Gilbert R, Brown M, Rainford N, Donohue C, Fraser C, Sinha A, Dorling J, Gray J, McGuire W, Gamble C, Oddie SJ, PREVAIL trial team.",,The Lancet. Child & adolescent health,2019,2019-04-27,N,,"Better, Faster and More Efficient Clinical Trials",,"

Background

Bloodstream infection is associated with high mortality and serious morbidity in preterm babies. Evidence from clinical trials shows that antimicrobial-impregnated central venous catheters (CVCs) reduce catheter-related bloodstream infection in adults and children receiving intensive care, but there is a paucity of similar evidence for babies receiving neonatal intensive care.

Methods

This open-label, parallel-group, pragmatic, randomised controlled trial was done in 18 neonatal intensive care units in England. Newborn babies who needed a peripherally inserted CVC (PICC) were allocated randomly (1:1) to receive either a PICC impregnated with miconazole and rifampicin or a standard (non-antimicrobial-impregnated) PICC. Random allocation was done with a web-based program, which was centrally controlled to ensure allocation concealment. Randomisation sequences were computer-generated in random blocks of two and four, and stratified by site. Masking of clinicians to PICC allocation was impractical because rifampicin caused brown staining of the antimicrobial-impregnated PICC. However, participant inclusion in analyses and occurrence of outcome events were determined following an analysis plan that was specified before individuals saw the unblinded data. The primary outcome was the time from random allocation to first microbiologically confirmed bloodstream or cerebrospinal fluid (CSF) infection between 24 h after randomisation and 48 h after PICC removal or death. We analysed outcome data according to the intention-to-treat principle. We excluded babies for whom a PICC was not inserted from safety analyses, as these analyses were done with groups defined by the PICC used. This trial is registered with ISRCTN, number 81931394.

Findings

Between Aug 12, 2015, and Jan 11, 2017, we randomly assigned 861 babies (754 [88%] born before 32 weeks of gestation) to receive an antimicrobial-impregnated PICC (430 babies) or standard PICC (431 babies). The median time to PICC removal was 8·20 days (IQR 4·77-12·13) in the antimicrobial-impregnated PICC group versus 7·86 days (5·00-12·53) days in the standard PICC group (hazard ratio [HR] 1·03, 95% CI 0·89-1·18, p=0·73), with 46 (11%) of 430 babies versus 44 (10%) of 431 babies having a microbiologically confirmed bloodstream or CSF infection. The time from random allocation to first bloodstream or CSF infection was similar between the two groups (HR 1·11, 95% CI 0·73-1·67, p=0·63). Secondary outcomes relating to infection, rifampicin resistance in positive blood or CSF cultures, mortality, clinical outcomes at neonatal unit discharge, and time to PICC removal were similar between the two groups, although rifampicin resistance in positive cultures of PICC tips was higher in the antimicrobial-impregnated PICC group (relative risk 3·51, 95% CI 1·16-10·57, p=0·018). 60 adverse events were reported from 49 (13%) patients in the antimicrobial-impregnated PICC group and 50 events from 45 (10%) babies in the standard PICC group.

Interpretation

We found no evidence of benefit or harm associated with miconazole and rifampicin-impregnated PICCs compared with standard PICCs for newborn babies. Future research should focus on other types of antimicrobial impregnation of PICCs and alternative approaches for preventing infection.

Funding

UK National Institute for Health Research Health Technology Assessment programme.",,pdf:http://www.thelancet.com/article/S2352464219301142/pdf; doi:https://doi.org/10.1016/S2352-4642(19)30114-2 30014898,https://doi.org/10.1016/j.envres.2018.07.015,Estimation of TETRA radio use in the Airwave Health Monitoring Study of the British police forces.,"Vergnaud AC, Aresu M, Kongsgård HW, McRobie D, Singh D, Spear J, Heard A, Gao H, Carpenter JR, Elliott P.",,Environmental research,2018,2018-07-09,N,Tetra; Occupational Exposure; Occupational Cohort; Radiofrequency Electromagnetic Fields,Improving Public Health,,"

Background

The Airwave Health Monitoring Study aims to investigate the possible long-term health effects of Terrestrial Trunked Radio (TETRA) use among the police forces in Great Britain. Here, we investigate whether objective data from the network operator could be used to correct for misreporting in self-reported data and expand the radio usage availability in our cohort.

Methods

We estimated average monthly usage of personal radio in the 12 months prior to enrolment from a missing value imputation model and evaluated its performance against objective and self-reported data. Factors associated with TETRA radio usage variables were investigated using Chi-square tests and analysis of variance.

Results

The imputed data were better correlated with objective than self-reported usage (Spearman correlation coefficient = 0.72 vs. 0. 52 and kappa 0.56 [95% confidence interval 0.55, 0.56] vs. 0.46 [0.45, 0.47]), although the imputation model tended to under-estimate use for higher users. Participants with higher personal radio usage were more likely to be younger, men vs. women and officer vs. staff. The median average monthly usage level for the entire cohort was estimated to be 29.3 min (95% CI: [7.2, 66.6]).

Conclusion

The availability of objective personal radio records for a large proportion of users allowed us to develop a robust imputation model and hence obtain personal radio usage estimates for ~50,000 participants. This substantially reduced exposure misclassification compared to using self-reported data and will allow us to carry out analyses of TETRA usage for the entire cohort in future work.",,pdf:https://researchonline.lshtm.ac.uk/id/eprint/4648566/1/Estimation%20of%20TETRA%20radio_GREEN%20AAM.pdf; doi:https://doi.org/10.1016/j.envres.2018.07.015 37269091,https://doi.org/10.1177/10870547231172763,Remote Administration of ADHD-Sensitive Cognitive Tasks: A Pilot Study.,"Sun S, Denyer H, Sankesara H, Deng Q, Ranjan Y, Conde P, Rashid Z, Bendayan R, Asherson P, Bilbow A, Groom M, Hollis C, Folarin AA, Dobson RJB, Kuntsi J.",,Journal of attention disorders,2023,2023-06-02,Y,ADHD; Remote Monitoring; Response Inhibition; Attention Regulation; Radar-base,,,"

Objective

We assessed the feasibility and validity of remote researcher-led administration and self-administration of modified versions of two cognitive tasks sensitive to ADHD, a four-choice reaction time task (Fast task) and a combined Continuous Performance Test/Go No-Go task (CPT/GNG), through a new remote measurement technology system.

Method

We compared the cognitive performance measures (mean and variability of reaction times (MRT, RTV), omission errors (OE) and commission errors (CE)) at a remote baseline researcher-led administration and three remote self-administration sessions between participants with and without ADHD (n = 40).

Results

The most consistent group differences were found for RTV, MRT and CE at the baseline researcher-led administration and the first self-administration, with 8 of the 10 comparisons statistically significant and all comparisons indicating medium to large effect sizes.

Conclusion

Remote administration of cognitive tasks successfully captured the difficulties with response inhibition and regulation of attention, supporting the feasibility and validity of remote assessments.",,pdf:https://journals.sagepub.com/doi/pdf/10.1177/10870547231172763; doi:https://doi.org/10.1177/10870547231172763; html:https://europepmc.org/articles/PMC10291103; pdf:https://europepmc.org/articles/PMC10291103?pdf=render 32719032,https://doi.org/10.1128/jcm.00670-20,DNA Thermo-Protection Facilitates Whole-Genome Sequencing of Mycobacteria Direct from Clinical Samples.,"George S, Xu Y, Rodger G, Morgan M, Sanderson ND, Hoosdally SJ, Thulborn S, Robinson E, Rathod P, Walker AS, Peto TEA, Crook DW, Dingle KE.",,Journal of clinical microbiology,2020,2020-09-22,Y,DNA sequencing; Mycobacterium tuberculosis; Mycobacteria; Clinical Diagnostics; Nanopore Dna Sequencing; Direct-from-sample Sequencing,,,"Mycobacterium tuberculosis is the leading cause of death from bacterial infection. Improved rapid diagnosis and antimicrobial resistance determination, such as by whole-genome sequencing, are required. Our aim was to develop a simple, low-cost method of preparing DNA for sequencing direct from M. tuberculosis-positive clinical samples (without culture). Simultaneous sputum liquefaction, bacteria heat inactivation (99°C/30 min), and enrichment for mycobacteria DNA were achieved using an equal volume of thermo-protection buffer (4 M KCl, 0.05 M HEPES buffer, pH 7.5, 0.1% dithiothreitol [DTT]). The buffer emulated intracellular conditions found in hyperthermophiles, thus protecting DNA from rapid thermodegradation, which renders it a poor template for sequencing. Initial validation experiments employed mycobacteria DNA, either extracted or intracellular. Next, mock clinical samples (infection-negative human sputum spiked with 0 to 105Mycobacterium bovis BCG cells/ml) underwent liquefaction in thermo-protection buffer and heat inactivation. DNA was extracted and sequenced. Human DNA degraded faster than mycobacteria DNA, resulting in target enrichment. Four replicate experiments achieved M. tuberculosis detection at 101 BCG cells/ml, with 31 to 59 M. tuberculosis complex reads. Maximal genome coverage (>97% at 5× depth) occurred at 104 BCG cells/ml; >91% coverage (1× depth) occurred at 103 BCG cells/ml. Final validation employed M. tuberculosis-positive clinical samples (n = 20), revealing that initial sample volumes of ≥1 ml typically yielded higher mean depths of M. tuberculosis genome coverage, with an overall range of 0.55 to 81.02. A mean depth of 3 gave >96% 1-fold tuberculosis (TB) genome coverage (in 15/20 clinical samples). A mean depth of 15 achieved >99% 5-fold genome coverage (in 9/20 clinical samples). In summary, direct-from-sample sequencing of M. tuberculosis genomes was facilitated by a low-cost thermo-protection buffer.",,doi:https://doi.org/10.1128/jcm.00670-20; doi:https://doi.org/10.1128/JCM.00670-20; html:https://europepmc.org/articles/PMC7512152; pdf:https://europepmc.org/articles/PMC7512152?pdf=render 33664499,https://doi.org/10.1038/s41431-021-00835-8,Colocalization analysis of polycystic ovary syndrome to identify potential disease-mediating genes and proteins.,"Censin JC, Bovijn J, Holmes MV, Lindgren CM.",,European journal of human genetics : EJHG,2021,2021-03-04,Y,,,,"Polycystic ovary syndrome (PCOS) is a common complex disease in women with a strong genetic component and downstream consequences for reproductive, metabolic and psychological health. There are currently 19 known PCOS risk loci, primarily identified in women of Han Chinese or European ancestry, and 14 of these risk loci were identified or replicated in a genome-wide association study of PCOS performed in up to 10,074 cases and 103,164 controls of European descent. However, for most of these loci the gene responsible for the association is unknown. We therefore use a Bayesian colocalization approach (Coloc) to highlight genes in PCOS-associated regions that may have a role in mediating the disease risk. We evaluated the posterior probabilities of evidence consistent with shared causal variants between 14 PCOS genetic risk loci and intermediate cellular phenotypes in one protein (N = 3301) and two expression quantitative trait locus datasets (N = 31,684 and N = 80-491). Through these analyses, we identified seven proteins or genes with evidence of a possibly shared causal variant for almost 30% of known PCOS signals, including follicle stimulating hormone and ERBB3, IKZF4, RPS26, SUOX, ZFP36L2, and C8orf49. Several of these potential effector proteins and genes have been implicated in the hypothalamic-pituitary-gonadal signalling pathway and provide an avenue for functional follow-up in order to demonstrate a causal role in PCOS pathophysiology.",,pdf:https://www.nature.com/articles/s41431-021-00835-8.pdf; doi:https://doi.org/10.1038/s41431-021-00835-8; html:https://europepmc.org/articles/PMC8440598; pdf:https://europepmc.org/articles/PMC8440598?pdf=render -36706770,https://doi.org/10.1016/s2214-109x(23)00007-4,Global investments in pandemic preparedness and COVID-19: development assistance and domestic spending on health between 1990 and 2026.,Global Burden of Disease 2021 Health Financing Collaborator Network.,,The Lancet. Global health,2023,2023-01-24,Y,,,,"

Background

The COVID-19 pandemic highlighted gaps in health surveillance systems, disease prevention, and treatment globally. Among the many factors that might have led to these gaps is the issue of the financing of national health systems, especially in low-income and middle-income countries (LMICs), as well as a robust global system for pandemic preparedness. We aimed to provide a comparative assessment of global health spending at the onset of the pandemic; characterise the amount of development assistance for pandemic preparedness and response disbursed in the first 2 years of the COVID-19 pandemic; and examine expectations for future health spending and put into context the expected need for investment in pandemic preparedness.

Methods

In this analysis of global health spending between 1990 and 2021, and prediction from 2021 to 2026, we estimated four sources of health spending: development assistance for health (DAH), government spending, out-of-pocket spending, and prepaid private spending across 204 countries and territories. We used the Organisation for Economic Co-operation and Development (OECD)'s Creditor Reporting System (CRS) and the WHO Global Health Expenditure Database (GHED) to estimate spending. We estimated development assistance for general health, COVID-19 response, and pandemic preparedness and response using a keyword search. Health spending estimates were combined with estimates of resources needed for pandemic prevention and preparedness to analyse future health spending patterns, relative to need.

Findings

In 2019, at the onset of the COVID-19 pandemic, US$9·2 trillion (95% uncertainty interval [UI] 9·1-9·3) was spent on health worldwide. We found great disparities in the amount of resources devoted to health, with high-income countries spending $7·3 trillion (95% UI 7·2-7·4) in 2019; 293·7 times the $24·8 billion (95% UI 24·3-25·3) spent by low-income countries in 2019. That same year, $43·1 billion in development assistance was provided to maintain or improve health. The pandemic led to an unprecedented increase in development assistance targeted towards health; in 2020 and 2021, $1·8 billion in DAH contributions was provided towards pandemic preparedness in LMICs, and $37·8 billion was provided for the health-related COVID-19 response. Although the support for pandemic preparedness is 12·2% of the recommended target by the High-Level Independent Panel (HLIP), the support provided for the health-related COVID-19 response is 252·2% of the recommended target. Additionally, projected spending estimates suggest that between 2022 and 2026, governments in 17 (95% UI 11-21) of the 137 LMICs will observe an increase in national government health spending equivalent to an addition of 1% of GDP, as recommended by the HLIP.

Interpretation

There was an unprecedented scale-up in DAH in 2020 and 2021. We have a unique opportunity at this time to sustain funding for crucial global health functions, including pandemic preparedness. However, historical patterns of underfunding of pandemic preparedness suggest that deliberate effort must be made to ensure funding is maintained.

Funding

Bill & Melinda Gates Foundation.",,pdf:http://www.thelancet.com/article/S2214109X23000074/pdf; doi:https://doi.org/10.1016/S2214-109X(23)00007-4; html:https://europepmc.org/articles/PMC9998276 32548911,https://doi.org/10.1002/ehf2.12779,A registry-based algorithm to predict ejection fraction in patients with heart failure.,"Uijl A, Lund LH, Vaartjes I, Brugts JJ, Linssen GC, Asselbergs FW, Hoes AW, Dahlström U, Koudstaal S, Savarese G.",,ESC heart failure,2020,2020-06-17,Y,Prediction; Ejection fraction; Heart Failure; Electronic Health Records; Hfpef; Hfref; Hfmref,,,"

Aims

Left ventricular ejection fraction (EF) is required to categorize heart failure (HF) [i.e. HF with preserved (HFpEF), mid-range (HFmrEF), and reduced (HFrEF) EF] but is often not captured in population-based cohorts or non-HF registries. The aim was to create an algorithm that identifies EF subphenotypes for research purposes.

Methods and results

We included 42 061 HF patients from the Swedish Heart Failure Registry. As primary analysis, we performed two logistic regression models including 22 variables to predict (i) EF≥ vs. <50% and (ii) EF≥ vs. <40%. In the secondary analysis, we performed a multivariable multinomial analysis with 22 variables to create a model for all three separate EF subphenotypes: HFrEF vs. HFmrEF vs. HFpEF. The models were validated in the database from the CHECK-HF study, a cross-sectional survey of 10 627 patients from the Netherlands. The C-statistic (discrimination) was 0.78 [95% confidence interval (CI) 0.77-0.78] for EF ≥50% and 0.76 (95% CI 0.75-0.76) for EF ≥40%. Similar results were achieved for HFrEF and HFpEF in the multinomial model, but the C-statistic for HFmrEF was lower: 0.63 (95% CI 0.63-0.64). The external validation showed similar discriminative ability to the development cohort.

Conclusions

Routine clinical characteristics could potentially be used to identify different EF subphenotypes in databases where EF is not readily available. Accuracy was good for the prediction of HFpEF and HFrEF but lower for HFmrEF. The proposed algorithm enables more effective research on HF in the big data setting.",,doi:https://doi.org/10.1002/ehf2.12779; doi:https://doi.org/10.1002/ehf2.12779; html:https://europepmc.org/articles/PMC7524089; pdf:https://europepmc.org/articles/PMC7524089?pdf=render +36706770,https://doi.org/10.1016/s2214-109x(23)00007-4,Global investments in pandemic preparedness and COVID-19: development assistance and domestic spending on health between 1990 and 2026.,Global Burden of Disease 2021 Health Financing Collaborator Network.,,The Lancet. Global health,2023,2023-01-24,Y,,,,"

Background

The COVID-19 pandemic highlighted gaps in health surveillance systems, disease prevention, and treatment globally. Among the many factors that might have led to these gaps is the issue of the financing of national health systems, especially in low-income and middle-income countries (LMICs), as well as a robust global system for pandemic preparedness. We aimed to provide a comparative assessment of global health spending at the onset of the pandemic; characterise the amount of development assistance for pandemic preparedness and response disbursed in the first 2 years of the COVID-19 pandemic; and examine expectations for future health spending and put into context the expected need for investment in pandemic preparedness.

Methods

In this analysis of global health spending between 1990 and 2021, and prediction from 2021 to 2026, we estimated four sources of health spending: development assistance for health (DAH), government spending, out-of-pocket spending, and prepaid private spending across 204 countries and territories. We used the Organisation for Economic Co-operation and Development (OECD)'s Creditor Reporting System (CRS) and the WHO Global Health Expenditure Database (GHED) to estimate spending. We estimated development assistance for general health, COVID-19 response, and pandemic preparedness and response using a keyword search. Health spending estimates were combined with estimates of resources needed for pandemic prevention and preparedness to analyse future health spending patterns, relative to need.

Findings

In 2019, at the onset of the COVID-19 pandemic, US$9·2 trillion (95% uncertainty interval [UI] 9·1-9·3) was spent on health worldwide. We found great disparities in the amount of resources devoted to health, with high-income countries spending $7·3 trillion (95% UI 7·2-7·4) in 2019; 293·7 times the $24·8 billion (95% UI 24·3-25·3) spent by low-income countries in 2019. That same year, $43·1 billion in development assistance was provided to maintain or improve health. The pandemic led to an unprecedented increase in development assistance targeted towards health; in 2020 and 2021, $1·8 billion in DAH contributions was provided towards pandemic preparedness in LMICs, and $37·8 billion was provided for the health-related COVID-19 response. Although the support for pandemic preparedness is 12·2% of the recommended target by the High-Level Independent Panel (HLIP), the support provided for the health-related COVID-19 response is 252·2% of the recommended target. Additionally, projected spending estimates suggest that between 2022 and 2026, governments in 17 (95% UI 11-21) of the 137 LMICs will observe an increase in national government health spending equivalent to an addition of 1% of GDP, as recommended by the HLIP.

Interpretation

There was an unprecedented scale-up in DAH in 2020 and 2021. We have a unique opportunity at this time to sustain funding for crucial global health functions, including pandemic preparedness. However, historical patterns of underfunding of pandemic preparedness suggest that deliberate effort must be made to ensure funding is maintained.

Funding

Bill & Melinda Gates Foundation.",,pdf:http://www.thelancet.com/article/S2214109X23000074/pdf; doi:https://doi.org/10.1016/S2214-109X(23)00007-4; html:https://europepmc.org/articles/PMC9998276 37128097,https://doi.org/10.1038/s43016-020-0092-z,RETRACTED ARTICLE: Dietary metabotype modelling predicts individual responses to dietary interventions.,"Garcia-Perez I, Posma JM, Chambers ES, Mathers JC, Draper J, Beckmann M, Nicholson JK, Holmes E, Frost G.",,Nature food,2020,2020-06-17,N,,,,"Habitual consumption of poor quality diets is linked directly to risk factors for many non-communicable diseases. This has resulted in the vast majority of countries and the World Health Organization developing policies for healthy eating to reduce the prevalence of non-communicable diseases in the population. However, there is mounting evidence of variability in individual metabolic responses to any dietary intervention. We have developed a method for applying a pipeline for understanding interindividual differences in response to diet, based on coupling data from highly controlled dietary studies with deep metabolic phenotyping. In this feasibility study, we create an individual Dietary Metabotype Score (DMS) that embodies interindividual variability in dietary response and captures consequent dynamic changes in concentrations of urinary metabolites. We find an inverse relationship between the DMS and blood glucose concentration. There is also a relationship between the DMS and urinary metabolic energy loss. Furthermore, we use a metabolic entropy approach to visualize individual and collective responses to dietary interventions. Potentially, the DMS offers a method to target and to enhance dietary response at the individual level, thereby reducing the burden of non-communicable diseases at the population level.",,html:http://hdl.handle.net/10044/1/80100; doi:https://doi.org/10.1038/s43016-020-0092-z 32878619,https://doi.org/10.1186/s12916-020-01726-3,COVID-19 length of hospital stay: a systematic review and data synthesis.,"Rees EM, Nightingale ES, Jafari Y, Waterlow NR, Clifford S, B Pearson CA, Group CW, Jombart T, Procter SR, Knight GM.",,BMC medicine,2020,2020-09-03,Y,Length Of Stay; Hospitalisation; Icu Capacity; Covid-19; Sars-cov-2; Bed Demand,,,"

Background

The COVID-19 pandemic has placed an unprecedented strain on health systems, with rapidly increasing demand for healthcare in hospitals and intensive care units (ICUs) worldwide. As the pandemic escalates, determining the resulting needs for healthcare resources (beds, staff, equipment) has become a key priority for many countries. Projecting future demand requires estimates of how long patients with COVID-19 need different levels of hospital care.

Methods

We performed a systematic review of early evidence on length of stay (LoS) of patients with COVID-19 in hospital and in ICU. We subsequently developed a method to generate LoS distributions which combines summary statistics reported in multiple studies, accounting for differences in sample sizes. Applying this approach, we provide distributions for total hospital and ICU LoS from studies in China and elsewhere, for use by the community.

Results

We identified 52 studies, the majority from China (46/52). Median hospital LoS ranged from 4 to 53 days within China, and 4 to 21 days outside of China, across 45 studies. ICU LoS was reported by eight studies-four each within and outside China-with median values ranging from 6 to 12 and 4 to 19 days, respectively. Our summary distributions have a median hospital LoS of 14 (IQR 10-19) days for China, compared with 5 (IQR 3-9) days outside of China. For ICU, the summary distributions are more similar (median (IQR) of 8 (5-13) days for China and 7 (4-11) days outside of China). There was a visible difference by discharge status, with patients who were discharged alive having longer LoS than those who died during their admission, but no trend associated with study date.

Conclusion

Patients with COVID-19 in China appeared to remain in hospital for longer than elsewhere. This may be explained by differences in criteria for admission and discharge between countries, and different timing within the pandemic. In the absence of local data, the combined summary LoS distributions provided here can be used to model bed demands for contingency planning and then updated, with the novel method presented here, as more studies with aggregated statistics emerge outside China.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-020-01726-3; doi:https://doi.org/10.1186/s12916-020-01726-3; html:https://europepmc.org/articles/PMC7467845; pdf:https://europepmc.org/articles/PMC7467845?pdf=render 32724101,https://doi.org/10.1038/s41467-020-17477-x,Neonatal genetics of gene expression reveal potential origins of autoimmune and allergic disease risk.,"Huang QQ, Tang HHF, Teo SM, Mok D, Ritchie SC, Nath AP, Brozynska M, Salim A, Bakshi A, Holt BJ, Khor CC, Sly PD, Holt PG, Holt KE, Inouye M.",,Nature communications,2020,2020-07-28,Y,,,,"Chronic immune-mediated diseases of adulthood often originate in early childhood. To investigate genetic associations between neonatal immunity and disease, we map expression quantitative trait loci (eQTLs) in resting myeloid cells and CD4+ T cells from cord blood samples, as well as in response to lipopolysaccharide (LPS) or phytohemagglutinin (PHA) stimulation, respectively. Cis-eQTLs are largely specific to cell type or stimulation, and 31% and 52% of genes with cis-eQTLs have response eQTLs (reQTLs) in myeloid cells and T cells, respectively. We identified cis regulatory factors acting as mediators of trans effects. There is extensive colocalisation between condition-specific neonatal cis-eQTLs and variants associated with immune-mediated diseases, in particular CTSH had widespread colocalisation across diseases. Mendelian randomisation shows causal neonatal gene expression effects on disease risk for BTN3A2, HLA-C and others. Our study elucidates the genetics of gene expression in neonatal immune cells, and aetiological origins of autoimmune and allergic diseases.",,pdf:https://www.nature.com/articles/s41467-020-17477-x.pdf; doi:https://doi.org/10.1038/s41467-020-17477-x; html:https://europepmc.org/articles/PMC7387553; pdf:https://europepmc.org/articles/PMC7387553?pdf=render @@ -2108,12 +2108,12 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 35246709,https://doi.org/10.1007/s00127-022-02257-3,Ethnic inequalities in clozapine use among people with treatment-resistant schizophrenia: a retrospective cohort study using data from electronic clinical records.,"de Freitas DF, Patel I, Kadra-Scalzo G, Pritchard M, Shetty H, Broadbent M, Patel R, Downs J, Segev A, Khondoker M, MacCabe JH, Bhui K, Hayes RD.",,Social psychiatry and psychiatric epidemiology,2022,2022-03-04,Y,Clozapine; Health Inequalities; Benign Ethnic Neutropenia; Black British; Refractory Psychosis; Asian British,,,"

Purpose

Clozapine is the most effective intervention for treatment-resistant schizophrenia (TRS). Several studies report ethnic disparities in clozapine treatment. However, few studies restrict analyses to TRS cohorts alone or address confounding by benign ethnic neutropenia. This study investigates ethnic equity in access to clozapine treatment for people with treatment-resistant schizophrenia spectrum disorder.

Methods

A retrospective cohort study, using information from 11 years of clinical records (2007-2017) from the South London and Maudsley NHS Trust. We identified a cohort of service-users with TRS using a validated algorithm. We investigated associations between ethnicity and clozapine treatment, adjusting for sociodemographic factors, psychiatric multi-morbidity, substance misuse, neutropenia, and service-use.

Results

Among 2239 cases of TRS, Black service-users were less likely to be receive clozapine compared with White British service-users after adjusting for confounders (Black African aOR = 0.49, 95% CI [0.33, 0.74], p = 0.001; Black Caribbean aOR = 0.64, 95% CI [0.43, 0.93], p = 0.019; Black British aOR = 0.61, 95% CI [0.41, 0.91], p = 0.016). It was additionally observed that neutropenia was not related to treatment with clozapine. Also, a detention under the Mental Health Act was negatively associated clozapine receipt, suggesting people with TRS who were detained are less likely to be treated with clozapine.

Conclusion

Black service-users with TRS were less likely to receive clozapine than White British service-users. Considering the protective effect of treatment with clozapine, these inequities may place Black service-users at higher risk for hospital admissions and mortality.",,pdf:https://link.springer.com/content/pdf/10.1007/s00127-022-02257-3.pdf; doi:https://doi.org/10.1007/s00127-022-02257-3; html:https://europepmc.org/articles/PMC9246775; pdf:https://europepmc.org/articles/PMC9246775?pdf=render 36539756,https://doi.org/10.1186/s12888-022-04429-6,ADHD Remote Technology study of cardiometabolic risk factors and medication adherence (ART-CARMA): a multi-centre prospective cohort study protocol.,"Denyer H, Ramos-Quiroga JA, Folarin A, Ramos C, Nemeth P, Bilbow A, Woodward E, Whitwell S, Müller-Sedgwick U, Larsson H, Dobson RJ, Kuntsi J.",,BMC psychiatry,2022,2022-12-20,Y,ADHD; Cardiovascular disease; Attention Deficit Hyperactivity Disorder; Medication Adherence; Remote Monitoring; Mhealth; Digital Phenotyping; Remote Measurement Technology,,,"

Background

Emerging evidence points at substantial comorbidity between adult attention deficit hyperactivity disorder (ADHD) and cardiometabolic diseases, but our understanding of the comorbidity and how to manage cardiometabolic disease in adults with ADHD is limited. The ADHD Remote Technology study of cardiometabolic risk factors and medication adherence (ART-CARMA) project uses remote measurement technology to obtain real-world data from daily life to assess the extent to which ADHD medication treatment and physical activity, individually and jointly, may influence cardiometabolic risks in adults with ADHD. Our second main aim is to obtain valuable real-world data on adherence to pharmacological treatment and its predictors and correlates during daily life from adults with ADHD.

Methods

ART-CARMA is a multi-site prospective cohort study within the EU-funded collaboration 'TIMESPAN' (Management of chronic cardiometabolic disease and treatment discontinuity in adult ADHD patients) that will recruit 300 adults from adult ADHD waiting lists. The participants will be monitored remotely over a period of 12 months that starts from pre-treatment initiation. Passive monitoring, which involves the participants wearing a wrist-worn device (EmbracePlus) and downloading the RADAR-base Passive App and the Empatica Care App on their smartphone, provides ongoing data collection on a wide range of variables, such as physical activity, sleep, pulse rate (PR) and pulse rate variability (PRV), systolic peaks, electrodermal activity (EDA), oxygen saturation (SpO2), peripheral temperature, smartphone usage including social connectivity, and the environment (e.g. ambient noise, light levels, relative location). By combining data across these variables measured, processes such as physical activity, sleep, autonomic arousal, and indicators of cardiovascular health can be captured. Active remote monitoring involves the participant completing tasks using a smartphone app (such as completing clinical questionnaires or speech tasks), measuring their blood pressure and weight, or using a PC/laptop (cognitive tasks). The ART system is built on the RADAR-base mobile-health platform.

Discussion

The long-term goal is to use these data to improve the management of cardiometabolic disease in adults with ADHD, and to improve ADHD medication treatment adherence and the personalisation of treatment.",,pdf:https://bmcpsychiatry.biomedcentral.com/counter/pdf/10.1186/s12888-022-04429-6; doi:https://doi.org/10.1186/s12888-022-04429-6; html:https://europepmc.org/articles/PMC9764531; pdf:https://europepmc.org/articles/PMC9764531?pdf=render 30984759,https://doi.org/10.3389/fmed.2019.00048,"Direct-to-Consumer Genetic Testing's Red Herring: ""Genetic Ancestry"" and Personalized Medicine.","Blell M, Hunter MA.",,Frontiers in medicine,2019,2019-03-29,Y,RACE; Ethics; Ethnicity; Genetic Testing; Personalized Medicine,Understanding the Causes of Disease,,"The growth in the direct-to-consumer genetic testing industry poses a number of challenges for healthcare practice, among a number of other areas of concern. Several companies providing this service send their customers reports including information variously referred to as genetic ethnicity, genetic heritage, biogeographic ancestry, and genetic ancestry. In this article, we argue that such information should not be used in healthcare consultations or to assess health risks. Far from representing a move toward personalized medicine, use of this information poses risks both to patients as individuals and to racialized ethnic groups because of the way it misrepresents human genetic diversity.",,pdf:https://www.frontiersin.org/articles/10.3389/fmed.2019.00048/pdf; doi:https://doi.org/10.3389/fmed.2019.00048; html:https://europepmc.org/articles/PMC6449432; pdf:https://europepmc.org/articles/PMC6449432?pdf=render -36204496,https://doi.org/10.1177/23992026211048421,Beyond trust: Amplifying unheard voices on concerns about harm resulting from health data-sharing.,"Mulrine S, Blell M, Murtagh M.",,Medicine access @ point of care,2021,2021-01-01,Y,Data; Qualitative Methods; Data-sharing; Underrepresented Groups,,,"

Background

The point of care in many health systems is increasingly a point of health data generation, data which may be shared and used in a variety of ways by a range of different actors.

Aim

We set out to gather data about the perspectives on health data-sharing of people living in North East England who have been underrepresented within other public engagement activities and who are marginalized in society.

Methods

Multi-site ethnographic fieldwork was carried out in the Teesside region of England over a 6-month period in 2019 as part of a large-scale health data innovation program called Connected Health Cities. Organizations working with marginalized groups were contacted to recruit staff, volunteers, and beneficiaries for participation in qualitative research. The data gathered were analyzed thematically and vignettes constructed to illustrate findings.

Results

Previous encounters with health and social care professionals and the broader socio-political contexts of people's lives shape the perspectives of people from marginalized groups about sharing of data from their health records. While many would welcome improved care, the risks to people with socially produced vulnerabilities must be appreciated by those advocating systems that share data for personalized medicine or other forms of data-driven care.

Conclusion

Forms of innovation in medicine which rely on greater data-sharing may present risks to groups and individuals with existing vulnerabilities, and advocates of these innovations should address the lack of trustworthiness of those receiving data before asking that people trust new systems to provide health benefits.",,pdf:https://journals.sagepub.com/doi/pdf/10.1177/23992026211048421; doi:https://doi.org/10.1177/23992026211048421; html:https://europepmc.org/articles/PMC9413596; pdf:https://europepmc.org/articles/PMC9413596?pdf=render 31358974,https://doi.org/10.1038/s41562-019-0653-z,New alcohol-related genes suggest shared genetic mechanisms with neuropsychiatric disorders.,"Evangelou E, Gao H, Chu C, Ntritsos G, Blakeley P, Butts AR, Pazoki R, Suzuki H, Koskeridis F, Yiorkas AM, Karaman I, Elliott J, Luo Q, Aeschbacher S, Bartz TM, Baumeister SE, Braund PS, Brown MR, Brody JA, Clarke TK, Dimou N, Faul JD, Homuth G, Jackson AU, Kentistou KA, Joshi PK, Lemaitre RN, Lind PA, Lyytikäinen LP, Mangino M, Milaneschi Y, Nelson CP, Nolte IM, Perälä MM, Polasek O, Porteous D, Ratliff SM, Smith JA, Stančáková A, Teumer A, Tuominen S, Thériault S, Vangipurapu J, Whitfield JB, Wood A, Yao J, Yu B, Zhao W, Arking DE, Auvinen J, Liu C, Männikkö M, Risch L, Rotter JI, Snieder H, Veijola J, Blakemore AI, Boehnke M, Campbell H, Conen D, Eriksson JG, Grabe HJ, Guo X, van der Harst P, Hartman CA, Hayward C, Heath AC, Jarvelin MR, Kähönen M, Kardia SLR, Kühne M, Kuusisto J, Laakso M, Lahti J, Lehtimäki T, McIntosh AM, Mohlke KL, Morrison AC, Martin NG, Oldehinkel AJ, Penninx BWJH, Psaty BM, Raitakari OT, Rudan I, Samani NJ, Scott LJ, Spector TD, Verweij N, Weir DR, Wilson JF, Levy D, Tzoulaki I, Bell JD, Matthews PM, Rothenfluh A, Desrivières S, Schumann G, Elliott P.",,Nature human behaviour,2019,2019-07-29,N,,,,"Excessive alcohol consumption is one of the main causes of death and disability worldwide. Alcohol consumption is a heritable complex trait. Here we conducted a meta-analysis of genome-wide association studies of alcohol consumption (g d-1) from the UK Biobank, the Alcohol Genome-Wide Consortium and the Cohorts for Heart and Aging Research in Genomic Epidemiology Plus consortia, collecting data from 480,842 people of European descent to decipher the genetic architecture of alcohol intake. We identified 46 new common loci and investigated their potential functional importance using magnetic resonance imaging data and gene expression studies. We identify genetic pathways associated with alcohol consumption and suggest genetic mechanisms that are shared with neuropsychiatric disorders such as schizophrenia.",,pdf:https://boris.unibe.ch/174991/1/nihms-1649425.pdf; doi:https://doi.org/10.1038/s41562-019-0653-z; html:https://europepmc.org/articles/PMC7711277; pdf:https://europepmc.org/articles/PMC7711277?pdf=render; doi:https://doi.org/10.1038/s41562-019-0653-z +36204496,https://doi.org/10.1177/23992026211048421,Beyond trust: Amplifying unheard voices on concerns about harm resulting from health data-sharing.,"Mulrine S, Blell M, Murtagh M.",,Medicine access @ point of care,2021,2021-01-01,Y,Data; Qualitative Methods; Data-sharing; Underrepresented Groups,,,"

Background

The point of care in many health systems is increasingly a point of health data generation, data which may be shared and used in a variety of ways by a range of different actors.

Aim

We set out to gather data about the perspectives on health data-sharing of people living in North East England who have been underrepresented within other public engagement activities and who are marginalized in society.

Methods

Multi-site ethnographic fieldwork was carried out in the Teesside region of England over a 6-month period in 2019 as part of a large-scale health data innovation program called Connected Health Cities. Organizations working with marginalized groups were contacted to recruit staff, volunteers, and beneficiaries for participation in qualitative research. The data gathered were analyzed thematically and vignettes constructed to illustrate findings.

Results

Previous encounters with health and social care professionals and the broader socio-political contexts of people's lives shape the perspectives of people from marginalized groups about sharing of data from their health records. While many would welcome improved care, the risks to people with socially produced vulnerabilities must be appreciated by those advocating systems that share data for personalized medicine or other forms of data-driven care.

Conclusion

Forms of innovation in medicine which rely on greater data-sharing may present risks to groups and individuals with existing vulnerabilities, and advocates of these innovations should address the lack of trustworthiness of those receiving data before asking that people trust new systems to provide health benefits.",,pdf:https://journals.sagepub.com/doi/pdf/10.1177/23992026211048421; doi:https://doi.org/10.1177/23992026211048421; html:https://europepmc.org/articles/PMC9413596; pdf:https://europepmc.org/articles/PMC9413596?pdf=render 36208161,https://doi.org/10.1093/eurheartj/ehac426,CODE-EHR best practice framework for the use of structured electronic healthcare records in clinical research.,"Kotecha D, Asselbergs FW, Achenbach S, Anker SD, Atar D, Baigent C, Banerjee A, Beger B, Brobert G, Casadei B, Ceccarelli C, Cowie MR, Crea F, Cronin M, Denaxas S, Derix A, Fitzsimons D, Fredriksson M, Gale CP, Gkoutos GV, Goettsch W, Hemingway H, Ingvar M, Jonas A, Kazmierski R, Løgstrup S, Thomas Lumbers R, Lüscher TF, McGreavy P, Piña IL, Roessig L, Steinbeisser C, Sundgren M, Tyl B, van Thiel G, van Bochove K, Vardas PE, Villanueva T, Vrana M, Weber W, Weidinger F, Windecker S, Wood A, Grobbee DE, Innovative Medicines Initiative BigData@Heart Consortium, European Society of Cardiology, CODE-EHR international consensus group.",,European heart journal,2022,2022-10-01,Y,,,,"Big data is central to new developments in global clinical science aiming to improve the lives of patients. Technological advances have led to the routine use of structured electronic healthcare records with the potential to address key gaps in clinical evidence. The covid-19 pandemic has demonstrated the potential of big data and related analytics, but also important pitfalls. Verification, validation, and data privacy, as well as the social mandate to undertake research are key challenges. The European Society of Cardiology and the BigData@Heart consortium have brought together a range of international stakeholders, including patient representatives, clinicians, scientists, regulators, journal editors and industry. We propose the CODE-EHR Minimum Standards Framework as a means to improve the design of studies, enhance transparency and develop a roadmap towards more robust and effective utilisation of healthcare data for research purposes.",,pdf:https://academic.oup.com/eurheartj/article-pdf/43/37/3578/46535456/ehac426.pdf; doi:https://doi.org/10.1093/eurheartj/ehac426; html:https://europepmc.org/articles/PMC9452067; pdf:https://europepmc.org/articles/PMC9452067?pdf=render 34442458,https://doi.org/10.3390/jpm11080814,Reduced MIP-1β as a Trait Marker and Reduced IL-7 and IL-12 as State Markers of Anorexia Nervosa.,"Keeler JL, Patsalos O, Chung R, Schmidt U, Breen G, Treasure J, Himmerich H, Dalton B.",,Journal of personalized medicine,2021,2021-08-20,Y,Cytokines; Chemokines; Brain-derived neurotrophic factor; Anorexia Nervosa; cross-sectional; Inflammatory Markers,,,"Alterations in certain inflammatory markers have been found in individuals with anorexia nervosa (AN). However, their relation to clinical characteristics has not been extensively explored, nor is it clear whether they are trait or state features of the disorder. This cross-sectional study measured serum concentrations of 36 inflammatory markers in people with acute AN (n = 56), recovered AN (rec-AN; n = 24) and healthy controls (HC; n = 51). The relationship between body mass index (BMI), eating disorder psychopathology, depression symptoms and inflammatory markers was assessed. Statistical models controlled for variables known to influence cytokine concentrations (i.e., age, ethnicity, smoking status and medication usage). Overall, most inflammatory markers including pro-inflammatory cytokines were unchanged in AN and rec-AN. However, in AN and rec-AN, concentrations of macrophage inflammatory protein (MIP)-1β were lower than HCs. Interleukin (IL)-7 and IL-12/IL-23p40 were reduced in AN, and concentrations of macrophage-derived chemokine, MIP-1α and tumor necrosis factor-α were reduced in rec-AN compared to HC. In conclusion, a reduction in MIP-1β may be a trait marker of the illness, whereas reductions in IL-7 and IL-12/IL-23p40 may be state markers. The absence of increased pro-inflammatory cytokines in AN is contradictory to the wider literature, although the inclusion of covariates may explain our differing findings.",,pdf:https://www.mdpi.com/2075-4426/11/8/814/pdf?version=1629458822; doi:https://doi.org/10.3390/jpm11080814; html:https://europepmc.org/articles/PMC8399452; pdf:https://europepmc.org/articles/PMC8399452?pdf=render -38701403,https://doi.org/10.1212/wnl.0000000000209388,Patent Foramen Ovale Closure in Older Patients With Stroke: Patient Selection for Trial Feasibility.,"Wang AY, Rothwell PM, Nelson J, Saver JL, Kasner SE, Carroll J, Mas JL, Derumeaux G, Chatellier G, Furlan AJ, Herrmann HC, Jüni P, Kim JS, Koethe B, Lee PH, Lefebvre B, Mattle HP, Meier B, Reisman M, Smalling RW, Sondergaard L, Song JK, Di Angelantonio E, DiTullio M, Elkind MSV, Homma S, Jaigobin C, Michel P, Mono ML, Nedeltchev K, Papetti F, Serena J, Weimar C, Li L, Mazzucco S, Silver LE, van Klaveren D, Thaler DE, Kent DM.",,Neurology,2024,2024-05-03,N,,,,"

Background and objectives

Whether patent foramen ovale (PFO) closure benefits older patients with PFO and cryptogenic stroke is unknown because randomized controlled trials (RCTs) have predominantly enrolled patients younger than 60 years of age. Our objective was to estimate anticipated effects of PFO closure in older patients to predict the numbers needed to plan an RCT.

Methods

Effectiveness estimates are derived from major observational studies (Risk of Paradoxical Embolism [RoPE] Study and Oxford Vascular Study, together referred to as the ""RoPE-Ox"" database) and all 6 major RCTs (Systematic, Collaborative, PFO Closure Evaluation [SCOPE] Consortium). To estimate stroke recurrence risk, observed outcomes were calculated for patients older than 60 years in the age-inclusive observational databases (n = 549). To estimate the reduction in the rate of recurrent stroke associated with PFO closure vs medical therapy based on the RoPE score and the presence of high-risk PFO features, a Cox proportional hazards regression model was developed on the RCT data in the SCOPE database (n = 3,740). These estimates were used to calculate sample sizes required for a future RCT.

Results

Five-year risk of stroke recurrence using Kaplan-Meier estimates was 13.7 (95% CI 10.5-17.9) overall, 14.9% (95% CI 10.2-21.6) in those with high-risk PFO features. Predicted relative reduction in the event rate with PFO closure was 12.9% overall, 48.8% in those with a high-risk PFO feature. Using these estimates, enrolling all older patients with cryptogenic stroke and PFO would require much larger samples than those used for prior PFO closure trials, but selectively enrolling patients with high-risk PFO features would require totals of 630 patients for 90% power and 471 patients for 80% power, with an average of 5 years of follow-up.

Discussion

Based on our projections, anticipated effect sizes in older patients with high-risk features make a trial in these subjects feasible. With lengthening life expectancy in almost all regions of the world, the utility of PFO closure in older adults is increasingly important to explore.",,doi:https://doi.org/10.1212/WNL.0000000000209388 34167318,https://doi.org/10.1161/circulationaha.121.054302,Cardiac Troponin Thresholds and Kinetics to Differentiate Myocardial Injury and Myocardial Infarction.,"Wereski R, Kimenai DM, Taggart C, Doudesis D, Lee KK, Lowry MTH, Bularga A, Lowe DJ, Fujisawa T, Apple FS, Collinson PO, Anand A, Chapman AR, Mills NL.",,Circulation,2021,2021-06-25,Y,Kinetics; Troponin; Myocardial infarction; Predictive Value Of Tests,,,"

Background

Although the 99th percentile is the recommended diagnostic threshold for myocardial infarction, some guidelines also advocate the use of higher troponin thresholds to rule in myocardial infarction at presentation. It is unclear whether the magnitude or change in troponin concentration can differentiate causes of myocardial injury and infarction in practice.

Methods

In a secondary analysis of a multicenter randomized controlled trial, we identified 46 092 consecutive patients presenting with suspected acute coronary syndrome without ST-segment-elevation myocardial infarction. High-sensitivity cardiac troponin I concentrations at presentation and on serial testing were compared between patients with myocardial injury and infarction. The positive predictive value and specificity were determined at the sex-specific 99th percentile upper reference limit and rule-in thresholds of 64 ng/L and 5-fold of the upper reference limit for a diagnosis of type 1 myocardial infarction.

Results

Troponin was above the 99th percentile in 8188 patients (18%). The diagnosis was type 1 or type 2 myocardial infarction in 50% and 14% and acute or chronic myocardial injury in 20% and 16%, respectively. Troponin concentrations were similar at presentation in type 1 (median [25th-75th percentile] 91 [30-493] ng/L) and type 2 (50 [22-147] ng/L) myocardial infarction and in acute (50 [26-134] ng/L) and chronic (51 [31-130] ng/L) myocardial injury. The 99th percentile and rule-in thresholds of 64 ng/L and 5-fold upper reference limit gave a positive predictive value of 57% (95% CI, 56%-58%), 59% (58%-61%), and 62% (60%-64%) and a specificity of 96% (96%-96%), 96% (96%-96%), and 98% (97%-98%), respectively. The absolute, relative, and rate of change in troponin concentration were highest in patients with type 1 myocardial infarction (P<0.001 for all). Discrimination improved when troponin concentration and change in troponin were combined compared with troponin concentration at presentation alone (area under the curve, 0.661 [0.642-0.680] versus 0.613 [0.594-0.633]).

Conclusions

Although we observed important differences in the kinetics, cardiac troponin concentrations at presentation are insufficient to distinguish type 1 myocardial infarction from other causes of myocardial injury or infarction in practice and should not guide management decisions in isolation. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01852123.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCULATIONAHA.121.054302; doi:https://doi.org/10.1161/CIRCULATIONAHA.121.054302; html:https://europepmc.org/articles/PMC8360674; pdf:https://europepmc.org/articles/PMC8360674?pdf=render +38701403,https://doi.org/10.1212/wnl.0000000000209388,Patent Foramen Ovale Closure in Older Patients With Stroke: Patient Selection for Trial Feasibility.,"Wang AY, Rothwell PM, Nelson J, Saver JL, Kasner SE, Carroll J, Mas JL, Derumeaux G, Chatellier G, Furlan AJ, Herrmann HC, Jüni P, Kim JS, Koethe B, Lee PH, Lefebvre B, Mattle HP, Meier B, Reisman M, Smalling RW, Sondergaard L, Song JK, Di Angelantonio E, DiTullio M, Elkind MSV, Homma S, Jaigobin C, Michel P, Mono ML, Nedeltchev K, Papetti F, Serena J, Weimar C, Li L, Mazzucco S, Silver LE, van Klaveren D, Thaler DE, Kent DM.",,Neurology,2024,2024-05-03,N,,,,"

Background and objectives

Whether patent foramen ovale (PFO) closure benefits older patients with PFO and cryptogenic stroke is unknown because randomized controlled trials (RCTs) have predominantly enrolled patients younger than 60 years of age. Our objective was to estimate anticipated effects of PFO closure in older patients to predict the numbers needed to plan an RCT.

Methods

Effectiveness estimates are derived from major observational studies (Risk of Paradoxical Embolism [RoPE] Study and Oxford Vascular Study, together referred to as the ""RoPE-Ox"" database) and all 6 major RCTs (Systematic, Collaborative, PFO Closure Evaluation [SCOPE] Consortium). To estimate stroke recurrence risk, observed outcomes were calculated for patients older than 60 years in the age-inclusive observational databases (n = 549). To estimate the reduction in the rate of recurrent stroke associated with PFO closure vs medical therapy based on the RoPE score and the presence of high-risk PFO features, a Cox proportional hazards regression model was developed on the RCT data in the SCOPE database (n = 3,740). These estimates were used to calculate sample sizes required for a future RCT.

Results

Five-year risk of stroke recurrence using Kaplan-Meier estimates was 13.7 (95% CI 10.5-17.9) overall, 14.9% (95% CI 10.2-21.6) in those with high-risk PFO features. Predicted relative reduction in the event rate with PFO closure was 12.9% overall, 48.8% in those with a high-risk PFO feature. Using these estimates, enrolling all older patients with cryptogenic stroke and PFO would require much larger samples than those used for prior PFO closure trials, but selectively enrolling patients with high-risk PFO features would require totals of 630 patients for 90% power and 471 patients for 80% power, with an average of 5 years of follow-up.

Discussion

Based on our projections, anticipated effect sizes in older patients with high-risk features make a trial in these subjects feasible. With lengthening life expectancy in almost all regions of the world, the utility of PFO closure in older adults is increasingly important to explore.",,doi:https://doi.org/10.1212/WNL.0000000000209388 31204027,https://doi.org/10.1016/j.injury.2019.06.012,"Comparing the outcomes of isolated, serious traumatic brain injury in older adults managed at major trauma centres and neurosurgical services: A registry-based cohort study.","Dunn MS, Beck B, Simpson PM, Cameron PA, Kennedy M, Maiden M, Judson R, Gabbe BJ.",,Injury,2019,2019-06-10,N,Traumatic brain injury; Functional Outcome; Older Adult; Tbi; Trauma Systems,,,"

Background

The incidence of older adult traumatic brain injury (TBI) is increasing in both high and middle to low-income countries. It is unknown whether older adults with isolated, serious TBI can be safely managed outside of major trauma centres. This registry based cohort study aimed to compare mortality and functional outcomes of older adults with isolated, serious TBI who were managed at specialised Major Trauma Services (MTS) and Metropolitan Neurosurgical Services (MNS).

Method

Older adults (65 years and over) who sustained an isolated, serious TBI following a low fall (from standing or ≤ 1 m) were extracted from the Victorian State Trauma Registry from 2007 to 2016. Multivariable models were fitted to assess the association between hospital designation (MTS vs. MNS) and the two outcomes of interest: in-hospital mortality and functional outcome, adjusting for potential confounders. Functional outcomes were measured using the Glasgow Outcome Scale Extended at six months post-injury.

Results

From 2007-2016, there were 1904 older adults who sustained an isolated, serious TBI from a low fall who received definitive care at an MTS (n = 1124) or an MNS (n = 780). After adjusting for confounders, there was no mortality benefit for patients managed at an MTS over an MNS (OR = 0.84; 95% CI: 0.65, 1.08; P = 0.17) or improvement in functional outcome six months post-injury (OR = 1.13; 95% CI: 0.94, 1.36; P = 0.21).

Conclusion

For older adults with isolated, serious TBI following a low fall, there was no difference in mortality or functional outcome based on definitive management at an MTS or an MNS. This confirms that MNS without the added designation of a major trauma centre are a suitable destination for the management of isolated, serious TBI in older adults.",,doi:https://doi.org/10.1016/j.injury.2019.06.012 32327693,https://doi.org/10.1038/s42003-020-0921-5,Predicted loss and gain of function mutations in ACO1 are associated with erythropoiesis.,"Oskarsson GR, Oddsson A, Magnusson MK, Kristjansson RP, Halldorsson GH, Ferkingstad E, Zink F, Helgadottir A, Ivarsdottir EV, Arnadottir GA, Jensson BO, Katrinardottir H, Sveinbjornsson G, Kristinsdottir AM, Lee AL, Saemundsdottir J, Stefansdottir L, Sigurdsson JK, Davidsson OB, Benonisdottir S, Jonasdottir A, Jonasdottir A, Jonsson S, Gudmundsson RL, Asselbergs FW, Tragante V, Gunnarsson B, Masson G, Thorleifsson G, Rafnar T, Holm H, Olafsson I, Onundarson PT, Gudbjartsson DF, Norddahl GL, Thorsteinsdottir U, Sulem P, Stefansson K.",,Communications biology,2020,2020-04-23,Y,,,,"Hemoglobin is the essential oxygen-carrying molecule in humans and is regulated by cellular iron and oxygen sensing mechanisms. To search for novel variants associated with hemoglobin concentration, we performed genome-wide association studies of hemoglobin concentration using a combined set of 684,122 individuals from Iceland and the UK. Notably, we found seven novel variants, six rare coding and one common, at the ACO1 locus associating with either decreased or increased hemoglobin concentration. Of these variants, the missense Cys506Ser and the stop-gained Lys334Ter mutations are specific to eight and ten generation pedigrees, respectively, and have the two largest effects in the study (EffectCys506Ser = -1.61 SD, CI95 = [-1.98, -1.35]; EffectLys334Ter = 0.63 SD, CI95 = [0.36, 0.91]). We also find Cys506Ser to associate with increased risk of persistent anemia (OR = 17.1, P = 2 × 10-14). The strong bidirectional effects seen in this study implicate ACO1, a known iron sensing molecule, as a major homeostatic regulator of hemoglobin concentration.",,pdf:https://www.nature.com/articles/s42003-020-0921-5.pdf; doi:https://doi.org/10.1038/s42003-020-0921-5; html:https://europepmc.org/articles/PMC7181819; pdf:https://europepmc.org/articles/PMC7181819?pdf=render 36696816,https://doi.org/10.1016/j.ebiom.2023.104441,Causal effects of maternal circulating amino acids on offspring birthweight: a Mendelian randomisation study.,"Zhao J, Stewart ID, Baird D, Mason D, Wright J, Zheng J, Gaunt TR, Evans DM, Freathy RM, Langenberg C, Warrington NM, Lawlor DA, Borges MC, MR-PREG Consortium.",,EBioMedicine,2023,2023-01-23,Y,Amino acids; Gwas; Birthweight; Causal Effect; Mendelian Randomisation,,,"

Background

Amino acids are key to protein synthesis, energy metabolism, cell signaling and gene expression; however, the contribution of specific maternal amino acids to fetal growth is unclear.

Methods

We explored the effect of maternal circulating amino acids on fetal growth, proxied by birthweight, using two-sample Mendelian randomisation (MR) and summary data from a genome-wide association study (GWAS) of serum amino acids levels (sample 1, n = 86,507) and a maternal GWAS of offspring birthweight in UK Biobank and Early Growth Genetics Consortium, adjusting for fetal genotype effects (sample 2, n = 406,063 with maternal and/or fetal genotype effect estimates). A total of 106 independent single nucleotide polymorphisms robustly associated with 19 amino acids (p < 4.9 × 10-10) were used as genetic instrumental variables (IV). Wald ratio and inverse variance weighted methods were used in MR main analysis. A series of sensitivity analyses were performed to explore IV assumption violations.

Findings

Our results provide evidence that maternal circulating glutamine (59 g offspring birthweight increase per standard deviation increase in maternal amino acid level, 95% CI: 7, 110) and serine (27 g, 95% CI: 9, 46) raise, while leucine (-59 g, 95% CI: -106, -11) and phenylalanine (-25 g, 95% CI: -47, -4) lower offspring birthweight. These findings are supported by sensitivity analyses.

Interpretation

Our findings strengthen evidence for key roles of maternal circulating amino acids during pregnancy in healthy fetal growth.

Funding

A full list of funding bodies that contributed to this study can be found under Acknowledgments.",,doi:https://doi.org/10.1016/j.ebiom.2023.104441; doi:https://doi.org/10.1016/j.ebiom.2023.104441; html:https://europepmc.org/articles/PMC9879767; pdf:https://europepmc.org/articles/PMC9879767?pdf=render @@ -2138,11 +2138,11 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 36084617,https://doi.org/10.1016/j.ebiom.2022.104243,Machine learning integration of multimodal data identifies key features of blood pressure regulation.,"Louca P, Tran TQB, Toit CD, Christofidou P, Spector TD, Mangino M, Suhre K, Padmanabhan S, Menni C.",,EBioMedicine,2022,2022-09-06,Y,Diet; Blood pressure; Genomics; Metabolomics; Machine Learning,,,"

Background

Association studies have identified several biomarkers for blood pressure and hypertension, but a thorough understanding of their mutual dependencies is lacking. By integrating two different high-throughput datasets, biochemical and dietary data, we aim to understand the multifactorial contributors of blood pressure (BP).

Methods

We included 4,863 participants from TwinsUK with concurrent BP, metabolomics, genomics, biochemical measures, and dietary data. We used 5-fold cross-validation with the machine learning XGBoost algorithm to identify features of importance in context of one another in TwinsUK (80% training, 20% test). The features tested in TwinsUK were then probed using the same algorithm in an independent dataset of 2,807 individuals from the Qatari Biobank (QBB).

Findings

Our model explained 39·2% [4·5%, MAE:11·32 mmHg (95%CI, +/- 0·65)] of the variance in systolic BP (SBP) in TwinsUK. Of the top 50 features, the most influential non-demographic variables were dihomo-linolenate, cis-4-decenoyl carnitine, lactate, chloride, urate, and creatinine along with dietary intakes of total, trans and saturated fat. We also highlight the incremental value of each included dimension. Furthermore, we replicated our model in the QBB [SBP variance explained = 45·2% (13·39%)] cohort and 30 of the top 50 features overlapped between cohorts.

Interpretation

We show that an integrated analysis of omics, biochemical and dietary data improves our understanding of their in-between relationships and expands the range of potential biomarkers for blood pressure. Our results point to potentially key biological pathways to be prioritised for mechanistic studies.

Funding

Chronic Disease Research Foundation, Medical Research Council, Wellcome Trust, Qatar Foundation.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9463529; doi:https://doi.org/10.1016/j.ebiom.2022.104243; html:https://europepmc.org/articles/PMC9463529; pdf:https://europepmc.org/articles/PMC9463529?pdf=render 34740937,https://doi.org/10.1136/bmjopen-2021-056601,Analysis of mental and physical disorders associated with COVID-19 in online health forums: a natural language processing study.,"Patel R, Smeraldi F, Abdollahyan M, Irving J, Bessant C.",,BMJ open,2021,2021-11-05,Y,information technology; Health Informatics; Covid-19,,,"

Objectives

Online health forums provide rich and untapped real-time data on population health. Through novel data extraction and natural language processing (NLP) techniques, we characterise the evolution of mental and physical health concerns relating to the COVID-19 pandemic among online health forum users.

Setting and design

We obtained data from three leading online health forums: HealthBoards, Inspire and HealthUnlocked, from the period 1 January 2020 to 31 May 2020. Using NLP, we analysed the content of posts related to COVID-19.

Primary outcome measures

(1) Proportion of forum posts containing COVID-19 keywords; (2) proportion of forum users making their very first post about COVID-19; (3) proportion of COVID-19-related posts containing content related to physical and mental health comorbidities.

Results

Data from 739 434 posts created by 53 134 unique users were analysed. A total of 35 581 posts (4.8%) contained a COVID-19 keyword. Posts discussing COVID-19 and related comorbid disorders spiked in early March to mid-March around the time of global implementation of lockdowns prompting a large number of users to post on online health forums for the first time. Over a quarter of COVID-19-related thread titles mentioned a physical or mental health comorbidity.

Conclusions

We demonstrate that it is feasible to characterise the content of online health forum user posts regarding COVID-19 and measure changes over time. The pandemic and corresponding public response has had a significant impact on posters' queries regarding mental health. Social media data sources such as online health forums can be harnessed to strengthen population-level mental health surveillance.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/11/e056601.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-056601; html:https://europepmc.org/articles/PMC8573296; pdf:https://europepmc.org/articles/PMC8573296?pdf=render 34732839,https://doi.org/10.1038/s41379-021-00953-0,Stratification of chemotherapy-treated stage III colorectal cancer patients using multiplexed imaging and single-cell analysis of T-cell populations.,"Stachtea X, Loughrey MB, Salvucci M, Lindner AU, Cho S, McDonough E, Sood A, Graf J, Santamaria-Pang A, Corwin A, Laurent-Puig P, Dasgupta S, Shia J, Owens JR, Abate S, Van Schaeybroeck S, Lawler M, Prehn JHM, Ginty F, Longley DB.",,"Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc",2022,2021-11-03,Y,,,,"Colorectal cancer (CRC) has one of the highest cancer incidences and mortality rates. In stage III, postoperative chemotherapy benefits <20% of patients, while more than 50% will develop distant metastases. Biomarkers for identification of patients at increased risk of disease recurrence following adjuvant chemotherapy are currently lacking. In this study, we assessed immune signatures in the tumor and tumor microenvironment (TME) using an in situ multiplexed immunofluorescence imaging and single-cell analysis technology (Cell DIVETM) and evaluated their correlations with patient outcomes. Tissue microarrays (TMAs) with up to three 1 mm diameter cores per patient were prepared from 117 stage III CRC patients treated with adjuvant fluoropyrimidine/oxaliplatin (FOLFOX) chemotherapy. Single sections underwent multiplexed immunofluorescence staining for immune cell markers (CD45, CD3, CD4, CD8, FOXP3, PD1) and tumor/cell segmentation markers (DAPI, pan-cytokeratin, AE1, NaKATPase, and S6). We used annotations and a probabilistic classification algorithm to build statistical models of immune cell types. Images were also qualitatively assessed independently by a Pathologist as 'high', 'moderate' or 'low', for stromal and total immune cell content. Excellent agreement was found between manual assessment and total automated scores (p < 0.0001). Moreover, compared to single markers, a multi-marker classification of regulatory T cells (Tregs: CD3+/CD4+FOXP3+/PD1-) was significantly associated with disease-free survival (DFS) and overall survival (OS) (p = 0.049 and 0.032) of FOLFOX-treated patients. Our results also showed that PD1- Tregs rather than PD1+ Tregs were associated with improved survival. These findings were supported by results from an independent FOLFOX-treated cohort of 191 stage III CRC patients, where higher PD1- Tregs were associated with an increase overall survival (p = 0.015) for CD3+/CD4+/FOXP3+/PD1-. Overall, compared to single markers, multi-marker classification provided more accurate quantitation of immune cell types with stronger correlations with outcomes.",,pdf:https://www.nature.com/articles/s41379-021-00953-0.pdf; doi:https://doi.org/10.1038/s41379-021-00953-0; html:https://europepmc.org/articles/PMC8964416; pdf:https://europepmc.org/articles/PMC8964416?pdf=render -38296292,https://doi.org/10.1136/bmjopen-2023-078135,"Risk factor associations for severe COVID-19, influenza and pneumonia in people with diabetes to inform future pandemic preparations: UK population-based cohort study.","Hopkins R, Young KG, Thomas NJ, Godwin J, Raja D, Mateen BA, Challen RJ, Vollmer SJ, Shields BM, McGovern AP, Dennis JM.",,BMJ open,2024,2024-01-31,Y,risk factors; Electronic Health Records; Diabetes & Endocrinology; Covid-19,,,"

Objective

This study aimed to compare clinical and sociodemographic risk factors for severe COVID-19, influenza and pneumonia, in people with diabetes.

Design

Population-based cohort study.

Setting

UK primary care records (Clinical Practice Research Datalink) linked to mortality and hospital records.

Participants

Individuals with type 1 and type 2 diabetes (COVID-19 cohort: n=43 033 type 1 diabetes and n=584 854 type 2 diabetes, influenza and pneumonia cohort: n=42 488 type 1 diabetes and n=585 289 type 2 diabetes).

Primary and secondary outcome measures

COVID-19 hospitalisation from 1 February 2020 to 31 October 2020 (pre-COVID-19 vaccination roll-out), and influenza and pneumonia hospitalisation from 1 September 2016 to 31 May 2019 (pre-COVID-19 pandemic). Secondary outcomes were COVID-19 and pneumonia mortality. Associations between clinical and sociodemographic risk factors and each outcome were assessed using multivariable Cox proportional hazards models. In people with type 2 diabetes, we explored modifying effects of glycated haemoglobin (HbA1c) and body mass index (BMI) by age, sex and ethnicity.

Results

In type 2 diabetes, poor glycaemic control and severe obesity were consistently associated with increased risk of hospitalisation for COVID-19, influenza and pneumonia. The highest HbA1c and BMI-associated relative risks were observed in people aged under 70 years. Sociodemographic-associated risk differed markedly by respiratory infection, particularly for ethnicity. Compared with people of white ethnicity, black and south Asian groups had a greater risk of COVID-19 hospitalisation, but a lesser risk of pneumonia hospitalisation. Risk factor associations for type 1 diabetes and for type 2 diabetes mortality were broadly consistent with the primary analysis.

Conclusions

Clinical risk factors of high HbA1c and severe obesity are consistently associated with severe outcomes from COVID-19, influenza and pneumonia, especially in younger people. In contrast, associations with sociodemographic risk factors differed by type of respiratory infection. This emphasises that risk stratification should be specific to individual respiratory infections.",,doi:https://doi.org/10.1136/bmjopen-2023-078135; html:https://europepmc.org/articles/PMC10831438; pdf:https://europepmc.org/articles/PMC10831438?pdf=render -35211795,https://doi.org/10.1007/s00467-022-05440-5,Exploring the relevance of NUP93 variants in steroid-resistant nephrotic syndrome using next generation sequencing and a fly kidney model.,"Bierzynska A, Bull K, Miellet S, Dean P, Neal C, Colby E, McCarthy HJ, Hegde S, Sinha MD, Bugarin Diz C, Stirrups K, Megy K, Mapeta R, Penkett C, Marsh S, Forrester N, Afzal M, Stark H, BioResource N, Williams M, Welsh GI, Koziell AB, Hartley PS, Saleem MA.",,"Pediatric nephrology (Berlin, Germany)",2022,2022-02-24,Y,Podocyte; Fsgs; Srns; Nephrocyte; Nup93,,,"

Background

Variants in genes encoding nuclear pore complex (NPC) proteins are a newly identified cause of paediatric steroid-resistant nephrotic syndrome (SRNS). Recent reports describing NUP93 variants suggest these could be a significant cause of paediatric onset SRNS. We report NUP93 cases in the UK and demonstrate in vivo functional effects of Nup93 depletion in a fly (Drosophila melanogaster) nephrocyte model.

Methods

Three hundred thirty-seven paediatric SRNS patients from the National cohort of patients with Nephrotic Syndrome (NephroS) were whole exome and/or whole genome sequenced. Patients were screened for over 70 genes known to be associated with Nephrotic Syndrome (NS). D. melanogaster Nup93 knockdown was achieved by RNA interference using nephrocyte-restricted drivers.

Results

Six novel homozygous and compound heterozygous NUP93 variants were detected in 3 sporadic and 2 familial paediatric onset SRNS characterised histologically by focal segmental glomerulosclerosis (FSGS) and progressing to kidney failure by 12 months from clinical diagnosis. Silencing of the two orthologs of human NUP93 expressed in D. melanogaster, Nup93-1, and Nup93-2 resulted in significant signal reduction of up to 82% in adult pericardial nephrocytes with concomitant disruption of NPC protein expression. Additionally, nephrocyte morphology was highly abnormal in Nup93-1 and Nup93-2 silenced flies surviving to adulthood.

Conclusion

We expand the spectrum of NUP93 variants detected in paediatric onset SRNS and demonstrate its incidence within a national cohort. Silencing of either D. melanogaster Nup93 ortholog caused a severe nephrocyte phenotype, signaling an important role for the nucleoporin complex in podocyte biology. A higher resolution version of the Graphical abstract is available as Supplementary information.",,pdf:https://link.springer.com/content/pdf/10.1007/s00467-022-05440-5.pdf; doi:https://doi.org/10.1007/s00467-022-05440-5; html:https://europepmc.org/articles/PMC9489583; pdf:https://europepmc.org/articles/PMC9489583?pdf=render 31021418,https://doi.org/10.1111/bjd.18046,'It's like the bad guy in a movie who just doesn't die': a qualitative exploration of young people's adaptation to eczema and implications for self-care.,"Ghio D, Muller I, Greenwell K, Roberts A, McNiven A, Langan SM, Santer M.",,The British journal of dermatology,2020,2019-07-28,Y,,,,"

Background

Eczema is a common childhood inflammatory skin condition, affecting more than one in five children. A popular perception is that children 'outgrow eczema', although epidemiological studies have shown that, for many, eczema follows a lifelong episodic course.

Objectives

To explore the perceptions of young people about the nature of their eczema and how these perceptions relate to their self-care and adapting to living with eczema.

Methods

This is a secondary inductive thematic analysis of interviews conducted for Healthtalk.org. In total 23 interviews with young people with eczema were included. Of the 23 participants, 17 were female and six male, ranging from 17 to 25 years old.

Results

Participants generally experienced eczema as an episodic long-term condition and reported a mismatch between information received about eczema and their experiences. The experience of eczema as long term and episodic had implications for self-care, challenging the process of identifying triggers of eczema flare-ups and evaluating the success of treatment regimens. Participants' experiences of eczema over time also had implications for adaptation and finding a balance between accepting eczema as long term and hoping it would go away. This linked to a gradual shift in treatment expectations from 'cure' to 'control' of eczema.

Conclusions

For young people who continue to experience eczema beyond childhood, a greater focus on self-care for a long-term condition may be helpful. Greater awareness of the impact of early messages around 'growing out of' eczema and provision of high-quality information may help patients to manage expectations and support adaptation to treatment regimens. What's already known about this topic? There is a common perception that people 'grow out of' eczema, but for many people eczema follows a lifelong episodic course. Qualitative work has shown that parents can find that being told their child will grow out of eczema is dismissive, and that they have difficulty with messages about 'control not cure' of eczema. It is unclear how young people perceive their eczema and the implications of this perception for their adaptation and self-care. What does this study add? The message that many people 'grow out of' eczema has a potentially detrimental effect for young people where the condition persists. This has implications for young people's perceptions of their eczema, their learning to self-care and how they adapt to living with eczema and eczema treatments. What are the clinical implications of this work? Clinicians need to promote awareness among young people that eczema is a long-term episodic condition in order to engage them with effective self-care. Young people transitioning to self-care need evidence-based information that is specific and relatable to them.", ,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/bjd.18046; doi:https://doi.org/10.1111/bjd.18046; html:https://europepmc.org/articles/PMC6972719; pdf:https://europepmc.org/articles/PMC6972719?pdf=render -37221222,https://doi.org/10.1038/s41397-023-00307-w,SLCO1B1*5 is protective against non-senile cataracts in cohort prescribed statins: analysis in a British-South Asian cohort.,"Magavern EF, van Heel DA, Genes & Health Research Team, Smedley D, Caulfield MJ.",,The pharmacogenomics journal,2023,2023-05-23,Y,,,,"

Background

Reported association between statin use and cataract risk is controversial. The SLCO1B1 gene encodes a transport protein responsible for statin clearance. The aim of this study was to investigate a possible association between the SLCO1B1*5 reduced function variant and cataract risk in statin users of South Asian ethnicity.

Methods

The Genes & Health cohort consists of British-Bangladeshi and British-Pakistani participants from East London, Manchester and Bradford, UK. SLCO1B1*5 genotype was assessed with the Illumina GSAMD-24v3-0-EA chip. Medication data from primary care health record linkage was used to compare those who had regularly used statins compared to those who had not. Multivariable logistic regression was used to test for association between statin use and cataracts, adjusting for population characteristics and potential confounders in 36,513 participants. Multivariable logistic regression was used to test association between SLCO1B1*5 heterozygotes or homozygotes and cataracts, in subgroups having been regularly prescribed statins versus not.

Results

Statins were prescribed to 35% (12,704) of participants (average age 41 years old, 45% male). Non-senile cataract was diagnosed in 5% (1686) of participants. An apparent association between statins and non-senile cataract (12% in statin users and 0.8% in non-statin users) was negated by inclusion of confounders. In those prescribed a statin, presence of the SLCO1B1*5 genotype was independently associated with a decreased risk of non-senile cataract (OR 0.7 (CI 0.5-0.9, p 0.007)).

Conclusions

Our findings suggest that there is no independent association between statin use and non-senile cataract risk after adjusting for confounders. Among statin users, the SLCO1B1*5 genotype is associated with a 30% risk reduction of non-senile cataracts. Stratification of on-drug cohorts by validated pharmacogenomic variants is a useful tool to support or repudiate adverse drug events in observational cohorts.",,pdf:https://www.nature.com/articles/s41397-023-00307-w.pdf; doi:https://doi.org/10.1038/s41397-023-00307-w; html:https://europepmc.org/articles/PMC10506906; pdf:https://europepmc.org/articles/PMC10506906?pdf=render +35211795,https://doi.org/10.1007/s00467-022-05440-5,Exploring the relevance of NUP93 variants in steroid-resistant nephrotic syndrome using next generation sequencing and a fly kidney model.,"Bierzynska A, Bull K, Miellet S, Dean P, Neal C, Colby E, McCarthy HJ, Hegde S, Sinha MD, Bugarin Diz C, Stirrups K, Megy K, Mapeta R, Penkett C, Marsh S, Forrester N, Afzal M, Stark H, BioResource N, Williams M, Welsh GI, Koziell AB, Hartley PS, Saleem MA.",,"Pediatric nephrology (Berlin, Germany)",2022,2022-02-24,Y,Podocyte; Fsgs; Srns; Nephrocyte; Nup93,,,"

Background

Variants in genes encoding nuclear pore complex (NPC) proteins are a newly identified cause of paediatric steroid-resistant nephrotic syndrome (SRNS). Recent reports describing NUP93 variants suggest these could be a significant cause of paediatric onset SRNS. We report NUP93 cases in the UK and demonstrate in vivo functional effects of Nup93 depletion in a fly (Drosophila melanogaster) nephrocyte model.

Methods

Three hundred thirty-seven paediatric SRNS patients from the National cohort of patients with Nephrotic Syndrome (NephroS) were whole exome and/or whole genome sequenced. Patients were screened for over 70 genes known to be associated with Nephrotic Syndrome (NS). D. melanogaster Nup93 knockdown was achieved by RNA interference using nephrocyte-restricted drivers.

Results

Six novel homozygous and compound heterozygous NUP93 variants were detected in 3 sporadic and 2 familial paediatric onset SRNS characterised histologically by focal segmental glomerulosclerosis (FSGS) and progressing to kidney failure by 12 months from clinical diagnosis. Silencing of the two orthologs of human NUP93 expressed in D. melanogaster, Nup93-1, and Nup93-2 resulted in significant signal reduction of up to 82% in adult pericardial nephrocytes with concomitant disruption of NPC protein expression. Additionally, nephrocyte morphology was highly abnormal in Nup93-1 and Nup93-2 silenced flies surviving to adulthood.

Conclusion

We expand the spectrum of NUP93 variants detected in paediatric onset SRNS and demonstrate its incidence within a national cohort. Silencing of either D. melanogaster Nup93 ortholog caused a severe nephrocyte phenotype, signaling an important role for the nucleoporin complex in podocyte biology. A higher resolution version of the Graphical abstract is available as Supplementary information.",,pdf:https://link.springer.com/content/pdf/10.1007/s00467-022-05440-5.pdf; doi:https://doi.org/10.1007/s00467-022-05440-5; html:https://europepmc.org/articles/PMC9489583; pdf:https://europepmc.org/articles/PMC9489583?pdf=render +38296292,https://doi.org/10.1136/bmjopen-2023-078135,"Risk factor associations for severe COVID-19, influenza and pneumonia in people with diabetes to inform future pandemic preparations: UK population-based cohort study.","Hopkins R, Young KG, Thomas NJ, Godwin J, Raja D, Mateen BA, Challen RJ, Vollmer SJ, Shields BM, McGovern AP, Dennis JM.",,BMJ open,2024,2024-01-31,Y,risk factors; Electronic Health Records; Diabetes & Endocrinology; Covid-19,,,"

Objective

This study aimed to compare clinical and sociodemographic risk factors for severe COVID-19, influenza and pneumonia, in people with diabetes.

Design

Population-based cohort study.

Setting

UK primary care records (Clinical Practice Research Datalink) linked to mortality and hospital records.

Participants

Individuals with type 1 and type 2 diabetes (COVID-19 cohort: n=43 033 type 1 diabetes and n=584 854 type 2 diabetes, influenza and pneumonia cohort: n=42 488 type 1 diabetes and n=585 289 type 2 diabetes).

Primary and secondary outcome measures

COVID-19 hospitalisation from 1 February 2020 to 31 October 2020 (pre-COVID-19 vaccination roll-out), and influenza and pneumonia hospitalisation from 1 September 2016 to 31 May 2019 (pre-COVID-19 pandemic). Secondary outcomes were COVID-19 and pneumonia mortality. Associations between clinical and sociodemographic risk factors and each outcome were assessed using multivariable Cox proportional hazards models. In people with type 2 diabetes, we explored modifying effects of glycated haemoglobin (HbA1c) and body mass index (BMI) by age, sex and ethnicity.

Results

In type 2 diabetes, poor glycaemic control and severe obesity were consistently associated with increased risk of hospitalisation for COVID-19, influenza and pneumonia. The highest HbA1c and BMI-associated relative risks were observed in people aged under 70 years. Sociodemographic-associated risk differed markedly by respiratory infection, particularly for ethnicity. Compared with people of white ethnicity, black and south Asian groups had a greater risk of COVID-19 hospitalisation, but a lesser risk of pneumonia hospitalisation. Risk factor associations for type 1 diabetes and for type 2 diabetes mortality were broadly consistent with the primary analysis.

Conclusions

Clinical risk factors of high HbA1c and severe obesity are consistently associated with severe outcomes from COVID-19, influenza and pneumonia, especially in younger people. In contrast, associations with sociodemographic risk factors differed by type of respiratory infection. This emphasises that risk stratification should be specific to individual respiratory infections.",,doi:https://doi.org/10.1136/bmjopen-2023-078135; html:https://europepmc.org/articles/PMC10831438; pdf:https://europepmc.org/articles/PMC10831438?pdf=render 31950891,https://doi.org/10.1192/bjo.2019.96,Predicting high-cost care in a mental health setting.,"Colling C, Khondoker M, Patel R, Fok M, Harland R, Broadbent M, McCrone P, Stewart R.",,BJPsych open,2020,2020-01-17,Y,Prediction; Natural Language Processing; Mental Health Service; Digital Health Records,,,"

Background

The density of information in digital health records offers new potential opportunities for automated prediction of cost-relevant outcomes.

Aims

We investigated the extent to which routinely recorded data held in the electronic health record (EHR) predict priority service outcomes and whether natural language processing tools enhance the predictions. We evaluated three high priority outcomes: in-patient duration, readmission following in-patient care and high service cost after first presentation.

Method

We used data obtained from a clinical database derived from the EHR of a large mental healthcare provider within the UK. We combined structured data with text-derived data relating to diagnosis statements, medication and psychiatric symptomatology. Predictors of the three different clinical outcomes were modelled using logistic regression with performance evaluated against a validation set to derive areas under receiver operating characteristic curves.

Results

In validation samples, the full models (using all available data) achieved areas under receiver operating characteristic curves between 0.59 and 0.85 (in-patient duration 0.63, readmission 0.59, high service use 0.85). Adding natural language processing-derived data to the models increased the variance explained across all clinical scenarios (observed increase in r2 = 12-46%).

Conclusions

EHR data offer the potential to improve routine clinical predictions by utilising previously inaccessible data. Of our scenarios, prediction of high service use after initial presentation achieved the highest performance.","This study uses data from a mental healthcare provider to predict 3 things: 1) extended duration of stay in a hospital, 2) the likelihood of needing to be admitted to hospital again after discharge, and 3) likehood of needing 'high intesity service' (high cost services). The authors developed a natural language processing model (a computer system than aims to interpret text and draw out useful information) to review the text, diagnoses, medications and the patient symptoms to work out which patients would fall within those 3 categories. They conclude that their model could be used to improve services through predicting users who will require the most intense and costly care.",pdf:https://www.cambridge.org/core/services/aop-cambridge-core/content/view/6EF9FC74DC5A744C9D841DD649992ABE/S2056472419000966a.pdf/div-class-title-predicting-high-cost-care-in-a-mental-health-setting-div.pdf; doi:https://doi.org/10.1192/bjo.2019.96; html:https://europepmc.org/articles/PMC7001466; pdf:https://europepmc.org/articles/PMC7001466?pdf=render +37221222,https://doi.org/10.1038/s41397-023-00307-w,SLCO1B1*5 is protective against non-senile cataracts in cohort prescribed statins: analysis in a British-South Asian cohort.,"Magavern EF, van Heel DA, Genes & Health Research Team, Smedley D, Caulfield MJ.",,The pharmacogenomics journal,2023,2023-05-23,Y,,,,"

Background

Reported association between statin use and cataract risk is controversial. The SLCO1B1 gene encodes a transport protein responsible for statin clearance. The aim of this study was to investigate a possible association between the SLCO1B1*5 reduced function variant and cataract risk in statin users of South Asian ethnicity.

Methods

The Genes & Health cohort consists of British-Bangladeshi and British-Pakistani participants from East London, Manchester and Bradford, UK. SLCO1B1*5 genotype was assessed with the Illumina GSAMD-24v3-0-EA chip. Medication data from primary care health record linkage was used to compare those who had regularly used statins compared to those who had not. Multivariable logistic regression was used to test for association between statin use and cataracts, adjusting for population characteristics and potential confounders in 36,513 participants. Multivariable logistic regression was used to test association between SLCO1B1*5 heterozygotes or homozygotes and cataracts, in subgroups having been regularly prescribed statins versus not.

Results

Statins were prescribed to 35% (12,704) of participants (average age 41 years old, 45% male). Non-senile cataract was diagnosed in 5% (1686) of participants. An apparent association between statins and non-senile cataract (12% in statin users and 0.8% in non-statin users) was negated by inclusion of confounders. In those prescribed a statin, presence of the SLCO1B1*5 genotype was independently associated with a decreased risk of non-senile cataract (OR 0.7 (CI 0.5-0.9, p 0.007)).

Conclusions

Our findings suggest that there is no independent association between statin use and non-senile cataract risk after adjusting for confounders. Among statin users, the SLCO1B1*5 genotype is associated with a 30% risk reduction of non-senile cataracts. Stratification of on-drug cohorts by validated pharmacogenomic variants is a useful tool to support or repudiate adverse drug events in observational cohorts.",,pdf:https://www.nature.com/articles/s41397-023-00307-w.pdf; doi:https://doi.org/10.1038/s41397-023-00307-w; html:https://europepmc.org/articles/PMC10506906; pdf:https://europepmc.org/articles/PMC10506906?pdf=render 34937765,https://doi.org/10.1136/injuryprev-2021-044309,Predictors of health-related quality of life following injury in childhood and adolescence: a pooled analysis.,"Dipnall JF, Rivara FP, Lyons RA, Ameratunga S, Brussoni M, Lecky FE, Bradley C, Beck B, Lyons J, Schneeberg A, Harrison JE, Gabbe BJ.",,Injury prevention : journal of the International Society for Child and Adolescent Injury Prevention,2022,2021-12-22,N,Public Health; Disability; Longitudinal,,,"

Background

Injury is a leading contributor to the global disease burden in children and places children at risk for adverse and lasting impacts on their health-related quality of life (HRQoL) and development. This study aimed to identify key predictors of HRQoL following injury in childhood and adolescence.

Methods

Data from 2259 injury survivors (<18 years when injured) were pooled from four longitudinal cohort studies (Australia, Canada, UK, USA) from the paediatric Validating Injury Burden Estimates Study (VIBES-Junior). Outcomes were the Paediatric Quality of Life Inventory (PedsQL) total, physical, psychosocial functioning scores at 1, 3-4, 6, 12, 24 months postinjury.

Results

Mean PedsQL total score increased with higher socioeconomic status and decreased with increasing age. It was lower for transport-related incidents, ≥1 comorbidities, intentional injuries, spinal cord injury, vertebral column fracture, moderate/severe traumatic brain injury and fracture of patella/tibia/fibula/ankle. Mean PedsQL physical score was lower for females, fracture of femur, fracture of pelvis and burns. Mean PedsQL psychosocial score was lower for asphyxiation/non-fatal submersion and muscle/tendon/dislocation injuries.

Conclusions

Postinjury HRQoL was associated with survivors' socioeconomic status, intent, mechanism of injury and comorbidity status. Patterns of physical and psychosocial functioning postinjury differed according to sex and nature of injury sustained. The findings improve understanding of the long-term individual and societal impacts of injury in the early part of life and guide the prioritisation of prevention efforts, inform health and social service planning to help reduce injury burden, and help guide future Global Burden of Disease estimates.",,doi:https://doi.org/10.1136/injuryprev-2021-044309 34151246,https://doi.org/10.1016/j.cjco.2021.05.020,Cardiovascular and Renal Risk Factors and Complications Associated With COVID-19.,"Touyz RM, Boyd MOE, Guzik T, Padmanabhan S, McCallum L, Delles C, Mark PB, Petrie JR, Rios F, Montezano AC, Sykes R, Berry C.",,CJC open,2021,2021-06-16,Y,,,,"The current COVID-19 pandemic, caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) virus, represents the largest medical challenge in decades. It has exposed unexpected cardiovascular vulnerabilities at all stages of the disease (pre-infection, acute phase, and subsequent chronic phase). The major cardiometabolic drivers identified as having epidemiologic and mechanistic associations with COVID-19 are abnormal adiposity, dysglycemia, dyslipidemia, and hypertension. Hypertension is of particular interest, because components of the renin-angiotensin system (RAS), which are critically involved in the pathophysiology of hypertension, are also implicated in COVID-19. Specifically, angiotensin-converting enzyme-2 (ACE2), a multifunctional protein of the RAS, which is part of the protective axis of the RAS, is also the receptor through which SARS-CoV-2 enters host cells, causing viral infection. Cardiovascular and cardiometabolic comorbidities not only predispose people to COVID-19, but also are complications of SARS-CoV-2 infection. In addition, increasing evidence indicates that acute kidney injury is common in COVID-19, occurs early and in temporal association with respiratory failure, and is associated with poor prognosis, especially in the presence of cardiovascular risk factors. Here, we discuss cardiovascular and kidney disease in the context of COVID-19 and provide recent advances on putative pathophysiological mechanisms linking cardiovascular disease and COVID-19, focusing on the RAS and ACE2, as well as the immune system and inflammation. We provide up-to-date information on the relationships among hypertension, diabetes, and COVID-19 and emphasize the major cardiovascular diseases associated with COVID-19. We also briefly discuss emerging cardiovascular complications associated with long COVID-19, notably postural tachycardia syndrome (POTS).",,pdf:http://www.cjcopen.ca/article/S2589790X21001554/pdf; doi:https://doi.org/10.1016/j.cjco.2021.05.020; html:https://europepmc.org/articles/PMC8205551; pdf:https://europepmc.org/articles/PMC8205551?pdf=render 34441449,https://doi.org/10.3390/diagnostics11081516,Stability of OCT and OCTA in the Intensive Therapy Unit Setting.,"Courtie EF, Kale AU, Hui BTK, Liu X, Capewell NI, Bishop JRB, Whitehouse T, Veenith T, Logan A, Denniston AK, Blanch RJ.",,"Diagnostics (Basel, Switzerland)",2021,2021-08-23,Y,Stability; Critical Care; Optical Coherence Tomography Angiography,,,"To assess the stability of retinal structure and blood flow measures over time and in different clinical settings using portable optical coherence tomography angiography (OCTA) as a potential biomarker of central perfusion in critical illness, 18 oesophagectomy patients completed retinal structure and blood flow measurements by portable OCT and OCTA in the eye clinic and intensive therapy unit (ITU) across three timepoints: (1) pre-operation in a clinic setting; (2) 24-48 h post-operation during ITU admission; and (3) seven days post-operation, if the patient was still admitted. Blood flow and macular structural measures were stable between the examination settings, with no consistent variation between pre- and post-operation scans, while retinal nerve fibre layer thickness increased in the post-operative scans (+2.31 µm, p = 0.001). Foveal avascular zone (FAZ) measurements were the most stable, with an intraclass correlation coefficient of up to 0.92 for right eye FAZ area. Blood flow and structural measures were lower in left eyes than right eyes. Retinal blood flow assessed in patients before and during an ITU stay using portable OCTA showed no systematic differences between the clinical settings. The stability of retinal blood flow measures suggests the potential for portable OCTA to provide clinically useful measures in ITU patients.",,pdf:https://www.mdpi.com/2075-4418/11/8/1516/pdf?version=1629792973; doi:https://doi.org/10.3390/diagnostics11081516; html:https://europepmc.org/articles/PMC8394026; pdf:https://europepmc.org/articles/PMC8394026?pdf=render @@ -2158,20 +2158,20 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 34857859,https://doi.org/10.1038/s42003-021-02867-8,A computational exploration of resilience and evolvability of protein-protein interaction networks.,"Klein B, Holmér L, Smith KM, Johnson MM, Swain A, Stolp L, Teufel AI, Kleppe AS.",,Communications biology,2021,2021-12-02,Y,,,,"Protein-protein interaction (PPI) networks represent complex intra-cellular protein interactions, and the presence or absence of such interactions can lead to biological changes in an organism. Recent network-based approaches have shown that a phenotype's PPI network's resilience to environmental perturbations is related to its placement in the tree of life; though we still do not know how or why certain intra-cellular factors can bring about this resilience. Here, we explore the influence of gene expression and network properties on PPI networks' resilience. We use publicly available data of PPIs for E. coli, S. cerevisiae, and H. sapiens, where we compute changes in network resilience as new nodes (proteins) are added to the networks under three node addition mechanisms-random, degree-based, and gene-expression-based attachments. By calculating the resilience of the resulting networks, we estimate the effectiveness of these node addition mechanisms. We demonstrate that adding nodes with gene-expression-based preferential attachment (as opposed to random or degree-based) preserves and can increase the original resilience of PPI network in all three species, regardless of gene expression distribution or network structure. These findings introduce a general notion of prospective resilience, which highlights the key role of network structures in understanding the evolvability of phenotypic traits.",,pdf:https://www.nature.com/articles/s42003-021-02867-8.pdf; doi:https://doi.org/10.1038/s42003-021-02867-8; html:https://europepmc.org/articles/PMC8639913; pdf:https://europepmc.org/articles/PMC8639913?pdf=render 34455223,https://doi.org/10.1016/j.media.2021.102213,Medical image segmentation automatic quality control: A multi-dimensional approach.,"Fournel J, Bartoli A, Bendahan D, Guye M, Bernard M, Rauseo E, Khanji MY, Petersen SE, Jacquier A, Ghattas B.",,Medical image analysis,2021,2021-08-12,N,Deep Learning; Cmr Image Segmentation; Medical Image Segmentation Automatic Quality Control; Multi-dimensional Quality Control,,,"In clinical applications, using erroneous segmentations of medical images can have dramatic consequences. Current approaches dedicated to medical image segmentation automatic quality control do not predict segmentation quality at slice-level (2D), resulting in sub-optimal evaluations. Our 2D-based deep learning method simultaneously performs quality control at 2D-level and 3D-level for cardiovascular MR image segmentations. We compared it with 3D approaches by training both on 36,540 (2D) / 3842 (3D) samples to predict Dice Similarity Coefficients (DSC) for 4 different structures from the left ventricle, i.e., trabeculations (LVT), myocardium (LVM), papillary muscles (LVPM) and blood (LVC). The 2D-based method outperformed the 3D method. At the 2D-level, the mean absolute errors (MAEs) of the DSC predictions for 3823 samples, were 0.02, 0.02, 0.05 and 0.02 for LVM, LVC, LVT and LVPM, respectively. At the 3D-level, for 402 samples, the corresponding MAEs were 0.02, 0.01, 0.02 and 0.04. The method was validated in a clinical practice evaluation against semi-qualitative scores provided by expert cardiologists for 1016 subjects of the UK BioBank. Finally, we provided evidence that a multi-level QC could be used to enhance clinical measurements derived from image segmentations.",,pdf:http://manuscript.elsevier.com/S1361841521002589/pdf/S1361841521002589.pdf; doi:https://doi.org/10.1016/j.media.2021.102213 31504409,https://doi.org/10.1093/eurheartj/ehz587,The relation between systemic inflammation and incident cancer in patients with stable cardiovascular disease: a cohort study.,"Van't Klooster CC, Ridker PM, Hjortnaes J, van der Graaf Y, Asselbergs FW, Westerink J, Aerts JGJV, Visseren FLJ.",,European heart journal,2019,2019-12-01,Y,Risk factor; High-sensitive C-reactive Protein; Incident Cancer; Chronic Systemic Low-grade Inflammation; Patients With Vascular Disease,,,"

Aims

Low-grade inflammation, measured by elevated plasma concentrations of high-sensitive C-reactive protein (CRP), is a risk factor for cardiovascular disease (CVD). There is evidence that low-grade inflammation is also related to a higher risk of cancer. The present prospective cohort study evaluates the relation between low-grade systemic inflammation and risk of cancer in patients with stable CVD.

Methods and results

In total, 7178 patients with stable CVD and plasma CRP levels ≤10 mg/L were included. Data were linked to the Dutch national cancer registry. Cox regression models were fitted to study the relation between CRP and incident CVD and cancer. After a median follow-up time of 8.3 years (interquartile range 4.6-12.3) 1072 incident cancer diagnoses were observed. C-reactive protein concentration was related to total cancer [hazard ratio (HR) 1.35; 95% confidence interval (CI) 1.10-1.65] comparing last quintile to first quintile of CRP. Especially lung cancer, independent of histopathological subtype, was related to CRP (HR 3.39; 95% CI 2.02-5.69 comparing last to first quintile of CRP). Incidence of epithelial neoplasms and especially squamous cell neoplasms were related to CRP concentration, irrespective of anatomical location. Sensitivity analyses after excluding patients with a cancer diagnosis within 1, 2, and 5 years of follow-up showed similar results. No effect modification was observed by smoking status or time since smoking cessation (P-values for interaction > 0.05).

Conclusion

Chronic systemic low-grade inflammation, measured by CRP levels ≤10 mg/L, is a risk factor for incident cancer, markedly lung cancer, in patients with stable CVD. The relation between inflammation and incident cancer is seen in former and current smokers and is uncertain in never smokers.","Inflammation is a risk factor for cardiovascular disease (CVD) and is linked with a higher risk of cancer. This study investigates the relationship between inflammation and risk of cancer in patients with stable CVD. The study reports that low-grade inflammation, is a risk factor for incident cancer, markedly lung cancer, in patients with stable CVD.",pdf:https://academic.oup.com/eurheartj/article-pdf/40/48/3901/32523962/ehz587.pdf; doi:https://doi.org/10.1093/eurheartj/ehz587; html:https://europepmc.org/articles/PMC6925382; pdf:https://europepmc.org/articles/PMC6925382?pdf=render -37918923,https://doi.org/10.1136/bmjopen-2023-072531,Evaluation of variation in special educational needs provision and its impact on health and education using administrative records for England: umbrella protocol for a mixed-methods research programme.,"Zylbersztejn A, Lewis K, Nguyen V, Matthews J, Winterburn I, Karwatowska L, Barnes S, Lilliman M, Saxton J, Stone A, Boddy K, Downs J, Logan S, Rahi J, Black-Hawkins K, Dearden L, Ford T, Harron K, De Stavola B, Gilbert R.",,BMJ open,2023,2023-11-02,Y,epidemiology; Public Health; Qualitative Research; Health Informatics; Statistics & Research Methods; Health Equity,,,"

Introduction

One-third of children in England have special educational needs (SEN) provision recorded during their school career. The proportion of children with SEN provision varies between schools and demographic groups, which may reflect variation in need, inequitable provision and/or systemic factors. There is scant evidence on whether SEN provision improves health and education outcomes.

Methods

The Health Outcomes of young People in Education (HOPE) research programme uses administrative data from the Education and Child Health Insights from Linked Data-ECHILD-which contains data from all state schools, and contacts with National Health Service hospitals in England, to explore variation in SEN provision and its impact on health and education outcomes. This umbrella protocol sets out analyses across four work packages (WP). WP1 defined a range of 'health phenotypes', that is health conditions expected to need SEN provision in primary school. Next, we describe health and education outcomes (WP1) and individual, school-level and area-level factors affecting variation in SEN provision across different phenotypes (WP2). WP3 assesses the impact of SEN provision on health and education outcomes for specific health phenotypes using a range of causal inference methods to account for confounding factors and possible selection bias. In WP4 we review local policies and synthesise findings from surveys, interviews and focus groups of service users and providers to understand factors associated with variation in and experiences of identification, assessment and provision for SEN. Triangulation of findings on outcomes, variation and impact of SEN provision for different health phenotypes in ECHILD, with experiences of SEN provision will inform interpretation of findings for policy, practice and families and methods for future evaluation.

Ethics and dissemination

Research ethics committees have approved the use of the ECHILD database and, separately, the survey, interviews and focus groups of young people, parents and service providers. These stakeholders will contribute to the design, interpretation and communication of findings.",,doi:https://doi.org/10.1136/bmjopen-2023-072531; html:https://europepmc.org/articles/PMC10626865; pdf:https://europepmc.org/articles/PMC10626865?pdf=render 35353173,https://doi.org/10.1001/jamapsychiatry.2022.0407,Inflammation and Brain Structure in Schizophrenia and Other Neuropsychiatric Disorders: A Mendelian Randomization Study.,"Williams JA, Burgess S, Suckling J, Lalousis PA, Batool F, Griffiths SL, Palmer E, Karwath A, Barsky A, Gkoutos GV, Wood S, Barnes NM, David AS, Donohoe G, Neill JC, Deakin B, Khandaker GM, Upthegrove R, PIMS Collaboration.",,JAMA psychiatry,2022,2022-05-01,Y,,,,"

Importance

Previous in vitro and postmortem research suggests that inflammation may lead to structural brain changes via activation of microglia and/or astrocytic dysfunction in a range of neuropsychiatric disorders.

Objective

To investigate the relationship between inflammation and changes in brain structures in vivo and to explore a transcriptome-driven functional basis with relevance to mental illness.

Design, setting, and participants

This study used multistage linked analyses, including mendelian randomization (MR), gene expression correlation, and connectivity analyses. A total of 20 688 participants in the UK Biobank, which includes clinical, genomic, and neuroimaging data, and 6 postmortem brains from neurotypical individuals in the Allen Human Brain Atlas (AHBA), including RNA microarray data. Data were extracted in February 2021 and analyzed between March and October 2021.

Exposures

Genetic variants regulating levels and activity of circulating interleukin 1 (IL-1), IL-2, IL-6, C-reactive protein (CRP), and brain-derived neurotrophic factor (BDNF) were used as exposures in MR analyses.

Main outcomes and measures

Brain imaging measures, including gray matter volume (GMV) and cortical thickness (CT), were used as outcomes. Associations were considered significant at a multiple testing-corrected threshold of P < 1.1 × 10-4. Differential gene expression in AHBA data was modeled in brain regions mapped to areas significant in MR analyses; genes were tested for biological and disease overrepresentation in annotation databases and for connectivity in protein-protein interaction networks.

Results

Of 20 688 participants in the UK Biobank sample, 10 828 (52.3%) were female, and the mean (SD) age was 55.5 (7.5) years. In the UK Biobank sample, genetically predicted levels of IL-6 were associated with GMV in the middle temporal cortex (z score, 5.76; P = 8.39 × 10-9), inferior temporal (z score, 3.38; P = 7.20 × 10-5), fusiform (z score, 4.70; P = 2.60 × 10-7), and frontal (z score, -3.59; P = 3.30 × 10-5) cortex together with CT in the superior frontal region (z score, -5.11; P = 3.22 × 10-7). No significant associations were found for IL-1, IL-2, CRP, or BDNF after correction for multiple comparison. In the AHBA sample, 5 of 6 participants (83%) were male, and the mean (SD) age was 42.5 (13.4) years. Brain-wide coexpression analysis showed a highly interconnected network of genes preferentially expressed in the middle temporal gyrus (MTG), which further formed a highly connected protein-protein interaction network with IL-6 (enrichment test of expected vs observed network given the prevalence and degree of interactions in the STRING database: 43 nodes/30 edges observed vs 8 edges expected; mean node degree, 1.4; genome-wide significance, P = 4.54 × 10-9). MTG differentially expressed genes that were functionally enriched for biological processes in schizophrenia, autism spectrum disorder, and epilepsy.

Conclusions and relevance

In this study, genetically determined IL-6 was associated with brain structure and potentially affects areas implicated in developmental neuropsychiatric disorders, including schizophrenia and autism.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8968718; doi:https://doi.org/10.1001/jamapsychiatry.2022.0407; html:https://europepmc.org/articles/PMC8968718 +37918923,https://doi.org/10.1136/bmjopen-2023-072531,Evaluation of variation in special educational needs provision and its impact on health and education using administrative records for England: umbrella protocol for a mixed-methods research programme.,"Zylbersztejn A, Lewis K, Nguyen V, Matthews J, Winterburn I, Karwatowska L, Barnes S, Lilliman M, Saxton J, Stone A, Boddy K, Downs J, Logan S, Rahi J, Black-Hawkins K, Dearden L, Ford T, Harron K, De Stavola B, Gilbert R.",,BMJ open,2023,2023-11-02,Y,epidemiology; Public Health; Qualitative Research; Health Informatics; Statistics & Research Methods; Health Equity,,,"

Introduction

One-third of children in England have special educational needs (SEN) provision recorded during their school career. The proportion of children with SEN provision varies between schools and demographic groups, which may reflect variation in need, inequitable provision and/or systemic factors. There is scant evidence on whether SEN provision improves health and education outcomes.

Methods

The Health Outcomes of young People in Education (HOPE) research programme uses administrative data from the Education and Child Health Insights from Linked Data-ECHILD-which contains data from all state schools, and contacts with National Health Service hospitals in England, to explore variation in SEN provision and its impact on health and education outcomes. This umbrella protocol sets out analyses across four work packages (WP). WP1 defined a range of 'health phenotypes', that is health conditions expected to need SEN provision in primary school. Next, we describe health and education outcomes (WP1) and individual, school-level and area-level factors affecting variation in SEN provision across different phenotypes (WP2). WP3 assesses the impact of SEN provision on health and education outcomes for specific health phenotypes using a range of causal inference methods to account for confounding factors and possible selection bias. In WP4 we review local policies and synthesise findings from surveys, interviews and focus groups of service users and providers to understand factors associated with variation in and experiences of identification, assessment and provision for SEN. Triangulation of findings on outcomes, variation and impact of SEN provision for different health phenotypes in ECHILD, with experiences of SEN provision will inform interpretation of findings for policy, practice and families and methods for future evaluation.

Ethics and dissemination

Research ethics committees have approved the use of the ECHILD database and, separately, the survey, interviews and focus groups of young people, parents and service providers. These stakeholders will contribute to the design, interpretation and communication of findings.",,doi:https://doi.org/10.1136/bmjopen-2023-072531; html:https://europepmc.org/articles/PMC10626865; pdf:https://europepmc.org/articles/PMC10626865?pdf=render 37253531,https://doi.org/10.1136/bmjgh-2022-009997,Effectiveness of a multicomponent intervention to face the COVID-19 pandemic in Rio de Janeiro's favelas: difference-in-differences analysis.,"Batista-da-Silva AA, Moraes CB, Bozza HR, Bastos LDSL, Ranzani OT, Hamacher S, Bozza FA, Comitê Gestor Conexão Saúde.",,BMJ global health,2023,2023-05-01,Y,"Control strategies; Public Health; Intervention Study; Infections, Diseases, Disorders, Injuries; Covid-19",,,"

Introduction

Few community-based interventions addressing the transmission control and clinical management of COVID-19 cases have been reported, especially in poor urban communities from low-income and middle-income countries. Here, we analyse the impact of a multicomponent intervention that combines community engagement, mobile surveillance, massive testing and telehealth on COVID-19 cases detection and mortality rates in a large vulnerable community (Complexo da Maré) in Rio de Janeiro, Brazil.

Methods

We performed a difference-in-differences (DID) analysis to estimate the impact of the multicomponent intervention in Maré, before (March-August 2020) and after the intervention (September 2020 to April 2021), compared with equivalent local vulnerable communities. We applied a negative binomial regression model to estimate the intervention effect in weekly cases and mortality rates in Maré.

Results

Before the intervention, Maré presented lower rates of reported COVID-19 cases compared with the control group (1373 vs 1579 cases/100 000 population), comparable mortality rates (309 vs 287 deaths/100 000 population) and higher case fatality rates (13.7% vs 12.2%). After the intervention, Maré displayed a 154% (95% CI 138.6% to 170.4%) relative increase in reported case rates. Relative changes in reported death rates were -60% (95% CI -69.0% to -47.9%) in Maré and -28% (95% CI -42.0% to -9.8%) in the control group. The case fatality rate was reduced by 77% (95% CI -93.1% to -21.1%) in Maré and 52% (95% CI -81.8% to -29.4%) in the control group. The DID showed a reduction of 46% (95% CI 17% to 65%) of weekly reported deaths and an increased 23% (95% CI 5% to 44%) of reported cases in Maré after intervention onset.

Conclusion

An integrated intervention combining communication, surveillance and telehealth, with a strong community engagement component, could reduce COVID-19 mortality and increase case detection in a large vulnerable community in Rio de Janeiro. These findings show that investment in community-based interventions may reduce mortality and improve pandemic control in poor communities from low-income and middle-income countries.",,doi:https://doi.org/10.1136/bmjgh-2022-009997; doi:https://doi.org/10.1136/bmjgh-2022-009997; html:https://europepmc.org/articles/PMC10230340; pdf:https://europepmc.org/articles/PMC10230340?pdf=render 34371093,https://doi.org/10.1016/j.jaad.2021.07.066,The impact of psoriasis and sexual orientation on mental and physical health among adults in the United States.,"Mansh MD, Mulick A, Langan SM.",,Journal of the American Academy of Dermatology,2022,2021-08-08,Y,,,,,,doi:https://doi.org/10.1016/j.jaad.2021.07.066; doi:https://doi.org/10.1016/j.jaad.2021.07.066; html:https://europepmc.org/articles/PMC7612892; pdf:https://europepmc.org/articles/PMC7612892?pdf=render 34110679,https://doi.org/10.1002/1878-0261.13038,Cost-effectiveness of precision diagnostic testing for precision medicine approaches against non-small-cell lung cancer: A systematic review.,"Henderson R, Keeling P, French D, Smart D, Sullivan R, Lawler M.",,Molecular oncology,2021,2021-07-19,Y,Biomarker; Economic evaluation; non-small-cell lung cancer; Cost-effectiveness Analysis; Precision Medicine; Precision Diagnostic Test,,,"Precision diagnostic testing (PDT) employs appropriate biomarkers to identify cancer patients that may optimally respond to precision medicine (PM) approaches, such as treatments with targeted agents and immuno-oncology drugs. To date, there are no published systematic appraisals evaluating the cost-effectiveness of PDT in non-small-cell lung cancer (NSCLC). To address this gap, we conducted Preferred Reporting Items for Systematic Reviews and Meta-Analyses searches for the years 2009-2019. Consolidated Health Economic Evaluation Reporting Standards were employed to screen, assess and extract data. Employing base costs, life years gained or quality-adjusted life years, as well as willingness-to-pay (WTP) threshold for each country, net monetary benefit was calculated to determine cost-effectiveness of each intervention. Thirty-seven studies (50%) were included for analysis; a further 37 (50%) were excluded, having failed population-, intervention-, comparator-, outcomes- and study-design criteria. Within the 37 studies included, we defined 64 scenarios. Eleven scenarios compared PDT-guided PM with non-guided therapy [epidermal growth factor receptor (EGFR), n = 5; programmed death-ligand 1 (PD-L1), n = 6]. Twenty-eight scenarios compared PDT-guided PM with chemotherapy alone (anaplastic lymphoma kinase, n = 3; EGFR, n = 17; PD-L1, n = 8). Twenty-five scenarios compared PDT-guided PM with chemotherapy alone, while varying the PDT approach. Thirty-four scenarios (53%) were cost-effective, 28 (44%) were not cost-effective, and two were marginal, dependent on their country's WTP threshold. When PDT-guided therapy was compared with a therapy-for-all patients approach, all scenarios (100%) proved cost-effective. Seven of 37 studies had been structured appropriately to assess PDT-PM cost-effectiveness. Within these seven studies, all evaluated scenarios were cost-effective. However, 81% of studies had been poorly designed. Our systematic analysis implies that more robust health economic evaluation could help identify additional approaches towards PDT cost-effectiveness, underpinning value-based care and enhanced outcomes for patients with NSCLC.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/1878-0261.13038; doi:https://doi.org/10.1002/1878-0261.13038; html:https://europepmc.org/articles/PMC8486593; pdf:https://europepmc.org/articles/PMC8486593?pdf=render 36245269,https://doi.org/10.15252/embj.2022111857,Cryo-EM structures of perforin-2 in isolation and assembled on a membrane suggest a mechanism for pore formation.,"Yu X, Ni T, Munson G, Zhang P, Gilbert RJC.",,The EMBO journal,2022,2022-10-17,Y,Cryo-electron Tomography; Cryo-em; Subtomogram Averaging; Pore-forming Protein; Perforin-2,,,"Perforin-2 (PFN2, MPEG1) is a key pore-forming protein in mammalian innate immunity restricting intracellular bacteria proliferation. It forms a membrane-bound pre-pore complex that converts to a pore-forming structure upon acidification; but its mechanism of conformational transition has been debated. Here we used cryo-electron microscopy, tomography and subtomogram averaging to determine structures of PFN2 in pre-pore and pore conformations in isolation and bound to liposomes. In isolation and upon acidification, the pre-assembled complete pre-pore rings convert to pores in both flat ring and twisted conformations. On membranes, in situ assembled PFN2 pre-pores display various degrees of completeness; whereas PFN2 pores are mainly incomplete arc structures that follow the same subunit packing arrangements as found in isolation. Both assemblies on membranes use their P2 β-hairpin for binding to the lipid membrane surface. Overall, these structural snapshots suggest a molecular mechanism for PFN2 pre-pore to pore transition on a targeted membrane, potentially using the twisted pore as an intermediate or alternative state to the flat conformation, with the capacity to cause bilayer distortion during membrane insertion.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.15252/embj.2022111857; doi:https://doi.org/10.15252/embj.2022111857; html:https://europepmc.org/articles/PMC9713709; pdf:https://europepmc.org/articles/PMC9713709?pdf=render 35051442,https://doi.org/10.1016/j.jviromet.2022.114471,Reduced amplification efficiency of the RNA-dependent-RNA-polymerase target enables tracking of the Delta SARS-CoV-2 variant using routine diagnostic tests.,"Valley-Omar Z, Marais G, Iranzadeh A, Naidoo M, Korsman S, Maponga T, Hussey H, Davies MA, Boulle A, Doolabh D, Laubscher M, Wojno J, Deetlefs JD, Maritz J, Scott L, Msomi N, Naicker C, Tegally H, de Oliveira T, Bhiman J, Williamson C, Preiser W, Hardie D, Hsiao NY.",,Journal of virological methods,2022,2022-01-18,Y,Surveillance; Diagnostic test; South Africa; Covid-19; Sars-cov-2; Delta Variant,,,"Routine SARS-CoV-2 surveillance in the Western Cape region of South Africa (January-August 2021) found a reduced RT-PCR amplification efficiency of the RdRp-gene target of the Seegene, Allplex 2019-nCoV diagnostic assay from June 2021 when detecting the Delta variant. We investigated whether the reduced amplification efficiency denoted by an increased RT-PCR cycle threshold value (RΔE) can be used as an indirect measure of SARS-CoV-2 Delta variant prevalence. We found a significant increase in the median RΔE for patient samples tested from June 2021, which coincided with the emergence of the SARS-CoV-2 Delta variant within our sample set. Whole genome sequencing on a subset of patient samples identified a highly conserved G15451A, non-synonymous mutation exclusively within the RdRp gene of Delta variants, which may cause reduced RT-PCR amplification efficiency. While whole genome sequencing plays an important in identifying novel SARS-CoV-2 variants, monitoring RΔE value can serve as a useful surrogate for rapid tracking of Delta variant prevalence.",,doi:https://doi.org/10.1016/j.jviromet.2022.114471; doi:https://doi.org/10.1016/j.jviromet.2022.114471; html:https://europepmc.org/articles/PMC8763409; pdf:https://europepmc.org/articles/PMC8763409?pdf=render 32576090,https://doi.org/10.1161/strokeaha.120.029042,Telemedicine Cognitive Behavioral Therapy for Anxiety After Stroke: Proof-of-Concept Randomized Controlled Trial.,"Chun HY, Carson AJ, Tsanas A, Dennis MS, Mead GE, Calabria C, Whiteley WN.",,Stroke,2020,2020-06-24,Y,Stroke; Anxiety; Workflow; Telemedicine; psychotherapy,,,"

Background and purpose

Disabling anxiety affects a quarter of stroke survivors but access to treatment is poor. We developed a telemedicine model for delivering guided self-help cognitive behavioral therapy (CBT) for anxiety after stroke (TASK-CBT). We aimed to evaluate the feasibility of TASK-CBT in a randomized controlled trial workflow that enabled all trial procedures to be carried out remotely. In addition, we explored the feasibility of wrist-worn actigraphy sensor as a way of measuring objective outcomes in this clinical trial.

Methods

We recruited adult community-based stroke patients (n=27) and randomly allocated them to TASK-CBT (n=14) or relaxation therapy (TASK-Relax), an active comparator (n=13).

Results

In our sample (mean age 65 [±10]; 56% men; 63% stroke, 37% transient ischemic attacks), remote self-enrolment, electronic signature, intervention delivery, and automated follow-up were feasible. All participants completed all TASK-CBT sessions (14/14). Lower levels of anxiety were observed in TASK-CBT when compared with TASK-Relax at both weeks 6 and 20. Mean actigraphy sensor wearing-time was 33 days (±15).

Conclusions

Our preliminary feasibility data from the current study support a larger definitive clinical trial and the use of wrist-worn actigraphy sensor in anxious stroke survivors. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03439813.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/STROKEAHA.120.029042; doi:https://doi.org/10.1161/STROKEAHA.120.029042; html:https://europepmc.org/articles/PMC7382539; pdf:https://europepmc.org/articles/PMC7382539?pdf=render -35477868,https://doi.org/10.1136/bmjopen-2021-057579,Public opinion on sharing data from health services for clinical and research purposes without explicit consent: an anonymous online survey in the UK.,"Jones LA, Nelder JR, Fryer JM, Alsop PH, Geary MR, Prince M, Cardinal RN.",,BMJ open,2022,2022-04-27,Y,Information management; Mental health; Health Policy; Health Informatics,,,"

Objectives

UK National Health Service/Health and Social Care (NHS/HSC) data are variably shared between healthcare organisations for direct care, and increasingly de-identified for research. Few large-scale studies have examined public opinion on sharing, including of mental health (MH) versus physical health (PH) data. We measured data sharing preferences.

Design/setting/interventions/outcomes

Pre-registered anonymous online survey, measuring expressed preferences, recruiting February to September 2020. Participants were randomised to one of three framing statements regarding MH versus PH data.

Participants

Open to all UK residents. Participants numbered 29 275; 40% had experienced an MH condition.

Results

Most (76%) supported identifiable data sharing for direct clinical care without explicit consent, but 20% opposed this. Preference for clinical/identifiable sharing decreased with geographical distance and was slightly less for MH than PH data, with small framing effects. Preference for research/de-identified data sharing without explicit consent showed the same small PH/MH and framing effects, plus greater preference for sharing structured data than de-identified free text. There was net support for research sharing to the NHS, academic institutions, and national research charities, net ambivalence about sharing to profit-making companies researching treatments, and net opposition to sharing to other companies (similar to sharing publicly). De-identified linkage to non-health data was generally supported, except to data held by private companies. We report demographic influences on preference. A majority (89%) supported a single NHS mechanism to choose uses of their data. Support for data sharing increased during COVID-19.

Conclusions

Support for healthcare data sharing for direct care without explicit consent is broad but not universal. There is net support for the sharing of de-identified data for research to the NHS, academia, and the charitable sector, but not the commercial sector. A single national NHS-hosted system for patients to control the use of their NHS data for clinical purposes and for research would have broad support.

Trial registration number

ISRCTN37444142.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/4/e057579.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-057579; html:https://europepmc.org/articles/PMC9058801; pdf:https://europepmc.org/articles/PMC9058801?pdf=render 31748235,https://doi.org/10.1136/bmj.l6055,Association of troponin level and age with mortality in 250 000 patients: cohort study across five UK acute care centres.,"Kaura A, Panoulas V, Glampson B, Davies J, Mulla A, Woods K, Omigie J, Shah AD, Channon KM, Weber JN, Thursz MR, Elliott P, Hemingway H, Williams B, Asselbergs FW, O'Sullivan M, Kharbanda R, Lord GM, Melikian N, Patel RS, Perera D, Shah AM, Francis DP, Mayet J.",,BMJ (Clinical research ed.),2019,2019-11-20,Y,,,,"

Objective

To determine the relation between age and troponin level and its prognostic implication.

Design

Retrospective cohort study.

Setting

Five cardiovascular centres in the UK National Institute for Health Research Health Informatics Collaborative (UK-NIHR HIC).

Participants

257 948 consecutive patients undergoing troponin testing for any clinical reason between 2010 and 2017.

Main outcome measure

All cause mortality.

Results

257 948 patients had troponin measured during the study period. Analyses on troponin were performed using the peak troponin level, which was the highest troponin level measured during the patient's hospital stay. Troponin levels were standardised as a multiple of each laboratory's 99th centile of the upper limit of normal (ULN). During a median follow-up of 1198 days (interquartile range 514-1866 days), 55 850 (21.7%) deaths occurred. A positive troponin result (that is, higher than the upper limit of normal) signified a 3.2 higher mortality hazard (95% confidence interval 3.1 to 3.2) over three years. Mortality varied noticeably with age, with a hazard ratio of 10.6 (8.5 to 13.3) in 18-29 year olds and 1.5 (1.4 to 1.6) in those older than 90. A positive troponin result was associated with an approximately 15 percentage points higher absolute three year mortality across all age groups. The excess mortality with a positive troponin result was heavily concentrated in the first few weeks. Results were analysed using multivariable adjusted restricted cubic spline Cox regression. A direct relation was seen between troponin level and mortality in patients without acute coronary syndrome (ACS, n=120 049), whereas an inverted U shaped relation was found in patients with ACS (n=14 468), with a paradoxical decline in mortality at peak troponin levels >70×ULN. In the group with ACS, the inverted U shaped relation persisted after multivariable adjustment in those who were managed invasively; however, a direct positive relation was found between troponin level and mortality in patients managed non-invasively.

Conclusions

A positive troponin result was associated with a clinically important increased mortality, regardless of age, even if the level was only slightly above normal. The excess mortality with a raised troponin was heavily concentrated in the first few weeks.

Study registration

ClinicalTrials.gov NCT03507309.",Kaura et al. used a large database of about a quarter of a million patients who had toponin measurements and concluded that there was an association between positive troponin results and mortality regardless of age ,pdf:https://www.bmj.com/content/bmj/367/bmj.l6055.full.pdf; doi:https://doi.org/10.1136/bmj.l6055; html:https://europepmc.org/articles/PMC6865859 +35477868,https://doi.org/10.1136/bmjopen-2021-057579,Public opinion on sharing data from health services for clinical and research purposes without explicit consent: an anonymous online survey in the UK.,"Jones LA, Nelder JR, Fryer JM, Alsop PH, Geary MR, Prince M, Cardinal RN.",,BMJ open,2022,2022-04-27,Y,Information management; Mental health; Health Policy; Health Informatics,,,"

Objectives

UK National Health Service/Health and Social Care (NHS/HSC) data are variably shared between healthcare organisations for direct care, and increasingly de-identified for research. Few large-scale studies have examined public opinion on sharing, including of mental health (MH) versus physical health (PH) data. We measured data sharing preferences.

Design/setting/interventions/outcomes

Pre-registered anonymous online survey, measuring expressed preferences, recruiting February to September 2020. Participants were randomised to one of three framing statements regarding MH versus PH data.

Participants

Open to all UK residents. Participants numbered 29 275; 40% had experienced an MH condition.

Results

Most (76%) supported identifiable data sharing for direct clinical care without explicit consent, but 20% opposed this. Preference for clinical/identifiable sharing decreased with geographical distance and was slightly less for MH than PH data, with small framing effects. Preference for research/de-identified data sharing without explicit consent showed the same small PH/MH and framing effects, plus greater preference for sharing structured data than de-identified free text. There was net support for research sharing to the NHS, academic institutions, and national research charities, net ambivalence about sharing to profit-making companies researching treatments, and net opposition to sharing to other companies (similar to sharing publicly). De-identified linkage to non-health data was generally supported, except to data held by private companies. We report demographic influences on preference. A majority (89%) supported a single NHS mechanism to choose uses of their data. Support for data sharing increased during COVID-19.

Conclusions

Support for healthcare data sharing for direct care without explicit consent is broad but not universal. There is net support for the sharing of de-identified data for research to the NHS, academia, and the charitable sector, but not the commercial sector. A single national NHS-hosted system for patients to control the use of their NHS data for clinical purposes and for research would have broad support.

Trial registration number

ISRCTN37444142.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/4/e057579.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-057579; html:https://europepmc.org/articles/PMC9058801; pdf:https://europepmc.org/articles/PMC9058801?pdf=render 35386118,https://doi.org/10.3389/fnagi.2022.840651,Genome-Wide Association Study of Alzheimer's Disease Brain Imaging Biomarkers and Neuropsychological Phenotypes in the European Medical Information Framework for Alzheimer's Disease Multimodal Biomarker Discovery Dataset.,"Homann J, Osburg T, Ohlei O, Dobricic V, Deecke L, Bos I, Vandenberghe R, Gabel S, Scheltens P, Teunissen CE, Engelborghs S, Frisoni G, Blin O, Richardson JC, Bordet R, Lleó A, Alcolea D, Popp J, Clark C, Peyratout G, Martinez-Lage P, Tainta M, Dobson RJB, Legido-Quigley C, Sleegers K, Van Broeckhoven C, Wittig M, Franke A, Lill CM, Blennow K, Zetterberg H, Lovestone S, Streffer J, Ten Kate M, Vos SJB, Barkhof F, Visser PJ, Bertram L.",,Frontiers in aging neuroscience,2022,2022-03-21,Y,X chromosome; MRI; Imaging; Cognitive function; Genome-wide Association Study; Gwas; Alzheimer’s Disease (Ad),,,"Alzheimer's disease (AD) is the most frequent neurodegenerative disease with an increasing prevalence in industrialized, aging populations. AD susceptibility has an established genetic basis which has been the focus of a large number of genome-wide association studies (GWAS) published over the last decade. Most of these GWAS used dichotomized clinical diagnostic status, i.e., case vs. control classification, as outcome phenotypes, without the use of biomarkers. An alternative and potentially more powerful study design is afforded by using quantitative AD-related phenotypes as GWAS outcome traits, an analysis paradigm that we followed in this work. Specifically, we utilized genotype and phenotype data from n = 931 individuals collected under the auspices of the European Medical Information Framework for Alzheimer's Disease Multimodal Biomarker Discovery (EMIF-AD MBD) study to perform a total of 19 separate GWAS analyses. As outcomes we used five magnetic resonance imaging (MRI) traits and seven cognitive performance traits. For the latter, longitudinal data from at least two timepoints were available in addition to cross-sectional assessments at baseline. Our GWAS analyses revealed several genome-wide significant associations for the neuropsychological performance measures, in particular those assayed longitudinally. Among the most noteworthy signals were associations in or near EHBP1 (EH domain binding protein 1; on chromosome 2p15) and CEP112 (centrosomal protein 112; 17q24.1) with delayed recall as well as SMOC2 (SPARC related modular calcium binding 2; 6p27) with immediate recall in a memory performance test. On the X chromosome, which is often excluded in other GWAS, we identified a genome-wide significant signal near IL1RAPL1 (interleukin 1 receptor accessory protein like 1; Xp21.3). While polygenic score (PGS) analyses showed the expected strong associations with SNPs highlighted in relevant previous GWAS on hippocampal volume and cognitive function, they did not show noteworthy associations with recent AD risk GWAS findings. In summary, our study highlights the power of using quantitative endophenotypes as outcome traits in AD-related GWAS analyses and nominates several new loci not previously implicated in cognitive decline.",,pdf:https://www.frontiersin.org/articles/10.3389/fnagi.2022.840651/pdf; doi:https://doi.org/10.3389/fnagi.2022.840651; html:https://europepmc.org/articles/PMC8979334; pdf:https://europepmc.org/articles/PMC8979334?pdf=render 34244281,https://doi.org/10.1136/bmjopen-2021-049611,"Ethnicity and COVID-19 outcomes among healthcare workers in the UK: UK-REACH ethico-legal research, qualitative research on healthcare workers' experiences and stakeholder engagement protocol.","Gogoi M, Reed-Berendt R, Al-Oraibi A, Hassan O, Wobi F, Gupta A, Abubakar I, Dove E, Nellums LB, Pareek M, UK-REACH Collaborative Group.",,BMJ open,2021,2021-07-09,Y,Medical Ethics; Qualitative Research; Medical Law; Covid-19,,,"

Introduction

As the world continues to grapple with the COVID-19 pandemic, emerging evidence suggests that individuals from ethnic minority backgrounds may be disproportionately affected. The United Kingdom Research study into Ethnicity And COVID-19 outcomes in Healthcare workers (UK-REACH) project has been initiated to generate rapid evidence on whether and why ethnicity affects COVID-19 diagnosis and clinical outcomes in healthcare workers (HCWs) in the UK, through five interlinked work packages/work streams, three of which form the basis of this protocol. The ethico-legal work (Work Package 3) aims to understand and address legal, ethical and acceptability issues around big data research; the HCWs' experiences study (Work Package 4) explores their work and personal experiences, perceptions of risk, support and coping mechanisms; the stakeholder engagement work (Work Package 5) aims to provide feedback and support with the formulation and dissemination of the project recommendations.

Methods and analysis

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

Ethics and dissemination

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

Trial registration number

ISRCTN11811602.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/7/e049611.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-049611; html:https://europepmc.org/articles/PMC8275361; pdf:https://europepmc.org/articles/PMC8275361?pdf=render -33664493,https://doi.org/10.1038/s41591-021-01275-z,The need for ethical guidance for the use of patient-reported outcomes in research and clinical practice.,"Cruz Rivera S, Mercieca-Bebber R, Aiyegbusi OL, Scott J, Hunn A, Fernandez C, Ives J, Ells C, Price G, Draper H, Calvert MJ.",,Nature medicine,2021,2021-04-01,N,,,,,,pdf:https://www.nature.com/articles/s41591-021-01275-z.pdf; doi:https://doi.org/10.1038/s41591-021-01275-z 31675503,https://doi.org/10.1016/j.cell.2019.10.004,Uganda Genome Resource Enables Insights into Population History and Genomic Discovery in Africa.,"Gurdasani D, Carstensen T, Fatumo S, Chen G, Franklin CS, Prado-Martinez J, Bouman H, Abascal F, Haber M, Tachmazidou I, Mathieson I, Ekoru K, DeGorter MK, Nsubuga RN, Finan C, Wheeler E, Chen L, Cooper DN, Schiffels S, Chen Y, Ritchie GRS, Pollard MO, Fortune MD, Mentzer AJ, Garrison E, Bergström A, Hatzikotoulas K, Adeyemo A, Doumatey A, Elding H, Wain LV, Ehret G, Auer PL, Kooperberg CL, Reiner AP, Franceschini N, Maher D, Montgomery SB, Kadie C, Widmer C, Xue Y, Seeley J, Asiki G, Kamali A, Young EH, Pomilla C, Soranzo N, Zeggini E, Pirie F, Morris AP, Heckerman D, Tyler-Smith C, Motala AA, Rotimi C, Kaleebu P, Barroso I, Sandhu MS.",,Cell,2019,2019-10-01,N,,,,"Genomic studies in African populations provide unique opportunities to understand disease etiology, human diversity, and population history. In the largest study of its kind, comprising genome-wide data from 6,400 individuals and whole-genome sequences from 1,978 individuals from rural Uganda, we find evidence of geographically correlated fine-scale population substructure. Historically, the ancestry of modern Ugandans was best represented by a mixture of ancient East African pastoralists. We demonstrate the value of the largest sequence panel from Africa to date as an imputation resource. Examining 34 cardiometabolic traits, we show systematic differences in trait heritability between European and African populations, probably reflecting the differential impact of genes and environment. In a multi-trait pan-African GWAS of up to 14,126 individuals, we identify novel loci associated with anthropometric, hematological, lipid, and glycemic traits. We find that several functionally important signals are driven by Africa-specific variants, highlighting the value of studying diverse populations across the region.",,pdf:http://www.cell.com/article/S0092867419311201/pdf; doi:https://doi.org/10.1016/j.cell.2019.10.004; html:https://europepmc.org/articles/PMC7202134; pdf:https://europepmc.org/articles/PMC7202134?pdf=render; doi:https://doi.org/10.1016/j.cell.2019.10.004 +33664493,https://doi.org/10.1038/s41591-021-01275-z,The need for ethical guidance for the use of patient-reported outcomes in research and clinical practice.,"Cruz Rivera S, Mercieca-Bebber R, Aiyegbusi OL, Scott J, Hunn A, Fernandez C, Ives J, Ells C, Price G, Draper H, Calvert MJ.",,Nature medicine,2021,2021-04-01,N,,,,,,pdf:https://www.nature.com/articles/s41591-021-01275-z.pdf; doi:https://doi.org/10.1038/s41591-021-01275-z 36647047,https://doi.org/10.1186/s12916-022-02722-5,"Polypharmacy during pregnancy and associated risk factors: a retrospective analysis of 577 medication exposures among 1.5 million pregnancies in the UK, 2000-2019.","Subramanian A, Azcoaga-Lorenzo A, Anand A, Phillips K, Lee SI, Cockburn N, Fagbamigbe AF, Damase-Michel C, Yau C, McCowan C, O'Reilly D, Santorelli G, Hope H, Kennedy JI, Abel KM, Eastwood KA, Locock L, Black M, Loane M, Moss N, Plachcinski R, Thangaratinam S, Brophy S, Agrawal U, Vowles Z, Brocklehurst P, Dolk H, Nelson-Piercy C, Nirantharakumar K, MuM-PreDiCT Group.",,BMC medicine,2023,2023-01-16,Y,Pregnancy; Prescriptions; Polypharmacy; Medications; Multimorbidity; Multiple Medications; Multiple Long-term Conditions,,,"

Background

The number of medications prescribed during pregnancy has increased over the past few decades. Few studies have described the prevalence of multiple medication use among pregnant women. This study aims to describe the overall prevalence over the last two decades among all pregnant women and those with multimorbidity and to identify risk factors for polypharmacy in pregnancy.

Methods

A retrospective cohort study was conducted between 2000 and 2019 using the Clinical Practice Research Datalink (CPRD) pregnancy register. Prescription records for 577 medication categories were obtained. Prevalence estimates for polypharmacy (ranging from 2+ to 11+ medications) were presented along with the medications commonly prescribed individually and in pairs during the first trimester and the entire pregnancy period. Logistic regression models were performed to identify risk factors for polypharmacy.

Results

During the first trimester (812,354 pregnancies), the prevalence of polypharmacy ranged from 24.6% (2+ medications) to 0.1% (11+ medications). During the entire pregnancy period (774,247 pregnancies), the prevalence ranged from 58.7 to 1.4%. Broad-spectrum penicillin (6.6%), compound analgesics (4.5%) and treatment of candidiasis (4.3%) were commonly prescribed. Pairs of medication prescribed to manage different long-term conditions commonly included selective beta 2 agonists or selective serotonin re-uptake inhibitors (SSRIs). Risk factors for being prescribed 2+ medications during the first trimester of pregnancy include being overweight or obese [aOR: 1.16 (1.14-1.18) and 1.55 (1.53-1.57)], belonging to an ethnic minority group [aOR: 2.40 (2.33-2.47), 1.71 (1.65-1.76), 1.41 (1.35-1.47) and 1.39 (1.30-1.49) among women from South Asian, Black, other and mixed ethnicities compared to white women] and smoking or previously smoking [aOR: 1.19 (1.18-1.20) and 1.05 (1.03-1.06)]. Higher and lower age, higher gravidity, increasing number of comorbidities and increasing level of deprivation were also associated with increased odds of polypharmacy.

Conclusions

The prevalence of polypharmacy during pregnancy has increased over the past two decades and is particularly high in younger and older women; women with high BMI, smokers and ex-smokers; and women with multimorbidity, higher gravidity and higher levels of deprivation. Well-conducted pharmaco-epidemiological research is needed to understand the effects of multiple medication use on the developing foetus.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-022-02722-5; doi:https://doi.org/10.1186/s12916-022-02722-5; html:https://europepmc.org/articles/PMC9843951; pdf:https://europepmc.org/articles/PMC9843951?pdf=render 34732073,https://doi.org/10.1161/strokeaha.121.034787,"Risk, Clinical Course, and Outcome of Ischemic Stroke in Patients Hospitalized With COVID-19: A Multicenter Cohort Study.","Sluis WM, Linschoten M, Buijs JE, Biesbroek JM, den Hertog HM, Ribbers T, Nieuwkamp DJ, van Houwelingen RC, Dias A, van Uden IWM, Kerklaan JP, Bienfait HP, Vermeer SE, de Jong SW, Ali M, Wermer MJH, de Graaf MT, Brouwers PJAM, Asselbergs FW, Kappelle LJ, van der Worp HB, Algra AM, CAPACITY-COVID Collaborative Consortium*.",,Stroke,2021,2021-11-04,N,Intensive care units; Pulmonary embolism; incidence; Hospital Mortality; Patient Discharge; Covid-19,,,"

Background and purpose

The frequency of ischemic stroke in patients with coronavirus disease 2019 (COVID-19) varies in the current literature, and risk factors are unknown. We assessed the incidence, risk factors, and outcomes of acute ischemic stroke in hospitalized patients with COVID-19.

Methods

We included patients with a laboratory-confirmed SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2) infection admitted in 16 Dutch hospitals participating in the international CAPACITY-COVID registry between March 1 and August 1, 2020. Patients were screened for the occurrence of acute ischemic stroke. We calculated the cumulative incidence of ischemic stroke and compared risk factors, cardiovascular complications, and in-hospital mortality in patients with and without ischemic stroke.

Results

We included 2147 patients with COVID-19, of whom 586 (27.3%) needed treatment at an intensive care unit. Thirty-eight patients (1.8%) had an ischemic stroke. Patients with stroke were older but did not differ in sex or cardiovascular risk factors. Median time between the onset of COVID-19 symptoms and diagnosis of stroke was 2 weeks. The incidence of ischemic stroke was higher among patients who were treated at an intensive care unit (16/586; 2.7% versus nonintensive care unit, 22/1561; 1.4%; P=0.039). Pulmonary embolism was more common in patients with (8/38; 21.1%) than in those without stroke (160/2109; 7.6%; adjusted risk ratio, 2.08 [95% CI, 1.52-2.84]). Twenty-seven patients with ischemic stroke (71.1%) died during admission or were functionally dependent at discharge. Patients with ischemic stroke were at a higher risk of in-hospital mortality (adjusted risk ratio, 1.56 [95% CI, 1.13-2.15]) than patients without stroke.

Conclusions

In this multicenter cohort study, the cumulative incidence of acute ischemic stroke in hospitalized patients with COVID-19 was ≈2%, with a higher risk in patients treated at an intensive care unit. The majority of stroke patients had a poor outcome. The association between ischemic stroke and pulmonary embolism warrants further investigation.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/STROKEAHA.121.034787; doi:https://doi.org/10.1161/STROKEAHA.121.034787; html:https://europepmc.org/articles/PMC8607920; pdf:https://europepmc.org/articles/PMC8607920?pdf=render; doi:https://doi.org/10.1161/strokeaha.121.034787 31073125,https://doi.org/10.1038/s41533-019-0132-z,Systematic review of clinical prediction models to support the diagnosis of asthma in primary care.,"Daines L, McLean S, Buelo A, Lewis S, Sheikh A, Pinnock H.",,NPJ primary care respiratory medicine,2019,2019-05-09,Y,,The Human Phenome,,"Diagnosing asthma is challenging. Misdiagnosis can lead to untreated symptoms, incorrect treatment and avoidable deaths. The best combination of clinical features and tests to achieve a diagnosis of asthma is unclear. As asthma is usually diagnosed in non-specialist settings, a clinical prediction model to aid the assessment of the probability of asthma in primary care may improve diagnostic accuracy. We aimed to identify and describe existing prediction models to support the diagnosis of asthma in children and adults in primary care. We searched Medline, Embase, CINAHL, TRIP and US National Guidelines Clearinghouse databases from 1 January 1990 to 23 November 17. We included prediction models designed for use in primary care or equivalent settings to aid the diagnostic decision-making of clinicians assessing patients with symptoms suggesting asthma. Two reviewers independently screened titles, abstracts and full texts for eligibility, extracted data and assessed risk of bias. From 13,798 records, 53 full-text articles were reviewed. We included seven modelling studies; all were at high risk of bias. Model performance varied, and the area under the receiving operating characteristic curve ranged from 0.61 to 0.82. Patient-reported wheeze, symptom variability and history of allergy or allergic rhinitis were associated with asthma. In conclusion, clinical prediction models may support the diagnosis of asthma in primary care, but existing models are at high risk of bias and thus unreliable for informing practice. Future studies should adhere to recognised standards, conduct model validation and include a broader range of clinical data to derive a prediction model of value for clinicians.",,pdf:https://www.nature.com/articles/s41533-019-0132-z.pdf; doi:https://doi.org/10.1038/s41533-019-0132-z; html:https://europepmc.org/articles/PMC6509212; pdf:https://europepmc.org/articles/PMC6509212?pdf=render @@ -2204,8 +2204,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 32080192,https://doi.org/10.1038/s41467-020-14717-y,Author Correction: Genomic risk score offers predictive performance comparable to clinical risk factors for ischaemic stroke.,"Abraham G, Malik R, Yonova-Doing E, Salim A, Wang T, Danesh J, Butterworth AS, Howson JMM, Inouye M, Dichgans M.",,Nature communications,2020,2020-02-20,Y,,,,An amendment to this paper has been published and can be accessed via a link at the top of the paper.,,pdf:https://www.nature.com/articles/s41467-020-14717-y.pdf; doi:https://doi.org/10.1038/s41467-020-14717-y; html:https://europepmc.org/articles/PMC7033171; pdf:https://europepmc.org/articles/PMC7033171?pdf=render 33714592,https://doi.org/10.1016/j.mayocp.2021.02.007,"Place and Underlying Cause of Death During the COVID-19 Pandemic: Retrospective Cohort Study of 3.5 Million Deaths in England and Wales, 2014 to 2020.","Wu J, Mafham M, Mamas MA, Rashid M, Kontopantelis E, Deanfield JE, de Belder MA, Gale CP.",,Mayo Clinic proceedings,2021,2021-02-16,Y,,,,"

Objective

To describe the place and cause of death during the coronavirus disease 2019 (COVID-19) pandemic to assess its impact on excess mortality.

Methods

This national death registry included all adult (aged ≥18 years) deaths in England and Wales between January 1, 2014, and June 30, 2020. Daily deaths during the COVID-19 pandemic were compared against the expected daily deaths, estimated with use of the Farrington surveillance algorithm for daily historical data between 2014 and 2020 by place and cause of death.

Results

Between March 2 and June 30, 2020, there was an excess mortality of 57,860 (a proportional increase of 35%) compared with the expected deaths, of which 50,603 (87%) were COVID-19 related. At home, only 14% (2267) of the 16,190 excess deaths were related to COVID-19, with 5963 deaths due to cancer and 2485 deaths due to cardiac disease, few of which involved COVID-19. In care homes or hospices, 61% (15,623) of the 25,611 excess deaths were related to COVID-19, 5539 of which were due to respiratory disease, and most of these (4315 deaths) involved COVID-19. In the hospital, there were 16,174 fewer deaths than expected that did not involve COVID-19, with 4088 fewer deaths due to cancer and 1398 fewer deaths due to cardiac disease than expected.

Conclusion

The COVID-19 pandemic has resulted in a large excess of deaths in care homes that were poorly characterized and likely to be the result of undiagnosed COVID-19. There was a smaller but important and ongoing excess in deaths at home, particularly from cancer and cardiac disease, suggesting public avoidance of hospital care for non-COVID-19 conditions.",,pdf:http://www.mayoclinicproceedings.org/article/S0025619621001397/pdf; doi:https://doi.org/10.1016/j.mayocp.2021.02.007; html:https://europepmc.org/articles/PMC7885692; pdf:https://europepmc.org/articles/PMC7885692?pdf=render 33617936,https://doi.org/10.1016/j.jhin.2021.02.012,Global and national estimates of the number of healthcare workers at high risk of SARS-CoV-2 infection.,"McCarthy CV, Sandmann FG, CMMID COVID-19 Working Group, Jit M.",,The Journal of hospital infection,2021,2021-02-20,Y,,,,,,pdf:https://researchonline.lshtm.ac.uk/id/eprint/4660358/1/Global%20and%20national%20estimates%20of%20the%20number%20of%20healthcare%20workers%20at%20high%20risk%20of%20SARS-CoV-2%20infection.pdf; doi:https://doi.org/10.1016/j.jhin.2021.02.012; html:https://europepmc.org/articles/PMC7896121; pdf:https://europepmc.org/articles/PMC7896121?pdf=render -38448586,https://doi.org/10.1038/s41586-024-07148-y,Genome-wide characterization of circulating metabolic biomarkers.,"Karjalainen MK, Karthikeyan S, Oliver-Williams C, Sliz E, Allara E, Fung WT, Surendran P, Zhang W, Jousilahti P, Kristiansson K, Salomaa V, Goodwin M, Hughes DA, Boehnke M, Fernandes Silva L, Yin X, Mahajan A, Neville MJ, van Zuydam NR, de Mutsert R, Li-Gao R, Mook-Kanamori DO, Demirkan A, Liu J, Noordam R, Trompet S, Chen Z, Kartsonaki C, Li L, Lin K, Hagenbeek FA, Hottenga JJ, Pool R, Ikram MA, van Meurs J, Haller T, Milaneschi Y, Kähönen M, Mishra PP, Joshi PK, Macdonald-Dunlop E, Mangino M, Zierer J, Acar IE, Hoyng CB, Lechanteur YTE, Franke L, Kurilshikov A, Zhernakova A, Beekman M, van den Akker EB, Kolcic I, Polasek O, Rudan I, Gieger C, Waldenberger M, Asselbergs FW, China Kadoorie Biobank Collaborative Group, Estonian Biobank Research Team, FinnGen, Hayward C, Fu J, den Hollander AI, Menni C, Spector TD, Wilson JF, Lehtimäki T, Raitakari OT, Penninx BWJH, Esko T, Walters RG, Jukema JW, Sattar N, Ghanbari M, Willems van Dijk K, Karpe F, McCarthy MI, Laakso M, Järvelin MR, Timpson NJ, Perola M, Kooner JS, Chambers JC, van Duijn C, Slagboom PE, Boomsma DI, Danesh J, Ala-Korpela M, Butterworth AS, Kettunen J.",,Nature,2024,2024-03-06,Y,,,,"Genome-wide association analyses using high-throughput metabolomics platforms have led to novel insights into the biology of human metabolism1-7. This detailed knowledge of the genetic determinants of systemic metabolism has been pivotal for uncovering how genetic pathways influence biological mechanisms and complex diseases8-11. Here we present a genome-wide association study for 233 circulating metabolic traits quantified by nuclear magnetic resonance spectroscopy in up to 136,016 participants from 33 cohorts. We identify more than 400 independent loci and assign probable causal genes at two-thirds of these using manual curation of plausible biological candidates. We highlight the importance of sample and participant characteristics that can have significant effects on genetic associations. We use detailed metabolic profiling of lipoprotein- and lipid-associated variants to better characterize how known lipid loci and novel loci affect lipoprotein metabolism at a granular level. We demonstrate the translational utility of comprehensively phenotyped molecular data, characterizing the metabolic associations of intrahepatic cholestasis of pregnancy. Finally, we observe substantial genetic pleiotropy for multiple metabolic pathways and illustrate the importance of careful instrument selection in Mendelian randomization analysis, revealing a putative causal relationship between acetone and hypertension. Our publicly available results provide a foundational resource for the community to examine the role of metabolism across diverse diseases.",,pdf:https://www.nature.com/articles/s41586-024-07148-y.pdf; doi:https://doi.org/10.1038/s41586-024-07148-y; html:https://europepmc.org/articles/PMC10990933; pdf:https://europepmc.org/articles/PMC10990933?pdf=render 33430602,https://doi.org/10.1161/circheartfailure.120.007022,Proteomic and Functional Studies Reveal Detyrosinated Tubulin as Treatment Target in Sarcomere Mutation-Induced Hypertrophic Cardiomyopathy.,"Schuldt M, Pei J, Harakalova M, Dorsch LM, Schlossarek S, Mokry M, Knol JC, Pham TV, Schelfhorst T, Piersma SR, Dos Remedios C, Dalinghaus M, Michels M, Asselbergs FW, Moutin MJ, Carrier L, Jimenez CR, van der Velden J, Kuster DWD.",,Circulation. Heart failure,2021,2021-01-12,Y,Mutation; Genotype; Tubulin; Heart diseases; Proteomics; Treatment; Cardiomyopathies,,,"

Background

Hypertrophic cardiomyopathy (HCM) is the most common genetic heart disease. While ≈50% of patients with HCM carry a sarcomere gene mutation (sarcomere mutation-positive, HCMSMP), the genetic background is unknown in the other half of the patients (sarcomere mutation-negative, HCMSMN). Genotype-specific differences have been reported in cardiac function. Moreover, HCMSMN patients have later disease onset and a better prognosis than HCMSMP patients. To define if genotype-specific derailments at the protein level may explain the heterogeneity in disease development, we performed a proteomic analysis in cardiac tissue from a clinically well-phenotyped HCM patient group.

Methods

A proteomics screen was performed in cardiac tissue from 39 HCMSMP patients, 11HCMSMN patients, and 8 nonfailing controls. Patients with HCM had obstructive cardiomyopathy with left ventricular outflow tract obstruction and diastolic dysfunction. A novel MYBPC32373insG mouse model was used to confirm functional relevance of our proteomic findings.

Results

In all HCM patient samples, we found lower levels of metabolic pathway proteins and higher levels of extracellular matrix proteins. Levels of total and detyrosinated α-tubulin were markedly higher in HCMSMP than in HCMSMN and controls. Higher tubulin detyrosination was also found in 2 unrelated MYBPC3 mouse models and its inhibition with parthenolide normalized contraction and relaxation time of isolated cardiomyocytes.

Conclusions

Our findings indicate that microtubules and especially its detyrosination contribute to the pathomechanism of patients with HCMSMP. This is of clinical importance since it represents a potential treatment target to improve cardiac function in patients with HCMSMP, whereas a beneficial effect may be limited in patients with HCMSMN.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCHEARTFAILURE.120.007022; doi:https://doi.org/10.1161/CIRCHEARTFAILURE.120.007022; html:https://europepmc.org/articles/PMC7819533; pdf:https://europepmc.org/articles/PMC7819533?pdf=render +38448586,https://doi.org/10.1038/s41586-024-07148-y,Genome-wide characterization of circulating metabolic biomarkers.,"Karjalainen MK, Karthikeyan S, Oliver-Williams C, Sliz E, Allara E, Fung WT, Surendran P, Zhang W, Jousilahti P, Kristiansson K, Salomaa V, Goodwin M, Hughes DA, Boehnke M, Fernandes Silva L, Yin X, Mahajan A, Neville MJ, van Zuydam NR, de Mutsert R, Li-Gao R, Mook-Kanamori DO, Demirkan A, Liu J, Noordam R, Trompet S, Chen Z, Kartsonaki C, Li L, Lin K, Hagenbeek FA, Hottenga JJ, Pool R, Ikram MA, van Meurs J, Haller T, Milaneschi Y, Kähönen M, Mishra PP, Joshi PK, Macdonald-Dunlop E, Mangino M, Zierer J, Acar IE, Hoyng CB, Lechanteur YTE, Franke L, Kurilshikov A, Zhernakova A, Beekman M, van den Akker EB, Kolcic I, Polasek O, Rudan I, Gieger C, Waldenberger M, Asselbergs FW, China Kadoorie Biobank Collaborative Group, Estonian Biobank Research Team, FinnGen, Hayward C, Fu J, den Hollander AI, Menni C, Spector TD, Wilson JF, Lehtimäki T, Raitakari OT, Penninx BWJH, Esko T, Walters RG, Jukema JW, Sattar N, Ghanbari M, Willems van Dijk K, Karpe F, McCarthy MI, Laakso M, Järvelin MR, Timpson NJ, Perola M, Kooner JS, Chambers JC, van Duijn C, Slagboom PE, Boomsma DI, Danesh J, Ala-Korpela M, Butterworth AS, Kettunen J.",,Nature,2024,2024-03-06,Y,,,,"Genome-wide association analyses using high-throughput metabolomics platforms have led to novel insights into the biology of human metabolism1-7. This detailed knowledge of the genetic determinants of systemic metabolism has been pivotal for uncovering how genetic pathways influence biological mechanisms and complex diseases8-11. Here we present a genome-wide association study for 233 circulating metabolic traits quantified by nuclear magnetic resonance spectroscopy in up to 136,016 participants from 33 cohorts. We identify more than 400 independent loci and assign probable causal genes at two-thirds of these using manual curation of plausible biological candidates. We highlight the importance of sample and participant characteristics that can have significant effects on genetic associations. We use detailed metabolic profiling of lipoprotein- and lipid-associated variants to better characterize how known lipid loci and novel loci affect lipoprotein metabolism at a granular level. We demonstrate the translational utility of comprehensively phenotyped molecular data, characterizing the metabolic associations of intrahepatic cholestasis of pregnancy. Finally, we observe substantial genetic pleiotropy for multiple metabolic pathways and illustrate the importance of careful instrument selection in Mendelian randomization analysis, revealing a putative causal relationship between acetone and hypertension. Our publicly available results provide a foundational resource for the community to examine the role of metabolism across diverse diseases.",,pdf:https://www.nature.com/articles/s41586-024-07148-y.pdf; doi:https://doi.org/10.1038/s41586-024-07148-y; html:https://europepmc.org/articles/PMC10990933; pdf:https://europepmc.org/articles/PMC10990933?pdf=render 35605170,https://doi.org/10.2196/37668,Differences in Clinical Presentation With Long COVID After Community and Hospital Infection and Associations With All-Cause Mortality: English Sentinel Network Database Study.,"Meza-Torres B, Delanerolle G, Okusi C, Mayor N, Anand S, Macartney J, Gatenby P, Glampson B, Chapman M, Curcin V, Mayer E, Joy M, Greenhalgh T, Delaney B, de Lusignan S.",,JMIR public health and surveillance,2022,2022-08-16,Y,Phenotype; Hospitalization; Social Class; General Practitioners; Ethnicity; Medical Record Systems; Covid-19; Sars-cov-2; Systematized Nomenclature Of Medicine; Biomedical Ontologies; Post–acute Covid-19 Syndrome; Data Extracts; Computerized; Data Accuracy; Long Covid; Post–covid-19 Syndrome,,,"

Background

Most studies of long COVID (symptoms of COVID-19 infection beyond 4 weeks) have focused on people hospitalized in their initial illness. Long COVID is thought to be underrecorded in UK primary care electronic records.

Objective

We sought to determine which symptoms people present to primary care after COVID-19 infection and whether presentation differs in people who were not hospitalized, as well as post-long COVID mortality rates.

Methods

We used routine data from the nationally representative primary care sentinel cohort of the Oxford-Royal College of General Practitioners Research and Surveillance Centre (N=7,396,702), applying a predefined long COVID phenotype and grouped by whether the index infection occurred in hospital or in the community. We included COVID-19 infection cases from March 1, 2020, to April 1, 2021. We conducted a before-and-after analysis of long COVID symptoms prespecified by the Office of National Statistics, comparing symptoms presented between 1 and 6 months after the index infection matched with the same months 1 year previously. We conducted logistic regression analysis, quoting odds ratios (ORs) with 95% CIs.

Results

In total, 5.63% (416,505/7,396,702) and 1.83% (7623/416,505) of the patients had received a coded diagnosis of COVID-19 infection and diagnosis of, or referral for, long COVID, respectively. People with diagnosis or referral of long COVID had higher odds of presenting the prespecified symptoms after versus before COVID-19 infection (OR 2.66, 95% CI 2.46-2.88, for those with index community infection and OR 2.42, 95% CI 2.03-2.89, for those hospitalized). After an index community infection, patients were more likely to present with nonspecific symptoms (OR 3.44, 95% CI 3.00-3.95; P<.001) compared with after a hospital admission (OR 2.09, 95% CI 1.56-2.80; P<.001). Mental health sequelae were more strongly associated with index hospital infections (OR 2.21, 95% CI 1.64-2.96) than with index community infections (OR 1.36, 95% CI 1.21-1.53; P<.001). People presenting to primary care after hospital infection were more likely to be men (OR 1.43, 95% CI 1.25-1.64; P<.001), more socioeconomically deprived (OR 1.42, 95% CI 1.24-1.63; P<.001), and with higher multimorbidity scores (OR 1.41, 95% CI 1.26-1.57; P<.001) than those presenting after an index community infection. All-cause mortality in people with long COVID was associated with increasing age, male sex (OR 3.32, 95% CI 1.34-9.24; P=.01), and higher multimorbidity score (OR 2.11, 95% CI 1.34-3.29; P<.001). Vaccination was associated with reduced odds of mortality (OR 0.10, 95% CI 0.03-0.35; P<.001).

Conclusions

The low percentage of people recorded as having long COVID after COVID-19 infection reflects either low prevalence or underrecording. The characteristics and comorbidities of those presenting with long COVID after a community infection are different from those hospitalized. This study provides insights into the presentation of long COVID in primary care and implications for workload.",,pdf:https://publichealth.jmir.org/2022/8/e37668/PDF; doi:https://doi.org/10.2196/37668; html:https://europepmc.org/articles/PMC9384859 36474045,https://doi.org/10.1038/s41588-022-01233-6,Discovery and systematic characterization of risk variants and genes for coronary artery disease in over a million participants.,"Aragam KG, Jiang T, Goel A, Kanoni S, Wolford BN, Atri DS, Weeks EM, Wang M, Hindy G, Zhou W, Grace C, Roselli C, Marston NA, Kamanu FK, Surakka I, Venegas LM, Sherliker P, Koyama S, Ishigaki K, Åsvold BO, Brown MR, Brumpton B, de Vries PS, Giannakopoulou O, Giardoglou P, Gudbjartsson DF, Güldener U, Haider SMI, Helgadottir A, Ibrahim M, Kastrati A, Kessler T, Kyriakou T, Konopka T, Li L, Ma L, Meitinger T, Mucha S, Munz M, Murgia F, Nielsen JB, Nöthen MM, Pang S, Reinberger T, Schnitzler G, Smedley D, Thorleifsson G, von Scheidt M, Ulirsch JC, Biobank Japan, EPIC-CVD, Arnar DO, Burtt NP, Costanzo MC, Flannick J, Ito K, Jang DK, Kamatani Y, Khera AV, Komuro I, Kullo IJ, Lotta LA, Nelson CP, Roberts R, Thorgeirsson G, Thorsteinsdottir U, Webb TR, Baras A, Björkegren JLM, Boerwinkle E, Dedoussis G, Holm H, Hveem K, Melander O, Morrison AC, Orho-Melander M, Rallidis LS, Ruusalepp A, Sabatine MS, Stefansson K, Zalloua P, Ellinor PT, Farrall M, Danesh J, Ruff CT, Finucane HK, Hopewell JC, Clarke R, Gupta RM, Erdmann J, Samani NJ, Schunkert H, Watkins H, Willer CJ, Deloukas P, Kathiresan S, Butterworth AS, CARDIoGRAMplusC4D Consortium.",,Nature genetics,2022,2022-12-06,Y,,,,"The discovery of genetic loci associated with complex diseases has outpaced the elucidation of mechanisms of disease pathogenesis. Here we conducted a genome-wide association study (GWAS) for coronary artery disease (CAD) comprising 181,522 cases among 1,165,690 participants of predominantly European ancestry. We detected 241 associations, including 30 new loci. Cross-ancestry meta-analysis with a Japanese GWAS yielded 38 additional new loci. We prioritized likely causal variants using functionally informed fine-mapping, yielding 42 associations with less than five variants in the 95% credible set. Similarity-based clustering suggested roles for early developmental processes, cell cycle signaling and vascular cell migration and proliferation in the pathogenesis of CAD. We prioritized 220 candidate causal genes, combining eight complementary approaches, including 123 supported by three or more approaches. Using CRISPR-Cas9, we experimentally validated the effect of an enhancer in MYO9B, which appears to mediate CAD risk by regulating vascular cell motility. Our analysis identifies and systematically characterizes >250 risk loci for CAD to inform experimental interrogation of putative causal mechanisms for CAD.",,pdf:https://www.nature.com/articles/s41588-022-01233-6.pdf; doi:https://doi.org/10.1038/s41588-022-01233-6; html:https://europepmc.org/articles/PMC9729111; pdf:https://europepmc.org/articles/PMC9729111?pdf=render 35948708,https://doi.org/10.1038/s41586-022-05023-2,Spatially resolved clonal copy number alterations in benign and malignant tissue.,"Erickson A, He M, Berglund E, Marklund M, Mirzazadeh R, Schultz N, Kvastad L, Andersson A, Bergenstråhle L, Bergenstråhle J, Larsson L, Alonso Galicia L, Shamikh A, Basmaci E, Díaz De Ståhl T, Rajakumar T, Doultsinos D, Thrane K, Ji AL, Khavari PA, Tarish F, Tanoglidi A, Maaskola J, Colling R, Mirtti T, Hamdy FC, Woodcock DJ, Helleday T, Mills IG, Lamb AD, Lundeberg J.",,Nature,2022,2022-08-10,Y,,,,"Defining the transition from benign to malignant tissue is fundamental to improving early diagnosis of cancer1. Here we use a systematic approach to study spatial genome integrity in situ and describe previously unidentified clonal relationships. We used spatially resolved transcriptomics2 to infer spatial copy number variations in >120,000 regions across multiple organs, in benign and malignant tissues. We demonstrate that genome-wide copy number variation reveals distinct clonal patterns within tumours and in nearby benign tissue using an organ-wide approach focused on the prostate. Our results suggest a model for how genomic instability arises in histologically benign tissue that may represent early events in cancer evolution. We highlight the power of capturing the molecular and spatial continuums in a tissue context and challenge the rationale for treatment paradigms, including focal therapy.",,pdf:https://www.nature.com/articles/s41586-022-05023-2.pdf; doi:https://doi.org/10.1038/s41586-022-05023-2; html:https://europepmc.org/articles/PMC9365699; pdf:https://europepmc.org/articles/PMC9365699?pdf=render @@ -2217,8 +2217,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 33531015,https://doi.org/10.1186/s12916-021-01906-9,The importance of supplementary immunisation activities to prevent measles outbreaks during the COVID-19 pandemic in Kenya.,"Mburu CN, Ojal J, Chebet R, Akech D, Karia B, Tuju J, Sigilai A, Abbas K, Jit M, Funk S, Smits G, van Gageldonk PGM, van der Klis FRM, Tabu C, Nokes DJ, LSHTM CMMID COVID-19 Working Group, Scott J, Flasche S, Adetifa I.",,BMC medicine,2021,2021-02-03,Y,outbreak; Measles; Vaccination Coverage; Supplementary Immunisation Activities; Covid-19,,,"

Background

The COVID-19 pandemic has disrupted routine measles immunisation and supplementary immunisation activities (SIAs) in most countries including Kenya. We assessed the risk of measles outbreaks during the pandemic in Kenya as a case study for the African Region.

Methods

Combining measles serological data, local contact patterns, and vaccination coverage into a cohort model, we predicted the age-adjusted population immunity in Kenya and estimated the probability of outbreaks when contact-reducing COVID-19 interventions are lifted. We considered various scenarios for reduced measles vaccination coverage from April 2020.

Results

In February 2020, when a scheduled SIA was postponed, population immunity was close to the herd immunity threshold and the probability of a large outbreak was 34% (8-54). As the COVID-19 contact restrictions are nearly fully eased, from December 2020, the probability of a large measles outbreak will increase to 38% (19-54), 46% (30-59), and 54% (43-64) assuming a 15%, 50%, and 100% reduction in measles vaccination coverage. By December 2021, this risk increases further to 43% (25-56), 54% (43-63), and 67% (59-72) for the same coverage scenarios respectively. However, the increased risk of a measles outbreak following the lifting of all restrictions can be overcome by conducting a SIA with ≥ 95% coverage in under-fives.

Conclusion

While contact restrictions sufficient for SAR-CoV-2 control temporarily reduce measles transmissibility and the risk of an outbreak from a measles immunity gap, this risk rises rapidly once these restrictions are lifted. Implementing delayed SIAs will be critical for prevention of measles outbreaks given the roll-back of contact restrictions in Kenya.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-021-01906-9; doi:https://doi.org/10.1186/s12916-021-01906-9; html:https://europepmc.org/articles/PMC7854026; pdf:https://europepmc.org/articles/PMC7854026?pdf=render 30609404,https://doi.org/10.1016/j.ajhg.2018.11.014,Integrating Genomics into Healthcare: A Global Responsibility.,"Stark Z, Dolman L, Manolio TA, Ozenberger B, Hill SL, Caulfied MJ, Levy Y, Glazer D, Wilson J, Lawler M, Boughtwood T, Braithwaite J, Goodhand P, Birney E, North KN.",,American journal of human genetics,2019,2019-01-01,N,,Understanding the Causes of Disease,,"Genomic sequencing is rapidly transitioning into clinical practice, and implementation into healthcare systems has been supported by substantial government investment, totaling over US$4 billion, in at least 14 countries. These national genomic-medicine initiatives are driving transformative change under real-life conditions while simultaneously addressing barriers to implementation and gathering evidence for wider adoption. We review the diversity of approaches and current progress made by national genomic-medicine initiatives in the UK, France, Australia, and US and provide a roadmap for sharing strategies, standards, and data internationally to accelerate implementation.",,pdf:http://www.cell.com/article/S0002929718304221/pdf; doi:https://doi.org/10.1016/j.ajhg.2018.11.014; html:https://europepmc.org/articles/PMC6323624; pdf:https://europepmc.org/articles/PMC6323624?pdf=render; doi:https://doi.org/10.1016/j.ajhg.2018.11.014 35861824,https://doi.org/10.1161/jaha.121.025935,Candidate Plasma Biomarkers to Detect Anthracycline-Related Cardiomyopathy in Childhood Cancer Survivors: A Case Control Study in the Dutch Childhood Cancer Survivor Study.,"Leerink JM, Feijen EAM, Moerland PD, de Baat EC, Merkx R, van der Pal HJH, Tissing WJE, Louwerens M, van den Heuvel-Eibrink MM, Versluys AB, Asselbergs FW, Sammani A, Teske AJ, van Dalen EC, van der Heiden-van der Loo M, van Dulmen-den Broeder E, de Vries ACH, Kapusta L, Loonen J, Pinto YM, Kremer LCM, Mavinkurve-Groothuis AMC, Kok WEM.",,Journal of the American Heart Association,2022,2022-07-13,Y,Biomarkers; Childhood Cancer Survivors; Cardio‐oncology; Chemokine Ligands; Cancer Therapy–related Cardiac Dysfunction; Anthracycline‐related Cardiomyopathy,,,"Background Plasma biomarkers may aid in the detection of anthracycline-related cardiomyopathy (ACMP). However, the currently available biomarkers have limited diagnostic value in long-term childhood cancer survivors. This study sought to identify diagnostic plasma biomarkers for ACMP in childhood cancer survivors. Methods and Results We measured 275 plasma proteins in 28 ACMP cases with left ventricular ejection fraction <45%, 29 anthracycline-treated controls with left ventricular ejection fraction ≥53% matched on sex, time after cancer, and anthracycline dose, and 29 patients with genetically determined dilated cardiomyopathy with left ventricular ejection fraction <45%. Multivariable linear regression was used to identify differentially expressed proteins. Elastic net model, including clinical characteristics, was used to assess discrimination of proteins diagnostic for ACMP. NT-proBNP (N-terminal pro-B-type natriuretic peptide) and the inflammatory markers CCL19 (C-C motif chemokine ligands 19) and CCL20, PSPD (pulmonary surfactant protein-D), and PTN (pleiotrophin) were significantly upregulated in ACMP compared with controls. An elastic net model selected 45 proteins, including NT-proBNP, CCL19, CCL20 and PSPD, but not PTN, that discriminated ACMP cases from controls with an area under the receiver operating characteristic curve (AUC) of 0.78. This model was not superior to a model including NT-proBNP and clinical characteristics (AUC=0.75; P=0.766). However, when excluding 8 ACMP cases with heart failure, the full model was superior to that including only NT-proBNP and clinical characteristics (AUC=0.75 versus AUC=0.50; P=0.022). The same 45 proteins also showed good discrimination between dilated cardiomyopathy and controls (AUC=0.89), underscoring their association with cardiomyopathy. Conclusions We identified 3 specific inflammatory proteins as candidate plasma biomarkers for ACMP in long-term childhood cancer survivors and demonstrated protein overlap with dilated cardiomyopathy.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/JAHA.121.025935; doi:https://doi.org/10.1161/JAHA.121.025935; html:https://europepmc.org/articles/PMC9707839; pdf:https://europepmc.org/articles/PMC9707839?pdf=render -34645462,https://doi.org/10.1186/s12974-021-02287-9,T lymphocyte senescence is attenuated in Parkinson's disease.,"Kouli A, Jensen M, Papastavrou V, Scott KM, Kolenda C, Parker C, Solim IH, Camacho M, Martin-Ruiz C, Williams-Gray CH.",,Journal of neuroinflammation,2021,2021-10-13,Y,T lymphocytes; Immunosenescence; Parkinson’s Disease; Ageing Markers,,,"

Background

Immune involvement is well-described in Parkinson's disease (PD), including an adaptive T lymphocyte response. Given the increasing prevalence of Parkinson's disease in older age, age-related dysregulation of T lymphocytes may be relevant in this disorder, and we have previously observed changes in age-associated CD8+ T cell subsets in mid-stage PD. This study aimed to further characterise T cell immunosenescence in newly diagnosed PD patients, including shifts in CD4+ and CD8+ subpopulations, and changes in markers of cellular ageing in CD8+ T lymphocytes.

Methods

Peripheral blood mononuclear cells were extracted from the blood of 61 newly diagnosed PD patients and 63 age- and sex-matched controls. Flow cytometric analysis was used for immunophenotyping of CD8+ and CD4+ lymphocyte subsets, and analysis of recent thymic emigrant cells. Telomere length within CD8+ T lymphocytes was assessed, as well as the expression of the telomerase reverse transcriptase enzyme (hTERT), and the cell-ageing markers p16INK4a and p21CIP1/Waf1.

Results

The number of CD8+ TEMRA T cells was found to be significantly reduced in PD patients compared to controls. The expression of p16INK4a in CD8+ lymphocytes was also lower in patients versus controls. Chronic latent CMV infection was associated with increased senescent CD8+ lymphocytes in healthy controls, but this shift was less apparent in PD patients.

Conclusions

Taken together, our data demonstrate a reduction in CD8+ T cell replicative senescence which is present at the earliest stages of Parkinson's disease.",,pdf:https://jneuroinflammation.biomedcentral.com/track/pdf/10.1186/s12974-021-02287-9; doi:https://doi.org/10.1186/s12974-021-02287-9; html:https://europepmc.org/articles/PMC8513368; pdf:https://europepmc.org/articles/PMC8513368?pdf=render 33777379,https://doi.org/10.1093/ckj/sfaa045,Accelerometer-measured physical activity and functional behaviours among people on dialysis.,"Nawab KA, Storey BC, Staplin N, Walmsley R, Haynes R, Sutherland S, Crosbie S, Pugh CW, Harper CHS, Landray MJ, Doherty A, Herrington WG.",,Clinical kidney journal,2021,2020-08-31,Y,Age; Haemodialysis; epidemiology; Physical Activity; cardiovascular,,,"

Background

The feasibility of wrist-worn accelerometers, and the patterns and determinants of physical activity, among people on dialysis are uncertain.

Methods

People on maintenance dialysis were fitted with a wrist-worn AxivityAX3 accelerometer. Subsets also wore a 14-day electrocardiograph patch (Zio®PatchXT) and wearable cameras. Age-, sex- and season-matched UK Biobank control groups were derived for comparison.

Results

Median (interquartile range) accelerometer wear time for the 101 recruits was 12.5 (10.4-13.5) days, of which 73 participants (mean age 66.5 years) had excellent wear on both dialysis and non-dialysis days. Mean (standard error) overall physical activity levels were 15.5 (0.7) milligravity units (mg), 14.8 (0.7) mg on dialysis days versus 16.2 (0.8) mg on non-dialysis days. This compared with 28.1 (0.5) mg for apparently healthy controls, 23.4 (0.4) mg for controls with prior cardiovascular disease (CVD) and/or diabetes mellitus and 22.9 (0.6) mg for heart failure controls. Each day, we estimated that those on dialysis spent an average of about 1 hour (h/day) walking, 0.6 h/day engaging in moderate-intensity activity, 0.7 h/day on light tasks, 13.2 h/day sedentary and 8.6 h/day asleep. Older age and self-reported leg weakness were associated with decreased levels of physical activity, but the presence of prior CVD, arrhythmias and listing for transplantation were not.

Conclusions

Wrist-worn accelerometers are an acceptable and reliable method to measure physical activity in people on dialysis and may also be used to estimate functional behaviours. Among people on dialysis, who are broadly half as active as general population controls, age and leg weakness appear to be more important determinants of low activity levels than CVD.",,pdf:https://academic.oup.com/ckj/article-pdf/14/3/950/36670473/sfaa045.pdf; doi:https://doi.org/10.1093/ckj/sfaa045; html:https://europepmc.org/articles/PMC7986362; pdf:https://europepmc.org/articles/PMC7986362?pdf=render +34645462,https://doi.org/10.1186/s12974-021-02287-9,T lymphocyte senescence is attenuated in Parkinson's disease.,"Kouli A, Jensen M, Papastavrou V, Scott KM, Kolenda C, Parker C, Solim IH, Camacho M, Martin-Ruiz C, Williams-Gray CH.",,Journal of neuroinflammation,2021,2021-10-13,Y,T lymphocytes; Immunosenescence; Parkinson’s Disease; Ageing Markers,,,"

Background

Immune involvement is well-described in Parkinson's disease (PD), including an adaptive T lymphocyte response. Given the increasing prevalence of Parkinson's disease in older age, age-related dysregulation of T lymphocytes may be relevant in this disorder, and we have previously observed changes in age-associated CD8+ T cell subsets in mid-stage PD. This study aimed to further characterise T cell immunosenescence in newly diagnosed PD patients, including shifts in CD4+ and CD8+ subpopulations, and changes in markers of cellular ageing in CD8+ T lymphocytes.

Methods

Peripheral blood mononuclear cells were extracted from the blood of 61 newly diagnosed PD patients and 63 age- and sex-matched controls. Flow cytometric analysis was used for immunophenotyping of CD8+ and CD4+ lymphocyte subsets, and analysis of recent thymic emigrant cells. Telomere length within CD8+ T lymphocytes was assessed, as well as the expression of the telomerase reverse transcriptase enzyme (hTERT), and the cell-ageing markers p16INK4a and p21CIP1/Waf1.

Results

The number of CD8+ TEMRA T cells was found to be significantly reduced in PD patients compared to controls. The expression of p16INK4a in CD8+ lymphocytes was also lower in patients versus controls. Chronic latent CMV infection was associated with increased senescent CD8+ lymphocytes in healthy controls, but this shift was less apparent in PD patients.

Conclusions

Taken together, our data demonstrate a reduction in CD8+ T cell replicative senescence which is present at the earliest stages of Parkinson's disease.",,pdf:https://jneuroinflammation.biomedcentral.com/track/pdf/10.1186/s12974-021-02287-9; doi:https://doi.org/10.1186/s12974-021-02287-9; html:https://europepmc.org/articles/PMC8513368; pdf:https://europepmc.org/articles/PMC8513368?pdf=render 36244350,https://doi.org/10.1016/s2468-2667(22)00225-0,The burden of bacterial antimicrobial resistance in the WHO European region in 2019: a cross-country systematic analysis.,European Antimicrobial Resistance Collaborators.,,The Lancet. Public health,2022,2022-10-14,Y,,,,"

Background

Antimicrobial resistance (AMR) represents one of the most crucial threats to public health and modern health care. Previous studies have identified challenges with estimating the magnitude of the problem and its downstream effect on human health and mortality. To our knowledge, this study presents the most comprehensive set of regional and country-level estimates of AMR burden in the WHO European region to date.

Methods

We estimated deaths and disability-adjusted life-years attributable to and associated with AMR for 23 bacterial pathogens and 88 pathogen-drug combinations for the WHO European region and its countries in 2019. Our methodological approach consisted of five broad components: the number of deaths in which infection had a role, the proportion of infectious deaths attributable to a given infectious syndrome, the proportion of infectious syndrome deaths attributable to a given pathogen, the percentage of a given pathogen resistant to an antimicrobial drug of interest, and the excess risk of mortality (or duration of an infection) associated with this resistance. These components were then used to estimate the disease burden by using two counterfactual scenarios: deaths attributable to AMR (considering an alternative scenario where infections with resistant pathogens are replaced with susceptible ones) and deaths associated with AMR (considering an alternative scenario where drug-resistant infections would not occur at all). Data were solicited from a wide array of international stakeholders; these included research hospitals, surveillance networks, and infection databases maintained by private laboratories and medical technology companies. We generated 95% uncertainty intervals (UIs) for final estimates as the 25th and 975th ordered values across 1000 posterior draws, and models were cross-validated for out-of-sample predictive validity.

Findings

We estimated 541 000 deaths (95% UI 370 000-763 000) associated with bacterial AMR and 133 000 deaths (90 100-188 000) attributable to bacterial AMR in the whole WHO European region in 2019. The largest fatal burden of AMR in the region came from bloodstream infections, with 195 000 deaths (104 000-333 000) associated with resistance, followed by intra-abdominal infections (127 000 deaths [81 900-185 000]) and respiratory infections (120 000 deaths [94 500-154 000]). Seven leading pathogens were responsible for about 457 000 deaths associated with resistance in 53 countries of this region; these pathogens were, in descending order of mortality, Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterococcus faecium, Streptococcus pneumoniae, and Acinetobacter baumannii. Methicillin-resistant S aureus was shown to be the leading pathogen-drug combination in 27 countries for deaths attributable to AMR, while aminopenicillin-resistant E coli predominated in 47 countries for deaths associated with AMR.

Interpretation

The high levels of resistance for several important bacterial pathogens and pathogen-drug combinations, together with the high mortality rates associated with these pathogens, show that AMR is a serious threat to public health in the WHO European region. Our regional and cross-country analyses open the door for strategies that can be tailored to leading pathogen-drug combinations and the available resources in a specific location. These results underscore that the most effective way to tackle AMR in this region will require targeted efforts and investments in conjunction with continuous outcome-based research endeavours.

Funding

Bill & Melinda Gates Foundation, Wellcome Trust, and Department of Health and Social Care using UK aid funding managed by the Fleming Fund.",,pdf:https://digital.library.adelaide.edu.au/dspace/bitstream/2440/136826/2/hdl_136826.pdf; doi:https://doi.org/10.1016/S2468-2667(22)00225-0; html:https://europepmc.org/articles/PMC9630253 33879569,https://doi.org/10.1073/pnas.2009808118,Mendelian randomization identifies blood metabolites previously linked to midlife cognition as causal candidates in Alzheimer's disease.,"Lord J, Jermy B, Green R, Wong A, Xu J, Legido-Quigley C, Dobson R, Richards M, Proitsi P.",,Proceedings of the National Academy of Sciences of the United States of America,2021,2021-04-01,Y,Biomarkers; Alzheimer’s disease; Metabolomics; Causality; Mendelian Randomization,,,"There are currently no disease-modifying treatments for Alzheimer's disease (AD), and an understanding of preclinical causal biomarkers to help target disease pathogenesis in the earliest phases remains elusive. Here, we investigated whether 19 metabolites previously associated with midlife cognition-a preclinical predictor of AD-translate to later clinical risk, using Mendelian randomization (MR) to tease out AD-specific causal relationships. Summary statistics from the largest genome-wide association studies (GWASs) for AD and metabolites were used to perform bidirectional univariable MR. Bayesian model averaging (BMA) was additionally performed to address high correlation between metabolites and identify metabolite combinations that may be on the AD causal pathway. Univariable MR indicated four extra-large high-density lipoproteins (XL.HDL) on the causal pathway to AD: free cholesterol (XL.HDL.FC: 95% CI = 0.78 to 0.94), total lipids (XL.HDL.L: 95% CI = 0.80 to 0.97), phospholipids (XL.HDL.PL: 95% CI = 0.81 to 0.97), and concentration of XL.HDL particles (95% CI = 0.79 to 0.96), significant at an adjusted P < 0.009. MR-BMA corroborated XL.HDL.FC to be among the top three causal metabolites, in addition to total cholesterol in XL.HDL (XL.HDL.C) and glycoprotein acetyls (GP). Both XL.HDL.C and GP demonstrated suggestive univariable evidence of causality (P < 0.05), and GP successfully replicated within an independent dataset. This study offers insight into the causal relationship between metabolites demonstrating association with midlife cognition and AD. It highlights GP in addition to several XL.HDLs-particularly XL.HDL.FC-as causal candidates warranting further investigation. As AD pathology is thought to develop decades prior to symptom onset, expanding on these findings could inform risk reduction strategies.",,doi:https://doi.org/10.1073/pnas.2009808118; doi:https://doi.org/10.1073/pnas.2009808118; html:https://europepmc.org/articles/PMC8072203; pdf:https://europepmc.org/articles/PMC8072203?pdf=render 35879886,https://doi.org/10.1017/s0033291722002501,"Depression, anxiety and PTSD symptoms before and during the COVID-19 pandemic in the UK.","Young KS, Purves KL, Hübel C, Davies MR, Thompson KN, Bristow S, Krebs G, Danese A, Hirsch C, Parsons CE, Vassos E, Adey BN, Bright S, Hegemann L, Lee YT, Kalsi G, Monssen D, Mundy J, Peel AJ, Rayner C, Rogers HC, Ter Kuile A, Ward C, York K, Lin Y, Palmos AB, Schmidt U, Veale D, Nicholson TR, Pollak TA, Stevelink SAM, Moukhtarian T, Martineau AR, Holt H, Maughan B, Al-Chalabi A, Chaudhuri KR, Richardson MP, Bradley JR, Chinnery PF, Kingston N, Papadia S, Stirrups KE, Linger R, Hotopf M, Eley TC, Breen G.",,Psychological medicine,2023,2022-07-26,Y,Depression; Anxiety; Ptsd; Covid-19,,,"

Background

The impact of the coronavirus disease 2019 (COVID-19) pandemic on mental health is still being unravelled. It is important to identify which individuals are at greatest risk of worsening symptoms. This study aimed to examine changes in depression, anxiety and post-traumatic stress disorder (PTSD) symptoms using prospective and retrospective symptom change assessments, and to find and examine the effect of key risk factors.

Method

Online questionnaires were administered to 34 465 individuals (aged 16 years or above) in April/May 2020 in the UK, recruited from existing cohorts or via social media. Around one-third (n = 12 718) of included participants had prior diagnoses of depression or anxiety and had completed pre-pandemic mental health assessments (between September 2018 and February 2020), allowing prospective investigation of symptom change.

Results

Prospective symptom analyses showed small decreases in depression (PHQ-9: -0.43 points) and anxiety [generalised anxiety disorder scale - 7 items (GAD)-7: -0.33 points] and increases in PTSD (PCL-6: 0.22 points). Conversely, retrospective symptom analyses demonstrated significant large increases (PHQ-9: 2.40; GAD-7 = 1.97), with 55% reported worsening mental health since the beginning of the pandemic on a global change rating. Across both prospective and retrospective measures of symptom change, worsening depression, anxiety and PTSD symptoms were associated with prior mental health diagnoses, female gender, young age and unemployed/student status.

Conclusions

We highlight the effect of prior mental health diagnoses on worsening mental health during the pandemic and confirm previously reported sociodemographic risk factors. Discrepancies between prospective and retrospective measures of changes in mental health may be related to recall bias-related underestimation of prior symptom severity.",,pdf:https://www.cambridge.org/core/services/aop-cambridge-core/content/view/8C3760ED596F1ED8B80F729AC5E47B9B/S0033291722002501a.pdf/div-class-title-depression-anxiety-and-ptsd-symptoms-before-and-during-the-covid-19-pandemic-in-the-uk-div.pdf; doi:https://doi.org/10.1017/S0033291722002501; html:https://europepmc.org/articles/PMC10482709; pdf:https://europepmc.org/articles/PMC10482709?pdf=render @@ -2237,8 +2237,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 33722066,https://doi.org/10.1161/circinterventions.120.009434,Clopidogrel Versus Ticagrelor or Prasugrel After Primary Percutaneous Coronary Intervention According to CYP2C19 Genotype: A POPular Genetics Subanalysis.,"Claassens DMF, Bergmeijer TO, Vos GJA, Hermanides RS, van 't Hof AWJ, van der Harst P, Barbato E, Morisco C, Tjon Joe Gin RM, Asselbergs FW, Mosterd A, Herrman JR, Dewilde WJM, Janssen PWA, Kelder JC, Mahmoodi BK, Deneer VHM, Ten Berg JM.",,Circulation. Cardiovascular interventions,2021,2021-03-16,N,Myocardial infarction; Percutaneous coronary intervention; acute coronary syndrome; Clopidogrel; Genetic Testing; Pharmacogenetics; Ticagrelor,,,[Figure: see text].,,pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCINTERVENTIONS.120.009434; doi:https://doi.org/10.1161/CIRCINTERVENTIONS.120.009434 32895551,https://doi.org/10.1038/s41588-020-0682-6,Phenome-wide Mendelian randomization mapping the influence of the plasma proteome on complex diseases.,"Zheng J, Haberland V, Baird D, Walker V, Haycock PC, Hurle MR, Gutteridge A, Erola P, Liu Y, Luo S, Robinson J, Richardson TG, Staley JR, Elsworth B, Burgess S, Sun BB, Danesh J, Runz H, Maranville JC, Martin HM, Yarmolinsky J, Laurin C, Holmes MV, Liu JZ, Estrada K, Santos R, McCarthy L, Waterworth D, Nelson MR, Smith GD, Butterworth AS, Hemani G, Scott RA, Gaunt TR.",,Nature genetics,2020,2020-09-07,Y,,,,"The human proteome is a major source of therapeutic targets. Recent genetic association analyses of the plasma proteome enable systematic evaluation of the causal consequences of variation in plasma protein levels. Here we estimated the effects of 1,002 proteins on 225 phenotypes using two-sample Mendelian randomization (MR) and colocalization. Of 413 associations supported by evidence from MR, 130 (31.5%) were not supported by results of colocalization analyses, suggesting that genetic confounding due to linkage disequilibrium is widespread in naïve phenome-wide association studies of proteins. Combining MR and colocalization evidence in cis-only analyses, we identified 111 putatively causal effects between 65 proteins and 52 disease-related phenotypes ( https://www.epigraphdb.org/pqtl/ ). Evaluation of data from historic drug development programs showed that target-indication pairs with MR and colocalization support were more likely to be approved, evidencing the value of this approach in identifying and prioritizing potential therapeutic targets.",,pdf:https://ueaeprints.uea.ac.uk/id/eprint/76368/1/Zheng_et_al_final_manuscript.pdf; doi:https://doi.org/10.1038/s41588-020-0682-6; html:https://europepmc.org/articles/PMC7610464; pdf:https://europepmc.org/articles/PMC7610464?pdf=render 35908569,https://doi.org/10.1016/s0140-6736(22)01109-6,"Baricitinib in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial and updated meta-analysis.",RECOVERY Collaborative Group.,,"Lancet (London, England)",2022,2022-07-01,Y,,,,"

Background

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

Methods

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

Findings

Between Feb 2 and Dec 29, 2021, from 10 852 enrolled, 8156 patients were randomly allocated to receive usual care plus baricitinib versus usual care alone. At randomisation, 95% of patients were receiving corticosteroids and 23% were receiving tocilizumab (with planned use within the next 24 h recorded for a further 9%). Overall, 514 (12%) of 4148 patients allocated to baricitinib versus 546 (14%) of 4008 patients allocated to usual care died within 28 days (age-adjusted rate ratio 0·87; 95% CI 0·77-0·99; p=0·028). This 13% proportional reduction in mortality was somewhat smaller than that seen in a meta-analysis of eight previous trials of a JAK inhibitor (involving 3732 patients and 425 deaths), in which allocation to a JAK inhibitor was associated with a 43% proportional reduction in mortality (rate ratio 0·57; 95% CI 0·45-0·72). Including the results from RECOVERY in an updated meta-analysis of all nine completed trials (involving 11 888 randomly assigned patients and 1485 deaths) allocation to baricitinib or another JAK inhibitor was associated with a 20% proportional reduction in mortality (rate ratio 0·80; 95% CI 0·72-0·89; p<0·0001). In RECOVERY, there was no significant excess in death or infection due to non-COVID-19 causes and no significant excess of thrombosis, or other safety outcomes.

Interpretation

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

Funding

UK Research and Innovation (Medical Research Council) and National Institute of Health Research.",,pdf:http://www.thelancet.com/article/S0140673622011096/pdf; doi:https://doi.org/10.1016/S0140-6736(22)01109-6; html:https://europepmc.org/articles/PMC9333998; pdf:https://europepmc.org/articles/PMC9333998?pdf=render -37188768,https://doi.org/10.1038/s42003-023-04836-9,Fine-mapping of retinal vascular complexity loci identifies Notch regulation as a shared mechanism with myocardial infarction outcomes.,"Villaplana-Velasco A, Pigeyre M, Engelmann J, Rawlik K, Canela-Xandri O, Tochel C, Lona-Durazo F, Mookiah MRK, Doney A, Parra EJ, Trucco E, MacGillivray T, Rannikmae K, Tenesa A, Pairo-Castineira E, Bernabeu MO.",,Communications biology,2023,2023-05-15,Y,,,,"There is increasing evidence that the complexity of the retinal vasculature measured as fractal dimension, Df, might offer earlier insights into the progression of coronary artery disease (CAD) before traditional biomarkers can be detected. This association could be partly explained by a common genetic basis; however, the genetic component of Df is poorly understood. We present a genome-wide association study (GWAS) of 38,000 individuals with white British ancestry from the UK Biobank aimed to comprehensively study the genetic component of Df and analyse its relationship with CAD. We replicated 5 Df loci and found 4 additional loci with suggestive significance (P < 1e-05) to contribute to Df variation, which previously were reported in retinal tortuosity and complexity, hypertension, and CAD studies. Significant negative genetic correlation estimates support the inverse relationship between Df and CAD, and between Df and myocardial infarction (MI), one of CAD's fatal outcomes. Fine-mapping of Df loci revealed Notch signalling regulatory variants supporting a shared mechanism with MI outcomes. We developed a predictive model for MI incident cases, recorded over a 10-year period following clinical and ophthalmic evaluation, combining clinical information, Df, and a CAD polygenic risk score. Internal cross-validation demonstrated a considerable improvement in the area under the curve (AUC) of our predictive model (AUC = 0.770 ± 0.001) when comparing with an established risk model, SCORE, (AUC = 0.741 ± 0.002) and extensions thereof leveraging the PRS (AUC = 0.728 ± 0.001). This evidences that Df provides risk information beyond demographic, lifestyle, and genetic risk factors. Our findings shed new light on the genetic basis of Df, unveiling a common control with MI, and highlighting the benefits of its application in individualised MI risk prediction.",,doi:https://doi.org/10.1038/s42003-023-04836-9; html:https://europepmc.org/articles/PMC10185685; pdf:https://europepmc.org/articles/PMC10185685?pdf=render 32546850,https://doi.org/10.1038/s41598-020-66737-9,Genetic aetiology of self-harm ideation and behaviour.,"Campos AI, Verweij KJH, Statham DJ, Madden PAF, Maciejewski DF, Davis KAS, John A, Hotopf M, Heath AC, Martin NG, Rentería ME.",,Scientific reports,2020,2020-06-16,Y,,,,"Family studies have identified a heritable component to self-harm that is partially independent from comorbid psychiatric disorders. However, the genetic aetiology of broad sense (non-suicidal and suicidal) self-harm has not been characterised on the molecular level. In addition, controversy exists about the degree to which suicidal and non-suicidal self-harm share a common genetic aetiology. In the present study, we conduct genome-wide association studies (GWAS) on lifetime self-harm ideation and self-harm behaviour (i.e. any lifetime self-harm act regardless of suicidal intent) using data from the UK Biobank (n > 156,000). We also perform genome wide gene-based tests and characterize the SNP heritability and genetic correlations between these traits. Finally, we test whether polygenic risk scores (PRS) for self-harm ideation and self-harm behaviour predict suicide attempt, suicide thoughts and non-suicidal self-harm (NSSH) in an independent target sample of 8,703 Australian adults. Our GWAS results identified one genome-wide significant locus associated with each of the two phenotypes. SNP heritability (hsnp2) estimates were ~10%, and both traits were highly genetically correlated (LDSC rg > 0.8). Gene-based tests identified seven genes associated with self-harm ideation and four with self-harm behaviour. Furthermore, in the target sample, PRS for self-harm ideation were significantly associated with suicide thoughts and NSSH, and PRS for self-harm behaviour predicted suicide thoughts and suicide attempt. Follow up regressions identified a shared genetic aetiology between NSSH and suicide thoughts, and between suicide thoughts and suicide attempt. Evidence for shared genetic aetiology between NSSH and suicide attempt was not statistically significant.",,pdf:https://www.nature.com/articles/s41598-020-66737-9.pdf; doi:https://doi.org/10.1038/s41598-020-66737-9; html:https://europepmc.org/articles/PMC7297971; pdf:https://europepmc.org/articles/PMC7297971?pdf=render +37188768,https://doi.org/10.1038/s42003-023-04836-9,Fine-mapping of retinal vascular complexity loci identifies Notch regulation as a shared mechanism with myocardial infarction outcomes.,"Villaplana-Velasco A, Pigeyre M, Engelmann J, Rawlik K, Canela-Xandri O, Tochel C, Lona-Durazo F, Mookiah MRK, Doney A, Parra EJ, Trucco E, MacGillivray T, Rannikmae K, Tenesa A, Pairo-Castineira E, Bernabeu MO.",,Communications biology,2023,2023-05-15,Y,,,,"There is increasing evidence that the complexity of the retinal vasculature measured as fractal dimension, Df, might offer earlier insights into the progression of coronary artery disease (CAD) before traditional biomarkers can be detected. This association could be partly explained by a common genetic basis; however, the genetic component of Df is poorly understood. We present a genome-wide association study (GWAS) of 38,000 individuals with white British ancestry from the UK Biobank aimed to comprehensively study the genetic component of Df and analyse its relationship with CAD. We replicated 5 Df loci and found 4 additional loci with suggestive significance (P < 1e-05) to contribute to Df variation, which previously were reported in retinal tortuosity and complexity, hypertension, and CAD studies. Significant negative genetic correlation estimates support the inverse relationship between Df and CAD, and between Df and myocardial infarction (MI), one of CAD's fatal outcomes. Fine-mapping of Df loci revealed Notch signalling regulatory variants supporting a shared mechanism with MI outcomes. We developed a predictive model for MI incident cases, recorded over a 10-year period following clinical and ophthalmic evaluation, combining clinical information, Df, and a CAD polygenic risk score. Internal cross-validation demonstrated a considerable improvement in the area under the curve (AUC) of our predictive model (AUC = 0.770 ± 0.001) when comparing with an established risk model, SCORE, (AUC = 0.741 ± 0.002) and extensions thereof leveraging the PRS (AUC = 0.728 ± 0.001). This evidences that Df provides risk information beyond demographic, lifestyle, and genetic risk factors. Our findings shed new light on the genetic basis of Df, unveiling a common control with MI, and highlighting the benefits of its application in individualised MI risk prediction.",,doi:https://doi.org/10.1038/s42003-023-04836-9; html:https://europepmc.org/articles/PMC10185685; pdf:https://europepmc.org/articles/PMC10185685?pdf=render 37538507,https://doi.org/10.1016/j.rpth.2023.100175,PIK3R3 is a candidate regulator of platelet count in people of Bangladeshi ancestry.,"Burley K, Fitzgibbon L, van Heel D, Genes & Health Research Team@EastLondonGenes, Vuckovic D, Mumford AD, Genes & Health Research Team.",,Research and practice in thrombosis and haemostasis,2023,2023-05-14,Y,Blood platelets; Cardiovascular diseases; Bangladesh; Genome-wide Association Study; Phosphatidylinositol 3-Kinases,,,"

Background

Blood platelets are mediators of atherothrombotic disease and are regulated by complex sets of genes. Association studies in European ancestry populations have already detected informative platelet regulatory loci. Studies in other ancestries can potentially reveal new associations because of different allele frequencies, linkage structures, and variant effects.

Objectives

To reveal new regulatory genes for platelet count (PLT).

Methods

Genome-wide association studies (GWAS) were performed in 20,218 Bangladeshi and 9198 Pakistani individuals from the Genes & Health study. Loci significantly associated with PLT underwent fine-mapping to identify candidate genes.

Results

Of 1588 significantly associated variants (P < 5 × 10-8) at 20 loci in the Bangladeshi analysis, most replicated findings in prior transancestry GWAS and in the Pakistani analysis. However, the Bangladeshi locus defined by rs946528 (chr1:46019890) did not associate with PLT in the Pakistani analysis but was in the same linkage disequilibrium block (r2 ≥ 0.5) as PLT-associated variants in prior East Asian GWAS. The single independent association signal was refined to a 95% credible set of 343 variants spanning 8 coding genes. Functional annotation, mapping to megakaryocyte regulatory regions, and colocalization with blood expression quantitative trait loci identified the likely mediator of the PLT phenotype to be PIK3R3 encoding a regulator of phosphoinositol 3-kinase (PI3K).

Conclusion

Abnormal PI3K activity in the vessel wall is already implicated in the pathogenesis of atherothrombosis. Our identification of a new association between PIK3R3 and PLT provides further mechanistic insights into the contribution of the PI3K pathway to platelet biology.",,doi:https://doi.org/10.1016/j.rpth.2023.100175; html:https://europepmc.org/articles/PMC10394561; pdf:https://europepmc.org/articles/PMC10394561?pdf=render 32505923,https://doi.org/10.1016/j.ebiom.2020.102818,"Children first, or last?",Modi N.,,EBioMedicine,2020,2020-06-04,Y,,,,,,pdf:http://www.thelancet.com/article/S2352396420301936/pdf; doi:https://doi.org/10.1016/j.ebiom.2020.102818; html:https://europepmc.org/articles/PMC7276509; pdf:https://europepmc.org/articles/PMC7276509?pdf=render 35300523,https://doi.org/10.1161/circulationaha.121.056663,Therapeutic Targets for Heart Failure Identified Using Proteomics and Mendelian Randomization.,"Henry A, Gordillo-Marañón M, Finan C, Schmidt AF, Ferreira JP, Karra R, Sundström J, Lind L, Ärnlöv J, Zannad F, Mälarstig A, Hingorani AD, Lumbers RT, HERMES and SCALLOP Consortia.",,Circulation,2022,2022-03-18,Y,Proteomics; Heart Failure; Drug Target Prediction; Mendelian Randomization Analysis,,,"

Background

Heart failure (HF) is a highly prevalent disorder for which disease mechanisms are incompletely understood. The discovery of disease-associated proteins with causal genetic evidence provides an opportunity to identify new therapeutic targets.

Methods

We investigated the observational and causal associations of 90 cardiovascular proteins, which were measured using affinity-based proteomic assays. First, we estimated the associations of 90 cardiovascular proteins with incident heart failure by means of a fixed-effect meta-analysis of 4 population-based studies, composed of a total of 3019 participants with 732 HF events. The causal effects of HF-associated proteins were then investigated by Mendelian randomization, using cis-protein quantitative loci genetic instruments identified from genomewide association studies in more than 30 000 individuals. To improve the precision of causal estimates, we implemented an Mendelian randomization model that accounted for linkage disequilibrium between instruments and tested the robustness of causal estimates through a multiverse sensitivity analysis that included up to 120 combinations of instrument selection parameters and Mendelian randomization models per protein. The druggability of candidate proteins was surveyed, and mechanism of action and potential on-target side effects were explored with cross-trait Mendelian randomization analysis.

Results

Forty-four of ninety proteins were positively associated with risk of incident HF (P<6.0×10-4). Among these, 8 proteins had evidence of a causal association with HF that was robust to multiverse sensitivity analysis: higher CSF-1 (macrophage colony-stimulating factor 1), Gal-3 (galectin-3) and KIM-1 (kidney injury molecule 1) were positively associated with risk of HF, whereas higher ADM (adrenomedullin), CHI3L1 (chitinase-3-like protein 1), CTSL1 (cathepsin L1), FGF-23 (fibroblast growth factor 23), and MMP-12 (matrix metalloproteinase-12) were protective. Therapeutics targeting ADM and Gal-3 are currently under evaluation in clinical trials, and all the remaining proteins were considered druggable, except KIM-1.

Conclusions

We identified 44 circulating proteins that were associated with incident HF, of which 8 showed evidence of a causal relationship and 7 were druggable, including adrenomedullin, which represents a particularly promising drug target. Our approach demonstrates a tractable roadmap for the triangulation of population genomic and proteomic data for the prioritization of therapeutic targets for complex human diseases.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCULATIONAHA.121.056663; doi:https://doi.org/10.1161/CIRCULATIONAHA.121.056663; html:https://europepmc.org/articles/PMC9010023; pdf:https://europepmc.org/articles/PMC9010023?pdf=render @@ -2268,13 +2268,13 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 37286573,https://doi.org/10.1038/s41467-023-38383-y,Elevated plasma complement factor H related 5 protein is associated with venous thromboembolism.,"Iglesias MJ, Sanchez-Rivera L, Ibrahim-Kosta M, Naudin C, Munsch G, Goumidi L, Farm M, Smith PM, Thibord F, Kral-Pointner JB, Hong MG, Suchon P, Germain M, Schrottmaier W, Dusart P, Boland A, Kotol D, Edfors F, Koprulu M, Pietzner M, Langenberg C, Damrauer SM, Johnson AD, Klarin DM, Smith NL, Smadja DM, Holmström M, Magnusson M, Silveira A, Uhlén M, Renné T, Martinez-Perez A, Emmerich J, Deleuze JF, Antovic J, Soria Fernandez JM, Assinger A, Schwenk JM, Souto Andres JC, Morange PE, Butler LM, Trégouët DA, Odeberg J.",,Nature communications,2023,2023-06-07,Y,,,,"Venous thromboembolism (VTE) is a common, multi-causal disease with potentially serious short- and long-term complications. In clinical practice, there is a need for improved plasma biomarker-based tools for VTE diagnosis and risk prediction. Here we show, using proteomics profiling to screen plasma from patients with suspected acute VTE, and several case-control studies for VTE, how Complement Factor H Related 5 protein (CFHR5), a regulator of the alternative pathway of complement activation, is a VTE-associated plasma biomarker. In plasma, higher CFHR5 levels are associated with increased thrombin generation potential and recombinant CFHR5 enhanced platelet activation in vitro. GWAS analysis of ~52,000 participants identifies six loci associated with CFHR5 plasma levels, but Mendelian randomization do not demonstrate causality between CFHR5 and VTE. Our results indicate an important role for the regulation of the alternative pathway of complement activation in VTE and that CFHR5 represents a potential diagnostic and/or risk predictive plasma biomarker.",,pdf:https://www.nature.com/articles/s41467-023-38383-y.pdf; doi:https://doi.org/10.1038/s41467-023-38383-y; html:https://europepmc.org/articles/PMC10247781; pdf:https://europepmc.org/articles/PMC10247781?pdf=render 32706893,https://doi.org/10.1182/bloodadvances.2020002230,Artificial intelligence-based morphological fingerprinting of megakaryocytes: a new tool for assessing disease in MPN patients.,"Sirinukunwattana K, Aberdeen A, Theissen H, Sousos N, Psaila B, Mead AJ, Turner GDH, Rees G, Rittscher J, Royston D.",,Blood advances,2020,2020-07-01,N,,,,"Accurate diagnosis and classification of myeloproliferative neoplasms (MPNs) requires integration of clinical, morphological, and genetic findings. Despite major advances in our understanding of the molecular and genetic basis of MPNs, the morphological assessment of bone marrow trephines (BMT) is critical in differentiating MPN subtypes and their reactive mimics. However, morphological assessment is heavily constrained by a reliance on subjective, qualitative, and poorly reproducible criteria. To improve the morphological assessment of MPNs, we have developed a machine learning approach for the automated identification, quantitative analysis, and abstract representation of megakaryocyte features using reactive/nonneoplastic BMT samples (n = 43) and those from patients with established diagnoses of essential thrombocythemia (n = 45), polycythemia vera (n = 18), or myelofibrosis (n = 25). We describe the application of an automated workflow for the identification and delineation of relevant histological features from routinely prepared BMTs. Subsequent analysis enabled the tissue diagnosis of MPN with a high predictive accuracy (area under the curve = 0.95) and revealed clear evidence of the potential to discriminate between important MPN subtypes. Our method of visually representing abstracted megakaryocyte features in the context of analyzed patient cohorts facilitates the interpretation and monitoring of samples in a manner that is beyond conventional approaches. The automated BMT phenotyping approach described here has significant potential as an adjunct to standard genetic and molecular testing in established or suspected MPN patients, either as part of the routine diagnostic pathway or in the assessment of disease progression/response to treatment.",,pdf:https://ashpublications.org/bloodadvances/article-pdf/4/14/3284/1749738/advancesadv2020002230.pdf; doi:https://doi.org/10.1182/bloodadvances.2020002230; html:https://europepmc.org/articles/PMC7391156; pdf:https://europepmc.org/articles/PMC7391156?pdf=render; doi:https://doi.org/10.1182/bloodadvances.2020002230 32184442,https://doi.org/10.1038/s42003-020-0857-9,Genome-wide association identifies seven loci for pelvic organ prolapse in Iceland and the UK Biobank.,"Olafsdottir T, Thorleifsson G, Sulem P, Stefansson OA, Medek H, Olafsson K, Ingthorsson O, Gudmundsson V, Jonsdottir I, Halldorsson GH, Kristjansson RP, Frigge ML, Stefansdottir L, Sigurdsson JK, Oddsson A, Sigurdsson A, Eggertsson HP, Melsted P, Halldorsson BV, Lund SH, Styrkarsdottir U, Steinthorsdottir V, Gudmundsson J, Holm H, Tragante V, Asselbergs FW, Thorsteinsdottir U, Gudbjartsson DF, Jonsdottir K, Rafnar T, Stefansson K.",,Communications biology,2020,2020-03-17,Y,,,,"Pelvic organ prolapse (POP) is a downward descent of one or more of the pelvic organs, resulting in a protrusion of the vaginal wall and/or uterus. We performed a genome-wide association study of POP using data from Iceland and the UK Biobank, a total of 15,010 cases with hospital-based diagnosis code and 340,734 female controls, and found eight sequence variants at seven loci associating with POP (P < 5 × 10-8); seven common (minor allele frequency >5%) and one with minor allele frequency of 4.87%. Some of the variants associating with POP also associated with traits of similar pathophysiology. Of these, rs3820282, which may alter the estrogen-based regulation of WNT4, also associates with leiomyoma of uterus, gestational duration and endometriosis. Rs3791675 at EFEMP1, a gene involved in connective tissue homeostasis, also associates with hernias and carpal tunnel syndrome. Our results highlight the role of connective tissue metabolism and estrogen exposure in the etiology of POP.",,pdf:https://www.nature.com/articles/s42003-020-0857-9.pdf; doi:https://doi.org/10.1038/s42003-020-0857-9; html:https://europepmc.org/articles/PMC7078216; pdf:https://europepmc.org/articles/PMC7078216?pdf=render -33905495,https://doi.org/10.1093/nar/gkab291,Endonuclease enrichment TAPS for cost-effective genome-wide base-resolution DNA methylation detection.,"Cheng J, Siejka-Zielińska P, Liu Y, Chandran A, Kriaucionis S, Song CX.",,Nucleic acids research,2021,2021-07-01,Y,,,,"Whole genome base-resolution methylome sequencing allows for the most comprehensive analysis of DNA methylation, however, the considerable sequencing cost often limits its applications. While reduced representation sequencing can be an affordable alternative, over 80% of CpGs in the genome are not covered. Building on our recently developed TET-assisted pyridine borane sequencing (TAPS) method, we here described endonuclease enrichment TAPS (eeTAPS), which utilizes dihydrouracil (DHU)-cleaving endonuclease digestion of TAPS-converted DNA to enrich methylated CpG sites (mCpGs). eeTAPS can accurately detect 87% of mCpGs in the mouse genome with a sequencing depth equivalent to 4× whole genome sequencing. In comparison, reduced representation TAPS (rrTAPS) detected less than 4% of mCpGs with 2.5× sequencing depth. Our results demonstrate eeTAPS to be a new strategy for cost-effective genome-wide methylation analysis at single-CpG resolution that can fill the gap between whole-genome and reduced representation sequencing.",,pdf:https://ora.ox.ac.uk/objects/uuid:3e48f9e0-d3c3-41ec-99ff-cc64d141d6cf/files/rcz30pt21m; doi:https://doi.org/10.1093/nar/gkab291; html:https://europepmc.org/articles/PMC8287915; pdf:https://europepmc.org/articles/PMC8287915?pdf=render 30681347,https://doi.org/10.1161/circgen.118.002328,Integrative Functional Annotation of 52 Genetic Loci Influencing Myocardial Mass Identifies Candidate Regulatory Variants and Target Genes.,"Hemerich D, Pei J, Harakalova M, van Setten J, Boymans S, Boukens BJ, Efimov IR, Michels M, van der Velden J, Vink A, Cheng C, van der Harst P, Moore JH, Mokry M, Tragante V, Asselbergs FW.",,Circulation. Genomic and precision medicine,2019,2019-02-01,N,Genetics; Electrocardiography; Acetylation; Heart Failure; Cardiomyopathies,The Human Phenome,,"

Background

Regulatory elements may be involved in the mechanisms by which 52 loci influence myocardial mass, reflected by abnormal amplitude and duration of the QRS complex on the ECG. Functional annotation thus far did not take into account how these elements are affected in disease context.

Methods

We generated maps of regulatory elements on hypertrophic cardiomyopathy patients (ChIP-seq N=14 and RNA-seq N=11) and nondiseased hearts (ChIP-seq N=4 and RNA-seq N=11). We tested enrichment of QRS-associated loci on elements differentially acetylated and directly regulating differentially expressed genes between hypertrophic cardiomyopathy patients and controls. We further performed functional annotation on QRS-associated loci using these maps of differentially active regulatory elements.

Results

Regions differentially affected in disease showed a stronger enrichment ( P=8.6×10-5) for QRS-associated variants than those not showing differential activity ( P=0.01). Promoters of genes differentially regulated between hypertrophic cardiomyopathy patients and controls showed more enrichment ( P=0.001) than differentially acetylated enhancers ( P=0.8) and super-enhancers ( P=0.025). We also identified 74 potential causal variants overlapping these differential regulatory elements. Eighteen of the genes mapped confirmed previous findings, now also pinpointing the potentially affected regulatory elements and candidate causal variants. Fourteen new genes were also mapped.

Conclusions

Our results suggest differentially active regulatory elements between hypertrophic cardiomyopathy patients and controls can offer more insights into the mechanisms of QRS-associated loci than elements not affected by disease.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCGEN.118.002328; doi:https://doi.org/10.1161/CIRCGEN.118.002328; html:https://europepmc.org/articles/PMC6380958; pdf:https://europepmc.org/articles/PMC6380958?pdf=render; doi:https://doi.org/10.1161/circgen.118.002328 +33905495,https://doi.org/10.1093/nar/gkab291,Endonuclease enrichment TAPS for cost-effective genome-wide base-resolution DNA methylation detection.,"Cheng J, Siejka-Zielińska P, Liu Y, Chandran A, Kriaucionis S, Song CX.",,Nucleic acids research,2021,2021-07-01,Y,,,,"Whole genome base-resolution methylome sequencing allows for the most comprehensive analysis of DNA methylation, however, the considerable sequencing cost often limits its applications. While reduced representation sequencing can be an affordable alternative, over 80% of CpGs in the genome are not covered. Building on our recently developed TET-assisted pyridine borane sequencing (TAPS) method, we here described endonuclease enrichment TAPS (eeTAPS), which utilizes dihydrouracil (DHU)-cleaving endonuclease digestion of TAPS-converted DNA to enrich methylated CpG sites (mCpGs). eeTAPS can accurately detect 87% of mCpGs in the mouse genome with a sequencing depth equivalent to 4× whole genome sequencing. In comparison, reduced representation TAPS (rrTAPS) detected less than 4% of mCpGs with 2.5× sequencing depth. Our results demonstrate eeTAPS to be a new strategy for cost-effective genome-wide methylation analysis at single-CpG resolution that can fill the gap between whole-genome and reduced representation sequencing.",,pdf:https://ora.ox.ac.uk/objects/uuid:3e48f9e0-d3c3-41ec-99ff-cc64d141d6cf/files/rcz30pt21m; doi:https://doi.org/10.1093/nar/gkab291; html:https://europepmc.org/articles/PMC8287915; pdf:https://europepmc.org/articles/PMC8287915?pdf=render 35103486,https://doi.org/10.1128/msystems.01132-21,Using Community Ecology Theory and Computational Microbiome Methods To Study Human Milk as a Biological System.,"Shenhav L, Azad MB.",,mSystems,2022,2022-02-01,Y,Lactation; Human Milk; Breastfeeding; Chronobiology; Computational Methods; System Biology; Human Microbiome; Community Ecology Theory,,,"Human milk is a complex and dynamic biological system that has evolved to optimally nourish and protect human infants. Yet, according to a recent priority-setting review, ""our current understanding of human milk composition and its individual components and their functions fails to fully recognize the importance of the chronobiology and systems biology of human milk in the context of milk synthesis, optimal timing and duration of feeding, and period of lactation"" (P. Christian et al., Am J Clin Nutr 113:1063-1072, 2021, https://doi.org/10.1093/ajcn/nqab075). We attribute this critical knowledge gap to three major reasons as follows. (i) Studies have typically examined each subsystem of the mother-milk-infant ""triad"" in isolation and often focus on a single element or component (e.g., maternal lactation physiology or milk microbiome or milk oligosaccharides or infant microbiome or infant gut physiology). This undermines our ability to develop comprehensive representations of the interactions between these elements and study their response to external perturbations. (ii) Multiomics studies are often cross-sectional, presenting a snapshot of milk composition, largely ignoring the temporal variability during lactation. The lack of temporal resolution precludes the characterization and inference of robust interactions between the dynamic subsystems of the triad. (iii) We lack computational methods to represent and decipher the complex ecosystem of the mother-milk-infant triad and its environment. In this review, we advocate for longitudinal multiomics data collection and demonstrate how incorporating knowledge gleaned from microbial community ecology and computational methods developed for microbiome research can serve as an anchor to advance the study of human milk and its many components as a ""system within a system.""",,doi:https://doi.org/10.1128/msystems.01132-21; doi:https://doi.org/10.1128/msystems.01132-21; html:https://europepmc.org/articles/PMC8805635; pdf:https://europepmc.org/articles/PMC8805635?pdf=render 30772400,https://doi.org/10.1016/j.neuroimage.2019.02.028,Hierarchical complexity of the adult human structural connectome.,"Smith K, Bastin ME, Cox SR, Valdés Hernández MC, Wiseman S, Escudero J, Sudlow C.",,NeuroImage,2019,2019-02-14,Y,MRI; Brain Networks; Hierarchical Complexity; Human Structural Connectome,The Human Phenome,,"The structural network of the human brain has a rich topology which many have sought to characterise using standard network science measures and concepts. However, this characterisation remains incomplete and the non-obvious features of this topology have largely confounded attempts towards comprehensive constructive modelling. This calls for new perspectives. Hierarchical complexity is an emerging paradigm of complex network topology based on the observation that complex systems are composed of hierarchies within which the roles of hierarchically equivalent nodes display highly variable connectivity patterns. Here we test the hierarchical complexity of the human structural connectomes of a group of seventy-nine healthy adults. Binary connectomes are found to be more hierarchically complex than three benchmark random network models. This provides a new key description of brain structure, revealing a rich diversity of connectivity patterns within hierarchically equivalent nodes. Dividing the connectomes into four tiers based on degree magnitudes indicates that the most complex nodes are neither those with the highest nor lowest degrees but are instead found in the middle tiers. Spatial mapping of the brain regions in each hierarchical tier reveals consistency with the current anatomical, functional and neuropsychological knowledge of the human brain. The most complex tier (Tier 3) involves regions believed to bridge high-order cognitive (Tier 1) and low-order sensorimotor processing (Tier 2). We then show that such diversity of connectivity patterns aligns with the diversity of functional roles played out across the brain, demonstrating that hierarchical complexity can characterise functional diversity strictly from the network topology.",,doi:https://doi.org/10.1016/j.neuroimage.2019.02.028; doi:https://doi.org/10.1016/j.neuroimage.2019.02.028; html:https://europepmc.org/articles/PMC6503942 35487729,https://doi.org/10.1136/bmjopen-2021-056541,"Associations of presenting symptoms and subsequent adverse clinical outcomes in people with unipolar depression: a prospective natural language processing (NLP), transdiagnostic, network analysis of electronic health record (EHR) data.","Patel R, Irving J, Brinn A, Taylor M, Shetty H, Pritchard M, Stewart R, Fusar-Poli P, McGuire P.",,BMJ open,2022,2022-04-29,Y,epidemiology; Health Informatics; Schizophrenia & Psychotic Disorders; Depression & Mood Disorders,,,"

Objective

To investigate the associations of symptoms of mania and depression with clinical outcomes in people with unipolar depression.

Design

A natural language processing electronic health record study. We used network analysis to determine symptom network structure and multivariable Cox regression to investigate associations with clinical outcomes.

Setting

The South London and Maudsley Clinical Record Interactive Search database.

Participants

All patients presenting with unipolar depression between 1 April 2006 and 31 March 2018.

Exposure

(1) Symptoms of mania: Elation; Grandiosity; Flight of ideas; Irritability; Pressured speech. (2) Symptoms of depression: Disturbed mood; Anhedonia; Guilt; Hopelessness; Helplessness; Worthlessness; Tearfulness; Low energy; Reduced appetite; Weight loss. (3) Symptoms of mania or depression (overlapping symptoms): Poor concentration; Insomnia; Disturbed sleep; Agitation; Mood instability.

Main outcomes

(1) Bipolar or psychotic disorder diagnosis. (2) Psychiatric hospital admission.

Results

Out of 19 707 patients, at least 1 depression, overlapping or mania symptom was present in 18 998 (96.4%), 15 954 (81.0%) and 4671 (23.7%) patients, respectively. 2772 (14.1%) patients subsequently developed bipolar or psychotic disorder during the follow-up period. The presence of at least one mania (HR 2.00, 95% CI 1.85 to 2.16), overlapping symptom (HR 1.71, 95% CI 1.52 to 1.92) or symptom of depression (HR 1.31, 95% CI 1.07 to 1.61) were associated with significantly increased risk of onset of a bipolar or psychotic disorder. Mania (HR 1.95, 95% CI 1.77 to 2.15) and overlapping symptoms (HR 1.76, 95% CI 1.52 to 2.04) were associated with greater risk for psychiatric hospital admission than symptoms of depression (HR 1.41, 95% CI 1.06 to 1.88).

Conclusions

The presence of mania or overlapping symptoms in people with unipolar depression is associated with worse clinical outcomes. Symptom-based approaches to defining clinical phenotype may facilitate a more personalised treatment approach and better predict subsequent clinical outcomes than psychiatric diagnosis alone.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/4/e056541.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-056541; html:https://europepmc.org/articles/PMC9058769; pdf:https://europepmc.org/articles/PMC9058769?pdf=render -37247330,https://doi.org/10.1093/eurheartj/ehad260,SCORE2-Diabetes: 10-year cardiovascular risk estimation in type 2 diabetes in Europe.,SCORE2-Diabetes Working Group and the ESC Cardiovascular Risk Collaboration.,,European heart journal,2023,2023-07-01,Y,Cardiovascular diseases; Prediction model; Diabetes,,,"

Aims

To develop and validate a recalibrated prediction model (SCORE2-Diabetes) to estimate the 10-year risk of cardiovascular disease (CVD) in individuals with type 2 diabetes in Europe.

Methods and results

SCORE2-Diabetes was developed by extending SCORE2 algorithms using individual-participant data from four large-scale datasets comprising 229 460 participants (43 706 CVD events) with type 2 diabetes and without previous CVD. Sex-specific competing risk-adjusted models were used including conventional risk factors (i.e. age, smoking, systolic blood pressure, total, and HDL-cholesterol), as well as diabetes-related variables (i.e. age at diabetes diagnosis, glycated haemoglobin [HbA1c] and creatinine-based estimated glomerular filtration rate [eGFR]). Models were recalibrated to CVD incidence in four European risk regions. External validation included 217 036 further individuals (38 602 CVD events), and showed good discrimination, and improvement over SCORE2 (C-index change from 0.009 to 0.031). Regional calibration was satisfactory. SCORE2-Diabetes risk predictions varied several-fold, depending on individuals' levels of diabetes-related factors. For example, in the moderate-risk region, the estimated 10-year CVD risk was 11% for a 60-year-old man, non-smoker, with type 2 diabetes, average conventional risk factors, HbA1c of 50 mmol/mol, eGFR of 90 mL/min/1.73 m2, and age at diabetes diagnosis of 60 years. By contrast, the estimated risk was 17% in a similar man, with HbA1c of 70 mmol/mol, eGFR of 60 mL/min/1.73 m2, and age at diabetes diagnosis of 50 years. For a woman with the same characteristics, the risk was 8% and 13%, respectively.

Conclusion

SCORE2-Diabetes, a new algorithm developed, calibrated, and validated to predict 10-year risk of CVD in individuals with type 2 diabetes, enhances identification of individuals at higher risk of developing CVD across Europe.",,pdf:https://academic.oup.com/eurheartj/advance-article-pdf/doi/10.1093/eurheartj/ehad260/50482240/ehad260.pdf; doi:https://doi.org/10.1093/eurheartj/ehad260; html:https://europepmc.org/articles/PMC10361012; pdf:https://europepmc.org/articles/PMC10361012?pdf=render 31794059,https://doi.org/10.1111/bjd.18778,What is the evidence for interactions between filaggrin null mutations and environmental exposures in the aetiology of atopic dermatitis? A systematic review.,"Blakeway H, Van-de-Velde V, Allen VB, Kravvas G, Palla L, Page MJ, Flohr C, Weller RB, Irvine AD, McPherson T, Roberts A, Williams HC, Reynolds N, Brown SJ, Paternoster L, Langan SM, (on behalf of UK TREND Eczema Network).",,The British journal of dermatology,2020,2020-02-11,Y,,,,"

Background

Epidemiological studies indicate that gene-environment interactions play a role in atopic dermatitis (AD).

Objectives

To review the evidence for gene-environment interactions in AD aetiology, focusing on filaggrin (FLG) loss-of-function mutations.

Methods

A systematic search from inception to September 2018 in Embase, MEDLINE and BIOSIS was performed. Search terms included all synonyms for AD and filaggrin/FLG; any genetic or epidemiological study design using any statistical methods were included. Quality assessment using criteria modified from guidance (ROBINS-I and Human Genome Epidemiology Network) for nonrandomized and genetic studies was completed, including consideration of power. Heterogeneity of study design and analyses precluded the use of meta-analysis.

Results

Of 1817 papers identified, 12 studies fulfilled the inclusion criteria required and performed formal interaction testing. There was some evidence for FLG-environment interactions in six of the studies (P-value for interaction ≤ 0·05), including early-life cat ownership, older siblings, water hardness, phthalate exposure, higher urinary phthalate metabolite levels (which all increased AD risk additional to FLG null genotype) and prolonged breastfeeding (which decreased AD risk in the context of FLG null genotype). Major limitations of published studies were the low numbers of individuals (ranging from five to 94) with AD and FLG loss-of-function mutations and exposure to specific environmental factors, and variation in exposure definitions.

Conclusions

Evidence on FLG-environment interactions in AD aetiology is limited. However, many of the studies lacked large enough sample sizes to assess these interactions fully. Further research is needed with larger sample sizes and clearly defined exposure assessment. Linked Comment: Park and Seo. Br J Dermatol 2020; 183:411.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/bjd.18778; doi:https://doi.org/10.1111/bjd.18778; html:https://europepmc.org/articles/PMC7496176; pdf:https://europepmc.org/articles/PMC7496176?pdf=render +37247330,https://doi.org/10.1093/eurheartj/ehad260,SCORE2-Diabetes: 10-year cardiovascular risk estimation in type 2 diabetes in Europe.,SCORE2-Diabetes Working Group and the ESC Cardiovascular Risk Collaboration.,,European heart journal,2023,2023-07-01,Y,Cardiovascular diseases; Prediction model; Diabetes,,,"

Aims

To develop and validate a recalibrated prediction model (SCORE2-Diabetes) to estimate the 10-year risk of cardiovascular disease (CVD) in individuals with type 2 diabetes in Europe.

Methods and results

SCORE2-Diabetes was developed by extending SCORE2 algorithms using individual-participant data from four large-scale datasets comprising 229 460 participants (43 706 CVD events) with type 2 diabetes and without previous CVD. Sex-specific competing risk-adjusted models were used including conventional risk factors (i.e. age, smoking, systolic blood pressure, total, and HDL-cholesterol), as well as diabetes-related variables (i.e. age at diabetes diagnosis, glycated haemoglobin [HbA1c] and creatinine-based estimated glomerular filtration rate [eGFR]). Models were recalibrated to CVD incidence in four European risk regions. External validation included 217 036 further individuals (38 602 CVD events), and showed good discrimination, and improvement over SCORE2 (C-index change from 0.009 to 0.031). Regional calibration was satisfactory. SCORE2-Diabetes risk predictions varied several-fold, depending on individuals' levels of diabetes-related factors. For example, in the moderate-risk region, the estimated 10-year CVD risk was 11% for a 60-year-old man, non-smoker, with type 2 diabetes, average conventional risk factors, HbA1c of 50 mmol/mol, eGFR of 90 mL/min/1.73 m2, and age at diabetes diagnosis of 60 years. By contrast, the estimated risk was 17% in a similar man, with HbA1c of 70 mmol/mol, eGFR of 60 mL/min/1.73 m2, and age at diabetes diagnosis of 50 years. For a woman with the same characteristics, the risk was 8% and 13%, respectively.

Conclusion

SCORE2-Diabetes, a new algorithm developed, calibrated, and validated to predict 10-year risk of CVD in individuals with type 2 diabetes, enhances identification of individuals at higher risk of developing CVD across Europe.",,pdf:https://academic.oup.com/eurheartj/advance-article-pdf/doi/10.1093/eurheartj/ehad260/50482240/ehad260.pdf; doi:https://doi.org/10.1093/eurheartj/ehad260; html:https://europepmc.org/articles/PMC10361012; pdf:https://europepmc.org/articles/PMC10361012?pdf=render 34321180,https://doi.org/10.1016/j.aucc.2021.05.013,The impact of distance on post-ICU disability.,"D'Arcy J, Haines K, Paul E, Doherty Z, Goodwin A, Bailey M, Barrett J, Bellomo R, Bucknall T, Gabbe BJ, Higgins AM, Iwashyna TJ, Murray LJ, Myles PS, Ponsford J, Pilcher D, Udy AA, Walker C, Young M, Cooper DJJ, Hodgson CL, ICU-Recovery Investigators.",,Australian critical care : official journal of the Confederation of Australian Critical Care Nurses,2022,2021-07-25,N,Quality of life; Mechanical ventilation; Distance; Disability; Intensive Care,,,"

Background

Nonurban residential living is associated with adverse outcomes for a number of chronic health conditions. However, it is unclear what effect it has amongst survivors of critical illness.

Objectives

The purpose of this study is to determine whether patients living greater than 50 km from the treating intensive care unit (ICU) have disability outcomes at 6 months that differ from people living within 50 km.

Methods

This was a multicentre, prospective cohort study conducted in five metropolitan ICUs. Participants were adults admitted to the ICU, who received >24 h of mechanical ventilation and survived to hospital discharge. In a secondary analysis of these data, the cohort was dichotomised based on residential distance from the treating ICU: <50 km and ≥50 km. The primary outcome was patient-reported disability using the 12-item World Health Organization's Disability Assessment Schedule (WHODAS 2.0). This was recorded at 6 months after ICU admission by telephone interview. Secondary outcomes included health status as measured by EQ-5D-5L return to work and psychological function as measured by the Hospital Anxiety and Depression Scale (HADS). Multivariable logistic regression was used to assess the association between distance from the ICU and moderate to severe disability, adjusted for potential confounders. Variables included in the multivariable model were deemed to be clinically relevant and had baseline imbalance between groups (p < 0.10). These included marital status and hours of mechanical ventilation. Sensitivity analysis was also conducted using distance in kilometres as a continuous variable.

Results

A total of 262 patients were enrolled, and 169 (65%) lived within 50 km of the treating ICU and 93 (35%) lived ≥50 km from the treating ICU (interquartile range [IQR] 10-664 km). There was no difference in patient-reported disability at 6 months between patients living <50 km and those living ≥50 km (WHODAS total disability % [IQR] 10.4 [2.08-25] v 14.6 [2.08-20.8], P = 0.74). There was also no difference between groups for the six major life domains of the WHODAS. There was no difference in rates of anxiety or depression as measured by HADS score (HADS anxiety median [IQR] 4 [1-7] v 3 [1-7], P = 0.60) (HADS depression median [IQR] 3 [1-6] v 3 [1-6], P = 0.62); health status as measured by EQ-5D (mean [SD] 66.7 [20] v 69.8 [22.2], P = 0.24); or health-related unemployment (% (N) 39 [26] v 25 [29.1], P = 0.61). After adjusting for confounders, living ≥50 km from the treating ICU was not associated with increased disability (odds ratio 0.61, 95% confidence interval: 0.33-1.16; P = 0.13) CONCLUSIONS: Survivors of intensive care in Victoria, Australia, who live at least 50 km from the treating ICU did not have greater disability than people living less than 50 km at 6 months after discharge. Living 50 km or more from the treating ICU was not associated with disability, nor was it associated with anxiety or depression, health status, or unemployment due to health.",,doi:https://doi.org/10.1016/j.aucc.2021.05.013 32862087,https://doi.org/10.1016/j.atherosclerosis.2020.07.014,Sex-specific predictors of PCSK9 levels in a European population: The IMPROVE study.,"Ferri N, Ruscica M, Coggi D, Bonomi A, Amato M, Frigerio B, Sansaro D, Ravani A, Veglia F, Capra N, Lupo MG, Macchi C, Castelnuovo S, Savonen K, Silveira A, Kurl S, Giral P, Pirro M, Strawbridge RJ, Gigante B, Smit AJ, Tremoli E, Colombo GI, Baldassarre D, IMPROVE study group.",,Atherosclerosis,2020,2020-07-30,N,Atherosclerosis; Cardiovascular risk factors; Sex differences; Pcsk9 Predictors,,,"

Background and aims

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is one of the key regulators of low-density lipoprotein cholesterol plasma levels. Circulating PCSK9, which differs between genders, represents a valid pharmacological target for preventing cardiovascular (CV) events. We aimed to investigate sex-related associations between PCSK9 plasma levels and biochemical and anthropomorphic factors, and familial and personal morbidities, in a large European cohort (n = 3673) of men (47.9%) and women (52.1%).

Methods

Individuals (aged 54-79 years) free of CV diseases were enrolled in seven centers of five European countries: Finland, France, Italy, the Netherlands, and Sweden. PCSK9 plasma levels were measured by ELISA.

Results

PCSK9 was higher in women than in men. Multiple linear regression analysis showed that latitude, sex, and treatments with statins and fibrates were the strongest predictors of PCSK9 in the whole group. These variables, together with triglycerides and high-density lipoprotein cholesterol, were also associated with PCSK9 in men or women. Mean corpuscular hemoglobin concentration and pack-years were PCSK9 independent predictors in women, whereas hypercholesterolemia and physical activity were independent predictors in men. The associations between PCSK9 and latitude, uric acid, diabetes, hypercholesterolemia and physical activity were significantly different in men and women (pinteraction <0.05 for all).

Conclusions

Besides confirming the association with lipids in the whole group, our study revealed previously unknown differences in PCSK9 predictors in men and women. These might be taken into account when defining individual risk for CV events and/or for refining PCSK9 lowering treatments.",,pdf:http://www.atherosclerosis-journal.com/article/S0021915020303816/pdf; doi:https://doi.org/10.1016/j.atherosclerosis.2020.07.014 37565978,https://doi.org/10.1016/j.jchf.2023.07.007,Penetrance and Prognosis of MYH7 Variant-Associated Cardiomyopathies: Results From a Dutch Multicenter Cohort Study.,"Jansen M, de Brouwer R, Hassanzada F, Schoemaker AE, Schmidt AF, Kooijman-Reumerman MD, Bracun V, Slieker MG, Dooijes D, Vermeer AMC, Wilde AAM, Amin AS, Lekanne Deprez RH, Herkert JC, Christiaans I, de Boer RA, Jongbloed JDH, van Tintelen JP, Asselbergs FW, Baas AF.",,JACC. Heart failure,2024,2023-08-09,N,Myosin; Screening; Prognosis; Cardiomyopathy; Penetrance; Myh7,,,"

Background

MYH7 variants cause hypertrophic cardiomyopathy (HCM), noncompaction cardiomyopathy (NCCM), and dilated cardiomyopathy (DCM). Screening of relatives of patients with genetic cardiomyopathy is recommended from 10 to 12 years of age onward, irrespective of the affected gene.

Objectives

This study sought to study the penetrance and prognosis of MYH7 variant-associated cardiomyopathies.

Methods

In this multicenter cohort study, penetrance and major cardiomyopathy-related events (MCEs) were assessed in carriers of (likely) pathogenic MYH7 variants by using Kaplan-Meier curves and log-rank tests. Prognostic factors were evaluated using Cox regression with time-dependent coefficients.

Results

In total, 581 subjects (30.1% index patients, 48.4% male, median age 37.0 years [IQR: 19.5-50.2 years]) were included. HCM was diagnosed in 226 subjects, NCCM in 70, and DCM in 55. Early penetrance and MCEs (age <12 years) were common among NCCM-associated variant carriers (21.2% and 12.0%, respectively) and DCM-associated variant carriers (15.3% and 10.0%, respectively), compared with HCM-associated variant carriers (2.9% and 2.1%, respectively). Penetrance was significantly increased in carriers of converter region variants (adjusted HR: 1.87; 95% CI: 1.15-3.04; P = 0.012) and at age ≤1 year in NCCM-associated or DCM-associated variant carriers (adjusted HR: 21.17; 95% CI: 4.81-93.20; P < 0.001) and subjects with a family history of early MCEs (adjusted HR: 2.45; 95% CI: 1.09-5.50; P = 0.030). The risk of MCE was increased in subjects with a family history of early MCEs (adjusted HR: 1.82; 95% CI: 1.15-2.87; P = 0.010) and at age ≤5 years in NCCM-associated or DCM-associated variant carriers (adjusted HR: 38.82; 95% CI: 5.16-291.88; P < 0.001).

Conclusions

MYH7 variants can cause cardiomyopathies and MCEs at a young age. Screening at younger ages may be warranted, particularly in carriers of NCCM- or DCM-associated variants and/or with a family history of MCEs at <12 years.",,doi:https://doi.org/10.1016/j.jchf.2023.07.007 @@ -2304,18 +2304,18 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 31013802,https://doi.org/10.3390/ijerph16081325,Using Patient-Reported Outcomes to Predict Revision Arthroplasty Following Femoral Neck Fracture: Enhancing the Value of Clinical Registries through Data Linkage.,"Ekegren CL, de Steiger R, Edwards ER, Page RS, Hau R, Liew S, Oppy A, Gabbe BJ.",,International journal of environmental research and public health,2019,2019-04-12,Y,Pain; Femoral neck fractures; Arthroplasty; Registries; Patient Reported Outcome Measures,Improving Public Health,,"The aim of this study was to determine the association between patient-reported outcome measures (PROMs) six months following femoral neck fracture after a low fall and future arthroplasty, and the factors associated with this. Six-month post-fracture PROMs were collected from the Victorian Orthopaedic Trauma Outcomes Registry (VOTOR) for patients aged >55 years who were admitted for a femoral neck fracture after a low fall between March 2007 and June 2015. These cases were linked with those registered by Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) up to October 2016. Multivariable analysis was performed using a Cox proportional hazards model to determine factors associated with future arthroplasty, including six-month PROMs. Of the 7077 hip fracture patients registered by VOTOR during the study period, 2325 met the inclusion criteria. Internal fixation being used for the initial hip fracture surgery, being younger and having no pre-injury disability were all independently associated with future revision or conversion to arthroplasty. Out of all PROMs, reporting pain and discomfort six months post-fracture was associated with a 9.5-fold increase in the risk of future arthroplasty (95% CI: 3.81, 23.67). The value of clinical registries can be enhanced via data linkage, in this case by using PROMs to predict arthroplasty following femoral neck fracture.",,pdf:https://www.mdpi.com/1660-4601/16/8/1325/pdf?version=1555077276; doi:https://doi.org/10.3390/ijerph16081325; html:https://europepmc.org/articles/PMC6517898; pdf:https://europepmc.org/articles/PMC6517898?pdf=render 31806382,https://doi.org/10.1016/j.injury.2019.11.023,Variation in documented inhalation injury rates following burn injury in Australia and New Zealand.,"Tracy LM, Dyson K, Mercier LL, Cleland H, McInnes JA, Cameron PA, Singer Y, Edgar DW, Darton A, Gabbe BJ.",,Injury,2020,2019-11-17,N,Variation; Australia; New Zealand; Inhalation Injury; Burn Registry,,,"

Introduction

The negative impact of inhalation injuries on in-hospital outcomes for burn patients is well known, but the burns community is yet to form a consensus on diagnostic criteria and clinical definitions. The diagnosis of inhalation injuries is consequently highly subjective. This study aimed to assess the variation in the rate of documented inhalation injury for adult patients in Australian and New Zealand burn units.

Methods

Data for sequential admissions collected from eight adult burn centres across Australia and New Zealand between July 2009 and June 2016 were extracted from the Burns Registry of Australia and New Zealand (BRANZ). Inhalation injury was classified in two ways: (i) a field in the BRANZ data dictionary, and (ii) through a series of International Classification of Disease 10th Revision Australian Modification (ICD-10-AM) codes. Variation in inhalation injury prevalence was assessed using descriptive statistics, funnel plots, logistic regression, and predicted probabilities.

Results

There were 11,206 admissions to BRANZ sites over the study period. Inhalation injury prevalence was the highest at Site D (13.1% for the BRANZ field and 11.8% for the ICD-10-AM codes), but there was significant variation between the contributing sites and the inhalation injury classification methods.

Conclusion

There is significant variation in the prevalence of documented inhalation injury among Australian and New Zealand burns units. The variation in the prevalence of documented inhalation injury across Australian and New Zealand sites reinforces the need for a consensus definition in the diagnosis of these injuries. Further work is required to improve data quality and reconcile the differences between clinical and ICD-10-AM coding prevalence before changes in clinical practice can be recommended from these data.",,doi:https://doi.org/10.1016/j.injury.2019.11.023 35523486,https://doi.org/10.1136/bmjopen-2021-059258,Using digital health tools for the Remote Assessment of Treatment Prognosis in Depression (RAPID): a study protocol for a feasibility study.,"de Angel V, Lewis S, Munir S, Matcham F, Dobson R, Hotopf M.",,BMJ open,2022,2022-05-06,Y,Mental health; Anxiety Disorders; Health Informatics; Depression & Mood Disorders,,,"

Introduction

Digital health tools such as smartphones and wearable devices could improve psychological treatment outcomes in depression through more accurate and comprehensive measures of patient behaviour. However, in this emerging field, most studies are small and based on student populations outside of a clinical setting. The current study aims to determine the feasibility and acceptability of using smartphones and wearable devices to collect behavioural and clinical data in people undergoing therapy for depressive disorders and establish the extent to which they can be potentially useful biomarkers of depression and recovery after treatment.

Methods and analysis

This is an observational, prospective cohort study of 65 people attending psychological therapy for depression in multiple London-based sites. It will collect continuous passive data from smartphone sensors and a Fitbit fitness tracker, and deliver questionnaires, speech tasks and cognitive assessments through smartphone-based apps. Objective data on sleep, physical activity, location, Bluetooth contact, smartphone use and heart rate will be gathered for 7 months, and compared with clinical and contextual data. A mixed methods design, including a qualitative interview of patient experiences, will be used to evaluate key feasibility indicators, digital phenotypes of depression and therapy prognosis. Patient and public involvement was sought for participant-facing documents and the study design of the current research proposal.

Ethics and dissemination

Ethical approval has been obtained from the London Westminster Research Ethics Committee, and the Health Research Authority, Integrated Research Application System (project ID: 270918). Privacy and confidentiality will be guaranteed and the procedures for handling, processing, storage and destruction of the data will comply with the General Data Protection Regulation. Findings from this study will form part of a doctoral thesis, will be presented at national and international meetings or academic conferences and will generate manuscripts to be submitted to peer-reviewed journals.

Trial registration number

https://doi.org/10.17605/OSF.IO/PMYTA.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/5/e059258.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-059258; html:https://europepmc.org/articles/PMC9083394; pdf:https://europepmc.org/articles/PMC9083394?pdf=render -36568709,https://doi.org/10.1136/bmjmed-2022-000215,Burden and treatment of chronic obstructive pulmonary disease among people using illicit opioids: matched cohort study in England.,"Lewer D, Cox S, Hurst JR, Padmanathan P, Petersen I, Quint JK.",,BMJ medicine,2022,2022-09-28,Y,"Substance-related disorders; Pulmonary disease, chronic obstructive; epidemiology; Health Services; Primary Health Care; Healthcare Disparities",,,"

Objective

To understand the burden of chronic obstructive pulmonary disease among people who use illicit opioids such as heroin, and evaluate inequalities in treatment.

Design

Cohort study.

Setting

Patients registered at primary care practices in England.

Participants

106 789 patients in the Clinical Practice Research Datalink with illicit opioid use recorded between 2001 and 2018, and a subcohort of 3903 patients with a diagnosis of chronic obstructive pulmonary disease. For both cohorts, the study sampled a comparison group with no history of illicit opioids that was matched by age, sex, and general practice.

Main outcome measures

In the base cohort: diagnosis of chronic obstructive pulmonary disease and death due to the disease. In the subcohort: five treatments (influenza vaccine, pneumococcal vaccine, pulmonary rehabilitation, bronchodilators or corticosteroids, and smoking cessation support) and exacerbations requiring hospital admission.

Results

680 of 106 789 participants died due to chronic obstructive pulmonary disease, representing 5.1% of all cause deaths. Illicit opioid use was associated with 14.59 times (95% confidence interval 12.28 to 17.33) the risk of death related to chronic obstructive pulmonary disease, and 5.89 times (5.62 to 6.18) the risk of a diagnosis of the disease. Among patients with a new diagnosis, comorbid illicit opioid use was associated with current smoking, underweight, worse lung function, and more severe breathlessness. After adjusting for these differences, illicit opioids were associated with 1.96 times (1.82 to 2.12) times the risk of exacerbations requiring hospital admission, but not associated with a substantially different probability of the five treatments.

Conclusions

Death due to chronic obstructive pulmonary disease is about 15 times more common among people who use illicit opioids than the general population. This inequality does not appear to be explained by differences in treatment, but late diagnosis of the disease among people who use illicit opioids might contribute.",,pdf:https://bmjmedicine.bmj.com/content/bmjmed/1/1/e000215.full.pdf; doi:https://doi.org/10.1136/bmjmed-2022-000215; html:https://europepmc.org/articles/PMC9770021; pdf:https://europepmc.org/articles/PMC9770021?pdf=render 35296488,https://doi.org/10.1136/bmjopen-2021-058552,"AlzEye: longitudinal record-level linkage of ophthalmic imaging and hospital admissions of 353 157 patients in London, UK.","Wagner SK, Hughes F, Cortina-Borja M, Pontikos N, Struyven R, Liu X, Montgomery H, Alexander DC, Topol E, Petersen SE, Balaskas K, Hindley J, Petzold A, Rahi JS, Denniston AK, Keane PA.",,BMJ open,2022,2022-03-16,Y,Ophthalmology; Health Informatics; Medical Retina; Medical Ophthalmology,,,"

Purpose

Retinal signatures of systemic disease ('oculomics') are increasingly being revealed through a combination of high-resolution ophthalmic imaging and sophisticated modelling strategies. Progress is currently limited not mainly by technical issues, but by the lack of large labelled datasets, a sine qua non for deep learning. Such data are derived from prospective epidemiological studies, in which retinal imaging is typically unimodal, cross-sectional, of modest number and relates to cohorts, which are not enriched with subpopulations of interest, such as those with systemic disease. We thus linked longitudinal multimodal retinal imaging from routinely collected National Health Service (NHS) data with systemic disease data from hospital admissions using a privacy-by-design third-party linkage approach.

Participants

Between 1 January 2008 and 1 April 2018, 353 157 participants aged 40 years or older, who attended Moorfields Eye Hospital NHS Foundation Trust, a tertiary ophthalmic institution incorporating a principal central site, four district hubs and five satellite clinics in and around London, UK serving a catchment population of approximately six million people.

Findings to date

Among the 353 157 individuals, 186 651 had a total of 1 337 711 Hospital Episode Statistics admitted patient care episodes. Systemic diagnoses recorded at these episodes include 12 022 patients with myocardial infarction, 11 735 with all-cause stroke and 13 363 with all-cause dementia. A total of 6 261 931 retinal images of seven different modalities and across three manufacturers were acquired from 1 54 830 patients. The majority of retinal images were retinal photographs (n=1 874 175) followed by optical coherence tomography (n=1 567 358).

Future plans

AlzEye combines the world's largest single institution retinal imaging database with nationally collected systemic data to create an exceptional large-scale, enriched cohort that reflects the diversity of the population served. First analyses will address cardiovascular diseases and dementia, with a view to identifying hidden retinal signatures that may lead to earlier detection and risk management of these life-threatening conditions.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/3/e058552.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-058552; html:https://europepmc.org/articles/PMC8928293; pdf:https://europepmc.org/articles/PMC8928293?pdf=render +36568709,https://doi.org/10.1136/bmjmed-2022-000215,Burden and treatment of chronic obstructive pulmonary disease among people using illicit opioids: matched cohort study in England.,"Lewer D, Cox S, Hurst JR, Padmanathan P, Petersen I, Quint JK.",,BMJ medicine,2022,2022-09-28,Y,"Substance-related disorders; Pulmonary disease, chronic obstructive; epidemiology; Health Services; Primary Health Care; Healthcare Disparities",,,"

Objective

To understand the burden of chronic obstructive pulmonary disease among people who use illicit opioids such as heroin, and evaluate inequalities in treatment.

Design

Cohort study.

Setting

Patients registered at primary care practices in England.

Participants

106 789 patients in the Clinical Practice Research Datalink with illicit opioid use recorded between 2001 and 2018, and a subcohort of 3903 patients with a diagnosis of chronic obstructive pulmonary disease. For both cohorts, the study sampled a comparison group with no history of illicit opioids that was matched by age, sex, and general practice.

Main outcome measures

In the base cohort: diagnosis of chronic obstructive pulmonary disease and death due to the disease. In the subcohort: five treatments (influenza vaccine, pneumococcal vaccine, pulmonary rehabilitation, bronchodilators or corticosteroids, and smoking cessation support) and exacerbations requiring hospital admission.

Results

680 of 106 789 participants died due to chronic obstructive pulmonary disease, representing 5.1% of all cause deaths. Illicit opioid use was associated with 14.59 times (95% confidence interval 12.28 to 17.33) the risk of death related to chronic obstructive pulmonary disease, and 5.89 times (5.62 to 6.18) the risk of a diagnosis of the disease. Among patients with a new diagnosis, comorbid illicit opioid use was associated with current smoking, underweight, worse lung function, and more severe breathlessness. After adjusting for these differences, illicit opioids were associated with 1.96 times (1.82 to 2.12) times the risk of exacerbations requiring hospital admission, but not associated with a substantially different probability of the five treatments.

Conclusions

Death due to chronic obstructive pulmonary disease is about 15 times more common among people who use illicit opioids than the general population. This inequality does not appear to be explained by differences in treatment, but late diagnosis of the disease among people who use illicit opioids might contribute.",,pdf:https://bmjmedicine.bmj.com/content/bmjmed/1/1/e000215.full.pdf; doi:https://doi.org/10.1136/bmjmed-2022-000215; html:https://europepmc.org/articles/PMC9770021; pdf:https://europepmc.org/articles/PMC9770021?pdf=render 36434067,https://doi.org/10.1038/s42003-022-04252-5,A conserved glutathione binding site in poliovirus is a target for antivirals and vaccine stabilisation.,"Bahar MW, Nasta V, Fox H, Sherry L, Grehan K, Porta C, Macadam AJ, Stonehouse NJ, Rowlands DJ, Fry EE, Stuart DI.",,Communications biology,2022,2022-11-25,Y,,,,"Strategies to prevent the recurrence of poliovirus (PV) after eradication may utilise non-infectious, recombinant virus-like particle (VLP) vaccines. Despite clear advantages over inactivated or attenuated virus vaccines, instability of VLPs can compromise their immunogenicity. Glutathione (GSH), an important cellular reducing agent, is a crucial co-factor for the morphogenesis of enteroviruses, including PV. We report cryo-EM structures of GSH bound to PV serotype 3 VLPs showing that it can enhance particle stability. GSH binds the positively charged pocket at the interprotomer interface shown recently to bind GSH in enterovirus F3 and putative antiviral benzene sulphonamide compounds in other enteroviruses. We show, using high-resolution cryo-EM, the binding of a benzene sulphonamide compound with a PV serotype 2 VLP, consistent with antiviral activity through over-stabilizing the interprotomer pocket, preventing the capsid rearrangements necessary for viral infection. Collectively, these results suggest GSH or an analogous tight-binding antiviral offers the potential for stabilizing VLP vaccines.",,pdf:https://www.nature.com/articles/s42003-022-04252-5.pdf; doi:https://doi.org/10.1038/s42003-022-04252-5; html:https://europepmc.org/articles/PMC9700776; pdf:https://europepmc.org/articles/PMC9700776?pdf=render 30921401,https://doi.org/10.1371/journal.pone.0214607,Effect of impregnated central venous catheters on thrombosis in paediatric intensive care: Post-hoc analyses of the CATCH trial.,"Wu Y, Fraser C, Gilbert R, Mok Q.",,PloS one,2019,2019-03-28,Y,,"Better, Faster and More Efficient Clinical Trials",,"

Purpose

The CATheter infections in CHildren (CATCH) trial reported reduced risks of bloodstream infection with antibiotic impregnated compared with heparin-bonded or standard central venous catheters (CVC) in paediatric intensive care. CVC impregnation did not increase the risk of thrombosis which was recorded in 24% of participants. This post-hoc analysis determines the effect of CVC impregnation on the risk of thrombosis leading to CVC removal or swollen limb.

Methods

We analysed patients in the CATCH trial, blind to CVC allocation, to define clinically relevant thrombosis based on the clinical sign most frequently recorded in patients where the CVC was removed because of concerns regarding thrombosis. In post-hoc, three-way comparisons of antibiotic, heparin and standard CVCs, we determined the effect of CVC type on time to clinically relevant thrombosis, using Cox proportional hazards regression.

Results

Of 1409 participants with a successful CVC insertion, the sign most frequently resulting in CVC removal was swollen limb (37.6%; 41/109), with lower rates of removal of CVC following 2 episodes of difficulty withdrawing blood or of flushing to unblock the CVC. In intention to treat analyses (n = 1485), clinically relevant thrombosis, defined by 1 or more record of swollen limb or CVC removal due to concerns about thrombosis, was recorded in 11.9% (58/486) of antibiotic CVCs, 12.1% (60/497) of heparin CVCs, and 10.2% (51/502) of standard CVCs. We found no differences in time to clinically relevant thrombosis according to type of CVC.

Conclusions

We found no evidence for an increased risk of clinically relevant thrombosis in antibiotic impregnated compared to heparin-bonded or standard CVCs in children receiving intensive care.",,pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0214607&type=printable; doi:https://doi.org/10.1371/journal.pone.0214607; html:https://europepmc.org/articles/PMC6438638; pdf:https://europepmc.org/articles/PMC6438638?pdf=render 36436752,https://doi.org/10.1016/j.ijid.2022.11.024,"Outcomes of laboratory-confirmed SARS-CoV-2 infection during resurgence driven by Omicron lineages BA.4 and BA.5 compared with previous waves in the Western Cape Province, South Africa.","Davies MA, Morden E, Rousseau P, Arendse J, Bam JL, Boloko L, Cloete K, Cohen C, Chetty N, Dane P, Heekes A, Hsiao NY, Hunter M, Hussey H, Jacobs T, Jassat W, Kariem S, Kassanjee R, Laenen I, Roux SL, Lessells R, Mahomed H, Maughan D, Meintjes G, Mendelson M, Mnguni A, Moodley M, Murie K, Naude J, Ntusi NAB, Paleker M, Parker A, Pienaar D, Preiser W, Prozesky H, Raubenheimer P, Rossouw L, Schrueder N, Smith B, Smith M, Solomon W, Symons G, Taljaard J, Wasserman S, Wilkinson RJ, Wolmarans M, Wolter N, Boulle A.",,International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases,2023,2022-11-24,Y,"Covid-19; Omicron; Ba.4; Ba.5; Death, Severe Hospitalization",,,"

Objectives

We aimed to compare the clinical severity of Omicron BA.4/BA.5 infection with BA.1 and earlier variant infections among laboratory-confirmed SARS-CoV-2 cases in the Western Cape, South Africa, using timing of infection to infer the lineage/variant causing infection.

Methods

We included public sector patients aged ≥20 years with laboratory-confirmed COVID-19 between May 01-May 21, 2022 (BA.4/BA.5 wave) and equivalent previous wave periods. We compared the risk between waves of (i) death and (ii) severe hospitalization/death (all within 21 days of diagnosis) using Cox regression adjusted for demographics, comorbidities, admission pressure, vaccination, and previous infection.

Results

Among 3793 patients from the BA.4/BA.5 wave and 190,836 patients from previous waves, the risk of severe hospitalization/death was similar in the BA.4/BA.5 and BA.1 waves (adjusted hazard ratio [aHR] 1.12; 95% confidence interval [CI] 0.93; 1.34). Both Omicron waves had a lower risk of severe outcomes than previous waves. Previous infection (aHR 0.29, 95% CI 0.24; 0.36) and vaccination (aHR 0.17; 95% CI 0.07; 0.40 for at least three doses vs no vaccine) were protective.

Conclusion

Disease severity was similar among diagnosed COVID-19 cases in the BA.4/BA.5 and BA.1 periods in the context of growing immunity against SARS-CoV-2 due to previous infection and vaccination, both of which were strongly protective.",,doi:https://doi.org/10.1016/j.ijid.2022.11.024; doi:https://doi.org/10.1016/j.ijid.2022.11.024; html:https://europepmc.org/articles/PMC9686046; pdf:https://europepmc.org/articles/PMC9686046?pdf=render 31666709,https://doi.org/10.1038/s41433-019-0657-y,Comment on: 'Quantification of anterior chamber reaction after intravitreal injections of conbercept and ranibizumab: a pilot study'.,"Minocha A, Liu X, Denniston AK, Petrushkin H, Solebo AL.",,"Eye (London, England)",2020,2019-10-30,N,,,,,,pdf:https://www.nature.com/articles/s41433-019-0657-y.pdf; doi:https://doi.org/10.1038/s41433-019-0657-y; html:https://europepmc.org/articles/PMC7376231; pdf:https://europepmc.org/articles/PMC7376231?pdf=render; doi:https://doi.org/10.1038/s41433-019-0657-y 38514079,https://doi.org/10.1136/bmj-2023-077764,Community based complex interventions to sustain independence in older people: systematic review and network meta-analysis.,"Crocker TF, Ensor J, Lam N, Jordão M, Bajpai R, Bond M, Forster A, Riley RD, Andre D, Brundle C, Ellwood A, Green J, Hale M, Mirza L, Morgan J, Patel I, Patetsini E, Prescott M, Ramiz R, Todd O, Walford R, Gladman J, Clegg A.",,BMJ (Clinical research ed.),2024,2024-03-21,Y,,,,"

Objective

To synthesise evidence of the effectiveness of community based complex interventions, grouped according to their intervention components, to sustain independence for older people.

Design

Systematic review and network meta-analysis.

Data sources

Medline, Embase, CINAHL, PsycINFO, CENTRAL, clinicaltrials.gov, and International Clinical Trials Registry Platform from inception to 9 August 2021 and reference lists of included studies.

Eligibility criteria

Randomised controlled trials or cluster randomised controlled trials with ≥24 weeks' follow-up studying community based complex interventions for sustaining independence in older people (mean age ≥65 years) living at home, with usual care, placebo, or another complex intervention as comparators.

Main outcomes

Living at home, activities of daily living (personal/instrumental), care home placement, and service/economic outcomes at 12 months.

Data synthesis

Interventions were grouped according to a specifically developed typology. Random effects network meta-analysis estimated comparative effects; Cochrane's revised tool (RoB 2) structured risk of bias assessment. Grading of recommendations assessment, development and evaluation (GRADE) network meta-analysis structured certainty assessment.

Results

The review included 129 studies (74 946 participants). Nineteen intervention components, including ""multifactorial action from individualised care planning"" (a process of multidomain assessment and management leading to tailored actions), were identified in 63 combinations. For living at home, compared with no intervention/placebo, evidence favoured multifactorial action from individualised care planning including medication review and regular follow-ups (routine review) (odds ratio 1.22, 95% confidence interval 0.93 to 1.59; moderate certainty); multifactorial action from individualised care planning including medication review without regular follow-ups (2.55, 0.61 to 10.60; low certainty); combined cognitive training, medication review, nutritional support, and exercise (1.93, 0.79 to 4.77; low certainty); and combined activities of daily living training, nutritional support, and exercise (1.79, 0.67 to 4.76; low certainty). Risk screening or the addition of education and self-management strategies to multifactorial action from individualised care planning and routine review with medication review may reduce odds of living at home. For instrumental activities of daily living, evidence favoured multifactorial action from individualised care planning and routine review with medication review (standardised mean difference 0.11, 95% confidence interval 0.00 to 0.21; moderate certainty). Two interventions may reduce instrumental activities of daily living: combined activities of daily living training, aids, and exercise; and combined activities of daily living training, aids, education, exercise, and multifactorial action from individualised care planning and routine review with medication review and self-management strategies. For personal activities of daily living, evidence favoured combined exercise, multifactorial action from individualised care planning, and routine review with medication review and self-management strategies (0.16, -0.51 to 0.82; low certainty). For homecare recipients, evidence favoured addition of multifactorial action from individualised care planning and routine review with medication review (0.60, 0.32 to 0.88; low certainty). High risk of bias and imprecise estimates meant that most evidence was low or very low certainty. Few studies contributed to each comparison, impeding evaluation of inconsistency and frailty.

Conclusions

The intervention most likely to sustain independence is individualised care planning including medicines optimisation and regular follow-up reviews resulting in multifactorial action. Homecare recipients may particularly benefit from this intervention. Unexpectedly, some combinations may reduce independence. Further research is needed to investigate which combinations of interventions work best for different participants and contexts.

Registration

PROSPERO CRD42019162195.",,doi:https://doi.org/10.1136/bmj-2023-077764; html:https://europepmc.org/articles/PMC10955723 35188868,https://doi.org/10.1080/19490976.2022.2038863,The potential of fecal microbiota and amino acids to detect and monitor patients with adenoma.,"Bosch S, Acharjee A, Quraishi MN, Rojas P, Bakkali A, Jansen EE, Brizzio Brentar M, Kuijvenhoven J, Stokkers P, Struys E, Beggs AD, Gkoutos GV, de Meij TG, de Boer NK.",,Gut microbes,2022,2022-01-01,Y,Biomarker; Surveillance; Adenoma; Colorectal Cancer; Omics,,,"The risk of recurrent dysplastic colonic lesions is increased following polypectomy. Yield of endoscopic surveillance after adenoma removal is low, while interval colorectal cancers occur. To longitudinally assess the dynamics of fecal microbiota and amino acids in the presence of adenomatous lesions and after their endoscopic removal. In this longitudinal case-control study, patients collected fecal samples prior to bowel preparation before scheduled colonoscopy and 3 months after this intervention. Based on colonoscopy outcomes, patients with advanced adenomas and nonadvanced adenomas (0.5-1.0 cm) who underwent polypectomy during endoscopy (n = 19) were strictly matched on age, body-mass index, and smoking habits to controls without endoscopic abnormalities (n = 19). Microbial taxa were measured by 16S RNA sequencing, and amino acids (AA) were measured by high-performance liquid chromatography (HPLC). Adenoma patients were discriminated from controls based on AA and microbial composition. Levels of proline (p = .001), ornithine (p = .02) and serine (p = .02) were increased in adenoma patients compared to controls but decreased to resemble those of controls after adenoma removal. These AAs were combined as a potential adenoma-specific panel (AUC 0.79(0.64-0.94)). For bacterial taxa, differences between patients with adenomas and controls were found (Bifidobacterium spp.↓, Anaerostipes spp.↓, Butyricimonas spp.↑, Faecalitalea spp.↑ and Catenibacterium spp.↑), but no alterations in relative abundance were observed after polypectomy. Furthermore, Faecalitalea spp. and Butyricimonas spp. were significantly correlated with adenoma-specific amino acids. We selected an amino acid panel specifically increased in the presence of adenomas and a microbial signature present in adenoma patients, irrespective of polypectomy. Upon validation, these panels may improve the effectiveness of the surveillance program by detection of high-risk individuals and determination of surveillance endoscopy timing, leading to less unnecessary endoscopies and less interval cancer.",,pdf:https://www.tandfonline.com/doi/pdf/10.1080/19490976.2022.2038863?needAccess=true; doi:https://doi.org/10.1080/19490976.2022.2038863; html:https://europepmc.org/articles/PMC8865277; pdf:https://europepmc.org/articles/PMC8865277?pdf=render -38508198,https://doi.org/10.1016/j.xgen.2024.100523,Integrative polygenic risk score improves the prediction accuracy of complex traits and diseases.,"Truong B, Hull LE, Ruan Y, Huang QQ, Hornsby W, Martin H, van Heel DA, Wang Y, Martin AR, Lee SH, Natarajan P.",,Cell genomics,2024,2024-03-19,Y,Combination; Clinical Utility; South Asian; Integrative; Prs; Cross Ancestry,,,"Polygenic risk scores (PRSs) are an emerging tool to predict the clinical phenotypes and outcomes of individuals. We propose PRSmix, a framework that leverages the PRS corpus of a target trait to improve prediction accuracy, and PRSmix+, which incorporates genetically correlated traits to better capture the human genetic architecture for 47 and 32 diseases/traits in European and South Asian ancestries, respectively. PRSmix demonstrated a mean prediction accuracy improvement of 1.20-fold (95% confidence interval [CI], [1.10; 1.3]; p = 9.17 × 10-5) and 1.19-fold (95% CI, [1.11; 1.27]; p = 1.92 × 10-6), and PRSmix+ improved the prediction accuracy by 1.72-fold (95% CI, [1.40; 2.04]; p = 7.58 × 10-6) and 1.42-fold (95% CI, [1.25; 1.59]; p = 8.01 × 10-7) in European and South Asian ancestries, respectively. Compared to the previously cross-trait-combination methods with scores from pre-defined correlated traits, we demonstrated that our method improved prediction accuracy for coronary artery disease up to 3.27-fold (95% CI, [2.1; 4.44]; p value after false discovery rate (FDR) correction = 2.6 × 10-4). Our method provides a comprehensive framework to benchmark and leverage the combined power of PRS for maximal performance in a desired target population.",,doi:https://doi.org/10.1016/j.xgen.2024.100523; html:https://europepmc.org/articles/PMC11019356; pdf:https://europepmc.org/articles/PMC11019356?pdf=render 34240696,https://doi.org/10.2807/1560-7917.es.2021.26.27.2000004,"Nanopore metagenomic sequencing of influenza virus directly from respiratory samples: diagnosis, drug resistance and nosocomial transmission, United Kingdom, 2018/19 influenza season.","Xu Y, Lewandowski K, Downs LO, Kavanagh J, Hender T, Lumley S, Jeffery K, Foster D, Sanderson ND, Vaughan A, Morgan M, Vipond R, Carroll M, Peto T, Crook D, Walker AS, Matthews PC, Pullan ST.",,Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin,2021,2021-07-01,Y,Genetic diversity; Influenza; Diagnosis; Metagenomics; Antiviral Drug Resistance; Nanopore; Respiratory Viruses; Nosocomial Transmission,,,"BackgroundInfluenza virus presents a considerable challenge to public health by causing seasonal epidemics and occasional pandemics. Nanopore metagenomic sequencing has the potential to be deployed for near-patient testing, providing rapid infection diagnosis, rationalising antimicrobial therapy, and supporting infection-control interventions.AimTo evaluate the applicability of this sequencing approach as a routine laboratory test for influenza in clinical settings.MethodsWe conducted Oxford Nanopore Technologies (Oxford, United Kingdom (UK)) metagenomic sequencing for 180 respiratory samples from a UK hospital during the 2018/19 influenza season, and compared results to routine molecular diagnostic standards (Xpert Xpress Flu/RSV assay; BioFire FilmArray Respiratory Panel 2 assay). We investigated drug resistance, genetic diversity, and nosocomial transmission using influenza sequence data.ResultsCompared to standard testing, Nanopore metagenomic sequencing was 83% (75/90) sensitive and 93% (84/90) specific for detecting influenza A viruses. Of 59 samples with haemagglutinin subtype determined, 40 were H1 and 19 H3. We identified an influenza A(H3N2) genome encoding the oseltamivir resistance S331R mutation in neuraminidase, potentially associated with an emerging distinct intra-subtype reassortant. Whole genome phylogeny refuted suspicions of a transmission cluster in a ward, but identified two other clusters that likely reflected nosocomial transmission, associated with a predominant community-circulating strain. We also detected other potentially pathogenic viruses and bacteria from the metagenome.ConclusionNanopore metagenomic sequencing can detect the emergence of novel variants and drug resistance, providing timely insights into antimicrobial stewardship and vaccine design. Full genome generation can help investigate and manage nosocomial outbreaks.",,pdf:https://www.eurosurveillance.org/deliver/fulltext/eurosurveillance/26/27/eurosurv-26-27-4.pdf?itemId=%2Fcontent%2F10.2807%2F1560-7917.ES.2021.26.27.2000004&mimeType=pdf&containerItemId=content/eurosurveillance; doi:https://doi.org/10.2807/1560-7917.ES.2021.26.27.2000004; html:https://europepmc.org/articles/PMC8268652; pdf:https://europepmc.org/articles/PMC8268652?pdf=render 33226834,https://doi.org/10.1164/rccm.202008-3211le,Proportion of Idiopathic Pulmonary Fibrosis Risk Explained by Known Common Genetic Loci in European Populations.,"Leavy OC, Ma SF, Molyneaux PL, Maher TM, Oldham JM, Flores C, Noth I, Jenkins RG, Dudbridge F, Wain LV, Allen RJ.",,American journal of respiratory and critical care medicine,2021,2021-03-01,Y,,,,,,pdf:https://europepmc.org/articles/pmc7958523?pdf=render; doi:https://doi.org/10.1164/rccm.202008-3211LE; html:https://europepmc.org/articles/PMC7958523; pdf:https://europepmc.org/articles/PMC7958523?pdf=render 34193492,https://doi.org/10.1136/bmjopen-2020-046450,"'Give Us The Tools!': development of knowledge transfer tools to support the involvement of patient partners in the development of clinical trial protocols with patient-reported outcomes (PROs), in accordance with SPIRIT-PRO Extension.","Cruz Rivera S, Stephens R, Mercieca-Bebber R, Retzer A, Rutherford C, Price G, Slade A, Aiyegbusi OL, Edge P, Roberts L, Gosden L, Verdi R, Wilson R, Calvert M.",,BMJ open,2021,2021-06-30,Y,Qualitative Research; Protocols & Guidelines; Quality In Health Care,,,"

Objectives

(a) To adapt the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT)-patient-reported outcome (PRO) Extension guidance to a user-friendly format for patient partners and (b) to codesign a web-based tool to support the dissemination and uptake of the SPIRIT-PRO Extension by patient partners.

Design

A 1-day patient and public involvement session.

Participants

Seven patient partners.

Methods

A patient partner produced an initial lay summary of the SPIRIT-PRO guideline and a glossary. We held a 1-day PPI session in November 2019 at the University of Birmingham. Five patient partners discussed the draft lay summary, agreed on the final wording, codesigned and agreed the final content for both tools. Two additional patient partners were involved in writing the manuscript. The study compiled with INVOLVE guidelines and was reported according to the Guidance for Reporting Involvement of Patients and the Public 2 checklist.

Results

Two user-friendly tools were developed to help patients and members of the public be involved in the codesign of clinical trials collecting PROs. The first tool presents a lay version of the SPIRIT-PRO Extension guidance. The second depicts the most relevant points, identified by the patient partners, of the guidance through an interactive flow diagram.

Conclusions

These tools have the potential to support the involvement of patient partners in making informed contributions to the development of PRO aspects of clinical trial protocols, in accordance with the SPIRIT-PRO Extension guidelines. The involvement of patient partners ensured the tools focused on issues most relevant to them.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/6/e046450.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-046450; html:https://europepmc.org/articles/PMC8246365; pdf:https://europepmc.org/articles/PMC8246365?pdf=render +38508198,https://doi.org/10.1016/j.xgen.2024.100523,Integrative polygenic risk score improves the prediction accuracy of complex traits and diseases.,"Truong B, Hull LE, Ruan Y, Huang QQ, Hornsby W, Martin H, van Heel DA, Wang Y, Martin AR, Lee SH, Natarajan P.",,Cell genomics,2024,2024-03-19,Y,Combination; Clinical Utility; South Asian; Integrative; Prs; Cross Ancestry,,,"Polygenic risk scores (PRSs) are an emerging tool to predict the clinical phenotypes and outcomes of individuals. We propose PRSmix, a framework that leverages the PRS corpus of a target trait to improve prediction accuracy, and PRSmix+, which incorporates genetically correlated traits to better capture the human genetic architecture for 47 and 32 diseases/traits in European and South Asian ancestries, respectively. PRSmix demonstrated a mean prediction accuracy improvement of 1.20-fold (95% confidence interval [CI], [1.10; 1.3]; p = 9.17 × 10-5) and 1.19-fold (95% CI, [1.11; 1.27]; p = 1.92 × 10-6), and PRSmix+ improved the prediction accuracy by 1.72-fold (95% CI, [1.40; 2.04]; p = 7.58 × 10-6) and 1.42-fold (95% CI, [1.25; 1.59]; p = 8.01 × 10-7) in European and South Asian ancestries, respectively. Compared to the previously cross-trait-combination methods with scores from pre-defined correlated traits, we demonstrated that our method improved prediction accuracy for coronary artery disease up to 3.27-fold (95% CI, [2.1; 4.44]; p value after false discovery rate (FDR) correction = 2.6 × 10-4). Our method provides a comprehensive framework to benchmark and leverage the combined power of PRS for maximal performance in a desired target population.",,doi:https://doi.org/10.1016/j.xgen.2024.100523; html:https://europepmc.org/articles/PMC11019356; pdf:https://europepmc.org/articles/PMC11019356?pdf=render 32724858,https://doi.org/10.1136/bmjophth-2020-000481,Outcomes important to patients with non-infectious posterior segment-involving uveitis: a qualitative study.,"Tallouzi MO, Moore DJ, Bucknall N, Murray PI, Calvert MJ, Denniston AK, Mathers JM.",,BMJ open ophthalmology,2020,2020-07-21,Y,Inflammation; Public Health; Treatment Other,,,"

Objective

Uveitis, a group of disorders characterised by intraocular inflammation, causes 10%-15% of total blindness in the developed world. The most sight-threatening forms of non-infectious uveitis are those affecting the posterior segment of the eye, collectively known as posterior segment-involving uveitis (PSIU). Numerous different clinical outcomes have been used in trials evaluating treatments for PSIU, but these may not represent patients' and carers' concerns. Therefore, the aims of this study were to understand the impact of PSIU on adult patients' and carers' lives and to explore what outcomes of treatment are important to them.

Methods and analysis

Four focus group discussions were undertaken to understand the perspectives of adult patients (=18) and carers (10) with PSIU. Participants were grouped according to whether or not their uveitis was complicated by the sight-threatening condition uveitic macular oedema. Discussions were audio-recorded, transcribed and analysed using the framework analytical approach. Outcomes were identified and grouped into outcome domains.

Results

Eleven core domains were identified as important to patients and carers undergoing treatment for PSIU, comprising (1) visual function, (2) symptoms, (3) functional ability, (4) impact on relationships, (5) financial impact, (6) psychological morbidity and emotional well-being, (7) psychosocial adjustment to uveitis, (8) doctor/patient/interprofessional relationships and access to healthcare, (9) treatment burden, (10) treatment side effects, and (11) disease control.

Conclusion

The domains identified represent patients' and carers' experience and perspectives and can be used to reflect on outcomes assessed in PSIU. They will directly inform the development of a core outcome set for PSIU clinical trials.",,pdf:https://bmjophth.bmj.com/content/bmjophth/5/1/e000481.full.pdf; doi:https://doi.org/10.1136/bmjophth-2020-000481; html:https://europepmc.org/articles/PMC7375431; pdf:https://europepmc.org/articles/PMC7375431?pdf=render 35042708,https://doi.org/10.1136/bmjopen-2021-055572,Use of the kidney failure risk equation to inform clinical care of patients with chronic kidney disease: a mixed-methods systematic review.,"Bhachu HK, Fenton A, Cockwell P, Aiyegbusi O, Kyte D, Calvert M.",,BMJ open,2022,2022-01-18,Y,Dialysis; Renal transplantation; Chronic Renal Failure; End Stage Renal Failure,,,"

Rationale and objective

The Kidney Failure Risk Equation (KFRE) predicts the risk of end-stage kidney disease in patients with chronic kidney disease (CKD). This study aimed to evaluate the impact of the utility of KFRE in clinical practice.

Study design

Systematic review.

Setting and study populations

Adult patients with CKD but not receiving renal replacement therapy enrolled in studies where KFRE was used in clinical care pathways.

Selection criteria for studies

All studies published from April 2011 to October 2021 identified from Medline, Cumulative Index to Nursing and Allied Health Literature, Embase and reference and citation searches of included studies.

Data extraction

Relevant data were extracted, and two reviewers independently assessed study quality using appropriate appraisal tools.

Analytical approach

Findings reported as a narrative synthesis due to heterogeneity of the included studies.

Results

Of 1635 studies identified, 440 duplicates were removed. The remaining 1195 titles and abstracts were screened. All five studies for full-text review were included in the analysis. Three uses of KFRE were assessed: (1) primary to specialty care interface; (2) general nephrology to multidisciplinary care transition; and (3) treatment planning. Evidence of impact on number of patient referrals into nephrology care was conflicting. However, wait times improved in one study. Although KFRE identified high-risk patients for increased multidisciplinary support, there was concern patients stepped down, no longer meeting eligibility criteria, may lack access to services.

Conclusions

This is the first systematic review of studies that have assessed the actual impact of KFRE in clinical practice with five studies of varying quality reported to date. Trials are in progress assessing the impact on clinical outcomes of using KFRE in clinical practice, and KFRE is being incorporated into guidelines for CKD management. Further studies are needed to assess the impact of KFRE on clinical care.

Trial registration number

Protocol registered on PROSPERO before initiation of the study (Ref: CRD42020219926).",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/1/e055572.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-055572; html:https://europepmc.org/articles/PMC8768913; pdf:https://europepmc.org/articles/PMC8768913?pdf=render 35585198,https://doi.org/10.1038/s41591-022-01772-9,Reporting guideline for the early-stage clinical evaluation of decision support systems driven by artificial intelligence: DECIDE-AI.,"Vasey B, Nagendran M, Campbell B, Clifton DA, Collins GS, Denaxas S, Denniston AK, Faes L, Geerts B, Ibrahim M, Liu X, Mateen BA, Mathur P, McCradden MD, Morgan L, Ordish J, Rogers C, Saria S, Ting DSW, Watkinson P, Weber W, Wheatstone P, McCulloch P, DECIDE-AI expert group.",,Nature medicine,2022,2022-05-18,N,,,,"A growing number of artificial intelligence (AI)-based clinical decision support systems are showing promising performance in preclinical, in silico evaluation, but few have yet demonstrated real benefit to patient care. Early-stage clinical evaluation is important to assess an AI system's actual clinical performance at small scale, ensure its safety, evaluate the human factors surrounding its use and pave the way to further large-scale trials. However, the reporting of these early studies remains inadequate. The present statement provides a multi-stakeholder, consensus-based reporting guideline for the Developmental and Exploratory Clinical Investigations of DEcision support systems driven by Artificial Intelligence (DECIDE-AI). We conducted a two-round, modified Delphi process to collect and analyze expert opinion on the reporting of early clinical evaluation of AI systems. Experts were recruited from 20 pre-defined stakeholder categories. The final composition and wording of the guideline was determined at a virtual consensus meeting. The checklist and the Explanation & Elaboration (E&E) sections were refined based on feedback from a qualitative evaluation process. In total, 123 experts participated in the first round of Delphi, 138 in the second round, 16 in the consensus meeting and 16 in the qualitative evaluation. The DECIDE-AI reporting guideline comprises 17 AI-specific reporting items (made of 28 subitems) and ten generic reporting items, with an E&E paragraph provided for each. Through consultation and consensus with a range of stakeholders, we developed a guideline comprising key items that should be reported in early-stage clinical studies of AI-based decision support systems in healthcare. By providing an actionable checklist of minimal reporting items, the DECIDE-AI guideline will facilitate the appraisal of these studies and replicability of their findings.",,pdf:https://www.nature.com/articles/s41591-022-01772-9.pdf; doi:https://doi.org/10.1038/s41591-022-01772-9 @@ -2324,23 +2324,23 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 36820079,https://doi.org/10.1183/23120541.00274-2022,Characteristics and risk factors for post-COVID-19 breathlessness after hospitalisation for COVID-19.,"Daines L, Zheng B, Elneima O, Harrison E, Lone NI, Hurst JR, Brown JS, Sapey E, Chalmers JD, Quint JK, Pfeffer P, Siddiqui S, Walker S, Poinasamy K, McAuley H, Sereno M, Shikotra A, Singapuri A, Docherty AB, Marks M, Toshner M, Howard LS, Horsley A, Jenkins G, Porter JC, Ho LP, Raman B, Wain LV, Brightling CE, Evans RA, Heaney LG, De Soyza A, Sheikh A.",,ERJ open research,2023,2023-01-01,Y,,,,"

Background

Persistence of respiratory symptoms, particularly breathlessness, after acute coronavirus disease 2019 (COVID-19) infection has emerged as a significant clinical problem. We aimed to characterise and identify risk factors for patients with persistent breathlessness following COVID-19 hospitalisation.

Methods

PHOSP-COVID is a multicentre prospective cohort study of UK adults hospitalised for COVID-19. Clinical data were collected during hospitalisation and at a follow-up visit. Breathlessness was measured by a numeric rating scale of 0-10. We defined post-COVID-19 breathlessness as an increase in score of ≥1 compared to the pre-COVID-19 level. Multivariable logistic regression was used to identify risk factors and to develop a prediction model for post-COVID-19 breathlessness.

Results

We included 1226 participants (37% female, median age 59 years, 22% mechanically ventilated). At a median 5 months after discharge, 50% reported post-COVID-19 breathlessness. Risk factors for post-COVID-19 breathlessness were socioeconomic deprivation (adjusted OR 1.67, 95% CI 1.14-2.44), pre-existing depression/anxiety (adjusted OR 1.58, 95% CI 1.06-2.35), female sex (adjusted OR 1.56, 95% CI 1.21-2.00) and admission duration (adjusted OR 1.01, 95% CI 1.00-1.02). Black ethnicity (adjusted OR 0.56, 95% CI 0.35-0.89) and older age groups (adjusted OR 0.31, 95% CI 0.14-0.66) were less likely to report post-COVID-19 breathlessness. Post-COVID-19 breathlessness was associated with worse performance on the shuttle walk test and forced vital capacity, but not with obstructive airflow limitation. The prediction model had fair discrimination (concordance statistic 0.66, 95% CI 0.63-0.69) and good calibration (calibration slope 1.00, 95% CI 0.80-1.21).

Conclusions

Post-COVID-19 breathlessness was commonly reported in this national cohort of patients hospitalised for COVID-19 and is likely to be a multifactorial problem with physical and emotional components.",,pdf:https://openres.ersjournals.com/content/erjor/early/2023/01/26/23120541.00274-2022.full.pdf; doi:https://doi.org/10.1183/23120541.00274-2022; html:https://europepmc.org/articles/PMC9790090; pdf:https://europepmc.org/articles/PMC9790090?pdf=render 34593009,https://doi.org/10.1186/s13058-021-01465-0,Genomic risk prediction of coronary artery disease in women with breast cancer: a prospective cohort study.,"Liou L, Kaptoge S, Dennis J, Shah M, Tyrer J, Inouye M, Easton DF, Pharoah PDP.",,Breast cancer research : BCR,2021,2021-09-30,Y,Breast cancer; Cardiovascular disease; coronary artery disease; Coronary Heart Disease; Search; Polygenic Risk Score,,,"

Background

Advancements in cancer therapeutics have resulted in increases in cancer-related survival; however, there is a growing clinical dilemma. The current balancing of survival benefits and future cardiotoxic harms of oncotherapies has resulted in an increased burden of cardiovascular disease in breast cancer survivors. Risk stratification may help address this clinical dilemma. This study is the first to assess the association between a coronary artery disease-specific polygenic risk score and incident coronary artery events in female breast cancer survivors.

Methods

We utilized the Studies in Epidemiology and Research in Cancer Heredity prospective cohort involving 12,413 women with breast cancer with genotype information and without a baseline history of cardiovascular disease. Cause-specific hazard ratios for association of the polygenic risk score and incident coronary artery disease (CAD) were obtained using left-truncated Cox regression adjusting for age, genotype array, conventional risk factors such as smoking and body mass index, as well as other sociodemographic, lifestyle, and medical variables.

Results

Over a median follow-up of 10.3 years (IQR: 16.8) years, 750 incident fatal or non-fatal coronary artery events were recorded. A 1 standard deviation higher polygenic risk score was associated with an adjusted hazard ratio of 1.33 (95% CI 1.20, 1.47) for incident CAD.

Conclusions

This study provides evidence that a coronary artery disease-specific polygenic risk score can risk-stratify breast cancer survivors independently of other established cardiovascular risk factors.",,pdf:https://breast-cancer-research.biomedcentral.com/track/pdf/10.1186/s13058-021-01465-0; doi:https://doi.org/10.1186/s13058-021-01465-0; html:https://europepmc.org/articles/PMC8482562; pdf:https://europepmc.org/articles/PMC8482562?pdf=render 32558637,https://doi.org/10.1099/mgen.0.000393,Evaluation of methods for detecting human reads in microbial sequencing datasets.,"Bush SJ, Connor TR, Peto TEA, Crook DW, Walker AS.",,Microbial genomics,2020,2020-07-01,Y,Human; Contamination; Read Depletion; Read Removal,,,"Sequencing data from host-associated microbes can often be contaminated by the body of the investigator or research subject. Human DNA is typically removed from microbial reads either by subtractive alignment (dropping all reads that map to the human genome) or by using a read classification tool to predict those of human origin, and then discarding them. To inform best practice guidelines, we benchmarked eight alignment-based and two classification-based methods of human read detection using simulated data from 10 clinically prevalent bacteria and three viruses, into which contaminating human reads had been added. While the majority of methods successfully detected >99 % of the human reads, they were distinguishable by variance. The most precise methods, with negligible variance, were Bowtie2 and SNAP, both of which misidentified few, if any, bacterial reads (and no viral reads) as human. While correctly detecting a similar number of human reads, methods based on taxonomic classification, such as Kraken2 and Centrifuge, could misclassify bacterial reads as human, although the extent of this was species-specific. Among the most sensitive methods of human read detection was BWA, although this also made the greatest number of false positive classifications. Across all methods, the set of human reads not identified as such, although often representing <0.1 % of the total reads, were non-randomly distributed along the human genome with many originating from the repeat-rich sex chromosomes. For viral reads and longer (>300 bp) bacterial reads, the highest performing approaches were classification-based, using Kraken2 or Centrifuge. For shorter (c. 150 bp) bacterial reads, combining multiple methods of human read detection maximized the recovery of human reads from contaminated short read datasets without being compromised by false positives. A particularly high-performance approach with shorter bacterial reads was a two-stage classification using Bowtie2 followed by SNAP. Using this approach, we re-examined 11 577 publicly archived bacterial read sets for hitherto undetected human contamination. We were able to extract a sufficient number of reads to call known human SNPs, including those with clinical significance, in 6 % of the samples. These results show that phenotypically distinct human sequence is detectable in publicly archived microbial read datasets.",,doi:https://doi.org/10.1099/mgen.0.000393; doi:https://doi.org/10.1099/mgen.0.000393; html:https://europepmc.org/articles/PMC7478626; pdf:https://europepmc.org/articles/PMC7478626?pdf=render -36029521,https://doi.org/10.1093/ije/dyac171,Cohort Profile: The United Kingdom Research study into Ethnicity and COVID-19 outcomes in Healthcare workers (UK-REACH).,"Bryant L, Free RC, Woolf K, Melbourne C, Guyatt AL, John C, Gupta A, Gray LJ, Nellums L, Martin CA, McManus IC, Garwood C, Modhawdia V, Carr S, Wain LV, Tobin MD, Khunti K, Akubakar I, Pareek M, UK-REACH Collaborative Group+.",,International journal of epidemiology,2023,2023-02-01,Y,,,,,,pdf:https://academic.oup.com/ije/article-pdf/52/1/e38/49127215/dyac171.pdf; doi:https://doi.org/10.1093/ije/dyac171; html:https://europepmc.org/articles/PMC9452183; pdf:https://europepmc.org/articles/PMC9452183?pdf=render 31171806,https://doi.org/10.1038/s41598-019-44907-8,On neighbourhood degree sequences of complex networks.,Smith KM.,,Scientific reports,2019,2019-06-06,Y,,Applied Analytics,,"Network topology is a fundamental aspect of network science that allows us to gather insights into the complicated relational architectures of the world we inhabit. We provide a first specific study of neighbourhood degree sequences in complex networks. We consider how to explicitly characterise important physical concepts such as similarity, heterogeneity and organization in these sequences, as well as updating the notion of hierarchical complexity to reflect previously unnoticed organizational principles. We also point out that neighbourhood degree sequences are related to a powerful subtree kernel for unlabeled graph classification. We study these newly defined sequence properties in a comprehensive array of graph models and over 200 real-world networks. We find that these indices are neither highly correlated with each other nor with classical network indices. Importantly, the sequences of a wide variety of real world networks are found to have greater similarity and organisation than is expected for networks of their given degree distributions. Notably, while biological, social and technological networks all showed consistently large neighbourhood similarity and organisation, hierarchical complexity was not a consistent feature of real world networks. Neighbourhood degree sequences are an interesting tool for describing unique and important characteristics of complex networks.",,pdf:https://www.nature.com/articles/s41598-019-44907-8.pdf; doi:https://doi.org/10.1038/s41598-019-44907-8; html:https://europepmc.org/articles/PMC6554413; pdf:https://europepmc.org/articles/PMC6554413?pdf=render +36029521,https://doi.org/10.1093/ije/dyac171,Cohort Profile: The United Kingdom Research study into Ethnicity and COVID-19 outcomes in Healthcare workers (UK-REACH).,"Bryant L, Free RC, Woolf K, Melbourne C, Guyatt AL, John C, Gupta A, Gray LJ, Nellums L, Martin CA, McManus IC, Garwood C, Modhawdia V, Carr S, Wain LV, Tobin MD, Khunti K, Akubakar I, Pareek M, UK-REACH Collaborative Group+.",,International journal of epidemiology,2023,2023-02-01,Y,,,,,,pdf:https://academic.oup.com/ije/article-pdf/52/1/e38/49127215/dyac171.pdf; doi:https://doi.org/10.1093/ije/dyac171; html:https://europepmc.org/articles/PMC9452183; pdf:https://europepmc.org/articles/PMC9452183?pdf=render 35587468,https://doi.org/10.1371/journal.pmed.1003981,Integrating polygenic risk scores in the prediction of type 2 diabetes risk and subtypes in British Pakistanis and Bangladeshis: A population-based cohort study.,"Hodgson S, Huang QQ, Sallah N, Genes & Health Research Team, Griffiths CJ, Newman WG, Trembath RC, Wright J, Lumbers RT, Kuchenbaecker K, van Heel DA, Mathur R, Martin HC, Finer S.",,PLoS medicine,2022,2022-05-19,Y,,,,"

Background

Type 2 diabetes (T2D) is highly prevalent in British South Asians, yet they are underrepresented in research. Genes & Health (G&H) is a large, population study of British Pakistanis and Bangladeshis (BPB) comprising genomic and routine health data. We assessed the extent to which genetic risk for T2D is shared between BPB and European populations (EUR). We then investigated whether the integration of a polygenic risk score (PRS) for T2D with an existing risk tool (QDiabetes) could improve prediction of incident disease and the characterisation of disease subtypes.

Methods and findings

In this observational cohort study, we assessed whether common genetic loci associated with T2D in EUR individuals were replicated in 22,490 BPB individuals in G&H. We replicated fewer loci in G&H (n = 76/338, 22%) than would be expected given power if all EUR-ascertained loci were transferable (n = 101, 30%; p = 0.001). Of the 27 transferable loci that were powered to interrogate this, only 9 showed evidence of shared causal variants. We constructed a T2D PRS and combined it with a clinical risk instrument (QDiabetes) in a novel, integrated risk tool (IRT) to assess risk of incident diabetes. To assess model performance, we compared categorical net reclassification index (NRI) versus QDiabetes alone. In 13,648 patients free from T2D followed up for 10 years, NRI was 3.2% for IRT versus QDiabetes (95% confidence interval (CI): 2.0% to 4.4%). IRT performed best in reclassification of individuals aged less than 40 years deemed low risk by QDiabetes alone (NRI 5.6%, 95% CI 3.6% to 7.6%), who tended to be free from comorbidities and slim. After adjustment for QDiabetes score, PRS was independently associated with progression to T2D after gestational diabetes (hazard ratio (HR) per SD of PRS 1.23, 95% CI 1.05 to 1.42, p = 0.028). Using cluster analysis of clinical features at diabetes diagnosis, we replicated previously reported disease subgroups, including Mild Age-Related, Mild Obesity-related, and Insulin-Resistant Diabetes, and showed that PRS distribution differs between subgroups (p = 0.002). Integrating PRS in this cluster analysis revealed a Probable Severe Insulin Deficient Diabetes (pSIDD) subgroup, despite the absence of clinical measures of insulin secretion or resistance. We also observed differences in rates of progression to micro- and macrovascular complications between subgroups after adjustment for confounders. Study limitations include the absence of an external replication cohort and the potential biases arising from missing or incorrect routine health data.

Conclusions

Our analysis of the transferability of T2D loci between EUR and BPB indicates the need for larger, multiancestry studies to better characterise the genetic contribution to disease and its varied aetiology. We show that a T2D PRS optimised for this high-risk BPB population has potential clinical application in BPB, improving the identification of T2D risk (especially in the young) on top of an established clinical risk algorithm and aiding identification of subgroups at diagnosis, which may help future efforts to stratify care and treatment of the disease.",,pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1003981&type=printable; doi:https://doi.org/10.1371/journal.pmed.1003981; html:https://europepmc.org/articles/PMC9119501; pdf:https://europepmc.org/articles/PMC9119501?pdf=render 30819382,https://doi.org/10.1016/j.jchf.2019.01.009,Adverse Drug Reactions to Guideline-Recommended Heart Failure Drugs in Women: A Systematic Review of the Literature.,"Bots SH, Groepenhoff F, Eikendal ALM, Tannenbaum C, Rochon PA, Regitz-Zagrosek V, Miller VM, Day D, Asselbergs FW, den Ruijter HM.",,JACC. Heart failure,2019,2019-03-01,N,Women; Sex differences; Heart Failure; Adverse drug reactions; Sex-specific Reporting,The Human Phenome,,"

Objectives

This study sought to summarize all available evidence on sex differences in adverse drug reactions (ADRs) to heart failure (HF) medication.

Background

Women are more likely to experience ADRs than men, and these reactions may negatively affect women's immediate and long-term health. HF in particular is associated with increased ADR risk because of the high number of comorbidities and older age. However, little is known about ADRs in women with HF who are treated with guideline-recommended drugs.

Methods

A systematic search of PubMed and EMBASE was performed to collect all available information on ADRs to angiotensin-converting enzyme inhibitors, β-blockers, angiotensin II receptor blockers, mineralocorticoid receptor antagonists, ivabradine, and digoxin in both women and men with HF.

Results

The search identified 155 eligible records, of which only 11 (7%) reported ADR data for women and men separately. Sex-stratified reporting of ADRs did not increase over the last decades. Six of the 11 studies did not report sex differences. Three studies reported a higher risk of angiotensin-converting enzyme inhibitor-related ADRs in women, 1 study showed higher digoxin-related mortality risk for women, and 1 study reported a higher risk of mineralocorticoid receptor antagonist-related ADRs in men. No sex differences in ADRs were reported for angiotensin II receptor blockers and β-blockers. Sex-stratified data were not available for ivabradine.

Conclusions

These results underline the scarcity of ADR data stratified by sex. The study investigators call for a change in standard scientific practice toward reporting of ADR data for women and men separately.",,doi:https://doi.org/10.1016/j.jchf.2019.01.009; doi:https://doi.org/10.1016/j.jchf.2019.01.009 36269859,https://doi.org/10.1073/pnas.2206083119,Metabolome-wide association study on ABCA7 indicates a role of ceramide metabolism in Alzheimer's disease.,"Dehghan A, Pinto RC, Karaman I, Huang J, Durainayagam BR, Ghanbari M, Nazeer A, Zhong Q, Liggi S, Whiley L, Mustafa R, Kivipelto M, Solomon A, Ngandu T, Kanekiyo T, Aikawa T, Radulescu CI, Barnes SJ, Graça G, Chekmeneva E, Camuzeaux S, Lewis MR, Kaluarachchi MR, Ikram MA, Holmes E, Tzoulaki I, Matthews PM, Griffin JL, Elliott P.",,Proceedings of the National Academy of Sciences of the United States of America,2022,2022-10-21,Y,Ceramide; Alzheimer’s disease; Metabolomics; Genome-wide Association Study; Abca7,,,"Genome-wide association studies (GWASs) have identified genetic loci associated with the risk of Alzheimer's disease (AD), but the molecular mechanisms by which they confer risk are largely unknown. We conducted a metabolome-wide association study (MWAS) of AD-associated loci from GWASs using untargeted metabolic profiling (metabolomics) by ultraperformance liquid chromatography-mass spectrometry (UPLC-MS). We identified an association of lactosylceramides (LacCer) with AD-related single-nucleotide polymorphisms (SNPs) in ABCA7 (P = 5.0 × 10-5 to 1.3 × 10-44). We showed that plasma LacCer concentrations are associated with cognitive performance and genetically modified levels of LacCer are associated with AD risk. We then showed that concentrations of sphingomyelins, ceramides, and hexosylceramides were altered in brain tissue from Abca7 knockout mice, compared with wild type (WT) (P = 0.049-1.4 × 10-5), but not in a mouse model of amyloidosis. Furthermore, activation of microglia increases intracellular concentrations of hexosylceramides in part through induction in the expression of sphingosine kinase, an enzyme with a high control coefficient for sphingolipid and ceramide synthesis. Our work suggests that the risk for AD arising from functional variations in ABCA7 is mediated at least in part through ceramides. Modulation of their metabolism or downstream signaling may offer new therapeutic opportunities for AD.",,doi:https://doi.org/10.1073/pnas.2206083119; doi:https://doi.org/10.1073/pnas.2206083119; html:https://europepmc.org/articles/PMC9618092; pdf:https://europepmc.org/articles/PMC9618092?pdf=render 37173061,https://doi.org/10.1016/j.ajcnut.2022.12.021,"Evidence for human milk as a biological system and recommendations for study design-a report from ""Breastmilk Ecology: Genesis of Infant Nutrition (BEGIN)"" Working Group 4.","Donovan SM, Aghaeepour N, Andres A, Azad MB, Becker M, Carlson SE, Järvinen KM, Lin W, Lönnerdal B, Slupsky CM, Steiber AL, Raiten DJ.",,The American journal of clinical nutrition,2023,2023-04-01,Y,Immune; systems biology; Human Milk; Microbiome; Infant Development,,,"Human milk contains all of the essential nutrients required by the infant within a complex matrix that enhances the bioavailability of many of those nutrients. In addition, human milk is a source of bioactive components, living cells and microbes that facilitate the transition to life outside the womb. Our ability to fully appreciate the importance of this matrix relies on the recognition of short- and long-term health benefits and, as highlighted in previous sections of this supplement, its ecology (i.e., interactions among the lactating parent and breastfed infant as well as within the context of the human milk matrix itself). Designing and interpreting studies to address this complexity depends on the availability of new tools and technologies that account for such complexity. Past efforts have often compared human milk to infant formula, which has provided some insight into the bioactivity of human milk, as a whole, or of individual milk components supplemented with formula. However, this experimental approach cannot capture the contributions of the individual components to the human milk ecology, the interaction between these components within the human milk matrix, or the significance of the matrix itself to enhance human milk bioactivity on outcomes of interest. This paper presents approaches to explore human milk as a biological system and the functional implications of that system and its components. Specifically, we discuss study design and data collection considerations and how emerging analytical technologies, bioinformatics, and systems biology approaches could be applied to advance our understanding of this critical aspect of human biology.",,doi:https://doi.org/10.1016/j.ajcnut.2022.12.021; html:https://europepmc.org/articles/PMC10356565; pdf:https://europepmc.org/articles/PMC10356565?pdf=render 36527096,https://doi.org/10.1186/s12910-022-00875-9,"""Data makes the story come to life:"" understanding the ethical and legal implications of Big Data research involving ethnic minority healthcare workers in the United Kingdom-a qualitative study.","Dove ES, Reed-Berendt R, Pareek M, UK-REACH Study Collaborative Group.",,BMC medical ethics,2022,2022-12-16,Y,Ethics; Public Health; United Kingdom; Healthcare Workers; Ethnic Minorities; Big Data; Covid-19,,,"The aim of UK-REACH (""The United Kingdom Research study into Ethnicity And COVID-19 outcomes in Healthcare workers"") is to understand if, how, and why healthcare workers (HCWs) in the United Kingdom (UK) from ethnic minority groups are at increased risk of poor outcomes from COVID-19. In this article, we present findings from the ethical and legal stream of the study, which undertook qualitative research seeking to understand and address legal, ethical, and social acceptability issues around data protection, privacy, and information governance associated with the linkage of HCWs' registration data and healthcare data. We interviewed 22 key opinion leaders in healthcare and health research from across the UK in two-to-one semi-structured interviews. Transcripts were coded using qualitative thematic analysis. Participants told us that a significant aspect of Big Data research in public health is varying drivers of mistrust-of the research itself, research staff and funders, and broader concerns of mistrust within participant communities, particularly in the context of COVID-19 and those situated in more marginalised community settings. However, despite the challenges, participants also identified ways in which legally compliant and ethically informed approaches to research can be crafted to mitigate or overcome mistrust and establish greater confidence in Big Data public health research. Overall, our research indicates that a ""Big Data Ethics by Design"" approach to research in this area can help assure (1) that meaningful community and participant engagement is taking place and that extant challenges are addressed, and (2) that any new challenges or hitherto unknown unknowns can be rapidly and properly considered to ensure potential (but material) harms are identified and minimised where necessary. Our findings indicate such an approach, in turn, will help drive better scientific breakthroughs that translate into medical innovations and effective public health interventions, which benefit the publics studied, including those who are often marginalised in research.",,pdf:https://bmcmedethics.biomedcentral.com/counter/pdf/10.1186/s12910-022-00875-9; doi:https://doi.org/10.1186/s12910-022-00875-9; html:https://europepmc.org/articles/PMC9756740; pdf:https://europepmc.org/articles/PMC9756740?pdf=render -36522333,https://doi.org/10.1038/s41467-022-35454-4,Multi-omics identify falling LRRC15 as a COVID-19 severity marker and persistent pro-thrombotic signals in convalescence.,"Gisby JS, Buang NB, Papadaki A, Clarke CL, Malik TH, Medjeral-Thomas N, Pinheiro D, Mortimer PM, Lewis S, Sandhu E, McAdoo SP, Prendecki MF, Willicombe M, Pickering MC, Botto M, Thomas DC, Peters JE.",,Nature communications,2022,2022-12-15,Y,,,,"Patients with end-stage kidney disease (ESKD) are at high risk of severe COVID-19. Here, we perform longitudinal blood sampling of ESKD haemodialysis patients with COVID-19, collecting samples pre-infection, serially during infection, and after clinical recovery. Using plasma proteomics, and RNA-sequencing and flow cytometry of immune cells, we identify transcriptomic and proteomic signatures of COVID-19 severity, and find distinct temporal molecular profiles in patients with severe disease. Supervised learning reveals that the plasma proteome is a superior indicator of clinical severity than the PBMC transcriptome. We show that a decreasing trajectory of plasma LRRC15, a proposed co-receptor for SARS-CoV-2, is associated with a more severe clinical course. We observe that two months after the acute infection, patients still display dysregulated gene expression related to vascular, platelet and coagulation pathways, including PF4 (platelet factor 4), which may explain the prolonged thrombotic risk following COVID-19.",,pdf:https://www.nature.com/articles/s41467-022-35454-4.pdf; doi:https://doi.org/10.1038/s41467-022-35454-4; html:https://europepmc.org/articles/PMC9753891; pdf:https://europepmc.org/articles/PMC9753891?pdf=render 34490590,https://doi.org/10.1007/s40256-021-00496-4,Cost Effectiveness of a CYP2C19 Genotype-Guided Strategy in Patients with Acute Myocardial Infarction: Results from the POPular Genetics Trial.,"Claassens DMF, van Dorst PWM, Vos GJA, Bergmeijer TO, Hermanides RS, van 't Hof AWJ, van der Harst P, Barbato E, Morisco C, Tjon Joe Gin RM, Asselbergs FW, Mosterd A, Herrman JR, Dewilde WJM, Postma MJ, Deneer VHM, Ten Berg JM, Boersma C.",,"American journal of cardiovascular drugs : drugs, devices, and other interventions",2022,2021-09-07,N,,,,"

Introduction

The POPular Genetics trial demonstrated that a CYP2C19 genotype-guided P2Y12 inhibitor strategy reduced bleeding rates compared with standard treatment with ticagrelor or prasugrel without increasing thrombotic event rates after primary percutaneous coronary intervention (PCI).

Objective

In this analysis, we aimed to evaluate the cost effectiveness of a genotype-guided strategy compared with standard treatment with ticagrelor or prasugrel.

Methods

A 1-year decision tree based on the POPular Genetics trial in combination with a lifelong Markov model was developed to compare costs and quality-adjusted life-years (QALYs) between a genotype-guided and a standard P2Y12 inhibitor strategy in patients with myocardial infarction undergoing primary PCI. The cost-effectiveness analysis was conducted from a Dutch healthcare system perspective. Within-trial survival and utility data were combined with lifetime projections to evaluate lifetime cost effectiveness for a cohort of 1000 patients. Costs and utilities were discounted at 4 and 1.5%, respectively, according to Dutch guidelines for health economic studies. Besides deterministic and probabilistic sensitivity analyses, several scenario analyses were also conducted (different time horizons, different discount rates, equal prices for P2Y12 inhibitors, and equal distribution of thrombotic events between the two strategies).

Results

Base-case analysis with a hypothetical cohort of 1000 subjects demonstrated 8.98 QALYs gained and €725,550.69 in cost savings for the genotype-guided strategy (dominant). The deterministic and probabilistic sensitivity analysis confirmed the robustness of the model and the cost-effectiveness results. In scenario analyses, the genotype-guided strategy remained dominant.

Conclusion

In patients undergoing primary PCI, a CYP2C19 genotype-guided strategy compared with standard treatment with ticagrelor or prasugrel resulted in QALYs gained and cost savings.

Trial registration

Clinicaltrials.gov number: NCT01761786, Netherlands trial register number: NL2872.",,pdf:https://pure.rug.nl/ws/files/223545267/Cost_Effectiveness_of_a_CYP2C19_Genotype_Guided_Strategy_in_Patients_with_Acute_Myocardial_Infarction_Results_from_the_POPular_Genetics_Trial.pdf; doi:https://doi.org/10.1007/s40256-021-00496-4 -37132645,https://doi.org/10.1017/s0033291721002257,"Life expectancy, mortality risks and cause of death in patients with serious mental illness in South East London: a comparison between 2008-2012 and 2013-2017.","Chang CK, Chesney E, Teng WN, Hollandt S, Pritchard M, Shetty H, Stewart R, McGuire P, Patel R.",,Psychological medicine,2023,2021-09-07,Y,Mortality; Schizophrenia; Life expectancy; Cause of death; Bipolar disorder; Standardised Mortality Ratio,,,"

Background

People with serious mental illness (SMI) have a significantly shorter life expectancy than the general population. This study investigates whether the mortality rate in this group has changed over the last decade.

Methods

Using Clinical Record Interactive Search software, we extracted data from a large electronic database of patients in South East London. All patients with schizophrenia, schizoaffective disorder or bipolar disorder from 2008 to 2012 and/or 2013 to 2017 were included. Estimates of life expectancy at birth, standardised mortality ratios and causes of death were obtained for each cohort according to diagnosis and gender. Comparisons were made between cohorts and with the general population using data obtained from the UK Office of National Statistics.

Results

In total, 26 005 patients were included. In men, life expectancy was greater in 2013-2017 (64.9 years; 95% CI 63.6-66.3) than in 2008-2012 (63.2 years; 95% CI 61.5-64.9). Similarly, in women, life expectancy was greater in 2013-2017 (69.1 years; 95% CI 67.5-70.7) than in 2008-2012 (68.1 years; 95% CI 66.2-69.9). The difference with general population life expectancy fell by 0.9 years between cohorts in men, and 0.5 years in women. In the 2013-2017 cohorts, cancer accounted for a similar proportion of deaths as cardiovascular disease.

Conclusions

Relative to the general population, life expectancy for people with SMI is still much worse, though it appears to be improving. The increased cancer-related mortality suggests that physical health monitoring should consider including cancer as well.",,pdf:https://www.cambridge.org/core/services/aop-cambridge-core/content/view/F28CB69D452C5EFDAFF77D0FE59FC094/S0033291721002257a.pdf/div-class-title-life-expectancy-mortality-risks-and-cause-of-death-in-patients-with-serious-mental-illness-in-south-east-london-a-comparison-between-2008-2012-and-2013-2017-div.pdf; doi:https://doi.org/10.1017/S0033291721002257; html:https://europepmc.org/articles/PMC9975985; pdf:https://europepmc.org/articles/PMC9975985?pdf=render +36522333,https://doi.org/10.1038/s41467-022-35454-4,Multi-omics identify falling LRRC15 as a COVID-19 severity marker and persistent pro-thrombotic signals in convalescence.,"Gisby JS, Buang NB, Papadaki A, Clarke CL, Malik TH, Medjeral-Thomas N, Pinheiro D, Mortimer PM, Lewis S, Sandhu E, McAdoo SP, Prendecki MF, Willicombe M, Pickering MC, Botto M, Thomas DC, Peters JE.",,Nature communications,2022,2022-12-15,Y,,,,"Patients with end-stage kidney disease (ESKD) are at high risk of severe COVID-19. Here, we perform longitudinal blood sampling of ESKD haemodialysis patients with COVID-19, collecting samples pre-infection, serially during infection, and after clinical recovery. Using plasma proteomics, and RNA-sequencing and flow cytometry of immune cells, we identify transcriptomic and proteomic signatures of COVID-19 severity, and find distinct temporal molecular profiles in patients with severe disease. Supervised learning reveals that the plasma proteome is a superior indicator of clinical severity than the PBMC transcriptome. We show that a decreasing trajectory of plasma LRRC15, a proposed co-receptor for SARS-CoV-2, is associated with a more severe clinical course. We observe that two months after the acute infection, patients still display dysregulated gene expression related to vascular, platelet and coagulation pathways, including PF4 (platelet factor 4), which may explain the prolonged thrombotic risk following COVID-19.",,pdf:https://www.nature.com/articles/s41467-022-35454-4.pdf; doi:https://doi.org/10.1038/s41467-022-35454-4; html:https://europepmc.org/articles/PMC9753891; pdf:https://europepmc.org/articles/PMC9753891?pdf=render 33199917,https://doi.org/10.1038/s41588-020-00725-7,Genome-wide association study of intracranial aneurysms identifies 17 risk loci and genetic overlap with clinical risk factors.,"Bakker MK, van der Spek RAA, van Rheenen W, Morel S, Bourcier R, Hostettler IC, Alg VS, van Eijk KR, Koido M, Akiyama M, Terao C, Matsuda K, Walters RG, Lin K, Li L, Millwood IY, Chen Z, Rouleau GA, Zhou S, Rannikmäe K, Sudlow CLM, Houlden H, van den Berg LH, Dina C, Naggara O, Gentric JC, Shotar E, Eugène F, Desal H, Winsvold BS, Børte S, Johnsen MB, Brumpton BM, Sandvei MS, Willer CJ, Hveem K, Zwart JA, Verschuren WMM, Friedrich CM, Hirsch S, Schilling S, Dauvillier J, Martin O, HUNT All-In Stroke, China Kadoorie Biobank Collaborative Group, BioBank Japan Project Consortium, ICAN Study Group, CADISP Group, Genetics and Observational Subarachnoid Haemorrhage (GOSH) Study investigators, International Stroke Genetics Consortium (ISGC), Jones GT, Bown MJ, Ko NU, Kim H, Coleman JRI, Breen G, Zaroff JG, Klijn CJM, Malik R, Dichgans M, Sargurupremraj M, Tatlisumak T, Amouyel P, Debette S, Rinkel GJE, Worrall BB, Pera J, Slowik A, Gaál-Paavola EI, Niemelä M, Jääskeläinen JE, von Und Zu Fraunberg M, Lindgren A, Broderick JP, Werring DJ, Woo D, Redon R, Bijlenga P, Kamatani Y, Veldink JH, Ruigrok YM.",,Nature genetics,2020,2020-11-16,N,,,,"Rupture of an intracranial aneurysm leads to subarachnoid hemorrhage, a severe type of stroke. To discover new risk loci and the genetic architecture of intracranial aneurysms, we performed a cross-ancestry, genome-wide association study in 10,754 cases and 306,882 controls of European and East Asian ancestry. We discovered 17 risk loci, 11 of which are new. We reveal a polygenic architecture and explain over half of the disease heritability. We show a high genetic correlation between ruptured and unruptured intracranial aneurysms. We also find a suggestive role for endothelial cells by using gene mapping and heritability enrichment. Drug-target enrichment shows pleiotropy between intracranial aneurysms and antiepileptic and sex hormone drugs, providing insights into intracranial aneurysm pathophysiology. Finally, genetic risks for smoking and high blood pressure, the two main clinical risk factors, play important roles in intracranial aneurysm risk, and drive most of the genetic correlation between intracranial aneurysms and other cerebrovascular traits.",,pdf:https://europepmc.org/articles/pmc7116530?pdf=render; doi:https://doi.org/10.1038/s41588-020-00725-7; html:https://europepmc.org/articles/PMC7116530; pdf:https://europepmc.org/articles/PMC7116530?pdf=render; doi:https://doi.org/10.1038/s41588-020-00725-7 -38783292,https://doi.org/10.1186/s12939-024-02198-0,"Discrimination, disadvantage and disempowerment during COVID-19: a qualitative intrasectional analysis of the lived experiences of an ethnically diverse healthcare workforce in the United Kingdom.","Gogoi M, Qureshi I, Chaloner J, Al-Oraibi A, Reilly H, Wobi F, Agbonmwandolor JO, Ekezie W, Hassan O, Lal Z, Kapilashrami A, Nellums L, Pareek M, UK-REACH Study Collaborative Group Members.",,International journal for equity in health,2024,2024-05-23,Y,Discrimination; Healthcare Workers; Disadvantage; Disempowerment; Covid-19 Pandemic; Intersectionality; Intrasectionalism,,,"

Background

Healthcare workers (HCWs) in the United Kingdom (UK) have faced many challenges during the COVID-19 pandemic, some of these arising out of their social positions. Existing literature explicating these challenges (e.g., lack of appropriate PPE, redeployment, understaffing) have highlighted inequities in how these have been experienced by HCWs based on ethnicity, gender or, job role. In this paper, we move a step ahead and examine how the intersection of these social positions have impacted HCWs' experiences of challenges during the pandemic.

Methods

We collected qualitative data, using interviews and focus groups, from 164 HCWs from different ethnicities, gender, job roles, migration statuses, and regions in the United Kingdom (UK) between December 2020 and July 2021. Interviews and focus groups were conducted online or by telephone, and recorded with participants' permission. Recordings were transcribed and a hybrid thematic analytical approach integrating inductive data-driven codes with deductive ones informed by an intersectional framework was adopted to analyse the transcripts.

Results

Thematic analysis of transcripts identified disempowerment, disadvantage and, discrimination as the three main themes around which HCWs' experiences of challenges were centred, based on their intersecting identities (e.g., ethnicity gender, and/or migration status). Our analysis also acknowledges that disadvantages faced by HCWs were linked to systemic and structural factors at the micro, meso and macro ecosystemic levels. This merging of analysis which is grounded in intersectionality and considers the ecosystemic levels has been termed as 'intrasectionalism'.

Discussion

Our research demonstrates how an intrasectional lens can help better understand how different forms of mutually reinforcing inequities exist at all levels within the healthcare workforce and how these impact HCWs from certain backgrounds who face greater disadvantage, discrimination and disempowerment, particularly during times of crisis like the COVID-19 pandemic.",,pdf:https://equityhealthj.biomedcentral.com/counter/pdf/10.1186/s12939-024-02198-0; doi:https://doi.org/10.1186/s12939-024-02198-0; html:https://europepmc.org/articles/PMC11118759; pdf:https://europepmc.org/articles/PMC11118759?pdf=render +37132645,https://doi.org/10.1017/s0033291721002257,"Life expectancy, mortality risks and cause of death in patients with serious mental illness in South East London: a comparison between 2008-2012 and 2013-2017.","Chang CK, Chesney E, Teng WN, Hollandt S, Pritchard M, Shetty H, Stewart R, McGuire P, Patel R.",,Psychological medicine,2023,2021-09-07,Y,Mortality; Schizophrenia; Life expectancy; Cause of death; Bipolar disorder; Standardised Mortality Ratio,,,"

Background

People with serious mental illness (SMI) have a significantly shorter life expectancy than the general population. This study investigates whether the mortality rate in this group has changed over the last decade.

Methods

Using Clinical Record Interactive Search software, we extracted data from a large electronic database of patients in South East London. All patients with schizophrenia, schizoaffective disorder or bipolar disorder from 2008 to 2012 and/or 2013 to 2017 were included. Estimates of life expectancy at birth, standardised mortality ratios and causes of death were obtained for each cohort according to diagnosis and gender. Comparisons were made between cohorts and with the general population using data obtained from the UK Office of National Statistics.

Results

In total, 26 005 patients were included. In men, life expectancy was greater in 2013-2017 (64.9 years; 95% CI 63.6-66.3) than in 2008-2012 (63.2 years; 95% CI 61.5-64.9). Similarly, in women, life expectancy was greater in 2013-2017 (69.1 years; 95% CI 67.5-70.7) than in 2008-2012 (68.1 years; 95% CI 66.2-69.9). The difference with general population life expectancy fell by 0.9 years between cohorts in men, and 0.5 years in women. In the 2013-2017 cohorts, cancer accounted for a similar proportion of deaths as cardiovascular disease.

Conclusions

Relative to the general population, life expectancy for people with SMI is still much worse, though it appears to be improving. The increased cancer-related mortality suggests that physical health monitoring should consider including cancer as well.",,pdf:https://www.cambridge.org/core/services/aop-cambridge-core/content/view/F28CB69D452C5EFDAFF77D0FE59FC094/S0033291721002257a.pdf/div-class-title-life-expectancy-mortality-risks-and-cause-of-death-in-patients-with-serious-mental-illness-in-south-east-london-a-comparison-between-2008-2012-and-2013-2017-div.pdf; doi:https://doi.org/10.1017/S0033291721002257; html:https://europepmc.org/articles/PMC9975985; pdf:https://europepmc.org/articles/PMC9975985?pdf=render 32127008,https://doi.org/10.1186/s13059-020-01969-6,Accurate targeted long-read DNA methylation and hydroxymethylation sequencing with TAPS.,"Liu Y, Cheng J, Siejka-Zielińska P, Weldon C, Roberts H, Lopopolo M, Magri A, D'Arienzo V, Harris JM, McKeating JA, Song CX.",,Genome biology,2020,2020-03-03,Y,DNA methylation; 5-methylcytosine; Long-read Sequencing; Bisulfite-free; Epigenetic Phasing,Understanding the Causes of Disease,infection,"We present long-read Tet-assisted pyridine borane sequencing (lrTAPS) for targeted base-resolution sequencing of DNA methylation and hydroxymethylation in regions up to 10 kb from nanogram-level input. Compatible with both Oxford Nanopore and PacBio Single-Molecule Real-Time (SMRT) sequencing, lrTAPS detects methylation with accuracy comparable to short-read Illumina sequencing but with long-range epigenetic phasing. We applied lrTAPS to sequence difficult-to-map regions in mouse embryonic stem cells and to identify distinct methylation events in the integrated hepatitis B virus genome.",,pdf:https://genomebiology.biomedcentral.com/track/pdf/10.1186/s13059-020-01969-6; doi:https://doi.org/10.1186/s13059-020-01969-6; html:https://europepmc.org/articles/PMC7053107; pdf:https://europepmc.org/articles/PMC7053107?pdf=render +38783292,https://doi.org/10.1186/s12939-024-02198-0,"Discrimination, disadvantage and disempowerment during COVID-19: a qualitative intrasectional analysis of the lived experiences of an ethnically diverse healthcare workforce in the United Kingdom.","Gogoi M, Qureshi I, Chaloner J, Al-Oraibi A, Reilly H, Wobi F, Agbonmwandolor JO, Ekezie W, Hassan O, Lal Z, Kapilashrami A, Nellums L, Pareek M, UK-REACH Study Collaborative Group Members.",,International journal for equity in health,2024,2024-05-23,Y,Discrimination; Healthcare Workers; Disadvantage; Disempowerment; Covid-19 Pandemic; Intersectionality; Intrasectionalism,,,"

Background

Healthcare workers (HCWs) in the United Kingdom (UK) have faced many challenges during the COVID-19 pandemic, some of these arising out of their social positions. Existing literature explicating these challenges (e.g., lack of appropriate PPE, redeployment, understaffing) have highlighted inequities in how these have been experienced by HCWs based on ethnicity, gender or, job role. In this paper, we move a step ahead and examine how the intersection of these social positions have impacted HCWs' experiences of challenges during the pandemic.

Methods

We collected qualitative data, using interviews and focus groups, from 164 HCWs from different ethnicities, gender, job roles, migration statuses, and regions in the United Kingdom (UK) between December 2020 and July 2021. Interviews and focus groups were conducted online or by telephone, and recorded with participants' permission. Recordings were transcribed and a hybrid thematic analytical approach integrating inductive data-driven codes with deductive ones informed by an intersectional framework was adopted to analyse the transcripts.

Results

Thematic analysis of transcripts identified disempowerment, disadvantage and, discrimination as the three main themes around which HCWs' experiences of challenges were centred, based on their intersecting identities (e.g., ethnicity gender, and/or migration status). Our analysis also acknowledges that disadvantages faced by HCWs were linked to systemic and structural factors at the micro, meso and macro ecosystemic levels. This merging of analysis which is grounded in intersectionality and considers the ecosystemic levels has been termed as 'intrasectionalism'.

Discussion

Our research demonstrates how an intrasectional lens can help better understand how different forms of mutually reinforcing inequities exist at all levels within the healthcare workforce and how these impact HCWs from certain backgrounds who face greater disadvantage, discrimination and disempowerment, particularly during times of crisis like the COVID-19 pandemic.",,pdf:https://equityhealthj.biomedcentral.com/counter/pdf/10.1186/s12939-024-02198-0; doi:https://doi.org/10.1186/s12939-024-02198-0; html:https://europepmc.org/articles/PMC11118759; pdf:https://europepmc.org/articles/PMC11118759?pdf=render 33075408,https://doi.org/10.1016/j.jaci.2020.10.007,Factors associated with adverse COVID-19 outcomes in patients with psoriasis-insights from a global registry-based study.,"Mahil SK, Dand N, Mason KJ, Yiu ZZN, Tsakok T, Meynell F, Coker B, McAteer H, Moorhead L, Mackenzie T, Rossi MT, Rivera R, Mahe E, Carugno A, Magnano M, Rech G, Balogh EA, Feldman SR, De La Cruz C, Choon SE, Naldi L, Lambert J, Spuls P, Jullien D, Bachelez H, McMahon DE, Freeman EE, Gisondi P, Puig L, Warren RB, Di Meglio P, Langan SM, Capon F, Griffiths CEM, Barker JN, Smith CH, PsoProtect study group.",,The Journal of allergy and clinical immunology,2021,2020-10-16,Y,Psoriasis; Immunosuppressants; risk factors; Hospitalization; Biologics; Covid-19,,,"

Background

The multimorbid burden and use of systemic immunosuppressants in people with psoriasis may confer greater risk of adverse outcomes of coronavirus disease 2019 (COVID-19), but the data are limited.

Objective

Our aim was to characterize the course of COVID-19 in patients with psoriasis and identify factors associated with hospitalization.

Methods

Clinicians reported patients with psoriasis with confirmed/suspected COVID-19 via an international registry, Psoriasis Patient Registry for Outcomes, Therapy and Epidemiology of COVID-19 Infection. Multiple logistic regression was used to assess the association between clinical and/or demographic characteristics and hospitalization. A separate patient-facing registry characterized risk-mitigating behaviors.

Results

Of 374 clinician-reported patients from 25 countries, 71% were receiving a biologic, 18% were receiving a nonbiologic, and 10% were not receiving any systemic treatment for psoriasis. In all, 348 patients (93%) were fully recovered from COVID-19, 77 (21%) were hospitalized, and 9 (2%) died. Increased hospitalization risk was associated with older age (multivariable-adjusted odds ratio [OR] = 1.59 per 10 years; 95% CI = 1.19-2.13), male sex (OR = 2.51; 95% CI = 1.23-5.12), nonwhite ethnicity (OR = 3.15; 95% CI = 1.24-8.03), and comorbid chronic lung disease (OR = 3.87; 95% CI = 1.52-9.83). Hospitalization was more frequent in patients using nonbiologic systemic therapy than in those using biologics (OR = 2.84; 95% CI = 1.31-6.18). No significant differences were found between classes of biologics. Independent patient-reported data (n = 1626 across 48 countries) suggested lower levels of social isolation in individuals receiving nonbiologic systemic therapy than in those receiving biologics (OR = 0.68; 95% CI = 0.50-0.94).

Conclusion

In this international case series of patients with moderate-to-severe psoriasis, biologic use was associated with lower risk of COVID-19-related hospitalization than with use of nonbiologic systemic therapies; however, further investigation is warranted on account of potential selection bias and unmeasured confounding. Established risk factors (being older, being male, being of nonwhite ethnicity, and having comorbidities) were associated with higher hospitalization rates.",,pdf:https://researchonline.lshtm.ac.uk/id/eprint/4659367/1/Factors%20associated%20with%20adverse%20COVID-19%20outcomes%20in%20patients%20with%20psoriasis-insights%20from%20a%20global%20registry-based%20study.pdf; doi:https://doi.org/10.1016/j.jaci.2020.10.007; html:https://europepmc.org/articles/PMC7566694; pdf:https://europepmc.org/articles/PMC7566694?pdf=render 35617980,https://doi.org/10.1016/s0140-6736(22)00532-3,Measuring the availability of human resources for health and its relationship to universal health coverage for 204 countries and territories from 1990 to 2019: a systematic analysis for the Global Burden of Disease Study 2019.,GBD 2019 Human Resources for Health Collaborators.,,"Lancet (London, England)",2022,2022-05-23,Y,,,,"

Background

Human resources for health (HRH) include a range of occupations that aim to promote or improve human health. The UN Sustainable Development Goals (SDGs) and the WHO Health Workforce 2030 strategy have drawn attention to the importance of HRH for achieving policy priorities such as universal health coverage (UHC). Although previous research has found substantial global disparities in HRH, the absence of comparable cross-national estimates of existing workforces has hindered efforts to quantify workforce requirements to meet health system goals. We aimed to use comparable and standardised data sources to estimate HRH densities globally, and to examine the relationship between a subset of HRH cadres and UHC effective coverage performance.

Methods

Through the International Labour Organization and Global Health Data Exchange databases, we identified 1404 country-years of data from labour force surveys and 69 country-years of census data, with detailed microdata on health-related employment. From the WHO National Health Workforce Accounts, we identified 2950 country-years of data. We mapped data from all occupational coding systems to the International Standard Classification of Occupations 1988 (ISCO-88), allowing for standardised estimation of densities for 16 categories of health workers across the full time series. Using data from 1990 to 2019 for 196 of 204 countries and territories, covering seven Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) super-regions and 21 regions, we applied spatiotemporal Gaussian process regression (ST-GPR) to model HRH densities from 1990 to 2019 for all countries and territories. We used stochastic frontier meta-regression to model the relationship between the UHC effective coverage index and densities for the four categories of health workers enumerated in SDG indicator 3.c.1 pertaining to HRH: physicians, nurses and midwives, dentistry personnel, and pharmaceutical personnel. We identified minimum workforce density thresholds required to meet a specified target of 80 out of 100 on the UHC effective coverage index, and quantified national shortages with respect to those minimum thresholds.

Findings

We estimated that, in 2019, the world had 104·0 million (95% uncertainty interval 83·5-128·0) health workers, including 12·8 million (9·7-16·6) physicians, 29·8 million (23·3-37·7) nurses and midwives, 4·6 million (3·6-6·0) dentistry personnel, and 5·2 million (4·0-6·7) pharmaceutical personnel. We calculated a global physician density of 16·7 (12·6-21·6) per 10 000 population, and a nurse and midwife density of 38·6 (30·1-48·8) per 10 000 population. We found the GBD super-regions of sub-Saharan Africa, south Asia, and north Africa and the Middle East had the lowest HRH densities. To reach 80 out of 100 on the UHC effective coverage index, we estimated that, per 10 000 population, at least 20·7 physicians, 70·6 nurses and midwives, 8·2 dentistry personnel, and 9·4 pharmaceutical personnel would be needed. In total, the 2019 national health workforces fell short of these minimum thresholds by 6·4 million physicians, 30·6 million nurses and midwives, 3·3 million dentistry personnel, and 2·9 million pharmaceutical personnel.

Interpretation

Considerable expansion of the world's health workforce is needed to achieve high levels of UHC effective coverage. The largest shortages are in low-income settings, highlighting the need for increased financing and coordination to train, employ, and retain human resources in the health sector. Actual HRH shortages might be larger than estimated because minimum thresholds for each cadre of health workers are benchmarked on health systems that most efficiently translate human resources into UHC attainment.

Funding

Bill & Melinda Gates Foundation.",,pdf:http://www.thelancet.com/article/S0140673622005323/pdf; doi:https://doi.org/10.1016/S0140-6736(22)00532-3; html:https://europepmc.org/articles/PMC9168805 -37263751,https://doi.org/10.1183/13993003.01667-2022,Genome-wide association study of chronic sputum production implicates loci involved in mucus production and infection.,"Packer RJ, Shrine N, Hall R, Melbourne CA, Thompson R, Williams AT, Paynton ML, Guyatt AL, Allen RJ, Lee PH, John C, Campbell A, Hayward C, de Vries M, Vonk JM, Davitte J, Hessel E, Michalovich D, Betts JC, Sayers I, Yeo A, Hall IP, Tobin MD, Wain LV.",,The European respiratory journal,2023,2023-06-15,Y,,,,"

Background

Chronic sputum production impacts on quality of life and is a feature of many respiratory diseases. Identification of the genetic variants associated with chronic sputum production in a disease agnostic sample could improve understanding of its causes and identify new molecular targets for treatment.

Methods

We conducted a genome-wide association study (GWAS) of chronic sputum production in UK Biobank. Signals meeting genome-wide significance (p<5×10-8) were investigated in additional independent studies, were fine-mapped and putative causal genes identified by gene expression analysis. GWASs of respiratory traits were interrogated to identify whether the signals were driven by existing respiratory disease among the cases and variants were further investigated for wider pleiotropic effects using phenome-wide association studies (PheWASs).

Results

From a GWAS of 9714 cases and 48 471 controls, we identified six novel genome-wide significant signals for chronic sputum production including signals in the human leukocyte antigen (HLA) locus, chromosome 11 mucin locus (containing MUC2, MUC5AC and MUC5B) and FUT2 locus. The four common variant associations were supported by independent studies with a combined sample size of up to 2203 cases and 17 627 controls. The mucin locus signal had previously been reported for association with moderate-to-severe asthma. The HLA signal was fine-mapped to an amino acid change of threonine to arginine (frequency 36.8%) in HLA-DRB1 (HLA-DRB1*03:147). The signal near FUT2 was associated with expression of several genes including FUT2, for which the direction of effect was tissue dependent. Our PheWAS identified a wide range of associations including blood cell traits, liver biomarkers, infections, gastrointestinal and thyroid-associated diseases, and respiratory disease.

Conclusions

Novel signals at the FUT2 and mucin loci suggest that mucin fucosylation may be a driver of chronic sputum production even in the absence of diagnosed respiratory disease and provide genetic support for this pathway as a target for therapeutic intervention.",,pdf:https://erj.ersjournals.com/content/erj/61/6/2201667.full.pdf; doi:https://doi.org/10.1183/13993003.01667-2022; html:https://europepmc.org/articles/PMC10284065; pdf:https://europepmc.org/articles/PMC10284065?pdf=render 32423943,https://doi.org/10.1136/bmjopen-2020-038974,Study protocol for a multicentre longitudinal mixed methods study to explore the Outcomes of ChildrEn and fAmilies in the first year after paediatric Intensive Care: the OCEANIC study.,"Manning JC, Latour JM, Curley MAQ, Draper ES, Jilani T, Quinlan PR, Watson RS, Rennick JE, Colville G, Pinto N, Latif A, Popejoy E, Coad J, OCEANIC Study Investigators.",,BMJ open,2020,2020-05-17,Y,Qualitative Research; Statistics & Research Methods; Paediatric Intensive & Critical Care,,,"

Introduction

Annually in the UK, 20 000 children become very ill or injured and need specialist care within a paediatric intensive care unit (PICU). Most children survive. However, some children and their families may experience problems after they have left the PICU including physical, functional and/or emotional problems. It is unknown which children and families experience such problems, when these occur or what causes them. The aim of this mixed-method longitudinal cohort study is to understand the physical, functional, emotional and social impact of children surviving PICU (aged: 1 month-17 years), their parents and siblings, during the first year after a PICU admission.

Methods and analysis

A quantitative study involving 300 child survivors of PICU; 300 parents; and 150-300 siblings will collect data (using self-completion questionnaires) at baseline, PICU discharge, 1, 3, 6 and 12 months post-PICU discharge. Questionnaires will comprise validated and reliable instruments. Demographic data, PICU admission and treatment data, health-related quality of life, functional status, strengths and difficulties behaviour and post-traumatic stress symptoms will be collected from the child. Parent and sibling data will be collected on the impact of paediatric health conditions on the family's functioning capabilities, levels of anxiety and social impact of the child's PICU admission. Data will be analysed using descriptive and inferential statistics. Concurrently, an embedded qualitative study involving semistructured interviews with 24 enrolled families at 3 months and 9 months post-PICU discharge will be undertaken. Framework analysis will be used to analyse the qualitative data.

Ethics and dissemination

The study has received ethical approval from the National Health Services Research Ethics Committee (Ref: 19/WM/0290) and full governance clearance. This will be the first UK study to comprehensively investigate physical, functional, emotional and social consequences of PICU survival in the first-year postdischarge.Clinical Trials Registration Number: ISRCTN28072812 [Pre-results].",,pdf:https://bmjopen.bmj.com/content/bmjopen/10/5/e038974.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-038974; html:https://europepmc.org/articles/PMC7239532; pdf:https://europepmc.org/articles/PMC7239532?pdf=render +37263751,https://doi.org/10.1183/13993003.01667-2022,Genome-wide association study of chronic sputum production implicates loci involved in mucus production and infection.,"Packer RJ, Shrine N, Hall R, Melbourne CA, Thompson R, Williams AT, Paynton ML, Guyatt AL, Allen RJ, Lee PH, John C, Campbell A, Hayward C, de Vries M, Vonk JM, Davitte J, Hessel E, Michalovich D, Betts JC, Sayers I, Yeo A, Hall IP, Tobin MD, Wain LV.",,The European respiratory journal,2023,2023-06-15,Y,,,,"

Background

Chronic sputum production impacts on quality of life and is a feature of many respiratory diseases. Identification of the genetic variants associated with chronic sputum production in a disease agnostic sample could improve understanding of its causes and identify new molecular targets for treatment.

Methods

We conducted a genome-wide association study (GWAS) of chronic sputum production in UK Biobank. Signals meeting genome-wide significance (p<5×10-8) were investigated in additional independent studies, were fine-mapped and putative causal genes identified by gene expression analysis. GWASs of respiratory traits were interrogated to identify whether the signals were driven by existing respiratory disease among the cases and variants were further investigated for wider pleiotropic effects using phenome-wide association studies (PheWASs).

Results

From a GWAS of 9714 cases and 48 471 controls, we identified six novel genome-wide significant signals for chronic sputum production including signals in the human leukocyte antigen (HLA) locus, chromosome 11 mucin locus (containing MUC2, MUC5AC and MUC5B) and FUT2 locus. The four common variant associations were supported by independent studies with a combined sample size of up to 2203 cases and 17 627 controls. The mucin locus signal had previously been reported for association with moderate-to-severe asthma. The HLA signal was fine-mapped to an amino acid change of threonine to arginine (frequency 36.8%) in HLA-DRB1 (HLA-DRB1*03:147). The signal near FUT2 was associated with expression of several genes including FUT2, for which the direction of effect was tissue dependent. Our PheWAS identified a wide range of associations including blood cell traits, liver biomarkers, infections, gastrointestinal and thyroid-associated diseases, and respiratory disease.

Conclusions

Novel signals at the FUT2 and mucin loci suggest that mucin fucosylation may be a driver of chronic sputum production even in the absence of diagnosed respiratory disease and provide genetic support for this pathway as a target for therapeutic intervention.",,pdf:https://erj.ersjournals.com/content/erj/61/6/2201667.full.pdf; doi:https://doi.org/10.1183/13993003.01667-2022; html:https://europepmc.org/articles/PMC10284065; pdf:https://europepmc.org/articles/PMC10284065?pdf=render 31844048,https://doi.org/10.1038/s41467-019-13585-5,Genome-wide analysis identifies molecular systems and 149 genetic loci associated with income.,"Hill WD, Davies NM, Ritchie SJ, Skene NG, Bryois J, Bell S, Di Angelantonio E, Roberts DJ, Xueyi S, Davies G, Liewald DCM, Porteous DJ, Hayward C, Butterworth AS, McIntosh AM, Gale CR, Deary IJ.",,Nature communications,2019,2019-12-16,Y,,Understanding the Causes of Disease,,"Socioeconomic position (SEP) is a multi-dimensional construct reflecting (and influencing) multiple socio-cultural, physical, and environmental factors. In a sample of 286,301 participants from UK Biobank, we identify 30 (29 previously unreported) independent-loci associated with income. Using a method to meta-analyze data from genetically-correlated traits, we identify an additional 120 income-associated loci. These loci show clear evidence of functionality, with transcriptional differences identified across multiple cortical tissues, and links to GABAergic and serotonergic neurotransmission. By combining our genome wide association study on income with data from eQTL studies and chromatin interactions, 24 genes are prioritized for follow up, 18 of which were previously associated with intelligence. We identify intelligence as one of the likely causal, partly-heritable phenotypes that might bridge the gap between molecular genetic inheritance and phenotypic consequence in terms of income differences. These results indicate that, in modern era Great Britain, genetic effects contribute towards some of the observed socioeconomic inequalities.","This study linked genetic sequencing data and information on household income to identify parts of the genome that are more common in people who live in more affluent households. The authors identified 150 parts of the genome that were associated with income, and found that these genetic regions were more commonly expressed in the brain and testes. The results indicate that intelligence and income are causally linked, and suggest that genetics partly explain a small amount of variation (~2%) in household income in the UK.",pdf:https://www.nature.com/articles/s41467-019-13585-5.pdf; doi:https://doi.org/10.1038/s41467-019-13585-5; html:https://europepmc.org/articles/PMC6915786; pdf:https://europepmc.org/articles/PMC6915786?pdf=render 31711539,https://doi.org/10.1186/s13326-019-0211-7,Text mining brain imaging reports.,"Alex B, Grover C, Tobin R, Sudlow C, Mair G, Whiteley W.",,Journal of biomedical semantics,2019,2019-11-12,Y,Stroke Classification; Text Mining; Electronic Healthcare Records; Neuroimaging Reports,,,"

Background

With the improvements to text mining technology and the availability of large unstructured Electronic Healthcare Records (EHR) datasets, it is now possible to extract structured information from raw text contained within EHR at reasonably high accuracy. We describe a text mining system for classifying radiologists' reports of CT and MRI brain scans, assigning labels indicating occurrence and type of stroke, as well as other observations. Our system, the Edinburgh Information Extraction for Radiology reports (EdIE-R) system, which we describe here, was developed and tested on a collection of radiology reports.The work reported in this paper is based on 1168 radiology reports from the Edinburgh Stroke Study (ESS), a hospital-based register of stroke and transient ischaemic attack patients. We manually created annotations for this data in parallel with developing the rule-based EdIE-R system to identify phenotype information related to stroke in radiology reports. This process was iterative and domain expert feedback was considered at each iteration to adapt and tune the EdIE-R text mining system which identifies entities, negation and relations between entities in each report and determines report-level labels (phenotypes).

Results

The inter-annotator agreement (IAA) for all types of annotations is high at 96.96 for entities, 96.46 for negation, 95.84 for relations and 94.02 for labels. The equivalent system scores on the blind test set are equally high at 95.49 for entities, 94.41 for negation, 98.27 for relations and 96.39 for labels for the first annotator and 96.86, 96.01, 96.53 and 92.61, respectively for the second annotator.

Conclusion

Automated reading of such EHR data at such high levels of accuracies opens up avenues for population health monitoring and audit, and can provide a resource for epidemiological studies. We are in the process of validating EdIE-R in separate larger cohorts in NHS England and Scotland. The manually annotated ESS corpus will be available for research purposes on application.",,pdf:https://jbiomedsem.biomedcentral.com/track/pdf/10.1186/s13326-019-0211-7; doi:https://doi.org/10.1186/s13326-019-0211-7; html:https://europepmc.org/articles/PMC6849161; pdf:https://europepmc.org/articles/PMC6849161?pdf=render 36914875,https://doi.org/10.1038/s41588-023-01314-0,Multi-ancestry genome-wide association analyses improve resolution of genes and pathways influencing lung function and chronic obstructive pulmonary disease risk.,"Shrine N, Izquierdo AG, Chen J, Packer R, Hall RJ, Guyatt AL, Batini C, Thompson RJ, Pavuluri C, Malik V, Hobbs BD, Moll M, Kim W, Tal-Singer R, Bakke P, Fawcett KA, John C, Coley K, Piga NN, Pozarickij A, Lin K, Millwood IY, Chen Z, Li L, China Kadoorie Biobank Collaborative Group, Wijnant SRA, Lahousse L, Brusselle G, Uitterlinden AG, Manichaikul A, Oelsner EC, Rich SS, Barr RG, Kerr SM, Vitart V, Brown MR, Wielscher M, Imboden M, Jeong A, Bartz TM, Gharib SA, Flexeder C, Karrasch S, Gieger C, Peters A, Stubbe B, Hu X, Ortega VE, Meyers DA, Bleecker ER, Gabriel SB, Gupta N, Smith AV, Luan J, Zhao JH, Hansen AF, Langhammer A, Willer C, Bhatta L, Porteous D, Smith BH, Campbell A, Sofer T, Lee J, Daviglus ML, Yu B, Lim E, Xu H, O'Connor GT, Thareja G, Albagha OME, Qatar Genome Program Research (QGPR) Consortium, Suhre K, Granell R, Faquih TO, Hiemstra PS, Slats AM, Mullin BH, Hui J, James A, Beilby J, Patasova K, Hysi P, Koskela JT, Wyss AB, Jin J, Sikdar S, Lee M, May-Wilson S, Pirastu N, Kentistou KA, Joshi PK, Timmers PRHJ, Williams AT, Free RC, Wang X, Morrison JL, Gilliland FD, Chen Z, Wang CA, Foong RE, Harris SE, Taylor A, Redmond P, Cook JP, Mahajan A, Lind L, Palviainen T, Lehtimäki T, Raitakari OT, Kaprio J, Rantanen T, Pietiläinen KH, Cox SR, Pennell CE, Hall GL, Gauderman WJ, Brightling C, Wilson JF, Vasankari T, Laitinen T, Salomaa V, Mook-Kanamori DO, Timpson NJ, Zeggini E, Dupuis J, Hayward C, Brumpton B, Langenberg C, Weiss S, Homuth G, Schmidt CO, Probst-Hensch N, Jarvelin MR, Morrison AC, Polasek O, Rudan I, Lee JH, Sayers I, Rawlins EL, Dudbridge F, Silverman EK, Strachan DP, Walters RG, Morris AP, London SJ, Cho MH, Wain LV, Hall IP, Tobin MD.",,Nature genetics,2023,2023-03-13,Y,,,,"Lung-function impairment underlies chronic obstructive pulmonary disease (COPD) and predicts mortality. In the largest multi-ancestry genome-wide association meta-analysis of lung function to date, comprising 580,869 participants, we identified 1,020 independent association signals implicating 559 genes supported by ≥2 criteria from a systematic variant-to-gene mapping framework. These genes were enriched in 29 pathways. Individual variants showed heterogeneity across ancestries, age and smoking groups, and collectively as a genetic risk score showed strong association with COPD across ancestry groups. We undertook phenome-wide association studies for selected associated variants as well as trait and pathway-specific genetic risk scores to infer possible consequences of intervening in pathways underlying lung function. We highlight new putative causal variants, genes, proteins and pathways, including those targeted by existing drugs. These findings bring us closer to understanding the mechanisms underlying lung function and COPD, and should inform functional genomics experiments and potentially future COPD therapies.",,pdf:https://www.nature.com/articles/s41588-023-01314-0.pdf; doi:https://doi.org/10.1038/s41588-023-01314-0; html:https://europepmc.org/articles/PMC10011137; pdf:https://europepmc.org/articles/PMC10011137?pdf=render @@ -2353,8 +2353,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 33847595,https://doi.org/10.2196/22397,Using General-purpose Sentiment Lexicons for Suicide Risk Assessment in Electronic Health Records: Corpus-Based Analysis.,"Bittar A, Velupillai S, Roberts A, Dutta R.",,JMIR medical informatics,2021,2021-04-13,Y,"Psychiatry; risk assessment; Suicide; Electronic Health Records; Natural Language Processing; Suicide, Attempted; Sentiment Analysis; Corpus Linguistics",,,"

Background

Suicide is a serious public health issue, accounting for 1.4% of all deaths worldwide. Current risk assessment tools are reported as performing little better than chance in predicting suicide. New methods for studying dynamic features in electronic health records (EHRs) are being increasingly explored. One avenue of research involves using sentiment analysis to examine clinicians' subjective judgments when reporting on patients. Several recent studies have used general-purpose sentiment analysis tools to automatically identify negative and positive words within EHRs to test correlations between sentiment extracted from the texts and specific medical outcomes (eg, risk of suicide or in-hospital mortality). However, little attention has been paid to analyzing the specific words identified by general-purpose sentiment lexicons when applied to EHR corpora.

Objective

This study aims to quantitatively and qualitatively evaluate the coverage of six general-purpose sentiment lexicons against a corpus of EHR texts to ascertain the extent to which such lexical resources are fit for use in suicide risk assessment.

Methods

The data for this study were a corpus of 198,451 EHR texts made up of two subcorpora drawn from a 1:4 case-control study comparing clinical notes written over the period leading up to a suicide attempt (cases, n=2913) with those not preceding such an attempt (controls, n=14,727). We calculated word frequency distributions within each subcorpus to identify representative keywords for both the case and control subcorpora. We quantified the relative coverage of the 6 lexicons with respect to this list of representative keywords in terms of weighted precision, recall, and F score.

Results

The six lexicons achieved reasonable precision (0.53-0.68) but very low recall (0.04-0.36). Many of the most representative keywords in the suicide-related (case) subcorpus were not identified by any of the lexicons. The sentiment-bearing status of these keywords for this use case is thus doubtful.

Conclusions

Our findings indicate that these 6 sentiment lexicons are not optimal for use in suicide risk assessment. We propose a set of guidelines for the creation of more suitable lexical resources for distinguishing suicide-related from non-suicide-related EHR texts.",,pdf:https://medinform.jmir.org/2021/4/e22397/PDF; doi:https://doi.org/10.2196/22397; html:https://europepmc.org/articles/PMC8080148 37302069,https://doi.org/10.1016/j.celrep.2023.112613,Proteomic analysis of circulating immune cells identifies cellular phenotypes associated with COVID-19 severity.,"Potts M, Fletcher-Etherington A, Nightingale K, Mescia F, Bergamaschi L, Calero-Nieto FJ, Antrobus R, Williamson J, Cambridge Institute of Therapeutic Immunology and Infectious Disease-National Institute of Health Research (CITIID-NIHR) COVID BioResource Collaboration, Parsons H, Huttlin EL, Kingston N, Göttgens B, Bradley JR, Lehner PJ, Matheson NJ, Smith KGC, Wills MR, Lyons PA, Weekes MP.",,Cell reports,2023,2023-05-29,Y,Cp: Immunology,,,"Certain serum proteins, including C-reactive protein (CRP) and D-dimer, have prognostic value in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Nonetheless, these factors are non-specific, providing limited mechanistic insight into the peripheral blood mononuclear cell (PBMC) populations that drive the pathogenesis of severe COVID-19. To identify cellular phenotypes associated with disease, we performed a comprehensive, unbiased analysis of total and plasma-membrane PBMC proteomes from 40 unvaccinated individuals with SARS-CoV-2, spanning the whole disease spectrum. Combined with RNA sequencing (RNA-seq) and flow cytometry from the same donors, we define a comprehensive multi-omic profile for each severity level, revealing that immune-cell dysregulation progresses with increasing disease. The cell-surface proteins CEACAMs1, 6, and 8, CD177, CD63, and CD89 are strongly associated with severe COVID-19, corresponding to the emergence of atypical CD3+CD4+CEACAM1/6/8+CD177+CD63+CD89+ and CD16+CEACAM1/6/8+ mononuclear cells. Utilization of these markers may facilitate real-time patient assessment by flow cytometry and identify immune populations that could be targeted to ameliorate immunopathology.",,pdf:http://www.cell.com/article/S2211124723006241/pdf; doi:https://doi.org/10.1016/j.celrep.2023.112613; html:https://europepmc.org/articles/PMC10243220; pdf:https://europepmc.org/articles/PMC10243220?pdf=render 36451358,https://doi.org/10.1016/j.nicl.2022.103253,Hospitalisation for COVID-19 predicts long lasting cerebrovascular impairment: A prospective observational cohort study.,"Tsvetanov KA, Spindler LRB, Stamatakis EA, Newcombe VFJ, Lupson VC, Chatfield DA, Manktelow AE, Outtrim JG, Elmer A, Kingston N, Bradley JR, Bullmore ET, Rowe JB, Menon DK, Cambridge NeuroCOVID Group, NIHR COVID-19 BioResource, Cambridge NIHR Clinical Research Facility, CITIID-NIHR BioResource COVID-19 Collaboration.",,NeuroImage. Clinical,2022,2022-11-07,Y,Cerebrovascular; Microvascular; Neurology; Cardiorespiratory; Covid-19; Sars-cov-2,,,"Human coronavirus disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has multiple neurological consequences, but its long-term effect on brain health is still uncertain. The cerebrovascular consequences of COVID-19 may also affect brain health. We studied the chronic effect of COVID-19 on cerebrovascular health, in relation to acute severity, adverse clinical outcomes and in contrast to control group data. Here we assess cerebrovascular health in 45 patients six months after hospitalisation for acute COVID-19 using the resting state fluctuation amplitudes (RSFA) from functional magnetic resonance imaging, in relation to disease severity and in contrast with 42 controls. Acute COVID-19 severity was indexed by COVID-19 WHO Progression Scale, inflammatory and coagulatory biomarkers. Chronic widespread changes in frontoparietal RSFA were related to the severity of the acute COVID-19 episode. This relationship was not explained by chronic cardiorespiratory dysfunction, age, or sex. The level of cerebrovascular dysfunction was associated with cognitive, mental, and physical health at follow-up. The principal findings were consistent across univariate and multivariate approaches. The results indicate chronic cerebrovascular impairment following severe acute COVID-19, with the potential for long-term consequences on cognitive function and mental wellbeing.",,doi:https://doi.org/10.1016/j.nicl.2022.103253; doi:https://doi.org/10.1016/j.nicl.2022.103253; html:https://europepmc.org/articles/PMC9639388; pdf:https://europepmc.org/articles/PMC9639388?pdf=render -36895957,https://doi.org/10.1093/braincomms/fcad037,Investigating genotype-phenotype relationship of extreme neuropathic pain disorders in a UK national cohort.,"Themistocleous AC, Baskozos G, Blesneac I, Comini M, Megy K, Chong S, Deevi SVV, Ginsberg L, Gosal D, Hadden RDM, Horvath R, Mahdi-Rogers M, Manzur A, Mapeta R, Marshall A, Matthews E, McCarthy MI, Reilly MM, Renton T, Rice ASC, Vale TA, van Zuydam N, Walker SM, Woods CG, Bennett DLH.",,Brain communications,2023,2023-02-20,Y,Sodium channels; Neuropathic pain; Peripheral Neuropathy; Whole Genome Sequencing,,,"The aims of our study were to use whole genome sequencing in a cross-sectional cohort of patients to identify new variants in genes implicated in neuropathic pain, to determine the prevalence of known pathogenic variants and to understand the relationship between pathogenic variants and clinical presentation. Patients with extreme neuropathic pain phenotypes (both sensory loss and gain) were recruited from secondary care clinics in the UK and underwent whole genome sequencing as part of the National Institute for Health and Care Research Bioresource Rare Diseases project. A multidisciplinary team assessed the pathogenicity of rare variants in genes previously known to cause neuropathic pain disorders and exploratory analysis of research candidate genes was completed. Association testing for genes carrying rare variants was completed using the gene-wise approach of the combined burden and variance-component test SKAT-O. Patch clamp analysis was performed on transfected HEK293T cells for research candidate variants of genes encoding ion channels. The results include the following: (i) Medically actionable variants were found in 12% of study participants (205 recruited), including known pathogenic variants: SCN9A(ENST00000409672.1): c.2544T>C, p.Ile848Thr that causes inherited erythromelalgia, and SPTLC1(ENST00000262554.2):c.340T>G, p.Cys133Tr variant that causes hereditary sensory neuropathy type-1. (ii) Clinically relevant variants were most common in voltage-gated sodium channels (Nav). (iii) SCN9A(ENST00000409672.1):c.554G>A, pArg185His variant was more common in non-freezing cold injury participants than controls and causes a gain of function of NaV1.7 after cooling (the environmental trigger for non-freezing cold injury). (iv) Rare variant association testing showed a significant difference in distribution for genes NGF, KIF1A, SCN8A, TRPM8, KIF1A, TRPA1 and the regulatory regions of genes SCN11A, FLVCR1, KIF1A and SCN9A between European participants with neuropathic pain and controls. (v) The TRPA1(ENST00000262209.4):c.515C>T, p.Ala172Val variant identified in participants with episodic somatic pain disorder demonstrated gain-of-channel function to agonist stimulation. Whole genome sequencing identified clinically relevant variants in over 10% of participants with extreme neuropathic pain phenotypes. The majority of these variants were found in ion channels. Combining genetic analysis with functional validation can lead to a better understanding as to how rare variants in ion channels lead to sensory neuron hyper-excitability, and how cold, as an environmental trigger, interacts with the gain-of-function NaV1.7 p.Arg185His variant. Our findings highlight the role of ion channel variants in the pathogenesis of extreme neuropathic pain disorders, likely mediated through changes in sensory neuron excitability and interaction with environmental triggers.",,pdf:https://academic.oup.com/braincomms/article-pdf/5/2/fcad037/49446967/fcad037.pdf; doi:https://doi.org/10.1093/braincomms/fcad037; html:https://europepmc.org/articles/PMC9991512; pdf:https://europepmc.org/articles/PMC9991512?pdf=render 35131700,https://doi.org/10.1016/j.media.2022.102366,Multi-dynamic modelling reveals strongly time-varying resting fMRI correlations.,"Pervaiz U, Vidaurre D, Gohil C, Smith SM, Woolrich MW.",,Medical image analysis,2022,2022-01-29,Y,Hidden Markov model; Functional Connectivity; Deep Learning; Dynamic Functional Connectivity; Lstm; Rnns; Time-varying Functional Connectivity; Adversarial Learning; Transient Brain Networks,,,"The activity of functional brain networks is responsible for the emergence of time-varying cognition and behaviour. Accordingly, time-varying correlations (Functional Connectivity) in resting fMRI have been shown to be predictive of behavioural traits, and psychiatric and neurological conditions. Typically, methods that measure time varying Functional Connectivity (FC), such as sliding windows approaches, do not separately model when changes occur in the mean activity levels from when changes occur in the FC, therefore conflating these two distinct types of modulation. We show that this can bias the estimation of time-varying FC to appear more stable over time than it actually is. Here, we propose an alternative approach that models changes in the mean brain activity and in the FC as being able to occur at different times to each other. We refer to this method as the Multi-dynamic Adversarial Generator Encoder (MAGE) model, which includes a model of the network dynamics that captures long-range time dependencies, and is estimated on fMRI data using principles of Generative Adversarial Networks. We evaluated the approach across several simulation studies and resting fMRI data from the Human Connectome Project (1003 subjects), as well as from UK Biobank (13301 subjects). Importantly, we find that separating fluctuations in the mean activity levels from those in the FC reveals much stronger changes in FC over time, and is a better predictor of individual behavioural variability.",,doi:https://doi.org/10.1016/j.media.2022.102366; doi:https://doi.org/10.1016/j.media.2022.102366; html:https://europepmc.org/articles/PMC8907871; pdf:https://europepmc.org/articles/PMC8907871?pdf=render +36895957,https://doi.org/10.1093/braincomms/fcad037,Investigating genotype-phenotype relationship of extreme neuropathic pain disorders in a UK national cohort.,"Themistocleous AC, Baskozos G, Blesneac I, Comini M, Megy K, Chong S, Deevi SVV, Ginsberg L, Gosal D, Hadden RDM, Horvath R, Mahdi-Rogers M, Manzur A, Mapeta R, Marshall A, Matthews E, McCarthy MI, Reilly MM, Renton T, Rice ASC, Vale TA, van Zuydam N, Walker SM, Woods CG, Bennett DLH.",,Brain communications,2023,2023-02-20,Y,Sodium channels; Neuropathic pain; Peripheral Neuropathy; Whole Genome Sequencing,,,"The aims of our study were to use whole genome sequencing in a cross-sectional cohort of patients to identify new variants in genes implicated in neuropathic pain, to determine the prevalence of known pathogenic variants and to understand the relationship between pathogenic variants and clinical presentation. Patients with extreme neuropathic pain phenotypes (both sensory loss and gain) were recruited from secondary care clinics in the UK and underwent whole genome sequencing as part of the National Institute for Health and Care Research Bioresource Rare Diseases project. A multidisciplinary team assessed the pathogenicity of rare variants in genes previously known to cause neuropathic pain disorders and exploratory analysis of research candidate genes was completed. Association testing for genes carrying rare variants was completed using the gene-wise approach of the combined burden and variance-component test SKAT-O. Patch clamp analysis was performed on transfected HEK293T cells for research candidate variants of genes encoding ion channels. The results include the following: (i) Medically actionable variants were found in 12% of study participants (205 recruited), including known pathogenic variants: SCN9A(ENST00000409672.1): c.2544T>C, p.Ile848Thr that causes inherited erythromelalgia, and SPTLC1(ENST00000262554.2):c.340T>G, p.Cys133Tr variant that causes hereditary sensory neuropathy type-1. (ii) Clinically relevant variants were most common in voltage-gated sodium channels (Nav). (iii) SCN9A(ENST00000409672.1):c.554G>A, pArg185His variant was more common in non-freezing cold injury participants than controls and causes a gain of function of NaV1.7 after cooling (the environmental trigger for non-freezing cold injury). (iv) Rare variant association testing showed a significant difference in distribution for genes NGF, KIF1A, SCN8A, TRPM8, KIF1A, TRPA1 and the regulatory regions of genes SCN11A, FLVCR1, KIF1A and SCN9A between European participants with neuropathic pain and controls. (v) The TRPA1(ENST00000262209.4):c.515C>T, p.Ala172Val variant identified in participants with episodic somatic pain disorder demonstrated gain-of-channel function to agonist stimulation. Whole genome sequencing identified clinically relevant variants in over 10% of participants with extreme neuropathic pain phenotypes. The majority of these variants were found in ion channels. Combining genetic analysis with functional validation can lead to a better understanding as to how rare variants in ion channels lead to sensory neuron hyper-excitability, and how cold, as an environmental trigger, interacts with the gain-of-function NaV1.7 p.Arg185His variant. Our findings highlight the role of ion channel variants in the pathogenesis of extreme neuropathic pain disorders, likely mediated through changes in sensory neuron excitability and interaction with environmental triggers.",,pdf:https://academic.oup.com/braincomms/article-pdf/5/2/fcad037/49446967/fcad037.pdf; doi:https://doi.org/10.1093/braincomms/fcad037; html:https://europepmc.org/articles/PMC9991512; pdf:https://europepmc.org/articles/PMC9991512?pdf=render 31922447,https://doi.org/10.1177/0141076819890551,Moving beyond project-specific patient and public involvement in research.,"Turner G, Aiyegbusi OL, Price G, Skrybant M, Calvert M.",,Journal of the Royal Society of Medicine,2020,2020-01-01,N,,,,,,pdf:https://journals.sagepub.com/doi/pdf/10.1177/0141076819890551; doi:https://doi.org/10.1177/0141076819890551; html:https://europepmc.org/articles/PMC6961168; pdf:https://europepmc.org/articles/PMC6961168?pdf=render; doi:https://doi.org/10.1177/0141076819890551 31992634,https://doi.org/10.1136/bmjhci-2019-100117,Optimising electronic prescribing in hospitals: a scoping review protocol.,"Williams J, Bates DW, Sheikh A.",,BMJ health & care informatics,2020,2020-01-01,Y,Health care; Patient Care; Medical Informatics; Information Systems; Record Systems,,,"

Introduction

Electronic prescribing (ePrescribing) systems can improve the quality of prescribing decisions and substantially reduce the risk of serious medication errors in hospitals. However, realising these benefits depends on ensuring that relevant sociotechnical considerations are addressed. Optimising ePrescribing systems is essential to maximise the associated benefits and minimise the accompanying risks of these large-scale and expensive health informatics infrastructures.

Methods

We will undertake a systematic scoping review of the literature to identify strategies to achieve optimisation of ePrescribing systems. We will search Medline, Embase and CINAHL for the period 1 January 2010 to 1 June 2019 and the grey literature by using Google Scholar. Independent reviewers will screen the results using predefined inclusion and exclusion criteria and will extract data for narrative and thematic synthesis.

Discussion

This work will be published in a peer-reviewed journal and we will ensure that the findings are both accessible and interpretable to the public, academics, policymakers and National Health Service leaders.",,pdf:https://informatics.bmj.com/content/bmjhci/27/1/e100117.full.pdf; doi:https://doi.org/10.1136/bmjhci-2019-100117; html:https://europepmc.org/articles/PMC7062357; pdf:https://europepmc.org/articles/PMC7062357?pdf=render 31197928,https://doi.org/10.1002/pds.4811,Methods to generate and validate a Pregnancy Register in the UK Clinical Practice Research Datalink primary care database.,"Minassian C, Williams R, Meeraus WH, Smeeth L, Campbell OMR, Thomas SL.",,Pharmacoepidemiology and drug safety,2019,2019-06-13,Y,Pregnancy; United Kingdom; Pregnancy Outcome; Pharmacoepidemiology; Electronic Health Records; Pregnancy Trimesters,"Applied Analytics, The Human Phenome",,"

Purpose

Primary care databases are increasingly used for researching pregnancy, eg, the effects of maternal drug exposures. However, ascertaining pregnancies, their timing, and outcomes in these data is challenging. While individual studies have adopted different methods, no systematic approach to characterise all pregnancies in a primary care database has yet been published. Therefore, we developed a new algorithm to establish a Pregnancy Register in the UK Clinical Practice Research Datalink (CPRD) GOLD primary care database.

Methods

We compiled over 4000 read and entity codes to identify pregnancy-related records among women aged 11 to 49 years in CPRD GOLD. Codes were categorised by the stage or outcome of pregnancy to facilitate delineation of pregnancy episodes. We constructed hierarchical rule systems to handle information from multiple sources. We assessed the validity of the Register to identify pregnancy outcomes by comparing our results to linked hospitalisation records and Office for National Statistics population rates.

Results

Our algorithm identified 5.8 million pregnancies among 2.4 million women (January 1987-February 2018). We observed close agreement with hospitalisation data regarding completeness of pregnancy outcomes (91% sensitivity for deliveries and 77% for pregnancy losses) and their timing (median 0 days difference, interquartile range 0-2 days). Miscarriage and prematurity rates were consistent with population figures, although termination and, to a lesser extent, live birth rates were underestimated in the Register.

Conclusions

The Pregnancy Register offers huge research potential because of its large size, high completeness, and availability. Further validation work is underway to enhance this data resource and identify optimal approaches for its use.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/pds.4811; doi:https://doi.org/10.1002/pds.4811; html:https://europepmc.org/articles/PMC6618019; pdf:https://europepmc.org/articles/PMC6618019?pdf=render @@ -2363,19 +2363,19 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 32156302,https://doi.org/10.1186/s13326-020-00220-2,Temporal information extraction from mental health records to identify duration of untreated psychosis.,"Viani N, Kam J, Yin L, Bittar A, Dutta R, Patel R, Stewart R, Velupillai S.",,Journal of biomedical semantics,2020,2020-03-10,Y,Schizophrenia; Mental health; Electronic Health Records; Natural Language Processing; Temporal Information Extraction,,,"

Background

Duration of untreated psychosis (DUP) is an important clinical construct in the field of mental health, as longer DUP can be associated with worse intervention outcomes. DUP estimation requires knowledge about when psychosis symptoms first started (symptom onset), and when psychosis treatment was initiated. Electronic health records (EHRs) represent a useful resource for retrospective clinical studies on DUP, but the core information underlying this construct is most likely to lie in free text, meaning it is not readily available for clinical research. Natural Language Processing (NLP) is a means to addressing this problem by automatically extracting relevant information in a structured form. As a first step, it is important to identify appropriate documents, i.e., those that are likely to include the information of interest. Next, temporal information extraction methods are needed to identify time references for early psychosis symptoms. This NLP challenge requires solving three different tasks: time expression extraction, symptom extraction, and temporal ""linking"". In this study, we focus on the first step, using two relevant EHR datasets.

Results

We applied a rule-based NLP system for time expression extraction that we had previously adapted to a corpus of mental health EHRs from patients with a diagnosis of schizophrenia (first referrals). We extended this work by applying this NLP system to a larger set of documents and patients, to identify additional texts that would be relevant for our long-term goal, and developed a new corpus from a subset of these new texts (early intervention services). Furthermore, we added normalized value annotations (""2011-05"") to the annotated time expressions (""May 2011"") in both corpora. The finalized corpora were used for further NLP development and evaluation, with promising results (normalization accuracy 71-86%). To highlight the specificities of our annotation task, we also applied the final adapted NLP system to a different temporally annotated clinical corpus.

Conclusions

Developing domain-specific methods is crucial to address complex NLP tasks such as symptom onset extraction and retrospective calculation of duration of a preclinical syndrome. To the best of our knowledge, this is the first clinical text resource annotated for temporal entities in the mental health domain.",,pdf:https://jbiomedsem.biomedcentral.com/track/pdf/10.1186/s13326-020-00220-2; doi:https://doi.org/10.1186/s13326-020-00220-2; html:https://europepmc.org/articles/PMC7063705; pdf:https://europepmc.org/articles/PMC7063705?pdf=render 34320164,https://doi.org/10.1093/cvr/cvab239,"The RECOVERY trial: cardiovascular implications of a large, simple randomized trial in COVID-19.","Pessoa-Amorim G, Mafham MM.",,Cardiovascular research,2021,2021-07-01,Y,Immunomodulation; Antiviral; Randomized Trial; Antithrombotic; Covid-19,,,,,pdf:https://academic.oup.com/cardiovascres/article-pdf/117/9/e110/39354428/cvab239.pdf; doi:https://doi.org/10.1093/cvr/cvab239; html:https://europepmc.org/articles/PMC8318096; pdf:https://europepmc.org/articles/PMC8318096?pdf=render 32198138,https://doi.org/10.1136/bmj.l6927,"Machine learning and artificial intelligence research for patient benefit: 20 critical questions on transparency, replicability, ethics, and effectiveness.","Vollmer S, Mateen BA, Bohner G, Király FJ, Ghani R, Jonsson P, Cumbers S, Jonas A, McAllister KSL, Myles P, Granger D, Birse M, Branson R, Moons KGM, Collins GS, Ioannidis JPA, Holmes C, Hemingway H.",,BMJ (Clinical research ed.),2020,2020-03-20,N,,,,,,pdf:https://www.bmj.com/content/bmj/368/bmj.l6927.full.pdf; doi:https://doi.org/10.1136/bmj.l6927 -35347521,https://doi.org/10.1007/s11136-022-03119-w,Knowledge translation concerns for the CONSORT-PRO extension reporting guidance: a review of reviews.,"Mercieca-Bebber R, Aiyegbusi OL, King MT, Brundage M, Snyder C, Calvert M.",,"Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation",2022,2022-03-26,Y,Quality of life; research methodology; Reporting; Patient-reported Outcomes; Research Waste; Consort-pro,,,"This review of reviews aimed to appraise the use of the CONSORT-PRO Extension as an evaluation tool for assessing the reporting of patient-reported outcome (PROs) in publications, and to describe the reporting of PRO research across reviews. We also outlined how variation in such evaluations impacts knowledge translation and may lead to potential misuse of the CONSORT-PRO Extension. We systematically searched Medline, Pubmed and CINAHL from 2013 to 2025 March 2021 for reviews of the completeness of reporting of PRO endpoints according to CONSORT-PRO criteria. Two reviewers extracted details of each review, the percentage of included studies that addressed each CONSORT-PRO item, and key recommendations from each review. Fourteen reviews met inclusion criteria, and only six of these used the full CONSORT-PRO checklist with minimal justified modifications. The remaining eight studies made significant or unjustified adjustments to the CONSORT-PRO Extension. Review studies also varied in how they scored multi-component CONSORT-PRO items. CONSORT-PRO items were often unreported in trial reports, and certain CONSORT-PRO items were reported less often than others. The reporting of statistical approaches to dealing with missing PRO data were poor in RCTs included in all 14 review articles. Studies reviewing PRO publications often omitted recommended CONSORT-PRO items from their evaluations, which may cause confusion among readers regarding how best to report their PRO research according to the CONSORT-PRO extension. Many trials published since CONSORT-PRO's release did not report recommended CONSORT-PRO items, which may lead to misinterpretation and consequently to research waste.",,pdf:https://link.springer.com/content/pdf/10.1007/s11136-022-03119-w.pdf; doi:https://doi.org/10.1007/s11136-022-03119-w; html:https://europepmc.org/articles/PMC9470606; pdf:https://europepmc.org/articles/PMC9470606?pdf=render 31112426,https://doi.org/10.1161/circgen.118.002436,Mortality Risk Associated With Truncating Founder Mutations in Titin.,"Jansen M, Baas AF, van Spaendonck-Zwarts KY, Ummels AS, van den Wijngaard A, Jongbloed JDH, van Slegtenhorst MA, Lekanne Deprez RH, Wessels MW, Michels M, Houweling AC, Hoorntje ET, Helderman-van den Enden PJTM, Barge-Schaapveld DQCM, Peter van Tintelen J, van den Berg MP, Wilde AAM, Ploos van Amstel HK, Hennekam EAM, Asselbergs FW, Sijbrands EJG, Dooijes D.",,Circulation. Genomic and precision medicine,2019,2019-05-01,N,"Mutation; Mortality; Natural history; Cardiomyopathy, Dilated; Titin",,,"Background Truncating titin variants (TTNtv) are the most prevalent genetic cause of dilated cardiomyopathy, found in ≤25% of familial cases. Moreover, TTNtv associated with dilated cardiomyopathy are estimated to be present in 0.5% of the general population. The prognosis of asymptomatic carriers of TTNtv is poorly understood because TTNtv are associated with a highly variable phenotype. We aim to assess the natural history and clinical relevance of TTNtv by analyzing standardized mortality ratios (SMR) in multigenerational pedigrees and in close relatives of present-day patients. Methods Haplotype and genealogical analyses were performed on 3 recurrent TTNtv. Subsequently, the family tree mortality ratio method was used to compare all-cause mortality of subjects at an a priori 50% risk of carrying TTNtv to the general Dutch population. SMRs were stratified for sex, age, and calendar period. Subgroups were compared with Poisson regression. Similarly, SMRs were calculated in parents of 128 present-day dilated cardiomyopathy probands with TTNtv using the reverse parent-offspring method. Results The TTNtv were established as founder mutations and traced to 18th century ancestors. In 20 522 person-years, overall mortality was not significantly increased (SMR, 1.06; 95% CI, 0.95-1.18; P=0.162). However, mortality was significantly increased in subjects living after 1965 (SMR, 1.27; 95% CI, 1.04-1.53; P=0.009) and aged ≥60 years (SMR, 1.17; 95% CI, 1.01-1.35; P=0.02). The reverse parent-offspring analysis showed overall excess mortality (SMR, 1.26; 95% CI, 1.07-1.48; P=0.003), driven by subjects aged ≥60 years. Conclusions The natural history of the analyzed TTNtv shows a relatively mild disease course with significant excess mortality in elderly patients. With increasing life expectancy, TTNtv-associated morbidity and mortality will likely become more prevalent.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCGEN.118.002436; doi:https://doi.org/10.1161/CIRCGEN.118.002436 +35347521,https://doi.org/10.1007/s11136-022-03119-w,Knowledge translation concerns for the CONSORT-PRO extension reporting guidance: a review of reviews.,"Mercieca-Bebber R, Aiyegbusi OL, King MT, Brundage M, Snyder C, Calvert M.",,"Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation",2022,2022-03-26,Y,Quality of life; research methodology; Reporting; Patient-reported Outcomes; Research Waste; Consort-pro,,,"This review of reviews aimed to appraise the use of the CONSORT-PRO Extension as an evaluation tool for assessing the reporting of patient-reported outcome (PROs) in publications, and to describe the reporting of PRO research across reviews. We also outlined how variation in such evaluations impacts knowledge translation and may lead to potential misuse of the CONSORT-PRO Extension. We systematically searched Medline, Pubmed and CINAHL from 2013 to 2025 March 2021 for reviews of the completeness of reporting of PRO endpoints according to CONSORT-PRO criteria. Two reviewers extracted details of each review, the percentage of included studies that addressed each CONSORT-PRO item, and key recommendations from each review. Fourteen reviews met inclusion criteria, and only six of these used the full CONSORT-PRO checklist with minimal justified modifications. The remaining eight studies made significant or unjustified adjustments to the CONSORT-PRO Extension. Review studies also varied in how they scored multi-component CONSORT-PRO items. CONSORT-PRO items were often unreported in trial reports, and certain CONSORT-PRO items were reported less often than others. The reporting of statistical approaches to dealing with missing PRO data were poor in RCTs included in all 14 review articles. Studies reviewing PRO publications often omitted recommended CONSORT-PRO items from their evaluations, which may cause confusion among readers regarding how best to report their PRO research according to the CONSORT-PRO extension. Many trials published since CONSORT-PRO's release did not report recommended CONSORT-PRO items, which may lead to misinterpretation and consequently to research waste.",,pdf:https://link.springer.com/content/pdf/10.1007/s11136-022-03119-w.pdf; doi:https://doi.org/10.1007/s11136-022-03119-w; html:https://europepmc.org/articles/PMC9470606; pdf:https://europepmc.org/articles/PMC9470606?pdf=render 33248277,https://doi.org/10.1016/j.jclinepi.2020.11.014,Text-mining in electronic healthcare records can be used as efficient tool for screening and data collection in cardiovascular trials: a multicenter validation study.,"van Dijk WB, Fiolet ATL, Schuit E, Sammani A, Groenhof TKJ, van der Graaf R, de Vries MC, Alings M, Schaap J, Asselbergs FW, Grobbee DE, Groenwold RHH, Mosterd A.",,Journal of clinical epidemiology,2021,2020-11-25,N,Screening; Recruitment; trials; Multicenter; cardiovascular; Text-mining; Data-mining; Electronic Medical Records (Emrs); Lodoco2; Data-collections; Electronic Healthcare Records (Ehrs),,,"

Objective

This study aimed to validate trial patient eligibility screening and baseline data collection using text-mining in electronic healthcare records (EHRs), comparing the results to those of an international trial.

Study design and setting

In three medical centers with different EHR vendors, EHR-based text-mining was used to automatically screen patients for trial eligibility and extract baseline data on nineteen characteristics. First, the yield of screening with automated EHR text-mining search was compared with manual screening by research personnel. Second, the accuracy of extracted baseline data by EHR text mining was compared to manual data entry by research personnel.

Results

Of the 92,466 patients visiting the out-patient cardiology departments, 568 (0.6%) were enrolled in the trial during its recruitment period using manual screening methods. Automated EHR data screening of all patients showed that the number of patients needed to screen could be reduced by 73,863 (79.9%). The remaining 18,603 (20.1%) contained 458 of the actual participants (82.4% of participants). In trial participants, automated EHR text-mining missed a median of 2.8% (Interquartile range [IQR] across all variables 0.4-8.5%) of all data points compared to manually collected data. The overall accuracy of automatically extracted data was 88.0% (IQR 84.7-92.8%).

Conclusion

Automatically extracting data from EHRs using text-mining can be used to identify trial participants and to collect baseline information.",,pdf:http://www.jclinepi.com/article/S0895435620311859/pdf; doi:https://doi.org/10.1016/j.jclinepi.2020.11.014 34972825,https://doi.org/10.1038/s41564-021-01029-0,Improving local prevalence estimates of SARS-CoV-2 infections using a causal debiasing framework.,"Nicholson G, Lehmann B, Padellini T, Pouwels KB, Jersakova R, Lomax J, King RE, Mallon AM, Diggle PJ, Richardson S, Blangiardo M, Holmes C.",,Nature microbiology,2022,2021-12-31,Y,,,,"Global and national surveillance of SARS-CoV-2 epidemiology is mostly based on targeted schemes focused on testing individuals with symptoms. These tested groups are often unrepresentative of the wider population and exhibit test positivity rates that are biased upwards compared with the true population prevalence. Such data are routinely used to infer infection prevalence and the effective reproduction number, Rt, which affects public health policy. Here, we describe a causal framework that provides debiased fine-scale spatiotemporal estimates by combining targeted test counts with data from a randomized surveillance study in the United Kingdom called REACT. Our probabilistic model includes a bias parameter that captures the increased probability of an infected individual being tested, relative to a non-infected individual, and transforms observed test counts to debiased estimates of the true underlying local prevalence and Rt. We validated our approach on held-out REACT data over a 7-month period. Furthermore, our local estimates of Rt are indicative of 1-week- and 2-week-ahead changes in SARS-CoV-2-positive case numbers. We also observed increases in estimated local prevalence and Rt that reflect the spread of the Alpha and Delta variants. Our results illustrate how randomized surveys can augment targeted testing to improve statistical accuracy in monitoring the spread of emerging and ongoing infectious disease.",,pdf:https://www.nature.com/articles/s41564-021-01029-0.pdf; doi:https://doi.org/10.1038/s41564-021-01029-0; html:https://europepmc.org/articles/PMC8727294; pdf:https://europepmc.org/articles/PMC8727294?pdf=render 36717224,https://doi.org/10.1136/archdischild-2022-324548,Parents' Experiences of Communication in Neonatal Care (PEC): a neonatal survey refined for real-time parent feedback.,"Sakonidou S, Kotzamanis S, Tallett A, Poots AJ, Modi N, Bell D, Gale C.",,Archives of disease in childhood. Fetal and neonatal edition,2023,2023-01-30,Y,"Intensive care units; Child Health Services; Paediatrics; Neonatology; Intensive Care Units, Neonatal",,,"

Objective

Assessing parent experiences of neonatal services can help improve quality of care; however, there is no formally evaluated UK instrument available to assess this prospectively. Our objective was to refine an existing retrospective survey for 'real-time' feedback.

Methods

Co-led by a parent representative, we recruited a convenience sample of parents of infants in a London tertiary neonatal unit. Our steering group selected questions from the existing retrospective 61-question Picker survey (2014), added and revised questions assessing communication and parent involvement. We established face validity, ensuring questions adequately captured the topic, conducted parent cognitive interviews to evaluate parental understanding of questions,and adapted the survey in three revision cycles. We evaluated survey performance.

Results

The revised Parents' Experiences of Communication in Neonatal Care (PEC) survey contains 28 questions (10 new) focusing on communication and parent involvement. We cognitively interviewed six parents, and 67 parents completed 197 PEC surveys in the survey performance evaluation. Missing entries exceeded 5% for nine questions; we removed one and format-adjusted the rest as they had performed well during cognitive testing. There was strong inter-item correlation between two question pairs; however, all were retained as they individually assessed important concepts.

Conclusion

Revised from the original 61-question Picker survey, the 28-question PEC survey is the first UK instrument formally evaluated to assess parent experience while infants are still receiving neonatal care. Developed with parents, it focuses on communication and parent involvement, enabling continuous assessment and iterative improvement of family-centred interventions in neonatal care.",,pdf:https://fn.bmj.com/content/fetalneonatal/early/2023/01/30/archdischild-2022-324548.full.pdf; doi:https://doi.org/10.1136/archdischild-2022-324548; html:https://europepmc.org/articles/PMC10314049; pdf:https://europepmc.org/articles/PMC10314049?pdf=render -37601966,https://doi.org/10.1016/j.xgen.2023.100361,Genotyping and population characteristics of the China Kadoorie Biobank.,"Walters RG, Millwood IY, Lin K, Schmidt Valle D, McDonnell P, Hacker A, Avery D, Edris A, Fry H, Cai N, Kretzschmar WW, Ansari MA, Lyons PA, Collins R, Donnelly P, Hill M, Peto R, Shen H, Jin X, Nie C, Xu X, Guo Y, Yu C, Lv J, Clarke RJ, Li L, Chen Z, China Kadoorie Biobank Collaborative Group.",,Cell genomics,2023,2023-07-20,Y,Genetics; Genetic epidemiology; Genotyping; complex disease; Gwas; Genetic Association Studies; Biobank; Omics; Prospective; Cardiovascular Health,,,"The China Kadoorie Biobank (CKB) is a population-based prospective cohort of >512,000 adults recruited from 2004 to 2008 from 10 geographically diverse regions across China. Detailed data from questionnaires and physical measurements were collected at baseline, with additional measurements at three resurveys involving ∼5% of surviving participants. Analyses of genome-wide genotyping, for >100,000 participants using custom-designed Axiom arrays, reveal extensive relatedness, recent consanguinity, and signatures reflecting large-scale population movements from recent Chinese history. Systematic genome-wide association studies of incident disease, captured through electronic linkage to death and disease registries and to the national health insurance system, replicate established disease loci and identify 14 novel disease associations. Together with studies of candidate drug targets and disease risk factors and contributions to international genetics consortia, these demonstrate the breadth, depth, and quality of the CKB data. Ongoing high-throughput omics assays of collected biosamples and planned whole-genome sequencing will further enhance the scientific value of this biobank.",,doi:https://doi.org/10.1016/j.xgen.2023.100361; doi:https://doi.org/10.1016/j.xgen.2023.100361; html:https://europepmc.org/articles/PMC10435379; pdf:https://europepmc.org/articles/PMC10435379?pdf=render 32435697,https://doi.org/10.1038/s41746-020-0267-x,Generation and evaluation of artificial mental health records for Natural Language Processing.,"Ive J, Viani N, Kam J, Yin L, Verma S, Puntis S, Cardinal RN, Roberts A, Stewart R, Velupillai S.",,NPJ digital medicine,2020,2020-05-14,Y,Medical research; Scientific Community,,,"A serious obstacle to the development of Natural Language Processing (NLP) methods in the clinical domain is the accessibility of textual data. The mental health domain is particularly challenging, partly because clinical documentation relies heavily on free text that is difficult to de-identify completely. This problem could be tackled by using artificial medical data. In this work, we present an approach to generate artificial clinical documents. We apply this approach to discharge summaries from a large mental healthcare provider and discharge summaries from an intensive care unit. We perform an extensive intrinsic evaluation where we (1) apply several measures of text preservation; (2) measure how much the model memorises training data; and (3) estimate clinical validity of the generated text based on a human evaluation task. Furthermore, we perform an extrinsic evaluation by studying the impact of using artificial text in a downstream NLP text classification task. We found that using this artificial data as training data can lead to classification results that are comparable to the original results. Additionally, using only a small amount of information from the original data to condition the generation of the artificial data is successful, which holds promise for reducing the risk of these artificial data retaining rare information from the original data. This is an important finding for our long-term goal of being able to generate artificial clinical data that can be released to the wider research community and accelerate advances in developing computational methods that use healthcare data.",,pdf:https://www.nature.com/articles/s41746-020-0267-x.pdf; doi:https://doi.org/10.1038/s41746-020-0267-x; html:https://europepmc.org/articles/PMC7224173; pdf:https://europepmc.org/articles/PMC7224173?pdf=render +37601966,https://doi.org/10.1016/j.xgen.2023.100361,Genotyping and population characteristics of the China Kadoorie Biobank.,"Walters RG, Millwood IY, Lin K, Schmidt Valle D, McDonnell P, Hacker A, Avery D, Edris A, Fry H, Cai N, Kretzschmar WW, Ansari MA, Lyons PA, Collins R, Donnelly P, Hill M, Peto R, Shen H, Jin X, Nie C, Xu X, Guo Y, Yu C, Lv J, Clarke RJ, Li L, Chen Z, China Kadoorie Biobank Collaborative Group.",,Cell genomics,2023,2023-07-20,Y,Genetics; Genetic epidemiology; Genotyping; complex disease; Gwas; Genetic Association Studies; Biobank; Omics; Prospective; Cardiovascular Health,,,"The China Kadoorie Biobank (CKB) is a population-based prospective cohort of >512,000 adults recruited from 2004 to 2008 from 10 geographically diverse regions across China. Detailed data from questionnaires and physical measurements were collected at baseline, with additional measurements at three resurveys involving ∼5% of surviving participants. Analyses of genome-wide genotyping, for >100,000 participants using custom-designed Axiom arrays, reveal extensive relatedness, recent consanguinity, and signatures reflecting large-scale population movements from recent Chinese history. Systematic genome-wide association studies of incident disease, captured through electronic linkage to death and disease registries and to the national health insurance system, replicate established disease loci and identify 14 novel disease associations. Together with studies of candidate drug targets and disease risk factors and contributions to international genetics consortia, these demonstrate the breadth, depth, and quality of the CKB data. Ongoing high-throughput omics assays of collected biosamples and planned whole-genome sequencing will further enhance the scientific value of this biobank.",,doi:https://doi.org/10.1016/j.xgen.2023.100361; doi:https://doi.org/10.1016/j.xgen.2023.100361; html:https://europepmc.org/articles/PMC10435379; pdf:https://europepmc.org/articles/PMC10435379?pdf=render 35189842,https://doi.org/10.1186/s12888-022-03753-1,"Remote Assessment of Disease and Relapse in Major Depressive Disorder (RADAR-MDD): recruitment, retention, and data availability in a longitudinal remote measurement study.","Matcham F, Leightley D, Siddi S, Lamers F, White KM, Annas P, de Girolamo G, Difrancesco S, Haro JM, Horsfall M, Ivan A, Lavelle G, Li Q, Lombardini F, Mohr DC, Narayan VA, Oetzmann C, Penninx BWJH, Bruce S, Nica R, Simblett SK, Wykes T, Brasen JC, Myin-Germeys I, Rintala A, Conde P, Dobson RJB, Folarin AA, Stewart C, Ranjan Y, Rashid Z, Cummins N, Manyakov NV, Vairavan S, Hotopf M, RADAR-CNS consortium.",,BMC psychiatry,2022,2022-02-21,Y,Cohort study; Longitudinal; Major Depressive Disorder; Multicentre; Remote Measurement Technologies,,,"

Background

Major Depressive Disorder (MDD) is prevalent, often chronic, and requires ongoing monitoring of symptoms to track response to treatment and identify early indicators of relapse. Remote Measurement Technologies (RMT) provide an opportunity to transform the measurement and management of MDD, via data collected from inbuilt smartphone sensors and wearable devices alongside app-based questionnaires and tasks. A key question for the field is the extent to which participants can adhere to research protocols and the completeness of data collected. We aimed to describe drop out and data completeness in a naturalistic multimodal longitudinal RMT study, in people with a history of recurrent MDD. We further aimed to determine whether those experiencing a depressive relapse at baseline contributed less complete data.

Methods

Remote Assessment of Disease and Relapse - Major Depressive Disorder (RADAR-MDD) is a multi-centre, prospective observational cohort study conducted as part of the Remote Assessment of Disease and Relapse - Central Nervous System (RADAR-CNS) program. People with a history of MDD were provided with a wrist-worn wearable device, and smartphone apps designed to: a) collect data from smartphone sensors; and b) deliver questionnaires, speech tasks, and cognitive assessments. Participants were followed-up for a minimum of 11 months and maximum of 24 months.

Results

Individuals with a history of MDD (n = 623) were enrolled in the study,. We report 80% completion rates for primary outcome assessments across all follow-up timepoints. 79.8% of people participated for the maximum amount of time available and 20.2% withdrew prematurely. We found no evidence of an association between the severity of depression symptoms at baseline and the availability of data. In total, 110 participants had > 50% data available across all data types.

Conclusions

RADAR-MDD is the largest multimodal RMT study in the field of mental health. Here, we have shown that collecting RMT data from a clinical population is feasible. We found comparable levels of data availability in active and passive forms of data collection, demonstrating that both are feasible in this patient group.",,pdf:https://bmcpsychiatry.biomedcentral.com/track/pdf/10.1186/s12888-022-03753-1; doi:https://doi.org/10.1186/s12888-022-03753-1; html:https://europepmc.org/articles/PMC8860359; pdf:https://europepmc.org/articles/PMC8860359?pdf=render 34480422,https://doi.org/10.1002/ehf2.13517,The genomics of heart failure: design and rationale of the HERMES consortium.,"Lumbers RT, Shah S, Lin H, Czuba T, Henry A, Swerdlow DI, Mälarstig A, Andersson C, Verweij N, Holmes MV, Ärnlöv J, Svensson P, Hemingway H, Sallah N, Almgren P, Aragam KG, Asselin G, Backman JD, Biggs ML, Bloom HL, Boersma E, Brandimarto J, Brown MR, Brunner-La Rocca HP, Carey DJ, Chaffin MD, Chasman DI, Chazara O, Chen X, Chen X, Chung JH, Chutkow W, Cleland JGF, Cook JP, de Denus S, Dehghan A, Delgado GE, Denaxas S, Doney AS, Dörr M, Dudley SC, Engström G, Esko T, Fatemifar G, Felix SB, Finan C, Ford I, Fougerousse F, Fouodjio R, Ghanbari M, Ghasemi S, Giedraitis V, Giulianini F, Gottdiener JS, Gross S, Guðbjartsson DF, Gui H, Gutmann R, Haggerty CM, van der Harst P, Hedman ÅK, Helgadottir A, Hillege H, Hyde CL, Jacob J, Jukema JW, Kamanu F, Kardys I, Kavousi M, Khaw KT, Kleber ME, Køber L, Koekemoer A, Kraus B, Kuchenbaecker K, Langenberg C, Lind L, Lindgren CM, London B, Lotta LA, Lovering RC, Luan J, Magnusson P, Mahajan A, Mann D, Margulies KB, Marston NA, März W, McMurray JJV, Melander O, Melloni G, Mordi IR, Morley MP, Morris AD, Morris AP, Morrison AC, Nagle MW, Nelson CP, Newton-Cheh C, Niessner A, Niiranen T, Nowak C, O'Donoghue ML, Owens AT, Palmer CNA, Paré G, Perola M, Perreault LL, Portilla-Fernandez E, Psaty BM, Rice KM, Ridker PM, Romaine SPR, Roselli C, Rotter JI, Ruff CT, Sabatine MS, Salo P, Salomaa V, van Setten J, Shalaby AA, Smelser DT, Smith NL, Stefansson K, Stender S, Stott DJ, Sveinbjörnsson G, Tammesoo ML, Tardif JC, Taylor KD, Teder-Laving M, Teumer A, Thorgeirsson G, Thorsteinsdottir U, Torp-Pedersen C, Trompet S, Tuckwell D, Tyl B, Uitterlinden AG, Vaura F, Veluchamy A, Visscher PM, Völker U, Voors AA, Wang X, Wareham NJ, Weeke PE, Weiss R, White HD, Wiggins KL, Xing H, Yang J, Yang Y, Yerges-Armstrong LM, Yu B, Zannad F, Zhao F, Regeneron Genetics Center, Wilk JB, Holm H, Sattar N, Lubitz SA, Lanfear DE, Shah S, Dunn ME, Wells QS, Asselbergs FW, Hingorani AD, Dubé MP, Samani NJ, Lang CC, Cappola TP, Ellinor PT, Vasan RS, Smith JG.",,ESC heart failure,2021,2021-09-03,Y,Genetics; Biomarkers; Cardiomyopathy; Heart Failure; Association Studies,,,"

Aims

The HERMES (HEart failure Molecular Epidemiology for Therapeutic targetS) consortium aims to identify the genomic and molecular basis of heart failure.

Methods and results

The consortium currently includes 51 studies from 11 countries, including 68 157 heart failure cases and 949 888 controls, with data on heart failure events and prognosis. All studies collected biological samples and performed genome-wide genotyping of common genetic variants. The enrolment of subjects into participating studies ranged from 1948 to the present day, and the median follow-up following heart failure diagnosis ranged from 2 to 116 months. Forty-nine of 51 individual studies enrolled participants of both sexes; in these studies, participants with heart failure were predominantly male (34-90%). The mean age at diagnosis or ascertainment across all studies ranged from 54 to 84 years. Based on the aggregate sample, we estimated 80% power to genetic variant associations with risk of heart failure with an odds ratio of ≥1.10 for common variants (allele frequency ≥ 0.05) and ≥1.20 for low-frequency variants (allele frequency 0.01-0.05) at P < 5 × 10-8 under an additive genetic model.

Conclusions

HERMES is a global collaboration aiming to (i) identify the genetic determinants of heart failure; (ii) generate insights into the causal pathways leading to heart failure and enable genetic approaches to target prioritization; and (iii) develop genomic tools for disease stratification and risk prediction.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ehf2.13517; doi:https://doi.org/10.1002/ehf2.13517; html:https://europepmc.org/articles/PMC8712846; pdf:https://europepmc.org/articles/PMC8712846?pdf=render 35294976,https://doi.org/10.1007/s00127-022-02221-1,Mental health service use among mothers involved in public family law proceedings: linked data cohort study in South London 2007-2019.,"Pearson RJ, Grant C, Wijlaars L, Finch E, Bedston S, Broadhurst K, Gilbert R.",,Social psychiatry and psychiatric epidemiology,2022,2022-03-16,Y,Substance Misuse; Child Protection; Record Linkage; Maternal Mental Health; Family Court,,,"

Purpose

Mental health problems and substance misuse are common among the mothers of children who experience court-mandated placement into care in England, yet there is limited research characterising these health needs to inform evidence-based policy. In this descriptive study, we aimed to generate evidence about the type, severity, and timing of mental health and substance misuse needs among women involved in public family law proceedings concerning child placement into care ('care proceedings').

Methods

This is a retrospective, matched cohort study using linked family court and mental health service records for 2137 (66%) of the 3226 women involved in care proceedings between 2007 and 2019 in the South London and Maudsley NHS Mental Health Trust (SLaM) catchment area. We compared mental health service use and risk of dying with 17,096 female-matched controls who accessed SLaM between 2007 and 2019, aged 16-55 years, and were not involved in care proceedings.

Results

Most women (79%) were known to SLaM before care proceedings began. Women had higher rates of schizophrenia spectrum disorders (19% vs 11% matched controls), personality disorders (21% vs 11%), and substance misuse (33% vs 12%). They were more likely to have a SLaM inpatient admission (27% vs 14%) or to be sectioned (19% vs 8%). Women had a 2.15 (95% CI 1.68-2.74) times greater hazard of dying, compared to matched controls, adjusted for age.

Conclusion

Women involved in care proceedings experience a particularly high burden of severe and complex mental health and substance misuse need. Women's increased risk of mortality following proceedings highlights that interventions responding to maternal mental health and substance misuse within family courts should offer continued, long-term support.",,pdf:https://link.springer.com/content/pdf/10.1007/s00127-022-02221-1.pdf; doi:https://doi.org/10.1007/s00127-022-02221-1; html:https://europepmc.org/articles/PMC9477900; pdf:https://europepmc.org/articles/PMC9477900?pdf=render 34151270,https://doi.org/10.1136/bmjno-2021-000133,"Variation in waiting times by diagnostic category: an observational study of 1,951 referrals to a neurology outpatient clinic.","Biggin F, Howcroft T, Davies Q, Knight J, Emsley HCA.",,BMJ neurology open,2021,2021-06-03,Y,Neurology; Outpatient; Observational Study; Waiting Times; Routinely Collected Data,,,"

Objective

To investigate the frequency of diagnoses seen among new referrals to neurology outpatient services; to understand how these services are used through exploratory analysis of diagnostic tests and follow-up appointments; and to examine the waiting times between referral and appointment.

Methods

Routine data from new National Health Service appointments at a single consultant-delivered clinic between September 2016 and January 2019 were collected. These clinical data were then linked to hospital administrative data. The combined data were assigned diagnostic categories based on working diagnoses to allow further analysis using descriptive statistics.

Results

Five diagnostic categories accounted for 62% of all patients seen within the study period, the most common of which was headache disorders. Following a first appointment, 50% of all patients were offered at least one diagnostic test, and 35% were offered a follow-up appointment, with variation in both measures by diagnostic category. Waiting times from referral to appointment also varied by diagnostic category. 65% of patients with a seizure/epilepsy disorder were seen within the 18-week referral to treatment target, compared with 38% of patients with a movement disorder.

Conclusions

A small number of diagnostic categories account for a large proportion of new patients. This information could be used in policy decision-making to describe a minimum subset of categories for diagnostic coding. We found significant differences in waiting times by diagnostic category, as well as tests ordered, and follow-up offered; further investigation could address causes of variation.",,pdf:https://neurologyopen.bmj.com/content/bmjno/3/1/e000133.full.pdf; doi:https://doi.org/10.1136/bmjno-2021-000133; html:https://europepmc.org/articles/PMC8183200; pdf:https://europepmc.org/articles/PMC8183200?pdf=render -35876478,https://doi.org/10.3201/eid2808.211787,Lack of Evidence for Ribavirin Treatment of Lassa Fever in Systematic Review of Published and Unpublished Studies1.,"Cheng HY, French CE, Salam AP, Dawson S, McAleenan A, McGuinness LA, Savović J, Horby PW, Sterne JAC.",,Emerging infectious diseases,2022,2022-08-01,Y,Viruses; Bias; Ribavirin; Systematic review; Observational Study; Lassa Fever,,,"Ribavirin has been used widely to treat Lassa fever in West Africa since the 1980s. However, few studies have systematically appraised the evidence for its use. We conducted a systematic review of published and unpublished literature retrieved from electronic databases and gray literature from inception to March 8, 2022. We identified 13 studies of the comparative effectiveness of ribavirin versus no ribavirin treatment on mortality outcomes, including unpublished data from a study in Sierra Leone provided through a US Freedom of Information Act request. Although ribavirin was associated with decreased mortality rates, results of these studies were at critical or serious risk for bias when appraised using the ROBINS-I tool. Important risks for bias related to lack of control for confounders, immortal time bias, and missing outcome data. Robust evidence supporting the use of ribavirin in Lassa fever is lacking. Well-conducted clinical trials to elucidate the effectiveness of ribavirin for Lassa fever are needed.",,pdf:https://wwwnc.cdc.gov/eid/article/28/8/pdfs/21-1787.pdf; doi:https://doi.org/10.3201/eid2808.211787; html:https://europepmc.org/articles/PMC9328902; pdf:https://europepmc.org/articles/PMC9328902?pdf=render 31160290,https://doi.org/10.1128/aac.00400-19,Improved Performance Predicting Clarithromycin Resistance in Mycobacterium abscessus on an Independent Data Set.,"Lipworth S, Hough N, Buchanan R, Smith EG, Robinson E, Alexander E, Peto T, Crook D, Walker T.",,Antimicrobial agents and chemotherapy,2019,2019-07-25,N,Macrolides; Nontuberculous Mycobacteria; Mycobacterium Abscessus; Whole-genome Sequencing,,cancer and neoplasms,,,pdf:https://aac.asm.org/content/aac/63/8/e00400-19.full.pdf; doi:https://doi.org/10.1128/AAC.00400-19; html:https://europepmc.org/articles/PMC6658746; pdf:https://europepmc.org/articles/PMC6658746?pdf=render; doi:https://doi.org/10.1128/aac.00400-19 +35876478,https://doi.org/10.3201/eid2808.211787,Lack of Evidence for Ribavirin Treatment of Lassa Fever in Systematic Review of Published and Unpublished Studies1.,"Cheng HY, French CE, Salam AP, Dawson S, McAleenan A, McGuinness LA, Savović J, Horby PW, Sterne JAC.",,Emerging infectious diseases,2022,2022-08-01,Y,Viruses; Bias; Ribavirin; Systematic review; Observational Study; Lassa Fever,,,"Ribavirin has been used widely to treat Lassa fever in West Africa since the 1980s. However, few studies have systematically appraised the evidence for its use. We conducted a systematic review of published and unpublished literature retrieved from electronic databases and gray literature from inception to March 8, 2022. We identified 13 studies of the comparative effectiveness of ribavirin versus no ribavirin treatment on mortality outcomes, including unpublished data from a study in Sierra Leone provided through a US Freedom of Information Act request. Although ribavirin was associated with decreased mortality rates, results of these studies were at critical or serious risk for bias when appraised using the ROBINS-I tool. Important risks for bias related to lack of control for confounders, immortal time bias, and missing outcome data. Robust evidence supporting the use of ribavirin in Lassa fever is lacking. Well-conducted clinical trials to elucidate the effectiveness of ribavirin for Lassa fever are needed.",,pdf:https://wwwnc.cdc.gov/eid/article/28/8/pdfs/21-1787.pdf; doi:https://doi.org/10.3201/eid2808.211787; html:https://europepmc.org/articles/PMC9328902; pdf:https://europepmc.org/articles/PMC9328902?pdf=render 38432242,https://doi.org/10.1016/s2352-3026(24)00030-9,Haemoglobin thresholds to define anaemia from age 6 months to 65 years: estimates from international data sources.,"Braat S, Fielding KL, Han J, Jackson VE, Zaloumis S, Xu JXH, Moir-Meyer G, Blaauwendraad SM, Jaddoe VWV, Gaillard R, Parkin PC, Borkhoff CM, Keown-Stoneman CDG, Birken CS, Maguire JL, Genes & Health Research Team, Bahlo M, Davidson EM, Pasricha SR.",,The Lancet. Haematology,2024,2024-02-29,Y,,,,"

Background

Detection of anaemia is crucial for clinical medicine and public health. Current WHO anaemia definitions are based on statistical thresholds (fifth centiles) set more than 50 years ago. We sought to establish evidence for the statistical haemoglobin thresholds for anaemia that can be applied globally and inform WHO and clinical guidelines.

Methods

In this analysis we identified international data sources from populations in the USA, England, Australia, China, the Netherlands, Canada, Ecuador, and Bangladesh with sufficient clinical and laboratory information collected between 1998 and 2020 to obtain a healthy reference sample. Individuals with clinical or biochemical evidence of a condition that could reduce haemoglobin concentrations were excluded. We estimated haemoglobin thresholds (ie, 5th centiles) for children aged 6-23 months, 24-59 months, 5-11 years, and 12-17 years, and adults aged 18-65 years (including during pregnancy) for individual datasets and pooled across data sources. We also collated findings from three large-scale genetic studies to summarise genetic variants affecting haemoglobin concentrations in different ancestral populations.

Findings

We identified eight data sources comprising 18 individual datasets that were eligible for inclusion in the analysis. In pooled analyses, the haemoglobin fifth centile was 104·4 g/L (90% CI 103·5-105·3) in 924 children aged 6-23 months, 110·2 g/L (109·5-110·9) in 1874 children aged 24-59 months, and 114·4 g/L (113·6-115·2) in 1839 children aged 5-11 years. Values diverged by sex in adolescents and adults. In pooled analyses, the fifth centile was 122·2 g/L (90% CI 121·3-123·1) in 1741 female adolescents aged 12-17 years and 128·2 g/L (126·4-130·0) in 1103 male adolescents aged 12-17 years. In pooled analyses of adults aged 18-65 years, the fifth centile was 119·7 g/L (90% CI 119·1-120·3) in 3640 non-pregnant females and 134·9 g/L (134·2-135·6) in 2377 males. Fifth centiles in pregnancy were 110·3 g/L (90% CI 109·5-111·0) in the first trimester (n=772) and 105·9 g/L (104·0-107·7) in the second trimester (n=111), with insufficient data for analysis in the third trimester. There were insufficient data for adults older than 65 years. We did not identify ancestry-specific high prevalence of non-clinically relevant genetic variants that influence haemoglobin concentrations.

Interpretation

Our results enable global harmonisation of clinical and public health haemoglobin thresholds for diagnosis of anaemia. Haemoglobin thresholds are similar between sexes until adolescence, after which males have higher thresholds than females. We did not find any evidence that thresholds should differ between people of differering ancestries.

Funding

World Health Organization and the Bill & Melinda Gates Foundation.",,doi:https://doi.org/10.1016/S2352-3026(24)00030-9; html:https://europepmc.org/articles/PMC10983828; pdf:https://europepmc.org/articles/PMC10983828?pdf=render 36180121,https://doi.org/10.1136/bmjopen-2021-057712,Development of a core outcome set and identification of patient-reportable outcomes for primary brain tumour trials: protocol for the COBra study.,"Retzer A, Sivell S, Scott H, Nelson A, Bulbeck H, Seddon K, Grant R, Adams R, Watts C, Aiyegbusi OL, Kearns P, Cruz Rivera S, Dirven L, Baddeley E, Calvert M, Byrne A.",,BMJ open,2022,2022-09-30,Y,Clinical Trials; Qualitative Research; Adult Palliative Care; Neurological Oncology,,,"

Introduction

Primary brain tumours, specifically gliomas, are a rare disease group. The disease and treatment negatively impacts on patients and those close to them. The high rates of physical and cognitive morbidity differ from other cancers causing reduced health-related quality of life. Glioma trials using outcomes that allow holistic analysis of treatment benefits and risks enable informed care decisions. Currently, outcome assessment in glioma trials is inconsistent, hindering evidence synthesis. A core outcome set (COS) - an agreed minimum set of outcomes to be measured and reported - may address this. International initiatives focus on defining core outcomes assessments across brain tumour types. This protocol describes the development of a COS involving UK stakeholders for use in glioma trials, applicable across glioma types, with provision to identify subsets as required. Due to stakeholder interest in data reported from the patient perspective, outcomes from the COS that can be patient-reported will be identified.

Methods and analysis

Stage I: (1) trial registry review to identify outcomes collected in glioma trials and (2) systematic review of qualitative literature exploring glioma patient and key stakeholder research priorities. Stage II: semi-structured interviews with glioma patients and caregivers. Outcome lists will be generated from stages I and II. Stage III: study team will remove duplicate items from the outcome lists and ensure accessible terminology for inclusion in the Delphi survey. Stage IV: a two-round Delphi process whereby the outcomes will be rated by key stakeholders. Stage V: a consensus meeting where participants will finalise the COS. The study team will identify the COS outcomes that can be patient-reported. Further research is needed to match patient-reported outcomes to available measures.

Ethics and dissemination

Ethical approval was obtained (REF SMREC 21/59, Cardiff University School of Medicine Research Ethics Committee). Study findings will be disseminated widely through conferences and journal publication. The final COS will be adopted and promoted by patient and carer groups and its use by funders encouraged.

Prospero registration number

CRD42021236979.",,pdf:https://bmjopen.bmj.com/content/bmjopen/12/9/e057712.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-057712; html:https://europepmc.org/articles/PMC9528585; pdf:https://europepmc.org/articles/PMC9528585?pdf=render 33323250,https://doi.org/10.1016/s2589-7500(19)30121-9,"Development and validation of multivariable prediction models of remission, recovery, and quality of life outcomes in people with first episode psychosis: a machine learning approach.","Leighton SP, Upthegrove R, Krishnadas R, Benros ME, Broome MR, Gkoutos GV, Liddle PF, Singh SP, Everard L, Jones PB, Fowler D, Sharma V, Freemantle N, Christensen RHB, Albert N, Nordentoft M, Schwannauer M, Cavanagh J, Gumley AI, Birchwood M, Mallikarjun PK.",,The Lancet. Digital health,2019,2019-09-12,N,,,,"

Background

Outcomes for people with first-episode psychosis are highly heterogeneous. Few reliable validated methods are available to predict the outcome for individual patients in the first clinical contact. In this study, we aimed to build multivariable prediction models of 1-year remission and recovery outcomes using baseline clinical variables in people with first-episode psychosis.

Methods

In this machine learning approach, we applied supervised machine learning, using regularised regression and nested leave-one-site-out cross-validation, to baseline clinical data from the English Evaluating the Development and Impact of Early Intervention Services (EDEN) study (n=1027), to develop and internally validate prediction models at 1-year follow-up. We assessed four binary outcomes that were recorded at 1 year: symptom remission, social recovery, vocational recovery, and quality of life (QoL). We externally validated the prediction models by selecting from the top predictor variables identified in the internal validation models the variables shared with the external validation datasets comprised of two Scottish longitudinal cohort studies (n=162) and the OPUS trial, a randomised controlled trial of specialised assertive intervention versus standard treatment (n=578).

Findings

The performance of prediction models was robust for the four 1-year outcomes of symptom remission (area under the receiver operating characteristic curve [AUC] 0·703, 95% CI 0·664-0·742), social recovery (0·731, 0·697-0·765), vocational recovery (0·736, 0·702-0·771), and QoL (0·704, 0·667-0·742; p<0·0001 for all outcomes), on internal validation. We externally validated the outcomes of symptom remission (AUC 0·680, 95% CI 0·587-0·773), vocational recovery (0·867, 0·805-0·930), and QoL (0·679, 0·522-0·836) in the Scottish datasets, and symptom remission (0·616, 0·553-0·679), social recovery (0·573, 0·504-0·643), vocational recovery (0·660, 0·610-0·710), and QoL (0·556, 0·481-0·631) in the OPUS dataset.

Interpretation

In our machine learning analysis, we showed that prediction models can reliably and prospectively identify poor remission and recovery outcomes at 1 year for patients with first-episode psychosis using baseline clinical variables at first clinical contact.

Funding

Lundbeck Foundation.",,pdf:http://www.thelancet.com/article/S2589750019301219/pdf; doi:https://doi.org/10.1016/S2589-7500(19)30121-9 @@ -2385,8 +2385,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 33245137,https://doi.org/10.1093/ije/dyaa155,"Plant foods, dietary fibre and risk of ischaemic heart disease in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.","Perez-Cornago A, Crowe FL, Appleby PN, Bradbury KE, Wood AM, Jakobsen MU, Johnson L, Sacerdote C, Steur M, Weiderpass E, Würtz AML, Kühn T, Katzke V, Trichopoulou A, Karakatsani A, La Vecchia C, Masala G, Tumino R, Panico S, Sluijs I, Skeie G, Imaz L, Petrova D, Quirós JR, Yohar SMC, Jakszyn P, Melander O, Sonestedt E, Andersson J, Wennberg M, Aune D, Riboli E, Schulze MB, di Angelantonio E, Wareham NJ, Danesh J, Forouhi NG, Butterworth AS, Key TJ.",,International journal of epidemiology,2021,2021-03-01,Y,Seeds; Fruit; Legumes; vegetables; Coronary Heart Disease; Nuts,,,"

Background

Epidemiological evidence indicates that diets rich in plant foods are associated with a lower risk of ischaemic heart disease (IHD), but there is sparse information on fruit and vegetable subtypes and sources of dietary fibre. This study examined the associations of major plant foods, their subtypes and dietary fibre with risk of IHD in the European Prospective Investigation into Cancer and Nutrition (EPIC).

Methods

We conducted a prospective analysis of 490 311 men and women without a history of myocardial infarction or stroke at recruitment (12.6 years of follow-up, n cases = 8504), in 10 European countries. Dietary intake was assessed using validated questionnaires, calibrated with 24-h recalls. Multivariable Cox regressions were used to estimate hazard ratios (HR) of IHD.

Results

There was a lower risk of IHD with a higher intake of fruit and vegetables combined [HR per 200 g/day higher intake 0.94, 95% confidence interval (CI): 0.90-0.99, P-trend = 0.009], and with total fruits (per 100 g/day 0.97, 0.95-1.00, P-trend = 0.021). There was no evidence for a reduced risk for fruit subtypes, except for bananas. Risk was lower with higher intakes of nuts and seeds (per 10 g/day 0.90, 0.82-0.98, P-trend = 0.020), total fibre (per 10 g/day 0.91, 0.85-0.98, P-trend = 0.015), fruit and vegetable fibre (per 4 g/day 0.95, 0.91-0.99, P-trend = 0.022) and fruit fibre (per 2 g/day 0.97, 0.95-1.00, P-trend = 0.045). No associations were observed between vegetables, vegetables subtypes, legumes, cereals and IHD risk.

Conclusions

In this large prospective study, we found some small inverse associations between plant foods and IHD risk, with fruit and vegetables combined being the most strongly inversely associated with risk. Whether these small associations are causal remains unclear.",,pdf:https://academic.oup.com/ije/article-pdf/50/1/212/36449032/dyaa155.pdf; doi:https://doi.org/10.1093/ije/dyaa155; html:https://europepmc.org/articles/PMC7938513; pdf:https://europepmc.org/articles/PMC7938513?pdf=render 35537820,https://doi.org/10.1136/thoraxjnl-2021-217993,Mendelian randomisation of eosinophils and other cell types in relation to lung function and disease.,"Guyatt A, John C, Williams AT, Shrine N, Reeve NF, SpiroMeta consortium, Sayers I, Hall I, Wain LV, Sheehan N, Dudbridge F, Tobin MD.",,Thorax,2023,2022-05-10,Y,respiratory infection; Copd Epidemiology; Eosinophil Biology; Asthma Mechanisms; Asthma Epidemiology; Asthma Genetics; Copd Exacerbations Mechanisms,,,"

Rationale

Eosinophils are associated with airway inflammation in respiratory disease. Eosinophil production and survival is controlled partly by interleukin-5: anti-interleukin-5 agents reduce asthma and response correlates with baseline eosinophil counts. However, whether raised eosinophils are causally related to chronic obstructive pulmonary disease (COPD) and other respiratory phenotypes is not well understood.

Objectives

We investigated causality between eosinophils and: lung function, acute exacerbations of COPD, asthma-COPD overlap (ACO), moderate-to-severe asthma and respiratory infections.

Methods

We performed Mendelian randomisation (MR) using 151 variants from genome-wide association studies of blood eosinophils in UK Biobank/INTERVAL, and respiratory traits in UK Biobank/SpiroMeta, using methods relying on different assumptions for validity. We performed multivariable analyses using eight cell types where there was possible evidence of causation by eosinophils.

Measurements and main results

Causal estimates derived from individual variants were highly heterogeneous, which may arise from pleiotropy. The average effect of raising eosinophils was to increase risk of ACO (weighted median OR per SD eosinophils, 1.44 (95%CI 1.19 to 1.74)), and moderate-severe asthma (weighted median OR 1.50 (95%CI 1.23 to 1.83)), and to reduce forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) and FEV1 (weighted median estimator, SD FEV1/FVC: -0.054 (95% CI -0.078 to -0.029), effect only prominent in individuals with asthma).

Conclusions

Broad consistency across MR methods may suggest causation by eosinophils (although of uncertain magnitude), yet heterogeneity necessitates caution: other important mechanisms may be responsible for the impairment of respiratory health by these eosinophil-raising variants. These results could suggest that anti-IL5 agents (designed to lower eosinophils) may be valuable in treating other respiratory conditions, including people with overlapping features of asthma and COPD.",,pdf:https://thorax.bmj.com/content/thoraxjnl/early/2022/05/10/thoraxjnl-2021-217993.full.pdf; doi:https://doi.org/10.1136/thoraxjnl-2021-217993; html:https://europepmc.org/articles/PMC10176352; pdf:https://europepmc.org/articles/PMC10176352?pdf=render 33758017,https://doi.org/10.1126/science.abf9648,The impact of population-wide rapid antigen testing on SARS-CoV-2 prevalence in Slovakia.,"Pavelka M, Van-Zandvoort K, Abbott S, Sherratt K, Majdan M, CMMID COVID-19 working group, Inštitút Zdravotných Analýz, Jarčuška P, Krajčí M, Flasche S, Funk S.",,"Science (New York, N.Y.)",2021,2021-03-23,Y,,,,"Slovakia conducted multiple rounds of population-wide rapid antigen testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in late 2020, combined with a period of additional contact restrictions. Observed prevalence decreased by 58% (95% confidence interval: 57 to 58%) within 1 week in the 45 counties that were subject to two rounds of mass testing, an estimate that remained robust when adjusting for multiple potential confounders. Adjusting for epidemic growth of 4.4% (1.1 to 6.9%) per day preceding the mass testing campaign, the estimated decrease in prevalence compared with a scenario of unmitigated growth was 70% (67 to 73%). Modeling indicated that this decrease could not be explained solely by infection control measures but required the addition of the isolation and quarantine of household members of those testing positive.",,pdf:https://www.science.org/cms/asset/e974db95-138d-4a9f-aa91-2f8f6c705f36/pap.pdf; doi:https://doi.org/10.1126/science.abf9648; html:https://europepmc.org/articles/PMC8139426; pdf:https://europepmc.org/articles/PMC8139426?pdf=render -37393924,https://doi.org/10.1016/s0140-6736(23)00860-7,"The unfinished agenda of communicable diseases among children and adolescents before the COVID-19 pandemic, 1990-2019: a systematic analysis of the Global Burden of Disease Study 2019.",GBD 2019 Child and Adolescent Communicable Disease Collaborators.,,"Lancet (London, England)",2023,2023-06-29,Y,,,,"

Background

Communicable disease control has long been a focus of global health policy. There have been substantial reductions in the burden and mortality of communicable diseases among children younger than 5 years, but we know less about this burden in older children and adolescents, and it is unclear whether current programmes and policies remain aligned with targets for intervention. This knowledge is especially important for policy and programmes in the context of the COVID-19 pandemic. We aimed to use the Global Burden of Disease (GBD) Study 2019 to systematically characterise the burden of communicable diseases across childhood and adolescence.

Methods

In this systematic analysis of the GBD study from 1990 to 2019, all communicable diseases and their manifestations as modelled within GBD 2019 were included, categorised as 16 subgroups of common diseases or presentations. Data were reported for absolute count, prevalence, and incidence across measures of cause-specific mortality (deaths and years of life lost), disability (years lived with disability [YLDs]), and disease burden (disability-adjusted life-years [DALYs]) for children and adolescents aged 0-24 years. Data were reported across the Socio-demographic Index (SDI) and across time (1990-2019), and for 204 countries and territories. For HIV, we reported the mortality-to-incidence ratio (MIR) as a measure of health system performance.

Findings

In 2019, there were 3·0 million deaths and 30·0 million years of healthy life lost to disability (as measured by YLDs), corresponding to 288·4 million DALYs from communicable diseases among children and adolescents globally (57·3% of total communicable disease burden across all ages). Over time, there has been a shift in communicable disease burden from young children to older children and adolescents (largely driven by the considerable reductions in children younger than 5 years and slower progress elsewhere), although children younger than 5 years still accounted for most of the communicable disease burden in 2019. Disease burden and mortality were predominantly in low-SDI settings, with high and high-middle SDI settings also having an appreciable burden of communicable disease morbidity (4·0 million YLDs in 2019 alone). Three cause groups (enteric infections, lower-respiratory-tract infections, and malaria) accounted for 59·8% of the global communicable disease burden in children and adolescents, with tuberculosis and HIV both emerging as important causes during adolescence. HIV was the only cause for which disease burden increased over time, particularly in children and adolescents older than 5 years, and especially in females. Excess MIRs for HIV were observed for males aged 15-19 years in low-SDI settings.

Interpretation

Our analysis supports continued policy focus on enteric infections and lower-respiratory-tract infections, with orientation to children younger than 5 years in settings of low socioeconomic development. However, efforts should also be targeted to other conditions, particularly HIV, given its increased burden in older children and adolescents. Older children and adolescents also experience a large burden of communicable disease, further highlighting the need for efforts to extend beyond the first 5 years of life. Our analysis also identified substantial morbidity caused by communicable diseases affecting child and adolescent health across the world.

Funding

The Australian National Health and Medical Research Council Centre for Research Excellence for Driving Investment in Global Adolescent Health and the Bill & Melinda Gates Foundation.",,pdf:http://www.thelancet.com/article/S0140673623008607/pdf; doi:https://doi.org/10.1016/S0140-6736(23)00860-7; html:https://europepmc.org/articles/PMC10375221; pdf:https://europepmc.org/articles/PMC10375221?pdf=render 34446501,https://doi.org/10.1136/bmjopen-2021-052629,Using patient-reported outcome measures during the management of patients with end-stage kidney disease requiring treatment with haemodialysis (PROM-HD): a qualitative study.,"Anderson NE, McMullan C, Calvert M, Dutton M, Cockwell P, Aiyegbusi OL, Kyte D.",,BMJ open,2021,2021-08-26,Y,Dialysis; Nephrology; Telemedicine; Qualitative Research; End Stage Renal Failure,,,"

Objectives

Patients undergoing haemodialysis report elevated symptoms and reduced health-related quality of life, and often prioritise improvements in psychosocial well-being over long-term survival. Systematic collection and use of patient-reported outcomes (PROs) may help support tailored healthcare and improve outcomes. This study investigates the methodological basis for routine PRO assessment, particularly using electronic formats (ePROs), to maximise the potential of PRO use, through exploration of the experiences, views and perceptions of patients and healthcare professionals (HCPs) on implementation and use of PROs in haemodialysis settings.

Study design

Qualitative study.

Setting and participants

Semistructured interviews with 22 patients undergoing haemodialysis, and 17 HCPs in the UK.

Analytical approach

Transcripts were analysed deductively using the Consolidated Framework for Implementation Research (CFIR) and inductively using thematic analysis.

Results

For effective implementation, the potential value of PROs needs to be demonstrated empirically to stakeholders. Any intervention must remain flexible enough for individual and aggregate use, measuring outcomes that matter to patients and clinicians, while maintaining operational simplicity. Any implementation must sit within a wider framework of education and support for both patients and clinicians who demonstrate varying previous experience of using PROs and often confuse related concepts. Implementation plans must recognise the multidimensionality of end-stage kidney disease and treatment by haemodialysis, while acknowledging the associated challenges of delivering care in a highly specialised environment. To support implementation, careful consideration needs to be given to barriers and facilitators including effective leadership, the role of champions, effective launch and ongoing evaluation.

Conclusions

Using the CFIR to explore the experiences, views and perceptions of key stakeholders, this study identified key factors at organisational and individual levels which could assist effective implementation of ePROs in haemodialysis settings. Further research will be required to evaluate subsequent ePRO interventions to demonstrate the impact and benefit to the dialysis community.",,pdf:https://bmjopen.bmj.com/content/bmjopen/11/8/e052629.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-052629; html:https://europepmc.org/articles/PMC8395280; pdf:https://europepmc.org/articles/PMC8395280?pdf=render +37393924,https://doi.org/10.1016/s0140-6736(23)00860-7,"The unfinished agenda of communicable diseases among children and adolescents before the COVID-19 pandemic, 1990-2019: a systematic analysis of the Global Burden of Disease Study 2019.",GBD 2019 Child and Adolescent Communicable Disease Collaborators.,,"Lancet (London, England)",2023,2023-06-29,Y,,,,"

Background

Communicable disease control has long been a focus of global health policy. There have been substantial reductions in the burden and mortality of communicable diseases among children younger than 5 years, but we know less about this burden in older children and adolescents, and it is unclear whether current programmes and policies remain aligned with targets for intervention. This knowledge is especially important for policy and programmes in the context of the COVID-19 pandemic. We aimed to use the Global Burden of Disease (GBD) Study 2019 to systematically characterise the burden of communicable diseases across childhood and adolescence.

Methods

In this systematic analysis of the GBD study from 1990 to 2019, all communicable diseases and their manifestations as modelled within GBD 2019 were included, categorised as 16 subgroups of common diseases or presentations. Data were reported for absolute count, prevalence, and incidence across measures of cause-specific mortality (deaths and years of life lost), disability (years lived with disability [YLDs]), and disease burden (disability-adjusted life-years [DALYs]) for children and adolescents aged 0-24 years. Data were reported across the Socio-demographic Index (SDI) and across time (1990-2019), and for 204 countries and territories. For HIV, we reported the mortality-to-incidence ratio (MIR) as a measure of health system performance.

Findings

In 2019, there were 3·0 million deaths and 30·0 million years of healthy life lost to disability (as measured by YLDs), corresponding to 288·4 million DALYs from communicable diseases among children and adolescents globally (57·3% of total communicable disease burden across all ages). Over time, there has been a shift in communicable disease burden from young children to older children and adolescents (largely driven by the considerable reductions in children younger than 5 years and slower progress elsewhere), although children younger than 5 years still accounted for most of the communicable disease burden in 2019. Disease burden and mortality were predominantly in low-SDI settings, with high and high-middle SDI settings also having an appreciable burden of communicable disease morbidity (4·0 million YLDs in 2019 alone). Three cause groups (enteric infections, lower-respiratory-tract infections, and malaria) accounted for 59·8% of the global communicable disease burden in children and adolescents, with tuberculosis and HIV both emerging as important causes during adolescence. HIV was the only cause for which disease burden increased over time, particularly in children and adolescents older than 5 years, and especially in females. Excess MIRs for HIV were observed for males aged 15-19 years in low-SDI settings.

Interpretation

Our analysis supports continued policy focus on enteric infections and lower-respiratory-tract infections, with orientation to children younger than 5 years in settings of low socioeconomic development. However, efforts should also be targeted to other conditions, particularly HIV, given its increased burden in older children and adolescents. Older children and adolescents also experience a large burden of communicable disease, further highlighting the need for efforts to extend beyond the first 5 years of life. Our analysis also identified substantial morbidity caused by communicable diseases affecting child and adolescent health across the world.

Funding

The Australian National Health and Medical Research Council Centre for Research Excellence for Driving Investment in Global Adolescent Health and the Bill & Melinda Gates Foundation.",,pdf:http://www.thelancet.com/article/S0140673623008607/pdf; doi:https://doi.org/10.1016/S0140-6736(23)00860-7; html:https://europepmc.org/articles/PMC10375221; pdf:https://europepmc.org/articles/PMC10375221?pdf=render 31995663,https://doi.org/10.1111/cts.12725,Using Real-World Data to Guide Ustekinumab Dosing Strategies for Psoriasis: A Prospective Pharmacokinetic-Pharmacodynamic Study.,"Pan S, Tsakok T, Dand N, Lonsdale DO, Loeff FC, Bloem K, de Vries A, Baudry D, Duckworth M, Mahil S, Pushpa-Rajah A, Russell A, Alsharqi A, Becher G, Murphy R, Wahie S, Wright A, Griffiths CEM, Reynolds NJ, Barker J, Warren RB, David Burden A, Rispens T, Standing JF, Smith CH, BADBIR Study Group, the BSTOP Study Group, the PSORT Consortium.",,Clinical and translational science,2020,2020-01-29,Y,,,skin,"Variation in response to biologic therapy for inflammatory diseases, such as psoriasis, is partly driven by variation in drug exposure. Real-world psoriasis data were used to develop a pharmacokinetic/pharmacodynamic (PK/PD) model for the first-line therapeutic antibody ustekinumab. The impact of differing dosing strategies on response was explored. Data were collected from a UK prospective multicenter observational cohort (491 patients on ustekinumab monotherapy, drug levels, and anti-drug antibody measurements on 797 serum samples, 1,590 measurements of Psoriasis Area Severity Index (PASI)). Ustekinumab PKs were described with a linear one-compartment model. A maximum effect (Emax ) model inhibited progression of psoriatic skin lesions in the turnover PD mechanism describing PASI evolution while on treatment. A mixture model on half-maximal effective concentration identified a potential nonresponder group, with simulations suggesting that, in future, the model could be incorporated into a Bayesian therapeutic drug monitoring ""dashboard"" to individualize dosing and improve treatment outcomes.",,pdf:https://ascpt.onlinelibrary.wiley.com/doi/pdfdirect/10.1111/cts.12725; doi:https://doi.org/10.1111/cts.12725; html:https://europepmc.org/articles/PMC7070790; pdf:https://europepmc.org/articles/PMC7070790?pdf=render 31647808,https://doi.org/10.1371/journal.pgen.1008405,Causal relationships between obesity and the leading causes of death in women and men.,"Censin JC, Peters SAE, Bovijn J, Ferreira T, Pulit SL, Mägi R, Mahajan A, Holmes MV, Lindgren CM.",,PLoS genetics,2019,2019-10-24,Y,,Understanding the Causes of Disease,,"Obesity traits are causally implicated with risk of cardiometabolic diseases. It remains unclear whether there are similar causal effects of obesity traits on other non-communicable diseases. Also, it is largely unexplored whether there are any sex-specific differences in the causal effects of obesity traits on cardiometabolic diseases and other leading causes of death. We constructed sex-specific genetic risk scores (GRS) for three obesity traits; body mass index (BMI), waist-hip ratio (WHR), and WHR adjusted for BMI, including 565, 324, and 337 genetic variants, respectively. These GRSs were then used as instrumental variables to assess associations between the obesity traits and leading causes of mortality in the UK Biobank using Mendelian randomization. We also investigated associations with potential mediators, including smoking, glycemic and blood pressure traits. Sex-differences were subsequently assessed by Cochran's Q-test (Phet). A Mendelian randomization analysis of 228,466 women and 195,041 men showed that obesity causes coronary artery disease, stroke (particularly ischemic), chronic obstructive pulmonary disease, lung cancer, type 2 and 1 diabetes mellitus, non-alcoholic fatty liver disease, chronic liver disease, and acute and chronic renal failure. Higher BMI led to higher risk of type 2 diabetes in women than in men (Phet = 1.4×10-5). Waist-hip-ratio led to a higher risk of chronic obstructive pulmonary disease (Phet = 3.7×10-6) and higher risk of chronic renal failure (Phet = 1.0×10-4) in men than women. Obesity traits have an etiological role in the majority of the leading global causes of death. Sex differences exist in the effects of obesity traits on risk of type 2 diabetes, chronic obstructive pulmonary disease, and renal failure, which may have downstream implications for public health.","This study aimed to quantify (as genetic risk scores) the causal effects of obesity on leading causes of death, separately, in men and women. Analysis of genetic data for 228,466 women and 195,041 men showed that obesity causes coronary artery disease, stroke, chronic obstructive pulmonary disease, lung cancer, type 2 and 1 diabetes mellitus, non-alcoholic fatty liver disease, chronic liver disease, and acute and chronic renal failure. The authors identified some important differences in these causal effects for men and women.",pdf:https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1008405&type=printable; doi:https://doi.org/10.1371/journal.pgen.1008405; html:https://europepmc.org/articles/PMC6812754; pdf:https://europepmc.org/articles/PMC6812754?pdf=render 32792438,https://doi.org/10.1136/bmjopen-2019-036564,Association between health indicators of maternal adversity and the rate of infant entry to local authority care in England: a longitudinal ecological study.,"Pearson RJ, Jay MA, Wijlaars LPMM, De Stavola B, Syed S, Bedston SJ, Gilbert R.",,BMJ open,2020,2020-08-13,Y,epidemiology; Public Health; Child Protection,,,"

Objective

Infants enter care at varying rates across local authorities (LAs) in England, but evidence is lacking on what is driving these differences. With this ecological study, we aimed to explore the extent to which adversity indicated within women's hospitalisation histories, predelivery, explained the rate of infant entry into care.

Methods

We used two longitudinal person-level data sets on hospitalisations and entries to care to create annual measures for 131 English LAs, between 2006/2007 and 2013/2014 (April-March). We combined these measures by LA and financial year, along with other publicly available data on LA characteristics. We used linear mixed-effects models to analyse the relationship between the outcome-LA-specific rate of infant entry into care (per 10 000 infants in the LA population) - and LA-specific percentage of live births with maternal history of adversity-related hospital admissions (ie, substance misuse, mental health problems or violence-related admissions in the 3 years before delivery), adjusted for other predictors of entry into care.

Results

Rate of infant entry into care (mean: 85.16 per 10 000, SD: 41.07) and percentage of live births with maternal history of adversity-related hospital admissions (4.62%, 2.44%) varied greatly by LA. The prevalence of maternal adversity accounted for 24% of the variation in rate of entry (95% CI 14% to 35%). After adjustment, a percentage point increase in prevalence of maternal adversity-both within and between LAs-was associated with an estimated 2.56 (per 10 000) more infants entering care (1.31-3.82).

Conclusions

The prevalence of maternal adversity before birth helped to explain the variation in LA rates of infant entry into care. Preventive interventions are needed to improve maternal well-being before and during pregnancy, and potentially reduce risk of child maltreatment and therefore entries to care. Evidence on who to target and data to evaluate change require linkage between parent-child healthcare data and administrative data from children's social care.",,pdf:https://bmjopen.bmj.com/content/bmjopen/10/8/e036564.full.pdf; doi:https://doi.org/10.1136/bmjopen-2019-036564; html:https://europepmc.org/articles/PMC7430489; pdf:https://europepmc.org/articles/PMC7430489?pdf=render @@ -2403,8 +2403,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 31678029,https://doi.org/10.1016/s1473-3099(19)30401-3,Quantifying risks and interventions that have affected the burden of diarrhoea among children younger than 5 years: an analysis of the Global Burden of Disease Study 2017.,GBD 2017 Diarrhoeal Disease Collaborators.,,The Lancet. Infectious diseases,2020,2019-10-31,Y,,,,"

Background

Many countries have shown marked declines in diarrhoeal disease mortality among children younger than 5 years. With this analysis, we provide updated results on diarrhoeal disease mortality among children younger than 5 years from the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017) and use the study's comparative risk assessment to quantify trends and effects of risk factors, interventions, and broader sociodemographic development on mortality changes in 195 countries and territories from 1990 to 2017.

Methods

This analysis for GBD 2017 had three main components. Diarrhoea mortality was modelled using vital registration data, demographic surveillance data, and verbal autopsy data in a predictive, Bayesian, ensemble modelling tool; and the attribution of risk factors and interventions for diarrhoea were modelled in a counterfactual framework that combines modelled population-level prevalence of the exposure to each risk or intervention with the relative risk of diarrhoea given exposure to that factor. We assessed the relative and absolute change in diarrhoea mortality rate between 1990 and 2017, and used the change in risk factor exposure and sociodemographic status to explain differences in the trends of diarrhoea mortality among children younger than 5 years.

Findings

Diarrhoea was responsible for an estimated 533 768 deaths (95% uncertainty interval 477 162-593 145) among children younger than 5 years globally in 2017, a rate of 78·4 deaths (70·1-87·1) per 100 000 children. The diarrhoea mortality rate ranged between countries by over 685 deaths per 100 000 children. Diarrhoea mortality per 100 000 globally decreased by 69·6% (63·1-74·6) between 1990 and 2017. Among the risk factors considered in this study, those responsible for the largest declines in the diarrhoea mortality rate were reduction in exposure to unsafe sanitation (13·3% decrease, 11·2-15·5), childhood wasting (9·9% decrease, 9·6-10·2), and low use of oral rehydration solution (6·9% decrease, 4·8-8·4).

Interpretation

Diarrhoea mortality has declined substantially since 1990, although there are variations by country. Improvements in sociodemographic indicators might explain some of these trends, but changes in exposure to risk factors-particularly unsafe sanitation, childhood growth failure, and low use of oral rehydration solution-appear to be related to the relative and absolute rates of decline in diarrhoea mortality. Although the most effective interventions might vary by country or region, identifying and scaling up the interventions aimed at preventing and protecting against diarrhoea that have already reduced diarrhoea mortality could further avert many thousands of deaths due to this illness.

Funding

Bill & Melinda Gates Foundation.",,pdf:http://www.thelancet.com/article/S1473309919304013/pdf; doi:https://doi.org/10.1016/S1473-3099(19)30401-3; html:https://europepmc.org/articles/PMC7340495 32283057,https://doi.org/10.1016/j.jid.2020.03.957,"Clinical Impact of Antibodies against Ustekinumab in Psoriasis: An Observational, Cross-Sectional, Multicenter Study.","Loeff FC, Tsakok T, Dijk L, Hart MH, Duckworth M, Baudry D, Russell A, Dand N, van Leeuwen A, Griffiths CEM, Reynolds NJ, Barker J, Burden AD, Warren RB, de Vries A, Bloem K, Wolbink GJ, Smith CH, Rispens T, BADBIR, BSTOP Study Groups, PSORT consortium.",,The Journal of investigative dermatology,2020,2020-04-10,N,,,,"Ustekinumab is an effective treatment for psoriasis, but response varies between patients. The formation of anti-drug antibodies (ADAs) may explain part of this variation by reducing the free ustekinumab level. Currently, published analyses of the clinical impact of ADAs are incomplete. In this observational cross-sectional multicenter study of 340 patients, we evaluated the impact of ADAs on ustekinumab level and clinical response as assessed by the PASI. Circulating ADA levels were measured using two assays: a drug-sensitive radioimmunoassay and a drug-tolerant ELISA. Circulating ustekinumab levels were measured using an ELISA. ADAs were detected in 3.8% (95% confidence interval [CI] = 3.2-4.2) and in 10.6% (95% CI = 7.9-13.9) of patients using the radioimmunoassay and drug-tolerant ELISA, respectively. At least 85% of the ADAs were neutralizing. Compared with patients negative for ADAs, ADA positivity in the radioimmunoassay and drug-tolerant ELISA were associated with lower median ustekinumab levels (-0.62 μg/ml [95% CI = -1.190 to -0.30] and -0.74 μg/ml [95% CI = -1.09 to -0.47], respectively) and higher absolute PASI (6.6 [95% CI = 3.0-9.9] and 1.9 [95% CI = 0.4-4.0], respectively). Absence of detectable ustekinumab regardless of ADA status correlated with poor clinical outcome (median sample PASI 10.1, 6.5 [95% CI = 3.9-8.8] compared with patients positive for ustekinumab). In conclusion, substantially reduced drug exposure resulting from ADAs formation is associated with impaired clinical response.",,pdf:http://www.jidonline.org/article/S0022202X20313701/pdf; doi:https://doi.org/10.1016/j.jid.2020.03.957 36845321,https://doi.org/10.12688/wellcomeopenres.17403.2,"Characteristics and outcomes of COVID-19 patients with COPD from the United States, South Korea, and Europe.","Moreno-Martos D, Verhamme K, Ostropolets A, Kostka K, Duarte-Sales T, Prieto-Alhambra D, Alshammari TM, Alghoul H, Ahmed WU, Blacketer C, DuVall S, Lai L, Matheny M, Nyberg F, Posada J, Rijnbeek P, Spotnitz M, Sena A, Shah N, Suchard M, Chan You S, Hripcsak G, Ryan P, Morales D.",,Wellcome open research,2022,2022-03-24,Y,COPD; Coronavirus; Epidemiology.; Sars-cov-2; Covid,,,"Background: Characterization studies of COVID-19 patients with chronic obstructive pulmonary disease (COPD) are limited in size and scope. The aim of the study is to provide a large-scale characterization of COVID-19 patients with COPD. Methods: We included thirteen databases contributing data from January-June 2020 from North America (US), Europe and Asia. We defined two cohorts of patients with COVID-19 namely a 'diagnosed' and 'hospitalized' cohort. We followed patients from COVID-19 index date to 30 days or death. We performed descriptive analysis and reported the frequency of characteristics and outcomes among COPD patients with COVID-19. Results: The study included 934,778 patients in the diagnosed COVID-19 cohort and 177,201 in the hospitalized COVID-19 cohort. Observed COPD prevalence in the diagnosed cohort ranged from 3.8% (95%CI 3.5-4.1%) in French data to 22.7% (95%CI 22.4-23.0) in US data, and from 1.9% (95%CI 1.6-2.2) in South Korean to 44.0% (95%CI 43.1-45.0) in US data, in the hospitalized cohorts. COPD patients in the hospitalized cohort had greater comorbidity than those in the diagnosed cohort, including hypertension, heart disease, diabetes and obesity. Mortality was higher in COPD patients in the hospitalized cohort and ranged from 7.6% (95%CI 6.9-8.4) to 32.2% (95%CI 28.0-36.7) across databases. ARDS, acute renal failure, cardiac arrhythmia and sepsis were the most common outcomes among hospitalized COPD patients.   Conclusion: COPD patients with COVID-19 have high levels of COVID-19-associated comorbidities and poor COVID-19 outcomes. Further research is required to identify patients with COPD at high risk of worse outcomes.",,doi:https://doi.org/10.12688/wellcomeopenres.17403.2; html:https://europepmc.org/articles/PMC9951545; pdf:https://europepmc.org/articles/PMC9951545?pdf=render -33208942,https://doi.org/10.1038/s41586-020-2927-z,Host ANP32A mediates the assembly of the influenza virus replicase.,"Carrique L, Fan H, Walker AP, Keown JR, Sharps J, Staller E, Barclay WS, Fodor E, Grimes JM.",,Nature,2020,2020-11-18,Y,,,,"Aquatic birds represent a vast reservoir from which new pandemic influenza A viruses can emerge1. Influenza viruses contain a negative-sense segmented RNA genome that is transcribed and replicated by the viral heterotrimeric RNA polymerase (FluPol) in the context of viral ribonucleoprotein complexes2,3. RNA polymerases of avian influenza A viruses (FluPolA) replicate viral RNA inefficiently in human cells because of species-specific differences in acidic nuclear phosphoprotein 32 (ANP32), a family of essential host proteins for FluPol activity4. Host-adaptive mutations, particularly a glutamic-acid-to-lysine mutation at amino acid residue 627 (E627K) in the 627 domain of the PB2 subunit, enable avian FluPolA to overcome this restriction and efficiently replicate viral RNA in the presence of human ANP32 proteins. However, the molecular mechanisms of genome replication and the interplay with ANP32 proteins remain largely unknown. Here we report cryo-electron microscopy structures of influenza C virus polymerase (FluPolC) in complex with human and chicken ANP32A. In both structures, two FluPolC molecules form an asymmetric dimer bridged by the N-terminal leucine-rich repeat domain of ANP32A. The C-terminal low-complexity acidic region of ANP32A inserts between the two juxtaposed PB2 627 domains of the asymmetric FluPolA dimer, suggesting a mechanism for how the adaptive PB2(E627K) mutation enables the replication of viral RNA in mammalian hosts. We propose that this complex represents a replication platform for the viral RNA genome, in which one of the FluPol molecules acts as a replicase while the other initiates the assembly of the nascent replication product into a viral ribonucleoprotein complex.",,pdf:https://www.nature.com/articles/s41586-020-2927-z.pdf; doi:https://doi.org/10.1038/s41586-020-2927-z; html:https://europepmc.org/articles/PMC7116770; pdf:https://europepmc.org/articles/PMC7116770?pdf=render 31978332,https://doi.org/10.1016/j.ajhg.2020.01.003,A Multi-tissue Transcriptome Analysis of Human Metabolites Guides Interpretability of Associations Based on Multi-SNP Models for Gene Expression.,"Ndungu A, Payne A, Torres JM, van de Bunt M, McCarthy MI.",,American journal of human genetics,2020,2020-01-23,Y,Metabolites; Gene regulation; colocalization; Gene Expression; Gwas; Eqtls; Twas; S-predixcan; Multi-tissue Gtex; Transcriptome Wide Association Studies,,,"There is particular interest in transcriptome-wide association studies (TWAS) gene-level tests based on multi-SNP predictive models of gene expression-for identifying causal genes at loci associated with complex traits. However, interpretation of TWAS associations may be complicated by divergent effects of model SNPs on phenotype and gene expression. We developed an iterative modeling scheme for obtaining multi-SNP models of gene expression and applied this framework to generate expression models for 43 human tissues from the Genotype-Tissue Expression (GTEx) Project. We characterized the performance of single- and multi-SNP models for identifying causal genes in GWAS data for 46 circulating metabolites. We show that: (A) multi-SNP models captured more variation in expression than did the top cis-eQTL (median 2-fold improvement); (B) predicted expression based on multi-SNP models was associated (false discovery rate < 0.01) with metabolite levels for 826 unique gene-metabolite pairs, but, after stepwise conditional analyses, 90% were dominated by a single eQTL SNP; (C) among the 35% of associations where a SNP in the expression model was a significant cis-eQTL and metabolomic-QTL (met-QTL), 92% demonstrated colocalization between these signals, but interpretation was often complicated by incomplete overlap of QTLs in multi-SNP models; and (D) using a ""truth"" set of causal genes at 61 met-QTLs, the sensitivity was high (67%), but the positive predictive value was low, as only 8% of TWAS associations (19% when restricted to colocalized associations at met-QTLs) involved true causal genes. These results guide the interpretation of TWAS and highlight the need for corroborative data to provide confident assignment of causality.", ,pdf:http://www.cell.com/article/S0002929720300033/pdf; doi:https://doi.org/10.1016/j.ajhg.2020.01.003; html:https://europepmc.org/articles/PMC7010967; pdf:https://europepmc.org/articles/PMC7010967?pdf=render +33208942,https://doi.org/10.1038/s41586-020-2927-z,Host ANP32A mediates the assembly of the influenza virus replicase.,"Carrique L, Fan H, Walker AP, Keown JR, Sharps J, Staller E, Barclay WS, Fodor E, Grimes JM.",,Nature,2020,2020-11-18,Y,,,,"Aquatic birds represent a vast reservoir from which new pandemic influenza A viruses can emerge1. Influenza viruses contain a negative-sense segmented RNA genome that is transcribed and replicated by the viral heterotrimeric RNA polymerase (FluPol) in the context of viral ribonucleoprotein complexes2,3. RNA polymerases of avian influenza A viruses (FluPolA) replicate viral RNA inefficiently in human cells because of species-specific differences in acidic nuclear phosphoprotein 32 (ANP32), a family of essential host proteins for FluPol activity4. Host-adaptive mutations, particularly a glutamic-acid-to-lysine mutation at amino acid residue 627 (E627K) in the 627 domain of the PB2 subunit, enable avian FluPolA to overcome this restriction and efficiently replicate viral RNA in the presence of human ANP32 proteins. However, the molecular mechanisms of genome replication and the interplay with ANP32 proteins remain largely unknown. Here we report cryo-electron microscopy structures of influenza C virus polymerase (FluPolC) in complex with human and chicken ANP32A. In both structures, two FluPolC molecules form an asymmetric dimer bridged by the N-terminal leucine-rich repeat domain of ANP32A. The C-terminal low-complexity acidic region of ANP32A inserts between the two juxtaposed PB2 627 domains of the asymmetric FluPolA dimer, suggesting a mechanism for how the adaptive PB2(E627K) mutation enables the replication of viral RNA in mammalian hosts. We propose that this complex represents a replication platform for the viral RNA genome, in which one of the FluPol molecules acts as a replicase while the other initiates the assembly of the nascent replication product into a viral ribonucleoprotein complex.",,pdf:https://www.nature.com/articles/s41586-020-2927-z.pdf; doi:https://doi.org/10.1038/s41586-020-2927-z; html:https://europepmc.org/articles/PMC7116770; pdf:https://europepmc.org/articles/PMC7116770?pdf=render 34319235,https://doi.org/10.2196/28873,Remote Assessment of Lung Disease and Impact on Physical and Mental Health (RALPMH): Protocol for a Prospective Observational Study.,"Ranjan Y, Althobiani M, Jacob J, Orini M, Dobson RJ, Porter J, Hurst J, Folarin AA.",,JMIR research protocols,2021,2021-10-07,Y,Lung diseases; Mental health; Remote Monitoring; Respiratory Health; Internet Of Things; Mhealth; Mobile Health; Wearables; Cardiopulmonary Diseases; Covid-19,,,"

Background

Chronic lung disorders like chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) are characterized by exacerbations. They are unpleasant for patients and sometimes severe enough to cause hospital admission and death. Moreover, due to the COVID-19 pandemic, vulnerable populations with these disorders are at high risk, and their routine care cannot be done properly. Remote monitoring offers a low cost and safe solution for gaining visibility into the health of people in their daily lives, making it useful for vulnerable populations.

Objective

The primary objective is to assess the feasibility and acceptability of remote monitoring using wearables and mobile phones in patients with pulmonary diseases. The secondary objective is to provide power calculations for future studies centered around understanding the number of exacerbations according to sample size and duration.

Methods

Twenty participants will be recruited in each of three cohorts (COPD, IPF, and posthospitalization COVID). Data collection will be done remotely using the RADAR-Base (Remote Assessment of Disease And Relapse) mobile health (mHealth) platform for different devices, including Garmin wearable devices and smart spirometers, mobile app questionnaires, surveys, and finger pulse oximeters. Passive data include wearable-derived continuous heart rate, oxygen saturation, respiration rate, activity, and sleep. Active data include disease-specific patient-reported outcome measures, mental health questionnaires, and symptom tracking to track disease trajectory. Analyses will assess the feasibility of lung disorder remote monitoring (including data quality, data completeness, system usability, and system acceptability). We will attempt to explore disease trajectory, patient stratification, and identification of acute clinical events such as exacerbations. A key aspect is understanding the potential of real-time data collection. We will simulate an intervention to acquire responses at the time of the event to assess model performance for exacerbation identification.

Results

The Remote Assessment of Lung Disease and Impact on Physical and Mental Health (RALPMH) study provides a unique opportunity to assess the use of remote monitoring in the evaluation of lung disorders. The study started in the middle of June 2021. The data collection apparatus, questionnaires, and wearable integrations were setup and tested by the clinical teams prior to the start of recruitment. While recruitment is ongoing, real-time exacerbation identification models are currently being constructed. The models will be pretrained daily on data of previous days, but the inference will be run in real time.

Conclusions

The RALPMH study will provide a reference infrastructure for remote monitoring of lung diseases. It specifically involves information regarding the feasibility and acceptability of remote monitoring and the potential of real-time data collection and analysis in the context of chronic lung disorders. It will help plan and inform decisions in future studies in the area of respiratory health.

Trial registration

ISRCTN Registry ISRCTN16275601; https://www.isrctn.com/ISRCTN16275601.

International registered report identifier (irrid)

PRR1-10.2196/28873.",,pdf:https://jmir.org/api/download?alt_name=resprot_v10i10e28873_app2.pdf&filename=4dda9f18456291d5d5d6facee1b77a71.pdf; doi:https://doi.org/10.2196/28873; html:https://europepmc.org/articles/PMC8500349 32597303,https://doi.org/10.1080/15476286.2020.1777768,Targeted RNA sequencing enhances gene expression profiling of ultra-low input samples.,"Curion F, Handel AE, Attar M, Gallone G, Bowden R, Cader MZ, Clark MB.",,RNA biology,2020,2020-06-28,Y,Method; Gene Expression; Rna-seq; Targeted Rna Sequencing; Low-input Sequencing; Captureseq; Stem-cell-derived Neurons,,,"RNA-seq is the standard method for profiling gene expression in many biological systems. Due to the wide dynamic range and complex nature of the transcriptome, RNA-seq provides an incomplete characterization, especially of lowly expressed genes and transcripts. Targeted RNA sequencing (RNA CaptureSeq) focuses sequencing on genes of interest, providing exquisite sensitivity for transcript detection and quantification. However, uses of CaptureSeq have focused on bulk samples and its performance on very small populations of cells is unknown. Here we show CaptureSeq greatly enhances transcriptomic profiling of target genes in ultra-low-input samples and provides equivalent performance to that on bulk samples. We validate the performance of CaptureSeq using multiple probe sets on samples of iPSC-derived cortical neurons. We demonstrate up to 275-fold enrichment for target genes, the detection of 10% additional genes and a greater than 5-fold increase in identified gene isoforms. Analysis of spike-in controls demonstrated CaptureSeq improved both detection sensitivity and expression quantification. Comparison to the CORTECON database of cerebral cortex development revealed CaptureSeq enhanced the identification of sample differentiation stage. CaptureSeq provides sensitive, reliable and quantitative expression measurements on hundreds-to-thousands of target genes from ultra-low-input samples and has the potential to greatly enhance transcriptomic profiling when samples are limiting.",,pdf:https://www.tandfonline.com/doi/pdf/10.1080/15476286.2020.1777768?needAccess=true; doi:https://doi.org/10.1080/15476286.2020.1777768; html:https://europepmc.org/articles/PMC7746246; pdf:https://europepmc.org/articles/PMC7746246?pdf=render 31182084,https://doi.org/10.1186/s12911-019-0824-x,The effect of computerized decision support systems on cardiovascular risk factors: a systematic review and meta-analysis.,"Groenhof TKJ, Asselbergs FW, Groenwold RHH, Grobbee DE, Visseren FLJ, Bots ML, UCC-SMART study group.",,BMC medical informatics and decision making,2019,2019-06-10,Y,Cdss; Computerized Decision Support; Cardiovascular Risk Management,,,"

Background

Cardiovascular risk management (CVRM) is notoriously difficult because of multi-morbidity and the different phenotypes and severities of cardiovascular disease. Computerized decision support systems (CDSS) enable the clinician to integrate the latest scientific evidence and patient information into tailored strategies. The effect on cardiovascular risk factor management is yet to be confirmed.

Methods

We performed a systematic review and meta-analysis evaluating the effects of CDSS on CVRM, defined as the change in absolute values and attainment of treatment goals of systolic blood pressure (SBP), low density lipoprotein cholesterol (LDL-c) and HbA1c. Also, CDSS characteristics related to more effective CVRM were identified. Eligible articles were methodologically appraised using the Cochrane risk of bias tool. We calculated mean differences, relative risks, and if appropriate (I2 < 70%), pooled the results using a random-effects model.

Results

Of the 14,335 studies identified, 22 were included. Four studies reported on SBP, 3 on LDL-c, 10 on CVRM in patients with type II diabetes and 5 on guideline adherence. The CDSSs varied considerably in technical performance and content. Heterogeneity of results was such that quantitative pooling was often not appropriate. Among CVRM patients, the results tended towards a beneficial effect of CDSS, but only LDL-c target attainment in diabetes patients reached statistical significance. Prompting, integration into the electronical health record, patient empowerment, and medication support were related to more effective CVRM.

Conclusion

We did not find a clear clinical benefit from CDSS in cardiovascular risk factor levels and target attainment. Some features of CDSS seem more promising than others. However, the variability in CDSS characteristics and heterogeneity of the results - emphasizing the immaturity of this research area - limit stronger conclusions. Clinical relevance of CDSS in CVRM might additionally be sought in the improvement of shared decision making and patient empowerment.",,pdf:https://bmcmedinformdecismak.biomedcentral.com/track/pdf/10.1186/s12911-019-0824-x; doi:https://doi.org/10.1186/s12911-019-0824-x; html:https://europepmc.org/articles/PMC6558725; pdf:https://europepmc.org/articles/PMC6558725?pdf=render @@ -2429,8 +2429,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 31317072,https://doi.org/10.1002/lrh2.10191,"Our data, our society, our health: A vision for inclusive and transparent health data science in the United Kingdom and beyond.","Ford E, Boyd A, Bowles JKF, Havard A, Aldridge RW, Curcin V, Greiver M, Harron K, Katikireddi V, Rodgers SE, Sperrin M.",,Learning health systems,2019,2019-03-25,Y,Transparency; Health Systems; Stakeholder Involvement; Data Flows; Health Data Science; Citizen‐driven Science,,,"The last 6 years have seen sustained investment in health data science in the United Kingdom and beyond, which should result in a data science community that is inclusive of all stakeholders, working together to use data to benefit society through the improvement of public health and well-being. However, opportunities made possible through the innovative use of data are still not being fully realised, resulting in research inefficiencies and avoidable health harms. In this paper, we identify the most important barriers to achieving higher productivity in health data science. We then draw on previous research, domain expertise, and theory to outline how to go about overcoming these barriers, applying our core values of inclusivity and transparency. We believe a step change can be achieved through meaningful stakeholder involvement at every stage of research planning, design, and execution and team-based data science, as well as harnessing novel and secure data technologies. Applying these values to health data science will safeguard a social licence for health data research and ensure transparent and secure data usage for public benefit.",,pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/lrh2.10191; doi:https://doi.org/10.1002/lrh2.10191; html:https://europepmc.org/articles/PMC6628981; pdf:https://europepmc.org/articles/PMC6628981?pdf=render 37414900,https://doi.org/10.1038/s41591-023-02429-x,A multi-ancestry polygenic risk score improves risk prediction for coronary artery disease.,"Patel AP, Wang M, Ruan Y, Koyama S, Clarke SL, Yang X, Tcheandjieu C, Agrawal S, Fahed AC, Ellinor PT, Genes & Health Research Team; the Million Veteran Program, Tsao PS, Sun YV, Cho K, Wilson PWF, Assimes TL, van Heel DA, Butterworth AS, Aragam KG, Natarajan P, Khera AV.",,Nature medicine,2023,2023-07-06,Y,,,,"Identification of individuals at highest risk of coronary artery disease (CAD)-ideally before onset-remains an important public health need. Prior studies have developed genome-wide polygenic scores to enable risk stratification, reflecting the substantial inherited component to CAD risk. Here we develop a new and significantly improved polygenic score for CAD, termed GPSMult, that incorporates genome-wide association data across five ancestries for CAD (>269,000 cases and >1,178,000 controls) and ten CAD risk factors. GPSMult strongly associated with prevalent CAD (odds ratio per standard deviation 2.14, 95% confidence interval 2.10-2.19, P < 0.001) in UK Biobank participants of European ancestry, identifying 20.0% of the population with 3-fold increased risk and conversely 13.9% with 3-fold decreased risk as compared with those in the middle quintile. GPSMult was also associated with incident CAD events (hazard ratio per standard deviation 1.73, 95% confidence interval 1.70-1.76, P < 0.001), identifying 3% of healthy individuals with risk of future CAD events equivalent to those with existing disease and significantly improving risk discrimination and reclassification. Across multiethnic, external validation datasets inclusive of 33,096, 124,467, 16,433 and 16,874 participants of African, European, Hispanic and South Asian ancestry, respectively, GPSMult demonstrated increased strength of associations across all ancestries and outperformed all available previously published CAD polygenic scores. These data contribute a new GPSMult for CAD to the field and provide a generalizable framework for how large-scale integration of genetic association data for CAD and related traits from diverse populations can meaningfully improve polygenic risk prediction.",,pdf:https://www.nature.com/articles/s41591-023-02429-x.pdf; doi:https://doi.org/10.1038/s41591-023-02429-x; html:https://europepmc.org/articles/PMC10353935; pdf:https://europepmc.org/articles/PMC10353935?pdf=render 35151371,https://doi.org/10.1016/j.immuni.2022.01.017,Immuno-proteomic profiling reveals aberrant immune cell regulation in the airways of individuals with ongoing post-COVID-19 respiratory disease.,"Vijayakumar B, Boustani K, Ogger PP, Papadaki A, Tonkin J, Orton CM, Ghai P, Suveizdyte K, Hewitt RJ, Desai SR, Devaraj A, Snelgrove RJ, Molyneaux PL, Garner JL, Peters JE, Shah PL, Lloyd CM, Harker JA.",,Immunity,2022,2022-01-26,Y,T cells; Proteomics; Respiratory Tract; Airways; Respiratory Viral Infection; Tissue-resident Memory; Covid-19; Sars-cov-2; Long Covid,,,"Some patients hospitalized with acute COVID-19 suffer respiratory symptoms that persist for many months. We delineated the immune-proteomic landscape in the airways and peripheral blood of healthy controls and post-COVID-19 patients 3 to 6 months after hospital discharge. Post-COVID-19 patients showed abnormal airway (but not plasma) proteomes, with an elevated concentration of proteins associated with apoptosis, tissue repair, and epithelial injury versus healthy individuals. Increased numbers of cytotoxic lymphocytes were observed in individuals with greater airway dysfunction, while increased B cell numbers and altered monocyte subsets were associated with more widespread lung abnormalities. A one-year follow-up of some post-COVID-19 patients indicated that these abnormalities resolved over time. In summary, COVID-19 causes a prolonged change to the airway immune landscape in those with persistent lung disease, with evidence of cell death and tissue repair linked to the ongoing activation of cytotoxic T cells.",,pdf:http://www.cell.com/article/S1074761322000462/pdf; doi:https://doi.org/10.1016/j.immuni.2022.01.017; html:https://europepmc.org/articles/PMC8789571; pdf:https://europepmc.org/articles/PMC8789571?pdf=render -34812717,https://doi.org/10.1099/mgen.0.000700,Antimicrobial resistance determinants are associated with Staphylococcus aureus bacteraemia and adaptation to the healthcare environment: a bacterial genome-wide association study.,"Young BC, Wu CH, Charlesworth J, Earle S, Price JR, Gordon NC, Cole K, Dunn L, Liu E, Oakley S, Godwin H, Fung R, Miller R, Knox K, Votintseva A, Quan TP, Tilley R, Scarborough M, Crook DW, Peto TE, Walker AS, Llewelyn MJ, Wilson DJ.",,Microbial genomics,2021,2021-11-01,Y,Nosocomial infection; Bacterial Pathogens; Bacteraemia; Microbial Genomics; Microbial Epidemiology,,,"Staphylococcus aureus is a major bacterial pathogen in humans, and a dominant cause of severe bloodstream infections. Globally, antimicrobial resistance (AMR) in S. aureus remains challenging. While human risk factors for infection have been defined, contradictory evidence exists for the role of bacterial genomic variation in S. aureus disease. To investigate the contribution of bacterial lineage and genomic variation to the development of bloodstream infection, we undertook a genome-wide association study comparing bacteria from 1017 individuals with bacteraemia to 984 adults with asymptomatic S. aureus nasal carriage. Within 984 carriage isolates, we also compared healthcare-associated (HA) carriage with community-associated (CA) carriage. All major global lineages were represented in both bacteraemia and carriage, with no evidence for different infection rates. However, kmers tagging trimethoprim resistance-conferring mutation F99Y in dfrB were significantly associated with bacteraemia-vs-carriage (P=10-8.9-10-9.3). Pooling variation within genes, bacteraemia-vs-carriage was associated with the presence of mecA (HMP=10-5.3) as well as the presence of SCCmec (HMP=10-4.4). Among S. aureus carriers, no lineages were associated with HA-vs-CA carriage. However, we found a novel signal of HA-vs-CA carriage in the foldase protein prsA, where kmers representing conserved sequence allele were associated with CA carriage (P=10-7.1-10-19.4), while in gyrA, a ciprofloxacin resistance-conferring mutation, L84S, was associated with HA carriage (P=10-7.2). In an extensive study of S. aureus bacteraemia and nasal carriage in the UK, we found strong evidence that all S. aureus lineages are equally capable of causing bloodstream infection, and of being carried in the healthcare environment. Genomic variation in the foldase protein prsA is a novel genomic marker of healthcare origin in S. aureus but was not associated with bacteraemia. AMR determinants were associated with both bacteraemia and healthcare-associated carriage, suggesting that AMR increases the propensity not only to survive in healthcare environments, but also to cause invasive disease.",,doi:https://doi.org/10.1099/mgen.0.000700; doi:https://doi.org/10.1099/mgen.0.000700; html:https://europepmc.org/articles/PMC8743558; pdf:https://europepmc.org/articles/PMC8743558?pdf=render 31951611,https://doi.org/10.1371/journal.pbio.3000586,Dating genomic variants and shared ancestry in population-scale sequencing data.,"Albers PK, McVean G.",,PLoS biology,2020,2020-01-17,Y,,The Human Phenome,,"The origin and fate of new mutations within species is the fundamental process underlying evolution. However, while much attention has been focused on characterizing the presence, frequency, and phenotypic impact of genetic variation, the evolutionary histories of most variants are largely unexplored. We have developed a nonparametric approach for estimating the date of origin of genetic variants in large-scale sequencing data sets. The accuracy and robustness of the approach is demonstrated through simulation. Using data from two publicly available human genomic diversity resources, we estimated the age of more than 45 million single-nucleotide polymorphisms (SNPs) in the human genome and release the Atlas of Variant Age as a public online database. We characterize the relationship between variant age and frequency in different geographical regions and demonstrate the value of age information in interpreting variants of functional and selective importance. Finally, we use allele age estimates to power a rapid approach for inferring the ancestry shared between individual genomes and to quantify genealogical relationships at different points in the past, as well as to describe and explore the evolutionary history of modern human populations.", ,pdf:https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3000586&type=printable; doi:https://doi.org/10.1371/journal.pbio.3000586; html:https://europepmc.org/articles/PMC6992231; pdf:https://europepmc.org/articles/PMC6992231?pdf=render +34812717,https://doi.org/10.1099/mgen.0.000700,Antimicrobial resistance determinants are associated with Staphylococcus aureus bacteraemia and adaptation to the healthcare environment: a bacterial genome-wide association study.,"Young BC, Wu CH, Charlesworth J, Earle S, Price JR, Gordon NC, Cole K, Dunn L, Liu E, Oakley S, Godwin H, Fung R, Miller R, Knox K, Votintseva A, Quan TP, Tilley R, Scarborough M, Crook DW, Peto TE, Walker AS, Llewelyn MJ, Wilson DJ.",,Microbial genomics,2021,2021-11-01,Y,Nosocomial infection; Bacterial Pathogens; Bacteraemia; Microbial Genomics; Microbial Epidemiology,,,"Staphylococcus aureus is a major bacterial pathogen in humans, and a dominant cause of severe bloodstream infections. Globally, antimicrobial resistance (AMR) in S. aureus remains challenging. While human risk factors for infection have been defined, contradictory evidence exists for the role of bacterial genomic variation in S. aureus disease. To investigate the contribution of bacterial lineage and genomic variation to the development of bloodstream infection, we undertook a genome-wide association study comparing bacteria from 1017 individuals with bacteraemia to 984 adults with asymptomatic S. aureus nasal carriage. Within 984 carriage isolates, we also compared healthcare-associated (HA) carriage with community-associated (CA) carriage. All major global lineages were represented in both bacteraemia and carriage, with no evidence for different infection rates. However, kmers tagging trimethoprim resistance-conferring mutation F99Y in dfrB were significantly associated with bacteraemia-vs-carriage (P=10-8.9-10-9.3). Pooling variation within genes, bacteraemia-vs-carriage was associated with the presence of mecA (HMP=10-5.3) as well as the presence of SCCmec (HMP=10-4.4). Among S. aureus carriers, no lineages were associated with HA-vs-CA carriage. However, we found a novel signal of HA-vs-CA carriage in the foldase protein prsA, where kmers representing conserved sequence allele were associated with CA carriage (P=10-7.1-10-19.4), while in gyrA, a ciprofloxacin resistance-conferring mutation, L84S, was associated with HA carriage (P=10-7.2). In an extensive study of S. aureus bacteraemia and nasal carriage in the UK, we found strong evidence that all S. aureus lineages are equally capable of causing bloodstream infection, and of being carried in the healthcare environment. Genomic variation in the foldase protein prsA is a novel genomic marker of healthcare origin in S. aureus but was not associated with bacteraemia. AMR determinants were associated with both bacteraemia and healthcare-associated carriage, suggesting that AMR increases the propensity not only to survive in healthcare environments, but also to cause invasive disease.",,doi:https://doi.org/10.1099/mgen.0.000700; doi:https://doi.org/10.1099/mgen.0.000700; html:https://europepmc.org/articles/PMC8743558; pdf:https://europepmc.org/articles/PMC8743558?pdf=render 37810217,https://doi.org/10.1016/j.isci.2023.107795,"Factor V Leiden, estrogen, and multimorbidity association with venous thromboembolism in a British-South Asian cohort.","Magavern EF, Genes & Health Research Team, Smedley D, Caulfield MJ.",,iScience,2023,2023-09-01,Y,Public Health; Cardiovascular Medicine; Clinical Endocrinology,,,"Multimorbidity, estrogen use, and Factor V Leiden (FVL) are known independent risk factors for venous thromboembolism (VTE). This cross-sectional analysis of women in the Genes & Health British-South Asian cohort (N 20,048) linked the F5 SNP rs6025 with estrogen prescribing data and VTE events. Multivariable logistic regression was used to test the association between estrogen use, FVL, common medical co-morbidities, and VTE. Estrogens were prescribed to 30% of women. 3% of participants were FVL carriers. 439 participants had a VTE event (2.2%), and VTE prevalence increased with obesity, hypertension, dyslipidemia, chronic kidney disease, estrogen use, and in the presence of FVL. One medical condition above was independently associated with VTE with an OR 1.6 (CI 1.2-2.0, p 0.001); two medical conditions OR 2.7 (CI 2.0-3.7, p < 0.001); three OR 5.3 (CI 3.8-7.4, p < 0.001); four OR 8.1 (CI 4.9-13.0, p < 0.001). Multimorbidity and FVL compound risk of VTE with estrogen use.",,doi:https://doi.org/10.1016/j.isci.2023.107795; html:https://europepmc.org/articles/PMC10550715; pdf:https://europepmc.org/articles/PMC10550715?pdf=render 37343968,https://doi.org/10.1136/bmj-2022-072976,Risk prediction of covid-19 related death or hospital admission in adults testing positive for SARS-CoV-2 infection during the omicron wave in England (QCOVID4): cohort study.,"Hippisley-Cox J, Khunti K, Sheikh A, Nguyen-Van-Tam JS, Coupland CAC.",,BMJ (Clinical research ed.),2023,2023-06-21,Y,,,,"

Objectives

To derive and validate risk prediction algorithms (QCOVID4) to estimate the risk of covid-19 related death and hospital admission in people with a positive SARS-CoV-2 test result during the period when the omicron variant of the virus was predominant in England, and to evaluate performance compared with a high risk cohort from NHS Digital.

Design

Cohort study.

Setting

QResearch database linked to English national data on covid-19 vaccinations, SARS-CoV-2 test results, hospital admissions, and cancer and mortality data, 11 December 2021 to 31 March 2022, with follow-up to 30 June 2022.

Participants

1.3 million adults in the derivation cohort and 0.15 million adults in the validation cohort, aged 18-100 years, with a positive test result for SARS-CoV-2 infection.

Main outcome measures

Primary outcome was covid-19 related death and secondary outcome was hospital admission for covid-19. Risk equations with predictor variables were derived from models fitted in the derivation cohort. Performance was evaluated in a separate validation cohort.

Results

Of 1 297 922 people with a positive test result for SARS-CoV-2 infection in the derivation cohort, 18 756 (1.5%) had a covid-19 related hospital admission and 3878 (0.3%) had a covid-19 related death during follow-up. The final QCOVID4 models included age, deprivation score and a range of health and sociodemographic factors, number of covid-19 vaccinations, and previous SARS-CoV-2 infection. The risk of death related to covid-19 was lower among those who had received a covid-19 vaccine, with evidence of a dose-response relation (42% risk reduction associated with one vaccine dose and 92% reduction with four or more doses in men). Previous SARS-CoV-2 infection was associated with a reduction in the risk of covid-19 related death (49% reduction in men). The QCOVID4 algorithm for covid-19 explained 76.0% (95% confidence interval 73.9% to 78.2%) of the variation in time to covid-19 related death in men with a D statistic of 3.65 (3.43 to 3.86) and Harrell's C statistic of 0.970 (0.962 to 0.979). Results were similar for women. QCOVID4 was well calibrated. QCOVID4 was substantially more efficient than the NHS Digital algorithm for correctly identifying patients at high risk of covid-19 related death. Of the 461 covid-19 related deaths in the validation cohort, 333 (72.2%) were in the QCOVID4 high risk group and 95 (20.6%) in the NHS Digital high risk group.

Conclusion

The QCOVID4 risk algorithm, modelled from data during the period when the omicron variant of the SARS-CoV-2 virus was predominant in England, now includes vaccination dose and previous SARS-CoV-2 infection, and predicted covid-19 related death among people with a positive test result. QCOVID4 more accurately identified individuals at the highest levels of absolute risk for targeted interventions than the approach adopted by NHS Digital. QCOVID4 performed well and could be used for targeting treatments for covid-19 disease.",,pdf:https://www.bmj.com/content/bmj/381/bmj-2022-072976.full.pdf; doi:https://doi.org/10.1136/bmj-2022-072976; html:https://europepmc.org/articles/PMC10282241; pdf:https://europepmc.org/articles/PMC10282241?pdf=render 34662334,https://doi.org/10.1371/journal.pgen.1009436,Machine learning to predict the source of campylobacteriosis using whole genome data.,"Arning N, Sheppard SK, Bayliss S, Clifton DA, Wilson DJ.",,PLoS genetics,2021,2021-10-18,Y,,,,"Campylobacteriosis is among the world's most common foodborne illnesses, caused predominantly by the bacterium Campylobacter jejuni. Effective interventions require determination of the infection source which is challenging as transmission occurs via multiple sources such as contaminated meat, poultry, and drinking water. Strain variation has allowed source tracking based upon allelic variation in multi-locus sequence typing (MLST) genes allowing isolates from infected individuals to be attributed to specific animal or environmental reservoirs. However, the accuracy of probabilistic attribution models has been limited by the ability to differentiate isolates based upon just 7 MLST genes. Here, we broaden the input data spectrum to include core genome MLST (cgMLST) and whole genome sequences (WGS), and implement multiple machine learning algorithms, allowing more accurate source attribution. We increase attribution accuracy from 64% using the standard iSource population genetic approach to 71% for MLST, 85% for cgMLST and 78% for kmerized WGS data using the classifier we named aiSource. To gain insight beyond the source model prediction, we use Bayesian inference to analyse the relative affinity of C. jejuni strains to infect humans and identified potential differences, in source-human transmission ability among clonally related isolates in the most common disease causing lineage (ST-21 clonal complex). Providing generalizable computationally efficient methods, based upon machine learning and population genetics, we provide a scalable approach to global disease surveillance that can continuously incorporate novel samples for source attribution and identify fine-scale variation in transmission potential.",,pdf:https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1009436&type=printable; doi:https://doi.org/10.1371/journal.pgen.1009436; html:https://europepmc.org/articles/PMC8553134; pdf:https://europepmc.org/articles/PMC8553134?pdf=render @@ -2478,8 +2478,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 34748544,https://doi.org/10.1371/journal.pbio.3001255,Predicting novel candidate human obesity genes and their site of action by systematic functional screening in Drosophila.,"Agrawal N, Lawler K, Davidson CM, Keogh JM, Legg R, INTERVAL, Barroso I, Farooqi IS, Brand AH.",,PLoS biology,2021,2021-11-08,Y,,,,"The discovery of human obesity-associated genes can reveal new mechanisms to target for weight loss therapy. Genetic studies of obese individuals and the analysis of rare genetic variants can identify novel obesity-associated genes. However, establishing a functional relationship between these candidate genes and adiposity remains a significant challenge. We uncovered a large number of rare homozygous gene variants by exome sequencing of severely obese children, including those from consanguineous families. By assessing the function of these genes in vivo in Drosophila, we identified 4 genes, not previously linked to human obesity, that regulate adiposity (itpr, dachsous, calpA, and sdk). Dachsous is a transmembrane protein upstream of the Hippo signalling pathway. We found that 3 further members of the Hippo pathway, fat, four-jointed, and hippo, also regulate adiposity and that they act in neurons, rather than in adipose tissue (fat body). Screening Hippo pathway genes in larger human cohorts revealed rare variants in TAOK2 associated with human obesity. Knockdown of Drosophila tao increased adiposity in vivo demonstrating the strength of our approach in predicting novel human obesity genes and signalling pathways and their site of action.",,pdf:https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3001255&type=printable; doi:https://doi.org/10.1371/journal.pbio.3001255; html:https://europepmc.org/articles/PMC8575313; pdf:https://europepmc.org/articles/PMC8575313?pdf=render 34876579,https://doi.org/10.1038/s41467-021-27326-0,Biological heterogeneity in idiopathic pulmonary arterial hypertension identified through unsupervised transcriptomic profiling of whole blood.,"Kariotis S, Jammeh E, Swietlik EM, Pickworth JA, Rhodes CJ, Otero P, Wharton J, Iremonger J, Dunning MJ, Pandya D, Mascarenhas TS, Errington N, Thompson AAR, Romanoski CE, Rischard F, Garcia JGN, Yuan JX, An TS, Desai AA, Coghlan G, Lordan J, Corris PA, Howard LS, Condliffe R, Kiely DG, Church C, Pepke-Zaba J, Toshner M, Wort S, Gräf S, Morrell NW, Wilkins MR, Lawrie A, Wang D, UK National PAH Cohort Study Consortium.",,Nature communications,2021,2021-12-07,Y,,,,"Idiopathic pulmonary arterial hypertension (IPAH) is a rare but fatal disease diagnosed by right heart catheterisation and the exclusion of other forms of pulmonary arterial hypertension, producing a heterogeneous population with varied treatment response. Here we show unsupervised machine learning identification of three major patient subgroups that account for 92% of the cohort, each with unique whole blood transcriptomic and clinical feature signatures. These subgroups are associated with poor, moderate, and good prognosis. The poor prognosis subgroup is associated with upregulation of the ALAS2 and downregulation of several immunoglobulin genes, while the good prognosis subgroup is defined by upregulation of the bone morphogenetic protein signalling regulator NOG, and the C/C variant of HLA-DPA1/DPB1 (independently associated with survival). These findings independently validated provide evidence for the existence of 3 major subgroups (endophenotypes) within the IPAH classification, could improve risk stratification and provide molecular insights into the pathogenesis of IPAH.",,pdf:https://www.nature.com/articles/s41467-021-27326-0.pdf; doi:https://doi.org/10.1038/s41467-021-27326-0; html:https://europepmc.org/articles/PMC8651638; pdf:https://europepmc.org/articles/PMC8651638?pdf=render 34988540,https://doi.org/10.1016/j.jadr.2021.100201,Comparison of depression and anxiety symptom networks in reporters and non-reporters of lifetime trauma in two samples of differing severity.,"Peel AJ, Armour C, Buckman JEJ, Coleman JRI, Curzons SCB, Davies MR, Hübel C, Jones I, Kalsi G, McAtarsney-Kovacs M, McIntosh AM, Monssen D, Mundy J, Rayner C, Rogers HC, Skelton M, Ter Kuile A, Thompson KN, Breen G, Danese A, Eley TC.",,Journal of affective disorders reports,2021,2021-12-01,Y,Trauma; Depression; Anxiety; Self-report; Network Analysis,,,"

Background

Reported trauma is associated with differences in the course and outcomes of depression and anxiety. However, no research has explored the association between reported trauma and patterns of clinically relevant symptoms of both depression and anxiety.

Methods

We used network analysis to investigate associations between reported trauma and depression and anxiety symptom interactions in affected individuals from the Genetic Links to Anxiety and Depression (GLAD) Study (n = 17720), and population volunteers from the UK Biobank (n = 11120). Participants with current moderate symptoms of depression or anxiety were grouped into reporters and non-reporters of lifetime trauma. Networks of 16 depression and anxiety symptoms in the two groups were compared using the network comparison test.

Results

In the GLAD Study, networks of reporters and non-reporters of lifetime trauma did not differ on any metric. In the UK Biobank, the symptom network of reporters had significantly greater density (7.80) than the network of non-reporters (7.05).

Limitations

The data collected in the GLAD Study and the UK Biobank are self-reported with validated or semi-validated questionnaires.

Conclusions

Reported lifetime trauma was associated with stronger interactions between symptoms of depression and anxiety in population volunteers. Differences between reporters and non-reporters may not be observed in individuals with severe depression and/or anxiety due to limited variance in the presentation of disorder.",,doi:https://doi.org/10.1016/j.jadr.2021.100201; doi:https://doi.org/10.1016/j.jadr.2021.100201; html:https://europepmc.org/articles/PMC8689407 -34820659,https://doi.org/10.1016/j.xgen.2021.100028,The Data Use Ontology to streamline responsible access to human biomedical datasets.,"Lawson J, Cabili MN, Kerry G, Boughtwood T, Thorogood A, Alper P, Bowers SR, Boyles RR, Brookes AJ, Brush M, Burdett T, Clissold H, Donnelly S, Dyke SOM, Freeberg MA, Haendel MA, Hata C, Holub P, Jeanson F, Jene A, Kawashima M, Kawashima S, Konopko M, Kyomugisha I, Li H, Linden M, Rodriguez LL, Morita M, Mulder N, Muller J, Nagaie S, Nasir J, Ogishima S, Ota Wang V, Paglione LD, Pandya RN, Parkinson H, Philippakis AA, Prasser F, Rambla J, Reinold K, Rushton GA, Saltzman A, Saunders G, Sofia HJ, Spalding JD, Swertz MA, Tulchinsky I, van Enckevort EJ, Varma S, Voisin C, Yamamoto N, Yamasaki C, Zass L, Guidry Auvil JM, Nyrönen TH, Courtot M.",,Cell genomics,2021,2021-11-10,Y,Standard; Consent; Ontology; Data Access; Fair; Secondary Data Use; Ga4gh; Data Restrictions; Controlled Access; Automated Data Access,,,"Human biomedical datasets that are critical for research and clinical studies to benefit human health also often contain sensitive or potentially identifying information of individual participants. Thus, care must be taken when they are processed and made available to comply with ethical and regulatory frameworks and informed consent data conditions. To enable and streamline data access for these biomedical datasets, the Global Alliance for Genomics and Health (GA4GH) Data Use and Researcher Identities (DURI) work stream developed and approved the Data Use Ontology (DUO) standard. DUO is a hierarchical vocabulary of human and machine-readable data use terms that consistently and unambiguously represents a dataset's allowable data uses. DUO has been implemented by major international stakeholders such as the Broad and Sanger Institutes and is currently used in annotation of over 200,000 datasets worldwide. Using DUO in data management and access facilitates researchers' discovery and access of relevant datasets. DUO annotations increase the FAIRness of datasets and support data linkages using common data use profiles when integrating the data for secondary analyses. DUO is implemented in the Web Ontology Language (OWL) and, to increase community awareness and engagement, hosted in an open, centralized GitHub repository. DUO, together with the GA4GH Passport standard, offers a new, efficient, and streamlined data authorization and access framework that has enabled increased sharing of biomedical datasets worldwide.",,doi:https://doi.org/10.1016/j.xgen.2021.100028; doi:https://doi.org/10.1016/j.xgen.2021.100028; html:https://europepmc.org/articles/PMC8591903; pdf:https://europepmc.org/articles/PMC8591903?pdf=render 33887342,https://doi.org/10.1016/j.ijcard.2021.04.029,Clopidogrel in noncarriers of CYP2C19 loss-of-function alleles versus ticagrelor in elderly patients with acute coronary syndrome: A pre-specified sub analysis from the POPular Genetics and POPular Age trials CYP2C19 alleles in elderly patients.,"Claassens DMF, Gimbel ME, Bergmeijer TO, Vos GJA, Hermanides RS, van der Harst P, Barbato E, Morisco C, Tjon Joe Gin RM, de Vrey EA, Heestermans TACM, Jukema JW, von Birgelen C, Waalewijn RA, Hofma SH, den Hartog FR, Voskuil M, Van't Hof AWJ, Asselbergs FW, Mosterd A, Herrman JR, Dewilde W, Mahmoodi BK, Deneer VHM, Ten Berg JM.",,International journal of cardiology,2021,2021-04-20,N,Genotyping; Myocardial infarction; CYP2C19; Pharmacogenetics; Older; P2y12,,,"

Background

Patients with acute coronary syndrome (ACS) who are carrying CYP2C19 loss-of-function alleles derive less benefit from clopidogrel treatment. Despite this, in elderly patients, clopidogrel might be preferred over more potent P2Y12 inhibitors due to a lower bleeding risk. Whether CYP2C19 genotype-guided antiplatelet treatment in the elderly could be of benefit has not been studied specifically.

Methods

Patients aged 70 years and older with known CYP2C19*2 and *3 genotype were identified from the POPular Genetics and POPular Age trials. Noncarriers of loss-of-function alleles treated with clopidogrel were compared to patients, irrespective of CYP2C19 genotype, treated with ticagrelor and to clopidogrel treated carriers of loss-of-function alleles. We assessed net clinical benefit (all-cause death, myocardial infarction, stroke and Platelet Inhibition and Patient Outcomes (PLATO) major bleeding), atherothrombotic outcomes (cardiovascular death, myocardial infarction, stroke) and bleeding outcomes (PLATO major and minor bleeding).

Results

A total of 991 patients were assessed. There was no significant difference in net clinical benefit (17.2% vs. 15.1%, adjusted hazard ratio (adjHR) 1.05, 95% confidence interval (CI) 0.77-1.44), atherothrombotic outcomes (9.7% vs. 9.2%, adjHR 1.00, 95%CI 0.66-1.50), and bleeding outcomes (17.7% vs. 19.8%, adjHR 0.80, 95%CI 0.62-1.12) between clopidogrel in noncarriers of loss-of-function alleles and ticagrelor respectively.

Conclusion

In ACS patients aged 70 years and older, there was no significant difference in net clinical benefit and atherothrombotic outcomes between noncarriers of a loss-of-function allele treated with clopidogrel and patients treated with ticagrelor. The bleeding rate was numerically; though not statistically significant, lower in patients using clopidogrel.",,pdf:https://pure.rug.nl/ws/files/200111410/1_s2.0_S0167527321006653_main.pdf; doi:https://doi.org/10.1016/j.ijcard.2021.04.029 +34820659,https://doi.org/10.1016/j.xgen.2021.100028,The Data Use Ontology to streamline responsible access to human biomedical datasets.,"Lawson J, Cabili MN, Kerry G, Boughtwood T, Thorogood A, Alper P, Bowers SR, Boyles RR, Brookes AJ, Brush M, Burdett T, Clissold H, Donnelly S, Dyke SOM, Freeberg MA, Haendel MA, Hata C, Holub P, Jeanson F, Jene A, Kawashima M, Kawashima S, Konopko M, Kyomugisha I, Li H, Linden M, Rodriguez LL, Morita M, Mulder N, Muller J, Nagaie S, Nasir J, Ogishima S, Ota Wang V, Paglione LD, Pandya RN, Parkinson H, Philippakis AA, Prasser F, Rambla J, Reinold K, Rushton GA, Saltzman A, Saunders G, Sofia HJ, Spalding JD, Swertz MA, Tulchinsky I, van Enckevort EJ, Varma S, Voisin C, Yamamoto N, Yamasaki C, Zass L, Guidry Auvil JM, Nyrönen TH, Courtot M.",,Cell genomics,2021,2021-11-10,Y,Standard; Consent; Ontology; Data Access; Fair; Secondary Data Use; Ga4gh; Data Restrictions; Controlled Access; Automated Data Access,,,"Human biomedical datasets that are critical for research and clinical studies to benefit human health also often contain sensitive or potentially identifying information of individual participants. Thus, care must be taken when they are processed and made available to comply with ethical and regulatory frameworks and informed consent data conditions. To enable and streamline data access for these biomedical datasets, the Global Alliance for Genomics and Health (GA4GH) Data Use and Researcher Identities (DURI) work stream developed and approved the Data Use Ontology (DUO) standard. DUO is a hierarchical vocabulary of human and machine-readable data use terms that consistently and unambiguously represents a dataset's allowable data uses. DUO has been implemented by major international stakeholders such as the Broad and Sanger Institutes and is currently used in annotation of over 200,000 datasets worldwide. Using DUO in data management and access facilitates researchers' discovery and access of relevant datasets. DUO annotations increase the FAIRness of datasets and support data linkages using common data use profiles when integrating the data for secondary analyses. DUO is implemented in the Web Ontology Language (OWL) and, to increase community awareness and engagement, hosted in an open, centralized GitHub repository. DUO, together with the GA4GH Passport standard, offers a new, efficient, and streamlined data authorization and access framework that has enabled increased sharing of biomedical datasets worldwide.",,doi:https://doi.org/10.1016/j.xgen.2021.100028; doi:https://doi.org/10.1016/j.xgen.2021.100028; html:https://europepmc.org/articles/PMC8591903; pdf:https://europepmc.org/articles/PMC8591903?pdf=render 31730918,https://doi.org/10.1016/j.jclinepi.2019.11.006,Data mining information from electronic health records produced high yield and accuracy for current smoking status.,"Groenhof TKJ, Koers LR, Blasse E, de Groot M, Grobbee DE, Bots ML, Asselbergs FW, Lely AT, Haitjema S, UPOD, UCC-CVRM Study Groups.",,Journal of clinical epidemiology,2020,2019-11-12,N,data mining; Data Quality; Electronic Health Records; Text Mining; Learning Healthcare System; Routine Clinical Data,The Human Phenome,,"

Objectives

Researchers are increasingly using routine clinical data for care evaluations and feedback to patients and clinicians. The quality of these evaluations depends on the quality and completeness of the input data.

Study design and setting

We assessed the performance of an electronic health record (EHR)-based data mining algorithm, using the example of the smoking status in a cardiovascular population. As a reference standard, we used the questionnaire from the Utrecht Cardiovascular Cohort (UCC). To assess diagnostic accuracy, we calculated sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV).

Results

We analyzed 1,661 patients included in the UCC to January 18, 2019. Of those, 14% (n = 238) had missing information on smoking status in the UCC questionnaire. Data mining provided information on smoking status in 99% of the 1,661 participants. Diagnostic accuracy for current smoking was sensitivity 88%, specificity 92%, NPV 98%, and PPV 63%. From false positives, 85% reported they had quit smoking at the time of the UCC.

Conclusion

Data mining showed great potential in retrieving information on smoking (a near complete yield). Its diagnostic performance is good for negative smoking statuses. The implications of misclassification with data mining are dependent on the application of the data.",Utilises data mining and routine data to identify a patients smoking status. Does not account for long term smoking behaviour and is limited by the smaller size the dataset.,pdf:http://www.jclinepi.com/article/S0895435619304846/pdf; doi:https://doi.org/10.1016/j.jclinepi.2019.11.006 34426706,https://doi.org/10.1038/s41591-021-01441-3,"Mitochondrial DNA variants modulate N-formylmethionine, proteostasis and risk of late-onset human diseases.","Cai N, Gomez-Duran A, Yonova-Doing E, Kundu K, Burgess AI, Golder ZJ, Calabrese C, Bonder MJ, Camacho M, Lawson RA, Li L, Williams-Gray CH, ICICLE-PD Study Group, Di Angelantonio E, Roberts DJ, Watkins NA, Ouwehand WH, Butterworth AS, Stewart ID, Pietzner M, Wareham NJ, Langenberg C, Danesh J, Walter K, Rothwell PM, Howson JMM, Stegle O, Chinnery PF, Soranzo N.",,Nature medicine,2021,2021-08-23,N,,,,"Mitochondrial DNA (mtDNA) variants influence the risk of late-onset human diseases, but the reasons for this are poorly understood. Undertaking a hypothesis-free analysis of 5,689 blood-derived biomarkers with mtDNA variants in 16,220 healthy donors, here we show that variants defining mtDNA haplogroups Uk and H4 modulate the level of circulating N-formylmethionine (fMet), which initiates mitochondrial protein translation. In human cytoplasmic hybrid (cybrid) lines, fMet modulated both mitochondrial and cytosolic proteins on multiple levels, through transcription, post-translational modification and proteolysis by an N-degron pathway, abolishing known differences between mtDNA haplogroups. In a further 11,966 individuals, fMet levels contributed to all-cause mortality and the disease risk of several common cardiovascular disorders. Together, these findings indicate that fMet plays a key role in common age-related disease through pleiotropic effects on cell proteostasis.",,pdf:https://push-zb.helmholtz-muenchen.de/deliver.php?id=34427; doi:https://doi.org/10.1038/s41591-021-01441-3 31504546,https://doi.org/10.1093/ije/dyz174,"Cohort Profile: East London Genes & Health (ELGH), a community-based population genomics and health study in British Bangladeshi and British Pakistani people.","Finer S, Martin HC, Khan A, Hunt KA, MacLaughlin B, Ahmed Z, Ashcroft R, Durham C, MacArthur DG, McCarthy MI, Robson J, Trivedi B, Griffiths C, Wright J, Trembath RC, van Heel DA.",,International journal of epidemiology,2020,2020-02-01,Y,,,,,,pdf:https://academic.oup.com/ije/article-pdf/49/1/20/32995529/dyz174.pdf; doi:https://doi.org/10.1093/ije/dyz174; html:https://europepmc.org/articles/PMC7124496; pdf:https://europepmc.org/articles/PMC7124496?pdf=render @@ -2506,13 +2506,13 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 29899974,https://doi.org/10.12688/f1000research.13830.2,Knowledge discovery for Deep Phenotyping serious mental illness from Electronic Mental Health records.,"Jackson R, Patel R, Velupillai S, Gkotsis G, Hoyle D, Stewart R.",,F1000Research,2018,2018-02-21,Y,Schizophrenia; Serious Mental Illness; Electronic Health Records; Natural Language Processing; Word2vec,,,"Background: Deep Phenotyping is the precise and comprehensive analysis of phenotypic features in which the individual components of the phenotype are observed and described. In UK mental health clinical practice, most clinically relevant information is recorded as free text in the Electronic Health Record, and offers a granularity of information beyond what is expressed in most medical knowledge bases. The SNOMED CT nomenclature potentially offers the means to model such information at scale, yet given a sufficiently large body of clinical text collected over many years, it is difficult to identify the language that clinicians favour to express concepts. Methods: By utilising a large corpus of healthcare data, we sought to make use of semantic modelling and clustering techniques to represent the relationship between the clinical vocabulary of internationally recognised SMI symptoms and the preferred language used by clinicians within a care setting. We explore how such models can be used for discovering novel vocabulary relevant to the task of phenotyping Serious Mental Illness (SMI) with only a small amount of prior knowledge.  Results: 20 403 terms were derived and curated via a two stage methodology. The list was reduced to 557 putative concepts based on eliminating redundant information content. These were then organised into 9 distinct categories pertaining to different aspects of psychiatric assessment. 235 concepts were found to be expressions of putative clinical significance. Of these, 53 were identified having novel synonymy with existing SNOMED CT concepts. 106 had no mapping to SNOMED CT. Conclusions: We demonstrate a scalable approach to discovering new concepts of SMI symptomatology based on real-world clinical observation. Such approaches may offer the opportunity to consider broader manifestations of SMI symptomatology than is typically assessed via current diagnostic frameworks, and create the potential for enhancing nomenclatures such as SNOMED CT based on real-world expressions.",,pdf:https://f1000research.com/articles/7-210/v2/pdf; doi:https://doi.org/10.12688/f1000research.13830.2; html:https://europepmc.org/articles/PMC5968362; pdf:https://europepmc.org/articles/PMC5968362?pdf=render 34662348,https://doi.org/10.1371/journal.ppat.1009992,Genome-wide association studies reveal the role of polymorphisms affecting factor H binding protein expression in host invasion by Neisseria meningitidis.,"Earle SG, Lobanovska M, Lavender H, Tang C, Exley RM, Ramos-Sevillano E, Browning DF, Kostiou V, Harrison OB, Bratcher HB, Varani G, Tang CM, Wilson DJ, Maiden MCJ.",,PLoS pathogens,2021,2021-10-18,Y,,,,"Many invasive bacterial diseases are caused by organisms that are ordinarily harmless components of the human microbiome. Effective interventions against these microbes require an understanding of the processes whereby symbiotic or commensal relationships transition into pathology. Here, we describe bacterial genome-wide association studies (GWAS) of Neisseria meningitidis, a common commensal of the human respiratory tract that is nevertheless a leading cause of meningitis and sepsis. An initial GWAS discovered bacterial genetic variants, including single nucleotide polymorphisms (SNPs), associated with invasive meningococcal disease (IMD) versus carriage in several loci across the meningococcal genome, encoding antigens and other extracellular components, confirming the polygenic nature of the invasive phenotype. In particular, there was a significant peak of association around the fHbp locus, encoding factor H binding protein (fHbp), which promotes bacterial immune evasion of human complement by recruiting complement factor H (CFH) to the meningococcal surface. The association around fHbp with IMD was confirmed by a validation GWAS, and we found that the SNPs identified in the validation affected the 5' region of fHbp mRNA, altering secondary RNA structures, thereby increasing fHbp expression and enhancing bacterial escape from complement-mediated killing. This finding is consistent with the known link between complement deficiencies and CFH variation with human susceptibility to IMD. These observations demonstrate the importance of human and bacterial genetic variation across the fHbp:CFH interface in determining IMD susceptibility, the transition from carriage to disease.",,pdf:https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1009992&type=printable; doi:https://doi.org/10.1371/journal.ppat.1009992; html:https://europepmc.org/articles/PMC8553145; pdf:https://europepmc.org/articles/PMC8553145?pdf=render 35048991,https://doi.org/10.1093/jnci/djac011,Associations Between Glycemic Traits and Colorectal Cancer: A Mendelian Randomization Analysis.,"Murphy N, Song M, Papadimitriou N, Carreras-Torres R, Langenberg C, Martin RM, Tsilidis KK, Barroso I, Chen J, Frayling TM, Bull CJ, Vincent EE, Cotterchio M, Gruber SB, Pai RK, Newcomb PA, Perez-Cornago A, van Duijnhoven FJB, Van Guelpen B, Vodicka P, Wolk A, Wu AH, Peters U, Chan AT, Gunter MJ.",,Journal of the National Cancer Institute,2022,2022-05-01,Y,,,,"

Background

Glycemic traits-such as hyperinsulinemia, hyperglycemia, and type 2 diabetes-have been associated with higher colorectal cancer risk in observational studies; however, causality of these associations is uncertain. We used Mendelian randomization (MR) to estimate the causal effects of fasting insulin, 2-hour glucose, fasting glucose, glycated hemoglobin (HbA1c), and type 2 diabetes with colorectal cancer.

Methods

Genome-wide association study summary data were used to identify genetic variants associated with circulating levels of fasting insulin (n = 34), 2-hour glucose (n = 13), fasting glucose (n = 70), HbA1c (n = 221), and type 2 diabetes (n = 268). Using 2-sample MR, we examined these variants in relation to colorectal cancer risk (48 214 case patient and 64 159 control patients).

Results

In inverse-variance models, higher fasting insulin levels increased colorectal cancer risk (odds ratio [OR] per 1-SD = 1.65, 95% confidence interval [CI] = 1.15 to 2.36). We found no evidence of any effect of 2-hour glucose (OR per 1-SD = 1.02, 95% CI = 0.86 to 1.21) or fasting glucose (OR per 1-SD = 1.04, 95% CI = 0.88 to 1.23) concentrations on colorectal cancer risk. Genetic liability to type 2 diabetes (OR per 1-unit increase in log odds = 1.04, 95% CI = 1.01 to 1.07) and higher HbA1c levels (OR per 1-SD = 1.09, 95% CI = 1.00 to 1.19) increased colorectal cancer risk, although these findings may have been biased by pleiotropy. Higher HbA1c concentrations increased rectal cancer risk in men (OR per 1-SD = 1.21, 95% CI = 1.05 to 1.40), but not in women.

Conclusions

Our results support a causal effect of higher fasting insulin, but not glucose traits or type 2 diabetes, on increased colorectal cancer risk. This suggests that pharmacological or lifestyle interventions that lower circulating insulin levels may be beneficial in preventing colorectal tumorigenesis.",,pdf:https://academic.oup.com/jnci/article-pdf/114/5/740/43623241/djac011.pdf; doi:https://doi.org/10.1093/jnci/djac011; html:https://europepmc.org/articles/PMC9086764; pdf:https://europepmc.org/articles/PMC9086764?pdf=render -36240095,https://doi.org/10.1212/wnl.0000000000201006,Contribution of Common Genetic Variants to Risk of Early-Onset Ischemic Stroke.,"Jaworek T, Xu H, Gaynor BJ, Cole JW, Rannikmae K, Stanne TM, Tomppo L, Abedi V, Amouyel P, Armstrong ND, Attia J, Bell S, Benavente OR, Boncoraglio GB, Butterworth A, Cervical Artery Dissections and Ischemic Stroke Patients (CADSIP) Consortium, Carcel-Marquez J, Chen Z, Chong M, Cruchaga C, Cushman M, Danesh J, Debette S, Duggan DJ, Durda JP, Engstrom G, Enzinger C, Faul JD, Fecteau NS, Fernandez-Cadenas I, Gieger C, Giese AK, Grewal RP, Grittner U, Havulinna AS, Heitsch L, Hochberg MC, Holliday E, Hu J, Hu J, Ilinca A, INVENT Consortium, Irvin MR, Jackson RD, Jacob MA, Rabionet R, Jimenez-Conde J, Johnson JA, Kamatani Y, Kardia SLR, Koido M, Kubo M, Lange L, Lee JM, Lemmens R, Levi CR, Li J, Li L, Lin K, Lopez H, Luke S, Maguire J, McArdle PF, McDonough CW, Meschia JF, Metso T, Müller-Nurasyid M, O'Connor TD, O'Donnell M, Peddareddygari LR, Pera J, Perry JA, Peters A, Putaala J, Ray D, Rexrode K, Ribases M, Rosand J, Rothwell PM, Rundek T, Ryan KA, Sacco RL, Salomaa V, Sanchez-Mora C, Schmidt R, Sharma P, Slowik A, Smith JA, Smith NL, Wassertheil-Smoller S, Söderholm M, Stine OC, Strbian D, Sudlow CLM, Tatlisumak T, Terao C, Thijs V, Torres-Aguila NP, Trégouët DA, Tuladhar AM, Veldink JH, Walters RG, Weir DR, Woo D, Worrall BB, Hong CC, Ross OA, Zand R, Leeuw FE, Lindgren AG, Pare G, Anderson CD, Markus HS, Jern C, Malik R, Dichgans M, Mitchell BD, Kittner SJ, Early Onset Stroke Genetics Consortium of the International Stroke Genetics Consortium (ISGC).",,Neurology,2022,2022-10-17,Y,,,,"

Background and objectives

Current genome-wide association studies of ischemic stroke have focused primarily on late-onset disease. As a complement to these studies, we sought to identify the contribution of common genetic variants to risk of early-onset ischemic stroke.

Methods

We performed a meta-analysis of genome-wide association studies of early-onset stroke (EOS), ages 18-59 years, using individual-level data or summary statistics in 16,730 cases and 599,237 nonstroke controls obtained across 48 different studies. We further compared effect sizes at associated loci between EOS and late-onset stroke (LOS) and compared polygenic risk scores (PRS) for venous thromboembolism (VTE) between EOS and LOS.

Results

We observed genome-wide significant associations of EOS with 2 variants in ABO, a known stroke locus. These variants tag blood subgroups O1 and A1, and the effect sizes of both variants were significantly larger in EOS compared with LOS. The odds ratio (OR) for rs529565, tagging O1, was 0.88 (95% confidence interval [CI]: 0.85-0.91) in EOS vs 0.96 (95% CI: 0.92-1.00) in LOS, and the OR for rs635634, tagging A1, was 1.16 (1.11-1.21) for EOS vs 1.05 (0.99-1.11) in LOS; p-values for interaction = 0.001 and 0.005, respectively. Using PRSs, we observed that greater genetic risk for VTE, another prothrombotic condition, was more strongly associated with EOS compared with LOS (p = 0.008).

Discussion

The ABO locus, genetically predicted blood group A, and higher genetic propensity for venous thrombosis are more strongly associated with EOS than with LOS, supporting a stronger role of prothrombotic factors in EOS.",,pdf:https://n.neurology.org/content/neurology/99/16/e1738.full.pdf; doi:https://doi.org/10.1212/WNL.0000000000201006; html:https://europepmc.org/articles/PMC9620803; pdf:https://europepmc.org/articles/PMC9620803?pdf=render 31488387,https://doi.org/10.1016/s2214-109x(19)30318-3,World Health Organization cardiovascular disease risk charts: revised models to estimate risk in 21 global regions.,WHO CVD Risk Chart Working Group.,,The Lancet. Global health,2019,2019-09-02,Y,,,,"

Background

To help adapt cardiovascular disease risk prediction approaches to low-income and middle-income countries, WHO has convened an effort to develop, evaluate, and illustrate revised risk models. Here, we report the derivation, validation, and illustration of the revised WHO cardiovascular disease risk prediction charts that have been adapted to the circumstances of 21 global regions.

Methods

In this model revision initiative, we derived 10-year risk prediction models for fatal and non-fatal cardiovascular disease (ie, myocardial infarction and stroke) using individual participant data from the Emerging Risk Factors Collaboration. Models included information on age, smoking status, systolic blood pressure, history of diabetes, and total cholesterol. For derivation, we included participants aged 40-80 years without a known baseline history of cardiovascular disease, who were followed up until the first myocardial infarction, fatal coronary heart disease, or stroke event. We recalibrated models using age-specific and sex-specific incidences and risk factor values available from 21 global regions. For external validation, we analysed individual participant data from studies distinct from those used in model derivation. We illustrated models by analysing data on a further 123 743 individuals from surveys in 79 countries collected with the WHO STEPwise Approach to Surveillance.

Findings

Our risk model derivation involved 376 177 individuals from 85 cohorts, and 19 333 incident cardiovascular events recorded during 10 years of follow-up. The derived risk prediction models discriminated well in external validation cohorts (19 cohorts, 1 096 061 individuals, 25 950 cardiovascular disease events), with Harrell's C indices ranging from 0·685 (95% CI 0·629-0·741) to 0·833 (0·783-0·882). For a given risk factor profile, we found substantial variation across global regions in the estimated 10-year predicted risk. For example, estimated cardiovascular disease risk for a 60-year-old male smoker without diabetes and with systolic blood pressure of 140 mm Hg and total cholesterol of 5 mmol/L ranged from 11% in Andean Latin America to 30% in central Asia. When applied to data from 79 countries (mostly low-income and middle-income countries), the proportion of individuals aged 40-64 years estimated to be at greater than 20% risk ranged from less than 1% in Uganda to more than 16% in Egypt.

Interpretation

We have derived, calibrated, and validated new WHO risk prediction models to estimate cardiovascular disease risk in 21 Global Burden of Disease regions. The widespread use of these models could enhance the accuracy, practicability, and sustainability of efforts to reduce the burden of cardiovascular disease worldwide.

Funding

World Health Organization, British Heart Foundation (BHF), BHF Cambridge Centre for Research Excellence, UK Medical Research Council, and National Institute for Health Research.",,pdf:http://www.thelancet.com/article/S2214109X19303183/pdf; doi:https://doi.org/10.1016/S2214-109X(19)30318-3; html:https://europepmc.org/articles/PMC7025029 31477934,https://doi.org/10.1038/s41588-019-0483-y,Inferring whole-genome histories in large population datasets.,"Kelleher J, Wong Y, Wohns AW, Fadil C, Albers PK, McVean G.",,Nature genetics,2019,2019-09-02,Y,,The Human Phenome,,"Inferring the full genealogical history of a set of DNA sequences is a core problem in evolutionary biology, because this history encodes information about the events and forces that have influenced a species. However, current methods are limited, and the most accurate techniques are able to process no more than a hundred samples. As datasets that consist of millions of genomes are now being collected, there is a need for scalable and efficient inference methods to fully utilize these resources. Here we introduce an algorithm that is able to not only infer whole-genome histories with comparable accuracy to the state-of-the-art but also process four orders of magnitude more sequences. The approach also provides an 'evolutionary encoding' of the data, enabling efficient calculation of relevant statistics. We apply the method to human data from the 1000 Genomes Project, Simons Genome Diversity Project and UK Biobank, showing that the inferred genealogies are rich in biological signal and efficient to process.",,pdf:https://europepmc.org/articles/pmc6726478?pdf=render; doi:https://doi.org/10.1038/s41588-019-0483-y; html:https://europepmc.org/articles/PMC6726478; pdf:https://europepmc.org/articles/PMC6726478?pdf=render +36240095,https://doi.org/10.1212/wnl.0000000000201006,Contribution of Common Genetic Variants to Risk of Early-Onset Ischemic Stroke.,"Jaworek T, Xu H, Gaynor BJ, Cole JW, Rannikmae K, Stanne TM, Tomppo L, Abedi V, Amouyel P, Armstrong ND, Attia J, Bell S, Benavente OR, Boncoraglio GB, Butterworth A, Cervical Artery Dissections and Ischemic Stroke Patients (CADSIP) Consortium, Carcel-Marquez J, Chen Z, Chong M, Cruchaga C, Cushman M, Danesh J, Debette S, Duggan DJ, Durda JP, Engstrom G, Enzinger C, Faul JD, Fecteau NS, Fernandez-Cadenas I, Gieger C, Giese AK, Grewal RP, Grittner U, Havulinna AS, Heitsch L, Hochberg MC, Holliday E, Hu J, Hu J, Ilinca A, INVENT Consortium, Irvin MR, Jackson RD, Jacob MA, Rabionet R, Jimenez-Conde J, Johnson JA, Kamatani Y, Kardia SLR, Koido M, Kubo M, Lange L, Lee JM, Lemmens R, Levi CR, Li J, Li L, Lin K, Lopez H, Luke S, Maguire J, McArdle PF, McDonough CW, Meschia JF, Metso T, Müller-Nurasyid M, O'Connor TD, O'Donnell M, Peddareddygari LR, Pera J, Perry JA, Peters A, Putaala J, Ray D, Rexrode K, Ribases M, Rosand J, Rothwell PM, Rundek T, Ryan KA, Sacco RL, Salomaa V, Sanchez-Mora C, Schmidt R, Sharma P, Slowik A, Smith JA, Smith NL, Wassertheil-Smoller S, Söderholm M, Stine OC, Strbian D, Sudlow CLM, Tatlisumak T, Terao C, Thijs V, Torres-Aguila NP, Trégouët DA, Tuladhar AM, Veldink JH, Walters RG, Weir DR, Woo D, Worrall BB, Hong CC, Ross OA, Zand R, Leeuw FE, Lindgren AG, Pare G, Anderson CD, Markus HS, Jern C, Malik R, Dichgans M, Mitchell BD, Kittner SJ, Early Onset Stroke Genetics Consortium of the International Stroke Genetics Consortium (ISGC).",,Neurology,2022,2022-10-17,Y,,,,"

Background and objectives

Current genome-wide association studies of ischemic stroke have focused primarily on late-onset disease. As a complement to these studies, we sought to identify the contribution of common genetic variants to risk of early-onset ischemic stroke.

Methods

We performed a meta-analysis of genome-wide association studies of early-onset stroke (EOS), ages 18-59 years, using individual-level data or summary statistics in 16,730 cases and 599,237 nonstroke controls obtained across 48 different studies. We further compared effect sizes at associated loci between EOS and late-onset stroke (LOS) and compared polygenic risk scores (PRS) for venous thromboembolism (VTE) between EOS and LOS.

Results

We observed genome-wide significant associations of EOS with 2 variants in ABO, a known stroke locus. These variants tag blood subgroups O1 and A1, and the effect sizes of both variants were significantly larger in EOS compared with LOS. The odds ratio (OR) for rs529565, tagging O1, was 0.88 (95% confidence interval [CI]: 0.85-0.91) in EOS vs 0.96 (95% CI: 0.92-1.00) in LOS, and the OR for rs635634, tagging A1, was 1.16 (1.11-1.21) for EOS vs 1.05 (0.99-1.11) in LOS; p-values for interaction = 0.001 and 0.005, respectively. Using PRSs, we observed that greater genetic risk for VTE, another prothrombotic condition, was more strongly associated with EOS compared with LOS (p = 0.008).

Discussion

The ABO locus, genetically predicted blood group A, and higher genetic propensity for venous thrombosis are more strongly associated with EOS than with LOS, supporting a stronger role of prothrombotic factors in EOS.",,pdf:https://n.neurology.org/content/neurology/99/16/e1738.full.pdf; doi:https://doi.org/10.1212/WNL.0000000000201006; html:https://europepmc.org/articles/PMC9620803; pdf:https://europepmc.org/articles/PMC9620803?pdf=render 33444330,https://doi.org/10.1371/journal.pmed.1003498,Polygenic risk scores in cardiovascular risk prediction: A cohort study and modelling analyses.,"Sun L, Pennells L, Kaptoge S, Nelson CP, Ritchie SC, Abraham G, Arnold M, Bell S, Bolton T, Burgess S, Dudbridge F, Guo Q, Sofianopoulou E, Stevens D, Thompson JR, Butterworth AS, Wood A, Danesh J, Samani NJ, Inouye M, Di Angelantonio E.",,PLoS medicine,2021,2021-01-14,Y,,,,"

Background

Polygenic risk scores (PRSs) can stratify populations into cardiovascular disease (CVD) risk groups. We aimed to quantify the potential advantage of adding information on PRSs to conventional risk factors in the primary prevention of CVD.

Methods and findings

Using data from UK Biobank on 306,654 individuals without a history of CVD and not on lipid-lowering treatments (mean age [SD]: 56.0 [8.0] years; females: 57%; median follow-up: 8.1 years), we calculated measures of risk discrimination and reclassification upon addition of PRSs to risk factors in a conventional risk prediction model (i.e., age, sex, systolic blood pressure, smoking status, history of diabetes, and total and high-density lipoprotein cholesterol). We then modelled the implications of initiating guideline-recommended statin therapy in a primary care setting using incidence rates from 2.1 million individuals from the Clinical Practice Research Datalink. The C-index, a measure of risk discrimination, was 0.710 (95% CI 0.703-0.717) for a CVD prediction model containing conventional risk predictors alone. Addition of information on PRSs increased the C-index by 0.012 (95% CI 0.009-0.015), and resulted in continuous net reclassification improvements of about 10% and 12% in cases and non-cases, respectively. If a PRS were assessed in the entire UK primary care population aged 40-75 years, assuming that statin therapy would be initiated in accordance with the UK National Institute for Health and Care Excellence guidelines (i.e., for persons with a predicted risk of ≥10% and for those with certain other risk factors, such as diabetes, irrespective of their 10-year predicted risk), then it could help prevent 1 additional CVD event for approximately every 5,750 individuals screened. By contrast, targeted assessment only among people at intermediate (i.e., 5% to <10%) 10-year CVD risk could help prevent 1 additional CVD event for approximately every 340 individuals screened. Such a targeted strategy could help prevent 7% more CVD events than conventional risk prediction alone. Potential gains afforded by assessment of PRSs on top of conventional risk factors would be about 1.5-fold greater than those provided by assessment of C-reactive protein, a plasma biomarker included in some risk prediction guidelines. Potential limitations of this study include its restriction to European ancestry participants and a lack of health economic evaluation.

Conclusions

Our results suggest that addition of PRSs to conventional risk factors can modestly enhance prediction of first-onset CVD and could translate into population health benefits if used at scale.",,pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1003498&type=printable; doi:https://doi.org/10.1371/journal.pmed.1003498; html:https://europepmc.org/articles/PMC7808664; pdf:https://europepmc.org/articles/PMC7808664?pdf=render 32979922,https://doi.org/10.1186/s12933-020-01130-4,Diabetes as a risk factor for incident peripheral arterial disease in women compared to men: a systematic review and meta-analysis.,"Chase-Vilchez AZ, Chan IHY, Peters SAE, Woodward M.",,Cardiovascular diabetology,2020,2020-09-26,Y,Sex difference; Diabetes; Cardiovascular disease; Peripheral Arterial Disease; Peripheral Vascular Disease,,,"

Aims/hypothesis

Previous meta-analyses have suggested that diabetes confers a greater excess risk of coronary heart disease, stroke, vascular dementia, and heart failure in women compared to men. While the underlying mechanism that explains such greater excess risk is unknown, in the current meta-analysis we hypothesized that we would find a similar sex difference in the relationship between diabetes and peripheral arterial disease (PAD).

Methods

PubMed MEDLINE, the Cochrane Database of Systematic Reviews, and Embase were systematically searched for prospective population-based cohort studies, with no restriction on publication date, language, or country. We included studies that reported the relative risk (RR), and its variability, for incident PAD associated with diabetes in both sexes. We excluded studies that did not adjust at least for age, and in which participants had pre-existing PAD. In cases where sex-specific results were not reported, study authors were contacted. Random-effects meta-analyses with inverse variance weighting were used to obtain summary sex-specific RRs and the women: men ratio of RRs for PAD. The Newcastle-Ottawa scale was used to assess study quality.

Results

Data from seven cohorts, totalling 2071,260 participants (49.8% women), were included. The relative risk for incident PAD associated with diabetes compared with no diabetes was 1.96 (95% CI 1.29-2.63) in women and 1.84 (95% CI 1.29-2.86) in men, after adjusting for potential confounders. The multiple-adjusted RR ratio was 1.05 (95% CI 0.90-1.22), with virtually no heterogeneity between studies (I2 = 0%). All studies scored 6-8, on the Newcastle-Ottawa scale of 0-9, indicating good quality. Eleven of the 12 studies that met review inclusion criteria did not report sex-specific relative risk, and these data were collected through direct correspondence with the study authors.

Conclusion/interpretation

Consistent with other studies, we found evidence that diabetes is an independent risk factor for PAD. However, in contrast to similar studies of other types of cardiovascular disease, we did not find evidence that diabetes confers a greater excess risk in women compared to men for PAD. More research is needed to explain this sex differential between PAD and other forms of CVD, in the sequelae of diabetes. In addition, we found that very few studies reported the sex-specific relative risk for the association between diabetes and PAD, adding to existing evidence for the need for improved reporting of sex-disaggregated results in cardiovascular disease research.",,pdf:https://cardiab.biomedcentral.com/track/pdf/10.1186/s12933-020-01130-4; doi:https://doi.org/10.1186/s12933-020-01130-4; html:https://europepmc.org/articles/PMC7520021; pdf:https://europepmc.org/articles/PMC7520021?pdf=render -38428419,https://doi.org/10.1016/j.xgen.2024.100511,Genomic evolution shapes prostate cancer disease type.,"Woodcock DJ, Sahli A, Teslo R, Bhandari V, Gruber AJ, Ziubroniewicz A, Gundem G, Xu Y, Butler A, Anokian E, Pope BJ, Jung CH, Tarabichi M, Dentro SC, Farmery JHR, CRUK ICGC Prostate Group, Van Loo P, Warren AY, Gnanapragasam V, Hamdy FC, Bova GS, Foster CS, Neal DE, Lu YJ, Kote-Jarai Z, Fraser M, Bristow RG, Boutros PC, Costello AJ, Corcoran NM, Hovens CM, Massie CE, Lynch AG, Brewer DS, Eeles RA, Cooper CS, Wedge DC.",,Cell genomics,2024,2024-02-29,Y,prostate cancer; Ordering; Cancer Evolution; Ar Binding; Evotype Model; Evotypes,,,"The development of cancer is an evolutionary process involving the sequential acquisition of genetic alterations that disrupt normal biological processes, enabling tumor cells to rapidly proliferate and eventually invade and metastasize to other tissues. We investigated the genomic evolution of prostate cancer through the application of three separate classification methods, each designed to investigate a different aspect of tumor evolution. Integrating the results revealed the existence of two distinct types of prostate cancer that arise from divergent evolutionary trajectories, designated as the Canonical and Alternative evolutionary disease types. We therefore propose the evotype model for prostate cancer evolution wherein Alternative-evotype tumors diverge from those of the Canonical-evotype through the stochastic accumulation of genetic alterations associated with disruptions to androgen receptor DNA binding. Our model unifies many previous molecular observations, providing a powerful new framework to investigate prostate cancer disease progression.",,doi:https://doi.org/10.1016/j.xgen.2024.100511; html:https://europepmc.org/articles/PMC10943594; pdf:https://europepmc.org/articles/PMC10943594?pdf=render 33442528,https://doi.org/10.1140/epjds/s13688-020-00257-4,Privacy preserving data visualizations.,"Avraam D, Wilson R, Butters O, Burton T, Nicolaides C, Jones E, Boyd A, Burton P.",,EPJ data science,2021,2021-01-07,Y,Privacy Protection; Anonymization; Sensitive Data; Data Visualizations; Disclosure Control,,,"Data visualizations are a valuable tool used during both statistical analysis and the interpretation of results as they graphically reveal useful information about the structure, properties and relationships between variables, which may otherwise be concealed in tabulated data. In disciplines like medicine and the social sciences, where collected data include sensitive information about study participants, the sharing and publication of individual-level records is controlled by data protection laws and ethico-legal norms. Thus, as data visualizations - such as graphs and plots - may be linked to other released information and used to identify study participants and their personal attributes, their creation is often prohibited by the terms of data use. These restrictions are enforced to reduce the risk of breaching data subject confidentiality, however they limit analysts from displaying useful descriptive plots for their research features and findings. Here we propose the use of anonymization techniques to generate privacy-preserving visualizations that retain the statistical properties of the underlying data while still adhering to strict data disclosure rules. We demonstrate the use of (i) the well-known k-anonymization process which preserves privacy by reducing the granularity of the data using suppression and generalization, (ii) a novel deterministic approach that replaces individual-level observations with the centroids of each k nearest neighbours, and (iii) a probabilistic procedure that perturbs individual attributes with the addition of random stochastic noise. We apply the proposed methods to generate privacy-preserving data visualizations for exploratory data analysis and inferential regression plot diagnostics, and we discuss their strengths and limitations.",,pdf:https://epjdatascience.springeropen.com/track/pdf/10.1140/epjds/s13688-020-00257-4; doi:https://doi.org/10.1140/epjds/s13688-020-00257-4; html:https://europepmc.org/articles/PMC7790778; pdf:https://europepmc.org/articles/PMC7790778?pdf=render +38428419,https://doi.org/10.1016/j.xgen.2024.100511,Genomic evolution shapes prostate cancer disease type.,"Woodcock DJ, Sahli A, Teslo R, Bhandari V, Gruber AJ, Ziubroniewicz A, Gundem G, Xu Y, Butler A, Anokian E, Pope BJ, Jung CH, Tarabichi M, Dentro SC, Farmery JHR, CRUK ICGC Prostate Group, Van Loo P, Warren AY, Gnanapragasam V, Hamdy FC, Bova GS, Foster CS, Neal DE, Lu YJ, Kote-Jarai Z, Fraser M, Bristow RG, Boutros PC, Costello AJ, Corcoran NM, Hovens CM, Massie CE, Lynch AG, Brewer DS, Eeles RA, Cooper CS, Wedge DC.",,Cell genomics,2024,2024-02-29,Y,prostate cancer; Ordering; Cancer Evolution; Ar Binding; Evotype Model; Evotypes,,,"The development of cancer is an evolutionary process involving the sequential acquisition of genetic alterations that disrupt normal biological processes, enabling tumor cells to rapidly proliferate and eventually invade and metastasize to other tissues. We investigated the genomic evolution of prostate cancer through the application of three separate classification methods, each designed to investigate a different aspect of tumor evolution. Integrating the results revealed the existence of two distinct types of prostate cancer that arise from divergent evolutionary trajectories, designated as the Canonical and Alternative evolutionary disease types. We therefore propose the evotype model for prostate cancer evolution wherein Alternative-evotype tumors diverge from those of the Canonical-evotype through the stochastic accumulation of genetic alterations associated with disruptions to androgen receptor DNA binding. Our model unifies many previous molecular observations, providing a powerful new framework to investigate prostate cancer disease progression.",,doi:https://doi.org/10.1016/j.xgen.2024.100511; html:https://europepmc.org/articles/PMC10943594; pdf:https://europepmc.org/articles/PMC10943594?pdf=render 32956399,https://doi.org/10.1371/journal.pmed.1003336,Antibiotic prescribing for lower UTI in elderly patients in primary care and risk of bloodstream infection: A cohort study using electronic health records in England.,"Shallcross L, Rockenschaub P, Blackburn R, Nazareth I, Freemantle N, Hayward A.",,PLoS medicine,2020,2020-09-21,Y,,,,"

Background

Research has questioned the safety of delaying or withholding antibiotics for suspected urinary tract infection (UTI) in older patients. We evaluated the association between antibiotic treatment for lower UTI and risk of bloodstream infection (BSI) in adults aged ≥65 years in primary care.

Methods and findings

We analyzed primary care records from patients aged ≥65 years in England with community-onset UTI using the Clinical Practice Research Datalink (2007-2015) linked to Hospital Episode Statistics and census data. The primary outcome was BSI within 60 days, comparing patients treated immediately with antibiotics and those not treated immediately. Crude and adjusted associations between exposure and outcome were estimated using generalized estimating equations. A total of 147,334 patients were included representing 280,462 episodes of lower UTI. BSI occurred in 0.4% (1,025/244,963) of UTI episodes with immediate antibiotics versus 0.6% (228/35,499) of episodes without immediate antibiotics. After adjusting for patient demographics, year of consultation, comorbidities, smoking status, recent hospitalizations, recent accident and emergency (A&E) attendances, recent antibiotic prescribing, and home visits, the odds of BSI were equivalent in patients who were not treated with antibiotics immediately and those who were treated on the date of their UTI consultation (adjusted odds ratio [aOR] 1.13, 95% CI 0.97-1.32, p-value = 0.105). Delaying or withholding antibiotics was associated with increased odds of death in the subsequent 60 days (aOR 1.17, 95% CI 1.09-1.26, p-value < 0.001), but there was limited evidence that increased deaths were attributable to urinary-source BSI. Limitations include overlap between the categories of immediate and delayed antibiotic prescribing, residual confounding underlying differences between patients who were/were not treated with antibiotics, and lack of microbiological diagnosis for BSI.

Conclusions

In this study, we observed that delaying or withholding antibiotics in older adults with suspected UTI did not increase patients' risk of BSI, in contrast with a previous study that analyzed the same dataset, but mortality was increased. Our findings highlight uncertainty around the risks of delaying or withholding antibiotic treatment, which is exacerbated by systematic differences between patients who were and were not treated immediately with antibiotics. Overall, our findings emphasize the need for improved diagnostic/risk prediction strategies to guide antibiotic prescribing for suspected UTI in older adults.",,pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1003336&type=printable; doi:https://doi.org/10.1371/journal.pmed.1003336; html:https://europepmc.org/articles/PMC7505443; pdf:https://europepmc.org/articles/PMC7505443?pdf=render 33385551,https://doi.org/10.1016/j.neuroimage.2020.117689,Deep learning-based unlearning of dataset bias for MRI harmonisation and confound removal.,"Dinsdale NK, Jenkinson M, Namburete AIL.",,NeuroImage,2021,2020-12-30,Y,MRI; Harmonization; Joint Domain Adaptation,,,"Increasingly large MRI neuroimaging datasets are becoming available, including many highly multi-site multi-scanner datasets. Combining the data from the different scanners is vital for increased statistical power; however, this leads to an increase in variance due to nonbiological factors such as the differences in acquisition protocols and hardware, which can mask signals of interest. We propose a deep learning based training scheme, inspired by domain adaptation techniques, which uses an iterative update approach to aim to create scanner-invariant features while simultaneously maintaining performance on the main task of interest, thus reducing the influence of scanner on network predictions. We demonstrate the framework for regression, classification and segmentation tasks with two different network architectures. We show that not only can the framework harmonise many-site datasets but it can also adapt to many data scenarios, including biased datasets and limited training labels. Finally, we show that the framework can be extended for the removal of other known confounds in addition to scanner. The overall framework is therefore flexible and should be applicable to a wide range of neuroimaging studies.",,doi:https://doi.org/10.1016/j.neuroimage.2020.117689; doi:https://doi.org/10.1016/j.neuroimage.2020.117689; html:https://europepmc.org/articles/PMC7903160; pdf:https://europepmc.org/articles/PMC7903160?pdf=render 36463938,https://doi.org/10.1016/j.jpeds.2022.11.027,"Summary of the Joint National Institutes of Health and the Food and Drug Administration Workshop Titled ""Exploring the Science Surrounding the Safe Use of Bioactive Ingredients in Infant Formula: Considerations for an Assessment Framework"".","Donovan SM, Abrams SA, Azad MB, Belfort MB, Bode L, Carlson SE, Dallas DC, Hettinga K, Järvinen K, Kim JH, Lebrilla CB, McGuire MK, Sela DA, Neu J.",,The Journal of pediatrics,2023,2022-12-02,N,Safety; Composition; Ingredients; formula; Human Milk; Bioactives,,,,,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10121942; doi:https://doi.org/10.1016/j.jpeds.2022.11.027; html:https://europepmc.org/articles/PMC10121942; pdf:https://europepmc.org/articles/PMC10121942?pdf=render; doi:https://doi.org/10.1016/j.jpeds.2022.11.027 @@ -2588,8 +2588,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 31795195,https://doi.org/10.3390/cancers11121895,Identification of Circulating Genomic and Metabolic Biomarkers in Intrahepatic Cholangiocarcinoma.,"Winter H, Kaisaki PJ, Harvey J, Giacopuzzi E, Ferla MP, Pentony MM, Knight SJL, Sharma RA, Taylor JC, McCullagh JSO.",,Cancers,2019,2019-11-28,Y,Metabolomics; Circulating DNA; CAD; Orotic Acid; Intrahepatic Cholangiocarcinoma; Dhodh; Idh1; 2-Hydroxyglutarate; Tyms; Umps,Understanding the Causes of Disease,cancer and neoplasms,"Intrahepatic cholangiocarcinoma (ICC) is an aggressive cancer arising from the bile ducts with a need for earlier diagnosis and a greater range of treatment options. KRAS/NRAS mutations are common in ICC tumours and 6-32% of patients also have isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) gene mutations associated with metabolic changes. This feasibility study investigated sequencing circulating tumour DNA (ctDNA) combined with metabolite profiling of plasma as a method for biomarker discovery in ICC patients. Plasma was collected from four ICC patients receiving radio-embolisation and healthy controls at multiple time points. ctDNA was sequenced using Ampliseq cancer hotspot panel-v2 on Ion Torrent PGM for single nucleotide variants (SNV) detection and with Illumina whole genome sequencing for copy number variants (CNV) and further targeted examination for SNVs. Untargeted analysis of metabolites from patient and control plasma was performed using liquid chromatography coupled with high-resolution tandem mass spectrometry (LC-MS/MS). Metabolite identification was performed using multi-parameter comparisons with analysis of authentic standards, and univariate statistical analysis was performed to identify differences in metabolite abundance between patient and control samples. Recurrent somatic SNVs and CNVs were identified in ctDNA from three out of four patients that included both NRAS and IDH1 mutations linked to ICC. Plasma metabolite analysis revealed biomarker metabolites associated with ICC and in particular 2-hydroxyglutarate (2-HG) levels were elevated in both samples from the only patient showing a variant allele in IDH1. A reduction in the number of CNVs was observed with treatment. This study demonstrates that ctDNA and metabolite levels can be identified and correlated in ICC patient blood samples and differentiated from healthy controls. We conclude that combining genomic and metabolic analysis of plasma offers an effective approach to biomarker identification with potential for disease stratification and early detection studies.",This was a feasibility study looking at whether blood samples from patients with cancer could be used to detect cancer tumours that are likely to be fast growing and hard to treat.,pdf:https://www.mdpi.com/2072-6694/11/12/1895/pdf?version=1576750751; doi:https://doi.org/10.3390/cancers11121895; html:https://europepmc.org/articles/PMC6966597; pdf:https://europepmc.org/articles/PMC6966597?pdf=render 34562388,https://doi.org/10.1016/s0140-6736(21)01258-7,"Tracking development assistance for health and for COVID-19: a review of development assistance, government, out-of-pocket, and other private spending on health for 204 countries and territories, 1990-2050.",Global Burden of Disease 2020 Health Financing Collaborator Network.,,"Lancet (London, England)",2021,2021-09-22,Y,,,,"

Background

The rapid spread of COVID-19 renewed the focus on how health systems across the globe are financed, especially during public health emergencies. Development assistance is an important source of health financing in many low-income countries, yet little is known about how much of this funding was disbursed for COVID-19. We aimed to put development assistance for health for COVID-19 in the context of broader trends in global health financing, and to estimate total health spending from 1995 to 2050 and development assistance for COVID-19 in 2020.

Methods

We estimated domestic health spending and development assistance for health to generate total health-sector spending estimates for 204 countries and territories. We leveraged data from the WHO Global Health Expenditure Database to produce estimates of domestic health spending. To generate estimates for development assistance for health, we relied on project-level disbursement data from the major international development agencies' online databases and annual financial statements and reports for information on income sources. To adjust our estimates for 2020 to include disbursements related to COVID-19, we extracted project data on commitments and disbursements from a broader set of databases (because not all of the data sources used to estimate the historical series extend to 2020), including the UN Office of Humanitarian Assistance Financial Tracking Service and the International Aid Transparency Initiative. We reported all the historic and future spending estimates in inflation-adjusted 2020 US$, 2020 US$ per capita, purchasing-power parity-adjusted US$ per capita, and as a proportion of gross domestic product. We used various models to generate future health spending to 2050.

Findings

In 2019, health spending globally reached $8·8 trillion (95% uncertainty interval [UI] 8·7-8·8) or $1132 (1119-1143) per person. Spending on health varied within and across income groups and geographical regions. Of this total, $40·4 billion (0·5%, 95% UI 0·5-0·5) was development assistance for health provided to low-income and middle-income countries, which made up 24·6% (UI 24·0-25·1) of total spending in low-income countries. We estimate that $54·8 billion in development assistance for health was disbursed in 2020. Of this, $13·7 billion was targeted toward the COVID-19 health response. $12·3 billion was newly committed and $1·4 billion was repurposed from existing health projects. $3·1 billion (22·4%) of the funds focused on country-level coordination and $2·4 billion (17·9%) was for supply chain and logistics. Only $714·4 million (7·7%) of COVID-19 development assistance for health went to Latin America, despite this region reporting 34·3% of total recorded COVID-19 deaths in low-income or middle-income countries in 2020. Spending on health is expected to rise to $1519 (1448-1591) per person in 2050, although spending across countries is expected to remain varied.

Interpretation

Global health spending is expected to continue to grow, but remain unequally distributed between countries. We estimate that development organisations substantially increased the amount of development assistance for health provided in 2020. Continued efforts are needed to raise sufficient resources to mitigate the pandemic for the most vulnerable, and to help curtail the pandemic for all.

Funding

Bill & Melinda Gates Foundation.",,pdf:http://www.thelancet.com/article/S0140673621012587/pdf; doi:https://doi.org/10.1016/S0140-6736(21)01258-7; html:https://europepmc.org/articles/PMC8457757; pdf:https://europepmc.org/articles/PMC8457757?pdf=render 35012533,https://doi.org/10.1186/s12916-021-02193-0,Circulating inflammatory cytokines and risk of five cancers: a Mendelian randomization analysis.,"Bouras E, Karhunen V, Gill D, Huang J, Haycock PC, Gunter MJ, Johansson M, Brennan P, Key T, Lewis SJ, Martin RM, Murphy N, Platz EA, Travis R, Yarmolinsky J, Zuber V, Martin P, Katsoulis M, Freisling H, Nøst TH, Schulze MB, Dossus L, Hung RJ, Amos CI, Ahola-Olli A, Palaniswamy S, Männikkö M, Auvinen J, Herzig KH, Keinänen-Kiukaanniemi S, Lehtimäki T, Salomaa V, Raitakari O, Salmi M, Jalkanen S, PRACTICAL consortium, Jarvelin MR, Dehghan A, Tsilidis KK.",,BMC medicine,2022,2022-01-11,Y,Cancer; Cytokines; Inflammation; Mendelian Randomisation,,,"

Background

Epidemiological and experimental evidence has linked chronic inflammation to cancer aetiology. It is unclear whether associations for specific inflammatory biomarkers are causal or due to bias. In order to examine whether altered genetically predicted concentration of circulating cytokines are associated with cancer development, we performed a two-sample Mendelian randomisation (MR) analysis.

Methods

Up to 31,112 individuals of European descent were included in genome-wide association study (GWAS) meta-analyses of 47 circulating cytokines. Single nucleotide polymorphisms (SNPs) robustly associated with the cytokines, located in or close to their coding gene (cis), were used as instrumental variables. Inverse-variance weighted MR was used as the primary analysis, and the MR assumptions were evaluated in sensitivity and colocalization analyses and a false discovery rate (FDR) correction for multiple comparisons was applied. Corresponding germline GWAS summary data for five cancer outcomes (breast, endometrial, lung, ovarian, and prostate), and their subtypes were selected from the largest cancer-specific GWASs available (cases ranging from 12,906 for endometrial to 133,384 for breast cancer).

Results

There was evidence of inverse associations of macrophage migration inhibitory factor with breast cancer (OR per SD = 0.88, 95% CI 0.83 to 0.94), interleukin-1 receptor antagonist with endometrial cancer (0.86, 0.80 to 0.93), interleukin-18 with lung cancer (0.87, 0.81 to 0.93), and beta-chemokine-RANTES with ovarian cancer (0.70, 0.57 to 0.85) and positive associations of monokine induced by gamma interferon with endometrial cancer (3.73, 1.86 to 7.47) and cutaneous T-cell attracting chemokine with lung cancer (1.51, 1.22 to 1.87). These associations were similar in sensitivity analyses and supported in colocalization analyses.

Conclusions

Our study adds to current knowledge on the role of specific inflammatory biomarker pathways in cancer aetiology. Further validation is needed to assess the potential of these cytokines as pharmacological or lifestyle targets for cancer prevention.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-021-02193-0; doi:https://doi.org/10.1186/s12916-021-02193-0; html:https://europepmc.org/articles/PMC8750876; pdf:https://europepmc.org/articles/PMC8750876?pdf=render -38373851,https://doi.org/10.3399/bjgp.2023.0198,Long-term cardiovascular risks and the impact of statin treatment on socioeconomic inequalities: a microsimulation model.,"Wu R, Williams C, Zhou J, Schlackow I, Emberson J, Reith C, Keech A, Robson J, Armitage J, Gray A, Simes J, Baigent C, Mihaylova B, CTT Collaboration secretariat, Armitage J, Baigent C, Barnes E, Blackwell L, Collins R, Davies K, Emberson J, Fulcher J, Halls H, Herrington WG, Holland L, Keech A, Kirby A, Mihaylova B, O'Connell R, Preiss D, Reith C, Simes J, Wilson K, CTT Collaboration trialists: A to Z trial (phase Z), Blazing M, Braunwald E, Lemos J, Murphy S, Pedersen TR, Pfeffer M, White H, Wiviott S, AFCAPS/TEXCAPS (AirForce/Texas Coronary Atherosclerosis Prevention Study), Clearfield M, Downs JR, Gotto A, Weis S, ALERT (Assessment of Lescol in Renal Transplantation), Fellström B, Holdaas H, Jardine A, Pedersen TR, ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial), Gordon D, Davis B, Furberg C, Grimm R, Pressel S, Probstfield JL, Rahman M, Simpson L, ALLIANCE (Aggressive Lipid-Lowering Initiation Abates New Cardiac Events), Koren M, ASCOT (Anglo-Scandinavian Cardiac Outcomes Trial), Dahlöf B, Gupta A, Poulter N, Sever P, Wedel H, ASPEN (Atorvastatin Study for the Prevention of Coronary Heart Disease Endpoints in Non-Insulin Dependent Diabetes Mellitus), Knopp RH, AURORA (A study to evaluate the Use of Rosuvastatin in subjects On Regular haemodialysis: an Assessment of survival and cardiovascular events), Cobbe S, Fellström B, Holdaas H, Jardine A, Schmieder R, Zannad F, CARDS (Collaborative Atorvastatin Diabetes Study), Betteridge DJ, Colhoun HM, Durrington PN, Fuller J, Hitman GA, Neil A, CARE (Cholesterol And Recurrent Events Study), Braunwald E, Davis B, Hawkins CM, Moyé L, Pfeffer M, Sacks F, CORONA (Controlled Rosuvastatin Multinational Trial in Heart Failure), Kjekshus J, Wedel H, Wikstrand J, 4D (Die Deutsche Diabetes Dialyse Studie), Wanner C, Krane V, GISSI (Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto miocardico) Heart Failure and Prevention trials, Franzosi MG, Latini R, Lucci D, Maggioni A, Marchioli R, Nicolis EB, Tavazzi L, Tognoni G, HOPE-3, Bosch J, Lonn E, Yusuf S, HPS (Heart Protection Study), Armitage J, Bowman L, Collins R, Keech A, Landray M, Parish S, Peto R, Sleight P, IDEAL (Incremental Decrease in Endpoints through Aggressive Lipid-lowering), Kastelein JJ, Pedersen TR, JUPITER (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin), Glynn R, Gotto A, Kastelein JJ, Koenig W, MacFadyen J, Ridker PM, LIPID (Long-term Intervention with Pravastatin in Ischaemic Disease), Keech A, MacMahon S, Marschner I, Tonkin A, Shaw J, Simes J, White H, LIPS (Lescol Intervention Prevention Study), Serruys PW, Post-CABG (Post-Coronary Artery Bypass Graft Study), Knatterud G, PROSPER (Prospective Study of Pravastatin in the Elderly at Risk), Blauw GJ, Cobbe S, Ford I, Macfarlane P, Packard C, Sattar N, Shepherd J, Trompet S, PROVE-IT (Pravastatin or Atorvastatin Evaluation and Infection Therapy), Braunwald E, Cannon CP, Murphy S, SEARCH (Study of Effectiveness of Additional Reductions in Cholesterol and Homocysteine), Collins R, Armitage J, Bowman L, Bulbulia R, Haynes R, Parish S, Peto R, Sleight P, SPARCL (Stroke Prevention by Aggressive Reduction in Cholesterol Levels), Amarenco P, Welch KM, 4S (Scandinavian Simvastatin Survival Study), Kjekshus J, Pedersen TR, Wilhelmsen L, TNT (Treating to New Targets), Barter P, Gotto A, LaRosa J, Kastelein JJ, Shepherd J, WOSCOPS (West of Scotland Coronary Prevention Study), Cobbe S, Ford I, Kean S, Macfarlane P, Packard C, Roberston M, Sattar N, Shepherd J, Young R, Other CTT Collaboration members, Arashi H, Clarke R, Flather M, Goto S, Goldbourt U, Hopewell J, Hovingh GK, Kitas G, Newman C, Sabatine MS, Schwartz GG, Smeeth L, Tobert J, Varigos J, Yamamguchi J.",,The British journal of general practice : the journal of the Royal College of General Practitioners,2024,2024-02-19,Y,Cardiovascular disease; Socioeconomic status; Quality-adjusted Life Years; Inequality; Markov Microsimulation Model; Individual Patient Characteristics,,,"

Background

UK cardiovascular disease (CVD) incidence and mortality have declined in recent decades but socioeconomic inequalities persist.

Aim

To present a new CVD model, and project health outcomes and the impact of guideline-recommended statin treatment across quintiles of socioeconomic deprivation in the UK.

Design and setting

A lifetime microsimulation model was developed using 117 896 participants in 16 statin trials, 501 854 UK Biobank (UKB) participants, and quality-of-life data from national health surveys.

Method

A CVD microsimulation model was developed using risk equations for myocardial infarction, stroke, coronary revascularisation, cancer, and vascular and non-vascular death, estimated using trial data. The authors calibrated and further developed this model in the UKB cohort, including further characteristics and a diabetes risk equation, and validated the model in UKB and Whitehall II cohorts. The model was used to predict CVD incidence, life expectancy, quality-adjusted life years (QALYs), and the impact of UK guideline-recommended statin treatment across socioeconomic deprivation quintiles.

Results

Age, sex, socioeconomic deprivation, smoking, hypertension, diabetes, and cardiovascular events were key CVD risk determinants. Model-predicted event rates corresponded well to observed rates across participant categories. The model projected strong gradients in remaining life expectancy, with 4-5-year (5-8 QALYs) gaps between the least and most socioeconomically deprived quintiles. Guideline-recommended statin treatment was projected to increase QALYs, with larger gains in quintiles of higher deprivation.

Conclusion

The study demonstrated the potential of guideline-recommended statin treatment to reduce socioeconomic inequalities. This CVD model is a novel resource for individualised long-term projections of health outcomes of CVD treatments.",,doi:https://doi.org/10.3399/BJGP.2023.0198; html:https://europepmc.org/articles/PMC10904120; pdf:https://europepmc.org/articles/PMC10904120?pdf=render 32134384,https://doi.org/10.7554/elife.52677,Brain aging comprises many modes of structural and functional change with distinct genetic and biophysical associations.,"Smith SM, Elliott LT, Alfaro-Almagro F, McCarthy P, Nichols TE, Douaud G, Miller KL.",,eLife,2020,2020-03-05,Y,Human; Neuroscience; Brain imaging; brain aging; Uk Biobank,,,"Brain imaging can be used to study how individuals' brains are aging, compared against population norms. This can inform on aspects of brain health; for example, smoking and blood pressure can be seen to accelerate brain aging. Typically, a single 'brain age' is estimated per subject, whereas here we identified 62 modes of subject variability, from 21,407 subjects' multimodal brain imaging data in UK Biobank. The modes represent different aspects of brain aging, showing distinct patterns of functional and structural brain change, and distinct patterns of association with genetics, lifestyle, cognition, physical measures and disease. While conventional brain-age modelling found no genetic associations, 34 modes had genetic associations. We suggest that it is important not to treat brain aging as a single homogeneous process, and that modelling of distinct patterns of structural and functional change will reveal more biologically meaningful markers of brain aging in health and disease.",,doi:https://doi.org/10.7554/elife.52677; doi:https://doi.org/10.7554/eLife.52677; html:https://europepmc.org/articles/PMC7162660; pdf:https://europepmc.org/articles/PMC7162660?pdf=render +38373851,https://doi.org/10.3399/bjgp.2023.0198,Long-term cardiovascular risks and the impact of statin treatment on socioeconomic inequalities: a microsimulation model.,"Wu R, Williams C, Zhou J, Schlackow I, Emberson J, Reith C, Keech A, Robson J, Armitage J, Gray A, Simes J, Baigent C, Mihaylova B, CTT Collaboration secretariat, Armitage J, Baigent C, Barnes E, Blackwell L, Collins R, Davies K, Emberson J, Fulcher J, Halls H, Herrington WG, Holland L, Keech A, Kirby A, Mihaylova B, O'Connell R, Preiss D, Reith C, Simes J, Wilson K, CTT Collaboration trialists: A to Z trial (phase Z), Blazing M, Braunwald E, Lemos J, Murphy S, Pedersen TR, Pfeffer M, White H, Wiviott S, AFCAPS/TEXCAPS (AirForce/Texas Coronary Atherosclerosis Prevention Study), Clearfield M, Downs JR, Gotto A, Weis S, ALERT (Assessment of Lescol in Renal Transplantation), Fellström B, Holdaas H, Jardine A, Pedersen TR, ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial), Gordon D, Davis B, Furberg C, Grimm R, Pressel S, Probstfield JL, Rahman M, Simpson L, ALLIANCE (Aggressive Lipid-Lowering Initiation Abates New Cardiac Events), Koren M, ASCOT (Anglo-Scandinavian Cardiac Outcomes Trial), Dahlöf B, Gupta A, Poulter N, Sever P, Wedel H, ASPEN (Atorvastatin Study for the Prevention of Coronary Heart Disease Endpoints in Non-Insulin Dependent Diabetes Mellitus), Knopp RH, AURORA (A study to evaluate the Use of Rosuvastatin in subjects On Regular haemodialysis: an Assessment of survival and cardiovascular events), Cobbe S, Fellström B, Holdaas H, Jardine A, Schmieder R, Zannad F, CARDS (Collaborative Atorvastatin Diabetes Study), Betteridge DJ, Colhoun HM, Durrington PN, Fuller J, Hitman GA, Neil A, CARE (Cholesterol And Recurrent Events Study), Braunwald E, Davis B, Hawkins CM, Moyé L, Pfeffer M, Sacks F, CORONA (Controlled Rosuvastatin Multinational Trial in Heart Failure), Kjekshus J, Wedel H, Wikstrand J, 4D (Die Deutsche Diabetes Dialyse Studie), Wanner C, Krane V, GISSI (Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto miocardico) Heart Failure and Prevention trials, Franzosi MG, Latini R, Lucci D, Maggioni A, Marchioli R, Nicolis EB, Tavazzi L, Tognoni G, HOPE-3, Bosch J, Lonn E, Yusuf S, HPS (Heart Protection Study), Armitage J, Bowman L, Collins R, Keech A, Landray M, Parish S, Peto R, Sleight P, IDEAL (Incremental Decrease in Endpoints through Aggressive Lipid-lowering), Kastelein JJ, Pedersen TR, JUPITER (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin), Glynn R, Gotto A, Kastelein JJ, Koenig W, MacFadyen J, Ridker PM, LIPID (Long-term Intervention with Pravastatin in Ischaemic Disease), Keech A, MacMahon S, Marschner I, Tonkin A, Shaw J, Simes J, White H, LIPS (Lescol Intervention Prevention Study), Serruys PW, Post-CABG (Post-Coronary Artery Bypass Graft Study), Knatterud G, PROSPER (Prospective Study of Pravastatin in the Elderly at Risk), Blauw GJ, Cobbe S, Ford I, Macfarlane P, Packard C, Sattar N, Shepherd J, Trompet S, PROVE-IT (Pravastatin or Atorvastatin Evaluation and Infection Therapy), Braunwald E, Cannon CP, Murphy S, SEARCH (Study of Effectiveness of Additional Reductions in Cholesterol and Homocysteine), Collins R, Armitage J, Bowman L, Bulbulia R, Haynes R, Parish S, Peto R, Sleight P, SPARCL (Stroke Prevention by Aggressive Reduction in Cholesterol Levels), Amarenco P, Welch KM, 4S (Scandinavian Simvastatin Survival Study), Kjekshus J, Pedersen TR, Wilhelmsen L, TNT (Treating to New Targets), Barter P, Gotto A, LaRosa J, Kastelein JJ, Shepherd J, WOSCOPS (West of Scotland Coronary Prevention Study), Cobbe S, Ford I, Kean S, Macfarlane P, Packard C, Roberston M, Sattar N, Shepherd J, Young R, Other CTT Collaboration members, Arashi H, Clarke R, Flather M, Goto S, Goldbourt U, Hopewell J, Hovingh GK, Kitas G, Newman C, Sabatine MS, Schwartz GG, Smeeth L, Tobert J, Varigos J, Yamamguchi J.",,The British journal of general practice : the journal of the Royal College of General Practitioners,2024,2024-02-19,Y,Cardiovascular disease; Socioeconomic status; Quality-adjusted Life Years; Inequality; Markov Microsimulation Model; Individual Patient Characteristics,,,"

Background

UK cardiovascular disease (CVD) incidence and mortality have declined in recent decades but socioeconomic inequalities persist.

Aim

To present a new CVD model, and project health outcomes and the impact of guideline-recommended statin treatment across quintiles of socioeconomic deprivation in the UK.

Design and setting

A lifetime microsimulation model was developed using 117 896 participants in 16 statin trials, 501 854 UK Biobank (UKB) participants, and quality-of-life data from national health surveys.

Method

A CVD microsimulation model was developed using risk equations for myocardial infarction, stroke, coronary revascularisation, cancer, and vascular and non-vascular death, estimated using trial data. The authors calibrated and further developed this model in the UKB cohort, including further characteristics and a diabetes risk equation, and validated the model in UKB and Whitehall II cohorts. The model was used to predict CVD incidence, life expectancy, quality-adjusted life years (QALYs), and the impact of UK guideline-recommended statin treatment across socioeconomic deprivation quintiles.

Results

Age, sex, socioeconomic deprivation, smoking, hypertension, diabetes, and cardiovascular events were key CVD risk determinants. Model-predicted event rates corresponded well to observed rates across participant categories. The model projected strong gradients in remaining life expectancy, with 4-5-year (5-8 QALYs) gaps between the least and most socioeconomically deprived quintiles. Guideline-recommended statin treatment was projected to increase QALYs, with larger gains in quintiles of higher deprivation.

Conclusion

The study demonstrated the potential of guideline-recommended statin treatment to reduce socioeconomic inequalities. This CVD model is a novel resource for individualised long-term projections of health outcomes of CVD treatments.",,doi:https://doi.org/10.3399/BJGP.2023.0198; html:https://europepmc.org/articles/PMC10904120; pdf:https://europepmc.org/articles/PMC10904120?pdf=render 30941398,https://doi.org/10.1093/aje/kwz090,Determinants of Transmission Risk During the Late Stage of the West African Ebola Epidemic.,"Robert A, Edmunds WJ, Watson CH, Henao-Restrepo AM, Gsell PS, Williamson E, Longini IM, Sakoba K, Kucharski AJ, Touré A, Nadlaou SD, Diallo B, Barry MS, Fofana TO, Camara L, Kaba IL, Sylla L, Diaby ML, Soumah O, Diallo A, Niare A, Diallo A, Eggo RM.",,American journal of epidemiology,2019,2019-07-01,Y,Regression analysis; Guinea; risk factors; Multiple Imputation; Ebola,"Applied Analytics, Improving Public Health",,"Understanding risk factors for Ebola transmission is key for effective prediction and design of interventions. We used data on 860 cases in 129 chains of transmission from the latter half of the 2013-2016 Ebola epidemic in Guinea. Using negative binomial regression, we determined characteristics associated with the number of secondary cases resulting from each infected individual. We found that attending an Ebola treatment unit was associated with a 38% decrease in secondary cases (incidence rate ratio (IRR) = 0.62, 95% confidence interval (CI): 0.38, 0.99) among individuals that did not survive. Unsafe burial was associated with a higher number of secondary cases (IRR = 1.82, 95% CI: 1.10, 3.02). The average number of secondary cases was higher for the first generation of a transmission chain (mean = 1.77) compared with subsequent generations (mean = 0.70). Children were least likely to transmit (IRR = 0.35, 95% CI: 0.21, 0.57) compared with adults, whereas older adults were associated with higher numbers of secondary cases. Men were less likely to transmit than women (IRR = 0.71, 95% CI: 0.55, 0.93). This detailed surveillance data set provided an invaluable insight into transmission routes and risks. Our analysis highlights the key role that age, receiving treatment, and safe burial played in the spread of EVD.",,pdf:https://academic.oup.com/aje/article-pdf/188/7/1319/28890395/kwz090.pdf; doi:https://doi.org/10.1093/aje/kwz090; html:https://europepmc.org/articles/PMC6601535; pdf:https://europepmc.org/articles/PMC6601535?pdf=render 32502389,https://doi.org/10.1016/s2468-2667(20)30133-x,"Effects of non-pharmaceutical interventions on COVID-19 cases, deaths, and demand for hospital services in the UK: a modelling study.","Davies NG, Kucharski AJ, Eggo RM, Gimma A, Edmunds WJ, Centre for the Mathematical Modelling of Infectious Diseases COVID-19 working group.",,The Lancet. Public health,2020,2020-06-02,Y,,,,"

Background

Non-pharmaceutical interventions have been implemented to reduce transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the UK. Projecting the size of an unmitigated epidemic and the potential effect of different control measures has been crucial to support evidence-based policy making during the early stages of the epidemic. This study assesses the potential impact of different control measures for mitigating the burden of COVID-19 in the UK.

Methods

We used a stochastic age-structured transmission model to explore a range of intervention scenarios, tracking 66·4 million people aggregated to 186 county-level administrative units in England, Wales, Scotland, and Northern Ireland. The four base interventions modelled were school closures, physical distancing, shielding of people aged 70 years or older, and self-isolation of symptomatic cases. We also modelled the combination of these interventions, as well as a programme of intensive interventions with phased lockdown-type restrictions that substantially limited contacts outside of the home for repeated periods. We simulated different triggers for the introduction of interventions, and estimated the impact of varying adherence to interventions across counties. For each scenario, we projected estimated new cases over time, patients requiring inpatient and critical care (ie, admission to the intensive care units [ICU]) treatment, and deaths, and compared the effect of each intervention on the basic reproduction number, R0.

Findings

We projected a median unmitigated burden of 23 million (95% prediction interval 13-30) clinical cases and 350 000 deaths (170 000-480 000) due to COVID-19 in the UK by December, 2021. We found that the four base interventions were each likely to decrease R0, but not sufficiently to prevent ICU demand from exceeding health service capacity. The combined intervention was more effective at reducing R0, but only lockdown periods were sufficient to bring R0 near or below 1; the most stringent lockdown scenario resulted in a projected 120 000 cases (46 000-700 000) and 50 000 deaths (9300-160 000). Intensive interventions with lockdown periods would need to be in place for a large proportion of the coming year to prevent health-care demand exceeding availability.

Interpretation

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

Funding

Medical Research Council.","The paper identifies the following; This paper identifies the influence of different interventions on COVID on cases, deaths, and demands for hospital services in the UK. This was achieved utilising modelling techniques. The paper concludes that the characteristics of SARS-CoV-2 mean that extreme measures are probably required to bring the epidemic under control and to prevent very large numbers of deaths and an excess of demand on hospital beds, especially those in ICUs. However, Biobank is not very representative of age, ethniticity and deprivation.",pdf:https://europepmc.org/articles/pmc7266572?pdf=render; doi:https://doi.org/10.1016/S2468-2667(20)30133-X; html:https://europepmc.org/articles/PMC7266572; pdf:https://europepmc.org/articles/PMC7266572?pdf=render 33239672,https://doi.org/10.1038/s41467-020-19742-5,The genetic architecture of sporadic and multiple consecutive miscarriage.,"Laisk T, Soares ALG, Ferreira T, Painter JN, Censin JC, Laber S, Bacelis J, Chen CY, Lepamets M, Lin K, Liu S, Millwood IY, Ramu A, Southcombe J, Andersen MS, Yang L, Becker CM, Børglum AD, Gordon SD, Bybjerg-Grauholm J, Helgeland Ø, Hougaard DM, Jin X, Johansson S, Juodakis J, Kartsonaki C, Kukushkina V, Lind PA, Metspalu A, Montgomery GW, Morris AP, Mors O, Mortensen PB, Njølstad PR, Nordentoft M, Nyholt DR, Lippincott M, Seminara S, Salumets A, Snieder H, Zondervan K, Werge T, Chen Z, Conrad DF, Jacobsson B, Li L, Martin NG, Neale BM, Nielsen R, Walters RG, Granne I, Medland SE, Mägi R, Lawlor DA, Lindgren CM.",,Nature communications,2020,2020-11-25,Y,,,,"Miscarriage is a common, complex trait affecting ~15% of clinically confirmed pregnancies. Here we present the results of large-scale genetic association analyses with 69,054 cases from five different ancestries for sporadic miscarriage, 750 cases of European ancestry for multiple (≥3) consecutive miscarriage, and up to 359,469 female controls. We identify one genome-wide significant association (rs146350366, minor allele frequency (MAF) 1.2%, P = 3.2 × 10-8, odds ratio (OR) = 1.4) for sporadic miscarriage in our European ancestry meta-analysis and three genome-wide significant associations for multiple consecutive miscarriage (rs7859844, MAF = 6.4%, P = 1.3 × 10-8, OR = 1.7; rs143445068, MAF = 0.8%, P = 5.2 × 10-9, OR = 3.4; rs183453668, MAF = 0.5%, P = 2.8 × 10-8, OR = 3.8). We further investigate the genetic architecture of miscarriage with biobank-scale Mendelian randomization, heritability, and genetic correlation analyses. Our results show that miscarriage etiopathogenesis is partly driven by genetic variation potentially related to placental biology, and illustrate the utility of large-scale biobank data for understanding this pregnancy complication.",,pdf:https://www.nature.com/articles/s41467-020-19742-5.pdf; doi:https://doi.org/10.1038/s41467-020-19742-5; html:https://europepmc.org/articles/PMC7689465; pdf:https://europepmc.org/articles/PMC7689465?pdf=render @@ -2601,8 +2601,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 32080354,https://doi.org/10.1038/s41397-020-0165-2,Genome-wide association study of angioedema induced by angiotensin-converting enzyme inhibitor and angiotensin receptor blocker treatment.,"Rasmussen ER, Hallberg P, Baranova EV, Eriksson N, Karawajczyk M, Johansson C, Cavalli M, Maroteau C, Veluchamy A, Islander G, Hugosson S, Terreehorst I, Asselbergs FW, Norling P, Johansson HE, Kohnke H, Syvänen AC, Siddiqui MK, Lang CC, Magnusson PKE, Yue QY, Wadelius C, von Buchwald C, Bygum A, Alfirevic A, Maitland-van der Zee AH, Palmer CNA, Wadelius M.",,The pharmacogenomics journal,2020,2020-02-21,Y,,,,"Angioedema in the mouth or upper airways is a feared adverse reaction to angiotensin-converting enzyme inhibitor (ACEi) and angiotensin receptor blocker (ARB) treatment, which is used for hypertension, heart failure and diabetes complications. This candidate gene and genome-wide association study aimed to identify genetic variants predisposing to angioedema induced by these drugs. The discovery cohort consisted of 173 cases and 4890 controls recruited in Sweden. In the candidate gene analysis, ETV6, BDKRB2, MME, and PRKCQ were nominally associated with angioedema (p < 0.05), but did not pass Bonferroni correction for multiple testing (p < 2.89 × 10-5). In the genome-wide analysis, intronic variants in the calcium-activated potassium channel subunit alpha-1 (KCNMA1) gene on chromosome 10 were significantly associated with angioedema (p < 5 × 10-8). Whilst the top KCNMA1 hit was not significant in the replication cohort (413 cases and 599 ACEi-exposed controls from the US and Northern Europe), a meta-analysis of the replication and discovery cohorts (in total 586 cases and 1944 ACEi-exposed controls) revealed that each variant allele increased the odds of experiencing angioedema 1.62 times (95% confidence interval 1.05-2.50, p = 0.030). Associated KCNMA1 variants are not known to be functional, but are in linkage disequilibrium with variants in transcription factor binding sites active in relevant tissues. In summary, our data suggest that common variation in KCNMA1 is associated with risk of angioedema induced by ACEi or ARB treatment. Future whole exome or genome sequencing studies will show whether rare variants in KCNMA1 or other genes contribute to the risk of ACEi- and ARB-induced angioedema.",,pdf:https://www.nature.com/articles/s41397-020-0165-2.pdf; doi:https://doi.org/10.1038/s41397-020-0165-2; html:https://europepmc.org/articles/PMC7674154; pdf:https://europepmc.org/articles/PMC7674154?pdf=render 33536631,https://doi.org/10.1038/s42003-020-01575-z,A genome-wide meta-analysis yields 46 new loci associating with biomarkers of iron homeostasis.,"Bell S, Rigas AS, Magnusson MK, Ferkingstad E, Allara E, Bjornsdottir G, Ramond A, Sørensen E, Halldorsson GH, Paul DS, Burgdorf KS, Eggertsson HP, Howson JMM, Thørner LW, Kristmundsdottir S, Astle WJ, Erikstrup C, Sigurdsson JK, Vuckovic D, Dinh KM, Tragante V, Surendran P, Pedersen OB, Vidarsson B, Jiang T, Paarup HM, Onundarson PT, Akbari P, Nielsen KR, Lund SH, Juliusson K, Magnusson MI, Frigge ML, Oddsson A, Olafsson I, Kaptoge S, Hjalgrim H, Runarsson G, Wood AM, Jonsdottir I, Hansen TF, Sigurdardottir O, Stefansson H, Rye D, DBDS Genomic Consortium, Peters JE, Westergaard D, Holm H, Soranzo N, Banasik K, Thorleifsson G, Ouwehand WH, Thorsteinsdottir U, Roberts DJ, Sulem P, Butterworth AS, Gudbjartsson DF, Danesh J, Brunak S, Di Angelantonio E, Ullum H, Stefansson K.",,Communications biology,2021,2021-02-03,Y,,,,"Iron is essential for many biological functions and iron deficiency and overload have major health implications. We performed a meta-analysis of three genome-wide association studies from Iceland, the UK and Denmark of blood levels of ferritin (N = 246,139), total iron binding capacity (N = 135,430), iron (N = 163,511) and transferrin saturation (N = 131,471). We found 62 independent sequence variants associating with iron homeostasis parameters at 56 loci, including 46 novel loci. Variants at DUOX2, F5, SLC11A2 and TMPRSS6 associate with iron deficiency anemia, while variants at TF, HFE, TFR2 and TMPRSS6 associate with iron overload. A HBS1L-MYB intergenic region variant associates both with increased risk of iron overload and reduced risk of iron deficiency anemia. The DUOX2 missense variant is present in 14% of the population, associates with all iron homeostasis biomarkers, and increases the risk of iron deficiency anemia by 29%. The associations implicate proteins contributing to the main physiological processes involved in iron homeostasis: iron sensing and storage, inflammation, absorption of iron from the gut, iron recycling, erythropoiesis and bleeding/menstruation.",,pdf:https://www.nature.com/articles/s42003-020-01575-z.pdf; doi:https://doi.org/10.1038/s42003-020-01575-z; html:https://europepmc.org/articles/PMC7859200; pdf:https://europepmc.org/articles/PMC7859200?pdf=render 32814572,https://doi.org/10.1186/s12916-020-01712-9,The effect of travel restrictions on the geographical spread of COVID-19 between large cities in China: a modelling study.,"Quilty BJ, Diamond C, Liu Y, Gibbs H, Russell TW, Jarvis CI, Prem K, Pearson CAB, Clifford S, Flasche S, CMMID COVID-19 working group, Klepac P, Eggo RM, Jit M.",,BMC medicine,2020,2020-08-19,Y,China; Wuhan; Mobility; Delay; Outbreaks; Modelling; Travel Restrictions; Covid-19; Sars-cov-2; Cordon Sanitaire,,,"

Background

To contain the spread of COVID-19, a cordon sanitaire was put in place in Wuhan prior to the Lunar New Year, on 23 January 2020. We assess the efficacy of the cordon sanitaire to delay the introduction and onset of local transmission of COVID-19 in other major cities in mainland China.

Methods

We estimated the number of infected travellers from Wuhan to other major cities in mainland China from November 2019 to February 2020 using previously estimated COVID-19 prevalence in Wuhan and publicly available mobility data. We focused on Beijing, Chongqing, Hangzhou, and Shenzhen as four representative major cities to identify the potential independent contribution of the cordon sanitaire and holiday travel. To do this, we simulated outbreaks generated by infected arrivals in these destination cities using stochastic branching processes. We also modelled the effect of the cordon sanitaire in combination with reduced transmissibility scenarios to simulate the effect of local non-pharmaceutical interventions.

Results

We find that in the four cities, given the potentially high prevalence of COVID-19 in Wuhan between December 2019 and early January 2020, local transmission may have been seeded as early as 1-8 January 2020. By the time the cordon sanitaire was imposed, infections were likely in the thousands. The cordon sanitaire alone did not substantially affect the epidemic progression in these cities, although it may have had some effect in smaller cities. Reduced transmissibility resulted in a notable decrease in the incidence of infection in the four studied cities.

Conclusions

Our results indicate that sustained transmission was likely occurring several weeks prior to the implementation of the cordon sanitaire in four major cities of mainland China and that the observed decrease in incidence was likely attributable to other non-pharmaceutical, transmission-reducing interventions.",,pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-020-01712-9; doi:https://doi.org/10.1186/s12916-020-01712-9; html:https://europepmc.org/articles/PMC7437104; pdf:https://europepmc.org/articles/PMC7437104?pdf=render -37880365,https://doi.org/10.1038/s41586-023-06630-3,Normative spatiotemporal fetal brain maturation with satisfactory development at 2 years.,"Namburete AIL, Papież BW, Fernandes M, Wyburd MK, Hesse LS, Moser FA, Ismail LC, Gunier RB, Squier W, Ohuma EO, Carvalho M, Jaffer Y, Gravett M, Wu Q, Lambert A, Winsey A, Restrepo-Méndez MC, Bertino E, Purwar M, Barros FC, Stein A, Noble JA, Molnár Z, Jenkinson M, Bhutta ZA, Papageorghiou AT, Villar J, Kennedy SH.",,Nature,2023,2023-10-25,Y,,,,"Maturation of the human fetal brain should follow precisely scheduled structural growth and folding of the cerebral cortex for optimal postnatal function1. We present a normative digital atlas of fetal brain maturation based on a prospective international cohort of healthy pregnant women2, selected using World Health Organization recommendations for growth standards3. Their fetuses were accurately dated in the first trimester, with satisfactory growth and neurodevelopment from early pregnancy to 2 years of age4,5. The atlas was produced using 1,059 optimal quality, three-dimensional ultrasound brain volumes from 899 of the fetuses and an automated analysis pipeline6-8. The atlas corresponds structurally to published magnetic resonance images9, but with finer anatomical details in deep grey matter. The between-study site variability represented less than 8.0% of the total variance of all brain measures, supporting pooling data from the eight study sites to produce patterns of normative maturation. We have thereby generated an average representation of each cerebral hemisphere between 14 and 31 weeks' gestation with quantification of intracranial volume variability and growth patterns. Emergent asymmetries were detectable from as early as 14 weeks, with peak asymmetries in regions associated with language development and functional lateralization between 20 and 26 weeks' gestation. These patterns were validated in 1,487 three-dimensional brain volumes from 1,295 different fetuses in the same cohort. We provide a unique spatiotemporal benchmark of fetal brain maturation from a large cohort with normative postnatal growth and neurodevelopment.",,pdf:https://www.nature.com/articles/s41586-023-06630-3.pdf; doi:https://doi.org/10.1038/s41586-023-06630-3; html:https://europepmc.org/articles/PMC10620088; pdf:https://europepmc.org/articles/PMC10620088?pdf=render 34098341,https://doi.org/10.1016/j.ebiom.2021.103414,Accuracy of four lateral flow immunoassays for anti SARS-CoV-2 antibodies: a head-to-head comparative study.,"Jones HE, Mulchandani R, Taylor-Phillips S, Ades AE, Shute J, Perry KR, Chandra NL, Brooks T, Charlett A, Hickman M, Oliver I, Kaptoge S, Danesh J, Di Angelantonio E, Wyllie D, COMPARE study investigators, EDSAB-HOME investigators.",,EBioMedicine,2021,2021-06-04,Y,Seroepidemiology; Rapid Testing; Serosurveillance; Lateral Flow Devices; Covid-19,,,"

Background

SARS-CoV-2 antibody tests are used for population surveillance and might have a future role in individual risk assessment. Lateral flow immunoassays (LFIAs) can deliver results rapidly and at scale, but have widely varying accuracy.

Methods

In a laboratory setting, we performed head-to-head comparisons of four LFIAs: the Rapid Test Consortium's AbC-19TM Rapid Test, OrientGene COVID IgG/IgM Rapid Test Cassette, SureScreen COVID-19 Rapid Test Cassette, and Biomerica COVID-19 IgG/IgM Rapid Test. We analysed blood samples from 2,847 key workers and 1,995 pre-pandemic blood donors with all four devices.

Findings

We observed a clear trade-off between sensitivity and specificity: the IgG band of the SureScreen device and the AbC-19TM device had higher specificities but OrientGene and Biomerica higher sensitivities. Based on analysis of pre-pandemic samples, SureScreen IgG band had the highest specificity (98.9%, 95% confidence interval 98.3 to 99.3%), which translated to the highest positive predictive value across any pre-test probability: for example, 95.1% (95% uncertainty interval 92.6, 96.8%) at 20% pre-test probability. All four devices showed higher sensitivity at higher antibody concentrations (""spectrum effects""), but the extent of this varied by device.

Interpretation

The estimates of sensitivity and specificity can be used to adjust for test error rates when using these devices to estimate the prevalence of antibody. If tests were used to determine whether an individual has SARS-CoV-2 antibodies, in an example scenario in which 20% of individuals have antibodies we estimate around 5% of positive results on the most specific device would be false positives.

Funding

Public Health England.",,pdf:https://research-information.bris.ac.uk/files/280339070/1_s2.0_S2352396421002073_main.pdf; doi:https://doi.org/10.1016/j.ebiom.2021.103414; html:https://europepmc.org/articles/PMC8176919; pdf:https://europepmc.org/articles/PMC8176919?pdf=render +37880365,https://doi.org/10.1038/s41586-023-06630-3,Normative spatiotemporal fetal brain maturation with satisfactory development at 2 years.,"Namburete AIL, Papież BW, Fernandes M, Wyburd MK, Hesse LS, Moser FA, Ismail LC, Gunier RB, Squier W, Ohuma EO, Carvalho M, Jaffer Y, Gravett M, Wu Q, Lambert A, Winsey A, Restrepo-Méndez MC, Bertino E, Purwar M, Barros FC, Stein A, Noble JA, Molnár Z, Jenkinson M, Bhutta ZA, Papageorghiou AT, Villar J, Kennedy SH.",,Nature,2023,2023-10-25,Y,,,,"Maturation of the human fetal brain should follow precisely scheduled structural growth and folding of the cerebral cortex for optimal postnatal function1. We present a normative digital atlas of fetal brain maturation based on a prospective international cohort of healthy pregnant women2, selected using World Health Organization recommendations for growth standards3. Their fetuses were accurately dated in the first trimester, with satisfactory growth and neurodevelopment from early pregnancy to 2 years of age4,5. The atlas was produced using 1,059 optimal quality, three-dimensional ultrasound brain volumes from 899 of the fetuses and an automated analysis pipeline6-8. The atlas corresponds structurally to published magnetic resonance images9, but with finer anatomical details in deep grey matter. The between-study site variability represented less than 8.0% of the total variance of all brain measures, supporting pooling data from the eight study sites to produce patterns of normative maturation. We have thereby generated an average representation of each cerebral hemisphere between 14 and 31 weeks' gestation with quantification of intracranial volume variability and growth patterns. Emergent asymmetries were detectable from as early as 14 weeks, with peak asymmetries in regions associated with language development and functional lateralization between 20 and 26 weeks' gestation. These patterns were validated in 1,487 three-dimensional brain volumes from 1,295 different fetuses in the same cohort. We provide a unique spatiotemporal benchmark of fetal brain maturation from a large cohort with normative postnatal growth and neurodevelopment.",,pdf:https://www.nature.com/articles/s41586-023-06630-3.pdf; doi:https://doi.org/10.1038/s41586-023-06630-3; html:https://europepmc.org/articles/PMC10620088; pdf:https://europepmc.org/articles/PMC10620088?pdf=render 34051920,https://doi.org/10.1016/s2468-2667(21)00065-7,"Spatial, temporal, and demographic patterns in prevalence of chewing tobacco use in 204 countries and territories, 1990-2019: a systematic analysis from the Global Burden of Disease Study 2019.",GBD 2019 Chewing Tobacco Collaborators.,,The Lancet. Public health,2021,2021-05-28,Y,,,,"

Background

Chewing tobacco and other types of smokeless tobacco use have had less attention from the global health community than smoked tobacco use. However, the practice is popular in many parts of the world and has been linked to several adverse health outcomes. Understanding trends in prevalence with age, over time, and by location and sex is important for policy setting and in relation to monitoring and assessing commitment to the WHO Framework Convention on Tobacco Control.

Methods

We estimated prevalence of chewing tobacco use as part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2019 using a modelling strategy that used information on multiple types of smokeless tobacco products. We generated a time series of prevalence of chewing tobacco use among individuals aged 15 years and older from 1990 to 2019 in 204 countries and territories, including age-sex specific estimates. We also compared these trends to those of smoked tobacco over the same time period.

Findings

In 2019, 273·9 million (95% uncertainty interval 258·5 to 290·9) people aged 15 years and older used chewing tobacco, and the global age-standardised prevalence of chewing tobacco use was 4·72% (4·46 to 5·01). 228·2 million (213·6 to 244·7; 83·29% [82·15 to 84·42]) chewing tobacco users lived in the south Asia region. Prevalence among young people aged 15-19 years was over 10% in seven locations in 2019. Although global age-standardised prevalence of smoking tobacco use decreased significantly between 1990 and 2019 (annualised rate of change: -1·21% [-1·26 to -1·16]), similar progress was not observed for chewing tobacco (0·46% [0·13 to 0·79]). Among the 12 highest prevalence countries (Bangladesh, Bhutan, Cambodia, India, Madagascar, Marshall Islands, Myanmar, Nepal, Pakistan, Palau, Sri Lanka, and Yemen), only Yemen had a significant decrease in the prevalence of chewing tobacco use, which was among males between 1990 and 2019 (-0·94% [-1·72 to -0·14]), compared with nine of 12 countries that had significant decreases in the prevalence of smoking tobacco. Among females, none of these 12 countries had significant decreases in prevalence of chewing tobacco use, whereas seven of 12 countries had a significant decrease in the prevalence of tobacco smoking use for the period.

Interpretation

Chewing tobacco remains a substantial public health problem in several regions of the world, and predominantly in south Asia. We found little change in the prevalence of chewing tobacco use between 1990 and 2019, and that control efforts have had much larger effects on the prevalence of smoking tobacco use than on chewing tobacco use in some countries. Mitigating the health effects of chewing tobacco requires stronger regulations and policies that specifically target use of chewing tobacco, especially in countries with high prevalence.

Funding

Bloomberg Philanthropies and the Bill & Melinda Gates Foundation.",,pdf:http://www.thelancet.com/article/S2468266721000657/pdf; doi:https://doi.org/10.1016/S2468-2667(21)00065-7; html:https://europepmc.org/articles/PMC8251505 31844323,https://doi.org/10.1038/s41588-019-0549-x,N6-methyladenosine regulates the stability of RNA:DNA hybrids in human cells.,"Abakir A, Giles TC, Cristini A, Foster JM, Dai N, Starczak M, Rubio-Roldan A, Li M, Eleftheriou M, Crutchley J, Flatt L, Young L, Gaffney DJ, Denning C, Dalhus B, Emes RD, Gackowski D, Corrêa IR, Garcia-Perez JL, Klungland A, Gromak N, Ruzov A.",,Nature genetics,2020,2019-12-16,Y,,,,"R-loops are nucleic acid structures formed by an RNA:DNA hybrid and unpaired single-stranded DNA that represent a source of genomic instability in mammalian cells1-4. Here we show that N6-methyladenosine (m6A) modification, contributing to different aspects of messenger RNA metabolism5,6, is detectable on the majority of RNA:DNA hybrids in human pluripotent stem cells. We demonstrate that m6A-containing R-loops accumulate during G2/M and are depleted at G0/G1 phases of the cell cycle, and that the m6A reader promoting mRNA degradation, YTHDF2 (ref. 7), interacts with R-loop-enriched loci in dividing cells. Consequently, YTHDF2 knockout leads to increased R-loop levels, cell growth retardation and accumulation of γH2AX, a marker for DNA double-strand breaks, in mammalian cells. Our results suggest that m6A regulates accumulation of R-loops, implying a role for this modification in safeguarding genomic stability.",,pdf:https://europepmc.org/articles/pmc6974403?pdf=render; doi:https://doi.org/10.1038/s41588-019-0549-x; html:https://europepmc.org/articles/PMC6974403; pdf:https://europepmc.org/articles/PMC6974403?pdf=render 33991015,https://doi.org/10.1002/alz.12330,TMEM106B and CPOX are genetic determinants of cerebrospinal fluid Alzheimer's disease biomarker levels.,"Hong S, Dobricic V, Ohlei O, Bos I, Vos SJB, Prokopenko D, Tijms BM, Andreasson U, Blennow K, Vandenberghe R, Gabel S, Scheltens P, Teunissen CE, Engelborghs S, Frisoni G, Blin O, Richardson JC, Bordet R, Alzheimer's Disease Neuroimaging Initiative (ADNI), Lleó A, Alcolea D, Popp J, Clark C, Peyratout G, Martinez-Lage P, Tainta M, Dobson RJB, Legido-Quigley C, Sleegers K, Van Broeckhoven C, Tanzi RE, Ten Kate M, Wittig M, Franke A, Lill CM, Barkhof F, Lovestone S, Streffer J, Zetterberg H, Visser PJ, Bertram L.",,Alzheimer's & dementia : the journal of the Alzheimer's Association,2021,2021-05-14,N,Cerebrospinal fluid; Alzheimer's disease; Biomarker; Genome-wide Association Study; Neurogranin; Neurofilament Light; Chitinase-3-like Protein 1,,,"

Introduction

Neurofilament light (NfL), chitinase-3-like protein 1 (YKL-40), and neurogranin (Ng) are biomarkers for Alzheimer's disease (AD) to monitor axonal damage, astroglial activation, and synaptic degeneration, respectively.

Methods

We performed genome-wide association studies (GWAS) using DNA and cerebrospinal fluid (CSF) samples from the EMIF-AD Multimodal Biomarker Discovery study for discovery, and the Alzheimer's Disease Neuroimaging Initiative study for validation analyses. GWAS were performed for all three CSF biomarkers using linear regression models adjusting for relevant covariates.

Results

We identify novel genome-wide significant associations between DNA variants in TMEM106B and CSF levels of NfL, and between CPOX and YKL-40. We confirm previous work suggesting that YKL-40 levels are associated with DNA variants in CHI3L1.

Discussion

Our study provides important new insights into the genetic architecture underlying interindividual variation in three AD-related CSF biomarkers. In particular, our data shed light on the sequence of events regarding the initiation and progression of neuropathological processes relevant in AD.",,pdf:https://ddd.uab.cat/pub/artpub/2021/270272/270272.pdf; doi:https://doi.org/10.1002/alz.12330 @@ -2614,8 +2614,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 36065116,https://doi.org/10.1093/brain/awac321,Brain injury in COVID-19 is associated with dysregulated innate and adaptive immune responses.,"Needham EJ, Ren AL, Digby RJ, Norton EJ, Ebrahimi S, Outtrim JG, Chatfield DA, Manktelow AE, Leibowitz MM, Newcombe VFJ, Doffinger R, Barcenas-Morales G, Fonseca C, Taussig MJ, Burnstein RM, Samanta RJ, Dunai C, Sithole N, Ashton NJ, Zetterberg H, Gisslén M, Edén A, Marklund E, Openshaw PJM, Dunning J, Griffiths MJ, Cavanagh J, Breen G, Irani SR, Elmer A, Kingston N, Summers C, Bradley JR, Taams LS, Michael BD, Bullmore ET, Smith KGC, Lyons PA, Coles AJ, Menon DK, Cambridge NeuroCOVID Group, CITIID-NIHR COVID-19 BioResource Collaboration, Cambridge NIHR Clinical Research Facility.",,Brain : a journal of neurology,2022,2022-11-01,Y,Autoantibodies; Brain injury; neuroinflammation; Covid-19,,,"COVID-19 is associated with neurological complications including stroke, delirium and encephalitis. Furthermore, a post-viral syndrome dominated by neuropsychiatric symptoms is common, and is seemingly unrelated to COVID-19 severity. The true frequency and underlying mechanisms of neurological injury are unknown, but exaggerated host inflammatory responses appear to be a key driver of COVID-19 severity. We investigated the dynamics of, and relationship between, serum markers of brain injury [neurofilament light (NfL), glial fibrillary acidic protein (GFAP) and total tau] and markers of dysregulated host response (autoantibody production and cytokine profiles) in 175 patients admitted with COVID-19 and 45 patients with influenza. During hospitalization, sera from patients with COVID-19 demonstrated elevations of NfL and GFAP in a severity-dependent manner, with evidence of ongoing active brain injury at follow-up 4 months later. These biomarkers were associated with elevations of pro-inflammatory cytokines and the presence of autoantibodies to a large number of different antigens. Autoantibodies were commonly seen against lung surfactant proteins but also brain proteins such as myelin associated glycoprotein. Commensurate findings were seen in the influenza cohort. A distinct process characterized by elevation of serum total tau was seen in patients at follow-up, which appeared to be independent of initial disease severity and was not associated with dysregulated immune responses unlike NfL and GFAP. These results demonstrate that brain injury is a common consequence of both COVID-19 and influenza, and is therefore likely to be a feature of severe viral infection more broadly. The brain injury occurs in the context of dysregulation of both innate and adaptive immune responses, with no single pathogenic mechanism clearly responsible.",,pdf:https://academic.oup.com/brain/article-pdf/145/11/4097/47170622/awac321.pdf; doi:https://doi.org/10.1093/brain/awac321; html:https://europepmc.org/articles/PMC9494359; pdf:https://europepmc.org/articles/PMC9494359?pdf=render 36314129,https://doi.org/10.1161/circulationaha.122.060700,Mild-to-Moderate Kidney Dysfunction and Cardiovascular Disease: Observational and Mendelian Randomization Analyses.,"Gaziano L, Sun L, Arnold M, Bell S, Cho K, Kaptoge SK, Song RJ, Burgess S, Posner DC, Mosconi K, Robinson-Cohen C, Mason AM, Bolton TR, Tao R, Allara E, Schubert P, Chen L, Staley JR, Staplin N, Altay S, Amiano P, Arndt V, Ärnlöv J, Barr ELM, Björkelund C, Boer JMA, Brenner H, Casiglia E, Chiodini P, Cooper JA, Coresh J, Cushman M, Dankner R, Davidson KW, de Jongh RT, Donfrancesco C, Engström G, Freisling H, de la Cámara AG, Gudnason V, Hankey GJ, Hansson PO, Heath AK, Hoorn EJ, Imano H, Jassal SK, Kaaks R, Katzke V, Kauhanen J, Kiechl S, Koenig W, Kronmal RA, Kyrø C, Lawlor DA, Ljungberg B, MacDonald C, Masala G, Meisinger C, Melander O, Moreno Iribas C, Ninomiya T, Nitsch D, Nordestgaard BG, Onland-Moret C, Palmieri L, Petrova D, Garcia JRQ, Rosengren A, Sacerdote C, Sakurai M, Santiuste C, Schulze MB, Sieri S, Sundström J, Tikhonoff V, Tjønneland A, Tong T, Tumino R, Tzoulaki I, van der Schouw YT, Monique Verschuren WM, Völzke H, Wallace RB, Wannamethee SG, Weiderpass E, Willeit P, Woodward M, Yamagishi K, Zamora-Ros R, Akwo EA, Pyarajan S, Gagnon DR, Tsao PS, Muralidhar S, Edwards TL, Damrauer SM, Joseph J, Pennells L, Wilson PWF, Harrison S, Gaziano TA, Inouye M, Baigent C, Casas JP, Langenberg C, Wareham N, Riboli E, Gaziano JM, Danesh J, Hung AM, Butterworth AS, Wood AM, Di Angelantonio E, Emerging Risk Factors Collaboration/EPIC-CVD/Million Veteran Program.",,Circulation,2022,2022-10-31,Y,Kidney diseases; Cardiovascular diseases; Coronary disease; Stroke,,,"

Background

End-stage renal disease is associated with a high risk of cardiovascular events. It is unknown, however, whether mild-to-moderate kidney dysfunction is causally related to coronary heart disease (CHD) and stroke.

Methods

Observational analyses were conducted using individual-level data from 4 population data sources (Emerging Risk Factors Collaboration, EPIC-CVD [European Prospective Investigation into Cancer and Nutrition-Cardiovascular Disease Study], Million Veteran Program, and UK Biobank), comprising 648 135 participants with no history of cardiovascular disease or diabetes at baseline, yielding 42 858 and 15 693 incident CHD and stroke events, respectively, during 6.8 million person-years of follow-up. Using a genetic risk score of 218 variants for estimated glomerular filtration rate (eGFR), we conducted Mendelian randomization analyses involving 413 718 participants (25 917 CHD and 8622 strokes) in EPIC-CVD, Million Veteran Program, and UK Biobank.

Results

There were U-shaped observational associations of creatinine-based eGFR with CHD and stroke, with higher risk in participants with eGFR values <60 or >105 mL·min-1·1.73 m-2, compared with those with eGFR between 60 and 105 mL·min-1·1.73 m-2. Mendelian randomization analyses for CHD showed an association among participants with eGFR <60 mL·min-1·1.73 m-2, with a 14% (95% CI, 3%-27%) higher CHD risk per 5 mL·min-1·1.73 m-2 lower genetically predicted eGFR, but not for those with eGFR >105 mL·min-1·1.73 m-2. Results were not materially different after adjustment for factors associated with the eGFR genetic risk score, such as lipoprotein(a), triglycerides, hemoglobin A1c, and blood pressure. Mendelian randomization results for stroke were nonsignificant but broadly similar to those for CHD.

Conclusions

In people without manifest cardiovascular disease or diabetes, mild-to-moderate kidney dysfunction is causally related to risk of CHD, highlighting the potential value of preventive approaches that preserve and modulate kidney function.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCULATIONAHA.122.060700; doi:https://doi.org/10.1161/CIRCULATIONAHA.122.060700; html:https://europepmc.org/articles/PMC9662821; pdf:https://europepmc.org/articles/PMC9662821?pdf=render 33990564,https://doi.org/10.1038/s41467-021-22752-6,Epigenome-wide association meta-analysis of DNA methylation with coffee and tea consumption.,"Karabegović I, Portilla-Fernandez E, Li Y, Ma J, Maas SCE, Sun D, Hu EA, Kühnel B, Zhang Y, Ambatipudi S, Fiorito G, Huang J, Castillo-Fernandez JE, Wiggins KL, de Klein N, Grioni S, Swenson BR, Polidoro S, Treur JL, Cuenin C, Tsai PC, Costeira R, Chajes V, Braun K, Verweij N, Kretschmer A, Franke L, van Meurs JBJ, Uitterlinden AG, de Knegt RJ, Ikram MA, Dehghan A, Peters A, Schöttker B, Gharib SA, Sotoodehnia N, Bell JT, Elliott P, Vineis P, Relton C, Herceg Z, Brenner H, Waldenberger M, Rebholz CM, Voortman T, Pan Q, Fornage M, Levy D, Kayser M, Ghanbari M.",,Nature communications,2021,2021-05-14,Y,,,,"Coffee and tea are extensively consumed beverages worldwide which have received considerable attention regarding health. Intake of these beverages is consistently linked to, among others, reduced risk of diabetes and liver diseases; however, the mechanisms of action remain elusive. Epigenetics is suggested as a mechanism mediating the effects of dietary and lifestyle factors on disease onset. Here we report the results from epigenome-wide association studies (EWAS) on coffee and tea consumption in 15,789 participants of European and African-American ancestries from 15 cohorts. EWAS meta-analysis of coffee consumption reveals 11 CpGs surpassing the epigenome-wide significance threshold (P-value <1.1×10-7), which annotated to the AHRR, F2RL3, FLJ43663, HDAC4, GFI1 and PHGDH genes. Among them, cg14476101 is significantly associated with expression of the PHGDH and risk of fatty liver disease. Knockdown of PHGDH expression in liver cells shows a correlation with expression levels of genes associated with circulating lipids, suggesting a role of PHGDH in hepatic-lipid metabolism. EWAS meta-analysis on tea consumption reveals no significant association, only two CpGs annotated to CACNA1A and PRDM16 genes show suggestive association (P-value <5.0×10-6). These findings indicate that coffee-associated changes in DNA methylation levels may explain the mechanism of action of coffee consumption in conferring risk of diseases.",,pdf:https://www.nature.com/articles/s41467-021-22752-6.pdf; doi:https://doi.org/10.1038/s41467-021-22752-6; html:https://europepmc.org/articles/PMC8121846; pdf:https://europepmc.org/articles/PMC8121846?pdf=render -35387486,https://doi.org/10.1161/circulationaha.121.057888,Genetic Landscape of the ACE2 Coronavirus Receptor.,"Yang Z, Macdonald-Dunlop E, Chen J, Zhai R, Li T, Richmond A, Klarić L, Pirastu N, Ning Z, Zheng C, Wang Y, Huang T, He Y, Guo H, Ying K, Gustafsson S, Prins B, Ramisch A, Dermitzakis ET, Png G, Eriksson N, Haessler J, Hu X, Zanetti D, Boutin T, Hwang SJ, Wheeler E, Pietzner M, Raffield LM, Kalnapenkis A, Peters JE, Viñuela A, Gilly A, Elmståhl S, Dedoussis G, Petrie JR, Polašek O, Folkersen L, Chen Y, Yao C, Võsa U, Pairo-Castineira E, Clohisey S, Bretherick AD, Rawlik K, GenOMICC Consortium†, IMI-DIRECT Consortium†, Esko T, Enroth S, Johansson Å, Gyllensten U, Langenberg C, Levy D, Hayward C, Assimes TL, Kooperberg C, Manichaikul AW, Siegbahn A, Wallentin L, Lind L, Zeggini E, Schwenk JM, Butterworth AS, Michaëlsson K, Pawitan Y, Joshi PK, Baillie JK, Mälarstig A, Reiner AP, Wilson JF, Shen X.",,Circulation,2022,2022-04-07,Y,Cardiovascular diseases; Angiotensin-converting Enzyme 2; Genome-wide Association Study; Covid-19; Sars-cov-2,,,"

Background

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

Methods

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

Results

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

Conclusions

Human plasma ACE2 shares a genetic basis with cardiovascular disease, COVID-19, and other related diseases. The genetic architecture of the ACE2 protein is mapped, providing a useful resource for further biological and clinical studies on this coronavirus receptor.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCULATIONAHA.121.057888; doi:https://doi.org/10.1161/CIRCULATIONAHA.121.057888; html:https://europepmc.org/articles/PMC9047645; pdf:https://europepmc.org/articles/PMC9047645?pdf=render 30498058,https://doi.org/10.1136/archdischild-2018-315866,Risk factors for permanent childhood hearing impairment.,"Butcher E, Dezateux C, Knowles RL.",,Archives of disease in childhood,2020,2018-11-28,Y,Deafness; epidemiology,Improving Public Health,,"

Objective

While several perinatal risk factors for permanent childhood hearing impairment (PCHI) are known, association with gestational length remains unclear. We hypothesised that shorter gestational length predicts higher PCHI risk.

Design

19 504 participants from the UK Millennium Cohort Study (born 2000-2002, prior to newborn screening).

Methods

Multivariable discrete-time survival analysis to examine associations between parent-reported PCHI by age 11 years and gestational length, plus other prespecified factors.

Results

PCHI affected 2.1 per 1000 children (95% CI 1.5 to 3.0) by age 11; however, gestational length did not predict PCHI risk (HR, 95% CI 1.00, 0.98 to 1.03 per day increase). Risk was increased in those with neonatal illness, with or without admission to neonatal care (6.33, 2.27 to 17.63 and 2.62, 1.15 to 5.97, respectively), of Bangladeshi or Pakistani ethnicity (2.78, 1.06 to 7.31) or born to younger mothers (0.92, 0.87 to 0.97 per year).

Conclusion

Neonatal illness, rather than gestational length, predicts PCHI risk. Further research should explore associations with ethnicity.","This study looked at whether there is a link between gestational length of a child (the length of time of pregnancy) and the likelihood of permanent hearing impairment. The authors looked at data from over 19000 children from a study called the Millenium Cohort Study. They found that shorter gestational length did not increase the likelihood of childhood permanent hearting impairment. However, they found that children who had neonatal illness (illness in the immediate days after birth), if they were Bangladeshi or Pakistani in ethnicity, or if they were born to younger mothers.",pdf:https://adc.bmj.com/content/archdischild/105/2/187.full.pdf; doi:https://doi.org/10.1136/archdischild-2018-315866; html:https://europepmc.org/articles/PMC7025723; pdf:https://europepmc.org/articles/PMC7025723?pdf=render +35387486,https://doi.org/10.1161/circulationaha.121.057888,Genetic Landscape of the ACE2 Coronavirus Receptor.,"Yang Z, Macdonald-Dunlop E, Chen J, Zhai R, Li T, Richmond A, Klarić L, Pirastu N, Ning Z, Zheng C, Wang Y, Huang T, He Y, Guo H, Ying K, Gustafsson S, Prins B, Ramisch A, Dermitzakis ET, Png G, Eriksson N, Haessler J, Hu X, Zanetti D, Boutin T, Hwang SJ, Wheeler E, Pietzner M, Raffield LM, Kalnapenkis A, Peters JE, Viñuela A, Gilly A, Elmståhl S, Dedoussis G, Petrie JR, Polašek O, Folkersen L, Chen Y, Yao C, Võsa U, Pairo-Castineira E, Clohisey S, Bretherick AD, Rawlik K, GenOMICC Consortium†, IMI-DIRECT Consortium†, Esko T, Enroth S, Johansson Å, Gyllensten U, Langenberg C, Levy D, Hayward C, Assimes TL, Kooperberg C, Manichaikul AW, Siegbahn A, Wallentin L, Lind L, Zeggini E, Schwenk JM, Butterworth AS, Michaëlsson K, Pawitan Y, Joshi PK, Baillie JK, Mälarstig A, Reiner AP, Wilson JF, Shen X.",,Circulation,2022,2022-04-07,Y,Cardiovascular diseases; Angiotensin-converting Enzyme 2; Genome-wide Association Study; Covid-19; Sars-cov-2,,,"

Background

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

Methods

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

Results

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

Conclusions

Human plasma ACE2 shares a genetic basis with cardiovascular disease, COVID-19, and other related diseases. The genetic architecture of the ACE2 protein is mapped, providing a useful resource for further biological and clinical studies on this coronavirus receptor.",,pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCULATIONAHA.121.057888; doi:https://doi.org/10.1161/CIRCULATIONAHA.121.057888; html:https://europepmc.org/articles/PMC9047645; pdf:https://europepmc.org/articles/PMC9047645?pdf=render 34516908,https://doi.org/10.1126/sciadv.abh0534,Cell-free DNA TAPS provides multimodal information for early cancer detection.,"Siejka-Zielińska P, Cheng J, Jackson F, Liu Y, Soonawalla Z, Reddy S, Silva M, Puta L, McCain MV, Culver EL, Bekkali N, Schuster-Böckler B, Palamara PF, Mann D, Reeves H, Barnes E, Sivakumar S, Song CX.",,Science advances,2021,2021-09-01,Y,,,,"Multimodal, genome-wide characterization of epigenetic and genetic information in circulating cell-free DNA (cfDNA) could enable more sensitive early cancer detection, but it is technologically challenging. Recently, we developed TET-assisted pyridine borane sequencing (TAPS), which is a mild, bisulfite-free method for base-resolution direct DNA methylation sequencing. Here, we optimized TAPS for cfDNA (cfTAPS) to provide high-quality and high-depth whole-genome cell-free methylomes. We applied cfTAPS to 85 cfDNA samples from patients with hepatocellular carcinoma (HCC) or pancreatic ductal adenocarcinoma (PDAC) and noncancer controls. From only 10 ng of cfDNA (1 to 3 ml of plasma), we generated the most comprehensive cfDNA methylome to date. We demonstrated that cfTAPS provides multimodal information about cfDNA characteristics, including DNA methylation, tissue of origin, and DNA fragmentation. Integrated analysis of these epigenetic and genetic features enables accurate identification of early HCC and PDAC.",,pdf:https://www.science.org/doi/pdf/10.1126/sciadv.abh0534?download=true; doi:https://doi.org/10.1126/sciadv.abh0534; html:https://europepmc.org/articles/PMC8442905; pdf:https://europepmc.org/articles/PMC8442905?pdf=render 34857774,https://doi.org/10.1038/s41598-021-00854-x,Application of information theoretic feature selection and machine learning methods for the development of genetic risk prediction models.,"Jalali-Najafabadi F, Stadler M, Dand N, Jadon D, Soomro M, Ho P, Marzo-Ortega H, Helliwell P, Korendowych E, Simpson MA, Packham J, Smith CH, Barker JN, McHugh N, Warren RB, Barton A, Bowes J, BADBIR Study Group, BSTOP Study Group.",,Scientific reports,2021,2021-12-02,Y,,,,"In view of the growth of clinical risk prediction models using genetic data, there is an increasing need for studies that use appropriate methods to select the optimum number of features from a large number of genetic variants with a high degree of redundancy between features due to linkage disequilibrium (LD). Filter feature selection methods based on information theoretic criteria, are well suited to this challenge and will identify a subset of the original variables that should result in more accurate prediction. However, data collected from cohort studies are often high-dimensional genetic data with potential confounders presenting challenges to feature selection and risk prediction machine learning models. Patients with psoriasis are at high risk of developing a chronic arthritis known as psoriatic arthritis (PsA). The prevalence of PsA in this patient group can be up to 30% and the identification of high risk patients represents an important clinical research which would allow early intervention and a reduction of disability. This also provides us with an ideal scenario for the development of clinical risk prediction models and an opportunity to explore the application of information theoretic criteria methods. In this study, we developed the feature selection and psoriatic arthritis (PsA) risk prediction models that were applied to a cross-sectional genetic dataset of 1462 PsA cases and 1132 cutaneous-only psoriasis (PsC) cases using 2-digit HLA alleles imputed using the SNP2HLA algorithm. We also developed stratification method to mitigate the impact of potential confounder features and illustrate that confounding features impact the feature selection. The mitigated dataset was used in training of seven supervised algorithms. 80% of data was randomly used for training of seven supervised machine learning methods using stratified nested cross validation and 20% was selected randomly as a holdout set for internal validation. The risk prediction models were then further validated in UK Biobank dataset containing data on 1187 participants and a set of features overlapping with the training dataset.Performance of these methods has been evaluated using the area under the curve (AUC), accuracy, precision, recall, F1 score and decision curve analysis(net benefit). The best model is selected based on three criteria: the 'lowest number of feature subset' with the 'maximal average AUC over the nested cross validation' and good generalisability to the UK Biobank dataset. In the original dataset, with over 100 different bootstraps and seven feature selection (FS) methods, HLA_C_*06 was selected as the most informative genetic variant. When the dataset is mitigated the single most important genetic features based on rank was identified as HLA_B_*27 by the seven different feature selection methods, consistent with previous analyses of this data using regression based methods. However, the predictive accuracy of these single features in post mitigation was found to be moderate (AUC= 0.54 (internal cross validation), AUC=0.53 (internal hold out set), AUC=0.55(external data set)). Sequentially adding additional HLA features based on rank improved the performance of the Random Forest classification model where 20 2-digit features selected by Interaction Capping (ICAP) demonstrated (AUC= 0.61 (internal cross validation), AUC=0.57 (internal hold out set), AUC=0.58 (external dataset)). The stratification method for mitigation of confounding features and filter information theoretic feature selection can be applied to a high dimensional dataset with the potential confounders.",,pdf:https://www.nature.com/articles/s41598-021-00854-x.pdf; doi:https://doi.org/10.1038/s41598-021-00854-x; html:https://europepmc.org/articles/PMC8640070; pdf:https://europepmc.org/articles/PMC8640070?pdf=render 32328990,https://doi.org/10.1007/s10654-020-00633-4,The Dementias Platform UK (DPUK) Data Portal.,"Bauermeister S, Orton C, Thompson S, Barker RA, Bauermeister JR, Ben-Shlomo Y, Brayne C, Burn D, Campbell A, Calvin C, Chandran S, Chaturvedi N, Chêne G, Chessell IP, Corbett A, Davis DHJ, Denis M, Dufouil C, Elliott P, Fox N, Hill D, Hofer SM, Hu MT, Jindra C, Kee F, Kim CH, Kim C, Kivimaki M, Koychev I, Lawson RA, Linden GJ, Lyons RA, Mackay C, Matthews PM, McGuiness B, Middleton L, Moody C, Moore K, Na DL, O'Brien JT, Ourselin S, Paranjothy S, Park KS, Porteous DJ, Richards M, Ritchie CW, Rohrer JD, Rossor MN, Rowe JB, Scahill R, Schnier C, Schott JM, Seo SW, South M, Steptoe M, Tabrizi SJ, Tales A, Tillin T, Timpson NJ, Toga AW, Visser PJ, Wade-Martins R, Wilkinson T, Williams J, Wong A, Gallacher JEJ.",,European journal of epidemiology,2020,2020-04-23,Y,Cohorts; epidemiology; data management; Data Access; Data Repository; Data Platform,,,"The Dementias Platform UK Data Portal is a data repository facilitating access to data for 3 370 929 individuals in 42 cohorts. The Data Portal is an end-to-end data management solution providing a secure, fully auditable, remote access environment for the analysis of cohort data. All projects utilising the data are by default collaborations with the cohort research teams generating the data. The Data Portal uses UK Secure eResearch Platform infrastructure to provide three core utilities: data discovery, access, and analysis. These are delivered using a 7 layered architecture comprising: data ingestion, data curation, platform interoperability, data discovery, access brokerage, data analysis and knowledge preservation. Automated, streamlined, and standardised procedures reduce the administrative burden for all stakeholders, particularly for requests involving multiple independent datasets, where a single request may be forwarded to multiple data controllers. Researchers are provided with their own secure 'lab' using VMware which is accessed using two factor authentication. Over the last 2 years, 160 project proposals involving 579 individual cohort data access requests were received. These were received from 268 applicants spanning 72 institutions (56 academic, 13 commercial, 3 government) in 16 countries with 84 requests involving multiple cohorts. Projects are varied including multi-modal, machine learning, and Mendelian randomisation analyses. Data access is usually free at point of use although a small number of cohorts require a data access fee.",,pdf:https://link.springer.com/content/pdf/10.1007/s10654-020-00633-4.pdf; doi:https://doi.org/10.1007/s10654-020-00633-4; html:https://europepmc.org/articles/PMC7320955; pdf:https://europepmc.org/articles/PMC7320955?pdf=render @@ -2636,8 +2636,8 @@ PMC8718341,https://doi.org/,"Loneliness, coping, suicidal thoughts and self-harm 34864818,https://doi.org/10.1038/s41398-021-01736-6,Association of low-frequency and rare coding variants with information processing speed.,"Bressler J, Davies G, Smith AV, Saba Y, Bis JC, Jian X, Hayward C, Yanek L, Smith JA, Mirza SS, Wang R, Adams HHH, Becker D, Boerwinkle E, Campbell A, Cox SR, Eiriksdottir G, Fawns-Ritchie C, Gottesman RF, Grove ML, Guo X, Hofer E, Kardia SLR, Knol MJ, Koini M, Lopez OL, Marioni RE, Nyquist P, Pattie A, Polasek O, Porteous DJ, Rudan I, Satizabal CL, Schmidt H, Schmidt R, Sidney S, Simino J, Smith BH, Turner ST, van der Lee SJ, Ware EB, Whitmer RA, Yaffe K, Yang Q, Zhao W, Gudnason V, Launer LJ, Fitzpatrick AL, Psaty BM, Fornage M, Arfan Ikram M, van Duijn CM, Seshadri S, Mosley TH, Deary IJ.",,Translational psychiatry,2021,2021-12-04,Y,,,,"Measures of information processing speed vary between individuals and decline with age. Studies of aging twins suggest heritability may be as high as 67%. The Illumina HumanExome Bead Chip genotyping array was used to examine the association of rare coding variants with performance on the Digit-Symbol Substitution Test (DSST) in community-dwelling adults participating in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. DSST scores were available for 30,576 individuals of European ancestry from nine cohorts and for 5758 individuals of African ancestry from four cohorts who were older than 45 years and free of dementia and clinical stroke. Linear regression models adjusted for age and gender were used for analysis of single genetic variants, and the T5, T1, and T01 burden tests that aggregate the number of rare alleles by gene were also applied. Secondary analyses included further adjustment for education. Meta-analyses to combine cohort-specific results were carried out separately for each ancestry group. Variants in RNF19A reached the threshold for statistical significance (p = 2.01 × 10-6) using the T01 test in individuals of European descent. RNF19A belongs to the class of E3 ubiquitin ligases that confer substrate specificity when proteins are ubiquitinated and targeted for degradation through the 26S proteasome. Variants in SLC22A7 and OR51A7 were suggestively associated with DSST scores after adjustment for education for African-American participants and in the European cohorts, respectively. Further functional characterization of its substrates will be required to confirm the role of RNF19A in cognitive function.",,pdf:https://www.nature.com/articles/s41398-021-01736-6.pdf; doi:https://doi.org/10.1038/s41398-021-01736-6; html:https://europepmc.org/articles/PMC8643353; pdf:https://europepmc.org/articles/PMC8643353?pdf=render 32553130,https://doi.org/10.1016/s2214-109x(20)30264-3,"Global, regional, and national estimates of the population at increased risk of severe COVID-19 due to underlying health conditions in 2020: a modelling study.","Clark A, Jit M, Warren-Gash C, Guthrie B, Wang HHX, Mercer SW, Sanderson C, McKee M, Troeger C, Ong KL, Checchi F, Perel P, Joseph S, Gibbs HP, Banerjee A, Eggo RM, Centre for the Mathematical Modelling of Infectious Diseases COVID-19 working group.",,The Lancet. Global health,2020,2020-06-15,Y,,,,"

Background

The risk of severe COVID-19 if an individual becomes infected is known to be higher in older individuals and those with underlying health conditions. Understanding the number of individuals at increased risk of severe COVID-19 and how this varies between countries should inform the design of possible strategies to shield or vaccinate those at highest risk.

Methods

We estimated the number of individuals at increased risk of severe disease (defined as those with at least one condition listed as ""at increased risk of severe COVID-19"" in current guidelines) by age (5-year age groups), sex, and country for 188 countries using prevalence data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 and UN population estimates for 2020. The list of underlying conditions relevant to COVID-19 was determined by mapping the conditions listed in GBD 2017 to those listed in guidelines published by WHO and public health agencies in the UK and the USA. We analysed data from two large multimorbidity studies to determine appropriate adjustment factors for clustering and multimorbidity. To help interpretation of the degree of risk among those at increased risk, we also estimated the number of individuals at high risk (defined as those that would require hospital admission if infected) using age-specific infection-hospitalisation ratios for COVID-19 estimated for mainland China and making adjustments to reflect country-specific differences in the prevalence of underlying conditions and frailty. We assumed males were twice at likely as females to be at high risk. We also calculated the number of individuals without an underlying condition that could be considered at increased risk because of their age, using minimum ages from 50 to 70 years. We generated uncertainty intervals (UIs) for our estimates by running low and high scenarios using the lower and upper 95% confidence limits for country population size, disease prevalences, multimorbidity fractions, and infection-hospitalisation ratios, and plausible low and high estimates for the degree of clustering, informed by multimorbidity studies.

Findings

We estimated that 1·7 billion (UI 1·0-2·4) people, comprising 22% (UI 15-28) of the global population, have at least one underlying condition that puts them at increased risk of severe COVID-19 if infected (ranging from <5% of those younger than 20 years to >66% of those aged 70 years or older). We estimated that 349 million (186-787) people (4% [3-9] of the global population) are at high risk of severe COVID-19 and would require hospital admission if infected (ranging from <1% of those younger than 20 years to approximately 20% of those aged 70 years or older). We estimated 6% (3-12) of males to be at high risk compared with 3% (2-7) of females. The share of the population at increased risk was highest in countries with older populations, African countries with high HIV/AIDS prevalence, and small island nations with high diabetes prevalence. Estimates of the number of individuals at increased risk were most sensitive to the prevalence of chronic kidney disease, diabetes, cardiovascular disease, and chronic respiratory disease.

Interpretation

About one in five individuals worldwide could be at increased risk of severe COVID-19, should they become infected, due to underlying health conditions, but this risk varies considerably by age. Our estimates are uncertain, and focus on underlying conditions rather than other risk factors such as ethnicity, socioeconomic deprivation, and obesity, but provide a starting point for considering the number of individuals that might need to be shielded or vaccinated as the global pandemic unfolds.

Funding

UK Department for International Development, Wellcome Trust, Health Data Research UK, Medical Research Council, and National Institute for Health Research.",,pdf:http://www.thelancet.com/article/S2214109X20302643/pdf; doi:https://doi.org/10.1016/S2214-109X(20)30264-3; html:https://europepmc.org/articles/PMC7295519 33887194,https://doi.org/10.1016/j.ajhg.2021.04.003,Whole-genome sequencing association analysis of quantitative red blood cell phenotypes: The NHLBI TOPMed program.,"Hu Y, Stilp AM, McHugh CP, Rao S, Jain D, Zheng X, Lane J, Méric de Bellefon S, Raffield LM, Chen MH, Yanek LR, Wheeler M, Yao Y, Ren C, Broome J, Moon JY, de Vries PS, Hobbs BD, Sun Q, Surendran P, Brody JA, Blackwell TW, Choquet H, Ryan K, Duggirala R, Heard-Costa N, Wang Z, Chami N, Preuss MH, Min N, Ekunwe L, Lange LA, Cushman M, Faraday N, Curran JE, Almasy L, Kundu K, Smith AV, Gabriel S, Rotter JI, Fornage M, Lloyd-Jones DM, Vasan RS, Smith NL, North KE, Boerwinkle E, Becker LC, Lewis JP, Abecasis GR, Hou L, O'Connell JR, Morrison AC, Beaty TH, Kaplan R, Correa A, Blangero J, Jorgenson E, Psaty BM, Kooperberg C, Walton RT, Kleinstiver BP, Tang H, Loos RJF, Soranzo N, Butterworth AS, Nickerson D, Rich SS, Mitchell BD, Johnson AD, Auer PL, Li Y, Mathias RA, Lettre G, Pankratz N, Laurie CC, Laurie CA, Bauer DE, Conomos MP, Reiner AP, NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium.",,American journal of human genetics,2021,2021-04-21,N,Whole-genome Sequencing; Base Editing; Red Blood Cell Traits,,,"Whole-genome sequencing (WGS), a powerful tool for detecting novel coding and non-coding disease-causing variants, has largely been applied to clinical diagnosis of inherited disorders. Here we leveraged WGS data in up to 62,653 ethnically diverse participants from the NHLBI Trans-Omics for Precision Medicine (TOPMed) program and assessed statistical association of variants with seven red blood cell (RBC) quantitative traits. We discovered 14 single variant-RBC trait associations at 12 genomic loci, which have not been reported previously. Several of the RBC trait-variant associations (RPN1, ELL2, MIDN, HBB, HBA1, PIEZO1, and G6PD) were replicated in independent GWAS datasets imputed to the TOPMed reference panel. Most of these discovered variants are rare/low frequency, and several are observed disproportionately among non-European Ancestry (African, Hispanic/Latino, or East Asian) populations. We identified a 3 bp indel p.Lys2169del (g.88717175_88717177TCT[4]) (common only in the Ashkenazi Jewish population) of PIEZO1, a gene responsible for the Mendelian red cell disorder hereditary xerocytosis (MIM: 194380), associated with higher mean corpuscular hemoglobin concentration (MCHC). In stepwise conditional analysis and in gene-based rare variant aggregated association analysis, we identified several of the variants in HBB, HBA1, TMPRSS6, and G6PD that represent the carrier state for known coding, promoter, or splice site loss-of-function variants that cause inherited RBC disorders. Finally, we applied base and nuclease editing to demonstrate that the sentinel variant rs112097551 (nearest gene RPN1) acts through a cis-regulatory element that exerts long-range control of the gene RUVBL1 which is essential for hematopoiesis. Together, these results demonstrate the utility of WGS in ethnically diverse population-based samples and gene editing for expanding knowledge of the genetic architecture of quantitative hematologic traits and suggest a continuum between complex trait and Mendelian red cell disorders.",,pdf:http://www.cell.com/article/S0002929721001348/pdf; doi:https://doi.org/10.1016/j.ajhg.2021.04.003; html:https://europepmc.org/articles/PMC8206199; pdf:https://europepmc.org/articles/PMC8206199?pdf=render; doi:https://doi.org/10.1016/j.ajhg.2021.04.003 -38554713,https://doi.org/10.1016/s2213-8587(24)00040-8,Effects of statin therapy on diagnoses of new-onset diabetes and worsening glycaemia in large-scale randomised blinded statin trials: an individual participant data meta-analysis.,"Cholesterol Treatment Trialists’ (CTT) Collaboration. Electronic address: ctt@ndph.ox.ac.uk, Cholesterol Treatment Trialists’ (CTT) Collaboration.",,The lancet. Diabetes & endocrinology,2024,2024-03-27,Y,,,,"

Background

Previous meta-analyses of summary data from randomised controlled trials have shown that statin therapy increases the risk of diabetes, but less is known about the size or timing of this effect, or who is at greatest risk. We aimed to address these gaps in knowledge through analysis of individual participant data from large, long-term, randomised, double-blind trials of statin therapy.

Methods

We conducted a meta-analysis of individual participant data from randomised controlled trials of statin therapy that participated in the CTT Collaboration. All double-blind randomised controlled trials of statin therapy of at least 2 years' scheduled duration and with at least 1000 participants were eligible for inclusion in this meta-analysis. All recorded diabetes-related adverse events, treatments, and measures of glycaemia were sought from eligible trials. Meta-analyses assessed the effects of allocation to statin therapy on new-onset diabetes (defined by diabetes-related adverse events, use of new glucose-lowering medications, glucose concentrations, or HbA1c values) and on worsening glycaemia in people with diabetes (defined by complications of glucose control, increased use of glucose-lowering medication, or HbA1c increase of ≥0·5%). Standard inverse-variance-weighted meta-analyses of the effects on these outcomes were conducted according to a prespecified protocol.

Findings

Of the trials participating in the CTT Collaboration, 19 trials compared statin versus placebo (123 940 participants, 25 701 [21%] with diabetes; median follow-up of 4·3 years), and four trials compared more versus less intensive statin therapy (30 724 participants, 5340 [17%] with diabetes, median follow-up of 4·9 years). Compared with placebo, allocation to low-intensity or moderate-intensity statin therapy resulted in a 10% proportional increase in new-onset diabetes (2420 of 39 179 participants assigned to receive a statin [1·3% per year] vs 2214 of 39 266 participants assigned to receive placebo [1·2% per year]; rate ratio [RR] 1·10, 95% CI 1·04-1·16), and allocation to high-intensity statin therapy resulted in a 36% proportional increase (1221 of 9935 participants assigned to receive a statin [4·8% per year] vs 905 of 9859 participants assigned to receive placebo [3·5% per year]; 1·36, 1·25-1·48). For each trial, the rate of new-onset diabetes among participants allocated to receive placebo depended mostly on the proportion of participants who had at least one follow-up HbA1c measurement; this proportion was much higher in the high-intensity than the low-intensity or moderate-intensity trials. Consequently, the main determinant of the magnitude of the absolute excesses in the two types of trial was the extent of HbA1c measurement rather than the proportional increase in risk associated with statin therapy. In participants without baseline diabetes, mean glucose increased by 0·04 mmol/L with both low-intensity or moderate-intensity (95% CI 0·03-0·05) and high-intensity statins (0·02-0·06), and mean HbA1c increased by 0·06% (0·00-0·12) with low-intensity or moderate-intensity statins and 0·08% (0·07-0·09) with high-intensity statins. Among those with a baseline measure of glycaemia, approximately 62% of new-onset diabetes cases were among participants who were already in the top quarter of the baseline distribution. The relative effects of statin therapy on new-onset diabetes were similar among different types of participants and over time. Among participants with baseline diabetes, the RRs for worsening glycaemia were 1·10 (1·06-1·14) for low-intensity or moderate-intensity statin therapy and 1·24 (1·06-1·44) for high-intensity statin therapy compared with placebo.

Interpretation

Statins cause a moderate dose-dependent increase in new diagnoses of diabetes that is consistent with a small upwards shift in glycaemia, with the majority of new diagnoses of diabetes occurring in people with baseline glycaemic markers that are close to the diagnostic threshold for diabetes. Importantly, however, any theoretical adverse effects of statins on cardiovascular risk that might arise from these small increases in glycaemia (or, indeed, from any other mechanism) are already accounted for in the overall reduction in cardiovascular risk that is seen with statin therapy in these trials. These findings should further inform clinical guidelines regarding clinical management of people taking statin therapy.

Funding

British Heart Foundation, UK Medical Research Council, and Australian National Health and Medical Research Council.",,pdf:http://www.thelancet.com/article/S2213858724000408/pdf; doi:https://doi.org/10.1016/S2213-8587(24)00040-8; html:https://europepmc.org/articles/PMC7615958; pdf:https://europepmc.org/articles/PMC7615958?pdf=render 34087097,https://doi.org/10.1016/s2352-3018(21)00051-5,"Subnational mapping of HIV incidence and mortality among individuals aged 15-49 years in sub-Saharan Africa, 2000-18: a modelling study.",Local Burden of Disease HIV Collaborators.,,The lancet. HIV,2021,2021-06-01,Y,,,,"

Background

High-resolution estimates of HIV burden across space and time provide an important tool for tracking and monitoring the progress of prevention and control efforts and assist with improving the precision and efficiency of targeting efforts. We aimed to assess HIV incidence and HIV mortality for all second-level administrative units across sub-Saharan Africa.

Methods

In this modelling study, we developed a framework that used the geographically specific HIV prevalence data collected in seroprevalence surveys and antenatal care clinics to train a model that estimates HIV incidence and mortality among individuals aged 15-49 years. We used a model-based geostatistical framework to estimate HIV prevalence at the second administrative level in 44 countries in sub-Saharan Africa for 2000-18 and sought data on the number of individuals on antiretroviral therapy (ART) by second-level administrative unit. We then modified the Estimation and Projection Package (EPP) to use these HIV prevalence and treatment estimates to estimate HIV incidence and mortality by second-level administrative unit.

Findings

The estimates suggest substantial variation in HIV incidence and mortality rates both between and within countries in sub-Saharan Africa, with 15 countries having a ten-times or greater difference in estimated HIV incidence between the second-level administrative units with the lowest and highest estimated incidence levels. Across all 44 countries in 2018, HIV incidence ranged from 2·8 (95% uncertainty interval 2·1-3·8) in Mauritania to 1585·9 (1369·4-1824·8) cases per 100 000 people in Lesotho and HIV mortality ranged from 0·8 (0·7-0·9) in Mauritania to 676·5 (513·6-888·0) deaths per 100 000 people in Lesotho. Variation in both incidence and mortality was substantially greater at the subnational level than at the national level and the highest estimated rates were accordingly higher. Among second-level administrative units, Guijá District, Gaza Province, Mozambique, had the highest estimated HIV incidence (4661·7 [2544·8-8120·3]) cases per 100 000 people in 2018 and Inhassunge District, Zambezia Province, Mozambique, had the highest estimated HIV mortality rate (1163·0 [679·0-1866·8]) deaths per 100 000 people. Further, the rate of reduction in HIV incidence and mortality from 2000 to 2018, as well as the ratio of new infections to the number of people living with HIV was highly variable. Although most second-level administrative units had declines in the number of new cases (3316 [81·1%] of 4087 units) and number of deaths (3325 [81·4%]), nearly all appeared well short of the targeted 75% reduction in new cases and deaths between 2010 and 2020.

Interpretation

Our estimates suggest that most second-level administrative units in sub-Saharan Africa are falling short of the targeted 75% reduction in new cases and deaths by 2020, which is further compounded by substantial within-country variability. These estimates will help decision makers and programme implementers expand access to ART and better target health resources to higher burden subnational areas.

Funding

Bill & Melinda Gates Foundation.",,pdf:https://digital.library.adelaide.edu.au/dspace/bitstream/2440/131776/2/hdl_131776.pdf; doi:https://doi.org/10.1016/S2352-3018(21)00051-5; html:https://europepmc.org/articles/PMC8187986 +38554713,https://doi.org/10.1016/s2213-8587(24)00040-8,Effects of statin therapy on diagnoses of new-onset diabetes and worsening glycaemia in large-scale randomised blinded statin trials: an individual participant data meta-analysis.,"Cholesterol Treatment Trialists’ (CTT) Collaboration. Electronic address: ctt@ndph.ox.ac.uk, Cholesterol Treatment Trialists’ (CTT) Collaboration.",,The lancet. Diabetes & endocrinology,2024,2024-03-27,Y,,,,"

Background

Previous meta-analyses of summary data from randomised controlled trials have shown that statin therapy increases the risk of diabetes, but less is known about the size or timing of this effect, or who is at greatest risk. We aimed to address these gaps in knowledge through analysis of individual participant data from large, long-term, randomised, double-blind trials of statin therapy.

Methods

We conducted a meta-analysis of individual participant data from randomised controlled trials of statin therapy that participated in the CTT Collaboration. All double-blind randomised controlled trials of statin therapy of at least 2 years' scheduled duration and with at least 1000 participants were eligible for inclusion in this meta-analysis. All recorded diabetes-related adverse events, treatments, and measures of glycaemia were sought from eligible trials. Meta-analyses assessed the effects of allocation to statin therapy on new-onset diabetes (defined by diabetes-related adverse events, use of new glucose-lowering medications, glucose concentrations, or HbA1c values) and on worsening glycaemia in people with diabetes (defined by complications of glucose control, increased use of glucose-lowering medication, or HbA1c increase of ≥0·5%). Standard inverse-variance-weighted meta-analyses of the effects on these outcomes were conducted according to a prespecified protocol.

Findings

Of the trials participating in the CTT Collaboration, 19 trials compared statin versus placebo (123 940 participants, 25 701 [21%] with diabetes; median follow-up of 4·3 years), and four trials compared more versus less intensive statin therapy (30 724 participants, 5340 [17%] with diabetes, median follow-up of 4·9 years). Compared with placebo, allocation to low-intensity or moderate-intensity statin therapy resulted in a 10% proportional increase in new-onset diabetes (2420 of 39 179 participants assigned to receive a statin [1·3% per year] vs 2214 of 39 266 participants assigned to receive placebo [1·2% per year]; rate ratio [RR] 1·10, 95% CI 1·04-1·16), and allocation to high-intensity statin therapy resulted in a 36% proportional increase (1221 of 9935 participants assigned to receive a statin [4·8% per year] vs 905 of 9859 participants assigned to receive placebo [3·5% per year]; 1·36, 1·25-1·48). For each trial, the rate of new-onset diabetes among participants allocated to receive placebo depended mostly on the proportion of participants who had at least one follow-up HbA1c measurement; this proportion was much higher in the high-intensity than the low-intensity or moderate-intensity trials. Consequently, the main determinant of the magnitude of the absolute excesses in the two types of trial was the extent of HbA1c measurement rather than the proportional increase in risk associated with statin therapy. In participants without baseline diabetes, mean glucose increased by 0·04 mmol/L with both low-intensity or moderate-intensity (95% CI 0·03-0·05) and high-intensity statins (0·02-0·06), and mean HbA1c increased by 0·06% (0·00-0·12) with low-intensity or moderate-intensity statins and 0·08% (0·07-0·09) with high-intensity statins. Among those with a baseline measure of glycaemia, approximately 62% of new-onset diabetes cases were among participants who were already in the top quarter of the baseline distribution. The relative effects of statin therapy on new-onset diabetes were similar among different types of participants and over time. Among participants with baseline diabetes, the RRs for worsening glycaemia were 1·10 (1·06-1·14) for low-intensity or moderate-intensity statin therapy and 1·24 (1·06-1·44) for high-intensity statin therapy compared with placebo.

Interpretation

Statins cause a moderate dose-dependent increase in new diagnoses of diabetes that is consistent with a small upwards shift in glycaemia, with the majority of new diagnoses of diabetes occurring in people with baseline glycaemic markers that are close to the diagnostic threshold for diabetes. Importantly, however, any theoretical adverse effects of statins on cardiovascular risk that might arise from these small increases in glycaemia (or, indeed, from any other mechanism) are already accounted for in the overall reduction in cardiovascular risk that is seen with statin therapy in these trials. These findings should further inform clinical guidelines regarding clinical management of people taking statin therapy.

Funding

British Heart Foundation, UK Medical Research Council, and Australian National Health and Medical Research Council.",,pdf:http://www.thelancet.com/article/S2213858724000408/pdf; doi:https://doi.org/10.1016/S2213-8587(24)00040-8; html:https://europepmc.org/articles/PMC7615958; pdf:https://europepmc.org/articles/PMC7615958?pdf=render 34228774,https://doi.org/10.1001/jama.2021.11330,Association Between Administration of IL-6 Antagonists and Mortality Among Patients Hospitalized for COVID-19: A Meta-analysis.,"WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group, Shankar-Hari M, Vale CL, Godolphin PJ, Fisher D, Higgins JPT, Spiga F, Savovic J, Tierney J, Baron G, Benbenishty JS, Berry LR, Broman N, Cavalcanti AB, Colman R, De Buyser SL, Derde LPG, Domingo P, Omar SF, Fernandez-Cruz A, Feuth T, Garcia F, Garcia-Vicuna R, Gonzalez-Alvaro I, Gordon AC, Haynes R, Hermine O, Horby PW, Horick NK, Kumar K, Lambrecht BN, Landray MJ, Leal L, Lederer DJ, Lorenzi E, Mariette X, Merchante N, Misnan NA, Mohan SV, Nivens MC, Oksi J, Perez-Molina JA, Pizov R, Porcher R, Postma S, Rajasuriar R, Ramanan AV, Ravaud P, Reid PD, Rutgers A, Sancho-Lopez A, Seto TB, Sivapalasingam S, Soin AS, Staplin N, Stone JH, Strohbehn GW, Sunden-Cullberg J, Torre-Cisneros J, Tsai LW, van Hoogstraten H, van Meerten T, Veiga VC, Westerweel PE, Murthy S, Diaz JV, Marshall JC, Sterne JAC.",,JAMA,2021,2021-08-01,N,,,,"

Importance

Clinical trials assessing the efficacy of IL-6 antagonists in patients hospitalized for COVID-19 have variously reported benefit, no effect, and harm.

Objective

To estimate the association between administration of IL-6 antagonists compared with usual care or placebo and 28-day all-cause mortality and other outcomes.

Data sources

Trials were identified through systematic searches of electronic databases between October 2020 and January 2021. Searches were not restricted by trial status or language. Additional trials were identified through contact with experts.

Study selection

Eligible trials randomly assigned patients hospitalized for COVID-19 to a group in whom IL-6 antagonists were administered and to a group in whom neither IL-6 antagonists nor any other immunomodulators except corticosteroids were administered. Among 72 potentially eligible trials, 27 (37.5%) met study selection criteria.

Data extraction and synthesis

In this prospective meta-analysis, risk of bias was assessed using the Cochrane Risk of Bias Assessment Tool. Inconsistency among trial results was assessed using the I2 statistic. The primary analysis was an inverse variance-weighted fixed-effects meta-analysis of odds ratios (ORs) for 28-day all-cause mortality.

Main outcomes and measures

The primary outcome measure was all-cause mortality at 28 days after randomization. There were 9 secondary outcomes including progression to invasive mechanical ventilation or death and risk of secondary infection by 28 days.

Results

A total of 10 930 patients (median age, 61 years [range of medians, 52-68 years]; 3560 [33%] were women) participating in 27 trials were included. By 28 days, there were 1407 deaths among 6449 patients randomized to IL-6 antagonists and 1158 deaths among 4481 patients randomized to usual care or placebo (summary OR, 0.86 [95% CI, 0.79-0.95]; P = .003 based on a fixed-effects meta-analysis). This corresponds to an absolute mortality risk of 22% for IL-6 antagonists compared with an assumed mortality risk of 25% for usual care or placebo. The corresponding summary ORs were 0.83 (95% CI, 0.74-0.92; P < .001) for tocilizumab and 1.08 (95% CI, 0.86-1.36; P = .52) for sarilumab. The summary ORs for the association with mortality compared with usual care or placebo in those receiving corticosteroids were 0.77 (95% CI, 0.68-0.87) for tocilizumab and 0.92 (95% CI, 0.61-1.38) for sarilumab. The ORs for the association with progression to invasive mechanical ventilation or death, compared with usual care or placebo, were 0.77 (95% CI, 0.70-0.85) for all IL-6 antagonists, 0.74 (95% CI, 0.66-0.82) for tocilizumab, and 1.00 (95% CI, 0.74-1.34) for sarilumab. Secondary infections by 28 days occurred in 21.9% of patients treated with IL-6 antagonists vs 17.6% of patients treated with usual care or placebo (OR accounting for trial sample sizes, 0.99; 95% CI, 0.85-1.16).

Conclusions and relevance

In this prospective meta-analysis of clinical trials of patients hospitalized for COVID-19, administration of IL-6 antagonists, compared with usual care or placebo, was associated with lower 28-day all-cause mortality.

Trial registration

PROSPERO Identifier: CRD42021230155.",,pdf:https://biblio.ugent.be/publication/8716283/file/8716284.pdf; doi:https://doi.org/10.1001/jama.2021.11330; html:https://europepmc.org/articles/PMC8261689; doi:https://doi.org/10.1001/jama.2021.11330 37863501,https://doi.org/10.1136/bmj-2023-076387,Enhancing reporting quality and impact of early phase dose-finding clinical trials: CONSORT Dose-finding Extension (CONSORT-DEFINE) guidance.,"Yap C, Solovyeva O, de Bono J, Rekowski J, Patel D, Jaki T, Mander A, Evans TRJ, Peck R, Hayward KS, Hopewell S, Ursino M, Rantell KR, Calvert M, Lee S, Kightley A, Ashby D, Chan AW, Garrett-Mayer E, Isaacs JD, Golub R, Kholmanskikh O, Richards D, Boix O, Matcham J, Seymour L, Ivy SP, Marshall LV, Hommais A, Liu R, Tanaka Y, Berlin J, Espinasse A, Dimairo M, Weir CJ.",,BMJ (Clinical research ed.),2023,2023-10-20,Y,,,,,,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10583500; doi:https://doi.org/10.1136/bmj-2023-076387; html:https://europepmc.org/articles/PMC10583500 32573913,https://doi.org/10.1002/alz.12106,Genome-wide association study of rate of cognitive decline in Alzheimer's disease patients identifies novel genes and pathways.,"Sherva R, Gross A, Mukherjee S, Koesterer R, Amouyel P, Bellenguez C, Dufouil C, Bennett DA, Chibnik L, Cruchaga C, Del-Aguila J, Farrer LA, Mayeux R, Munsie L, Winslow A, Newhouse S, Saykin AJ, Kauwe JSK, Alzheimer's Disease Genetics Consortium, Crane PK, Green RC.",,Alzheimer's & dementia : the journal of the Alzheimer's Association,2020,2020-06-23,N,Disease Progression; Genetic Association; Cognitive Decline; Pathway analysis,,,"

Introduction

Variability exists in the disease trajectories of Alzheimer's disease (AD) patients. We performed a genome-wide association study to examine rate of cognitive decline (ROD) in patients with AD.

Methods

We tested for interactions between genetic variants and time since diagnosis to predict the ROD of a composite cognitive score in 3946 AD cases and performed pathway analysis on the top genes.

Results

Suggestive associations (P < 1.0 × 10-6 ) were observed on chromosome 15 in DNA polymerase-γ (rs3176205, P = 1.11 × 10-7 ), chromosome 7 (rs60465337,P = 4.06 × 10-7 ) in contactin-associated protein-2, in RP11-384F7.1 on chromosome 3 (rs28853947, P = 5.93 × 10-7 ), family with sequence similarity 214 member-A on chromosome 15 (rs2899492, P = 5.94 × 10-7 ), and intergenic regions on chromosomes 16 (rs4949142, P = 4.02 × 10-7 ) and 4 (rs1304013, P = 7.73 × 10-7 ). Significant pathways involving neuronal development and function, apoptosis, memory, and inflammation were identified.

Discussion

Pathways related to AD, intelligence, and neurological function determine AD progression, while previously identified AD risk variants, including the apolipoprotein (APOE) ε4 and ε2 variants, do not have a major impact.",,html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7924136; doi:https://doi.org/10.1002/alz.12106; html:https://europepmc.org/articles/PMC7924136; pdf:https://europepmc.org/articles/PMC7924136?pdf=render; doi:https://doi.org/10.1002/alz.12106 diff --git a/data/papers.json b/data/papers.json index 4b030e9a..38a3a27a 100644 --- a/data/papers.json +++ b/data/papers.json @@ -747,23 +747,6 @@ "laySummary": "", "urls": "pdf:http://pure-oai.bham.ac.uk/ws/files/172896799/Cancer_Medicine_2022_Bahcivanci_Associating_transcriptomics_data_with_inflammatory_markers_to_understand_tumour.pdf; doi:https://doi.org/10.1002/cam4.4941; html:https://europepmc.org/articles/PMC9844659; pdf:https://europepmc.org/articles/PMC9844659?pdf=render" }, - { - "id": "38630417", - "doi": "https://doi.org/10.1007/s44192-024-00066-5", - "title": "Cerebrospinal fluid metabolomes of treatment-resistant depression subtypes and ketamine response: a pilot study.", - "authorString": "Berner J, Acharjee A.", - "authorAffiliations": "", - "journalTitle": "Discover mental health", - "pubYear": "2024", - "date": "2024-04-17", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Depression is a disorder with variable presentation. Selecting treatments and dose-finding is, therefore, challenging and time-consuming. In addition, novel antidepressants such as ketamine have sparse optimization evidence. Insights obtained from metabolomics may improve the management of patients. The objective of this study was to determine whether compounds in the cerebrospinal fluid (CSF) metabolome correlate with scores on questionnaires and response to medication. We performed a retrospective pilot study to evaluate phenotypic and metabolomic variability in patients with treatment-resistant depression using multivariate data compression algorithms. Twenty-nine patients with treatment-resistant depression provided fasting CSF samples. Over 300 metabolites were analyzed in these samples with liquid chromatography-mass spectrometry. Chart review provided basic demographic information, clinical status with self-reported questionnaires, and response to medication. Of the 300 metabolites analyzed, 151 were present in all CSF samples and used in the analyses. Hypothesis-free multivariate analysis compressed the resultant data set into two dimensions using Principal Component (PC) analysis, accounting for\u2009~\u200932% of the variance. PC1 accounted for 16.9% of the variance and strongly correlated with age in one direction and 5-methyltetrahydrofolate, homocarnosine, and depression and anxiety scores in the opposite direction. PC2 accounted for 15.4% of the variance, with one end strongly correlated with autism scores, male gender, and cognitive fatigue scores, and the other end with bipolar diagnosis, lithium use, and ethylmalonate disturbance. This small pilot study suggests that complex treatment-resistant depression can be mapped onto a 2-dimensional pathophysiological domain. The results may have implications for treatment selection for depression subtypes.", - "laySummary": "", - "urls": "pdf:https://link.springer.com/content/pdf/10.1007/s44192-024-00066-5.pdf; doi:https://doi.org/10.1007/s44192-024-00066-5; html:https://europepmc.org/articles/PMC11024073; pdf:https://europepmc.org/articles/PMC11024073?pdf=render" - }, { "id": "36647111", "doi": "https://doi.org/10.1186/s12911-022-02093-0", @@ -781,6 +764,23 @@ "laySummary": "", "urls": "pdf:https://bmcmedinformdecismak.biomedcentral.com/counter/pdf/10.1186/s12911-022-02093-0; doi:https://doi.org/10.1186/s12911-022-02093-0; html:https://europepmc.org/articles/PMC9842203; pdf:https://europepmc.org/articles/PMC9842203?pdf=render" }, + { + "id": "38630417", + "doi": "https://doi.org/10.1007/s44192-024-00066-5", + "title": "Cerebrospinal fluid metabolomes of treatment-resistant depression subtypes and ketamine response: a pilot study.", + "authorString": "Berner J, Acharjee A.", + "authorAffiliations": "", + "journalTitle": "Discover mental health", + "pubYear": "2024", + "date": "2024-04-17", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Depression is a disorder with variable presentation. Selecting treatments and dose-finding is, therefore, challenging and time-consuming. In addition, novel antidepressants such as ketamine have sparse optimization evidence. Insights obtained from metabolomics may improve the management of patients. The objective of this study was to determine whether compounds in the cerebrospinal fluid (CSF) metabolome correlate with scores on questionnaires and response to medication. We performed a retrospective pilot study to evaluate phenotypic and metabolomic variability in patients with treatment-resistant depression using multivariate data compression algorithms. Twenty-nine patients with treatment-resistant depression provided fasting CSF samples. Over 300 metabolites were analyzed in these samples with liquid chromatography-mass spectrometry. Chart review provided basic demographic information, clinical status with self-reported questionnaires, and response to medication. Of the 300 metabolites analyzed, 151 were present in all CSF samples and used in the analyses. Hypothesis-free multivariate analysis compressed the resultant data set into two dimensions using Principal Component (PC) analysis, accounting for\u2009~\u200932% of the variance. PC1 accounted for 16.9% of the variance and strongly correlated with age in one direction and 5-methyltetrahydrofolate, homocarnosine, and depression and anxiety scores in the opposite direction. PC2 accounted for 15.4% of the variance, with one end strongly correlated with autism scores, male gender, and cognitive fatigue scores, and the other end with bipolar diagnosis, lithium use, and ethylmalonate disturbance. This small pilot study suggests that complex treatment-resistant depression can be mapped onto a 2-dimensional pathophysiological domain. The results may have implications for treatment selection for depression subtypes.", + "laySummary": "", + "urls": "pdf:https://link.springer.com/content/pdf/10.1007/s44192-024-00066-5.pdf; doi:https://doi.org/10.1007/s44192-024-00066-5; html:https://europepmc.org/articles/PMC11024073; pdf:https://europepmc.org/articles/PMC11024073?pdf=render" + }, { "id": "38645891", "doi": "https://doi.org/10.1136/bmjmed-2023-000807", @@ -2158,23 +2158,6 @@ "laySummary": "", "urls": "pdf:https://www.nature.com/articles/s41416-022-01830-6.pdf; doi:https://doi.org/10.1038/s41416-022-01830-6; html:https://europepmc.org/articles/PMC9060409; pdf:https://europepmc.org/articles/PMC9060409?pdf=render" }, - { - "id": "37193316", - "doi": "https://doi.org/10.1016/j.xops.2023.100293", - "title": "A Datasheet for the INSIGHT Birmingham, Solihull, and Black Country Diabetic Retinopathy Screening Dataset.", - "authorString": "Kale AU, Mills A, Guggenheim E, Gee D, Bodza S, Anumakonda A, Doal R, Williams R, Gallier S, Lee WH, Galsworthy P, Benning M, Fanning H, Keane PA, Denniston AK, Mollan SP.", - "authorAffiliations": "", - "journalTitle": "Ophthalmology science", - "pubYear": "2023", - "date": "2023-02-26", - "isOpenAccess": "Y", - "keywords": "Diabetes mellitus; Diabetic retinopathy; Imaging; Dataset; Biomedical Data", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Purpose

Diabetic retinopathy\u00a0(DR) is the most common microvascular complication associated with diabetes mellitus (DM), affecting approximately 40% of this patient population. Early detection of DR is vital to ensure monitoring of disease progression and prompt sight saving treatments as required. This article describes the data contained within the INSIGHT Birmingham, Solihull, and Black Country Diabetic Retinopathy Dataset.

Design

Dataset descriptor for routinely collected eye screening data.

Participants

All diabetic patients aged 12 years and older, attending annual digital retinal photography-based screening within the Birmingham, Solihull, and Black Country Eye Screening Programme.

Methods

The INSIGHT Health Data Research Hub for Eye Health is a National Health Service (NHS)-led ophthalmic bioresource that provides researchers with safe access to anonymized, routinely collected data from contributing NHS hospitals to advance research for patient benefit. This report describes the INSIGHT Birmingham, Solihull, and Black Country DR Screening Dataset, a dataset of anonymized images and linked screening data derived from the United Kingdom's largest regional DR screening program.

Main outcome measures

This dataset consists of routinely collected data from the eye screening program. The data primarily include retinal photographs with the associated DR grading data. Additional data such as corresponding demographic details, information regarding patients' diabetic status, and visual acuity data are also available. Further details regarding available data points are available in the supplementary information, in addition to the INSIGHT webpage included below.

Results

At the time point of this analysis (December 31, 2019), the dataset comprised 6\u2009202\u2009161 images from 246\u2009180 patients, with a dataset inception date of January 1, 2007. The dataset includes 1\u2009360\u2009547 grading episodes between R0M0 and R3M1.

Conclusions

This dataset descriptor article summarizes the content of the dataset, how it has been curated, and what its potential uses are. Data are available through a structured application process for research studies that support discovery, clinical evidence analyses, and innovation in artificial intelligence technologies for patient benefit. Further information regarding the data repository and contact details can be found at https://www.insight.hdrhub.org/.

Financial disclosures

Proprietary or commercial disclosure may be found after the references.", - "laySummary": "", - "urls": "pdf:http://www.ophthalmologyscience.org/article/S2666914523000258/pdf; doi:https://doi.org/10.1016/j.xops.2023.100293; html:https://europepmc.org/articles/PMC10182318; pdf:https://europepmc.org/articles/PMC10182318?pdf=render" - }, { "id": "33484944", "doi": "https://doi.org/10.1016/j.compbiomed.2021.104216", @@ -2192,6 +2175,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.compbiomed.2021.104216; doi:https://doi.org/10.1016/j.compbiomed.2021.104216; html:https://europepmc.org/articles/PMC7910278" }, + { + "id": "37193316", + "doi": "https://doi.org/10.1016/j.xops.2023.100293", + "title": "A Datasheet for the INSIGHT Birmingham, Solihull, and Black Country Diabetic Retinopathy Screening Dataset.", + "authorString": "Kale AU, Mills A, Guggenheim E, Gee D, Bodza S, Anumakonda A, Doal R, Williams R, Gallier S, Lee WH, Galsworthy P, Benning M, Fanning H, Keane PA, Denniston AK, Mollan SP.", + "authorAffiliations": "", + "journalTitle": "Ophthalmology science", + "pubYear": "2023", + "date": "2023-02-26", + "isOpenAccess": "Y", + "keywords": "Diabetes mellitus; Diabetic retinopathy; Imaging; Dataset; Biomedical Data", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Purpose

Diabetic retinopathy\u00a0(DR) is the most common microvascular complication associated with diabetes mellitus (DM), affecting approximately 40% of this patient population. Early detection of DR is vital to ensure monitoring of disease progression and prompt sight saving treatments as required. This article describes the data contained within the INSIGHT Birmingham, Solihull, and Black Country Diabetic Retinopathy Dataset.

Design

Dataset descriptor for routinely collected eye screening data.

Participants

All diabetic patients aged 12 years and older, attending annual digital retinal photography-based screening within the Birmingham, Solihull, and Black Country Eye Screening Programme.

Methods

The INSIGHT Health Data Research Hub for Eye Health is a National Health Service (NHS)-led ophthalmic bioresource that provides researchers with safe access to anonymized, routinely collected data from contributing NHS hospitals to advance research for patient benefit. This report describes the INSIGHT Birmingham, Solihull, and Black Country DR Screening Dataset, a dataset of anonymized images and linked screening data derived from the United Kingdom's largest regional DR screening program.

Main outcome measures

This dataset consists of routinely collected data from the eye screening program. The data primarily include retinal photographs with the associated DR grading data. Additional data such as corresponding demographic details, information regarding patients' diabetic status, and visual acuity data are also available. Further details regarding available data points are available in the supplementary information, in addition to the INSIGHT webpage included below.

Results

At the time point of this analysis (December 31, 2019), the dataset comprised 6\u2009202\u2009161 images from 246\u2009180 patients, with a dataset inception date of January 1, 2007. The dataset includes 1\u2009360\u2009547 grading episodes between R0M0 and R3M1.

Conclusions

This dataset descriptor article summarizes the content of the dataset, how it has been curated, and what its potential uses are. Data are available through a structured application process for research studies that support discovery, clinical evidence analyses, and innovation in artificial intelligence technologies for patient benefit. Further information regarding the data repository and contact details can be found at https://www.insight.hdrhub.org/.

Financial disclosures

Proprietary or commercial disclosure may be found after the references.", + "laySummary": "", + "urls": "pdf:http://www.ophthalmologyscience.org/article/S2666914523000258/pdf; doi:https://doi.org/10.1016/j.xops.2023.100293; html:https://europepmc.org/articles/PMC10182318; pdf:https://europepmc.org/articles/PMC10182318?pdf=render" + }, { "id": "37228015", "doi": "https://doi.org/10.1371/journal.pbio.3002118", @@ -2209,23 +2209,6 @@ "laySummary": "", "urls": "pdf:https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3002118&type=printable; doi:https://doi.org/10.1371/journal.pbio.3002118; html:https://europepmc.org/articles/PMC10212114; pdf:https://europepmc.org/articles/PMC10212114?pdf=render" }, - { - "id": "38237625", - "doi": "https://doi.org/10.1016/s0140-6736(23)02467-4", - "title": "Undervaccination and severe COVID-19 outcomes: meta-analysis of national cohort studies in England, Northern Ireland, Scotland, and Wales.", - "authorString": "HDR UK COALESCE Consortium.", - "authorAffiliations": "", - "journalTitle": "Lancet (London, England)", - "pubYear": "2024", - "date": "2024-01-15", - "isOpenAccess": "N", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Undervaccination (receiving fewer than the recommended number of SARS-CoV-2 vaccine doses) could be associated with increased risk of severe COVID-19 outcomes-ie, COVID-19 hospitalisation or death-compared with full vaccination (receiving the recommended number of SARS-CoV-2 vaccine doses). We sought to determine the factors associated with undervaccination, and to investigate the risk of severe COVID-19 outcomes in people who were undervaccinated in each UK nation and across the UK.

Methods

We used anonymised, harmonised electronic health record data with whole population coverage to carry out cohort studies in England, Northern Ireland, Scotland, and Wales. Participants were required to be at least 5 years of age to be included in the cohorts. We estimated adjusted odds ratios for undervaccination as of June 1, 2022. We also estimated adjusted hazard ratios (aHRs) for severe COVID-19 outcomes during the period June 1 to Sept 30, 2022, with undervaccination as a time-dependent exposure. We combined results from nation-specific analyses in a UK-wide fixed-effect meta-analysis. We estimated the reduction in severe COVID-19 outcomes associated with a counterfactual scenario in which everyone in the UK was fully vaccinated on June 1, 2022.

Findings

The numbers of people undervaccinated on June 1, 2022 were 26\u2005985\u2005570 (45\u00b78%) of 58\u2005967\u2005360 in England, 938\u2005420 (49\u00b78%) of 1\u2005885\u2005670 in Northern Ireland, 1\u2005709\u2005786 (34\u00b72%) of 4\u2005992\u2005498 in Scotland, and 773\u2005850 (32\u00b78%) of 2\u2005358\u2005740 in Wales. People who were younger, from more deprived backgrounds, of non-White ethnicity, or had a lower number of comorbidities were less likely to be fully vaccinated. There was a total of 40\u2005393 severe COVID-19 outcomes in the cohorts, with 14\u2005156 of these in undervaccinated participants. We estimated the reduction in severe COVID-19 outcomes in the UK over 4 months of follow-up associated with a counterfactual scenario in which everyone was fully vaccinated on June 1, 2022 as 210 (95% CI 94-326) in the 5-15 years age group, 1544 (1399-1689) in those aged 16-74 years, and 5426 (5340-5512) in those aged 75 years or older. aHRs for severe COVID-19 outcomes in the meta-analysis for the age group of 75 years or older were 2\u00b770 (2\u00b761-2\u00b778) for one dose fewer than recommended, 3\u00b713 (2\u00b793-3\u00b734) for two fewer, 3\u00b761 (3\u00b713-4\u00b717) for three fewer, and 3\u00b708 (2\u00b789-3\u00b729) for four fewer.

Interpretation

Rates of undervaccination against COVID-19 ranged from 32\u00b78% to 49\u00b78% across the four UK nations in summer, 2022. Undervaccination was associated with an elevated risk of severe COVID-19 outcomes.

Funding

UK Research and Innovation National Core Studies: Data and Connectivity.", - "laySummary": "", - "urls": "pdf:http://www.thelancet.com/article/S0140673623024674/pdf; doi:https://doi.org/10.1016/S0140-6736(23)02467-4" - }, { "id": "34706900", "doi": "https://doi.org/10.1136/emermed-2021-211706", @@ -2243,6 +2226,23 @@ "laySummary": "", "urls": "pdf:https://emj.bmj.com/content/emermed/early/2022/04/27/emermed-2021-211706.full.pdf; doi:https://doi.org/10.1136/emermed-2021-211706; html:https://europepmc.org/articles/PMC9510399; pdf:https://europepmc.org/articles/PMC9510399?pdf=render" }, + { + "id": "38237625", + "doi": "https://doi.org/10.1016/s0140-6736(23)02467-4", + "title": "Undervaccination and severe COVID-19 outcomes: meta-analysis of national cohort studies in England, Northern Ireland, Scotland, and Wales.", + "authorString": "HDR UK COALESCE Consortium.", + "authorAffiliations": "", + "journalTitle": "Lancet (London, England)", + "pubYear": "2024", + "date": "2024-01-15", + "isOpenAccess": "N", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Undervaccination (receiving fewer than the recommended number of SARS-CoV-2 vaccine doses) could be associated with increased risk of severe COVID-19 outcomes-ie, COVID-19 hospitalisation or death-compared with full vaccination (receiving the recommended number of SARS-CoV-2 vaccine doses). We sought to determine the factors associated with undervaccination, and to investigate the risk of severe COVID-19 outcomes in people who were undervaccinated in each UK nation and across the UK.

Methods

We used anonymised, harmonised electronic health record data with whole population coverage to carry out cohort studies in England, Northern Ireland, Scotland, and Wales. Participants were required to be at least 5 years of age to be included in the cohorts. We estimated adjusted odds ratios for undervaccination as of June 1, 2022. We also estimated adjusted hazard ratios (aHRs) for severe COVID-19 outcomes during the period June 1 to Sept 30, 2022, with undervaccination as a time-dependent exposure. We combined results from nation-specific analyses in a UK-wide fixed-effect meta-analysis. We estimated the reduction in severe COVID-19 outcomes associated with a counterfactual scenario in which everyone in the UK was fully vaccinated on June 1, 2022.

Findings

The numbers of people undervaccinated on June 1, 2022 were 26\u2005985\u2005570 (45\u00b78%) of 58\u2005967\u2005360 in England, 938\u2005420 (49\u00b78%) of 1\u2005885\u2005670 in Northern Ireland, 1\u2005709\u2005786 (34\u00b72%) of 4\u2005992\u2005498 in Scotland, and 773\u2005850 (32\u00b78%) of 2\u2005358\u2005740 in Wales. People who were younger, from more deprived backgrounds, of non-White ethnicity, or had a lower number of comorbidities were less likely to be fully vaccinated. There was a total of 40\u2005393 severe COVID-19 outcomes in the cohorts, with 14\u2005156 of these in undervaccinated participants. We estimated the reduction in severe COVID-19 outcomes in the UK over 4 months of follow-up associated with a counterfactual scenario in which everyone was fully vaccinated on June 1, 2022 as 210 (95% CI 94-326) in the 5-15 years age group, 1544 (1399-1689) in those aged 16-74 years, and 5426 (5340-5512) in those aged 75 years or older. aHRs for severe COVID-19 outcomes in the meta-analysis for the age group of 75 years or older were 2\u00b770 (2\u00b761-2\u00b778) for one dose fewer than recommended, 3\u00b713 (2\u00b793-3\u00b734) for two fewer, 3\u00b761 (3\u00b713-4\u00b717) for three fewer, and 3\u00b708 (2\u00b789-3\u00b729) for four fewer.

Interpretation

Rates of undervaccination against COVID-19 ranged from 32\u00b78% to 49\u00b78% across the four UK nations in summer, 2022. Undervaccination was associated with an elevated risk of severe COVID-19 outcomes.

Funding

UK Research and Innovation National Core Studies: Data and Connectivity.", + "laySummary": "", + "urls": "pdf:http://www.thelancet.com/article/S0140673623024674/pdf; doi:https://doi.org/10.1016/S0140-6736(23)02467-4" + }, { "id": "37644002", "doi": "https://doi.org/10.1038/s41467-023-40965-9", @@ -2294,23 +2294,6 @@ "laySummary": "", "urls": "pdf:https://www.nature.com/articles/s41598-023-48894-9.pdf; doi:https://doi.org/10.1038/s41598-023-48894-9; html:https://europepmc.org/articles/PMC10716386; pdf:https://europepmc.org/articles/PMC10716386?pdf=render" }, - { - "id": "36102210", - "doi": "https://doi.org/10.1002/prp2.1007", - "title": "What is the evidence that a pharmacy team working in an acute or emergency medicine department improves outcomes for patients: A systematic review.", - "authorString": "Punj E, Collins A, Agravedi N, Marriott J, Sapey E.", - "authorAffiliations": "", - "journalTitle": "Pharmacology research & perspectives", - "pubYear": "2022", - "date": "2022-10-01", - "isOpenAccess": "Y", - "keywords": "Emergency Medicine; Medication Errors; Medication Reconciliation; Pharmac*", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Pharmacy services within hospitals are changing, with more taking on medication reconciliation activities. This systematic review was conducted to determine the measured impacts of Pharmacy teams working in an acute or emergency medicine department. The protocol followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and was prospectively registered on PROSPERO, National Institute for Health and Care Research, UK registration number: CRD42020187487. The systematic review had two co-primary aims: a reduction in the number of incorrect prescriptions on admission by comparing the medication list from primary care to secondary care, and a reduction in the severity of harm caused by these incorrect prescriptions; chosen to determine the impact of pharmacy-led medication reconciliation services in the emergency and acute medicine setting. Seventeen articles were included. Fifteen were non-randomized controlled trials and two were randomized controlled trials. The number of patients combined for all studies was 7630. No studies included were based within the UK. All studies showed benefits in terms of a reduction in medicine errors and patient harm, compared to control arms. Nine articles were included in a statistical analysis comparing the pharmacy intervention arm with the non-pharmacy control arm, with a Chi2 of 101.10 and I2 value\u00a0=\u00a092%. However, studies were heterogenous with different outcome measures and many showed evidence of bias. The included studies consistently indicated that pharmacy services based within acute or emergency medicine departments in hospitals were associated with fewer medication errors. Further studies are needed to understand the health and economic impact of deploying a pharmacy service in acute medical settings including out-of-hours working.", - "laySummary": "", - "urls": "html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9471999; doi:https://doi.org/10.1002/prp2.1007; html:https://europepmc.org/articles/PMC9471999; pdf:https://europepmc.org/articles/PMC9471999?pdf=render" - }, { "id": "33045103", "doi": "https://doi.org/10.1002/gps.5446", @@ -2328,6 +2311,23 @@ "laySummary": "", "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/gps.5446; doi:https://doi.org/10.1002/gps.5446; html:https://europepmc.org/articles/PMC7984448; pdf:https://europepmc.org/articles/PMC7984448?pdf=render" }, + { + "id": "36102210", + "doi": "https://doi.org/10.1002/prp2.1007", + "title": "What is the evidence that a pharmacy team working in an acute or emergency medicine department improves outcomes for patients: A systematic review.", + "authorString": "Punj E, Collins A, Agravedi N, Marriott J, Sapey E.", + "authorAffiliations": "", + "journalTitle": "Pharmacology research & perspectives", + "pubYear": "2022", + "date": "2022-10-01", + "isOpenAccess": "Y", + "keywords": "Emergency Medicine; Medication Errors; Medication Reconciliation; Pharmac*", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Pharmacy services within hospitals are changing, with more taking on medication reconciliation activities. This systematic review was conducted to determine the measured impacts of Pharmacy teams working in an acute or emergency medicine department. The protocol followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and was prospectively registered on PROSPERO, National Institute for Health and Care Research, UK registration number: CRD42020187487. The systematic review had two co-primary aims: a reduction in the number of incorrect prescriptions on admission by comparing the medication list from primary care to secondary care, and a reduction in the severity of harm caused by these incorrect prescriptions; chosen to determine the impact of pharmacy-led medication reconciliation services in the emergency and acute medicine setting. Seventeen articles were included. Fifteen were non-randomized controlled trials and two were randomized controlled trials. The number of patients combined for all studies was 7630. No studies included were based within the UK. All studies showed benefits in terms of a reduction in medicine errors and patient harm, compared to control arms. Nine articles were included in a statistical analysis comparing the pharmacy intervention arm with the non-pharmacy control arm, with a Chi2 of 101.10 and I2 value\u00a0=\u00a092%. However, studies were heterogenous with different outcome measures and many showed evidence of bias. The included studies consistently indicated that pharmacy services based within acute or emergency medicine departments in hospitals were associated with fewer medication errors. Further studies are needed to understand the health and economic impact of deploying a pharmacy service in acute medical settings including out-of-hours working.", + "laySummary": "", + "urls": "html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9471999; doi:https://doi.org/10.1002/prp2.1007; html:https://europepmc.org/articles/PMC9471999; pdf:https://europepmc.org/articles/PMC9471999?pdf=render" + }, { "id": "34238721", "doi": "https://doi.org/10.1016/s2589-7500(21)00105-9", @@ -2889,23 +2889,6 @@ "laySummary": "", "urls": "pdf:https://academic.oup.com/ije/advance-article-pdf/doi/10.1093/ije/dyad022/49393500/dyad022.pdf; doi:https://doi.org/10.1093/ije/dyad022; html:https://europepmc.org/articles/PMC10555861; pdf:https://europepmc.org/articles/PMC10555861?pdf=render" }, - { - "id": "38539097", - "doi": "https://doi.org/10.1186/s12877-024-04804-w", - "title": "'In the shower crying\u2026but we came back in the following day and did it all again'. Distress and resilience in care home staff during the COVID-19 pandemic- A qualitative interview study.", - "authorString": "Cockshott Z, Russell S, Stocker R, Knight J, Mason S, Hanratty B, Preston N.", - "authorAffiliations": "", - "journalTitle": "BMC geriatrics", - "pubYear": "2024", - "date": "2024-03-27", - "isOpenAccess": "Y", - "keywords": "Resilience; Nursing Homes; Care Homes; Coping; Long-term Care Facilities; Staff Well-being; Covid-19; Staff Mental Health", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Care homes (long-term care facilities) were profoundly impacted early in the COVID-19 pandemic, both in terms of resident mortality and restrictions for infection control. This study investigated the impact on the emotional well-being of care home staff of challenges faced at this time, and the strategies used to manage them.

Methods

Semi-structured interviews conducted October 2020-June 2021 with care home staff and health service staff working with them explored the impact of the early waves of the COVID-19 pandemic (March 2020-June 2021). Interview data were analysed using reflexive thematic analysis.

Results

Interview participants were 16 care home staff and 10 health service staff. Analysis generated four key themes: 1)Anxiety and distress, 2)Overwhelming workload, 3)Pulling through; and 4)Resilience in a time of crisis. Care home staff experienced Anxiety and distress due to uncertainty of what to expect; witnessing illness and deaths of residents; concerns regarding their own health, and sometimes feeling their work was under-recognised. They also experienced an Overwhelming workload due to infection control measures, caring for sick residents and reduction in external healthcare support. Our theme of Pulling through reflects the peer support and problem-solving strategies with which care home staff managed the impact of the pandemic, along with a sense of responsibility and meaning towards their work. An overarching theme of Resilience in a time of crisis drew on the other three themes and describes how many staff managed, maintained, and often increased their work despite the challenges of the pandemic. Participants also described increasing emotional fatigue as the pandemic continued.

Conclusions

This paper builds on literature on the emotional impact of the pandemic on care home staff, also exploring ways that staff responded to this impact. These findings can help inform planning for future crises including disease outbreaks, and raise important questions for further work to develop pandemic preparedness in care homes and beyond. They also raise wider questions about the current cultural status of care work, which may have exposed care home staff to greater risk of distress, and which contrasts with the professionalism and responsibility shown by staff in response to pandemic challenges.", - "laySummary": "", - "urls": "pdf:https://bmcgeriatr.biomedcentral.com/counter/pdf/10.1186/s12877-024-04804-w; doi:https://doi.org/10.1186/s12877-024-04804-w; html:https://europepmc.org/articles/PMC10967173; pdf:https://europepmc.org/articles/PMC10967173?pdf=render" - }, { "id": "37126810", "doi": "https://doi.org/10.7326/m21-4269", @@ -2923,6 +2906,23 @@ "laySummary": "", "urls": "html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10152408; doi:https://doi.org/10.7326/M21-4269; html:https://europepmc.org/articles/PMC10152408; pdf:https://europepmc.org/articles/PMC10152408?pdf=render; doi:https://doi.org/10.7326/m21-4269" }, + { + "id": "38539097", + "doi": "https://doi.org/10.1186/s12877-024-04804-w", + "title": "'In the shower crying\u2026but we came back in the following day and did it all again'. Distress and resilience in care home staff during the COVID-19 pandemic- A qualitative interview study.", + "authorString": "Cockshott Z, Russell S, Stocker R, Knight J, Mason S, Hanratty B, Preston N.", + "authorAffiliations": "", + "journalTitle": "BMC geriatrics", + "pubYear": "2024", + "date": "2024-03-27", + "isOpenAccess": "Y", + "keywords": "Resilience; Nursing Homes; Care Homes; Coping; Long-term Care Facilities; Staff Well-being; Covid-19; Staff Mental Health", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Care homes (long-term care facilities) were profoundly impacted early in the COVID-19 pandemic, both in terms of resident mortality and restrictions for infection control. This study investigated the impact on the emotional well-being of care home staff of challenges faced at this time, and the strategies used to manage them.

Methods

Semi-structured interviews conducted October 2020-June 2021 with care home staff and health service staff working with them explored the impact of the early waves of the COVID-19 pandemic (March 2020-June 2021). Interview data were analysed using reflexive thematic analysis.

Results

Interview participants were 16 care home staff and 10 health service staff. Analysis generated four key themes: 1)Anxiety and distress, 2)Overwhelming workload, 3)Pulling through; and 4)Resilience in a time of crisis. Care home staff experienced Anxiety and distress due to uncertainty of what to expect; witnessing illness and deaths of residents; concerns regarding their own health, and sometimes feeling their work was under-recognised. They also experienced an Overwhelming workload due to infection control measures, caring for sick residents and reduction in external healthcare support. Our theme of Pulling through reflects the peer support and problem-solving strategies with which care home staff managed the impact of the pandemic, along with a sense of responsibility and meaning towards their work. An overarching theme of Resilience in a time of crisis drew on the other three themes and describes how many staff managed, maintained, and often increased their work despite the challenges of the pandemic. Participants also described increasing emotional fatigue as the pandemic continued.

Conclusions

This paper builds on literature on the emotional impact of the pandemic on care home staff, also exploring ways that staff responded to this impact. These findings can help inform planning for future crises including disease outbreaks, and raise important questions for further work to develop pandemic preparedness in care homes and beyond. They also raise wider questions about the current cultural status of care work, which may have exposed care home staff to greater risk of distress, and which contrasts with the professionalism and responsibility shown by staff in response to pandemic challenges.", + "laySummary": "", + "urls": "pdf:https://bmcgeriatr.biomedcentral.com/counter/pdf/10.1186/s12877-024-04804-w; doi:https://doi.org/10.1186/s12877-024-04804-w; html:https://europepmc.org/articles/PMC10967173; pdf:https://europepmc.org/articles/PMC10967173?pdf=render" + }, { "id": "38467603", "doi": "https://doi.org/10.1038/s41467-024-46497-0", @@ -3076,23 +3076,6 @@ "laySummary": "", "urls": "pdf:https://www.frontiersin.org/articles/10.3389/fimmu.2023.1146702/pdf; doi:https://doi.org/10.3389/fimmu.2023.1146702; html:https://europepmc.org/articles/PMC10087108; pdf:https://europepmc.org/articles/PMC10087108?pdf=render" }, - { - "id": "37368589", - "doi": "https://doi.org/10.3390/toxics11060489", - "title": "Association between Residential Exposure to Air Pollution and Incident Coronary Heart Disease Is Not Mediated by Leukocyte Telomere Length: A UK Biobank Study.", - "authorString": "Kuo CL, Liu R, Godoy LDC, Pilling LC, Fortinsky RH, Brugge D.", - "authorAffiliations": "", - "journalTitle": "Toxics", - "pubYear": "2023", - "date": "2023-05-28", - "isOpenAccess": "Y", - "keywords": "Pm10; Pm2.5; No2; Nox; Pm2.5 Absorbance; Pm2.5\u201310", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Higher air pollution exposure and shorter leukocyte telomere length (LTL) are both associated with increased risk of coronary heart disease (CHD), and share plausible mechanisms, including inflammation. LTL may serve as a biomarker of air pollution exposure and may be intervened with to reduce the risk of CHD. To the best of our knowledge, we are the first to test the mediation effect of LTL in the relationship between air pollution exposure and incident CHD. Using the UK Biobank (UKB) data (n = 317,601), we conducted a prospective study linking residential air pollution exposure (PM2.5, PM10, NO2, NOx) and LTL to incident CHD during a mean follow-up of 12.6 years. Cox proportional hazards models and generalized additive models with penalized spline functions were used to model the associations of pollutant concentrations and LTL with incident CHD. We found non-linear associations of air pollution exposure with LTL and CHD. Pollutant concentrations in the lower range were decreasingly associated with longer LTL and reduced risk of CHD. The associations between lower pollutant concentrations and reduced risk of CHD, however, were minimally mediated by LTL (<3%). Our findings suggest that air pollution influences CHD through pathways that do not involve LTL. Replication is needed with improved measurements of air pollution that more accurately assesses personal exposure.", - "laySummary": "", - "urls": "doi:https://doi.org/10.3390/toxics11060489; html:https://europepmc.org/articles/PMC10301073; pdf:https://europepmc.org/articles/PMC10301073?pdf=render" - }, { "id": "34864250", "doi": "https://doi.org/10.1016/j.seizure.2021.11.017", @@ -3110,6 +3093,23 @@ "laySummary": "", "urls": "pdf:http://www.seizure-journal.com/article/S1059131121003757/pdf; doi:https://doi.org/10.1016/j.seizure.2021.11.017; html:https://europepmc.org/articles/PMC8626872" }, + { + "id": "37368589", + "doi": "https://doi.org/10.3390/toxics11060489", + "title": "Association between Residential Exposure to Air Pollution and Incident Coronary Heart Disease Is Not Mediated by Leukocyte Telomere Length: A UK Biobank Study.", + "authorString": "Kuo CL, Liu R, Godoy LDC, Pilling LC, Fortinsky RH, Brugge D.", + "authorAffiliations": "", + "journalTitle": "Toxics", + "pubYear": "2023", + "date": "2023-05-28", + "isOpenAccess": "Y", + "keywords": "Pm10; Pm2.5; No2; Nox; Pm2.5 Absorbance; Pm2.5\u201310", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Higher air pollution exposure and shorter leukocyte telomere length (LTL) are both associated with increased risk of coronary heart disease (CHD), and share plausible mechanisms, including inflammation. LTL may serve as a biomarker of air pollution exposure and may be intervened with to reduce the risk of CHD. To the best of our knowledge, we are the first to test the mediation effect of LTL in the relationship between air pollution exposure and incident CHD. Using the UK Biobank (UKB) data (n = 317,601), we conducted a prospective study linking residential air pollution exposure (PM2.5, PM10, NO2, NOx) and LTL to incident CHD during a mean follow-up of 12.6 years. Cox proportional hazards models and generalized additive models with penalized spline functions were used to model the associations of pollutant concentrations and LTL with incident CHD. We found non-linear associations of air pollution exposure with LTL and CHD. Pollutant concentrations in the lower range were decreasingly associated with longer LTL and reduced risk of CHD. The associations between lower pollutant concentrations and reduced risk of CHD, however, were minimally mediated by LTL (<3%). Our findings suggest that air pollution influences CHD through pathways that do not involve LTL. Replication is needed with improved measurements of air pollution that more accurately assesses personal exposure.", + "laySummary": "", + "urls": "doi:https://doi.org/10.3390/toxics11060489; html:https://europepmc.org/articles/PMC10301073; pdf:https://europepmc.org/articles/PMC10301073?pdf=render" + }, { "id": "35858680", "doi": "https://doi.org/10.1136/bmj-2021-068946", @@ -3416,23 +3416,6 @@ "laySummary": "", "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/11/11/e054861.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-054861; html:https://europepmc.org/articles/PMC8609490; pdf:https://europepmc.org/articles/PMC8609490?pdf=render" }, - { - "id": "38429771", - "doi": "https://doi.org/10.1186/s13643-024-02477-5", - "title": "Accuracy of heart failure ascertainment using routinely collected healthcare data: a systematic review and meta-analysis.", - "authorString": "Goonasekera MA, Offer A, Karsan W, El-Nayir M, Mallorie AE, Parish S, Haynes RJ, Mafham MM.", - "authorAffiliations": "", - "journalTitle": "Systematic reviews", - "pubYear": "2024", - "date": "2024-03-01", - "isOpenAccess": "Y", - "keywords": "Meta-analysis; Systematic Review,; Methods Comparison,; Outcome Ascertainment,; Randomized Trials,; Streamlined Clinical Trials,", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Ascertainment of heart failure (HF) hospitalizations in cardiovascular trials is costly and complex, involving processes that could be streamlined by using routinely collected healthcare data (RCD). The utility of coded RCD for HF outcome ascertainment in randomized trials requires assessment. We systematically reviewed studies assessing RCD-based HF outcome ascertainment against \"gold standard\" (GS) methods to study the feasibility of using such methods in clinical trials.

Methods

Studies assessing International Classification of Disease (ICD) coded RCD-based HF outcome ascertainment against GS methods and reporting at least one agreement statistic were identified by searching MEDLINE and Embase from inception to May 2021. Data on study characteristics, details of RCD and GS data sources and definitions, and test statistics were reviewed. Summary sensitivities and specificities for studies ascertaining acute and prevalent HF were estimated using a bivariate random effects meta-analysis. Heterogeneity was evaluated using I2 statistics and hierarchical summary receiver operating characteristic (HSROC) curves.

Results

A total of 58 studies of 48,643 GS-adjudicated HF events were included in this review. Strategies used to improve case identification included the use of broader coding definitions, combining multiple data sources, and using machine learning algorithms to search free text data, but these methods were not always successful and at times reduced specificity in individual studies. Meta-analysis of 17 acute HF studies showed that RCD algorithms have high specificity (96.2%, 95% confidence interval [CI] 91.5-98.3), but lacked sensitivity (63.5%, 95% CI 51.3-74.1) with similar results for 21 prevalent HF studies. There was considerable heterogeneity between studies.

Conclusions

RCD can correctly identify HF outcomes but may miss approximately one-third of events. Methods used to improve case identification should also focus on minimizing false positives.", - "laySummary": "", - "urls": "pdf:https://systematicreviewsjournal.biomedcentral.com/counter/pdf/10.1186/s13643-024-02477-5; doi:https://doi.org/10.1186/s13643-024-02477-5; html:https://europepmc.org/articles/PMC10905869; pdf:https://europepmc.org/articles/PMC10905869?pdf=render" - }, { "id": "36543718", "doi": "https://doi.org/10.1016/j.ebiom.2022.104402", @@ -3450,6 +3433,23 @@ "laySummary": "", "urls": "pdf:http://bura.brunel.ac.uk/bitstream/2438/26835/1/FullText.pdf; doi:https://doi.org/10.1016/j.ebiom.2022.104402; html:https://europepmc.org/articles/PMC9762734; pdf:https://europepmc.org/articles/PMC9762734?pdf=render" }, + { + "id": "38429771", + "doi": "https://doi.org/10.1186/s13643-024-02477-5", + "title": "Accuracy of heart failure ascertainment using routinely collected healthcare data: a systematic review and meta-analysis.", + "authorString": "Goonasekera MA, Offer A, Karsan W, El-Nayir M, Mallorie AE, Parish S, Haynes RJ, Mafham MM.", + "authorAffiliations": "", + "journalTitle": "Systematic reviews", + "pubYear": "2024", + "date": "2024-03-01", + "isOpenAccess": "Y", + "keywords": "Meta-analysis; Systematic Review,; Methods Comparison,; Outcome Ascertainment,; Randomized Trials,; Streamlined Clinical Trials,", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Ascertainment of heart failure (HF) hospitalizations in cardiovascular trials is costly and complex, involving processes that could be streamlined by using routinely collected healthcare data (RCD). The utility of coded RCD for HF outcome ascertainment in randomized trials requires assessment. We systematically reviewed studies assessing RCD-based HF outcome ascertainment against \"gold standard\" (GS) methods to study the feasibility of using such methods in clinical trials.

Methods

Studies assessing International Classification of Disease (ICD) coded RCD-based HF outcome ascertainment against GS methods and reporting at least one agreement statistic were identified by searching MEDLINE and Embase from inception to May 2021. Data on study characteristics, details of RCD and GS data sources and definitions, and test statistics were reviewed. Summary sensitivities and specificities for studies ascertaining acute and prevalent HF were estimated using a bivariate random effects meta-analysis. Heterogeneity was evaluated using I2 statistics and hierarchical summary receiver operating characteristic (HSROC) curves.

Results

A total of 58 studies of 48,643 GS-adjudicated HF events were included in this review. Strategies used to improve case identification included the use of broader coding definitions, combining multiple data sources, and using machine learning algorithms to search free text data, but these methods were not always successful and at times reduced specificity in individual studies. Meta-analysis of 17 acute HF studies showed that RCD algorithms have high specificity (96.2%, 95% confidence interval [CI] 91.5-98.3), but lacked sensitivity (63.5%, 95% CI 51.3-74.1) with similar results for 21 prevalent HF studies. There was considerable heterogeneity between studies.

Conclusions

RCD can correctly identify HF outcomes but may miss approximately one-third of events. Methods used to improve case identification should also focus on minimizing false positives.", + "laySummary": "", + "urls": "pdf:https://systematicreviewsjournal.biomedcentral.com/counter/pdf/10.1186/s13643-024-02477-5; doi:https://doi.org/10.1186/s13643-024-02477-5; html:https://europepmc.org/articles/PMC10905869; pdf:https://europepmc.org/articles/PMC10905869?pdf=render" + }, { "id": "37494295", "doi": "https://doi.org/10.1371/journal.pone.0286840", @@ -5558,23 +5558,6 @@ "laySummary": "", "urls": "pdf:https://www.nature.com/articles/s41586-023-06034-3.pdf; doi:https://doi.org/10.1038/s41586-023-06034-3; html:https://europepmc.org/articles/PMC10208981; pdf:https://europepmc.org/articles/PMC10208981?pdf=render" }, - { - "id": "38106617", - "doi": "https://doi.org/10.1016/j.patter.2023.100892", - "title": "Mortality prediction with adaptive feature importance recalibration for peritoneal dialysis patients.", - "authorString": "Ma L, Zhang C, Gao J, Jiao X, Yu Z, Zhu Y, Wang T, Ma X, Wang Y, Tang W, Zhao X, Ruan W, Wang T.", - "authorAffiliations": "", - "journalTitle": "Patterns (New York, N.Y.)", - "pubYear": "2023", - "date": "2023-12-08", - "isOpenAccess": "Y", - "keywords": "Peritoneal dialysis; PD; End-stage Renal Disease; Electronic Medical Record; Emr; Esrd; Mortality Prediction; Deep Learning; Model Interpretability", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "The study aims to develop AICare, an interpretable mortality prediction model, using electronic medical records (EMR) from follow-up visits for end-stage renal disease (ESRD) patients. AICare includes a multichannel feature extraction module and an adaptive feature importance recalibration module. It integrates dynamic records and static features to perform personalized health context representation learning. The dataset encompasses 13,091 visits and demographic data of 656 peritoneal dialysis (PD) patients spanning 12 years. An additional public dataset of 4,789 visits from 1,363 hemodialysis (HD) patients is also considered. AICare outperforms traditional deep learning models in mortality prediction while retaining interpretability. It uncovers mortality-feature relationships and variations in feature importance and provides reference values. An AI-doctor interaction system is developed for visualizing patients' health trajectories and risk indicators.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1016/j.patter.2023.100892; html:https://europepmc.org/articles/PMC10724364; pdf:https://europepmc.org/articles/PMC10724364?pdf=render" - }, { "id": "36629015", "doi": "https://doi.org/10.1177/17407745221143449", @@ -5592,6 +5575,23 @@ "laySummary": "", "urls": "pdf:https://journals.sagepub.com/doi/pdf/10.1177/17407745221143449; doi:https://doi.org/10.1177/17407745221143449; html:https://europepmc.org/articles/PMC10021127; pdf:https://europepmc.org/articles/PMC10021127?pdf=render" }, + { + "id": "38106617", + "doi": "https://doi.org/10.1016/j.patter.2023.100892", + "title": "Mortality prediction with adaptive feature importance recalibration for peritoneal dialysis patients.", + "authorString": "Ma L, Zhang C, Gao J, Jiao X, Yu Z, Zhu Y, Wang T, Ma X, Wang Y, Tang W, Zhao X, Ruan W, Wang T.", + "authorAffiliations": "", + "journalTitle": "Patterns (New York, N.Y.)", + "pubYear": "2023", + "date": "2023-12-08", + "isOpenAccess": "Y", + "keywords": "Peritoneal dialysis; PD; End-stage Renal Disease; Electronic Medical Record; Emr; Esrd; Mortality Prediction; Deep Learning; Model Interpretability", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "The study aims to develop AICare, an interpretable mortality prediction model, using electronic medical records (EMR) from follow-up visits for end-stage renal disease (ESRD) patients. AICare includes a multichannel feature extraction module and an adaptive feature importance recalibration module. It integrates dynamic records and static features to perform personalized health context representation learning. The dataset encompasses 13,091 visits and demographic data of 656 peritoneal dialysis (PD) patients spanning 12 years. An additional public dataset of 4,789 visits from 1,363 hemodialysis (HD) patients is also considered. AICare outperforms traditional deep learning models in mortality prediction while retaining interpretability. It uncovers mortality-feature relationships and variations in feature importance and provides reference values. An AI-doctor interaction system is developed for visualizing patients' health trajectories and risk indicators.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1016/j.patter.2023.100892; html:https://europepmc.org/articles/PMC10724364; pdf:https://europepmc.org/articles/PMC10724364?pdf=render" + }, { "id": "34446426", "doi": "https://doi.org/10.1136/bmj.n1931", @@ -5677,23 +5677,6 @@ "laySummary": "", "urls": "pdf:https://www.mdpi.com/1422-0067/22/16/8527/pdf?version=1628431894; doi:https://doi.org/10.3390/ijms22168527; html:https://europepmc.org/articles/PMC8395220; pdf:https://europepmc.org/articles/PMC8395220?pdf=render" }, - { - "id": "35165107", - "doi": "https://doi.org/10.1136/bmjopen-2021-050062", - "title": "Investigating the uptake, effectiveness and safety of COVID-19 vaccines: protocol for an observational study using linked UK national data.", - "authorString": "Vasileiou E, Shi T, Kerr S, Robertson C, Joy M, Tsang R, McGagh D, Williams J, Hobbs R, de Lusignan S, de Lusignan S, Bradley D, OReilly D, Murphy S, Chuter A, Beggs J, Ford D, Orton C, Akbari A, Bedston S, Davies G, Griffiths LJ, Griffiths R, Lowthian E, Lyons J, Lyons RA, North L, Perry M, Torabi F, Pickett J, McMenamin J, McCowan C, Agrawal U, Wood R, Stock SJ, Moore E, Henery P, Simpson CR, Sheikh A.", - "authorAffiliations": "", - "journalTitle": "BMJ open", - "pubYear": "2022", - "date": "2022-02-14", - "isOpenAccess": "Y", - "keywords": "epidemiology; Public Health; Respiratory Infections; Covid-19", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Introduction

The novel coronavirus SARS-CoV-2, which emerged in December 2019, has caused millions of deaths and severe illness worldwide. Numerous vaccines are currently under development of which a few have now been authorised for population-level administration by several countries. As of 20 September 2021, over 48\u2009million people have received their first vaccine dose and over 44\u2009million people have received their second vaccine dose across the UK. We aim to assess the uptake rates, effectiveness, and safety of all currently approved COVID-19 vaccines in the UK.

Methods and analysis

We will use prospective cohort study designs to assess vaccine uptake, effectiveness and safety against clinical outcomes and deaths. Test-negative case-control study design will be used to assess vaccine effectiveness (VE) against laboratory confirmed SARS-CoV-2 infection. Self-controlled case series and retrospective cohort study designs will be carried out to assess vaccine safety against mild-to-moderate and severe adverse events, respectively. Individual-level pseudonymised data from primary care, secondary care, laboratory test and death records will be linked and analysed in secure research environments in each UK nation. Univariate and multivariate logistic regression models will be carried out to estimate vaccine uptake levels in relation to various population characteristics. VE estimates against laboratory confirmed SARS-CoV-2 infection will be generated using a generalised additive logistic model. Time-dependent Cox models will be used to estimate the VE against clinical outcomes and deaths. The safety of the vaccines will be assessed using logistic regression models with an offset for the length of the risk period. Where possible, data will be meta-analysed across the UK nations.

Ethics and dissemination

We obtained approvals from the National Research Ethics Service Committee, Southeast Scotland 02 (12/SS/0201), the Secure Anonymised Information Linkage independent Information Governance Review Panel project number 0911. Concerning English data, University of Oxford is compliant with the General Data Protection Regulation and the National Health Service (NHS) Digital Data Security and Protection Policy. This is an approved study (Integrated Research Application ID 301740, Health Research Authority (HRA) Research Ethics Committee 21/HRA/2786). The Oxford-Royal College of General Practitioners Clinical Informatics Digital Hub meets NHS Digital's Data Security and Protection Toolkit requirements. In Northern Ireland, the project was approved by the Honest Broker Governance Board, project number 0064. Findings will be made available to national policy-makers, presented at conferences and published in peer-reviewed journals.", - "laySummary": "", - "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/12/2/e050062.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-050062; html:https://europepmc.org/articles/PMC8844955; pdf:https://europepmc.org/articles/PMC8844955?pdf=render" - }, { "id": "34829865", "doi": "https://doi.org/10.3390/biomedicines9111636", @@ -5711,6 +5694,23 @@ "laySummary": "", "urls": "pdf:https://www.mdpi.com/2227-9059/9/11/1636/pdf?version=1637024773; doi:https://doi.org/10.3390/biomedicines9111636; html:https://europepmc.org/articles/PMC8615894; pdf:https://europepmc.org/articles/PMC8615894?pdf=render" }, + { + "id": "35165107", + "doi": "https://doi.org/10.1136/bmjopen-2021-050062", + "title": "Investigating the uptake, effectiveness and safety of COVID-19 vaccines: protocol for an observational study using linked UK national data.", + "authorString": "Vasileiou E, Shi T, Kerr S, Robertson C, Joy M, Tsang R, McGagh D, Williams J, Hobbs R, de Lusignan S, de Lusignan S, Bradley D, OReilly D, Murphy S, Chuter A, Beggs J, Ford D, Orton C, Akbari A, Bedston S, Davies G, Griffiths LJ, Griffiths R, Lowthian E, Lyons J, Lyons RA, North L, Perry M, Torabi F, Pickett J, McMenamin J, McCowan C, Agrawal U, Wood R, Stock SJ, Moore E, Henery P, Simpson CR, Sheikh A.", + "authorAffiliations": "", + "journalTitle": "BMJ open", + "pubYear": "2022", + "date": "2022-02-14", + "isOpenAccess": "Y", + "keywords": "epidemiology; Public Health; Respiratory Infections; Covid-19", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Introduction

The novel coronavirus SARS-CoV-2, which emerged in December 2019, has caused millions of deaths and severe illness worldwide. Numerous vaccines are currently under development of which a few have now been authorised for population-level administration by several countries. As of 20 September 2021, over 48\u2009million people have received their first vaccine dose and over 44\u2009million people have received their second vaccine dose across the UK. We aim to assess the uptake rates, effectiveness, and safety of all currently approved COVID-19 vaccines in the UK.

Methods and analysis

We will use prospective cohort study designs to assess vaccine uptake, effectiveness and safety against clinical outcomes and deaths. Test-negative case-control study design will be used to assess vaccine effectiveness (VE) against laboratory confirmed SARS-CoV-2 infection. Self-controlled case series and retrospective cohort study designs will be carried out to assess vaccine safety against mild-to-moderate and severe adverse events, respectively. Individual-level pseudonymised data from primary care, secondary care, laboratory test and death records will be linked and analysed in secure research environments in each UK nation. Univariate and multivariate logistic regression models will be carried out to estimate vaccine uptake levels in relation to various population characteristics. VE estimates against laboratory confirmed SARS-CoV-2 infection will be generated using a generalised additive logistic model. Time-dependent Cox models will be used to estimate the VE against clinical outcomes and deaths. The safety of the vaccines will be assessed using logistic regression models with an offset for the length of the risk period. Where possible, data will be meta-analysed across the UK nations.

Ethics and dissemination

We obtained approvals from the National Research Ethics Service Committee, Southeast Scotland 02 (12/SS/0201), the Secure Anonymised Information Linkage independent Information Governance Review Panel project number 0911. Concerning English data, University of Oxford is compliant with the General Data Protection Regulation and the National Health Service (NHS) Digital Data Security and Protection Policy. This is an approved study (Integrated Research Application ID 301740, Health Research Authority (HRA) Research Ethics Committee 21/HRA/2786). The Oxford-Royal College of General Practitioners Clinical Informatics Digital Hub meets NHS Digital's Data Security and Protection Toolkit requirements. In Northern Ireland, the project was approved by the Honest Broker Governance Board, project number 0064. Findings will be made available to national policy-makers, presented at conferences and published in peer-reviewed journals.", + "laySummary": "", + "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/12/2/e050062.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-050062; html:https://europepmc.org/articles/PMC8844955; pdf:https://europepmc.org/articles/PMC8844955?pdf=render" + }, { "id": "34879829", "doi": "https://doi.org/10.1186/s12911-021-01693-6", @@ -5745,23 +5745,6 @@ "laySummary": "", "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/13/7/e069635.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-069635; html:https://europepmc.org/articles/PMC10357777; pdf:https://europepmc.org/articles/PMC10357777?pdf=render" }, - { - "id": "38177425", - "doi": "https://doi.org/10.1038/s43588-023-00461-y", - "title": "GREENER principles for environmentally sustainable computational science.", - "authorString": "Lannelongue L, Aronson HG, Bateman A, Birney E, Caplan T, Juckes M, McEntyre J, Morris AD, Reilly G, Inouye M.", - "authorAffiliations": "", - "journalTitle": "Nature computational science", - "pubYear": "2023", - "date": "2023-06-26", - "isOpenAccess": "N", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "The carbon footprint of scientific computing is substantial, but environmentally sustainable computational science (ESCS) is a nascent field with many opportunities to thrive. To realize the immense green opportunities and continued, yet sustainable, growth of computer science, we must take a coordinated approach to our current challenges, including greater awareness and transparency, improved estimation and wider reporting of environmental impacts. Here, we present a snapshot of where ESCS stands today and introduce the GREENER set of principles, as well as guidance for best practices moving forward.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1038/s43588-023-00461-y" - }, { "id": "31799783", "doi": "https://doi.org/10.1002/cnm.3267", @@ -5779,6 +5762,23 @@ "laySummary": "", "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/cnm.3267; doi:https://doi.org/10.1002/cnm.3267; html:https://europepmc.org/articles/PMC9286682; pdf:https://europepmc.org/articles/PMC9286682?pdf=render" }, + { + "id": "38177425", + "doi": "https://doi.org/10.1038/s43588-023-00461-y", + "title": "GREENER principles for environmentally sustainable computational science.", + "authorString": "Lannelongue L, Aronson HG, Bateman A, Birney E, Caplan T, Juckes M, McEntyre J, Morris AD, Reilly G, Inouye M.", + "authorAffiliations": "", + "journalTitle": "Nature computational science", + "pubYear": "2023", + "date": "2023-06-26", + "isOpenAccess": "N", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "The carbon footprint of scientific computing is substantial, but environmentally sustainable computational science (ESCS) is a nascent field with many opportunities to thrive. To realize the immense green opportunities and continued, yet sustainable, growth of computer science, we must take a coordinated approach to our current challenges, including greater awareness and transparency, improved estimation and wider reporting of environmental impacts. Here, we present a snapshot of where ESCS stands today and introduce the GREENER set of principles, as well as guidance for best practices moving forward.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1038/s43588-023-00461-y" + }, { "id": "37346822", "doi": "https://doi.org/10.12688/wellcomeopenres.18735.2", @@ -5915,23 +5915,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1161/JAHA.123.029552; html:https://europepmc.org/articles/PMC10757541; pdf:https://europepmc.org/articles/PMC10757541?pdf=render" }, - { - "id": "38355631", - "doi": "https://doi.org/10.1186/s12916-024-03284-4", - "title": "Association between pregnancy-related complications and development of type 2 diabetes and hypertension in women: an umbrella review.", - "authorString": "Wambua S, Singh M, Okoth K, Snell KIE, Riley RD, Yau C, Thangaratinam S, Nirantharakumar K, Crowe FL, MuM-PreDiCT Group.", - "authorAffiliations": "", - "journalTitle": "BMC medicine", - "pubYear": "2024", - "date": "2024-02-14", - "isOpenAccess": "Y", - "keywords": "Hypertension; Type 2 diabetes; Pregnancy complications; Obstetrics And Gynaecology; Umbrella Review", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Despite many systematic reviews and meta-analyses examining the associations of pregnancy complications with risk of type 2 diabetes mellitus (T2DM) and hypertension, previous umbrella reviews have only examined a single pregnancy complication. Here we have synthesised evidence from systematic reviews and meta-analyses on the associations of a wide range of pregnancy-related complications with risk of developing T2DM and hypertension.

Methods

Medline, Embase and Cochrane Database of Systematic Reviews were searched from inception until 26 September 2022 for systematic reviews and meta-analysis examining the association between pregnancy complications and risk of T2DM and hypertension. Screening of articles, data extraction and quality appraisal (AMSTAR2) were conducted independently by two reviewers using Covidence software. Data were extracted for studies that examined the risk of T2DM and hypertension in pregnant women with the pregnancy complication compared to pregnant women without the pregnancy complication. Summary estimates of each review were presented using tables, forest plots and narrative synthesis and reported following Preferred Reporting Items for Overviews of Reviews (PRIOR) guidelines.

Results

Ten systematic reviews were included. Two pregnancy complications were identified. Gestational diabetes mellitus (GDM): One review showed GDM was associated with a 10-fold higher risk of T2DM at least 1\u00a0year after pregnancy (relative risk (RR) 9.51 (95% confidence interval (CI) 7.14 to 12.67) and although the association differed by ethnicity (white: RR 16.28 (95% CI 15.01 to 17.66), non-white: RR 10.38 (95% CI 4.61 to 23.39), mixed: RR 8.31 (95% CI 5.44 to 12.69)), the between subgroups difference were not statistically significant at 5% significance level. Another review showed GDM was associated with higher mean blood pressure at least 3\u00a0months postpartum (mean difference in systolic blood pressure: 2.57 (95% CI 1.74 to 3.40) mmHg and mean difference in diastolic blood pressure: 1.89 (95% CI 1.32 to 2.46) mmHg). Hypertensive disorders of pregnancy (HDP): Three reviews showed women with a history of HDP were 3 to 6 times more likely to develop hypertension at least 6\u00a0weeks after pregnancy compared to women without HDP (meta-analysis with largest number of studies: odds ratio (OR) 4.33 (3.51 to 5.33)) and one review reported a higher rate of T2DM after HDP (hazard ratio (HR) 2.24 (1.95 to 2.58)) at least a year after pregnancy. One of the three reviews and five other reviews reported women with a history of preeclampsia were 3 to 7 times more likely to develop hypertension at least 6\u00a0weeks postpartum (meta-analysis with the largest number of studies: OR 3.90 (3.16 to 4.82) with one of these reviews reporting the association was greatest in women from Asia (Asia: OR 7.54 (95% CI 2.49 to 22.81), Europe: OR 2.19 (95% CI 0.30 to 16.02), North and South America: OR 3.32 (95% CI 1.26 to 8.74)).

Conclusions

GDM and HDP are associated with a greater risk of developing T2DM and hypertension. Common confounders adjusted for across the included studies in the reviews were maternal age, body mass index (BMI), socioeconomic status, smoking status, pre-pregnancy and current BMI, parity, family history of T2DM or cardiovascular disease, ethnicity, and time of delivery. Further research is needed to evaluate the value of embedding these pregnancy complications as part of assessment for future risk of T2DM and chronic hypertension.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1186/s12916-024-03284-4; html:https://europepmc.org/articles/PMC10865714; pdf:https://europepmc.org/articles/PMC10865714?pdf=render" - }, { "id": "34108714", "doi": "https://doi.org/10.1038/s41591-021-01408-4", @@ -5949,6 +5932,23 @@ "laySummary": "", "urls": "pdf:https://www.nature.com/articles/s41591-021-01408-4.pdf; doi:https://doi.org/10.1038/s41591-021-01408-4; html:https://europepmc.org/articles/PMC8282499; pdf:https://europepmc.org/articles/PMC8282499?pdf=render" }, + { + "id": "38355631", + "doi": "https://doi.org/10.1186/s12916-024-03284-4", + "title": "Association between pregnancy-related complications and development of type 2 diabetes and hypertension in women: an umbrella review.", + "authorString": "Wambua S, Singh M, Okoth K, Snell KIE, Riley RD, Yau C, Thangaratinam S, Nirantharakumar K, Crowe FL, MuM-PreDiCT Group.", + "authorAffiliations": "", + "journalTitle": "BMC medicine", + "pubYear": "2024", + "date": "2024-02-14", + "isOpenAccess": "Y", + "keywords": "Hypertension; Type 2 diabetes; Pregnancy complications; Obstetrics And Gynaecology; Umbrella Review", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Despite many systematic reviews and meta-analyses examining the associations of pregnancy complications with risk of type 2 diabetes mellitus (T2DM) and hypertension, previous umbrella reviews have only examined a single pregnancy complication. Here we have synthesised evidence from systematic reviews and meta-analyses on the associations of a wide range of pregnancy-related complications with risk of developing T2DM and hypertension.

Methods

Medline, Embase and Cochrane Database of Systematic Reviews were searched from inception until 26 September 2022 for systematic reviews and meta-analysis examining the association between pregnancy complications and risk of T2DM and hypertension. Screening of articles, data extraction and quality appraisal (AMSTAR2) were conducted independently by two reviewers using Covidence software. Data were extracted for studies that examined the risk of T2DM and hypertension in pregnant women with the pregnancy complication compared to pregnant women without the pregnancy complication. Summary estimates of each review were presented using tables, forest plots and narrative synthesis and reported following Preferred Reporting Items for Overviews of Reviews (PRIOR) guidelines.

Results

Ten systematic reviews were included. Two pregnancy complications were identified. Gestational diabetes mellitus (GDM): One review showed GDM was associated with a 10-fold higher risk of T2DM at least 1\u00a0year after pregnancy (relative risk (RR) 9.51 (95% confidence interval (CI) 7.14 to 12.67) and although the association differed by ethnicity (white: RR 16.28 (95% CI 15.01 to 17.66), non-white: RR 10.38 (95% CI 4.61 to 23.39), mixed: RR 8.31 (95% CI 5.44 to 12.69)), the between subgroups difference were not statistically significant at 5% significance level. Another review showed GDM was associated with higher mean blood pressure at least 3\u00a0months postpartum (mean difference in systolic blood pressure: 2.57 (95% CI 1.74 to 3.40) mmHg and mean difference in diastolic blood pressure: 1.89 (95% CI 1.32 to 2.46) mmHg). Hypertensive disorders of pregnancy (HDP): Three reviews showed women with a history of HDP were 3 to 6 times more likely to develop hypertension at least 6\u00a0weeks after pregnancy compared to women without HDP (meta-analysis with largest number of studies: odds ratio (OR) 4.33 (3.51 to 5.33)) and one review reported a higher rate of T2DM after HDP (hazard ratio (HR) 2.24 (1.95 to 2.58)) at least a year after pregnancy. One of the three reviews and five other reviews reported women with a history of preeclampsia were 3 to 7 times more likely to develop hypertension at least 6\u00a0weeks postpartum (meta-analysis with the largest number of studies: OR 3.90 (3.16 to 4.82) with one of these reviews reporting the association was greatest in women from Asia (Asia: OR 7.54 (95% CI 2.49 to 22.81), Europe: OR 2.19 (95% CI 0.30 to 16.02), North and South America: OR 3.32 (95% CI 1.26 to 8.74)).

Conclusions

GDM and HDP are associated with a greater risk of developing T2DM and hypertension. Common confounders adjusted for across the included studies in the reviews were maternal age, body mass index (BMI), socioeconomic status, smoking status, pre-pregnancy and current BMI, parity, family history of T2DM or cardiovascular disease, ethnicity, and time of delivery. Further research is needed to evaluate the value of embedding these pregnancy complications as part of assessment for future risk of T2DM and chronic hypertension.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1186/s12916-024-03284-4; html:https://europepmc.org/articles/PMC10865714; pdf:https://europepmc.org/articles/PMC10865714?pdf=render" + }, { "id": "36243955", "doi": "https://doi.org/10.1093/ndt/gfac287", @@ -6595,23 +6595,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1136/bmjopen-2023-076296; doi:https://doi.org/10.1136/bmjopen-2023-076296; html:https://europepmc.org/articles/PMC10445367; pdf:https://europepmc.org/articles/PMC10445367?pdf=render" }, - { - "id": "38096890", - "doi": "https://doi.org/10.1016/s1470-2045(23)00530-2", - "title": "Mortality from leading cancers in districts of England from 2002 to 2019: a population-based, spatiotemporal study.", - "authorString": "Rashid T, Bennett JE, Muller DC, Cross AJ, Pearson-Stuttard J, Asaria P, Daby HI, Fecht D, Davies B, Ezzati M.", - "authorAffiliations": "", - "journalTitle": "The Lancet. Oncology", - "pubYear": "2024", - "date": "2023-12-11", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Cancers are the leading cause of death in England. We aimed to estimate trends in mortality from leading cancers from 2002 to 2019 for the 314 districts in England.

Methods

We did a high-resolution spatiotemporal analysis of vital registration data from the UK Office for National Statistics using data on all deaths from the ten leading cancers in England from 2002 to 2019. We used a Bayesian hierarchical model to obtain robust estimates of age-specific and cause-specific death rates. We used life table methods to calculate the primary outcome, the unconditional probability of dying between birth and age 80 years by sex, cancer cause of death, local district, and year. We reported Spearman rank correlations between the probability of dying from a cancer and district-level poverty in 2019.

Findings

In 2019, the probability of dying from a cancer before age 80 years ranged from 0\u00b710 (95% credible interval [CrI] 0\u00b710-0\u00b711) to 0\u00b717 (0\u00b716-0\u00b718) for women and from 0\u00b712 (0\u00b712-0\u00b713) to 0\u00b722 (0\u00b721-0\u00b723) for men. Variation in the probability of dying was largest for lung cancer among women, being 3\u00b77 times (95% CrI 3\u00b72-4\u00b74) higher in the district with the highest probability than in the district with the lowest probability; and for stomach cancer for men, being 3\u00b72 times (2\u00b76-4\u00b71) higher in the district with the highest probability than in the one with the lowest probability. The variation in the probability of dying was smallest across districts for lymphoma and multiple myeloma (95% CrI 1\u00b72 times [1\u00b71-1\u00b74] higher in the district with the highest probability than the lowest probability for women and 1\u00b72 times [1\u00b70-1\u00b74] for men), and leukaemia (1\u00b71 times [1\u00b70-1\u00b74] for women and 1\u00b72 times [1\u00b70-1\u00b75] for men). The Spearman rank correlation between probability of dying from a cancer and district poverty was 0\u00b774 (95% CrI 0\u00b772-0\u00b776) for women and 0\u00b779 (0\u00b778-0\u00b781) for men. From 2002 to 2019, the overall probability of dying from a cancer declined in all districts: the reductions ranged from 6\u00b76% (95% CrI 0\u00b73-13\u00b71) to 30\u00b71% (25\u00b76-34\u00b75) for women and from 12\u00b78% (7\u00b71-18\u00b78) to 36\u00b77% (32\u00b72-41\u00b72) for men. However, there were increases in mortality for liver cancer among men, lung cancer and corpus uteri cancer among women, and pancreatic cancer in both sexes in some or all districts with posterior probability greater than 0\u00b780.

Interpretation

Cancers with modifiable risk factors and potential for screening for precancerous lesions had heterogeneous trends and the greatest geographical inequality. To reduce these inequalities, factors affecting both incidence and survival need to be addressed at the local level.

Funding

Wellcome Trust, Imperial College London, UK Medical Research Council, and the National Institute of Health Research.", - "laySummary": "", - "urls": "pdf:http://www.thelancet.com/article/S1470204523005302/pdf; doi:https://doi.org/10.1016/S1470-2045(23)00530-2; html:https://europepmc.org/articles/PMC7615518; pdf:https://europepmc.org/articles/PMC7615518?pdf=render" - }, { "id": "35793922", "doi": "https://doi.org/10.1136/bmjopen-2021-059385", @@ -6630,21 +6613,21 @@ "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/12/7/e059385.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-059385; html:https://europepmc.org/articles/PMC9260199; pdf:https://europepmc.org/articles/PMC9260199?pdf=render" }, { - "id": "36530697", - "doi": "https://doi.org/10.3389/fpubh.2022.1035415", - "title": "Associations between air pollution and multimorbidity in the UK Biobank: A cross-sectional study.", - "authorString": "Ronaldson A, Arias de la Torre J, Ashworth M, Hansell AL, Hotopf M, Mudway I, Stewart R, Dregan A, Bakolis I.", + "id": "38096890", + "doi": "https://doi.org/10.1016/s1470-2045(23)00530-2", + "title": "Mortality from leading cancers in districts of England from 2002 to 2019: a population-based, spatiotemporal study.", + "authorString": "Rashid T, Bennett JE, Muller DC, Cross AJ, Pearson-Stuttard J, Asaria P, Daby HI, Fecht D, Davies B, Ezzati M.", "authorAffiliations": "", - "journalTitle": "Frontiers in public health", - "pubYear": "2022", - "date": "2022-12-02", + "journalTitle": "The Lancet. Oncology", + "pubYear": "2024", + "date": "2023-12-11", "isOpenAccess": "Y", - "keywords": "Air pollution; Nitrogen dioxide; particulate matter; Health Status; Exploratory Factor Analysis; Multimorbidity", + "keywords": "", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Background

Long-term exposure to air pollution concentrations is known to be adversely associated with a broad range of single non-communicable diseases, but its role in multimorbidity has not been investigated in the UK. We aimed to assess associations between long-term air pollution exposure and multimorbidity status, severity, and patterns using the UK Biobank cohort.

Methods

Multimorbidity status was calculated based on 41 physical and mental conditions. We assessed cross-sectional associations between annual modeled particulate matter (PM)2.5, PMcoarse, PM10, and nitrogen dioxide (NO2) concentrations (\u03bcg/m3-modeled to residential address) and multimorbidity status at the baseline assessment (2006-2010) in 364,144 people (mean age: 52.2 \u00b1 8.1 years, 52.6% female). Air pollutants were categorized into quartiles to assess dose-response associations. Among those with multimorbidity (\u22652 conditions; n = 156,395) we assessed associations between air pollutant exposure levels and multimorbidity severity and multimorbidity patterns, which were identified using exploratory factor analysis. Associations were explored using generalized linear models adjusted for sociodemographic, behavioral, and environmental indicators.

Results

Higher exposures to PM2.5, and NO2 were associated with multimorbidity status in a dose-dependent manner. These associations were strongest when we compared the highest air pollution quartile (quartile 4: Q4) with the lowest quartile (Q1) [PM2.5: adjusted odds ratio (adjOR) = 1.21 (95% CI = 1.18, 1.24); NO2: adjOR = 1.19 (95 % CI = 1.16, 1.23)]. We also observed dose-response associations between air pollutant exposures and multimorbidity severity scores. We identified 11 multimorbidity patterns. Air pollution was associated with several multimorbidity patterns with strongest associations (Q4 vs. Q1) observed for neurological (stroke, epilepsy, alcohol/substance dependency) [PM2.5: adjOR = 1.31 (95% CI = 1.14, 1.51); NO2: adjOR = 1.33 (95% CI = 1.11, 1.60)] and respiratory patterns (COPD, asthma) [PM2.5: adjOR = 1.24 (95% CI = 1.16, 1.33); NO2: adjOR = 1.26 (95% CI = 1.15, 1.38)].

Conclusions

This cross-sectional study provides evidence that exposure to air pollution might be associated with having multimorbid, multi-organ conditions. Longitudinal studies are needed to further explore these associations.", + "abstract": "

Background

Cancers are the leading cause of death in England. We aimed to estimate trends in mortality from leading cancers from 2002 to 2019 for the 314 districts in England.

Methods

We did a high-resolution spatiotemporal analysis of vital registration data from the UK Office for National Statistics using data on all deaths from the ten leading cancers in England from 2002 to 2019. We used a Bayesian hierarchical model to obtain robust estimates of age-specific and cause-specific death rates. We used life table methods to calculate the primary outcome, the unconditional probability of dying between birth and age 80 years by sex, cancer cause of death, local district, and year. We reported Spearman rank correlations between the probability of dying from a cancer and district-level poverty in 2019.

Findings

In 2019, the probability of dying from a cancer before age 80 years ranged from 0\u00b710 (95% credible interval [CrI] 0\u00b710-0\u00b711) to 0\u00b717 (0\u00b716-0\u00b718) for women and from 0\u00b712 (0\u00b712-0\u00b713) to 0\u00b722 (0\u00b721-0\u00b723) for men. Variation in the probability of dying was largest for lung cancer among women, being 3\u00b77 times (95% CrI 3\u00b72-4\u00b74) higher in the district with the highest probability than in the district with the lowest probability; and for stomach cancer for men, being 3\u00b72 times (2\u00b76-4\u00b71) higher in the district with the highest probability than in the one with the lowest probability. The variation in the probability of dying was smallest across districts for lymphoma and multiple myeloma (95% CrI 1\u00b72 times [1\u00b71-1\u00b74] higher in the district with the highest probability than the lowest probability for women and 1\u00b72 times [1\u00b70-1\u00b74] for men), and leukaemia (1\u00b71 times [1\u00b70-1\u00b74] for women and 1\u00b72 times [1\u00b70-1\u00b75] for men). The Spearman rank correlation between probability of dying from a cancer and district poverty was 0\u00b774 (95% CrI 0\u00b772-0\u00b776) for women and 0\u00b779 (0\u00b778-0\u00b781) for men. From 2002 to 2019, the overall probability of dying from a cancer declined in all districts: the reductions ranged from 6\u00b76% (95% CrI 0\u00b73-13\u00b71) to 30\u00b71% (25\u00b76-34\u00b75) for women and from 12\u00b78% (7\u00b71-18\u00b78) to 36\u00b77% (32\u00b72-41\u00b72) for men. However, there were increases in mortality for liver cancer among men, lung cancer and corpus uteri cancer among women, and pancreatic cancer in both sexes in some or all districts with posterior probability greater than 0\u00b780.

Interpretation

Cancers with modifiable risk factors and potential for screening for precancerous lesions had heterogeneous trends and the greatest geographical inequality. To reduce these inequalities, factors affecting both incidence and survival need to be addressed at the local level.

Funding

Wellcome Trust, Imperial College London, UK Medical Research Council, and the National Institute of Health Research.", "laySummary": "", - "urls": "pdf:https://www.frontiersin.org/articles/10.3389/fpubh.2022.1035415/pdf; doi:https://doi.org/10.3389/fpubh.2022.1035415; html:https://europepmc.org/articles/PMC9755180; pdf:https://europepmc.org/articles/PMC9755180?pdf=render" + "urls": "pdf:http://www.thelancet.com/article/S1470204523005302/pdf; doi:https://doi.org/10.1016/S1470-2045(23)00530-2; html:https://europepmc.org/articles/PMC7615518; pdf:https://europepmc.org/articles/PMC7615518?pdf=render" }, { "id": "32635913", @@ -6663,6 +6646,23 @@ "laySummary": "", "urls": "pdf:https://bmcmedinformdecismak.biomedcentral.com/track/pdf/10.1186/s12911-020-01169-z; doi:https://doi.org/10.1186/s12911-020-01169-z; html:https://europepmc.org/articles/PMC7339522; pdf:https://europepmc.org/articles/PMC7339522?pdf=render" }, + { + "id": "36530697", + "doi": "https://doi.org/10.3389/fpubh.2022.1035415", + "title": "Associations between air pollution and multimorbidity in the UK Biobank: A cross-sectional study.", + "authorString": "Ronaldson A, Arias de la Torre J, Ashworth M, Hansell AL, Hotopf M, Mudway I, Stewart R, Dregan A, Bakolis I.", + "authorAffiliations": "", + "journalTitle": "Frontiers in public health", + "pubYear": "2022", + "date": "2022-12-02", + "isOpenAccess": "Y", + "keywords": "Air pollution; Nitrogen dioxide; particulate matter; Health Status; Exploratory Factor Analysis; Multimorbidity", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Long-term exposure to air pollution concentrations is known to be adversely associated with a broad range of single non-communicable diseases, but its role in multimorbidity has not been investigated in the UK. We aimed to assess associations between long-term air pollution exposure and multimorbidity status, severity, and patterns using the UK Biobank cohort.

Methods

Multimorbidity status was calculated based on 41 physical and mental conditions. We assessed cross-sectional associations between annual modeled particulate matter (PM)2.5, PMcoarse, PM10, and nitrogen dioxide (NO2) concentrations (\u03bcg/m3-modeled to residential address) and multimorbidity status at the baseline assessment (2006-2010) in 364,144 people (mean age: 52.2 \u00b1 8.1 years, 52.6% female). Air pollutants were categorized into quartiles to assess dose-response associations. Among those with multimorbidity (\u22652 conditions; n = 156,395) we assessed associations between air pollutant exposure levels and multimorbidity severity and multimorbidity patterns, which were identified using exploratory factor analysis. Associations were explored using generalized linear models adjusted for sociodemographic, behavioral, and environmental indicators.

Results

Higher exposures to PM2.5, and NO2 were associated with multimorbidity status in a dose-dependent manner. These associations were strongest when we compared the highest air pollution quartile (quartile 4: Q4) with the lowest quartile (Q1) [PM2.5: adjusted odds ratio (adjOR) = 1.21 (95% CI = 1.18, 1.24); NO2: adjOR = 1.19 (95 % CI = 1.16, 1.23)]. We also observed dose-response associations between air pollutant exposures and multimorbidity severity scores. We identified 11 multimorbidity patterns. Air pollution was associated with several multimorbidity patterns with strongest associations (Q4 vs. Q1) observed for neurological (stroke, epilepsy, alcohol/substance dependency) [PM2.5: adjOR = 1.31 (95% CI = 1.14, 1.51); NO2: adjOR = 1.33 (95% CI = 1.11, 1.60)] and respiratory patterns (COPD, asthma) [PM2.5: adjOR = 1.24 (95% CI = 1.16, 1.33); NO2: adjOR = 1.26 (95% CI = 1.15, 1.38)].

Conclusions

This cross-sectional study provides evidence that exposure to air pollution might be associated with having multimorbid, multi-organ conditions. Longitudinal studies are needed to further explore these associations.", + "laySummary": "", + "urls": "pdf:https://www.frontiersin.org/articles/10.3389/fpubh.2022.1035415/pdf; doi:https://doi.org/10.3389/fpubh.2022.1035415; html:https://europepmc.org/articles/PMC9755180; pdf:https://europepmc.org/articles/PMC9755180?pdf=render" + }, { "id": "35050151", "doi": "https://doi.org/10.3390/metabo12010029", @@ -6986,23 +6986,6 @@ "laySummary": "", "urls": "pdf:https://www.nature.com/articles/s41467-022-29521-z.pdf; doi:https://doi.org/10.1038/s41467-022-29521-z; html:https://europepmc.org/articles/PMC9005552; pdf:https://europepmc.org/articles/PMC9005552?pdf=render" }, - { - "id": "37400731", - "doi": "https://doi.org/10.1007/s10802-023-01086-5", - "title": "Maternal Mental Health and Children's Problem Behaviours: A Bi-directional Relationship?", - "authorString": "Lowthian E, Bedston S, Kristensen SM, Akbari A, Fry R, Huxley K, Johnson R, Kim HS, Owen RK, Taylor C, Griffiths L.", - "authorAffiliations": "", - "journalTitle": "Research on child and adolescent psychopathology", - "pubYear": "2023", - "date": "2023-07-04", - "isOpenAccess": "Y", - "keywords": "Child Development; Bayesian analysis; Structural Equation Modelling; Maternal Mental Health; Millennium Cohort Study", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Transactional theory and the coercive family process model have illustrated how the parent-child relationship is reciprocal. Emerging research using advanced statistical methods has examined these theories, but further investigations are necessary. In this study, we utilised linked health data on maternal mental health disorders and explored their relationship with child problem behaviours via the Strengths and Difficulties Questionnaire for over 13 years. We accessed data from the Millennium Cohort Study, linked to anonymised individual-level population-scale health and administrative data within the Secure Anonymised Information Linkage (SAIL) Databank. We used Bayesian Structural Equation Modelling, specifically Random-Intercept Cross-Lagged Panel Models, to analyse the relationships between mothers and their children. We then explored these models with the addition of time-invariant covariates. We found that a mother's mental health was strongly associated over time, as were children's problem behaviours. We found mixed evidence for bi-directional relationships, with only emotional problems showing bi-directional associations in mid to late childhood. Only child-to-mother pathways were identified for the overall problem behaviour score and peer problems; no associations were found for conduct problems or hyperactivity. All models had strong between-effects and clear socioeconomic and sex differences. We encourage the use of whole family-based support for mental health and problem behaviours, and recommend that socioeconomic, sex and wider differences should be considered as factors in tailoring family-based interventions and support.", - "laySummary": "", - "urls": "pdf:https://link.springer.com/content/pdf/10.1007/s10802-023-01086-5.pdf; doi:https://doi.org/10.1007/s10802-023-01086-5; html:https://europepmc.org/articles/PMC10628040; pdf:https://europepmc.org/articles/PMC10628040?pdf=render" - }, { "id": "33948220", "doi": "https://doi.org/10.1177/20552076211007661", @@ -7020,6 +7003,23 @@ "laySummary": "", "urls": "pdf:https://journals.sagepub.com/doi/pdf/10.1177/20552076211007661; doi:https://doi.org/10.1177/20552076211007661; html:https://europepmc.org/articles/PMC8054217; pdf:https://europepmc.org/articles/PMC8054217?pdf=render" }, + { + "id": "37400731", + "doi": "https://doi.org/10.1007/s10802-023-01086-5", + "title": "Maternal Mental Health and Children's Problem Behaviours: A Bi-directional Relationship?", + "authorString": "Lowthian E, Bedston S, Kristensen SM, Akbari A, Fry R, Huxley K, Johnson R, Kim HS, Owen RK, Taylor C, Griffiths L.", + "authorAffiliations": "", + "journalTitle": "Research on child and adolescent psychopathology", + "pubYear": "2023", + "date": "2023-07-04", + "isOpenAccess": "Y", + "keywords": "Child Development; Bayesian analysis; Structural Equation Modelling; Maternal Mental Health; Millennium Cohort Study", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Transactional theory and the coercive family process model have illustrated how the parent-child relationship is reciprocal. Emerging research using advanced statistical methods has examined these theories, but further investigations are necessary. In this study, we utilised linked health data on maternal mental health disorders and explored their relationship with child problem behaviours via the Strengths and Difficulties Questionnaire for over 13 years. We accessed data from the Millennium Cohort Study, linked to anonymised individual-level population-scale health and administrative data within the Secure Anonymised Information Linkage (SAIL) Databank. We used Bayesian Structural Equation Modelling, specifically Random-Intercept Cross-Lagged Panel Models, to analyse the relationships between mothers and their children. We then explored these models with the addition of time-invariant covariates. We found that a mother's mental health was strongly associated over time, as were children's problem behaviours. We found mixed evidence for bi-directional relationships, with only emotional problems showing bi-directional associations in mid to late childhood. Only child-to-mother pathways were identified for the overall problem behaviour score and peer problems; no associations were found for conduct problems or hyperactivity. All models had strong between-effects and clear socioeconomic and sex differences. We encourage the use of whole family-based support for mental health and problem behaviours, and recommend that socioeconomic, sex and wider differences should be considered as factors in tailoring family-based interventions and support.", + "laySummary": "", + "urls": "pdf:https://link.springer.com/content/pdf/10.1007/s10802-023-01086-5.pdf; doi:https://doi.org/10.1007/s10802-023-01086-5; html:https://europepmc.org/articles/PMC10628040; pdf:https://europepmc.org/articles/PMC10628040?pdf=render" + }, { "id": "36944118", "doi": "https://doi.org/10.2337/dc22-1238", @@ -7207,23 +7207,6 @@ "laySummary": "", "urls": "pdf:https://www.nature.com/articles/s41746-024-01065-0.pdf; doi:https://doi.org/10.1038/s41746-024-01065-0; html:https://europepmc.org/articles/PMC11106264; pdf:https://europepmc.org/articles/PMC11106264?pdf=render" }, - { - "id": "38642997", - "doi": "https://doi.org/10.1136/bmjopen-2023-079923", - "title": "Distributions of recorded pain in mental health records: a natural language processing based study.", - "authorString": "Chaturvedi J, Stewart R, Ashworth M, Roberts A.", - "authorAffiliations": "", - "journalTitle": "BMJ open", - "pubYear": "2024", - "date": "2024-04-19", - "isOpenAccess": "Y", - "keywords": "Chronic pain; Mental health; epidemiology; Electronic Health Records; Natural Language Processing", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Objective

The objective of this study is to determine demographic and diagnostic distributions of physical pain recorded in clinical notes of a mental health electronic health records database by using natural language processing and examine the overlap in recorded physical pain between primary and secondary care.

Design, setting and participants

The data were extracted from an anonymised version of the electronic health records of a large secondary mental healthcare provider serving a catchment of 1.3 million residents in south London. These included patients under active referral, aged 18+ at the index date of 1 July 2018 and having at least one clinical document (\u226530 characters) between 1 July 2017 and 1 July 2019. This cohort was compared with linked primary care records from one of the four local government areas.

Outcome

The primary outcome of interest was the presence of recorded physical pain within the clinical notes of the patients, not including psychological or metaphorical pain.

Results

A total of 27\u2009211 patients were retrieved. Of these, 52% (14,202) had narrative text containing relevant mentions of physical pain. Older patients (OR 1.17, 95% CI 1.15 to 1.19), females (OR 1.42, 95% CI 1.35 to 1.49), Asians (OR 1.30, 95% CI 1.16 to 1.45) or black (OR 1.49, 95% CI 1.40 to 1.59) ethnicities, living in deprived neighbourhoods (OR 1.64, 95% CI 1.55 to 1.73) showed higher odds of recorded pain. Patients with severe mental illnesses were found to be less likely to report pain (OR 0.43, 95% CI 0.41 to 0.46, p<0.001). 17% of the cohort from secondary care also had records from primary care.

Conclusion

The findings of this study show sociodemographic and diagnostic differences in recorded pain. Specifically, lower documentation across certain groups indicates the need for better screening protocols and training on recognising varied pain presentations. Additionally, targeting improved detection of pain for minority and disadvantaged groups by care providers can promote health equity.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1136/bmjopen-2023-079923; html:https://europepmc.org/articles/PMC11033644; pdf:https://europepmc.org/articles/PMC11033644?pdf=render" - }, { "id": "33079204", "doi": "https://doi.org/10.1093/ehjqcco/qcaa079", @@ -7241,6 +7224,23 @@ "laySummary": "", "urls": "pdf:https://academic.oup.com/ehjqcco/article-pdf/7/3/247/37776880/qcaa079.pdf; doi:https://doi.org/10.1093/ehjqcco/qcaa079; html:https://europepmc.org/articles/PMC7665465; pdf:https://europepmc.org/articles/PMC7665465?pdf=render" }, + { + "id": "38642997", + "doi": "https://doi.org/10.1136/bmjopen-2023-079923", + "title": "Distributions of recorded pain in mental health records: a natural language processing based study.", + "authorString": "Chaturvedi J, Stewart R, Ashworth M, Roberts A.", + "authorAffiliations": "", + "journalTitle": "BMJ open", + "pubYear": "2024", + "date": "2024-04-19", + "isOpenAccess": "Y", + "keywords": "Chronic pain; Mental health; epidemiology; Electronic Health Records; Natural Language Processing", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Objective

The objective of this study is to determine demographic and diagnostic distributions of physical pain recorded in clinical notes of a mental health electronic health records database by using natural language processing and examine the overlap in recorded physical pain between primary and secondary care.

Design, setting and participants

The data were extracted from an anonymised version of the electronic health records of a large secondary mental healthcare provider serving a catchment of 1.3 million residents in south London. These included patients under active referral, aged 18+ at the index date of 1 July 2018 and having at least one clinical document (\u226530 characters) between 1 July 2017 and 1 July 2019. This cohort was compared with linked primary care records from one of the four local government areas.

Outcome

The primary outcome of interest was the presence of recorded physical pain within the clinical notes of the patients, not including psychological or metaphorical pain.

Results

A total of 27\u2009211 patients were retrieved. Of these, 52% (14,202) had narrative text containing relevant mentions of physical pain. Older patients (OR 1.17, 95% CI 1.15 to 1.19), females (OR 1.42, 95% CI 1.35 to 1.49), Asians (OR 1.30, 95% CI 1.16 to 1.45) or black (OR 1.49, 95% CI 1.40 to 1.59) ethnicities, living in deprived neighbourhoods (OR 1.64, 95% CI 1.55 to 1.73) showed higher odds of recorded pain. Patients with severe mental illnesses were found to be less likely to report pain (OR 0.43, 95% CI 0.41 to 0.46, p<0.001). 17% of the cohort from secondary care also had records from primary care.

Conclusion

The findings of this study show sociodemographic and diagnostic differences in recorded pain. Specifically, lower documentation across certain groups indicates the need for better screening protocols and training on recognising varied pain presentations. Additionally, targeting improved detection of pain for minority and disadvantaged groups by care providers can promote health equity.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1136/bmjopen-2023-079923; html:https://europepmc.org/articles/PMC11033644; pdf:https://europepmc.org/articles/PMC11033644?pdf=render" + }, { "id": "37558806", "doi": "https://doi.org/10.1038/s41598-023-40215-4", @@ -7309,23 +7309,6 @@ "laySummary": "", "urls": "pdf:https://www.nature.com/articles/s41598-023-42331-7.pdf; doi:https://doi.org/10.1038/s41598-023-42331-7; html:https://europepmc.org/articles/PMC10556075; pdf:https://europepmc.org/articles/PMC10556075?pdf=render" }, - { - "id": "36333839", - "doi": "https://doi.org/10.1002/gps.5834", - "title": "The impact of the first UK COVID-19 lockdown on presentations with psychosis to mental health services for older adults: An electronic health records study in South London.", - "authorString": "Simkin L, Yung P, Greig F, Perera G, Tsamakis K, Rizos E, Stewart R, Velayudhan L, Mueller C.", - "authorAffiliations": "", - "journalTitle": "International journal of geriatric psychiatry", - "pubYear": "2022", - "date": "2022-10-24", - "isOpenAccess": "Y", - "keywords": "Dementia; Hallucinations; Delusions; Psychosis; Older Adults; Lockdown; Covid-19; Non-white Ethnicity", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Objectives

Social distancing restrictions in the COVID-19 pandemic may have had adverse effects on older adults' mental health. Whereby the impact on mood is well-described, less is known about psychotic symptoms. The aim of this study was to compare characteristics associated with psychotic symptoms during the first UK lockdown and a pre-pandemic comparison period.

Methods

In this retrospective observational study we analysed anonymised records from patients referred to mental health services for older adults in South London in the 16-week period of the UK lockdown starting in March 2020, and in the comparable pre-pandemic period in 2019. We used logistic regression models to compare the associations of different patient characteristics with increased odds of presenting with any psychotic symptom (defined as hallucinations and/or delusion), hallucinations, or delusions, during lockdown and the corresponding pre-pandemic period.

Results

1991 referrals were identified. There were fewer referrals during lockdown but a higher proportion of presentations with any psychotic symptom (48.7% vs. 42.8%, p\u00a0=\u00a00.018), particularly hallucinations (41.0% vs. 27.8%, p\u00a0<\u00a00.001). Patients of non-White ethnicity (adjusted odds ratio (OR): 1.83; 95% confidence interval (CI): 1.13-2.99) and patients with dementia (adjusted OR: 3.09; 95% CI: 1.91-4.99) were more likely to be referred with psychotic symptoms during lockdown. While a weaker association between dementia and psychotic symptoms was found in the pre-COVID period (adjusted OR: 1.55; 95% CI: 1.19-2.03), interaction terms indicated higher odds of patients of non-White ethnicity or dementia to present with psychosis during the lockdown period.

Conclusions

During lockdown, referrals to mental health services for adults decreased, but contained a higher proportion with psychotic symptoms. The stronger association with psychotic symptoms in non-White ethnic groups and patients with dementia during lockdown suggests that barriers in accessing care might have increased during the COVID-19 pandemic.", - "laySummary": "", - "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/gps.5834; doi:https://doi.org/10.1002/gps.5834; html:https://europepmc.org/articles/PMC9828419; pdf:https://europepmc.org/articles/PMC9828419?pdf=render" - }, { "id": "35607618", "doi": "https://doi.org/10.1016/j.patter.2022.100471", @@ -7343,6 +7326,23 @@ "laySummary": "", "urls": "pdf:http://www.cell.com/article/S2666389922000514/pdf; doi:https://doi.org/10.1016/j.patter.2022.100471; html:https://europepmc.org/articles/PMC9122960; pdf:https://europepmc.org/articles/PMC9122960?pdf=render" }, + { + "id": "36333839", + "doi": "https://doi.org/10.1002/gps.5834", + "title": "The impact of the first UK COVID-19 lockdown on presentations with psychosis to mental health services for older adults: An electronic health records study in South London.", + "authorString": "Simkin L, Yung P, Greig F, Perera G, Tsamakis K, Rizos E, Stewart R, Velayudhan L, Mueller C.", + "authorAffiliations": "", + "journalTitle": "International journal of geriatric psychiatry", + "pubYear": "2022", + "date": "2022-10-24", + "isOpenAccess": "Y", + "keywords": "Dementia; Hallucinations; Delusions; Psychosis; Older Adults; Lockdown; Covid-19; Non-white Ethnicity", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Objectives

Social distancing restrictions in the COVID-19 pandemic may have had adverse effects on older adults' mental health. Whereby the impact on mood is well-described, less is known about psychotic symptoms. The aim of this study was to compare characteristics associated with psychotic symptoms during the first UK lockdown and a pre-pandemic comparison period.

Methods

In this retrospective observational study we analysed anonymised records from patients referred to mental health services for older adults in South London in the 16-week period of the UK lockdown starting in March 2020, and in the comparable pre-pandemic period in 2019. We used logistic regression models to compare the associations of different patient characteristics with increased odds of presenting with any psychotic symptom (defined as hallucinations and/or delusion), hallucinations, or delusions, during lockdown and the corresponding pre-pandemic period.

Results

1991 referrals were identified. There were fewer referrals during lockdown but a higher proportion of presentations with any psychotic symptom (48.7% vs. 42.8%, p\u00a0=\u00a00.018), particularly hallucinations (41.0% vs. 27.8%, p\u00a0<\u00a00.001). Patients of non-White ethnicity (adjusted odds ratio (OR): 1.83; 95% confidence interval (CI): 1.13-2.99) and patients with dementia (adjusted OR: 3.09; 95% CI: 1.91-4.99) were more likely to be referred with psychotic symptoms during lockdown. While a weaker association between dementia and psychotic symptoms was found in the pre-COVID period (adjusted OR: 1.55; 95% CI: 1.19-2.03), interaction terms indicated higher odds of patients of non-White ethnicity or dementia to present with psychosis during the lockdown period.

Conclusions

During lockdown, referrals to mental health services for adults decreased, but contained a higher proportion with psychotic symptoms. The stronger association with psychotic symptoms in non-White ethnic groups and patients with dementia during lockdown suggests that barriers in accessing care might have increased during the COVID-19 pandemic.", + "laySummary": "", + "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/gps.5834; doi:https://doi.org/10.1002/gps.5834; html:https://europepmc.org/articles/PMC9828419; pdf:https://europepmc.org/articles/PMC9828419?pdf=render" + }, { "id": "37006328", "doi": "https://doi.org/10.1093/braincomms/fcad065", @@ -7734,23 +7734,6 @@ "laySummary": "", "urls": "pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0285979&type=printable; doi:https://doi.org/10.1371/journal.pone.0285979; html:https://europepmc.org/articles/PMC10194890; pdf:https://europepmc.org/articles/PMC10194890?pdf=render" }, - { - "id": "37263602", - "doi": "https://doi.org/10.1093/eurpub/ckad075", - "title": "Community factors and excess mortality in the COVID-19 pandemic in England, Italy and Sweden.", - "authorString": "Parkes B, Stafoggia M, Fecht D, Davies B, Bonander C, De' Donato F, Michelozzi P, Piel FB, Str\u00f6mberg U, Blangiardo M.", - "authorAffiliations": "", - "journalTitle": "European journal of public health", - "pubYear": "2023", - "date": "2023-08-01", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Analyses of coronavirus disease 19 suggest specific risk factors make communities more or less vulnerable to pandemic-related deaths within countries. What is unclear is whether the characteristics affecting vulnerability of small communities within countries produce similar patterns of excess mortality across countries with different demographics and public health responses to the pandemic. Our aim is to quantify community-level variations in excess mortality within England, Italy and Sweden and identify how such spatial variability was driven by community-level characteristics.

Methods

We applied a two-stage Bayesian model to quantify inequalities in excess mortality in people aged 40\u2009years and older at the community level in England, Italy and Sweden during the first year of the pandemic (March 2020-February 2021). We used community characteristics measuring deprivation, air pollution, living conditions, population density and movement of people as covariates to quantify their associations with excess mortality.

Results

We found just under half of communities in England (48.1%) and Italy (45.8%) had an excess mortality of over 300 per 100\u200a000 males over the age of 40, while for Sweden that covered 23.1% of communities. We showed that deprivation is a strong predictor of excess mortality across the three countries, and communities with high levels of overcrowding were associated with higher excess mortality in England and Sweden.

Conclusion

These results highlight some international similarities in factors affecting mortality that will help policy makers target public health measures to increase resilience to the mortality impacts of this and future pandemics.", - "laySummary": "", - "urls": "pdf:https://academic.oup.com/eurpub/advance-article-pdf/doi/10.1093/eurpub/ckad075/50504334/ckad075.pdf; doi:https://doi.org/10.1093/eurpub/ckad075; html:https://europepmc.org/articles/PMC10393497; pdf:https://europepmc.org/articles/PMC10393497?pdf=render" - }, { "id": "38222382", "doi": "https://doi.org/", @@ -7768,6 +7751,23 @@ "laySummary": "", "urls": "html:https://europepmc.org/articles/PMC10785867; pdf:https://europepmc.org/articles/PMC10785867?pdf=render" }, + { + "id": "37263602", + "doi": "https://doi.org/10.1093/eurpub/ckad075", + "title": "Community factors and excess mortality in the COVID-19 pandemic in England, Italy and Sweden.", + "authorString": "Parkes B, Stafoggia M, Fecht D, Davies B, Bonander C, De' Donato F, Michelozzi P, Piel FB, Str\u00f6mberg U, Blangiardo M.", + "authorAffiliations": "", + "journalTitle": "European journal of public health", + "pubYear": "2023", + "date": "2023-08-01", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Analyses of coronavirus disease 19 suggest specific risk factors make communities more or less vulnerable to pandemic-related deaths within countries. What is unclear is whether the characteristics affecting vulnerability of small communities within countries produce similar patterns of excess mortality across countries with different demographics and public health responses to the pandemic. Our aim is to quantify community-level variations in excess mortality within England, Italy and Sweden and identify how such spatial variability was driven by community-level characteristics.

Methods

We applied a two-stage Bayesian model to quantify inequalities in excess mortality in people aged 40\u2009years and older at the community level in England, Italy and Sweden during the first year of the pandemic (March 2020-February 2021). We used community characteristics measuring deprivation, air pollution, living conditions, population density and movement of people as covariates to quantify their associations with excess mortality.

Results

We found just under half of communities in England (48.1%) and Italy (45.8%) had an excess mortality of over 300 per 100\u200a000 males over the age of 40, while for Sweden that covered 23.1% of communities. We showed that deprivation is a strong predictor of excess mortality across the three countries, and communities with high levels of overcrowding were associated with higher excess mortality in England and Sweden.

Conclusion

These results highlight some international similarities in factors affecting mortality that will help policy makers target public health measures to increase resilience to the mortality impacts of this and future pandemics.", + "laySummary": "", + "urls": "pdf:https://academic.oup.com/eurpub/advance-article-pdf/doi/10.1093/eurpub/ckad075/50504334/ckad075.pdf; doi:https://doi.org/10.1093/eurpub/ckad075; html:https://europepmc.org/articles/PMC10393497; pdf:https://europepmc.org/articles/PMC10393497?pdf=render" + }, { "id": "33240522", "doi": "https://doi.org/10.1177/2055207620965046", @@ -7785,23 +7785,6 @@ "laySummary": "", "urls": "pdf:https://journals.sagepub.com/doi/pdf/10.1177/2055207620965046; doi:https://doi.org/10.1177/2055207620965046; html:https://europepmc.org/articles/PMC7675911; pdf:https://europepmc.org/articles/PMC7675911?pdf=render" }, - { - "id": "36193673", - "doi": "https://doi.org/10.1192/j.eurpsy.2022.2324", - "title": "Cardiac surgery receipt and outcomes for people using secondary mental healthcare services: Retrospective cohort study using a large mental healthcare database in South London.", - "authorString": "Brooks G, Weerakkody R, Harris M, Harris M, Stewart R, Perera G.", - "authorAffiliations": "", - "journalTitle": "European psychiatry : the journal of the Association of European Psychiatrists", - "pubYear": "2022", - "date": "2022-10-04", - "isOpenAccess": "Y", - "keywords": "Cardiac surgery; Length Of Stay; Emergency Admissions; Mental Healthcare Services", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Patients diagnosed with mental health problems are more predisposed to cardiovascular disease, including cardiac surgery. Nevertheless, health outcomes after cardiac surgery for patients with mental health problems as a discrete group are unknown. This study examined the association between secondary care mental health service use and postoperative health outcomes following cardiac surgery.

Methods

We conducted a retrospective observational research, utilizing data from a large South London mental healthcare supplier linked to national hospitalization data. OPCS-4 codes were applied to classify cardiac surgery. Health results were compared between those individuals with a mental health disorder diagnosis from secondary care and other local residents, including the length of hospital stay (LOS), inpatient mortality, and 30-day emergency hospital readmission.

Results

Twelve thousand three hundred and eighty-four patients received cardiac surgery, including 1,481 with a mental disorder diagnosis. Patients with mental health diagnosis were at greater risk of emergency admissions for cardiac surgery (odds ratio [OR] 1.60; 1.43, 1.79), longer index LOS (incidence rate ratio 1.28; 1.26, 1.30), and at higher risk of 30-day emergency readmission (OR 1.53; 1.31, 1.78). Those who underwent pacemaker insertion and major open surgery had worse postoperative outcomes during index surgery hospital admission while those who had major endovascular surgery had worse health outcomes subsequent 30-day emergency hospital readmission.

Conclusion

People with a mental health disorder diagnosis undertaking cardiac surgery have significantly worse health outcomes. Personalized guidelines and policies to manage preoperative risk factors require consideration and evaluation.", - "laySummary": "", - "urls": "pdf:https://www.cambridge.org/core/services/aop-cambridge-core/content/view/63FA124CF816896E02CAEE14215D590E/S0924933822023240a.pdf/div-class-title-cardiac-surgery-receipt-and-outcomes-for-people-using-secondary-mental-health-care-services-retrospective-cohort-study-using-a-large-mental-healthcare-database-in-south-london-div.pdf; doi:https://doi.org/10.1192/j.eurpsy.2022.2324; html:https://europepmc.org/articles/PMC9677442; pdf:https://europepmc.org/articles/PMC9677442?pdf=render" - }, { "id": "31757986", "doi": "https://doi.org/10.1038/s41598-019-53454-1", @@ -7819,6 +7802,23 @@ "laySummary": "This study investigated which genes encourage cancer tumors to grow. The study identifies genes and distinguishes their role in different types of cancers. Their method is validated using whole exome and whole genome sequencing", "urls": "pdf:https://www.nature.com/articles/s41598-019-53454-1.pdf; doi:https://doi.org/10.1038/s41598-019-53454-1; html:https://europepmc.org/articles/PMC6874647; pdf:https://europepmc.org/articles/PMC6874647?pdf=render" }, + { + "id": "36193673", + "doi": "https://doi.org/10.1192/j.eurpsy.2022.2324", + "title": "Cardiac surgery receipt and outcomes for people using secondary mental healthcare services: Retrospective cohort study using a large mental healthcare database in South London.", + "authorString": "Brooks G, Weerakkody R, Harris M, Harris M, Stewart R, Perera G.", + "authorAffiliations": "", + "journalTitle": "European psychiatry : the journal of the Association of European Psychiatrists", + "pubYear": "2022", + "date": "2022-10-04", + "isOpenAccess": "Y", + "keywords": "Cardiac surgery; Length Of Stay; Emergency Admissions; Mental Healthcare Services", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Patients diagnosed with mental health problems are more predisposed to cardiovascular disease, including cardiac surgery. Nevertheless, health outcomes after cardiac surgery for patients with mental health problems as a discrete group are unknown. This study examined the association between secondary care mental health service use and postoperative health outcomes following cardiac surgery.

Methods

We conducted a retrospective observational research, utilizing data from a large South London mental healthcare supplier linked to national hospitalization data. OPCS-4 codes were applied to classify cardiac surgery. Health results were compared between those individuals with a mental health disorder diagnosis from secondary care and other local residents, including the length of hospital stay (LOS), inpatient mortality, and 30-day emergency hospital readmission.

Results

Twelve thousand three hundred and eighty-four patients received cardiac surgery, including 1,481 with a mental disorder diagnosis. Patients with mental health diagnosis were at greater risk of emergency admissions for cardiac surgery (odds ratio [OR] 1.60; 1.43, 1.79), longer index LOS (incidence rate ratio 1.28; 1.26, 1.30), and at higher risk of 30-day emergency readmission (OR 1.53; 1.31, 1.78). Those who underwent pacemaker insertion and major open surgery had worse postoperative outcomes during index surgery hospital admission while those who had major endovascular surgery had worse health outcomes subsequent 30-day emergency hospital readmission.

Conclusion

People with a mental health disorder diagnosis undertaking cardiac surgery have significantly worse health outcomes. Personalized guidelines and policies to manage preoperative risk factors require consideration and evaluation.", + "laySummary": "", + "urls": "pdf:https://www.cambridge.org/core/services/aop-cambridge-core/content/view/63FA124CF816896E02CAEE14215D590E/S0924933822023240a.pdf/div-class-title-cardiac-surgery-receipt-and-outcomes-for-people-using-secondary-mental-health-care-services-retrospective-cohort-study-using-a-large-mental-healthcare-database-in-south-london-div.pdf; doi:https://doi.org/10.1192/j.eurpsy.2022.2324; html:https://europepmc.org/articles/PMC9677442; pdf:https://europepmc.org/articles/PMC9677442?pdf=render" + }, { "id": "34599903", "doi": "https://doi.org/10.1016/s2213-2600(21)00380-5", @@ -7870,23 +7870,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1177/08862605231163885; doi:https://doi.org/10.1177/08862605231163885; html:https://europepmc.org/articles/PMC10064198; pdf:https://europepmc.org/articles/PMC10064198?pdf=render" }, - { - "id": "38200587", - "doi": "https://doi.org/10.1093/bioinformatics/btae012", - "title": "Pitfalls of machine learning models for protein-protein interaction networks.", - "authorString": "Lannelongue L, Inouye M.", - "authorAffiliations": "", - "journalTitle": "Bioinformatics (Oxford, England)", - "pubYear": "2024", - "date": "2024-02-01", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Motivation

Protein-protein interactions (PPIs) are essential to understanding biological pathways as well as their roles in development and disease. Computational tools, based on classic machine learning, have been successful at predicting PPIs in silico, but the lack of consistent and reliable frameworks for this task has led to network models that are difficult to compare and discrepancies between algorithms that remain unexplained.

Results

To better understand the underlying inference mechanisms that underpin these models, we designed an open-source framework for benchmarking that accounts for a range of biological and statistical pitfalls while facilitating reproducibility. We use it to shed light on the impact of network topology and how different algorithms deal with highly connected proteins. By studying functional genomics-based and sequence-based models on human PPIs, we show their complementarity as the former performs best on lone proteins while the latter specializes in interactions involving hubs. We also show that algorithm design has little impact on performance with functional genomic data. We replicate our results between both human and S. cerevisiae data and demonstrate that models using functional genomics are better suited to PPI prediction across species. With rapidly increasing amounts of sequence and functional genomics data, our study provides a principled foundation for future construction, comparison, and application of PPI networks.

Availability and implementation

The code and data are available on GitHub: https://github.com/Llannelongue/B4PPI.", - "laySummary": "", - "urls": "pdf:https://academic.oup.com/bioinformatics/advance-article-pdf/doi/10.1093/bioinformatics/btae012/55399607/btae012.pdf; doi:https://doi.org/10.1093/bioinformatics/btae012; html:https://europepmc.org/articles/PMC10868344; pdf:https://europepmc.org/articles/PMC10868344?pdf=render" - }, { "id": "34461893", "doi": "https://doi.org/10.1186/s12916-021-02096-0", @@ -7904,6 +7887,23 @@ "laySummary": "", "urls": "pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-021-02096-0; doi:https://doi.org/10.1186/s12916-021-02096-0; html:https://europepmc.org/articles/PMC8404408; pdf:https://europepmc.org/articles/PMC8404408?pdf=render" }, + { + "id": "38200587", + "doi": "https://doi.org/10.1093/bioinformatics/btae012", + "title": "Pitfalls of machine learning models for protein-protein interaction networks.", + "authorString": "Lannelongue L, Inouye M.", + "authorAffiliations": "", + "journalTitle": "Bioinformatics (Oxford, England)", + "pubYear": "2024", + "date": "2024-02-01", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Motivation

Protein-protein interactions (PPIs) are essential to understanding biological pathways as well as their roles in development and disease. Computational tools, based on classic machine learning, have been successful at predicting PPIs in silico, but the lack of consistent and reliable frameworks for this task has led to network models that are difficult to compare and discrepancies between algorithms that remain unexplained.

Results

To better understand the underlying inference mechanisms that underpin these models, we designed an open-source framework for benchmarking that accounts for a range of biological and statistical pitfalls while facilitating reproducibility. We use it to shed light on the impact of network topology and how different algorithms deal with highly connected proteins. By studying functional genomics-based and sequence-based models on human PPIs, we show their complementarity as the former performs best on lone proteins while the latter specializes in interactions involving hubs. We also show that algorithm design has little impact on performance with functional genomic data. We replicate our results between both human and S. cerevisiae data and demonstrate that models using functional genomics are better suited to PPI prediction across species. With rapidly increasing amounts of sequence and functional genomics data, our study provides a principled foundation for future construction, comparison, and application of PPI networks.

Availability and implementation

The code and data are available on GitHub: https://github.com/Llannelongue/B4PPI.", + "laySummary": "", + "urls": "pdf:https://academic.oup.com/bioinformatics/advance-article-pdf/doi/10.1093/bioinformatics/btae012/55399607/btae012.pdf; doi:https://doi.org/10.1093/bioinformatics/btae012; html:https://europepmc.org/articles/PMC10868344; pdf:https://europepmc.org/articles/PMC10868344?pdf=render" + }, { "id": "36649943", "doi": "https://doi.org/10.1136/bmjoq-2021-001704", @@ -8533,23 +8533,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.lanepe.2023.100741; doi:https://doi.org/10.1016/j.lanepe.2023.100741; html:https://europepmc.org/articles/PMC10624988; pdf:https://europepmc.org/articles/PMC10624988?pdf=render" }, - { - "id": "37311808", - "doi": "https://doi.org/10.1038/s41467-023-39193-y", - "title": "Natural history of long-COVID in a nationwide, population cohort study.", - "authorString": "Hastie CE, Lowe DJ, McAuley A, Mills NL, Winter AJ, Black C, Scott JT, O'Donnell CA, Blane DN, Browne S, Ibbotson TR, Pell JP.", - "authorAffiliations": "", - "journalTitle": "Nature communications", - "pubYear": "2023", - "date": "2023-06-13", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Previous studies on the natural history of long-COVID have been few and selective. Without comparison groups, disease progression cannot be differentiated from symptoms originating from other causes. The Long-COVID in Scotland Study (Long-CISS) is a Scotland-wide, general population cohort of adults who had laboratory-confirmed SARS-CoV-2 infection matched to PCR-negative adults. Serial, self-completed, online questionnaires collected information on pre-existing health conditions and current health six, 12 and 18 months after index test. Of those with previous symptomatic infection, 35% reported persistent incomplete/no recovery, 12% improvement and 12% deterioration. At six and 12 months, one or more symptom was reported by 71.5% and 70.7% respectively of those previously infected, compared with 53.5% and 56.5% of those never infected. Altered taste, smell and confusion improved over time compared to the never infected group and adjusted for confounders. Conversely, late onset dry and productive cough, and hearing problems were more likely following SARS-CoV-2 infection.", - "laySummary": "", - "urls": "pdf:https://www.nature.com/articles/s41467-023-39193-y.pdf; doi:https://doi.org/10.1038/s41467-023-39193-y; html:https://europepmc.org/articles/PMC10263377; pdf:https://europepmc.org/articles/PMC10263377?pdf=render" - }, { "id": "32877922", "doi": "https://doi.org/10.1093/gerona/glaa216", @@ -8567,6 +8550,23 @@ "laySummary": "", "urls": "pdf:https://academic.oup.com/biomedgerontology/article-pdf/75/12/2320/34289886/glaa216.pdf; doi:https://doi.org/10.1093/gerona/glaa216; html:https://europepmc.org/articles/PMC7662170; pdf:https://europepmc.org/articles/PMC7662170?pdf=render" }, + { + "id": "37311808", + "doi": "https://doi.org/10.1038/s41467-023-39193-y", + "title": "Natural history of long-COVID in a nationwide, population cohort study.", + "authorString": "Hastie CE, Lowe DJ, McAuley A, Mills NL, Winter AJ, Black C, Scott JT, O'Donnell CA, Blane DN, Browne S, Ibbotson TR, Pell JP.", + "authorAffiliations": "", + "journalTitle": "Nature communications", + "pubYear": "2023", + "date": "2023-06-13", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Previous studies on the natural history of long-COVID have been few and selective. Without comparison groups, disease progression cannot be differentiated from symptoms originating from other causes. The Long-COVID in Scotland Study (Long-CISS) is a Scotland-wide, general population cohort of adults who had laboratory-confirmed SARS-CoV-2 infection matched to PCR-negative adults. Serial, self-completed, online questionnaires collected information on pre-existing health conditions and current health six, 12 and 18 months after index test. Of those with previous symptomatic infection, 35% reported persistent incomplete/no recovery, 12% improvement and 12% deterioration. At six and 12 months, one or more symptom was reported by 71.5% and 70.7% respectively of those previously infected, compared with 53.5% and 56.5% of those never infected. Altered taste, smell and confusion improved over time compared to the never infected group and adjusted for confounders. Conversely, late onset dry and productive cough, and hearing problems were more likely following SARS-CoV-2 infection.", + "laySummary": "", + "urls": "pdf:https://www.nature.com/articles/s41467-023-39193-y.pdf; doi:https://doi.org/10.1038/s41467-023-39193-y; html:https://europepmc.org/articles/PMC10263377; pdf:https://europepmc.org/articles/PMC10263377?pdf=render" + }, { "id": "33611594", "doi": "https://doi.org/10.1093/eurjpc/zwaa155", @@ -8924,23 +8924,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1371/journal.pdig.0000218; doi:https://doi.org/10.1371/journal.pdig.0000218; html:https://europepmc.org/articles/PMC10168555; pdf:https://europepmc.org/articles/PMC10168555?pdf=render" }, - { - "id": "36841835", - "doi": "https://doi.org/10.1038/s41541-023-00614-0", - "title": "Incidence determinants and serological correlates of reactive symptoms following SARS-CoV-2 vaccination.", - "authorString": "Holt H, Jolliffe DA, Talaei M, Faustini S, Vivaldi G, Greenig M, Richter AG, Lyons RA, Griffiths CJ, Kee F, Sheikh A, Davies GA, Shaheen SO, Martineau AR.", - "authorAffiliations": "", - "journalTitle": "NPJ vaccines", - "pubYear": "2023", - "date": "2023-02-25", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Prospective population-based studies investigating associations between reactive symptoms following SARS-CoV-2 vaccination and serologic responses to vaccination are lacking. We therefore conducted a study in 9003 adults from the UK general population receiving SARS-CoV-2 vaccines as part of the national vaccination programme. Titres of combined IgG/IgA/IgM responses to SARS-CoV-2 spike (S) glycoprotein were determined in eluates of dried blood spots collected from all participants before and after vaccination. 4262 (47.3%) participants experienced systemic reactive symptoms after a first vaccine dose. Factors associating with lower risk of such symptoms included older age (aOR per additional 10 years of age 0.85, 95% CI: 0.81-0.90), male vs. female sex (0.59, 0.53-0.65) and receipt of an mRNA vaccine vs. ChAdOx1 nCoV-19 (0.29, 0.26-0.32 for BNT162b2; 0.06, 0.01-0.26 for mRNA-1273). Higher risk of such symptoms was associated with SARS-CoV-2 seropositivity and COVID-19 symptoms prior to vaccination (2.23, 1.78-2.81), but not with SARS-CoV-2 seropositivity in the absence of COVID-19 symptoms (0.94, 0.81-1.09). Presence vs. absence of self-reported anxiety or depression at enrolment associated with higher risk of such symptoms (1.24, 1.12-1.39). Post-vaccination anti-S titres were higher among participants who experienced reactive symptoms after vaccination vs. those who did not (P\u2009<\u20090.001). We conclude that factors influencing risk of systemic symptoms after SARS-CoV-2 vaccination include demographic characteristics, pre-vaccination SARS-CoV-2 serostatus and vaccine type. Participants experiencing reactive symptoms following SARS-CoV-2 vaccination had higher post-vaccination titres of IgG/A/M anti-S antibodies. Improved public understanding of the frequency of reactogenic symptoms and their positive association with vaccine immunogenicity could potentially increase vaccine uptake.", - "laySummary": "", - "urls": "pdf:https://www.nature.com/articles/s41541-023-00614-0.pdf; doi:https://doi.org/10.1038/s41541-023-00614-0; html:https://europepmc.org/articles/PMC9959934; pdf:https://europepmc.org/articles/PMC9959934?pdf=render" - }, { "id": "36224173", "doi": "https://doi.org/10.1038/s41467-022-33415-5", @@ -8958,6 +8941,23 @@ "laySummary": "", "urls": "pdf:https://researchonline.gcu.ac.uk/files/64233779/s41467_022_33415_5.pdf; doi:https://doi.org/10.1038/s41467-022-33415-5; html:https://europepmc.org/articles/PMC9556711; pdf:https://europepmc.org/articles/PMC9556711?pdf=render" }, + { + "id": "36841835", + "doi": "https://doi.org/10.1038/s41541-023-00614-0", + "title": "Incidence determinants and serological correlates of reactive symptoms following SARS-CoV-2 vaccination.", + "authorString": "Holt H, Jolliffe DA, Talaei M, Faustini S, Vivaldi G, Greenig M, Richter AG, Lyons RA, Griffiths CJ, Kee F, Sheikh A, Davies GA, Shaheen SO, Martineau AR.", + "authorAffiliations": "", + "journalTitle": "NPJ vaccines", + "pubYear": "2023", + "date": "2023-02-25", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Prospective population-based studies investigating associations between reactive symptoms following SARS-CoV-2 vaccination and serologic responses to vaccination are lacking. We therefore conducted a study in 9003 adults from the UK general population receiving SARS-CoV-2 vaccines as part of the national vaccination programme. Titres of combined IgG/IgA/IgM responses to SARS-CoV-2 spike (S) glycoprotein were determined in eluates of dried blood spots collected from all participants before and after vaccination. 4262 (47.3%) participants experienced systemic reactive symptoms after a first vaccine dose. Factors associating with lower risk of such symptoms included older age (aOR per additional 10 years of age 0.85, 95% CI: 0.81-0.90), male vs. female sex (0.59, 0.53-0.65) and receipt of an mRNA vaccine vs. ChAdOx1 nCoV-19 (0.29, 0.26-0.32 for BNT162b2; 0.06, 0.01-0.26 for mRNA-1273). Higher risk of such symptoms was associated with SARS-CoV-2 seropositivity and COVID-19 symptoms prior to vaccination (2.23, 1.78-2.81), but not with SARS-CoV-2 seropositivity in the absence of COVID-19 symptoms (0.94, 0.81-1.09). Presence vs. absence of self-reported anxiety or depression at enrolment associated with higher risk of such symptoms (1.24, 1.12-1.39). Post-vaccination anti-S titres were higher among participants who experienced reactive symptoms after vaccination vs. those who did not (P\u2009<\u20090.001). We conclude that factors influencing risk of systemic symptoms after SARS-CoV-2 vaccination include demographic characteristics, pre-vaccination SARS-CoV-2 serostatus and vaccine type. Participants experiencing reactive symptoms following SARS-CoV-2 vaccination had higher post-vaccination titres of IgG/A/M anti-S antibodies. Improved public understanding of the frequency of reactogenic symptoms and their positive association with vaccine immunogenicity could potentially increase vaccine uptake.", + "laySummary": "", + "urls": "pdf:https://www.nature.com/articles/s41541-023-00614-0.pdf; doi:https://doi.org/10.1038/s41541-023-00614-0; html:https://europepmc.org/articles/PMC9959934; pdf:https://europepmc.org/articles/PMC9959934?pdf=render" + }, { "id": "34282121", "doi": "https://doi.org/10.1038/s41398-021-01522-4", @@ -9009,23 +9009,6 @@ "laySummary": "", "urls": "pdf:https://www.mdpi.com/2227-9059/9/7/841/pdf?version=1626837519; doi:https://doi.org/10.3390/biomedicines9070841; html:https://europepmc.org/articles/PMC8301759; pdf:https://europepmc.org/articles/PMC8301759?pdf=render" }, - { - "id": "37068951", - "doi": "https://doi.org/10.1136/thorax-2022-219901", - "title": "Asthma hospitalisations and heat exposure in England: a case-crossover study during 2002-2019.", - "authorString": "Konstantinoudis G, Minelli C, Lam HCY, Fuertes E, Ballester J, Davies B, Vicedo-Cabrera AM, Gasparrini A, Blangiardo M.", - "authorAffiliations": "", - "journalTitle": "Thorax", - "pubYear": "2023", - "date": "2023-04-17", - "isOpenAccess": "Y", - "keywords": "Asthma Epidemiology", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Previous studies have reported an association between warm temperature and asthma hospitalisation. They have reported different sex-related and age-related vulnerabilities; nevertheless, little is known about how this effect has changed over time and how it varies in space. This study aims to evaluate the association between asthma hospitalisation and warm temperature and investigate vulnerabilities by age, sex, time and space.

Methods

We retrieved individual-level data on summer asthma hospitalisation at high temporal (daily) and spatial (postcodes) resolutions during 2002-2019 in England from the NHS Digital. Daily mean temperature at 1 km\u00d71 km resolution was retrieved from the UK Met Office. We focused on lag 0-3\u2009days. We employed a case-crossover study design and fitted Bayesian hierarchical Poisson models accounting for possible confounders (rainfall, relative humidity, wind speed and national holidays).

Results

After accounting for confounding, we found an increase of 1.11% (95% credible interval: 0.88% to 1.34%) in the asthma hospitalisation risk for every 1\u00b0C increase in the ambient summer temperature. The effect was highest for males aged 16-64 (2.10%, 1.59% to 2.61%) and during the early years of our analysis. We also found evidence of a decreasing linear trend of the effect over time. Populations in Yorkshire and the Humber and East and West Midlands were the most vulnerable.

Conclusion

This study provides evidence of an association between warm temperature and hospital admission for asthma. The effect has decreased over time with potential explanations including temporal differences in patterns of heat exposure, adaptive mechanisms, asthma management, lifestyle, comorbidities and occupation.", - "laySummary": "", - "urls": "pdf:https://thorax.bmj.com/content/thoraxjnl/early/2023/04/17/thorax-2022-219901.full.pdf; doi:https://doi.org/10.1136/thorax-2022-219901; html:https://europepmc.org/articles/PMC10447396; pdf:https://europepmc.org/articles/PMC10447396?pdf=render" - }, { "id": "33838587", "doi": "https://doi.org/10.1016/j.epidem.2021.100460", @@ -9043,6 +9026,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.epidem.2021.100460; doi:https://doi.org/10.1016/j.epidem.2021.100460; html:https://europepmc.org/articles/PMC8193815" }, + { + "id": "37068951", + "doi": "https://doi.org/10.1136/thorax-2022-219901", + "title": "Asthma hospitalisations and heat exposure in England: a case-crossover study during 2002-2019.", + "authorString": "Konstantinoudis G, Minelli C, Lam HCY, Fuertes E, Ballester J, Davies B, Vicedo-Cabrera AM, Gasparrini A, Blangiardo M.", + "authorAffiliations": "", + "journalTitle": "Thorax", + "pubYear": "2023", + "date": "2023-04-17", + "isOpenAccess": "Y", + "keywords": "Asthma Epidemiology", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Previous studies have reported an association between warm temperature and asthma hospitalisation. They have reported different sex-related and age-related vulnerabilities; nevertheless, little is known about how this effect has changed over time and how it varies in space. This study aims to evaluate the association between asthma hospitalisation and warm temperature and investigate vulnerabilities by age, sex, time and space.

Methods

We retrieved individual-level data on summer asthma hospitalisation at high temporal (daily) and spatial (postcodes) resolutions during 2002-2019 in England from the NHS Digital. Daily mean temperature at 1 km\u00d71 km resolution was retrieved from the UK Met Office. We focused on lag 0-3\u2009days. We employed a case-crossover study design and fitted Bayesian hierarchical Poisson models accounting for possible confounders (rainfall, relative humidity, wind speed and national holidays).

Results

After accounting for confounding, we found an increase of 1.11% (95% credible interval: 0.88% to 1.34%) in the asthma hospitalisation risk for every 1\u00b0C increase in the ambient summer temperature. The effect was highest for males aged 16-64 (2.10%, 1.59% to 2.61%) and during the early years of our analysis. We also found evidence of a decreasing linear trend of the effect over time. Populations in Yorkshire and the Humber and East and West Midlands were the most vulnerable.

Conclusion

This study provides evidence of an association between warm temperature and hospital admission for asthma. The effect has decreased over time with potential explanations including temporal differences in patterns of heat exposure, adaptive mechanisms, asthma management, lifestyle, comorbidities and occupation.", + "laySummary": "", + "urls": "pdf:https://thorax.bmj.com/content/thoraxjnl/early/2023/04/17/thorax-2022-219901.full.pdf; doi:https://doi.org/10.1136/thorax-2022-219901; html:https://europepmc.org/articles/PMC10447396; pdf:https://europepmc.org/articles/PMC10447396?pdf=render" + }, { "id": "37587484", "doi": "https://doi.org/10.1186/s12874-023-02000-9", @@ -9094,23 +9094,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1080/09553002.2023.2173823; doi:https://doi.org/10.1080/09553002.2023.2173823" }, - { - "id": "38552327", - "doi": "https://doi.org/10.1093/bioinformatics/btae172", - "title": "shinyExprPortal: a configurable 'shiny' portal for sharing analysis of molecular expression data.", - "authorString": "Henkin R, Goldmann K, Lewis M, Barnes MR.", - "authorAffiliations": "", - "journalTitle": "Bioinformatics (Oxford, England)", - "pubYear": "2024", - "date": "2024-03-01", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Motivation

The scale of omics research presents many obstacles to full sharing and access to analysis results. Current publication models impose limits on the number of pages and figures, requiring careful preparation and selection of content. At the same time, depositing data in open repositories significantly shifts the burden of access and reproduction to readers, who may include people who are not programmers or analysts.

Results

We introduce shinyExprPortal, an R package that implements omics web portals with minimal coding effort. The portals allow exploration of transcriptomic or proteomic expression data and phenotypes, showcasing results of various types of analysis including differential expression, co-expression and pathways analysis. The integration with bioinformatics workflows enables researchers to focus on their results and share findings using interactive and publication-quality plots.

Availability and implementation

The shinyExprPortal package is available to download and install from CRAN and https://github.com/C4TB/shinyExprPortal.", - "laySummary": "", - "urls": "pdf:https://academic.oup.com/bioinformatics/advance-article-pdf/doi/10.1093/bioinformatics/btae172/57122310/btae172.pdf; doi:https://doi.org/10.1093/bioinformatics/btae172; html:https://europepmc.org/articles/PMC11021805; pdf:https://europepmc.org/articles/PMC11021805?pdf=render" - }, { "id": "30474191", "doi": "https://doi.org/10.1111/dme.13870", @@ -9128,6 +9111,23 @@ "laySummary": "The aim of this article was to investigate the relationship between HbA1c and glucose in patients with diabetes awaiting transplant due to a co-existing liver disease, and in those with diabetes but no liver disease. Statistical analyses results indicated that HbA1c is not an appropriate test for blood glucose in people with cirrhosis and diabetes awaiting transplant, and it might cause misdiagnosis of diabetes and inappropirate clinical care in people with cirrhotic liver disease.", "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/dme.13870; doi:https://doi.org/10.1111/dme.13870; html:https://europepmc.org/articles/PMC6850030; pdf:https://europepmc.org/articles/PMC6850030?pdf=render" }, + { + "id": "38552327", + "doi": "https://doi.org/10.1093/bioinformatics/btae172", + "title": "shinyExprPortal: a configurable 'shiny' portal for sharing analysis of molecular expression data.", + "authorString": "Henkin R, Goldmann K, Lewis M, Barnes MR.", + "authorAffiliations": "", + "journalTitle": "Bioinformatics (Oxford, England)", + "pubYear": "2024", + "date": "2024-03-01", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Motivation

The scale of omics research presents many obstacles to full sharing and access to analysis results. Current publication models impose limits on the number of pages and figures, requiring careful preparation and selection of content. At the same time, depositing data in open repositories significantly shifts the burden of access and reproduction to readers, who may include people who are not programmers or analysts.

Results

We introduce shinyExprPortal, an R package that implements omics web portals with minimal coding effort. The portals allow exploration of transcriptomic or proteomic expression data and phenotypes, showcasing results of various types of analysis including differential expression, co-expression and pathways analysis. The integration with bioinformatics workflows enables researchers to focus on their results and share findings using interactive and publication-quality plots.

Availability and implementation

The shinyExprPortal package is available to download and install from CRAN and https://github.com/C4TB/shinyExprPortal.", + "laySummary": "", + "urls": "pdf:https://academic.oup.com/bioinformatics/advance-article-pdf/doi/10.1093/bioinformatics/btae172/57122310/btae172.pdf; doi:https://doi.org/10.1093/bioinformatics/btae172; html:https://europepmc.org/articles/PMC11021805; pdf:https://europepmc.org/articles/PMC11021805?pdf=render" + }, { "id": "34514500", "doi": "https://doi.org/10.1093/infdis/jiab459", @@ -9434,23 +9434,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1136/bmjdrc-2024-004191; doi:https://doi.org/10.1136/bmjdrc-2024-004191" }, - { - "id": "37144149", - "doi": "https://doi.org/10.3389/fped.2023.1148975", - "title": "The psychosocial impact of microtia and ear reconstruction: A national data-linkage study.", - "authorString": "Jovic TH, Gibson JAG, Jovic M, Dobbs TD, Griffiths R, Akbari A, Whitaker IS.", - "authorAffiliations": "", - "journalTitle": "Frontiers in pediatrics", - "pubYear": "2023", - "date": "2023-04-18", - "isOpenAccess": "Y", - "keywords": "Depression; Anxiety; Education; Microtia; Data Science", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Introduction

Children with visible facial differences are believed to be at increased risk of negative psychosocial behaviours which may manifest as affective disorders. The aim of this study was to determine whether a diagnosis of microtia, and the associated surgical intervention, is associated with psychosocial implications including impaired educational attainment and a diagnosis of an affective disorder.

Methods

A retrospective case-control study was conducted using data linkage to identify patients in Wales with a diagnosis of microtia. Matched controls were sought on the basis of age, gender and socioeconomic deprivation status to yield a total sample size of 709. incidence was calculated using annual and geographic birth rates. Surgical operation codes were used to classify patients into those that had no surgery, autologous reconstruction or prosthetic reconstruction. Educational attainment at 11 years of age, plus a diagnosis of depression or anxiety were used as markers of adverse psychosocial outcomes and the relative risk was attained using logistic regression analyses.

Results

There were no significant associations between a diagnosis of microtia and an increased risk of adverse educational attainment or a risk of an affective disorder diagnosis. Male gender and higher deprivation scores were significantly associated with poorer educational attainment, irrespective of a diagnosis of microtia. Surgical intervention of any nature was also not associated with any increased risk of adverse educational or psychosocial outcomes in microtia patients.

Discussion

Microtia patients in Wales do not appear to be at greater risk of developing affective disorders or impaired academic performance as a result of their diagnosis or associated surgical intervention. Whilst reassuring, the need for appropriate support mechanisms to maintain positive psychosocial wellbeing and academic achievement in this patient cohort is reinforced.", - "laySummary": "", - "urls": "pdf:https://www.frontiersin.org/articles/10.3389/fped.2023.1148975/pdf; doi:https://doi.org/10.3389/fped.2023.1148975; html:https://europepmc.org/articles/PMC10152550; pdf:https://europepmc.org/articles/PMC10152550?pdf=render" - }, { "id": "32180562", "doi": "https://doi.org/10.1016/j.molmet.2020.01.009", @@ -9468,6 +9451,23 @@ "laySummary": "How the body breaks down fat is poorly understood, and, if this mechanism does not happen effiently in the body it can lead to metabolic diseases including obesity and type 2 diabetes. The goal of this study was to identify the genetic regulators of how the body break down fat and explain their molecular mechanisms.", "urls": "doi:https://doi.org/10.1016/j.molmet.2020.01.009; doi:https://doi.org/10.1016/j.molmet.2020.01.009; html:https://europepmc.org/articles/PMC7021539; pdf:https://europepmc.org/articles/PMC7021539?pdf=render" }, + { + "id": "37144149", + "doi": "https://doi.org/10.3389/fped.2023.1148975", + "title": "The psychosocial impact of microtia and ear reconstruction: A national data-linkage study.", + "authorString": "Jovic TH, Gibson JAG, Jovic M, Dobbs TD, Griffiths R, Akbari A, Whitaker IS.", + "authorAffiliations": "", + "journalTitle": "Frontiers in pediatrics", + "pubYear": "2023", + "date": "2023-04-18", + "isOpenAccess": "Y", + "keywords": "Depression; Anxiety; Education; Microtia; Data Science", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Introduction

Children with visible facial differences are believed to be at increased risk of negative psychosocial behaviours which may manifest as affective disorders. The aim of this study was to determine whether a diagnosis of microtia, and the associated surgical intervention, is associated with psychosocial implications including impaired educational attainment and a diagnosis of an affective disorder.

Methods

A retrospective case-control study was conducted using data linkage to identify patients in Wales with a diagnosis of microtia. Matched controls were sought on the basis of age, gender and socioeconomic deprivation status to yield a total sample size of 709. incidence was calculated using annual and geographic birth rates. Surgical operation codes were used to classify patients into those that had no surgery, autologous reconstruction or prosthetic reconstruction. Educational attainment at 11 years of age, plus a diagnosis of depression or anxiety were used as markers of adverse psychosocial outcomes and the relative risk was attained using logistic regression analyses.

Results

There were no significant associations between a diagnosis of microtia and an increased risk of adverse educational attainment or a risk of an affective disorder diagnosis. Male gender and higher deprivation scores were significantly associated with poorer educational attainment, irrespective of a diagnosis of microtia. Surgical intervention of any nature was also not associated with any increased risk of adverse educational or psychosocial outcomes in microtia patients.

Discussion

Microtia patients in Wales do not appear to be at greater risk of developing affective disorders or impaired academic performance as a result of their diagnosis or associated surgical intervention. Whilst reassuring, the need for appropriate support mechanisms to maintain positive psychosocial wellbeing and academic achievement in this patient cohort is reinforced.", + "laySummary": "", + "urls": "pdf:https://www.frontiersin.org/articles/10.3389/fped.2023.1148975/pdf; doi:https://doi.org/10.3389/fped.2023.1148975; html:https://europepmc.org/articles/PMC10152550; pdf:https://europepmc.org/articles/PMC10152550?pdf=render" + }, { "id": "33842409", "doi": "https://doi.org/10.3389/fped.2021.630036", @@ -9604,23 +9604,6 @@ "laySummary": "", "urls": "pdf:https://discovery.ucl.ac.uk/10149895/1/afac098.pdf; doi:https://doi.org/10.1093/ageing/afac098; html:https://europepmc.org/articles/PMC9113942; pdf:https://europepmc.org/articles/PMC9113942?pdf=render" }, - { - "id": "38429012", - "doi": "https://doi.org/10.1016/s2468-2667(24)00025-2", - "title": "Social and spatial inequalities in premature mortality across Europe.", - "authorString": "Bragg F, Lacey B.", - "authorAffiliations": "", - "journalTitle": "The Lancet. Public health", - "pubYear": "2024", - "date": "2024-03-01", - "isOpenAccess": "N", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "", - "laySummary": "", - "urls": "doi:https://doi.org/10.1016/S2468-2667(24)00025-2" - }, { "id": "34183342", "doi": "https://doi.org/10.1136/bmjopen-2020-046392", @@ -9638,6 +9621,23 @@ "laySummary": "", "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/11/6/e046392.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-046392; html:https://europepmc.org/articles/PMC8245289; pdf:https://europepmc.org/articles/PMC8245289?pdf=render" }, + { + "id": "38429012", + "doi": "https://doi.org/10.1016/s2468-2667(24)00025-2", + "title": "Social and spatial inequalities in premature mortality across Europe.", + "authorString": "Bragg F, Lacey B.", + "authorAffiliations": "", + "journalTitle": "The Lancet. Public health", + "pubYear": "2024", + "date": "2024-03-01", + "isOpenAccess": "N", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "", + "laySummary": "", + "urls": "doi:https://doi.org/10.1016/S2468-2667(24)00025-2" + }, { "id": "33182605", "doi": "https://doi.org/10.3390/genes11111326", @@ -10046,23 +10046,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.ejvs.2024.05.010" }, - { - "id": "38505485", - "doi": "https://doi.org/10.1093/ehjdh/ztae001", - "title": "Explainable machine learning using echocardiography to improve risk prediction in patients with chronic coronary syndrome.", - "authorString": "Molenaar MA, Bouma BJ, Asselbergs FW, Verouden NJ, Selder JL, Chamuleau SAJ, Schuuring MJ.", - "authorAffiliations": "", - "journalTitle": "European heart journal. Digital health", - "pubYear": "2024", - "date": "2024-01-22", - "isOpenAccess": "Y", - "keywords": "Artificial intelligence; Mortality; Prognosis; coronary artery disease; risk; Machine Learning", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Aims

The European Society of Cardiology guidelines recommend risk stratification with limited clinical parameters such as left ventricular (LV) function in patients with chronic coronary syndrome (CCS). Machine learning (ML) methods enable an analysis of complex datasets including transthoracic echocardiography (TTE) studies. We aimed to evaluate the accuracy of ML using clinical and TTE data to predict all-cause 5-year mortality in patients with CCS and to compare its performance with traditional risk stratification scores.

Methods and results

Data of consecutive patients with CCS were retrospectively collected if they attended the outpatient clinic of Amsterdam UMC location AMC between 2015 and 2017 and had a TTE assessment of the LV function. An eXtreme Gradient Boosting (XGBoost) model was trained to predict all-cause 5-year mortality. The performance of this ML model was evaluated using data from the Amsterdam UMC location VUmc and compared with the reference standard of traditional risk scores. A total of 1253 patients (775 training set and 478 testing set) were included, of which 176 patients (105 training set and 71 testing set) died during the 5-year follow-up period. The ML model demonstrated a superior performance [area under the receiver operating characteristic curve (AUC) 0.79] compared with traditional risk stratification tools (AUC 0.62-0.76) and showed good external performance. The most important TTE risk predictors included in the ML model were LV dysfunction and significant tricuspid regurgitation.

Conclusion

This study demonstrates that an explainable ML model using TTE and clinical data can accurately identify high-risk CCS patients, with a prognostic value superior to traditional risk scores.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1093/ehjdh/ztae001; html:https://europepmc.org/articles/PMC10944683; pdf:https://europepmc.org/articles/PMC10944683?pdf=render" - }, { "id": "33419870", "doi": "https://doi.org/10.1136/bmjhci-2020-100254", @@ -10080,6 +10063,23 @@ "laySummary": "", "urls": "pdf:https://informatics.bmj.com/content/bmjhci/28/1/e100254.full.pdf; doi:https://doi.org/10.1136/bmjhci-2020-100254; html:https://europepmc.org/articles/PMC7798427; pdf:https://europepmc.org/articles/PMC7798427?pdf=render" }, + { + "id": "38505485", + "doi": "https://doi.org/10.1093/ehjdh/ztae001", + "title": "Explainable machine learning using echocardiography to improve risk prediction in patients with chronic coronary syndrome.", + "authorString": "Molenaar MA, Bouma BJ, Asselbergs FW, Verouden NJ, Selder JL, Chamuleau SAJ, Schuuring MJ.", + "authorAffiliations": "", + "journalTitle": "European heart journal. Digital health", + "pubYear": "2024", + "date": "2024-01-22", + "isOpenAccess": "Y", + "keywords": "Artificial intelligence; Mortality; Prognosis; coronary artery disease; risk; Machine Learning", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Aims

The European Society of Cardiology guidelines recommend risk stratification with limited clinical parameters such as left ventricular (LV) function in patients with chronic coronary syndrome (CCS). Machine learning (ML) methods enable an analysis of complex datasets including transthoracic echocardiography (TTE) studies. We aimed to evaluate the accuracy of ML using clinical and TTE data to predict all-cause 5-year mortality in patients with CCS and to compare its performance with traditional risk stratification scores.

Methods and results

Data of consecutive patients with CCS were retrospectively collected if they attended the outpatient clinic of Amsterdam UMC location AMC between 2015 and 2017 and had a TTE assessment of the LV function. An eXtreme Gradient Boosting (XGBoost) model was trained to predict all-cause 5-year mortality. The performance of this ML model was evaluated using data from the Amsterdam UMC location VUmc and compared with the reference standard of traditional risk scores. A total of 1253 patients (775 training set and 478 testing set) were included, of which 176 patients (105 training set and 71 testing set) died during the 5-year follow-up period. The ML model demonstrated a superior performance [area under the receiver operating characteristic curve (AUC) 0.79] compared with traditional risk stratification tools (AUC 0.62-0.76) and showed good external performance. The most important TTE risk predictors included in the ML model were LV dysfunction and significant tricuspid regurgitation.

Conclusion

This study demonstrates that an explainable ML model using TTE and clinical data can accurately identify high-risk CCS patients, with a prognostic value superior to traditional risk scores.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1093/ehjdh/ztae001; html:https://europepmc.org/articles/PMC10944683; pdf:https://europepmc.org/articles/PMC10944683?pdf=render" + }, { "id": "29992526", "doi": "https://doi.org/10.1007/s11906-018-0877-8", @@ -10403,23 +10403,6 @@ "laySummary": "", "urls": "pdf:https://www.rhinologyjournal.com/download.php?id=1882; doi:https://doi.org/10.4193/Rhin18.237" }, - { - "id": "37185641", - "doi": "https://doi.org/10.1136/bmjopen-2022-070022", - "title": "EXAcerbations of COPD and their OutcomeS on CardioVascular diseases (EXACOS-CV) Programme: protocol of multicountry observational cohort studies.", - "authorString": "Nordon C, Rhodes K, Quint JK, Vogelmeier CF, Simons SO, Hawkins NM, Marshall J, Ouwens M, Garbe E, M\u00fcllerov\u00e1 H.", - "authorAffiliations": "", - "journalTitle": "BMJ open", - "pubYear": "2023", - "date": "2023-04-26", - "isOpenAccess": "Y", - "keywords": "epidemiology; Cardiology; Vascular Medicine; Chronic Airways Disease", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Introduction

In patients with chronic obstructive pulmonary disease (COPD), the risk of certain cardiovascular (CV) events is increased by threefold to fivefold in the year following acute exacerbation of COPD (AECOPD), compared with a non-exacerbation period. While the effect of severe AECOPD is well established, the relationship of moderate exacerbation or prior exacerbation to elevated risk of CV events is less clear. We will conduct cohort studies in multiple countries to further characterise the association between AECOPD and CV events.

Methods and analysis

Retrospective longitudinal cohort studies will be conducted within routinely collected electronic healthcare records or claims databases. The study cohorts will include patients meeting inclusion criteria for COPD between 1 January 2014 and 31 December 2018. Moderate exacerbation is defined as an outpatient visit and/or medication dispensation/prescription for exacerbation; severe exacerbation is defined as hospitalisation for COPD. The primary outcomes of interest are the time to (1) first hospitalisation for a CV event (including acute coronary syndrome, heart failure, arrhythmias or cerebral ischaemia) since cohort entry or (2) death. Time-dependent Cox proportional hazards models will compare the hazard of a CV event between exposed periods following exacerbation (split into these periods: 1-7, 8-14, 15-30, 31-180 and 181-365 days) and the unexposed reference time period, adjusted on time-fixed and time-varying confounders.

Ethics and dissemination

Studies have been approved in Canada, Japan, the Netherlands, Spain and the UK, where an institutional review board is mandated. For each study, the results will be published in peer-reviewed journals.", - "laySummary": "", - "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/13/4/e070022.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-070022; html:https://europepmc.org/articles/PMC10151875; pdf:https://europepmc.org/articles/PMC10151875?pdf=render" - }, { "id": "35151397", "doi": "https://doi.org/10.1016/s0140-6736(22)00163-5", @@ -10437,6 +10420,23 @@ "laySummary": "", "urls": "pdf:http://spiral.imperial.ac.uk/bitstream/10044/1/95149/5/1-s2.0-S0140673622001635-main.pdf; doi:https://doi.org/10.1016/S0140-6736(22)00163-5; html:https://europepmc.org/articles/PMC8830904" }, + { + "id": "37185641", + "doi": "https://doi.org/10.1136/bmjopen-2022-070022", + "title": "EXAcerbations of COPD and their OutcomeS on CardioVascular diseases (EXACOS-CV) Programme: protocol of multicountry observational cohort studies.", + "authorString": "Nordon C, Rhodes K, Quint JK, Vogelmeier CF, Simons SO, Hawkins NM, Marshall J, Ouwens M, Garbe E, M\u00fcllerov\u00e1 H.", + "authorAffiliations": "", + "journalTitle": "BMJ open", + "pubYear": "2023", + "date": "2023-04-26", + "isOpenAccess": "Y", + "keywords": "epidemiology; Cardiology; Vascular Medicine; Chronic Airways Disease", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Introduction

In patients with chronic obstructive pulmonary disease (COPD), the risk of certain cardiovascular (CV) events is increased by threefold to fivefold in the year following acute exacerbation of COPD (AECOPD), compared with a non-exacerbation period. While the effect of severe AECOPD is well established, the relationship of moderate exacerbation or prior exacerbation to elevated risk of CV events is less clear. We will conduct cohort studies in multiple countries to further characterise the association between AECOPD and CV events.

Methods and analysis

Retrospective longitudinal cohort studies will be conducted within routinely collected electronic healthcare records or claims databases. The study cohorts will include patients meeting inclusion criteria for COPD between 1 January 2014 and 31 December 2018. Moderate exacerbation is defined as an outpatient visit and/or medication dispensation/prescription for exacerbation; severe exacerbation is defined as hospitalisation for COPD. The primary outcomes of interest are the time to (1) first hospitalisation for a CV event (including acute coronary syndrome, heart failure, arrhythmias or cerebral ischaemia) since cohort entry or (2) death. Time-dependent Cox proportional hazards models will compare the hazard of a CV event between exposed periods following exacerbation (split into these periods: 1-7, 8-14, 15-30, 31-180 and 181-365 days) and the unexposed reference time period, adjusted on time-fixed and time-varying confounders.

Ethics and dissemination

Studies have been approved in Canada, Japan, the Netherlands, Spain and the UK, where an institutional review board is mandated. For each study, the results will be published in peer-reviewed journals.", + "laySummary": "", + "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/13/4/e070022.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-070022; html:https://europepmc.org/articles/PMC10151875; pdf:https://europepmc.org/articles/PMC10151875?pdf=render" + }, { "id": "34518162", "doi": "https://doi.org/10.1136/bjophthalmol-2021-319383", @@ -10454,23 +10454,6 @@ "laySummary": "", "urls": "pdf:https://discovery.ucl.ac.uk/10164981/1/267.full.pdf; doi:https://doi.org/10.1136/bjophthalmol-2021-319383; html:https://europepmc.org/articles/PMC9887382; pdf:https://europepmc.org/articles/PMC9887382?pdf=render" }, - { - "id": "38053867", - "doi": "https://doi.org/10.1016/j.heliyon.2023.e21734", - "title": "Wastewater-based surveillance models for COVID-19: A focused review on spatio-temporal models.", - "authorString": "Torabi F, Li G, Mole C, Nicholson G, Rowlingson B, Smith CR, Jersakova R, Diggle PJ, Blangiardo M.", - "authorAffiliations": "", - "journalTitle": "Heliyon", - "pubYear": "2023", - "date": "2023-11-08", - "isOpenAccess": "Y", - "keywords": "Wastewater-based Epidemiology; Covid-19; Wastewater-Based Surveillance; Spatio-Temporal Statistical Modelling", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "The evident shedding of the SARS-CoV-2 RNA particles from infected individuals into the wastewater opened up a tantalizing array of possibilities for prediction of COVID-19 prevalence prior to symptomatic case identification through community testing. Many countries have therefore explored the use of wastewater metrics as a surveillance tool, replacing traditional direct measurement of prevalence with cost-effective approaches based on SARS-CoV-2 RNA concentrations in wastewater samples. Two important aspects in building prediction models are: time over which the prediction occurs and space for which the predicted case numbers is shown. In this review, our main focus was on finding mathematical models which take into the account both the time-varying and spatial nature of wastewater-based metrics into account. We used six main characteristics as our assessment criteria: i) modelling approach; ii) temporal coverage; iii) spatial coverage; iv) sample size; v) wastewater sampling method; and vi) covariates included in the modelling. The majority of studies in the early phases of the pandemic recognized the temporal association of SARS-CoV-2 RNA concentration level in wastewater with the number of COVID-19 cases, ignoring their spatial context. We examined 15 studies up to April 2023, focusing on models considering both temporal and spatial aspects of wastewater metrics. Most early studies correlated temporal SARS-CoV-2 RNA levels with COVID-19 cases but overlooked spatial factors. Linear regression and SEIR models were commonly used (n\u00a0=\u00a010, 66.6\u00a0% of studies), along with machine learning (n\u00a0=\u00a01, 6.6\u00a0%) and Bayesian approaches (n\u00a0=\u00a01, 6.6\u00a0%) in some cases. Three studies employed spatio-temporal modelling approach (n\u00a0=\u00a03, 20.0\u00a0%). We conclude that the development, validation and calibration of further spatio-temporally explicit models should be done in parallel with the advancement of wastewater metrics before the potential of wastewater as a surveillance tool can be fully realised.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1016/j.heliyon.2023.e21734; html:https://europepmc.org/articles/PMC10694161; pdf:https://europepmc.org/articles/PMC10694161?pdf=render" - }, { "id": "35749561", "doi": "https://doi.org/10.1371/journal.pcbi.1010234", @@ -10488,6 +10471,23 @@ "laySummary": "", "urls": "pdf:https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1010234&type=printable; doi:https://doi.org/10.1371/journal.pcbi.1010234; html:https://europepmc.org/articles/PMC9262224; pdf:https://europepmc.org/articles/PMC9262224?pdf=render" }, + { + "id": "38053867", + "doi": "https://doi.org/10.1016/j.heliyon.2023.e21734", + "title": "Wastewater-based surveillance models for COVID-19: A focused review on spatio-temporal models.", + "authorString": "Torabi F, Li G, Mole C, Nicholson G, Rowlingson B, Smith CR, Jersakova R, Diggle PJ, Blangiardo M.", + "authorAffiliations": "", + "journalTitle": "Heliyon", + "pubYear": "2023", + "date": "2023-11-08", + "isOpenAccess": "Y", + "keywords": "Wastewater-based Epidemiology; Covid-19; Wastewater-Based Surveillance; Spatio-Temporal Statistical Modelling", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "The evident shedding of the SARS-CoV-2 RNA particles from infected individuals into the wastewater opened up a tantalizing array of possibilities for prediction of COVID-19 prevalence prior to symptomatic case identification through community testing. Many countries have therefore explored the use of wastewater metrics as a surveillance tool, replacing traditional direct measurement of prevalence with cost-effective approaches based on SARS-CoV-2 RNA concentrations in wastewater samples. Two important aspects in building prediction models are: time over which the prediction occurs and space for which the predicted case numbers is shown. In this review, our main focus was on finding mathematical models which take into the account both the time-varying and spatial nature of wastewater-based metrics into account. We used six main characteristics as our assessment criteria: i) modelling approach; ii) temporal coverage; iii) spatial coverage; iv) sample size; v) wastewater sampling method; and vi) covariates included in the modelling. The majority of studies in the early phases of the pandemic recognized the temporal association of SARS-CoV-2 RNA concentration level in wastewater with the number of COVID-19 cases, ignoring their spatial context. We examined 15 studies up to April 2023, focusing on models considering both temporal and spatial aspects of wastewater metrics. Most early studies correlated temporal SARS-CoV-2 RNA levels with COVID-19 cases but overlooked spatial factors. Linear regression and SEIR models were commonly used (n\u00a0=\u00a010, 66.6\u00a0% of studies), along with machine learning (n\u00a0=\u00a01, 6.6\u00a0%) and Bayesian approaches (n\u00a0=\u00a01, 6.6\u00a0%) in some cases. Three studies employed spatio-temporal modelling approach (n\u00a0=\u00a03, 20.0\u00a0%). We conclude that the development, validation and calibration of further spatio-temporally explicit models should be done in parallel with the advancement of wastewater metrics before the potential of wastewater as a surveillance tool can be fully realised.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1016/j.heliyon.2023.e21734; html:https://europepmc.org/articles/PMC10694161; pdf:https://europepmc.org/articles/PMC10694161?pdf=render" + }, { "id": "PMC9644860", "doi": "https://doi.org/", @@ -10709,23 +10709,6 @@ "laySummary": "", "urls": "pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1004124&type=printable; doi:https://doi.org/10.1371/journal.pmed.1004124; html:https://europepmc.org/articles/PMC9725132; pdf:https://europepmc.org/articles/PMC9725132?pdf=render" }, - { - "id": "38479735", - "doi": "https://doi.org/10.1136/bmjopen-2023-081926", - "title": "HFE genotypes, haemochromatosis diagnosis and clinical outcomes at age 80 years: a prospective cohort study in the UK Biobank.", - "authorString": "Lucas MR, Atkins JL, Pilling LC, Shearman JD, Melzer D.", - "authorAffiliations": "", - "journalTitle": "BMJ open", - "pubYear": "2024", - "date": "2024-03-13", - "isOpenAccess": "Y", - "keywords": "Genetics; Mortality; Hepatology; Other Metabolic, E.g. Iron, Porphyria", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Objectives

HFE haemochromatosis genetic variants have an uncertain clinical penetrance, especially to older ages and in undiagnosed groups. We estimated p.C282Y and p.H63D variant cumulative incidence of multiple clinical outcomes in a large community cohort.

Design

Prospective cohort study.

Setting

22 assessment centres across England, Scotland, and Wales in the UK Biobank (2006-2010).

Participants

451\u2009270 participants genetically similar to the 1000 Genomes European reference population, with a mean of 13.3-year follow-up through hospital inpatient, cancer registries and death certificate data.

Main outcome measures

Cox proportional HRs of incident clinical outcomes and mortality in those with HFE p.C282Y/p.H63D mutations compared with those with no variants, stratified by sex and adjusted for age, assessment centre and genetic stratification. Cumulative incidences were estimated from age 40 years to 80 years.

Results

12.1% of p.C282Y+/+ males had baseline (mean age 57 years) haemochromatosis diagnoses, with a cumulative incidence of 56.4% at age 80 years. 33.1% died vs 25.4% without HFE variants (HR 1.29, 95%\u2009CI: 1.12 to 1.48, p=4.7\u00d710-4); 27.9% vs 17.1% had joint replacements, 20.3% vs 8.3% had liver disease, and there were excess delirium, dementia, and Parkinson's disease but not depression. Associations, including excess mortality, were similar in the group undiagnosed with haemochromatosis. 3.4% of women with p.C282Y+/+ had baseline haemochromatosis diagnoses, with a cumulative incidence of 40.5% at age 80 years. There were excess incident liver disease (8.9% vs 6.8%; HR 1.62, 95%\u2009CI: 1.27 to 2.05, p=7.8\u00d710-5), joint replacements and delirium, with similar results in the undiagnosed. p.C282Y/p.H63D and p.H63D+/+ men\u2009or women had no statistically significant excess fatigue or depression at baseline and no excess incident outcomes.

Conclusions

Male and female p.C282Y homozygotes experienced greater excess morbidity than previously documented, including those undiagnosed with haemochromatosis in the community. As haemochromatosis diagnosis rates were low at baseline despite treatment being considered effective, trials of screening to identify people with p.C282Y homozygosity early appear justified.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1136/bmjopen-2023-081926; html:https://europepmc.org/articles/PMC10936495; pdf:https://europepmc.org/articles/PMC10936495?pdf=render" - }, { "id": "36921681", "doi": "https://doi.org/10.1016/j.cca.2023.117271", @@ -10743,6 +10726,23 @@ "laySummary": "", "urls": "html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10009995; doi:https://doi.org/10.1016/j.cca.2023.117271; html:https://europepmc.org/articles/PMC10009995; pdf:https://europepmc.org/articles/PMC10009995?pdf=render" }, + { + "id": "38479735", + "doi": "https://doi.org/10.1136/bmjopen-2023-081926", + "title": "HFE genotypes, haemochromatosis diagnosis and clinical outcomes at age 80 years: a prospective cohort study in the UK Biobank.", + "authorString": "Lucas MR, Atkins JL, Pilling LC, Shearman JD, Melzer D.", + "authorAffiliations": "", + "journalTitle": "BMJ open", + "pubYear": "2024", + "date": "2024-03-13", + "isOpenAccess": "Y", + "keywords": "Genetics; Mortality; Hepatology; Other Metabolic, E.g. Iron, Porphyria", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Objectives

HFE haemochromatosis genetic variants have an uncertain clinical penetrance, especially to older ages and in undiagnosed groups. We estimated p.C282Y and p.H63D variant cumulative incidence of multiple clinical outcomes in a large community cohort.

Design

Prospective cohort study.

Setting

22 assessment centres across England, Scotland, and Wales in the UK Biobank (2006-2010).

Participants

451\u2009270 participants genetically similar to the 1000 Genomes European reference population, with a mean of 13.3-year follow-up through hospital inpatient, cancer registries and death certificate data.

Main outcome measures

Cox proportional HRs of incident clinical outcomes and mortality in those with HFE p.C282Y/p.H63D mutations compared with those with no variants, stratified by sex and adjusted for age, assessment centre and genetic stratification. Cumulative incidences were estimated from age 40 years to 80 years.

Results

12.1% of p.C282Y+/+ males had baseline (mean age 57 years) haemochromatosis diagnoses, with a cumulative incidence of 56.4% at age 80 years. 33.1% died vs 25.4% without HFE variants (HR 1.29, 95%\u2009CI: 1.12 to 1.48, p=4.7\u00d710-4); 27.9% vs 17.1% had joint replacements, 20.3% vs 8.3% had liver disease, and there were excess delirium, dementia, and Parkinson's disease but not depression. Associations, including excess mortality, were similar in the group undiagnosed with haemochromatosis. 3.4% of women with p.C282Y+/+ had baseline haemochromatosis diagnoses, with a cumulative incidence of 40.5% at age 80 years. There were excess incident liver disease (8.9% vs 6.8%; HR 1.62, 95%\u2009CI: 1.27 to 2.05, p=7.8\u00d710-5), joint replacements and delirium, with similar results in the undiagnosed. p.C282Y/p.H63D and p.H63D+/+ men\u2009or women had no statistically significant excess fatigue or depression at baseline and no excess incident outcomes.

Conclusions

Male and female p.C282Y homozygotes experienced greater excess morbidity than previously documented, including those undiagnosed with haemochromatosis in the community. As haemochromatosis diagnosis rates were low at baseline despite treatment being considered effective, trials of screening to identify people with p.C282Y homozygosity early appear justified.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1136/bmjopen-2023-081926; html:https://europepmc.org/articles/PMC10936495; pdf:https://europepmc.org/articles/PMC10936495?pdf=render" + }, { "id": "38383380", "doi": "https://doi.org/10.1186/s12939-024-02114-6", @@ -10879,23 +10879,6 @@ "laySummary": "", "urls": "pdf:https://heart.bmj.com/content/heartjnl/106/24/1890.full.pdf; doi:https://doi.org/10.1136/heartjnl-2020-317870; html:https://europepmc.org/articles/PMC7536637; pdf:https://europepmc.org/articles/PMC7536637?pdf=render" }, - { - "id": "36812617", - "doi": "https://doi.org/10.1371/journal.pdig.0000162", - "title": "Informing antimicrobial stewardship with explainable AI.", - "authorString": "Cavallaro M, Moran E, Collyer B, McCarthy ND, Green C, Keeling MJ.", - "authorAffiliations": "", - "journalTitle": "PLOS digital health", - "pubYear": "2023", - "date": "2023-01-05", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "The accuracy and flexibility of artificial intelligence (AI) systems often comes at the cost of a decreased ability to offer an intuitive explanation of their predictions. This hinders trust and discourage adoption of AI in healthcare, exacerbated by concerns over liabilities and risks to patients' health in case of misdiagnosis. Providing an explanation for a model's prediction is possible due to recent advances in the field of interpretable machine learning. We considered a data set of hospital admissions linked to records of antibiotic prescriptions and susceptibilities of bacterial isolates. An appropriately trained gradient boosted decision tree algorithm, supplemented by a Shapley explanation model, predicts the likely antimicrobial drug resistance, with the odds of resistance informed by characteristics of the patient, admission data, and historical drug treatments and culture test results. Applying this AI-based system, we found that it substantially reduces the risk of mismatched treatment compared with the observed prescriptions. The Shapley values provide an intuitive association between observations/data and outcomes; the associations identified are broadly consistent with expectations based on prior knowledge from health specialists. The results, and the ability to attribute confidence and explanations, support the wider adoption of AI in healthcare.", - "laySummary": "", - "urls": "pdf:https://journals.plos.org/digitalhealth/article/file?id=10.1371/journal.pdig.0000162&type=printable; doi:https://doi.org/10.1371/journal.pdig.0000162; html:https://europepmc.org/articles/PMC9931350; pdf:https://europepmc.org/articles/PMC9931350?pdf=render" - }, { "id": "35953587", "doi": "https://doi.org/10.1038/s41588-022-01153-5", @@ -10913,6 +10896,23 @@ "laySummary": "", "urls": "pdf:https://europepmc.org/articles/pmc7613894?pdf=render; doi:https://doi.org/10.1038/s41588-022-01153-5; html:https://europepmc.org/articles/PMC7613894; pdf:https://europepmc.org/articles/PMC7613894?pdf=render" }, + { + "id": "36812617", + "doi": "https://doi.org/10.1371/journal.pdig.0000162", + "title": "Informing antimicrobial stewardship with explainable AI.", + "authorString": "Cavallaro M, Moran E, Collyer B, McCarthy ND, Green C, Keeling MJ.", + "authorAffiliations": "", + "journalTitle": "PLOS digital health", + "pubYear": "2023", + "date": "2023-01-05", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "The accuracy and flexibility of artificial intelligence (AI) systems often comes at the cost of a decreased ability to offer an intuitive explanation of their predictions. This hinders trust and discourage adoption of AI in healthcare, exacerbated by concerns over liabilities and risks to patients' health in case of misdiagnosis. Providing an explanation for a model's prediction is possible due to recent advances in the field of interpretable machine learning. We considered a data set of hospital admissions linked to records of antibiotic prescriptions and susceptibilities of bacterial isolates. An appropriately trained gradient boosted decision tree algorithm, supplemented by a Shapley explanation model, predicts the likely antimicrobial drug resistance, with the odds of resistance informed by characteristics of the patient, admission data, and historical drug treatments and culture test results. Applying this AI-based system, we found that it substantially reduces the risk of mismatched treatment compared with the observed prescriptions. The Shapley values provide an intuitive association between observations/data and outcomes; the associations identified are broadly consistent with expectations based on prior knowledge from health specialists. The results, and the ability to attribute confidence and explanations, support the wider adoption of AI in healthcare.", + "laySummary": "", + "urls": "pdf:https://journals.plos.org/digitalhealth/article/file?id=10.1371/journal.pdig.0000162&type=printable; doi:https://doi.org/10.1371/journal.pdig.0000162; html:https://europepmc.org/articles/PMC9931350; pdf:https://europepmc.org/articles/PMC9931350?pdf=render" + }, { "id": "35131989", "doi": "https://doi.org/10.1097/mcp.0000000000000863", @@ -11321,23 +11321,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.xgen.2023.100385; doi:https://doi.org/10.1016/j.xgen.2023.100385; html:https://europepmc.org/articles/PMC10589627; pdf:https://europepmc.org/articles/PMC10589627?pdf=render" }, - { - "id": "38727134", - "doi": "https://doi.org/10.1002/epi4.12957", - "title": "Hospital-acquired infections as a risk factor for post-traumatic epilepsy: A registry-based cohort study.", - "authorString": "Chen Z, Laing J, Li J, O'Brien TJ, Gabbe BJ, Semple BD.", - "authorAffiliations": "", - "journalTitle": "Epilepsia open", - "pubYear": "2024", - "date": "2024-05-10", - "isOpenAccess": "N", - "keywords": "Epilepsy; Sepsis; Bacterial; Meningitis; Seizure; Nosocomial", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Objective

Hospital-acquired infections are a common complication for patients with moderate or severe traumatic brain injury (TBI), contributing to morbidity and mortality. As infection-mediated immune responses can predispose towards epilepsy, we hypothesized that post-injury hospital-acquired infections increase the risk of post-traumatic epilepsy (PTE).

Methods

A retrospective cohort study of adults with moderate to severe TBI was conducted using data from the Victorian State Trauma Registry in Australia. Infections were identified from the International Statistical Classification of Diseases and Related Health Problems 10th Revision-Australian Modification (ICD-10-AM) codes, and diagnosis of PTE was determined by the Glasgow Outcome Scale - Extended questionnaire regarding epileptic fits at 24\u2009months follow-up.

Results

Of all TBI patients (n\u2009=\u200915\u2009152), 24% had evidence of having had any type of infection, with the most common being pneumonia, urinary tract, and respiratory infections. Of those who responded to the PTE question at 24\u2009months (n\u2009=\u20091361), 11% had developed PTE. Univariable analysis found that the incidence of PTE was higher in patients who had any type of infection compared to patients without an infection (p\u2009<\u20090.001). After adjustment for covariates associated with both development of PTE and risk of infection, multivariable analysis found a solid association between infection and PTE (adjusted RR\u2009=\u20091.59; 95% CI: 1.11-2.28; p\u2009=\u20090.011). Having any type of complicating infection acquired during admission was also associated with poor GOSE outcomes at subsequent follow-ups (adjusted OR\u2009=\u20090.20; 95% CI: 0.11-0.35, p\u2009<\u20090.001).

Significance

These findings suggest that hospital-acquired infections contribute to PTE development after TBI. Future investigation into infections as a modifiable target to reduce poor outcomes after TBI is warranted.

Plain language summary

Hospital-acquired infections are common in patients with traumatic brain injuries. A database study of adults with moderate or severe brain injuries in Australia examined whether these infections are associated with the development of epilepsy after a brain injury. 24% of patients had infections, with pneumonia and urinary tract infections being the most common. Of those surveyed 2\u2009years after the injury, 11% developed post-traumatic epilepsy. Patients with infections had a significantly higher risk of epilepsy, even when accounting for other known risk factors, and infections were also linked to poor outcomes more broadly. The study suggests that preventing hospital-acquired infections could be a crucial target for improving outcomes after traumatic brain injuries.", - "laySummary": "", - "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/epi4.12957; doi:https://doi.org/10.1002/epi4.12957" - }, { "id": "33845909", "doi": "https://doi.org/10.1186/s13326-021-00241-5", @@ -11355,6 +11338,23 @@ "laySummary": "", "urls": "pdf:https://jbiomedsem.biomedcentral.com/track/pdf/10.1186/s13326-021-00241-5; doi:https://doi.org/10.1186/s13326-021-00241-5; html:https://europepmc.org/articles/PMC8042947; pdf:https://europepmc.org/articles/PMC8042947?pdf=render" }, + { + "id": "38727134", + "doi": "https://doi.org/10.1002/epi4.12957", + "title": "Hospital-acquired infections as a risk factor for post-traumatic epilepsy: A registry-based cohort study.", + "authorString": "Chen Z, Laing J, Li J, O'Brien TJ, Gabbe BJ, Semple BD.", + "authorAffiliations": "", + "journalTitle": "Epilepsia open", + "pubYear": "2024", + "date": "2024-05-10", + "isOpenAccess": "N", + "keywords": "Epilepsy; Sepsis; Bacterial; Meningitis; Seizure; Nosocomial", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Objective

Hospital-acquired infections are a common complication for patients with moderate or severe traumatic brain injury (TBI), contributing to morbidity and mortality. As infection-mediated immune responses can predispose towards epilepsy, we hypothesized that post-injury hospital-acquired infections increase the risk of post-traumatic epilepsy (PTE).

Methods

A retrospective cohort study of adults with moderate to severe TBI was conducted using data from the Victorian State Trauma Registry in Australia. Infections were identified from the International Statistical Classification of Diseases and Related Health Problems 10th Revision-Australian Modification (ICD-10-AM) codes, and diagnosis of PTE was determined by the Glasgow Outcome Scale - Extended questionnaire regarding epileptic fits at 24\u2009months follow-up.

Results

Of all TBI patients (n\u2009=\u200915\u2009152), 24% had evidence of having had any type of infection, with the most common being pneumonia, urinary tract, and respiratory infections. Of those who responded to the PTE question at 24\u2009months (n\u2009=\u20091361), 11% had developed PTE. Univariable analysis found that the incidence of PTE was higher in patients who had any type of infection compared to patients without an infection (p\u2009<\u20090.001). After adjustment for covariates associated with both development of PTE and risk of infection, multivariable analysis found a solid association between infection and PTE (adjusted RR\u2009=\u20091.59; 95% CI: 1.11-2.28; p\u2009=\u20090.011). Having any type of complicating infection acquired during admission was also associated with poor GOSE outcomes at subsequent follow-ups (adjusted OR\u2009=\u20090.20; 95% CI: 0.11-0.35, p\u2009<\u20090.001).

Significance

These findings suggest that hospital-acquired infections contribute to PTE development after TBI. Future investigation into infections as a modifiable target to reduce poor outcomes after TBI is warranted.

Plain language summary

Hospital-acquired infections are common in patients with traumatic brain injuries. A database study of adults with moderate or severe brain injuries in Australia examined whether these infections are associated with the development of epilepsy after a brain injury. 24% of patients had infections, with pneumonia and urinary tract infections being the most common. Of those surveyed 2\u2009years after the injury, 11% developed post-traumatic epilepsy. Patients with infections had a significantly higher risk of epilepsy, even when accounting for other known risk factors, and infections were also linked to poor outcomes more broadly. The study suggests that preventing hospital-acquired infections could be a crucial target for improving outcomes after traumatic brain injuries.", + "laySummary": "", + "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/epi4.12957; doi:https://doi.org/10.1002/epi4.12957" + }, { "id": "36720882", "doi": "https://doi.org/10.1038/s41597-023-01949-y", @@ -11475,21 +11475,21 @@ "urls": "pdf:https://bmjopenrespres.bmj.com/content/bmjresp/7/1/e000770.full.pdf; doi:https://doi.org/10.1136/bmjresp-2020-000770; html:https://europepmc.org/articles/PMC7754643; pdf:https://europepmc.org/articles/PMC7754643?pdf=render" }, { - "id": "38627354", - "doi": "https://doi.org/10.1007/s15010-024-02235-8", - "title": "Sepsis and case fatality rates and associations with deprivation, ethnicity, and clinical characteristics: population-based case-control study with linked primary care and hospital data in England.", - "authorString": "van Staa TP, Pate A, Martin GP, Sharma A, Dark P, Felton T, Zhong X, Bladon S, Cunningham N, Gilham EL, Brown CS, Mirfenderesky M, Palin V, Ashiru-Oredope D.", + "id": "36929232", + "doi": "https://doi.org/10.1002/jmri.28675", + "title": "Image-Based Biological Heart Age Estimation Reveals Differential Aging Patterns Across Cardiac Chambers.", + "authorString": "Salih AM, Pujadas ER, Campello VM, McCracken C, Harvey NC, Neubauer S, Lekadir K, Nichols TE, Petersen SE, Raisi-Estabragh Z.", "authorAffiliations": "", - "journalTitle": "Infection", - "pubYear": "2024", - "date": "2024-04-16", - "isOpenAccess": "N", - "keywords": "Sepsis; RACE; Frailty; Primary Care; Deprivation", + "journalTitle": "Journal of magnetic resonance imaging : JMRI", + "pubYear": "2023", + "date": "2023-03-16", + "isOpenAccess": "Y", + "keywords": "Aging; Cardiac Imaging; Cardiac Health; Radiomics", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Purpose

Sepsis is a life-threatening organ dysfunction caused by dysregulated host response to infection. The purpose of the study was to measure the associations of specific exposures (deprivation, ethnicity, and clinical characteristics) with incident sepsis and case fatality.

Methods

Two research databases in England were used including anonymized patient-level records from primary care linked to hospital admission, death certificate, and small-area deprivation. Sepsis cases aged 65-100 years were matched to up to six controls. Predictors for sepsis (including 60 clinical conditions) were evaluated using logistic and random forest models; case fatality rates were analyzed using logistic models.

Results

108,317 community-acquired sepsis cases were analyzed. Severe frailty was strongly associated with the risk of developing sepsis (crude odds ratio [OR] 14.93; 95% confidence interval [CI] 14.37-15.52). The quintile with most deprived patients showed an increased sepsis risk (crude OR 1.48; 95% CI 1.45-1.51) compared to least deprived quintile. Strong predictors for sepsis included antibiotic exposure in prior 2 months, being house bound, having cancer, learning disability, and diabetes mellitus. Severely frail patients had a case fatality rate of 42.0% compared to 24.0% in non-frail patients (adjusted OR 1.53; 95% CI 1.41-1.65). Sepsis cases with recent prior antibiotic exposure died less frequently compared to non-users (adjusted OR 0.7; 95% CI 0.72-0.76). Case fatality strongly decreased over calendar time.

Conclusion

Given the variety of predictors and their level of associations for developing sepsis, there is a need for prediction models for risk of developing sepsis that can help to target preventative antibiotic therapy.", + "abstract": "

Background

Biological heart age estimation can provide insights into cardiac aging. However, existing studies do not consider differential aging across cardiac regions.

Purpose

To estimate biological age of the left ventricle (LV), right ventricle (RV), myocardium, left atrium, and right atrium using magnetic resonance imaging radiomics phenotypes and to investigate determinants of aging by cardiac region.

Study type

Cross-sectional.

Population

A total of 18,117 healthy UK Biobank participants including 8338 men (mean age\u00a0=\u00a064.2\u00a0\u00b1\u20097.5) and 9779 women (mean age\u00a0=\u00a063.0\u2009\u00b1\u20097.4).

Field strength/sequence

A 1.5\u00a0T/balanced steady-state free precession.

Assessment

An automated algorithm was used to segment the five cardiac regions, from which radiomic features were extracted. Bayesian ridge regression was used to estimate biological age of each cardiac region with radiomics features as predictors and chronological age as the output. The \"age gap\" was the difference between biological and chronological age. Linear regression was used to calculate associations of age gap from each cardiac region with socioeconomic, lifestyle, body composition, blood pressure and arterial stiffness, blood biomarkers, mental well-being, multiorgan health, and sex hormone exposures (n\u00a0=\u200949).

Statistical test

Multiple testing correction with false discovery method (threshold\u00a0=\u00a05%).

Results

The largest model error was with RV and the smallest with LV age (mean absolute error in men: 5.26 vs. 4.96\u2009years). There were 172 statistically significant age gap associations. Greater visceral adiposity was the strongest correlate of larger age gaps, for example, myocardial age gap in women (Beta\u00a0=\u00a00.85, P\u00a0=\u20091.69\u2009\u00d7\u200910-26 ). Poor mental health associated with large age gaps, for example, \"disinterested\" episodes and myocardial age gap in men (Beta\u00a0=\u00a00.25, P\u00a0=\u20090.001), as did a history of dental problems (eg LV in men Beta\u00a0=\u00a00.19, P\u00a0=\u20090.02). Higher bone mineral density was the strongest associate of smaller age gaps, for example, myocardial age gap in men (Beta\u00a0=\u00a0-1.52, P\u00a0=\u20097.44\u2009\u00d7\u200910-6 ).

Data conclusion

This work demonstrates image-based heart age estimation as a novel method for understanding cardiac aging.

Evidence level

1.

Technical efficacy

Stage 1.", "laySummary": "", - "urls": "pdf:https://link.springer.com/content/pdf/10.1007/s15010-024-02235-8.pdf; doi:https://doi.org/10.1007/s15010-024-02235-8" + "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/jmri.28675; doi:https://doi.org/10.1002/jmri.28675; html:https://europepmc.org/articles/PMC10947470; pdf:https://europepmc.org/articles/PMC10947470?pdf=render" }, { "id": "37550086", @@ -11509,21 +11509,21 @@ "urls": "doi:https://doi.org/10.1136/bmjment-2023-300762; html:https://europepmc.org/articles/PMC10577765; pdf:https://europepmc.org/articles/PMC10577765?pdf=render" }, { - "id": "36929232", - "doi": "https://doi.org/10.1002/jmri.28675", - "title": "Image-Based Biological Heart Age Estimation Reveals Differential Aging Patterns Across Cardiac Chambers.", - "authorString": "Salih AM, Pujadas ER, Campello VM, McCracken C, Harvey NC, Neubauer S, Lekadir K, Nichols TE, Petersen SE, Raisi-Estabragh Z.", + "id": "38627354", + "doi": "https://doi.org/10.1007/s15010-024-02235-8", + "title": "Sepsis and case fatality rates and associations with deprivation, ethnicity, and clinical characteristics: population-based case-control study with linked primary care and hospital data in England.", + "authorString": "van Staa TP, Pate A, Martin GP, Sharma A, Dark P, Felton T, Zhong X, Bladon S, Cunningham N, Gilham EL, Brown CS, Mirfenderesky M, Palin V, Ashiru-Oredope D.", "authorAffiliations": "", - "journalTitle": "Journal of magnetic resonance imaging : JMRI", - "pubYear": "2023", - "date": "2023-03-16", - "isOpenAccess": "Y", - "keywords": "Aging; Cardiac Imaging; Cardiac Health; Radiomics", + "journalTitle": "Infection", + "pubYear": "2024", + "date": "2024-04-16", + "isOpenAccess": "N", + "keywords": "Sepsis; RACE; Frailty; Primary Care; Deprivation", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Background

Biological heart age estimation can provide insights into cardiac aging. However, existing studies do not consider differential aging across cardiac regions.

Purpose

To estimate biological age of the left ventricle (LV), right ventricle (RV), myocardium, left atrium, and right atrium using magnetic resonance imaging radiomics phenotypes and to investigate determinants of aging by cardiac region.

Study type

Cross-sectional.

Population

A total of 18,117 healthy UK Biobank participants including 8338 men (mean age\u00a0=\u00a064.2\u00a0\u00b1\u20097.5) and 9779 women (mean age\u00a0=\u00a063.0\u2009\u00b1\u20097.4).

Field strength/sequence

A 1.5\u00a0T/balanced steady-state free precession.

Assessment

An automated algorithm was used to segment the five cardiac regions, from which radiomic features were extracted. Bayesian ridge regression was used to estimate biological age of each cardiac region with radiomics features as predictors and chronological age as the output. The \"age gap\" was the difference between biological and chronological age. Linear regression was used to calculate associations of age gap from each cardiac region with socioeconomic, lifestyle, body composition, blood pressure and arterial stiffness, blood biomarkers, mental well-being, multiorgan health, and sex hormone exposures (n\u00a0=\u200949).

Statistical test

Multiple testing correction with false discovery method (threshold\u00a0=\u00a05%).

Results

The largest model error was with RV and the smallest with LV age (mean absolute error in men: 5.26 vs. 4.96\u2009years). There were 172 statistically significant age gap associations. Greater visceral adiposity was the strongest correlate of larger age gaps, for example, myocardial age gap in women (Beta\u00a0=\u00a00.85, P\u00a0=\u20091.69\u2009\u00d7\u200910-26 ). Poor mental health associated with large age gaps, for example, \"disinterested\" episodes and myocardial age gap in men (Beta\u00a0=\u00a00.25, P\u00a0=\u20090.001), as did a history of dental problems (eg LV in men Beta\u00a0=\u00a00.19, P\u00a0=\u20090.02). Higher bone mineral density was the strongest associate of smaller age gaps, for example, myocardial age gap in men (Beta\u00a0=\u00a0-1.52, P\u00a0=\u20097.44\u2009\u00d7\u200910-6 ).

Data conclusion

This work demonstrates image-based heart age estimation as a novel method for understanding cardiac aging.

Evidence level

1.

Technical efficacy

Stage 1.", + "abstract": "

Purpose

Sepsis is a life-threatening organ dysfunction caused by dysregulated host response to infection. The purpose of the study was to measure the associations of specific exposures (deprivation, ethnicity, and clinical characteristics) with incident sepsis and case fatality.

Methods

Two research databases in England were used including anonymized patient-level records from primary care linked to hospital admission, death certificate, and small-area deprivation. Sepsis cases aged 65-100 years were matched to up to six controls. Predictors for sepsis (including 60 clinical conditions) were evaluated using logistic and random forest models; case fatality rates were analyzed using logistic models.

Results

108,317 community-acquired sepsis cases were analyzed. Severe frailty was strongly associated with the risk of developing sepsis (crude odds ratio [OR] 14.93; 95% confidence interval [CI] 14.37-15.52). The quintile with most deprived patients showed an increased sepsis risk (crude OR 1.48; 95% CI 1.45-1.51) compared to least deprived quintile. Strong predictors for sepsis included antibiotic exposure in prior 2 months, being house bound, having cancer, learning disability, and diabetes mellitus. Severely frail patients had a case fatality rate of 42.0% compared to 24.0% in non-frail patients (adjusted OR 1.53; 95% CI 1.41-1.65). Sepsis cases with recent prior antibiotic exposure died less frequently compared to non-users (adjusted OR 0.7; 95% CI 0.72-0.76). Case fatality strongly decreased over calendar time.

Conclusion

Given the variety of predictors and their level of associations for developing sepsis, there is a need for prediction models for risk of developing sepsis that can help to target preventative antibiotic therapy.", "laySummary": "", - "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/jmri.28675; doi:https://doi.org/10.1002/jmri.28675; html:https://europepmc.org/articles/PMC10947470; pdf:https://europepmc.org/articles/PMC10947470?pdf=render" + "urls": "pdf:https://link.springer.com/content/pdf/10.1007/s15010-024-02235-8.pdf; doi:https://doi.org/10.1007/s15010-024-02235-8" }, { "id": "37650026", @@ -11542,23 +11542,6 @@ "laySummary": "", "urls": "pdf:https://ijpds.org/article/download/1727/3395; doi:https://doi.org/10.23889/ijpds.v7i1.1727; html:https://europepmc.org/articles/PMC10464868; pdf:https://europepmc.org/articles/PMC10464868?pdf=render" }, - { - "id": "38849195", - "doi": "https://doi.org/10.1136/archdischild-2023-326756", - "title": "Utility and acceptability of remote 6-lead electrocardiographic monitoring in children with inherited cardiac conditions.", - "authorString": "Lawley CM, Luczak-Wozniak K, Chung SC, Field E, Barnes A, Starling L, Cervi E, Kaski JP.", - "authorAffiliations": "", - "journalTitle": "Archives of disease in childhood", - "pubYear": "2024", - "date": "2024-06-07", - "isOpenAccess": "N", - "keywords": "Cardiology; Paediatrics", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Objective

This pilot study sought to investigate the utility and acceptability of the KardiaMobile 6-lead ECG (KM6LECG) as a tool for remote monitoring in children with inherited cardiac conditions.

Design

A single-centre prospective cohort study. Children underwent standard clinical evaluation including a 12-lead ECG and a KM6LECG in the clinic. Participants recorded KM6LECGs monthly at home for 3 months. Families completed a questionnaire on their experience.

Setting

Great Ormond Street Hospital Centre for Inherited Cardiovascular Diseases.

Participants

64 children: 22 with hypertrophic cardiomyopathy (HCM); 22 with long QT syndrome and 20 unaffected siblings (controls).

Main outcome measures

Comparison of data extracted from the clinic 12-lead ECG and supervised KM6LECG, and the supervised and unsupervised KM6LECG recording.

Results

Of 64 children (35% female, mean age 12 years), 58 had a baseline 12-lead ECG and appropriate baseline KM6LECG. In children with HCM, abnormalities in ventricular depolarisation/repolarisation in the limb leads of the 12-lead ECG were reliably reproduced. From the whole cohort, there was a strong positive correlation between the corrected QT interval from the 12-lead ECG and baseline KM6LECG (intraclass correlation coefficient=0.839) and baseline KM6LECG with an unsupervised KM6LECG (intraclass correlation coefficient=0.736). Suspected 'lead' misplacement impacted 18% of unsupervised recordings. Overall, the acceptability of the KM6LECG to families was good.

Conclusions

The KM6LECG provides an accurate tool for assessing some ECG abnormalities associated with paediatric inherited cardiovascular disease and may provide a useful at-home adjunct to face-to-face clinical care of children requiring ECG assessment.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1136/archdischild-2023-326756" - }, { "id": "33632765", "doi": "https://doi.org/10.1136/thoraxjnl-2020-215986", @@ -11576,6 +11559,23 @@ "laySummary": "", "urls": "pdf:https://thorax.bmj.com/content/thoraxjnl/76/8/835.full.pdf; doi:https://doi.org/10.1136/thoraxjnl-2020-215986; html:https://europepmc.org/articles/PMC8311087; pdf:https://europepmc.org/articles/PMC8311087?pdf=render" }, + { + "id": "38849195", + "doi": "https://doi.org/10.1136/archdischild-2023-326756", + "title": "Utility and acceptability of remote 6-lead electrocardiographic monitoring in children with inherited cardiac conditions.", + "authorString": "Lawley CM, Luczak-Wozniak K, Chung SC, Field E, Barnes A, Starling L, Cervi E, Kaski JP.", + "authorAffiliations": "", + "journalTitle": "Archives of disease in childhood", + "pubYear": "2024", + "date": "2024-06-07", + "isOpenAccess": "N", + "keywords": "Cardiology; Paediatrics", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Objective

This pilot study sought to investigate the utility and acceptability of the KardiaMobile 6-lead ECG (KM6LECG) as a tool for remote monitoring in children with inherited cardiac conditions.

Design

A single-centre prospective cohort study. Children underwent standard clinical evaluation including a 12-lead ECG and a KM6LECG in the clinic. Participants recorded KM6LECGs monthly at home for 3 months. Families completed a questionnaire on their experience.

Setting

Great Ormond Street Hospital Centre for Inherited Cardiovascular Diseases.

Participants

64 children: 22 with hypertrophic cardiomyopathy (HCM); 22 with long QT syndrome and 20 unaffected siblings (controls).

Main outcome measures

Comparison of data extracted from the clinic 12-lead ECG and supervised KM6LECG, and the supervised and unsupervised KM6LECG recording.

Results

Of 64 children (35% female, mean age 12 years), 58 had a baseline 12-lead ECG and appropriate baseline KM6LECG. In children with HCM, abnormalities in ventricular depolarisation/repolarisation in the limb leads of the 12-lead ECG were reliably reproduced. From the whole cohort, there was a strong positive correlation between the corrected QT interval from the 12-lead ECG and baseline KM6LECG (intraclass correlation coefficient=0.839) and baseline KM6LECG with an unsupervised KM6LECG (intraclass correlation coefficient=0.736). Suspected 'lead' misplacement impacted 18% of unsupervised recordings. Overall, the acceptability of the KM6LECG to families was good.

Conclusions

The KM6LECG provides an accurate tool for assessing some ECG abnormalities associated with paediatric inherited cardiovascular disease and may provide a useful at-home adjunct to face-to-face clinical care of children requiring ECG assessment.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1136/archdischild-2023-326756" + }, { "id": "35531432", "doi": "https://doi.org/10.1016/s2666-7568(22)00093-9", @@ -11712,23 +11712,6 @@ "laySummary": "", "urls": "pdf:https://www.mdpi.com/2072-6643/11/8/1839/pdf?version=1565745447; doi:https://doi.org/10.3390/nu11081839; html:https://europepmc.org/articles/PMC6722677; pdf:https://europepmc.org/articles/PMC6722677?pdf=render" }, - { - "id": "38102763", - "doi": "https://doi.org/10.1177/15353702231214253", - "title": "Explainable hierarchical clustering for patient subtyping and risk prediction.", - "authorString": "Werner E, Clark JN, Hepburn A, Bhamber RS, Ambler M, Bourdeaux CP, McWilliams CJ, Santos-Rodriguez R.", - "authorAffiliations": "", - "journalTitle": "Experimental biology and medicine (Maywood, N.J.)", - "pubYear": "2023", - "date": "2023-12-15", - "isOpenAccess": "Y", - "keywords": "Clinical evaluation; hierarchical clustering; Mortality Prediction; Early Warning Score; Explainability; Patient Subtypes", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "We present a pipeline in which machine learning techniques are used to automatically identify and evaluate subtypes of hospital patients admitted between 2017 and 2021 in a large UK teaching hospital. Patient clusters are determined using routinely collected hospital data, such as those used in the UK's National Early Warning Score 2 (NEWS2). An iterative, hierarchical clustering process was used to identify the minimum set of relevant features for cluster separation. With the use of state-of-the-art explainability techniques, the identified subtypes are interpreted and assigned clinical meaning, illustrating their robustness. In parallel, clinicians assessed intracluster similarities and intercluster differences of the identified patient subtypes within the context of their clinical knowledge. For each cluster, outcome prediction models were trained and their forecasting ability was illustrated against the NEWS2 of the unclustered patient cohort. These preliminary results suggest that subtype models can outperform the established NEWS2 method, providing improved prediction of patient deterioration. By considering both the computational outputs and clinician-based explanations in patient subtyping, we aim to highlight the mutual benefit of combining machine learning techniques with clinical expertise.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1177/15353702231214253; html:https://europepmc.org/articles/PMC10854470; pdf:https://europepmc.org/articles/PMC10854470?pdf=render" - }, { "id": "36329425", "doi": "https://doi.org/10.1186/s12890-022-02189-3", @@ -11746,6 +11729,23 @@ "laySummary": "", "urls": "pdf:https://bmcpulmmed.biomedcentral.com/counter/pdf/10.1186/s12890-022-02189-3; doi:https://doi.org/10.1186/s12890-022-02189-3; html:https://europepmc.org/articles/PMC9635147; pdf:https://europepmc.org/articles/PMC9635147?pdf=render" }, + { + "id": "38102763", + "doi": "https://doi.org/10.1177/15353702231214253", + "title": "Explainable hierarchical clustering for patient subtyping and risk prediction.", + "authorString": "Werner E, Clark JN, Hepburn A, Bhamber RS, Ambler M, Bourdeaux CP, McWilliams CJ, Santos-Rodriguez R.", + "authorAffiliations": "", + "journalTitle": "Experimental biology and medicine (Maywood, N.J.)", + "pubYear": "2023", + "date": "2023-12-15", + "isOpenAccess": "Y", + "keywords": "Clinical evaluation; hierarchical clustering; Mortality Prediction; Early Warning Score; Explainability; Patient Subtypes", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "We present a pipeline in which machine learning techniques are used to automatically identify and evaluate subtypes of hospital patients admitted between 2017 and 2021 in a large UK teaching hospital. Patient clusters are determined using routinely collected hospital data, such as those used in the UK's National Early Warning Score 2 (NEWS2). An iterative, hierarchical clustering process was used to identify the minimum set of relevant features for cluster separation. With the use of state-of-the-art explainability techniques, the identified subtypes are interpreted and assigned clinical meaning, illustrating their robustness. In parallel, clinicians assessed intracluster similarities and intercluster differences of the identified patient subtypes within the context of their clinical knowledge. For each cluster, outcome prediction models were trained and their forecasting ability was illustrated against the NEWS2 of the unclustered patient cohort. These preliminary results suggest that subtype models can outperform the established NEWS2 method, providing improved prediction of patient deterioration. By considering both the computational outputs and clinician-based explanations in patient subtyping, we aim to highlight the mutual benefit of combining machine learning techniques with clinical expertise.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1177/15353702231214253; html:https://europepmc.org/articles/PMC10854470; pdf:https://europepmc.org/articles/PMC10854470?pdf=render" + }, { "id": "38772405", "doi": "https://doi.org/10.1016/s0140-6736(24)00537-3", @@ -12103,23 +12103,6 @@ "laySummary": "", "urls": "pdf:https://www.nature.com/articles/s43856-022-00146-z.pdf; doi:https://doi.org/10.1038/s43856-022-00146-z; html:https://europepmc.org/articles/PMC9259560; pdf:https://europepmc.org/articles/PMC9259560?pdf=render" }, - { - "id": "33933206", - "doi": "https://doi.org/10.1016/s0140-6736(21)00676-0", - "title": "Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial.", - "authorString": "RECOVERY Collaborative Group.", - "authorAffiliations": "", - "journalTitle": "Lancet (London, England)", - "pubYear": "2021", - "date": "2021-05-01", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

In this study, we aimed to evaluate the effects of tocilizumab in adult patients admitted to hospital with COVID-19 with both hypoxia and systemic inflammation.

Methods

This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. Those trial participants with hypoxia (oxygen saturation <92% on air or requiring oxygen therapy) and evidence of systemic inflammation (C-reactive protein \u226575 mg/L) were eligible for random assignment in a 1:1 ratio to usual standard of care alone versus usual standard of care plus tocilizumab at a dose of 400 mg-800 mg (depending on weight) given intravenously. A second dose could be given 12-24 h later if the patient's condition had not improved. The primary outcome was 28-day mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936).

Findings

Between April 23, 2020, and Jan 24, 2021, 4116 adults of 21\u2008550 patients enrolled into the RECOVERY trial were included in the assessment of tocilizumab, including 3385 (82%) patients receiving systemic corticosteroids. Overall, 621 (31%) of the 2022 patients allocated tocilizumab and 729 (35%) of the 2094 patients allocated to usual care died within 28 days (rate ratio 0\u00b785; 95% CI 0\u00b776-0\u00b794; p=0\u00b70028). Consistent results were seen in all prespecified subgroups of patients, including those receiving systemic corticosteroids. Patients allocated to tocilizumab were more likely to be discharged from hospital within 28 days (57% vs 50%; rate ratio 1\u00b722; 1\u00b712-1\u00b733; p<0\u00b70001). Among those not receiving invasive mechanical ventilation at baseline, patients allocated tocilizumab were less likely to reach the composite endpoint of invasive mechanical ventilation or death (35% vs 42%; risk ratio 0\u00b784; 95% CI 0\u00b777-0\u00b792; p<0\u00b70001).

Interpretation

In hospitalised COVID-19 patients with hypoxia and systemic inflammation, tocilizumab improved survival and other clinical outcomes. These benefits were seen regardless of the amount of respiratory support and were additional to the benefits of systemic corticosteroids.

Funding

UK Research and Innovation (Medical Research Council) and National Institute of Health Research.", - "laySummary": "", - "urls": "pdf:https://aura.abdn.ac.uk/bitstream/2164/16630/1/Recovery_etal_TL_Tocilizumab_In_Patients_VoR.pdf; doi:https://doi.org/10.1016/S0140-6736(21)00676-0; html:https://europepmc.org/articles/PMC8084355" - }, { "id": "31256764", "doi": "https://doi.org/10.1192/bjp.2019.153", @@ -12137,6 +12120,23 @@ "laySummary": "", "urls": "pdf:https://www.cambridge.org/core/services/aop-cambridge-core/content/view/A00E32E32B0FB324075CF2CF0973687F/S0007125019001533a.pdf/div-class-title-shining-the-light-on-eating-disorders-incidence-prognosis-and-profiling-of-patients-in-primary-and-secondary-care-national-data-linkage-study-div.pdf; doi:https://doi.org/10.1192/bjp.2019.153; html:https://europepmc.org/articles/PMC7557634; pdf:https://europepmc.org/articles/PMC7557634?pdf=render" }, + { + "id": "33933206", + "doi": "https://doi.org/10.1016/s0140-6736(21)00676-0", + "title": "Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial.", + "authorString": "RECOVERY Collaborative Group.", + "authorAffiliations": "", + "journalTitle": "Lancet (London, England)", + "pubYear": "2021", + "date": "2021-05-01", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

In this study, we aimed to evaluate the effects of tocilizumab in adult patients admitted to hospital with COVID-19 with both hypoxia and systemic inflammation.

Methods

This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. Those trial participants with hypoxia (oxygen saturation <92% on air or requiring oxygen therapy) and evidence of systemic inflammation (C-reactive protein \u226575 mg/L) were eligible for random assignment in a 1:1 ratio to usual standard of care alone versus usual standard of care plus tocilizumab at a dose of 400 mg-800 mg (depending on weight) given intravenously. A second dose could be given 12-24 h later if the patient's condition had not improved. The primary outcome was 28-day mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936).

Findings

Between April 23, 2020, and Jan 24, 2021, 4116 adults of 21\u2008550 patients enrolled into the RECOVERY trial were included in the assessment of tocilizumab, including 3385 (82%) patients receiving systemic corticosteroids. Overall, 621 (31%) of the 2022 patients allocated tocilizumab and 729 (35%) of the 2094 patients allocated to usual care died within 28 days (rate ratio 0\u00b785; 95% CI 0\u00b776-0\u00b794; p=0\u00b70028). Consistent results were seen in all prespecified subgroups of patients, including those receiving systemic corticosteroids. Patients allocated to tocilizumab were more likely to be discharged from hospital within 28 days (57% vs 50%; rate ratio 1\u00b722; 1\u00b712-1\u00b733; p<0\u00b70001). Among those not receiving invasive mechanical ventilation at baseline, patients allocated tocilizumab were less likely to reach the composite endpoint of invasive mechanical ventilation or death (35% vs 42%; risk ratio 0\u00b784; 95% CI 0\u00b777-0\u00b792; p<0\u00b70001).

Interpretation

In hospitalised COVID-19 patients with hypoxia and systemic inflammation, tocilizumab improved survival and other clinical outcomes. These benefits were seen regardless of the amount of respiratory support and were additional to the benefits of systemic corticosteroids.

Funding

UK Research and Innovation (Medical Research Council) and National Institute of Health Research.", + "laySummary": "", + "urls": "pdf:https://aura.abdn.ac.uk/bitstream/2164/16630/1/Recovery_etal_TL_Tocilizumab_In_Patients_VoR.pdf; doi:https://doi.org/10.1016/S0140-6736(21)00676-0; html:https://europepmc.org/articles/PMC8084355" + }, { "id": "35497059", "doi": "https://doi.org/10.1016/j.eclinm.2022.101392", @@ -12154,23 +12154,6 @@ "laySummary": "", "urls": "pdf:http://www.thelancet.com/article/S2589537022001225/pdf; doi:https://doi.org/10.1016/j.eclinm.2022.101392; html:https://europepmc.org/articles/PMC9046106; pdf:https://europepmc.org/articles/PMC9046106?pdf=render" }, - { - "id": "37649988", - "doi": "https://doi.org/10.1093/jamiaopen/ooad078", - "title": "Determining prescriptions in electronic healthcare record data: methods for development of standardized, reproducible drug codelists.", - "authorString": "Graul EL, Stone PW, Massen GM, Hatam S, Adamson A, Denaxas S, Peters NS, Quint JK.", - "authorAffiliations": "", - "journalTitle": "JAMIA open", - "pubYear": "2023", - "date": "2023-08-29", - "isOpenAccess": "Y", - "keywords": "epidemiology; Electronic Medical Records; Misclassification Bias; Value Sets; Health Data Science; Code Sets", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Objective

To develop a standardizable, reproducible method for creating drug codelists that incorporates clinical expertise and is adaptable to other studies and databases.

Materials and methods

We developed methods to generate drug codelists and tested this using the Clinical Practice Research Datalink (CPRD) Aurum database, accounting for missing data in the database. We generated codelists for: (1) cardiovascular disease and (2) inhaled Chronic Obstructive Pulmonary Disease (COPD) therapies, applying them to a sample cohort of 335\u00a0931 COPD patients. We compared searching all drug dictionary variables (A) against searching only (B) chemical or (C) ontological variables.

Results

In Search A, we identified 165\u00a0150 patients prescribed cardiovascular drugs (49.2% of cohort), and 317\u00a0963 prescribed COPD inhalers (94.7% of cohort). Evaluating output per search strategy, Search C missed numerous prescriptions, including vasodilator anti-hypertensives (A and B:19\u00a0696 prescriptions; C:1145) and SAMA inhalers (A and B:35\u00a0310; C:564).

Discussion

We recommend the full search (A) for comprehensiveness. There are special considerations when generating adaptable and generalizable drug codelists, including fluctuating status, cohort-specific drug indications, underlying hierarchical ontology, and statistical analyses.

Conclusions

Methods must have end-to-end clinical input, and be standardizable, reproducible, and understandable to all researchers across data contexts.", - "laySummary": "", - "urls": "pdf:https://academic.oup.com/jamiaopen/article-pdf/6/3/ooad078/51279371/ooad078.pdf; doi:https://doi.org/10.1093/jamiaopen/ooad078; html:https://europepmc.org/articles/PMC10463548; pdf:https://europepmc.org/articles/PMC10463548?pdf=render" - }, { "id": "33545096", "doi": "https://doi.org/10.1016/s0140-6736(21)00149-5", @@ -12188,6 +12171,23 @@ "laySummary": "", "urls": "pdf:http://www.thelancet.com/article/S0140673621001495/pdf; doi:https://doi.org/10.1016/S0140-6736(21)00149-5; html:https://europepmc.org/articles/PMC7884931; pdf:https://europepmc.org/articles/PMC7884931?pdf=render" }, + { + "id": "37649988", + "doi": "https://doi.org/10.1093/jamiaopen/ooad078", + "title": "Determining prescriptions in electronic healthcare record data: methods for development of standardized, reproducible drug codelists.", + "authorString": "Graul EL, Stone PW, Massen GM, Hatam S, Adamson A, Denaxas S, Peters NS, Quint JK.", + "authorAffiliations": "", + "journalTitle": "JAMIA open", + "pubYear": "2023", + "date": "2023-08-29", + "isOpenAccess": "Y", + "keywords": "epidemiology; Electronic Medical Records; Misclassification Bias; Value Sets; Health Data Science; Code Sets", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Objective

To develop a standardizable, reproducible method for creating drug codelists that incorporates clinical expertise and is adaptable to other studies and databases.

Materials and methods

We developed methods to generate drug codelists and tested this using the Clinical Practice Research Datalink (CPRD) Aurum database, accounting for missing data in the database. We generated codelists for: (1) cardiovascular disease and (2) inhaled Chronic Obstructive Pulmonary Disease (COPD) therapies, applying them to a sample cohort of 335\u00a0931 COPD patients. We compared searching all drug dictionary variables (A) against searching only (B) chemical or (C) ontological variables.

Results

In Search A, we identified 165\u00a0150 patients prescribed cardiovascular drugs (49.2% of cohort), and 317\u00a0963 prescribed COPD inhalers (94.7% of cohort). Evaluating output per search strategy, Search C missed numerous prescriptions, including vasodilator anti-hypertensives (A and B:19\u00a0696 prescriptions; C:1145) and SAMA inhalers (A and B:35\u00a0310; C:564).

Discussion

We recommend the full search (A) for comprehensiveness. There are special considerations when generating adaptable and generalizable drug codelists, including fluctuating status, cohort-specific drug indications, underlying hierarchical ontology, and statistical analyses.

Conclusions

Methods must have end-to-end clinical input, and be standardizable, reproducible, and understandable to all researchers across data contexts.", + "laySummary": "", + "urls": "pdf:https://academic.oup.com/jamiaopen/article-pdf/6/3/ooad078/51279371/ooad078.pdf; doi:https://doi.org/10.1093/jamiaopen/ooad078; html:https://europepmc.org/articles/PMC10463548; pdf:https://europepmc.org/articles/PMC10463548?pdf=render" + }, { "id": "33577558", "doi": "https://doi.org/10.1371/journal.pmed.1003497", @@ -12545,23 +12545,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.lanepe.2022.100475; doi:https://doi.org/10.1016/j.lanepe.2022.100475; html:https://europepmc.org/articles/PMC9340533; pdf:https://europepmc.org/articles/PMC9340533?pdf=render" }, - { - "id": "38198154", - "doi": "https://doi.org/10.1093/bjs/znad347", - "title": "Natural language processing to automate a web-based model of care and modernize skin cancer multidisciplinary team meetings.", - "authorString": "Ali SR, Dobbs TD, Tarafdar A, Strafford H, Fonferko-Shadrach B, Lacey AS, Pickrell WO, Hutchings HA, Whitaker IS.", - "authorAffiliations": "", - "journalTitle": "The British journal of surgery", - "pubYear": "2024", - "date": "2024-01-01", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Cancer multidisciplinary team (MDT) meetings are under intense pressure to reform given the rapidly rising incidence of cancer and national mandates for protocolized streaming of cases. The aim of this study was to validate a natural language processing (NLP)-based web platform to automate evidence-based MDT decisions for skin cancer with basal cell carcinoma as a use case.

Methods

A novel and validated NLP information extraction model was used to extract perioperative tumour and surgical factors from histopathology reports. A web application with a bespoke application programming interface used data from this model to provide an automated clinical decision support system, mapped to national guidelines and generating a patient letter to communicate ongoing management. Performance was assessed against retrospectively derived recommendations by two independent and blinded expert clinicians.

Results

There were 893 patients (1045 lesions) used to internally validate the model. High accuracy was observed when compared against human predictions, with an overall value of 0.92. Across all classifiers the virtual skin MDT was highly specific (0.96), while sensitivity was lower (0.72).

Conclusion

This study demonstrates the feasibility of a fully automated, virtual, web-based service model to host the skin MDT with good system performance. This platform could be used to support clinical decision-making during MDTs as 'human in the loop' approach to aid protocolized streaming. Future prospective studies are needed to validate the model in tumour types where guidelines are more complex.", - "laySummary": "", - "urls": "pdf:https://academic.oup.com/bjs/article-pdf/111/1/znad347/55374438/znad347.pdf; doi:https://doi.org/10.1093/bjs/znad347; html:https://europepmc.org/articles/PMC10782209; pdf:https://europepmc.org/articles/PMC10782209?pdf=render" - }, { "id": "32424068", "doi": "https://doi.org/10.1101/gr.250704.119", @@ -12579,6 +12562,23 @@ "laySummary": "", "urls": "pdf:https://genome.cshlp.org/content/30/5/790.full.pdf; doi:https://doi.org/10.1101/gr.250704.119; html:https://europepmc.org/articles/PMC7263193; pdf:https://europepmc.org/articles/PMC7263193?pdf=render" }, + { + "id": "38198154", + "doi": "https://doi.org/10.1093/bjs/znad347", + "title": "Natural language processing to automate a web-based model of care and modernize skin cancer multidisciplinary team meetings.", + "authorString": "Ali SR, Dobbs TD, Tarafdar A, Strafford H, Fonferko-Shadrach B, Lacey AS, Pickrell WO, Hutchings HA, Whitaker IS.", + "authorAffiliations": "", + "journalTitle": "The British journal of surgery", + "pubYear": "2024", + "date": "2024-01-01", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Cancer multidisciplinary team (MDT) meetings are under intense pressure to reform given the rapidly rising incidence of cancer and national mandates for protocolized streaming of cases. The aim of this study was to validate a natural language processing (NLP)-based web platform to automate evidence-based MDT decisions for skin cancer with basal cell carcinoma as a use case.

Methods

A novel and validated NLP information extraction model was used to extract perioperative tumour and surgical factors from histopathology reports. A web application with a bespoke application programming interface used data from this model to provide an automated clinical decision support system, mapped to national guidelines and generating a patient letter to communicate ongoing management. Performance was assessed against retrospectively derived recommendations by two independent and blinded expert clinicians.

Results

There were 893 patients (1045 lesions) used to internally validate the model. High accuracy was observed when compared against human predictions, with an overall value of 0.92. Across all classifiers the virtual skin MDT was highly specific (0.96), while sensitivity was lower (0.72).

Conclusion

This study demonstrates the feasibility of a fully automated, virtual, web-based service model to host the skin MDT with good system performance. This platform could be used to support clinical decision-making during MDTs as 'human in the loop' approach to aid protocolized streaming. Future prospective studies are needed to validate the model in tumour types where guidelines are more complex.", + "laySummary": "", + "urls": "pdf:https://academic.oup.com/bjs/article-pdf/111/1/znad347/55374438/znad347.pdf; doi:https://doi.org/10.1093/bjs/znad347; html:https://europepmc.org/articles/PMC10782209; pdf:https://europepmc.org/articles/PMC10782209?pdf=render" + }, { "id": "35256633", "doi": "https://doi.org/10.1038/s41598-022-07291-4", @@ -12647,23 +12647,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1177/01410768211032850; doi:https://doi.org/10.1177/01410768211032850; html:https://europepmc.org/articles/PMC8450986; pdf:https://europepmc.org/articles/PMC8450986?pdf=render" }, - { - "id": "36350656", - "doi": "https://doi.org/10.1093/nar/gkac1010", - "title": "The NHGRI-EBI GWAS Catalog: knowledgebase and deposition resource.", - "authorString": "Sollis E, Mosaku A, Abid A, Buniello A, Cerezo M, Gil L, Groza T, G\u00fcne\u015f O, Hall P, Hayhurst J, Ibrahim A, Ji Y, John S, Lewis E, MacArthur JAL, McMahon A, Osumi-Sutherland D, Panoutsopoulou K, Pendlington Z, Ramachandran S, Stefancsik R, Stewart J, Whetzel P, Wilson R, Hindorff L, Cunningham F, Lambert SA, Inouye M, Parkinson H, Harris LW.", - "authorAffiliations": "", - "journalTitle": "Nucleic acids research", - "pubYear": "2023", - "date": "2023-01-01", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "The NHGRI-EBI GWAS Catalog (www.ebi.ac.uk/gwas) is a FAIR knowledgebase providing detailed, structured, standardised and interoperable genome-wide association study (GWAS) data to\u00a0>200 000 users per year from academic research, healthcare and industry. The Catalog contains variant-trait associations and supporting metadata for\u00a0>45 000 published GWAS across\u00a0>5000 human traits, and\u00a0>40 000 full P-value summary statistics datasets. Content is curated from publications or acquired via author submission of prepublication summary statistics through a new submission portal and validation tool. GWAS data volume has vastly increased in recent years. We have updated our software to meet this scaling challenge and to enable rapid release of submitted summary statistics. The scope of the repository has expanded to include additional data types of high interest to the community, including sequencing-based GWAS, gene-based analyses and copy number variation analyses. Community outreach has increased the number of shared datasets from under-represented traits, e.g. cancer, and we continue to contribute to awareness of the lack of population diversity in GWAS. Interoperability of the Catalog has been enhanced through links to other resources including the Polygenic Score Catalog and the International Mouse Phenotyping Consortium, refinements to GWAS trait annotation, and the development of a standard format for GWAS data.", - "laySummary": "", - "urls": "pdf:https://academic.oup.com/nar/article-pdf/51/D1/D977/48440802/gkac1010.pdf; doi:https://doi.org/10.1093/nar/gkac1010; html:https://europepmc.org/articles/PMC9825413; pdf:https://europepmc.org/articles/PMC9825413?pdf=render" - }, { "id": "31315158", "doi": "https://doi.org/10.1002/cnm.3235", @@ -12682,21 +12665,21 @@ "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/cnm.3235; doi:https://doi.org/10.1002/cnm.3235; html:https://europepmc.org/articles/PMC6851543; pdf:https://europepmc.org/articles/PMC6851543?pdf=render" }, { - "id": "34148732", - "doi": "https://doi.org/10.1016/j.bja.2021.05.001", - "title": "Surgical activity in England and Wales during the COVID-19 pandemic: a nationwide observational cohort study.", - "authorString": "Dobbs TD, Gibson JAG, Fowler AJ, Abbott TE, Shahid T, Torabi F, Griffiths R, Lyons RA, Pearse RM, Whitaker IS.", + "id": "36350656", + "doi": "https://doi.org/10.1093/nar/gkac1010", + "title": "The NHGRI-EBI GWAS Catalog: knowledgebase and deposition resource.", + "authorString": "Sollis E, Mosaku A, Abid A, Buniello A, Cerezo M, Gil L, Groza T, G\u00fcne\u015f O, Hall P, Hayhurst J, Ibrahim A, Ji Y, John S, Lewis E, MacArthur JAL, McMahon A, Osumi-Sutherland D, Panoutsopoulou K, Pendlington Z, Ramachandran S, Stefancsik R, Stewart J, Whetzel P, Wilson R, Hindorff L, Cunningham F, Lambert SA, Inouye M, Parkinson H, Harris LW.", "authorAffiliations": "", - "journalTitle": "British journal of anaesthesia", - "pubYear": "2021", - "date": "2021-06-18", + "journalTitle": "Nucleic acids research", + "pubYear": "2023", + "date": "2023-01-01", "isOpenAccess": "Y", - "keywords": "Surgery; Anaesthesia; Public Policy; Waiting List; Surgical Activity; Covid-19", + "keywords": "", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Background

A significant proportion of healthcare resource has been diverted to the care of those with COVID-19. This study reports the volume of surgical activity and the number of cancelled surgical procedures during the COVID-19 pandemic.

Methods

We used hospital episode statistics for all adult patients undergoing surgery between January 1, 2020 and December 31, 2020 in England and Wales. We identified surgical procedures using a previously published list of procedure codes. Procedures were stratified by urgency of surgery as defined by NHS England. We calculated the deficit of surgical activity by comparing the expected number of procedures from 2016 to 2019 with the actual number of procedures in 2020. Using a linear regression model, we calculated the expected cumulative number of cancelled procedures by December 31, 2021.

Results

The total number of surgical procedures carried out in England and Wales in 2020 was 3 102 674 compared with the predicted number of 4 671 338 (95% confidence interval [CI]: 4 218 740-5 123 932). This represents a 33.6% reduction in the national volume of surgical activity. There were 763 730 emergency surgical procedures (13.4% reduction) compared with 2 338 944 elective surgical procedures (38.6% reduction). The cumulative number of cancelled or postponed procedures was 1 568 664 (95% CI: 1 116 066-2 021 258). We estimate that this will increase to 2 358 420 (95% CI: 1 667 587-3 100 808) up to December 31, 2021.

Conclusions

The volume of surgical activity in England and Wales was reduced by 33.6% in 2020, resulting in more than 1.5 million cancelled operations. This deficit will continue to grow in 2021.", + "abstract": "The NHGRI-EBI GWAS Catalog (www.ebi.ac.uk/gwas) is a FAIR knowledgebase providing detailed, structured, standardised and interoperable genome-wide association study (GWAS) data to\u00a0>200 000 users per year from academic research, healthcare and industry. The Catalog contains variant-trait associations and supporting metadata for\u00a0>45 000 published GWAS across\u00a0>5000 human traits, and\u00a0>40 000 full P-value summary statistics datasets. Content is curated from publications or acquired via author submission of prepublication summary statistics through a new submission portal and validation tool. GWAS data volume has vastly increased in recent years. We have updated our software to meet this scaling challenge and to enable rapid release of submitted summary statistics. The scope of the repository has expanded to include additional data types of high interest to the community, including sequencing-based GWAS, gene-based analyses and copy number variation analyses. Community outreach has increased the number of shared datasets from under-represented traits, e.g. cancer, and we continue to contribute to awareness of the lack of population diversity in GWAS. Interoperability of the Catalog has been enhanced through links to other resources including the Polygenic Score Catalog and the International Mouse Phenotyping Consortium, refinements to GWAS trait annotation, and the development of a standard format for GWAS data.", "laySummary": "", - "urls": "pdf:http://www.bjanaesthesia.org/article/S0007091221002737/pdf; doi:https://doi.org/10.1016/j.bja.2021.05.001; html:https://europepmc.org/articles/PMC8277602; pdf:https://europepmc.org/articles/PMC8277602?pdf=render" + "urls": "pdf:https://academic.oup.com/nar/article-pdf/51/D1/D977/48440802/gkac1010.pdf; doi:https://doi.org/10.1093/nar/gkac1010; html:https://europepmc.org/articles/PMC9825413; pdf:https://europepmc.org/articles/PMC9825413?pdf=render" }, { "id": "30950797", @@ -12715,6 +12698,23 @@ "laySummary": "", "urls": "pdf:https://www.jmir.org/2019/4/e12286/PDF; doi:https://doi.org/10.2196/12286; html:https://europepmc.org/articles/PMC6473205" }, + { + "id": "34148732", + "doi": "https://doi.org/10.1016/j.bja.2021.05.001", + "title": "Surgical activity in England and Wales during the COVID-19 pandemic: a nationwide observational cohort study.", + "authorString": "Dobbs TD, Gibson JAG, Fowler AJ, Abbott TE, Shahid T, Torabi F, Griffiths R, Lyons RA, Pearse RM, Whitaker IS.", + "authorAffiliations": "", + "journalTitle": "British journal of anaesthesia", + "pubYear": "2021", + "date": "2021-06-18", + "isOpenAccess": "Y", + "keywords": "Surgery; Anaesthesia; Public Policy; Waiting List; Surgical Activity; Covid-19", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

A significant proportion of healthcare resource has been diverted to the care of those with COVID-19. This study reports the volume of surgical activity and the number of cancelled surgical procedures during the COVID-19 pandemic.

Methods

We used hospital episode statistics for all adult patients undergoing surgery between January 1, 2020 and December 31, 2020 in England and Wales. We identified surgical procedures using a previously published list of procedure codes. Procedures were stratified by urgency of surgery as defined by NHS England. We calculated the deficit of surgical activity by comparing the expected number of procedures from 2016 to 2019 with the actual number of procedures in 2020. Using a linear regression model, we calculated the expected cumulative number of cancelled procedures by December 31, 2021.

Results

The total number of surgical procedures carried out in England and Wales in 2020 was 3 102 674 compared with the predicted number of 4 671 338 (95% confidence interval [CI]: 4 218 740-5 123 932). This represents a 33.6% reduction in the national volume of surgical activity. There were 763 730 emergency surgical procedures (13.4% reduction) compared with 2 338 944 elective surgical procedures (38.6% reduction). The cumulative number of cancelled or postponed procedures was 1 568 664 (95% CI: 1 116 066-2 021 258). We estimate that this will increase to 2 358 420 (95% CI: 1 667 587-3 100 808) up to December 31, 2021.

Conclusions

The volume of surgical activity in England and Wales was reduced by 33.6% in 2020, resulting in more than 1.5 million cancelled operations. This deficit will continue to grow in 2021.", + "laySummary": "", + "urls": "pdf:http://www.bjanaesthesia.org/article/S0007091221002737/pdf; doi:https://doi.org/10.1016/j.bja.2021.05.001; html:https://europepmc.org/articles/PMC8277602; pdf:https://europepmc.org/articles/PMC8277602?pdf=render" + }, { "id": "33212507", "doi": "https://doi.org/10.1093/molbev/msaa279", @@ -12749,23 +12749,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.jbi.2021.103916; doi:https://doi.org/10.1016/j.jbi.2021.103916; html:https://europepmc.org/articles/PMC8524321" }, - { - "id": "38837310", - "doi": "https://doi.org/10.1002/ejhf.3306", - "title": "A nationwide, population-based study on specialized care for acute heart failure throughout the COVID-19 pandemic.", - "authorString": "Cannata A, Mizani MA, Bromage DI, Piper SE, Hardman SMC, Sudlow C, de Belder M, Deanfield J, Gardner RS, Clark AL, Cleland JGF, McDonagh TA, \u2009on behalf of the CVD\u2010COVID\u2010UK/COVID\u2010IMPACT Consortium.", - "authorAffiliations": "", - "journalTitle": "European journal of heart failure", - "pubYear": "2024", - "date": "2024-06-04", - "isOpenAccess": "N", - "keywords": "Heart Failure; Specialist Care; Covid\u201019; National Heart Failure Audit", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Aims

The COVID-19 pandemic disrupted the delivery of care for patients with heart failure (HF), leading to fewer HF hospitalizations and increased mortality. However, nationwide data on quality of care and long-term outcomes across the pandemic are scarce.

Methods and results

We used data from the National Heart Failure Audit (NHFA) linked to national records for hospitalization and deaths. We compared pre-COVID (2018-2019), COVID (2020), and late/post-COVID (2021-2022) periods. Data for 227\u2009250 patients admitted to hospital with HF were analysed and grouped according to the admission year and the presence of HF with (HFrEF) or without reduced ejection fraction (non-HFrEF). The median age at admission was 81\u2009years (interquartile range 72-88), 55% were men (n\u2009=\u2009125\u2009975), 87% were of white ethnicity (n\u2009=\u2009102\u2009805), and 51% had HFrEF (n\u2009=\u2009116\u2009990). In-hospital management and specialized cardiology care were maintained throughout the pandemic with an increasing percentage of patients discharged on disease-modifying medications over time (p\u2009<\u20090.001). Long-term outcomes improved over time (hazard ratio [HR] 0.92, 95% confidence interval [CI] 0.90-0.95, p\u2009<\u20090.001), mainly driven by a reduction in cardiovascular death. Receiving specialized cardiology care was associated with better long-term outcomes both for those who had HFrEF (HR 0.79, 95% CI 0.77-0.82, p\u2009<\u20090.001) and for those who had non-HFrEF (HR 0.87, 95% CI 0.85-0.90, p\u2009<\u20090.001).

Conclusions

Despite the disruption of healthcare systems, the clinical characteristics of patients admitted with HF were similar and the overall standard of care was maintained throughout the pandemic. Long-term survival of patients hospitalized with HF continued to improve after COVID-19, especially for HFrEF.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1002/ejhf.3306; doi:https://doi.org/10.1002/ejhf.3306" - }, { "id": "37272361", "doi": "https://doi.org/10.2340/actadv.v103.5268", @@ -12783,6 +12766,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.2340/actadv.v103.5268; html:https://europepmc.org/articles/PMC10259463; pdf:https://europepmc.org/articles/PMC10259463?pdf=render" }, + { + "id": "38837310", + "doi": "https://doi.org/10.1002/ejhf.3306", + "title": "A nationwide, population-based study on specialized care for acute heart failure throughout the COVID-19 pandemic.", + "authorString": "Cannata A, Mizani MA, Bromage DI, Piper SE, Hardman SMC, Sudlow C, de Belder M, Deanfield J, Gardner RS, Clark AL, Cleland JGF, McDonagh TA, \u2009on behalf of the CVD\u2010COVID\u2010UK/COVID\u2010IMPACT Consortium.", + "authorAffiliations": "", + "journalTitle": "European journal of heart failure", + "pubYear": "2024", + "date": "2024-06-04", + "isOpenAccess": "N", + "keywords": "Heart Failure; Specialist Care; Covid\u201019; National Heart Failure Audit", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Aims

The COVID-19 pandemic disrupted the delivery of care for patients with heart failure (HF), leading to fewer HF hospitalizations and increased mortality. However, nationwide data on quality of care and long-term outcomes across the pandemic are scarce.

Methods and results

We used data from the National Heart Failure Audit (NHFA) linked to national records for hospitalization and deaths. We compared pre-COVID (2018-2019), COVID (2020), and late/post-COVID (2021-2022) periods. Data for 227\u2009250 patients admitted to hospital with HF were analysed and grouped according to the admission year and the presence of HF with (HFrEF) or without reduced ejection fraction (non-HFrEF). The median age at admission was 81\u2009years (interquartile range 72-88), 55% were men (n\u2009=\u2009125\u2009975), 87% were of white ethnicity (n\u2009=\u2009102\u2009805), and 51% had HFrEF (n\u2009=\u2009116\u2009990). In-hospital management and specialized cardiology care were maintained throughout the pandemic with an increasing percentage of patients discharged on disease-modifying medications over time (p\u2009<\u20090.001). Long-term outcomes improved over time (hazard ratio [HR] 0.92, 95% confidence interval [CI] 0.90-0.95, p\u2009<\u20090.001), mainly driven by a reduction in cardiovascular death. Receiving specialized cardiology care was associated with better long-term outcomes both for those who had HFrEF (HR 0.79, 95% CI 0.77-0.82, p\u2009<\u20090.001) and for those who had non-HFrEF (HR 0.87, 95% CI 0.85-0.90, p\u2009<\u20090.001).

Conclusions

Despite the disruption of healthcare systems, the clinical characteristics of patients admitted with HF were similar and the overall standard of care was maintained throughout the pandemic. Long-term survival of patients hospitalized with HF continued to improve after COVID-19, especially for HFrEF.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1002/ejhf.3306; doi:https://doi.org/10.1002/ejhf.3306" + }, { "id": "38833617", "doi": "https://doi.org/10.1093/cvr/cvae123", @@ -12885,23 +12885,6 @@ "laySummary": "", "urls": "pdf:https://academic.oup.com/eurheartj/advance-article-pdf/doi/10.1093/eurheartj/ehad748/53515704/ehad748.pdf; doi:https://doi.org/10.1093/eurheartj/ehad748" }, - { - "id": "35780515", - "doi": "https://doi.org/10.1016/j.epidem.2022.100604", - "title": "Appropriately smoothing prevalence data to inform estimates of growth rate and reproduction number.", - "authorString": "Eales O, Ainslie KEC, Walters CE, Wang H, Atchison C, Ashby D, Donnelly CA, Cooke G, Barclay W, Ward H, Darzi A, Elliott P, Riley S.", - "authorAffiliations": "", - "journalTitle": "Epidemics", - "pubYear": "2022", - "date": "2022-06-22", - "isOpenAccess": "Y", - "keywords": "Cross-sectional study; Reproduction Number; Covid-19; Sars-cov-2; Bayesian P-Spline", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "The time-varying reproduction number (Rt) can change rapidly over the course of a pandemic due to changing restrictions, behaviours, and levels of population immunity. Many methods exist that allow the estimation of Rt from case data. However, these are not easily adapted to point prevalence data nor can they infer Rt across periods of missing data. We developed a Bayesian P-spline model suitable for fitting to a wide range of epidemic time-series, including point-prevalence data. We demonstrate the utility of the model by fitting to periodic daily SARS-CoV-2 swab-positivity data in England from the first 7 rounds (May 2020-December 2020) of the REal-time Assessment of Community Transmission-1 (REACT-1) study. Estimates of Rt over the period of two subsequent rounds (6-8 weeks) and single rounds (2-3 weeks) inferred using the Bayesian P-spline model were broadly consistent with estimates from a simple exponential model, with overlapping credible intervals. However, there were sometimes substantial differences in point estimates. The Bayesian P-spline model was further able to infer changes in Rt over shorter periods tracking a temporary increase above one during late-May 2020, a gradual increase in Rt over the summer of 2020 as restrictions were eased, and a reduction in Rt during England's second national lockdown followed by an increase as the Alpha variant surged. The model is robust against both under-fitting and over-fitting and is able to interpolate between periods of available data; it is a particularly versatile model when growth rate can change over small timescales, as in the current SARS-CoV-2 pandemic. This work highlights the importance of pairing robust methods with representative samples to track pandemics.", - "laySummary": "", - "urls": "html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9220254; doi:https://doi.org/10.1016/j.epidem.2022.100604; html:https://europepmc.org/articles/PMC9220254; pdf:https://europepmc.org/articles/PMC9220254?pdf=render" - }, { "id": "33634312", "doi": "https://doi.org/10.1093/bib/bbab006", @@ -12919,6 +12902,23 @@ "laySummary": "", "urls": "pdf:https://www.pure.ed.ac.uk/ws/files/198917679/bbab006.pdf; doi:https://doi.org/10.1093/bib/bbab006; html:https://europepmc.org/articles/PMC8425308; pdf:https://europepmc.org/articles/PMC8425308?pdf=render" }, + { + "id": "35780515", + "doi": "https://doi.org/10.1016/j.epidem.2022.100604", + "title": "Appropriately smoothing prevalence data to inform estimates of growth rate and reproduction number.", + "authorString": "Eales O, Ainslie KEC, Walters CE, Wang H, Atchison C, Ashby D, Donnelly CA, Cooke G, Barclay W, Ward H, Darzi A, Elliott P, Riley S.", + "authorAffiliations": "", + "journalTitle": "Epidemics", + "pubYear": "2022", + "date": "2022-06-22", + "isOpenAccess": "Y", + "keywords": "Cross-sectional study; Reproduction Number; Covid-19; Sars-cov-2; Bayesian P-Spline", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "The time-varying reproduction number (Rt) can change rapidly over the course of a pandemic due to changing restrictions, behaviours, and levels of population immunity. Many methods exist that allow the estimation of Rt from case data. However, these are not easily adapted to point prevalence data nor can they infer Rt across periods of missing data. We developed a Bayesian P-spline model suitable for fitting to a wide range of epidemic time-series, including point-prevalence data. We demonstrate the utility of the model by fitting to periodic daily SARS-CoV-2 swab-positivity data in England from the first 7 rounds (May 2020-December 2020) of the REal-time Assessment of Community Transmission-1 (REACT-1) study. Estimates of Rt over the period of two subsequent rounds (6-8 weeks) and single rounds (2-3 weeks) inferred using the Bayesian P-spline model were broadly consistent with estimates from a simple exponential model, with overlapping credible intervals. However, there were sometimes substantial differences in point estimates. The Bayesian P-spline model was further able to infer changes in Rt over shorter periods tracking a temporary increase above one during late-May 2020, a gradual increase in Rt over the summer of 2020 as restrictions were eased, and a reduction in Rt during England's second national lockdown followed by an increase as the Alpha variant surged. The model is robust against both under-fitting and over-fitting and is able to interpolate between periods of available data; it is a particularly versatile model when growth rate can change over small timescales, as in the current SARS-CoV-2 pandemic. This work highlights the importance of pairing robust methods with representative samples to track pandemics.", + "laySummary": "", + "urls": "html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9220254; doi:https://doi.org/10.1016/j.epidem.2022.100604; html:https://europepmc.org/articles/PMC9220254; pdf:https://europepmc.org/articles/PMC9220254?pdf=render" + }, { "id": "35611160", "doi": "https://doi.org/10.1016/j.eclinm.2022.101462", @@ -13004,23 +13004,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.3389/fcvm.2023.1141026; html:https://europepmc.org/articles/PMC10541220; pdf:https://europepmc.org/articles/PMC10541220?pdf=render" }, - { - "id": "37053113", - "doi": "https://doi.org/10.1097/bot.0000000000002612", - "title": "The Translated Proximal Humerus Fracture: A Comparison of Operative and Nonoperative Management.", - "authorString": "Cosic F, Kirzner N, Edwards E, Page R, Kimmel L, Gabbe B.", - "authorAffiliations": "", - "journalTitle": "Journal of orthopaedic trauma", - "pubYear": "2023", - "date": "2023-09-01", - "isOpenAccess": "N", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Objectives

To report on the long-term outcomes of the management of translated proximal humerus fractures.

Design

A prospective cohort study was conducted from January 2010 to December 2018.

Setting

Academic Level 1 trauma center.

Participants/patients

A total of 108 patients with a proximal humerus fracture with \u2265100% translation, defined as no cortical bony contact between the shaft and humeral head fragments, were included.

Intervention

Patients were managed nonoperatively with sling immobilization or with operative management as determined by the treating surgeon.

Main outcome measures

Outcome measures were the Oxford Shoulder Score, EQ-5D-5L, return to work, and radiological outcomes. Complications recorded included further surgery, loss of position/fixation, nonunion/malunion, and avascular necrosis.

Results

Of the 108 patients, 76 underwent operative intervention and 32 were managed nonoperatively. The mean (SD) age in the operative group was 54.3 (\u00b120.2) years and in the nonoperative group was 73.3 (\u00b115.3) years ( P < 0.001). There was no association between Oxford Shoulder Score and management options (mean 38.5 [\u00b19.5] operative versus mean 41.3 [\u00b18.5] nonoperative, P = 0.48). Operative management was associated with improved health status outcomes; EQ-5D utility score adjusted mean difference was 0.16 (95% CI, 0.04-0.27; P = 0.008); EQ-5D VAS adjusted mean difference was 19.2 (95% CI, 5.2-33.2; P = 0.008). Operative management was associated with a lower odds of nonunion (adjusted OR 0.30; 95% CI, 0.09-0.97; P = 0.04), malunion (adjusted OR 0.14; 95% CI, 0.04-0.51; P = 0.003), and complications (adjusted OR 0.07; 95% CI, 0.02-0.32; P = 0.001).

Conclusion

Translated proximal humerus fractures with \u2265100% displacement demonstrate improved health status and radiological outcomes after surgical fixation.

Level of evidence

Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1097/BOT.0000000000002612" - }, { "id": "33635829", "doi": "https://doi.org/10.1530/eje-20-1163", @@ -13038,6 +13021,23 @@ "laySummary": "", "urls": "pdf:https://academic.oup.com/ejendo/article-pdf/184/5/637/45221794/eje-20-1163.pdf; doi:https://doi.org/10.1530/EJE-20-1163; html:https://europepmc.org/articles/PMC8052516; pdf:https://europepmc.org/articles/PMC8052516?pdf=render" }, + { + "id": "37053113", + "doi": "https://doi.org/10.1097/bot.0000000000002612", + "title": "The Translated Proximal Humerus Fracture: A Comparison of Operative and Nonoperative Management.", + "authorString": "Cosic F, Kirzner N, Edwards E, Page R, Kimmel L, Gabbe B.", + "authorAffiliations": "", + "journalTitle": "Journal of orthopaedic trauma", + "pubYear": "2023", + "date": "2023-09-01", + "isOpenAccess": "N", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Objectives

To report on the long-term outcomes of the management of translated proximal humerus fractures.

Design

A prospective cohort study was conducted from January 2010 to December 2018.

Setting

Academic Level 1 trauma center.

Participants/patients

A total of 108 patients with a proximal humerus fracture with \u2265100% translation, defined as no cortical bony contact between the shaft and humeral head fragments, were included.

Intervention

Patients were managed nonoperatively with sling immobilization or with operative management as determined by the treating surgeon.

Main outcome measures

Outcome measures were the Oxford Shoulder Score, EQ-5D-5L, return to work, and radiological outcomes. Complications recorded included further surgery, loss of position/fixation, nonunion/malunion, and avascular necrosis.

Results

Of the 108 patients, 76 underwent operative intervention and 32 were managed nonoperatively. The mean (SD) age in the operative group was 54.3 (\u00b120.2) years and in the nonoperative group was 73.3 (\u00b115.3) years ( P < 0.001). There was no association between Oxford Shoulder Score and management options (mean 38.5 [\u00b19.5] operative versus mean 41.3 [\u00b18.5] nonoperative, P = 0.48). Operative management was associated with improved health status outcomes; EQ-5D utility score adjusted mean difference was 0.16 (95% CI, 0.04-0.27; P = 0.008); EQ-5D VAS adjusted mean difference was 19.2 (95% CI, 5.2-33.2; P = 0.008). Operative management was associated with a lower odds of nonunion (adjusted OR 0.30; 95% CI, 0.09-0.97; P = 0.04), malunion (adjusted OR 0.14; 95% CI, 0.04-0.51; P = 0.003), and complications (adjusted OR 0.07; 95% CI, 0.02-0.32; P = 0.001).

Conclusion

Translated proximal humerus fractures with \u2265100% displacement demonstrate improved health status and radiological outcomes after surgical fixation.

Level of evidence

Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1097/BOT.0000000000002612" + }, { "id": "31857590", "doi": "https://doi.org/10.1038/s41597-019-0337-6", @@ -13157,23 +13157,6 @@ "laySummary": "", "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/10/11/e043828.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-043828; html:https://europepmc.org/articles/PMC7674020; pdf:https://europepmc.org/articles/PMC7674020?pdf=render" }, - { - "id": "38336974", - "doi": "https://doi.org/10.1038/s41598-023-49923-3", - "title": "VertXNet: an ensemble method for vertebral body segmentation and identification from cervical and lumbar spinal X-rays.", - "authorString": "Chen Y, Mo Y, Readie A, Ligozio G, Mandal I, Jabbar F, Coroller T, Papie\u017c BW.", - "authorAffiliations": "", - "journalTitle": "Scientific reports", - "pubYear": "2024", - "date": "2024-02-09", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Accurate annotation of vertebral bodies is crucial for automating the analysis of spinal X-ray images. However, manual annotation of these structures is a laborious and costly process due to their complex nature, including small sizes and varying shapes. To address this challenge and expedite the annotation process, we propose an ensemble pipeline called VertXNet. This pipeline currently combines two segmentation mechanisms, semantic segmentation using U-Net, and instance segmentation using Mask R-CNN, to automatically segment and label vertebral bodies in lateral cervical and lumbar spinal X-ray images. VertXNet enhances its effectiveness by adopting a rule-based strategy (termed the ensemble rule) for effectively combining segmentation outcomes from U-Net and Mask R-CNN. It determines vertebral body labels by recognizing specific reference vertebral instances, such as cervical vertebra 2 ('C2') in cervical spine X-rays and sacral vertebra 1 ('S1') in lumbar spine X-rays. Those references are commonly relatively easy to identify at the edge of the spine. To assess the performance of our proposed pipeline, we conducted evaluations on three spinal X-ray datasets, including two in-house datasets and one publicly available dataset. The ground truth annotations were provided by radiologists for comparison. Our experimental results have shown that the proposed pipeline outperformed two state-of-the-art (SOTA) segmentation models on our test dataset with a mean Dice of 0.90, vs. a mean Dice of 0.73 for Mask R-CNN and 0.72 for U-Net. We also demonstrated that VertXNet is a modular pipeline that enables using other SOTA model, like nnU-Net to further improve its performance. Furthermore, to evaluate the generalization ability of VertXNet on spinal X-rays, we directly tested the pre-trained pipeline on two additional datasets. A consistently strong performance was observed, with mean Dice coefficients of 0.89 and 0.88, respectively. In summary, VertXNet demonstrated significantly improved performance in vertebral body segmentation and labeling for spinal X-ray imaging. Its robustness and generalization were presented through the evaluation of both in-house clinical trial data and publicly available datasets.", - "laySummary": "", - "urls": "pdf:https://www.nature.com/articles/s41598-023-49923-3.pdf; doi:https://doi.org/10.1038/s41598-023-49923-3; html:https://europepmc.org/articles/PMC10858234; pdf:https://europepmc.org/articles/PMC10858234?pdf=render" - }, { "id": "34249083", "doi": "https://doi.org/10.3389/fgene.2021.652878", @@ -13208,6 +13191,23 @@ "laySummary": "", "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ijc.34548; doi:https://doi.org/10.1002/ijc.34548; html:https://europepmc.org/articles/PMC10952206; pdf:https://europepmc.org/articles/PMC10952206?pdf=render" }, + { + "id": "38336974", + "doi": "https://doi.org/10.1038/s41598-023-49923-3", + "title": "VertXNet: an ensemble method for vertebral body segmentation and identification from cervical and lumbar spinal X-rays.", + "authorString": "Chen Y, Mo Y, Readie A, Ligozio G, Mandal I, Jabbar F, Coroller T, Papie\u017c BW.", + "authorAffiliations": "", + "journalTitle": "Scientific reports", + "pubYear": "2024", + "date": "2024-02-09", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Accurate annotation of vertebral bodies is crucial for automating the analysis of spinal X-ray images. However, manual annotation of these structures is a laborious and costly process due to their complex nature, including small sizes and varying shapes. To address this challenge and expedite the annotation process, we propose an ensemble pipeline called VertXNet. This pipeline currently combines two segmentation mechanisms, semantic segmentation using U-Net, and instance segmentation using Mask R-CNN, to automatically segment and label vertebral bodies in lateral cervical and lumbar spinal X-ray images. VertXNet enhances its effectiveness by adopting a rule-based strategy (termed the ensemble rule) for effectively combining segmentation outcomes from U-Net and Mask R-CNN. It determines vertebral body labels by recognizing specific reference vertebral instances, such as cervical vertebra 2 ('C2') in cervical spine X-rays and sacral vertebra 1 ('S1') in lumbar spine X-rays. Those references are commonly relatively easy to identify at the edge of the spine. To assess the performance of our proposed pipeline, we conducted evaluations on three spinal X-ray datasets, including two in-house datasets and one publicly available dataset. The ground truth annotations were provided by radiologists for comparison. Our experimental results have shown that the proposed pipeline outperformed two state-of-the-art (SOTA) segmentation models on our test dataset with a mean Dice of 0.90, vs. a mean Dice of 0.73 for Mask R-CNN and 0.72 for U-Net. We also demonstrated that VertXNet is a modular pipeline that enables using other SOTA model, like nnU-Net to further improve its performance. Furthermore, to evaluate the generalization ability of VertXNet on spinal X-rays, we directly tested the pre-trained pipeline on two additional datasets. A consistently strong performance was observed, with mean Dice coefficients of 0.89 and 0.88, respectively. In summary, VertXNet demonstrated significantly improved performance in vertebral body segmentation and labeling for spinal X-ray imaging. Its robustness and generalization were presented through the evaluation of both in-house clinical trial data and publicly available datasets.", + "laySummary": "", + "urls": "pdf:https://www.nature.com/articles/s41598-023-49923-3.pdf; doi:https://doi.org/10.1038/s41598-023-49923-3; html:https://europepmc.org/articles/PMC10858234; pdf:https://europepmc.org/articles/PMC10858234?pdf=render" + }, { "id": "36933612", "doi": "https://doi.org/10.1016/j.cct.2023.107162", @@ -13259,23 +13259,6 @@ "laySummary": "", "urls": "pdf:https://jogh.org/wp-content/uploads/2022/07/jogh-12-05025.pdf; doi:https://doi.org/10.7189/jogh.12.05025; html:https://europepmc.org/articles/PMC9269984; pdf:https://europepmc.org/articles/PMC9269984?pdf=render" }, - { - "id": "38528230", - "doi": "https://doi.org/10.1038/s43587-024-00590-7", - "title": "Integration of polygenic and gut metagenomic risk prediction for common diseases.", - "authorString": "Liu Y, Ritchie SC, Teo SM, Ruuskanen MO, Kambur O, Zhu Q, Sanders J, V\u00e1zquez-Baeza Y, Verspoor K, Jousilahti P, Lahti L, Niiranen T, Salomaa V, Havulinna AS, Knight R, M\u00e9ric G, Inouye M.", - "authorAffiliations": "", - "journalTitle": "Nature aging", - "pubYear": "2024", - "date": "2024-03-25", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Multiomics has shown promise in noninvasive risk profiling and early detection of various common diseases. In the present study, in a prospective population-based cohort with ~18\u2009years of e-health record follow-up, we investigated the incremental and combined value of genomic and gut metagenomic risk assessment compared with conventional risk factors for predicting incident coronary artery disease (CAD), type 2 diabetes (T2D), Alzheimer disease and prostate cancer. We found that polygenic risk scores (PRSs) improved prediction over conventional risk factors for all diseases. Gut microbiome scores improved predictive capacity over baseline age for CAD, T2D and prostate cancer. Integrated risk models of PRSs, gut microbiome scores and conventional risk factors achieved the highest predictive performance for all diseases studied compared with models based on conventional risk factors alone. The present study demonstrates that integrated PRSs and gut metagenomic risk models improve the predictive value over conventional risk factors for common chronic diseases.", - "laySummary": "", - "urls": "pdf:https://www.nature.com/articles/s43587-024-00590-7.pdf; doi:https://doi.org/10.1038/s43587-024-00590-7; html:https://europepmc.org/articles/PMC11031402; pdf:https://europepmc.org/articles/PMC11031402?pdf=render" - }, { "id": "35105585", "doi": "https://doi.org/10.1136/bmjopen-2021-054376", @@ -13293,6 +13276,23 @@ "laySummary": "", "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/12/2/e054376.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-054376; html:https://europepmc.org/articles/PMC8808438; pdf:https://europepmc.org/articles/PMC8808438?pdf=render" }, + { + "id": "38528230", + "doi": "https://doi.org/10.1038/s43587-024-00590-7", + "title": "Integration of polygenic and gut metagenomic risk prediction for common diseases.", + "authorString": "Liu Y, Ritchie SC, Teo SM, Ruuskanen MO, Kambur O, Zhu Q, Sanders J, V\u00e1zquez-Baeza Y, Verspoor K, Jousilahti P, Lahti L, Niiranen T, Salomaa V, Havulinna AS, Knight R, M\u00e9ric G, Inouye M.", + "authorAffiliations": "", + "journalTitle": "Nature aging", + "pubYear": "2024", + "date": "2024-03-25", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Multiomics has shown promise in noninvasive risk profiling and early detection of various common diseases. In the present study, in a prospective population-based cohort with ~18\u2009years of e-health record follow-up, we investigated the incremental and combined value of genomic and gut metagenomic risk assessment compared with conventional risk factors for predicting incident coronary artery disease (CAD), type 2 diabetes (T2D), Alzheimer disease and prostate cancer. We found that polygenic risk scores (PRSs) improved prediction over conventional risk factors for all diseases. Gut microbiome scores improved predictive capacity over baseline age for CAD, T2D and prostate cancer. Integrated risk models of PRSs, gut microbiome scores and conventional risk factors achieved the highest predictive performance for all diseases studied compared with models based on conventional risk factors alone. The present study demonstrates that integrated PRSs and gut metagenomic risk models improve the predictive value over conventional risk factors for common chronic diseases.", + "laySummary": "", + "urls": "pdf:https://www.nature.com/articles/s43587-024-00590-7.pdf; doi:https://doi.org/10.1038/s43587-024-00590-7; html:https://europepmc.org/articles/PMC11031402; pdf:https://europepmc.org/articles/PMC11031402?pdf=render" + }, { "id": "32206896", "doi": "https://doi.org/10.1007/s00394-020-02220-5", @@ -13463,23 +13463,6 @@ "laySummary": "", "urls": "pdf:https://bmcmedicine.biomedcentral.com/track/pdf/10.1186/s12916-021-02045-x; doi:https://doi.org/10.1186/s12916-021-02045-x; html:https://europepmc.org/articles/PMC8344166; pdf:https://europepmc.org/articles/PMC8344166?pdf=render" }, - { - "id": "37000839", - "doi": "https://doi.org/10.1371/journal.pone.0279076", - "title": "Predicting a diagnosis of ankylosing spondylitis using primary care health records-A machine learning approach.", - "authorString": "Kennedy J, Kennedy N, Cooksey R, Choy E, Siebert S, Rahman M, Brophy S.", - "authorAffiliations": "", - "journalTitle": "PloS one", - "pubYear": "2023", - "date": "2023-03-31", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Ankylosing spondylitis is the second most common cause of inflammatory arthritis. However, a successful diagnosis can take a decade to confirm from symptom onset (via x-rays). The aim of this study was to use machine learning methods to develop a profile of the characteristics of people who are likely to be given a diagnosis of AS in future. The Secure Anonymised Information Linkage databank was used. Patients with ankylosing spondylitis were identified using their routine data and matched with controls who had no record of a diagnosis of ankylosing spondylitis or axial spondyloarthritis. Data was analysed separately for men and women. The model was developed using feature/variable selection and principal component analysis to develop decision trees. The decision tree with the highest average F value was selected and validated with a test dataset. The model for men indicated that lower back pain, uveitis, and NSAID use under age 20 is associated with AS development. The model for women showed an older age of symptom presentation compared to men with back pain and multiple pain relief medications. The models showed good prediction (positive predictive value 70%-80%) in test data but in the general population where prevalence is very low (0.09% of the population in this dataset) the positive predictive value would be very low (0.33%-0.25%). Machine learning can be used to help profile and understand the characteristics of people who will develop AS, and in test datasets with artificially high prevalence, will perform well. However, when applied to a general population with low prevalence rates, such as that in primary care, the positive predictive value for even the best model would be 1.4%. Multiple models may be needed to narrow down the population over time to improve the predictive value and therefore reduce the time to diagnosis of ankylosing spondylitis.", - "laySummary": "", - "urls": "pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0279076&type=printable; doi:https://doi.org/10.1371/journal.pone.0279076; html:https://europepmc.org/articles/PMC10065228; pdf:https://europepmc.org/articles/PMC10065228?pdf=render" - }, { "id": "33446033", "doi": "https://doi.org/10.1177/1460458220977579", @@ -13497,6 +13480,23 @@ "laySummary": "", "urls": "pdf:https://journals.sagepub.com/doi/pdf/10.1177/1460458220977579; doi:https://doi.org/10.1177/1460458220977579" }, + { + "id": "37000839", + "doi": "https://doi.org/10.1371/journal.pone.0279076", + "title": "Predicting a diagnosis of ankylosing spondylitis using primary care health records-A machine learning approach.", + "authorString": "Kennedy J, Kennedy N, Cooksey R, Choy E, Siebert S, Rahman M, Brophy S.", + "authorAffiliations": "", + "journalTitle": "PloS one", + "pubYear": "2023", + "date": "2023-03-31", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Ankylosing spondylitis is the second most common cause of inflammatory arthritis. However, a successful diagnosis can take a decade to confirm from symptom onset (via x-rays). The aim of this study was to use machine learning methods to develop a profile of the characteristics of people who are likely to be given a diagnosis of AS in future. The Secure Anonymised Information Linkage databank was used. Patients with ankylosing spondylitis were identified using their routine data and matched with controls who had no record of a diagnosis of ankylosing spondylitis or axial spondyloarthritis. Data was analysed separately for men and women. The model was developed using feature/variable selection and principal component analysis to develop decision trees. The decision tree with the highest average F value was selected and validated with a test dataset. The model for men indicated that lower back pain, uveitis, and NSAID use under age 20 is associated with AS development. The model for women showed an older age of symptom presentation compared to men with back pain and multiple pain relief medications. The models showed good prediction (positive predictive value 70%-80%) in test data but in the general population where prevalence is very low (0.09% of the population in this dataset) the positive predictive value would be very low (0.33%-0.25%). Machine learning can be used to help profile and understand the characteristics of people who will develop AS, and in test datasets with artificially high prevalence, will perform well. However, when applied to a general population with low prevalence rates, such as that in primary care, the positive predictive value for even the best model would be 1.4%. Multiple models may be needed to narrow down the population over time to improve the predictive value and therefore reduce the time to diagnosis of ankylosing spondylitis.", + "laySummary": "", + "urls": "pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0279076&type=printable; doi:https://doi.org/10.1371/journal.pone.0279076; html:https://europepmc.org/articles/PMC10065228; pdf:https://europepmc.org/articles/PMC10065228?pdf=render" + }, { "id": "33469151", "doi": "https://doi.org/10.1038/s42003-020-01613-w", @@ -13514,23 +13514,6 @@ "laySummary": "", "urls": "pdf:https://www.nature.com/articles/s42003-020-01613-w.pdf; doi:https://doi.org/10.1038/s42003-020-01613-w; html:https://europepmc.org/articles/PMC7815736; pdf:https://europepmc.org/articles/PMC7815736?pdf=render" }, - { - "id": "38304287", - "doi": "https://doi.org/10.3389/fpsyt.2024.1347358", - "title": "How will AI make sense of our messy lives and improve our mental health?", - "authorString": "Speechley J, McTernan M.", - "authorAffiliations": "", - "journalTitle": "Frontiers in psychiatry", - "pubYear": "2024", - "date": "2024-01-18", - "isOpenAccess": "Y", - "keywords": "Artificial intelligence; Data; Mental health; TRUST; Patient And Public Engagement", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "", - "laySummary": "", - "urls": "doi:https://doi.org/10.3389/fpsyt.2024.1347358; html:https://europepmc.org/articles/PMC10832992; pdf:https://europepmc.org/articles/PMC10832992?pdf=render" - }, { "id": "36377225", "doi": "https://doi.org/10.1177/18333583221135710", @@ -13548,6 +13531,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1177/18333583221135710" }, + { + "id": "38304287", + "doi": "https://doi.org/10.3389/fpsyt.2024.1347358", + "title": "How will AI make sense of our messy lives and improve our mental health?", + "authorString": "Speechley J, McTernan M.", + "authorAffiliations": "", + "journalTitle": "Frontiers in psychiatry", + "pubYear": "2024", + "date": "2024-01-18", + "isOpenAccess": "Y", + "keywords": "Artificial intelligence; Data; Mental health; TRUST; Patient And Public Engagement", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "", + "laySummary": "", + "urls": "doi:https://doi.org/10.3389/fpsyt.2024.1347358; html:https://europepmc.org/articles/PMC10832992; pdf:https://europepmc.org/articles/PMC10832992?pdf=render" + }, { "id": "30727941", "doi": "https://doi.org/10.1186/s12859-019-2633-8", @@ -13854,23 +13854,6 @@ "laySummary": "", "urls": "pdf:https://diabetesjournals.org/care/article-pdf/44/12/2758/631597/dc210437.pdf; doi:https://doi.org/10.2337/dc21-0437; html:https://europepmc.org/articles/PMC8669537; pdf:https://europepmc.org/articles/PMC8669537?pdf=render" }, - { - "id": "36895179", - "doi": "https://doi.org/10.1093/eurjpc/zwad055", - "title": "Determining cardiovascular risk in patients with unattributed chest pain in UK primary care: an electronic health record study.", - "authorString": "Jordan KP, Rathod-Mistry T, van der Windt DA, Bailey J, Chen Y, Clarson L, Denaxas S, Hayward RA, Hemingway H, Kyriacou T, Mamas MA.", - "authorAffiliations": "", - "journalTitle": "European journal of preventive cardiology", - "pubYear": "2023", - "date": "2023-08-01", - "isOpenAccess": "Y", - "keywords": "Cardiovascular disease; Chest pain; epidemiology; Primary Health Care; risk; Electronic Health Records", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Aims

Most adults presenting in primary care with chest pain symptoms will not receive a diagnosis ('unattributed' chest pain) but are at increased risk of cardiovascular events. To assess within patients with unattributed chest pain, risk factors for cardiovascular events and whether those at greatest risk of cardiovascular disease can be ascertained by an existing general population risk prediction model or by development of a new model.

Methods and results

The study used UK primary care electronic health records from the Clinical Practice Research Datalink linked to admitted hospitalizations. Study population was patients aged 18 plus with recorded unattributed chest pain 2002-2018. Cardiovascular risk prediction models were developed with external validation and comparison of performance to QRISK3, a general population risk prediction model. There were 374 917 patients with unattributed chest pain in the development data set. The strongest risk factors for cardiovascular disease included diabetes, atrial fibrillation, and hypertension. Risk was increased in males, patients of Asian ethnicity, those in more deprived areas, obese patients, and smokers. The final developed model had good predictive performance (external validation c-statistic 0.81, calibration slope 1.02). A model using a subset of key risk factors for cardiovascular disease gave nearly identical performance. QRISK3 underestimated cardiovascular risk.

Conclusion

Patients presenting with unattributed chest pain are at increased risk of cardiovascular events. It is feasible to accurately estimate individual risk using routinely recorded information in the primary care record, focusing on a small number of risk factors. Patients at highest risk could be targeted for preventative measures.", - "laySummary": "", - "urls": "pdf:https://academic.oup.com/eurjpc/advance-article-pdf/doi/10.1093/eurjpc/zwad055/49604587/zwad055.pdf; doi:https://doi.org/10.1093/eurjpc/zwad055; html:https://europepmc.org/articles/PMC10442054; pdf:https://europepmc.org/articles/PMC10442054?pdf=render" - }, { "id": "33123364", "doi": "https://doi.org/10.1093/ckj/sfaa192", @@ -13888,6 +13871,23 @@ "laySummary": "", "urls": "pdf:https://academic.oup.com/ckj/article-pdf/13/5/889/33980535/sfaa192.pdf; doi:https://doi.org/10.1093/ckj/sfaa192; html:https://europepmc.org/articles/PMC7577776; pdf:https://europepmc.org/articles/PMC7577776?pdf=render" }, + { + "id": "36895179", + "doi": "https://doi.org/10.1093/eurjpc/zwad055", + "title": "Determining cardiovascular risk in patients with unattributed chest pain in UK primary care: an electronic health record study.", + "authorString": "Jordan KP, Rathod-Mistry T, van der Windt DA, Bailey J, Chen Y, Clarson L, Denaxas S, Hayward RA, Hemingway H, Kyriacou T, Mamas MA.", + "authorAffiliations": "", + "journalTitle": "European journal of preventive cardiology", + "pubYear": "2023", + "date": "2023-08-01", + "isOpenAccess": "Y", + "keywords": "Cardiovascular disease; Chest pain; epidemiology; Primary Health Care; risk; Electronic Health Records", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Aims

Most adults presenting in primary care with chest pain symptoms will not receive a diagnosis ('unattributed' chest pain) but are at increased risk of cardiovascular events. To assess within patients with unattributed chest pain, risk factors for cardiovascular events and whether those at greatest risk of cardiovascular disease can be ascertained by an existing general population risk prediction model or by development of a new model.

Methods and results

The study used UK primary care electronic health records from the Clinical Practice Research Datalink linked to admitted hospitalizations. Study population was patients aged 18 plus with recorded unattributed chest pain 2002-2018. Cardiovascular risk prediction models were developed with external validation and comparison of performance to QRISK3, a general population risk prediction model. There were 374 917 patients with unattributed chest pain in the development data set. The strongest risk factors for cardiovascular disease included diabetes, atrial fibrillation, and hypertension. Risk was increased in males, patients of Asian ethnicity, those in more deprived areas, obese patients, and smokers. The final developed model had good predictive performance (external validation c-statistic 0.81, calibration slope 1.02). A model using a subset of key risk factors for cardiovascular disease gave nearly identical performance. QRISK3 underestimated cardiovascular risk.

Conclusion

Patients presenting with unattributed chest pain are at increased risk of cardiovascular events. It is feasible to accurately estimate individual risk using routinely recorded information in the primary care record, focusing on a small number of risk factors. Patients at highest risk could be targeted for preventative measures.", + "laySummary": "", + "urls": "pdf:https://academic.oup.com/eurjpc/advance-article-pdf/doi/10.1093/eurjpc/zwad055/49604587/zwad055.pdf; doi:https://doi.org/10.1093/eurjpc/zwad055; html:https://europepmc.org/articles/PMC10442054; pdf:https://europepmc.org/articles/PMC10442054?pdf=render" + }, { "id": "36447757", "doi": "https://doi.org/10.1136/gpsych-2022-100819", @@ -14296,23 +14296,6 @@ "laySummary": "", "urls": "pdf:https://bmchealthservres.biomedcentral.com/counter/pdf/10.1186/s12913-023-09545-x; doi:https://doi.org/10.1186/s12913-023-09545-x; html:https://europepmc.org/articles/PMC10308762; pdf:https://europepmc.org/articles/PMC10308762?pdf=render" }, - { - "id": "36879385", - "doi": "https://doi.org/10.1097/ta.0000000000003950", - "title": "Cost-effectiveness of a purpose-built ward environment and new allied health model of care for major trauma.", - "authorString": "Gabbe BJ, Reeder S, Ekegren CL, Mather A, Kimmel L, Cameron PA, Higgins AM.", - "authorAffiliations": "", - "journalTitle": "The journal of trauma and acute care surgery", - "pubYear": "2023", - "date": "2023-03-07", - "isOpenAccess": "N", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Targeted rehabilitation within the acute inpatient setting could have a substantial impact on improving outcomes for major trauma patients. The aim of this study was to investigate the cost-effectiveness of the introduction of a purpose-built ward environment, and a new allied health model of care (AHMOC) delivered in the acute inpatient setting, in a major trauma population.

Methods

The statewide trauma registry, the trauma center's data warehouse, and electronic medical record data were used for this observational study. There were three phases: baseline, new ward, and new AHMOC. Cost-effectiveness was measured as cost per quality-adjusted life year using preinjury, hospital discharge, 1-month and 6-month 5-level, EQ-5D utility scores. Total costs included initial acute and inpatient rehabilitation care, as well as outpatient, readmission and ED presentations to 6-months.

Results

Four hundred eleven patients were included. Case-mix was stable between phases. The median (IQR) number of allied health services received by patients was 8 (5-17) at baseline, 10 (5-19) in the new ward phase, and 17 (9-23) in the AHMOC phase. The proportion discharged to rehabilitation was 37% at baseline, 45% with the new ward and 28% with the new AHMOC. Mean (SD) total Australian dollar costs were $69,335 ($141,175) at baseline, $55,943 ($82,706) with the new ward and $37,833 ($49,004) with the AHMOC. The probability of the AHMOC being cost-effective at a willingness-to-pay threshold of $50,000 per quality-adjusted life year was 99.4% compared with baseline and 98% compared with the new ward.

Conclusion

The new allied health model of care was found to be a cost-effective intervention. Uptake of this model of allied health care at other trauma centers has the potential to reduce the cost and burden of major trauma.

Level of evidence

Economic and Value-based Evaluations; Level III.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1097/TA.0000000000003950" - }, { "id": "31797917", "doi": "https://doi.org/10.1038/s41398-019-0635-y", @@ -14330,6 +14313,23 @@ "laySummary": "This study assessed for genetic correlation between anhedonia and neuropsychiatric conditions. A polygenic risk score approach was applied to test for association between anhedonia and brain structure and brain function. Findings confirm that using anhedonia as a marker of vulnerability to mental illness. Findings also suggest that genetic risk for state anhedonia influences brain structure", "urls": "pdf:https://www.nature.com/articles/s41398-019-0635-y.pdf; doi:https://doi.org/10.1038/s41398-019-0635-y; html:https://europepmc.org/articles/PMC6892870; pdf:https://europepmc.org/articles/PMC6892870?pdf=render" }, + { + "id": "36879385", + "doi": "https://doi.org/10.1097/ta.0000000000003950", + "title": "Cost-effectiveness of a purpose-built ward environment and new allied health model of care for major trauma.", + "authorString": "Gabbe BJ, Reeder S, Ekegren CL, Mather A, Kimmel L, Cameron PA, Higgins AM.", + "authorAffiliations": "", + "journalTitle": "The journal of trauma and acute care surgery", + "pubYear": "2023", + "date": "2023-03-07", + "isOpenAccess": "N", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Targeted rehabilitation within the acute inpatient setting could have a substantial impact on improving outcomes for major trauma patients. The aim of this study was to investigate the cost-effectiveness of the introduction of a purpose-built ward environment, and a new allied health model of care (AHMOC) delivered in the acute inpatient setting, in a major trauma population.

Methods

The statewide trauma registry, the trauma center's data warehouse, and electronic medical record data were used for this observational study. There were three phases: baseline, new ward, and new AHMOC. Cost-effectiveness was measured as cost per quality-adjusted life year using preinjury, hospital discharge, 1-month and 6-month 5-level, EQ-5D utility scores. Total costs included initial acute and inpatient rehabilitation care, as well as outpatient, readmission and ED presentations to 6-months.

Results

Four hundred eleven patients were included. Case-mix was stable between phases. The median (IQR) number of allied health services received by patients was 8 (5-17) at baseline, 10 (5-19) in the new ward phase, and 17 (9-23) in the AHMOC phase. The proportion discharged to rehabilitation was 37% at baseline, 45% with the new ward and 28% with the new AHMOC. Mean (SD) total Australian dollar costs were $69,335 ($141,175) at baseline, $55,943 ($82,706) with the new ward and $37,833 ($49,004) with the AHMOC. The probability of the AHMOC being cost-effective at a willingness-to-pay threshold of $50,000 per quality-adjusted life year was 99.4% compared with baseline and 98% compared with the new ward.

Conclusion

The new allied health model of care was found to be a cost-effective intervention. Uptake of this model of allied health care at other trauma centers has the potential to reduce the cost and burden of major trauma.

Level of evidence

Economic and Value-based Evaluations; Level III.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1097/TA.0000000000003950" + }, { "id": "35945198", "doi": "https://doi.org/10.1038/s41467-022-32095-5", @@ -14347,23 +14347,6 @@ "laySummary": "", "urls": "pdf:https://www.nature.com/articles/s41467-022-32095-5.pdf; doi:https://doi.org/10.1038/s41467-022-32095-5; html:https://europepmc.org/articles/PMC9363492; pdf:https://europepmc.org/articles/PMC9363492?pdf=render" }, - { - "id": "37526977", - "doi": "https://doi.org/10.5830/cvja-2023-037", - "title": "Yield of family screening in dilated cardiomyopathy within low-income setting: Tanzanian experience.", - "authorString": "Fundikira LS, Julius J, Chillo P, Mayala H, Kifai E, van Laake LW, Kamuhabwa A, Kwesigabo G, Asselbergs FW.", - "authorAffiliations": "", - "journalTitle": "Cardiovascular journal of Africa", - "pubYear": "2023", - "date": "2023-07-25", - "isOpenAccess": "N", - "keywords": "Screening; Dilated cardiomyopathy; First\u2010degree Relatives", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Dilated cardiomyopathy (DCM) is often familial and screening of relatives is recommended. However, studies on the yield of screening are scarce in developing countries.

Aim

The aim of the study was to identify and characterise First-degree relatives of patients with DCM in Tanzania.

Methods

We recruited first-degree relatives of 57 DCM patients. DCM in the relatives was diagnosed using the 2016 revised definition by the European Society of Cardiology working group on myocardial and pericardial diseases.

Results

We screened 120 first-degree relatives. All were asymptomatic (100%) with a median age of 39.0 years (29.5-49.0), slightly over a half (53.3%) were females and 17 (14.1%) were found to have previously unknown DCM. The mean (\u00b1 SD) indexed left ventricular end-diastolic volume was significantly higher in relatives with DCM (71 \u00b1 11.5 ml) compared to relatives without DCM (50 \u00b1 11.5) (p = 0.001).

Conclusion

First-degree relatives of patients with DCM are at risk of developing asymptomatic DCM at a young age.", - "laySummary": "", - "urls": "doi:https://doi.org/10.5830/CVJA-2023-037" - }, { "id": "29938349", "doi": "https://doi.org/10.1007/s11892-018-1021-5", @@ -14381,6 +14364,23 @@ "laySummary": "", "urls": "pdf:https://link.springer.com/content/pdf/10.1007/s11892-018-1021-5.pdf; doi:https://doi.org/10.1007/s11892-018-1021-5; html:https://europepmc.org/articles/PMC6015804; pdf:https://europepmc.org/articles/PMC6015804?pdf=render" }, + { + "id": "37526977", + "doi": "https://doi.org/10.5830/cvja-2023-037", + "title": "Yield of family screening in dilated cardiomyopathy within low-income setting: Tanzanian experience.", + "authorString": "Fundikira LS, Julius J, Chillo P, Mayala H, Kifai E, van Laake LW, Kamuhabwa A, Kwesigabo G, Asselbergs FW.", + "authorAffiliations": "", + "journalTitle": "Cardiovascular journal of Africa", + "pubYear": "2023", + "date": "2023-07-25", + "isOpenAccess": "N", + "keywords": "Screening; Dilated cardiomyopathy; First\u2010degree Relatives", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Dilated cardiomyopathy (DCM) is often familial and screening of relatives is recommended. However, studies on the yield of screening are scarce in developing countries.

Aim

The aim of the study was to identify and characterise First-degree relatives of patients with DCM in Tanzania.

Methods

We recruited first-degree relatives of 57 DCM patients. DCM in the relatives was diagnosed using the 2016 revised definition by the European Society of Cardiology working group on myocardial and pericardial diseases.

Results

We screened 120 first-degree relatives. All were asymptomatic (100%) with a median age of 39.0 years (29.5-49.0), slightly over a half (53.3%) were females and 17 (14.1%) were found to have previously unknown DCM. The mean (\u00b1 SD) indexed left ventricular end-diastolic volume was significantly higher in relatives with DCM (71 \u00b1 11.5 ml) compared to relatives without DCM (50 \u00b1 11.5) (p = 0.001).

Conclusion

First-degree relatives of patients with DCM are at risk of developing asymptomatic DCM at a young age.", + "laySummary": "", + "urls": "doi:https://doi.org/10.5830/CVJA-2023-037" + }, { "id": "36805366", "doi": "https://doi.org/10.2196/43419", @@ -14806,23 +14806,6 @@ "laySummary": "", "urls": "pdf:https://academic.oup.com/bioinformatics/article-pdf/34/17/i857/25702307/bty605.pdf; doi:https://doi.org/10.1093/bioinformatics/bty605; html:https://europepmc.org/articles/PMC6129279; pdf:https://europepmc.org/articles/PMC6129279?pdf=render" }, - { - "id": "37907891", - "doi": "https://doi.org/10.1186/s12888-023-05217-6", - "title": "Association between 5-min Apgar score and attention deficit hyperactivity disorder: a Scotland-wide record linkage study of 758,423 school children.", - "authorString": "Bala JJ, Bala JD, Pell JP, Fleming M.", - "authorAffiliations": "", - "journalTitle": "BMC psychiatry", - "pubYear": "2023", - "date": "2023-10-31", - "isOpenAccess": "Y", - "keywords": "attention deficit disorder with hyperactivity; Cohort studies; Education; Medical Record Linkage; Apgar Score", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Attention-deficit hyperactivity disorder (ADHD) affects around 1 in 20 children and is associated with life-long sequelae. Previous studies of the association between Apgar score and ADHD have reported inconsistent findings.

Methods

Record linkage of maternity, prescribing and school pupil census databases was used to conduct a population e-cohort study of singleton children born in Scotland and attending school in Scotland at any point between 2009 and 2013. Binary logistic regression analysis was used to investigate the association between 5-min Apgar score and treated ADHD adjusting for sociodemographic and maternity confounders.

Results

Of the 758,423 children, 7,292 (0.96%) received ADHD medication. The results suggested a potential dose-response relationship between Apgar score and treated ADHD independent of confounders. Referent to an Apgar score of 10, risk of treated ADHD was higher for scores of 0-3 (adjusted OR 1.76, 95% CI 1.32-2.34), 4-6 (adjusted OR 1.50, 95% CI 1.21-1.86) and even 7-9 (adjusted OR 1.26, 95% CI 1.18-1.36) which are traditionally considered within the normal range.

Conclusions

In addition to reinforcing the need to maximise Apgar score through good obstetric practice, the findings suggest that Apgar score may be useful in predicting future risk of ADHD and therefore facilitating early diagnosis and treatment.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1186/s12888-023-05217-6; html:https://europepmc.org/articles/PMC10619264; pdf:https://europepmc.org/articles/PMC10619264?pdf=render" - }, { "id": "34135032", "doi": "https://doi.org/10.1136/bmjopen-2020-043906", @@ -14841,21 +14824,21 @@ "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/11/6/e043906.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-043906; html:https://europepmc.org/articles/PMC8211043; pdf:https://europepmc.org/articles/PMC8211043?pdf=render" }, { - "id": "37657941", - "doi": "https://doi.org/10.1212/wnl.0000000000207777", - "title": "Exploring the Role of Plasma Lipids and Statin Interventions on Multiple Sclerosis Risk and Severity: A Mendelian Randomization Study.", - "authorString": "Almramhi MM, Finan C, Storm CS, Schmidt AF, Kia DA, Coneys R, Chopade S, Hingorani AD, Wood NW.", + "id": "37907891", + "doi": "https://doi.org/10.1186/s12888-023-05217-6", + "title": "Association between 5-min Apgar score and attention deficit hyperactivity disorder: a Scotland-wide record linkage study of 758,423 school children.", + "authorString": "Bala JJ, Bala JD, Pell JP, Fleming M.", "authorAffiliations": "", - "journalTitle": "Neurology", + "journalTitle": "BMC psychiatry", "pubYear": "2023", - "date": "2023-09-01", + "date": "2023-10-31", "isOpenAccess": "Y", - "keywords": "", + "keywords": "attention deficit disorder with hyperactivity; Cohort studies; Education; Medical Record Linkage; Apgar Score", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Background and objectives

There has been considerable interest in statins because of their pleiotropic effects beyond their lipid-lowering properties. Many of these pleiotropic effects are predominantly ascribed to Rho small guanosine triphosphatases (Rho GTPases) proteins. We aimed to genetically investigate the role of lipids and statin interventions on multiple sclerosis (MS) risk and severity.

Method

We used two-sample Mendelian randomization (MR) to investigate (1) the causal role of genetically mimic both cholesterol-dependent (through low-density lipoprotein cholesterol (LDL-C) and cholesterol biosynthesis pathway) and cholesterol-independent (through Rho GTPases) effects of statins on MS risk and MS severity, (2) the causal link between lipids (high-density lipoprotein cholesterol [HDL-C] and triglycerides [TG]) levels and MS risk and severity, and (3) the reverse causation between lipid fractions and MS risk. We used summary statistics from the Global Lipids Genetics Consortium (GLGC), eQTLGen Consortium, and the International MS Genetics Consortium (IMSGC) for lipids, expression quantitative trait loci, and MS, respectively (GLGC: n = 188,577; eQTLGen: n = 31,684; IMSGC (MS risk): n = 41,505; IMSGC (MS severity): n = 7,069).

Results

The results of MR using the inverse-variance weighted method show that genetically predicted RAC2, a member of cholesterol-independent pathway (OR 0.86 [95% CI 0.78-0.95], p-value 3.80E-03), is implicated causally in reducing MS risk. We found no evidence for the causal role of LDL-C and the member of cholesterol biosynthesis pathway on MS risk. The MR results also show that lifelong higher HDL-C (OR 1.14 [95% CI 1.04-1.26], p-value 7.94E-03) increases MS risk but TG was not. Furthermore, we found no evidence for the causal role of lipids and genetically mimicked statins on MS severity. There is no evidence of reverse causation between MS risk and lipids.

Discussion

Evidence from this study suggests that RAC2 is a genetic modifier of MS risk. Because RAC2 has been reported to mediate some of the pleiotropic effects of statins, we suggest that statins may reduce MS risk through a cholesterol-independent pathway (that is, RAC2-related mechanism(s)). MR analyses also support a causal effect of HDL-C on MS risk.", + "abstract": "

Background

Attention-deficit hyperactivity disorder (ADHD) affects around 1 in 20 children and is associated with life-long sequelae. Previous studies of the association between Apgar score and ADHD have reported inconsistent findings.

Methods

Record linkage of maternity, prescribing and school pupil census databases was used to conduct a population e-cohort study of singleton children born in Scotland and attending school in Scotland at any point between 2009 and 2013. Binary logistic regression analysis was used to investigate the association between 5-min Apgar score and treated ADHD adjusting for sociodemographic and maternity confounders.

Results

Of the 758,423 children, 7,292 (0.96%) received ADHD medication. The results suggested a potential dose-response relationship between Apgar score and treated ADHD independent of confounders. Referent to an Apgar score of 10, risk of treated ADHD was higher for scores of 0-3 (adjusted OR 1.76, 95% CI 1.32-2.34), 4-6 (adjusted OR 1.50, 95% CI 1.21-1.86) and even 7-9 (adjusted OR 1.26, 95% CI 1.18-1.36) which are traditionally considered within the normal range.

Conclusions

In addition to reinforcing the need to maximise Apgar score through good obstetric practice, the findings suggest that Apgar score may be useful in predicting future risk of ADHD and therefore facilitating early diagnosis and treatment.", "laySummary": "", - "urls": "pdf:https://n.neurology.org/content/neurology/early/2023/09/01/WNL.0000000000207777.full.pdf; doi:https://doi.org/10.1212/WNL.0000000000207777; html:https://europepmc.org/articles/PMC10624499; pdf:https://europepmc.org/articles/PMC10624499?pdf=render" + "urls": "doi:https://doi.org/10.1186/s12888-023-05217-6; html:https://europepmc.org/articles/PMC10619264; pdf:https://europepmc.org/articles/PMC10619264?pdf=render" }, { "id": "37042240", @@ -14891,6 +14874,23 @@ "laySummary": "", "urls": "pdf:https://jech.bmj.com/content/jech/72/10/896.full.pdf; doi:https://doi.org/10.1136/jech-2017-210370; html:https://europepmc.org/articles/PMC6161658; pdf:https://europepmc.org/articles/PMC6161658?pdf=render" }, + { + "id": "37657941", + "doi": "https://doi.org/10.1212/wnl.0000000000207777", + "title": "Exploring the Role of Plasma Lipids and Statin Interventions on Multiple Sclerosis Risk and Severity: A Mendelian Randomization Study.", + "authorString": "Almramhi MM, Finan C, Storm CS, Schmidt AF, Kia DA, Coneys R, Chopade S, Hingorani AD, Wood NW.", + "authorAffiliations": "", + "journalTitle": "Neurology", + "pubYear": "2023", + "date": "2023-09-01", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background and objectives

There has been considerable interest in statins because of their pleiotropic effects beyond their lipid-lowering properties. Many of these pleiotropic effects are predominantly ascribed to Rho small guanosine triphosphatases (Rho GTPases) proteins. We aimed to genetically investigate the role of lipids and statin interventions on multiple sclerosis (MS) risk and severity.

Method

We used two-sample Mendelian randomization (MR) to investigate (1) the causal role of genetically mimic both cholesterol-dependent (through low-density lipoprotein cholesterol (LDL-C) and cholesterol biosynthesis pathway) and cholesterol-independent (through Rho GTPases) effects of statins on MS risk and MS severity, (2) the causal link between lipids (high-density lipoprotein cholesterol [HDL-C] and triglycerides [TG]) levels and MS risk and severity, and (3) the reverse causation between lipid fractions and MS risk. We used summary statistics from the Global Lipids Genetics Consortium (GLGC), eQTLGen Consortium, and the International MS Genetics Consortium (IMSGC) for lipids, expression quantitative trait loci, and MS, respectively (GLGC: n = 188,577; eQTLGen: n = 31,684; IMSGC (MS risk): n = 41,505; IMSGC (MS severity): n = 7,069).

Results

The results of MR using the inverse-variance weighted method show that genetically predicted RAC2, a member of cholesterol-independent pathway (OR 0.86 [95% CI 0.78-0.95], p-value 3.80E-03), is implicated causally in reducing MS risk. We found no evidence for the causal role of LDL-C and the member of cholesterol biosynthesis pathway on MS risk. The MR results also show that lifelong higher HDL-C (OR 1.14 [95% CI 1.04-1.26], p-value 7.94E-03) increases MS risk but TG was not. Furthermore, we found no evidence for the causal role of lipids and genetically mimicked statins on MS severity. There is no evidence of reverse causation between MS risk and lipids.

Discussion

Evidence from this study suggests that RAC2 is a genetic modifier of MS risk. Because RAC2 has been reported to mediate some of the pleiotropic effects of statins, we suggest that statins may reduce MS risk through a cholesterol-independent pathway (that is, RAC2-related mechanism(s)). MR analyses also support a causal effect of HDL-C on MS risk.", + "laySummary": "", + "urls": "pdf:https://n.neurology.org/content/neurology/early/2023/09/01/WNL.0000000000207777.full.pdf; doi:https://doi.org/10.1212/WNL.0000000000207777; html:https://europepmc.org/articles/PMC10624499; pdf:https://europepmc.org/articles/PMC10624499?pdf=render" + }, { "id": "36620207", "doi": "https://doi.org/10.3389/fphys.2022.1089343", @@ -14959,23 +14959,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.2196/14306; doi:https://doi.org/10.2196/14306; html:https://europepmc.org/articles/PMC7199134" }, - { - "id": "37859783", - "doi": "https://doi.org/10.1136/bmjmed-2023-000554", - "title": "Performance of polygenic risk scores in screening, prediction, and risk stratification: secondary analysis of data in the Polygenic Score Catalog.", - "authorString": "Hingorani AD, Gratton J, Finan C, Schmidt AF, Patel R, Sofat R, Kuan V, Langenberg C, Hemingway H, Morris JK, Wald NJ.", - "authorAffiliations": "", - "journalTitle": "BMJ medicine", - "pubYear": "2023", - "date": "2023-10-17", - "isOpenAccess": "Y", - "keywords": "Public Health; Preventive Medicine", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Objective

To clarify the performance of polygenic risk scores in population screening, individual risk prediction, and population risk stratification.

Design

Secondary analysis of data in the Polygenic Score Catalog.

Setting

Polygenic Score Catalog, April 2022. Secondary analysis of 3915 performance metric estimates for 926 polygenic risk scores for 310 diseases to generate estimates of performance in population screening, individual risk, and population risk stratification.

Participants

Individuals contributing to the published studies in the Polygenic Score Catalog.

Main outcome measures

Detection rate for a 5% false positive rate (DR5) and the population odds of becoming affected given a positive result; individual odds of becoming affected for a person with a particular polygenic score; and odds of becoming affected for groups of individuals in different portions of a polygenic risk score distribution. Coronary artery disease and breast cancer were used as illustrative examples.

Results

For performance in population screening, median DR5 for all polygenic risk scores and all diseases studied was 11% (interquartile range 8-18%). Median DR5 was 12% (9-19%) for polygenic risk scores for coronary artery disease and 10% (9-12%) for breast cancer. The population odds of becoming affected given a positive results were 1:8 for coronary artery disease and 1:21 for breast cancer, with background 10\u2009year odds of 1:19 and 1:41, respectively, which are typical for these diseases at age 50. For individual risk prediction, the corresponding 10\u2009year odds of becoming affected for individuals aged 50 with a polygenic risk score at the 2.5th, 25th, 75th, and 97.5th centiles were 1:54, 1:29, 1:15, and 1:8 for coronary artery disease and 1:91, 1:56, 1:34, and 1:21 for breast cancer. In terms of population risk stratification, at age 50, the risk of coronary artery disease was divided into five groups, with 10\u2009year odds of 1:41 and 1:11 for the lowest and highest quintile groups, respectively. The 10\u2009year odds was 1:7 for the upper 2.5% of the polygenic risk score distribution for coronary artery disease, a group that contributed 7% of cases. The corresponding estimates for breast cancer were 1:72 and 1:26 for the lowest and highest quintile groups, and 1:19 for the upper 2.5% of the distribution, which contributed 6% of cases.

Conclusion

Polygenic risk scores performed poorly in population screening, individual risk prediction, and population risk stratification. Strong claims about the effect of polygenic risk scores on healthcare seem to be disproportionate to their performance.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1136/bmjmed-2023-000554; html:https://europepmc.org/articles/PMC10582890; pdf:https://europepmc.org/articles/PMC10582890?pdf=render" - }, { "id": "33780550", "doi": "https://doi.org/10.1111/anae.15457", @@ -14993,6 +14976,23 @@ "laySummary": "", "urls": "pdf:https://cronfa.swan.ac.uk/Record/cronfa56616/Download/56616__19761__8c6edaf906b846a69c8b19bdb94d015d.pdf; doi:https://doi.org/10.1111/anae.15457" }, + { + "id": "37859783", + "doi": "https://doi.org/10.1136/bmjmed-2023-000554", + "title": "Performance of polygenic risk scores in screening, prediction, and risk stratification: secondary analysis of data in the Polygenic Score Catalog.", + "authorString": "Hingorani AD, Gratton J, Finan C, Schmidt AF, Patel R, Sofat R, Kuan V, Langenberg C, Hemingway H, Morris JK, Wald NJ.", + "authorAffiliations": "", + "journalTitle": "BMJ medicine", + "pubYear": "2023", + "date": "2023-10-17", + "isOpenAccess": "Y", + "keywords": "Public Health; Preventive Medicine", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Objective

To clarify the performance of polygenic risk scores in population screening, individual risk prediction, and population risk stratification.

Design

Secondary analysis of data in the Polygenic Score Catalog.

Setting

Polygenic Score Catalog, April 2022. Secondary analysis of 3915 performance metric estimates for 926 polygenic risk scores for 310 diseases to generate estimates of performance in population screening, individual risk, and population risk stratification.

Participants

Individuals contributing to the published studies in the Polygenic Score Catalog.

Main outcome measures

Detection rate for a 5% false positive rate (DR5) and the population odds of becoming affected given a positive result; individual odds of becoming affected for a person with a particular polygenic score; and odds of becoming affected for groups of individuals in different portions of a polygenic risk score distribution. Coronary artery disease and breast cancer were used as illustrative examples.

Results

For performance in population screening, median DR5 for all polygenic risk scores and all diseases studied was 11% (interquartile range 8-18%). Median DR5 was 12% (9-19%) for polygenic risk scores for coronary artery disease and 10% (9-12%) for breast cancer. The population odds of becoming affected given a positive results were 1:8 for coronary artery disease and 1:21 for breast cancer, with background 10\u2009year odds of 1:19 and 1:41, respectively, which are typical for these diseases at age 50. For individual risk prediction, the corresponding 10\u2009year odds of becoming affected for individuals aged 50 with a polygenic risk score at the 2.5th, 25th, 75th, and 97.5th centiles were 1:54, 1:29, 1:15, and 1:8 for coronary artery disease and 1:91, 1:56, 1:34, and 1:21 for breast cancer. In terms of population risk stratification, at age 50, the risk of coronary artery disease was divided into five groups, with 10\u2009year odds of 1:41 and 1:11 for the lowest and highest quintile groups, respectively. The 10\u2009year odds was 1:7 for the upper 2.5% of the polygenic risk score distribution for coronary artery disease, a group that contributed 7% of cases. The corresponding estimates for breast cancer were 1:72 and 1:26 for the lowest and highest quintile groups, and 1:19 for the upper 2.5% of the distribution, which contributed 6% of cases.

Conclusion

Polygenic risk scores performed poorly in population screening, individual risk prediction, and population risk stratification. Strong claims about the effect of polygenic risk scores on healthcare seem to be disproportionate to their performance.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1136/bmjmed-2023-000554; html:https://europepmc.org/articles/PMC10582890; pdf:https://europepmc.org/articles/PMC10582890?pdf=render" + }, { "id": "35985824", "doi": "https://doi.org/10.1212/wnl.0000000000201064", @@ -15095,23 +15095,6 @@ "laySummary": "", "urls": "html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9047242; doi:https://doi.org/10.1093/infdis/jiac146; html:https://europepmc.org/articles/PMC9047242; pdf:https://europepmc.org/articles/PMC9047242?pdf=render" }, - { - "id": "38740716", - "doi": "https://doi.org/10.1007/s40266-024-01116-x", - "title": "Associations Between Midlife Anticholinergic Medication Use and Subsequent Cognitive Decline: A British Birth Cohort Study.", - "authorString": "Rawle MJ, Lau WCY, Gonzalez-Izquierdo A, Patalay P, Richards M, Davis D.", - "authorAffiliations": "", - "journalTitle": "Drugs & aging", - "pubYear": "2024", - "date": "2024-05-13", - "isOpenAccess": "N", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Anticholinergic medication use is associated with cognitive decline and incident dementia. Our study, a prospective birth\u00a0cohort\u00a0analysis, aimed to determine if repeated exposure to anticholinergic medications\u00a0was associated with greater decline, and whether decline was reversed with medication reduction.

Methods

From the Medical Research Council (MRC) National Survey of Health and Development, a British birth cohort with all participants born in a single week of March 1946, we quantified anticholinergic exposure between ages 53 and 69 years using the Anticholinergic Cognitive Burden Scale (ACBS). We used multinomial regression to estimate associations with global cognition, quantified by\u00a0the Addenbrooke's Cognitive Examination, 3rd Edition (ACE-III). Longitudinal associations between ACBS and cognitive test results (Verbal memory quantified\u00a0by the\u00a0Word Learning Test [WLT], and processing speed quantified by the\u00a0Timed Letter Search Task [TLST]) at three time points (age 53, 60-64 and 69) were assessed using mixed and fixed effects linear regression models. Analyses were adjusted for sex, childhood cognition, education, chronic disease count and severity, and mental health symptoms.

Results

Anticholinergic exposure was associated cross-sectionally with lower ACE-III scores at age 69, with the greatest effects in those with high exposure at ages 60-64 (mean difference -\u20092.34, 95% confidence interval [CI] -\u20093.51 to -\u20091.17). Longitudinally, both mild-moderate and high ACBS scores were linked to lower WLT scores, again with high exposure showing larger effects (mean difference with contemporaneous exposure -\u20090.90, 95% CI -\u20091.63 to -\u20090.17; mean difference with lagged exposure -\u20091.53, 95% CI -\u20092.43 to -\u20090.64). Associations remained in fixed effects models (mean difference with contemporaneous exposure -1.78, 95% CI -2.85 to -\u20090.71; mean difference with lagged exposure -\u20092.23, 95% CI -\u20093.33 to -\u20091.13). Associations with TLST were noted only in isolated contemporaneous exposure (mean difference -\u200913.14, 95% CI -\u200919.04 to -\u20097.23; p\u00a0<\u00a00.01).

Conclusions

Anticholinergic exposure throughout mid and later life was associated with lower cognitive function. Reduced processing speed was associated only with contemporaneous anticholinergic medication use, and not historical use. Associations with lower verbal recall were evident with both historical and contemporaneous use of anticholinergic medication, and associations with historical use persisted in individuals even when their anticholinergic medication use decreased over the course of the study.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1007/s40266-024-01116-x" - }, { "id": "36763324", "doi": "https://doi.org/10.1007/s12687-023-00635-1", @@ -15129,6 +15112,23 @@ "laySummary": "", "urls": "pdf:https://link.springer.com/content/pdf/10.1007/s12687-023-00635-1.pdf; doi:https://doi.org/10.1007/s12687-023-00635-1; html:https://europepmc.org/articles/PMC10576689; pdf:https://europepmc.org/articles/PMC10576689?pdf=render" }, + { + "id": "38740716", + "doi": "https://doi.org/10.1007/s40266-024-01116-x", + "title": "Associations Between Midlife Anticholinergic Medication Use and Subsequent Cognitive Decline: A British Birth Cohort Study.", + "authorString": "Rawle MJ, Lau WCY, Gonzalez-Izquierdo A, Patalay P, Richards M, Davis D.", + "authorAffiliations": "", + "journalTitle": "Drugs & aging", + "pubYear": "2024", + "date": "2024-05-13", + "isOpenAccess": "N", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Anticholinergic medication use is associated with cognitive decline and incident dementia. Our study, a prospective birth\u00a0cohort\u00a0analysis, aimed to determine if repeated exposure to anticholinergic medications\u00a0was associated with greater decline, and whether decline was reversed with medication reduction.

Methods

From the Medical Research Council (MRC) National Survey of Health and Development, a British birth cohort with all participants born in a single week of March 1946, we quantified anticholinergic exposure between ages 53 and 69 years using the Anticholinergic Cognitive Burden Scale (ACBS). We used multinomial regression to estimate associations with global cognition, quantified by\u00a0the Addenbrooke's Cognitive Examination, 3rd Edition (ACE-III). Longitudinal associations between ACBS and cognitive test results (Verbal memory quantified\u00a0by the\u00a0Word Learning Test [WLT], and processing speed quantified by the\u00a0Timed Letter Search Task [TLST]) at three time points (age 53, 60-64 and 69) were assessed using mixed and fixed effects linear regression models. Analyses were adjusted for sex, childhood cognition, education, chronic disease count and severity, and mental health symptoms.

Results

Anticholinergic exposure was associated cross-sectionally with lower ACE-III scores at age 69, with the greatest effects in those with high exposure at ages 60-64 (mean difference -\u20092.34, 95% confidence interval [CI] -\u20093.51 to -\u20091.17). Longitudinally, both mild-moderate and high ACBS scores were linked to lower WLT scores, again with high exposure showing larger effects (mean difference with contemporaneous exposure -\u20090.90, 95% CI -\u20091.63 to -\u20090.17; mean difference with lagged exposure -\u20091.53, 95% CI -\u20092.43 to -\u20090.64). Associations remained in fixed effects models (mean difference with contemporaneous exposure -1.78, 95% CI -2.85 to -\u20090.71; mean difference with lagged exposure -\u20092.23, 95% CI -\u20093.33 to -\u20091.13). Associations with TLST were noted only in isolated contemporaneous exposure (mean difference -\u200913.14, 95% CI -\u200919.04 to -\u20097.23; p\u00a0<\u00a00.01).

Conclusions

Anticholinergic exposure throughout mid and later life was associated with lower cognitive function. Reduced processing speed was associated only with contemporaneous anticholinergic medication use, and not historical use. Associations with lower verbal recall were evident with both historical and contemporaneous use of anticholinergic medication, and associations with historical use persisted in individuals even when their anticholinergic medication use decreased over the course of the study.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1007/s40266-024-01116-x" + }, { "id": "34716166", "doi": "https://doi.org/10.1136/bmjopen-2021-053268", @@ -15316,40 +15316,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.7554/elife.78427; doi:https://doi.org/10.7554/eLife.78427; html:https://europepmc.org/articles/PMC9596156; pdf:https://europepmc.org/articles/PMC9596156?pdf=render" }, - { - "id": "35776101", - "doi": "https://doi.org/10.1093/ije/dyac140", - "title": "Incremental value of risk factor variability for cardiovascular risk prediction in individuals with type 2 diabetes: results from UK primary care electronic health records.", - "authorString": "Xu Z, Arnold M, Sun L, Stevens D, Chung R, Ip S, Barrett J, Kaptoge S, Pennells L, Di Angelantonio E, Wood AM.", - "authorAffiliations": "", - "journalTitle": "International journal of epidemiology", - "pubYear": "2022", - "date": "2022-12-01", - "isOpenAccess": "Y", - "keywords": "Variability; Cardiovascular disease; Type 2 diabetes; Risk Prediction; Repeated Measurements; Electronic Health Records", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Cardiovascular disease (CVD) risk prediction models for individuals with type 2 diabetes are important tools to guide intensification of interventions for CVD prevention. We aimed to assess the added value of incorporating risk factors variability in CVD risk prediction for people with type 2 diabetes.

Methods

We used electronic health records (EHRs) data from 83\u200a910 adults with type 2 diabetes but without pre-existing CVD from the UK Clinical Practice Research Datalink for 2004-2017. Using a landmark-modelling approach, we developed and validated sex-specific Cox models, incorporating conventional predictors and trajectories plus variability of systolic blood pressure (SBP), total and high-density lipoprotein (HDL) cholesterol, and glycated haemoglobin (HbA1c). Such models were compared against simpler models using single last observed values or means.

Results

The standard deviations (SDs) of SBP, HDL cholesterol and HbA1c were associated with higher CVD risk (P\u2009<\u20090.05). Models incorporating trajectories and variability of continuous predictors demonstrated improvement in risk discrimination (C-index\u2009=\u20090.659, 95% CI: 0.654-0.663) as compared with using last observed values (C-index\u2009=\u20090.651, 95% CI: 0.646-0.656) or means (C-index\u2009=\u20090.650, 95% CI: 0.645-0.655). Inclusion of SDs of SBP yielded the greatest improvement in discrimination (C-index increase\u2009=\u20090.005, 95% CI: 0.004-0.007) in comparison to incorporating SDs of total cholesterol (C-index\u2009increase =\u20090.002, 95% CI: 0.000-0.003), HbA1c (C-index increase\u2009=\u20090.002, 95% CI: 0.000-0.003) or HDL cholesterol (C-index\u2009increase=\u20090.003, 95% CI: 0.002-0.005).

Conclusion

Incorporating variability of predictors from EHRs provides a modest improvement in CVD risk discrimination for individuals with type 2 diabetes. Given that repeat measures are readily available in EHRs especially for regularly monitored patients with diabetes, this improvement could easily be achieved.", - "laySummary": "", - "urls": "pdf:https://academic.oup.com/ije/advance-article-pdf/doi/10.1093/ije/dyac140/45030523/dyac140.pdf; doi:https://doi.org/10.1093/ije/dyac140; html:https://europepmc.org/articles/PMC9749723; pdf:https://europepmc.org/articles/PMC9749723?pdf=render" - }, - { - "id": "38563665", - "doi": "https://doi.org/10.1148/radiol.232455", - "title": "Left Ventricular Trabeculations at Cardiac MRI: Reference Ranges and Association with Cardiovascular Risk Factors in UK Biobank.", - "authorString": "Aung N, Bartoli A, Rauseo E, Cortaredona S, Sanghvi MM, Fournel J, Ghattas B, Khanji MY, Petersen SE, Jacquier A.", - "authorAffiliations": "", - "journalTitle": "Radiology", - "pubYear": "2024", - "date": "2024-04-01", - "isOpenAccess": "N", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Background The extent of left ventricular (LV) trabeculation and its relationship with cardiovascular (CV) risk factors is unclear. Purpose To apply automated segmentation to UK Biobank cardiac MRI scans to (a) assess the association between individual characteristics and CV risk factors and trabeculated LV mass (LVM) and (b) establish normal reference ranges in a selected group of healthy UK Biobank participants. Materials and Methods In this cross-sectional secondary analysis, prospectively collected data from the UK Biobank (2006 to 2010) were retrospectively analyzed. Automated segmentation of trabeculations was performed using a deep learning algorithm. After excluding individuals with known CV diseases, White adults without CV risk factors (reference group) and those with preexisting CV risk factors (hypertension, hyperlipidemia, diabetes mellitus, or smoking) (exposed group) were compared. Multivariable regression models, adjusted for potential confounders (age, sex, and height), were fitted to evaluate the associations between individual characteristics and CV risk factors and trabeculated LVM. Results Of 43\u2009038 participants (mean age, 64 years \u00b1 8 [SD]; 22\u2009360 women), 28\u2009672 individuals (mean age, 66 years \u00b1 7; 14\u2009918 men) were included in the exposed group, and 7384 individuals (mean age, 60 years \u00b1 7; 4729 women) were included in the reference group. Higher body mass index (BMI) (\u03b2 = 0.66 [95% CI: 0.63, 0.68]; P < .001), hypertension (\u03b2 = 0.42 [95% CI: 0.36, 0.48]; P < .001), and higher physical activity level (\u03b2 = 0.15 [95% CI: 0.12, 0.17]; P < .001) were associated with higher trabeculated LVM. In the reference group, the median trabeculated LVM was 6.3 g (IQR, 4.7-8.5 g) for men and 4.6 g (IQR, 3.4-6.0 g) for women. Median trabeculated LVM decreased with age for men from 6.5 g (IQR, 4.8-8.7 g) at age 45-50 years to 5.9 g (IQR, 4.3-7.8 g) at age 71-80 years (P = .03). Conclusion Higher trabeculated LVM was observed with hypertension, higher BMI, and higher physical activity level. Age- and sex-specific reference ranges of trabeculated LVM in a healthy middle-aged White population were established. \u00a9 RSNA, 2024 Supplemental material is available for this article. See also the editorial by Kawel-Boehm in this issue.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1148/radiol.232455" - }, { "id": "34161326", "doi": "https://doi.org/10.1371/journal.pcbi.1009121", @@ -15367,6 +15333,23 @@ "laySummary": "", "urls": "pdf:https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1009121&type=printable; doi:https://doi.org/10.1371/journal.pcbi.1009121; html:https://europepmc.org/articles/PMC8259985; pdf:https://europepmc.org/articles/PMC8259985?pdf=render" }, + { + "id": "35776101", + "doi": "https://doi.org/10.1093/ije/dyac140", + "title": "Incremental value of risk factor variability for cardiovascular risk prediction in individuals with type 2 diabetes: results from UK primary care electronic health records.", + "authorString": "Xu Z, Arnold M, Sun L, Stevens D, Chung R, Ip S, Barrett J, Kaptoge S, Pennells L, Di Angelantonio E, Wood AM.", + "authorAffiliations": "", + "journalTitle": "International journal of epidemiology", + "pubYear": "2022", + "date": "2022-12-01", + "isOpenAccess": "Y", + "keywords": "Variability; Cardiovascular disease; Type 2 diabetes; Risk Prediction; Repeated Measurements; Electronic Health Records", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Cardiovascular disease (CVD) risk prediction models for individuals with type 2 diabetes are important tools to guide intensification of interventions for CVD prevention. We aimed to assess the added value of incorporating risk factors variability in CVD risk prediction for people with type 2 diabetes.

Methods

We used electronic health records (EHRs) data from 83\u200a910 adults with type 2 diabetes but without pre-existing CVD from the UK Clinical Practice Research Datalink for 2004-2017. Using a landmark-modelling approach, we developed and validated sex-specific Cox models, incorporating conventional predictors and trajectories plus variability of systolic blood pressure (SBP), total and high-density lipoprotein (HDL) cholesterol, and glycated haemoglobin (HbA1c). Such models were compared against simpler models using single last observed values or means.

Results

The standard deviations (SDs) of SBP, HDL cholesterol and HbA1c were associated with higher CVD risk (P\u2009<\u20090.05). Models incorporating trajectories and variability of continuous predictors demonstrated improvement in risk discrimination (C-index\u2009=\u20090.659, 95% CI: 0.654-0.663) as compared with using last observed values (C-index\u2009=\u20090.651, 95% CI: 0.646-0.656) or means (C-index\u2009=\u20090.650, 95% CI: 0.645-0.655). Inclusion of SDs of SBP yielded the greatest improvement in discrimination (C-index increase\u2009=\u20090.005, 95% CI: 0.004-0.007) in comparison to incorporating SDs of total cholesterol (C-index\u2009increase =\u20090.002, 95% CI: 0.000-0.003), HbA1c (C-index increase\u2009=\u20090.002, 95% CI: 0.000-0.003) or HDL cholesterol (C-index\u2009increase=\u20090.003, 95% CI: 0.002-0.005).

Conclusion

Incorporating variability of predictors from EHRs provides a modest improvement in CVD risk discrimination for individuals with type 2 diabetes. Given that repeat measures are readily available in EHRs especially for regularly monitored patients with diabetes, this improvement could easily be achieved.", + "laySummary": "", + "urls": "pdf:https://academic.oup.com/ije/advance-article-pdf/doi/10.1093/ije/dyac140/45030523/dyac140.pdf; doi:https://doi.org/10.1093/ije/dyac140; html:https://europepmc.org/articles/PMC9749723; pdf:https://europepmc.org/articles/PMC9749723?pdf=render" + }, { "id": "36715329", "doi": "https://doi.org/10.1093/bjd/ljac090", @@ -15384,6 +15367,23 @@ "laySummary": "", "urls": "pdf:https://cronfa.swan.ac.uk/Record/cronfa62055/Download/62055__26915__ae11794993454389b6ceddbb7f50caaa.pdf; doi:https://doi.org/10.1093/bjd/ljac090" }, + { + "id": "38563665", + "doi": "https://doi.org/10.1148/radiol.232455", + "title": "Left Ventricular Trabeculations at Cardiac MRI: Reference Ranges and Association with Cardiovascular Risk Factors in UK Biobank.", + "authorString": "Aung N, Bartoli A, Rauseo E, Cortaredona S, Sanghvi MM, Fournel J, Ghattas B, Khanji MY, Petersen SE, Jacquier A.", + "authorAffiliations": "", + "journalTitle": "Radiology", + "pubYear": "2024", + "date": "2024-04-01", + "isOpenAccess": "N", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Background The extent of left ventricular (LV) trabeculation and its relationship with cardiovascular (CV) risk factors is unclear. Purpose To apply automated segmentation to UK Biobank cardiac MRI scans to (a) assess the association between individual characteristics and CV risk factors and trabeculated LV mass (LVM) and (b) establish normal reference ranges in a selected group of healthy UK Biobank participants. Materials and Methods In this cross-sectional secondary analysis, prospectively collected data from the UK Biobank (2006 to 2010) were retrospectively analyzed. Automated segmentation of trabeculations was performed using a deep learning algorithm. After excluding individuals with known CV diseases, White adults without CV risk factors (reference group) and those with preexisting CV risk factors (hypertension, hyperlipidemia, diabetes mellitus, or smoking) (exposed group) were compared. Multivariable regression models, adjusted for potential confounders (age, sex, and height), were fitted to evaluate the associations between individual characteristics and CV risk factors and trabeculated LVM. Results Of 43\u2009038 participants (mean age, 64 years \u00b1 8 [SD]; 22\u2009360 women), 28\u2009672 individuals (mean age, 66 years \u00b1 7; 14\u2009918 men) were included in the exposed group, and 7384 individuals (mean age, 60 years \u00b1 7; 4729 women) were included in the reference group. Higher body mass index (BMI) (\u03b2 = 0.66 [95% CI: 0.63, 0.68]; P < .001), hypertension (\u03b2 = 0.42 [95% CI: 0.36, 0.48]; P < .001), and higher physical activity level (\u03b2 = 0.15 [95% CI: 0.12, 0.17]; P < .001) were associated with higher trabeculated LVM. In the reference group, the median trabeculated LVM was 6.3 g (IQR, 4.7-8.5 g) for men and 4.6 g (IQR, 3.4-6.0 g) for women. Median trabeculated LVM decreased with age for men from 6.5 g (IQR, 4.8-8.7 g) at age 45-50 years to 5.9 g (IQR, 4.3-7.8 g) at age 71-80 years (P = .03). Conclusion Higher trabeculated LVM was observed with hypertension, higher BMI, and higher physical activity level. Age- and sex-specific reference ranges of trabeculated LVM in a healthy middle-aged White population were established. \u00a9 RSNA, 2024 Supplemental material is available for this article. See also the editorial by Kawel-Boehm in this issue.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1148/radiol.232455" + }, { "id": "37777816", "doi": "https://doi.org/10.1186/s13643-023-02337-8", @@ -15418,23 +15418,6 @@ "laySummary": "", "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/12/1/e049506.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-049506; html:https://europepmc.org/articles/PMC8764710; pdf:https://europepmc.org/articles/PMC8764710?pdf=render" }, - { - "id": "37840686", - "doi": "https://doi.org/10.3389/fdgth.2023.1184919", - "title": "Understanding the performance and reliability of NLP tools: a comparison of four NLP tools predicting stroke phenotypes in radiology reports.", - "authorString": "Casey A, Davidson E, Grover C, Tobin R, Grivas A, Zhang H, Schrempf P, O'Neil AQ, Lee L, Walsh M, Pellie F, Ferguson K, Cvoro V, Wu H, Whalley H, Mair G, Whiteley W, Alex B.", - "authorAffiliations": "", - "journalTitle": "Frontiers in digital health", - "pubYear": "2023", - "date": "2023-09-28", - "isOpenAccess": "Y", - "keywords": "Electronic Health Records; Natural Language Processing; Stroke Phenotype; Brain Radiology", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Natural language processing (NLP) has the potential to automate the reading of radiology reports, but there is a need to demonstrate that NLP methods are adaptable and reliable for use in real-world clinical applications.

Methods

We tested the F1 score, precision, and recall to compare NLP tools on a cohort from a study on delirium using images and radiology reports from NHS Fife and a population-based cohort (Generation Scotland) that spans multiple National Health Service health boards. We compared four off-the-shelf rule-based and neural NLP tools (namely, EdIE-R, ALARM+, ESPRESSO, and Sem-EHR) and reported on their performance for three cerebrovascular phenotypes, namely, ischaemic stroke, small vessel disease (SVD), and atrophy. Clinical experts from the EdIE-R team defined phenotypes using labelling techniques developed in the development of EdIE-R, in conjunction with an expert researcher who read underlying images.

Results

EdIE-R obtained the highest F1 score in both cohorts for ischaemic stroke, \u226593%, followed by ALARM+, \u226587%. The F1 score of ESPRESSO was \u226574%, whilst that of Sem-EHR is \u226566%, although ESPRESSO had the highest precision in both cohorts, 90% and 98%. For F1 scores for SVD, EdIE-R scored \u226598% and ALARM+ \u226590%. ESPRESSO scored lowest with \u226577% and Sem-EHR \u226581%. In NHS Fife, F1 scores for atrophy by EdIE-R and ALARM+ were 99%, dropping in Generation Scotland to 96% for EdIE-R and 91% for ALARM+. Sem-EHR performed lowest for atrophy at 89% in NHS Fife and 73% in Generation Scotland. When comparing NLP tool output with brain image reads using F1 scores, ALARM+ scored 80%, outperforming EdIE-R at 66% in ischaemic stroke. For SVD, EdIE-R performed best, scoring 84%, with Sem-EHR 82%. For atrophy, EdIE-R and both ALARM+ versions were comparable at 80%.

Conclusions

The four NLP tools show varying F1 (and precision/recall) scores across all three phenotypes, although more apparent for ischaemic stroke. If NLP tools are to be used in clinical settings, this cannot be performed \"out of the box.\" It is essential to understand the context of their development to assess whether they are suitable for the task at hand or whether further training, re-training, or modification is required to adapt tools to the target task.", - "laySummary": "", - "urls": "pdf:https://www.frontiersin.org/articles/10.3389/fdgth.2023.1184919/pdf?isPublishedV2=False; doi:https://doi.org/10.3389/fdgth.2023.1184919; html:https://europepmc.org/articles/PMC10569314; pdf:https://europepmc.org/articles/PMC10569314?pdf=render" - }, { "id": "31960476", "doi": "https://doi.org/10.1111/ppe.12627", @@ -15452,6 +15435,23 @@ "laySummary": "This study identifies children born with congenital anomalies from administrative health data. The the prevalence of congenital anomalies and prognostic outcomes for children with congenital anomalies are compared using three different code lists. The study found that the prevalence of congenital anomalies varied by code list, over time and between countries. This reflects differences in hospital coding practices and admission thresholds.", "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/ppe.12627; doi:https://doi.org/10.1111/ppe.12627; html:https://europepmc.org/articles/PMC7003968; pdf:https://europepmc.org/articles/PMC7003968?pdf=render" }, + { + "id": "37840686", + "doi": "https://doi.org/10.3389/fdgth.2023.1184919", + "title": "Understanding the performance and reliability of NLP tools: a comparison of four NLP tools predicting stroke phenotypes in radiology reports.", + "authorString": "Casey A, Davidson E, Grover C, Tobin R, Grivas A, Zhang H, Schrempf P, O'Neil AQ, Lee L, Walsh M, Pellie F, Ferguson K, Cvoro V, Wu H, Whalley H, Mair G, Whiteley W, Alex B.", + "authorAffiliations": "", + "journalTitle": "Frontiers in digital health", + "pubYear": "2023", + "date": "2023-09-28", + "isOpenAccess": "Y", + "keywords": "Electronic Health Records; Natural Language Processing; Stroke Phenotype; Brain Radiology", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Natural language processing (NLP) has the potential to automate the reading of radiology reports, but there is a need to demonstrate that NLP methods are adaptable and reliable for use in real-world clinical applications.

Methods

We tested the F1 score, precision, and recall to compare NLP tools on a cohort from a study on delirium using images and radiology reports from NHS Fife and a population-based cohort (Generation Scotland) that spans multiple National Health Service health boards. We compared four off-the-shelf rule-based and neural NLP tools (namely, EdIE-R, ALARM+, ESPRESSO, and Sem-EHR) and reported on their performance for three cerebrovascular phenotypes, namely, ischaemic stroke, small vessel disease (SVD), and atrophy. Clinical experts from the EdIE-R team defined phenotypes using labelling techniques developed in the development of EdIE-R, in conjunction with an expert researcher who read underlying images.

Results

EdIE-R obtained the highest F1 score in both cohorts for ischaemic stroke, \u226593%, followed by ALARM+, \u226587%. The F1 score of ESPRESSO was \u226574%, whilst that of Sem-EHR is \u226566%, although ESPRESSO had the highest precision in both cohorts, 90% and 98%. For F1 scores for SVD, EdIE-R scored \u226598% and ALARM+ \u226590%. ESPRESSO scored lowest with \u226577% and Sem-EHR \u226581%. In NHS Fife, F1 scores for atrophy by EdIE-R and ALARM+ were 99%, dropping in Generation Scotland to 96% for EdIE-R and 91% for ALARM+. Sem-EHR performed lowest for atrophy at 89% in NHS Fife and 73% in Generation Scotland. When comparing NLP tool output with brain image reads using F1 scores, ALARM+ scored 80%, outperforming EdIE-R at 66% in ischaemic stroke. For SVD, EdIE-R performed best, scoring 84%, with Sem-EHR 82%. For atrophy, EdIE-R and both ALARM+ versions were comparable at 80%.

Conclusions

The four NLP tools show varying F1 (and precision/recall) scores across all three phenotypes, although more apparent for ischaemic stroke. If NLP tools are to be used in clinical settings, this cannot be performed \"out of the box.\" It is essential to understand the context of their development to assess whether they are suitable for the task at hand or whether further training, re-training, or modification is required to adapt tools to the target task.", + "laySummary": "", + "urls": "pdf:https://www.frontiersin.org/articles/10.3389/fdgth.2023.1184919/pdf?isPublishedV2=False; doi:https://doi.org/10.3389/fdgth.2023.1184919; html:https://europepmc.org/articles/PMC10569314; pdf:https://europepmc.org/articles/PMC10569314?pdf=render" + }, { "id": "35139069", "doi": "https://doi.org/10.1371/journal.pcbi.1009806", @@ -15537,23 +15537,6 @@ "laySummary": "", "urls": "pdf:https://genomemedicine.biomedcentral.com/counter/pdf/10.1186/s13073-020-00822-6; doi:https://doi.org/10.1186/s13073-020-00822-6; html:https://europepmc.org/articles/PMC7790334; pdf:https://europepmc.org/articles/PMC7790334?pdf=render" }, - { - "id": "37294923", - "doi": "https://doi.org/10.1093/eurjpc/zwad192", - "title": "Incidence of 12 common cardiovascular diseases and subsequent mortality risk in the general population.", - "authorString": "Prugger C, Perier MC, Gonzalez-Izquierdo A, Hemingway H, Denaxas S, Empana JP.", - "authorAffiliations": "", - "journalTitle": "European journal of preventive cardiology", - "pubYear": "2023", - "date": "2023-10-01", - "isOpenAccess": "N", - "keywords": "Prevention; Survival analysis; Stroke; epidemiology; Coronary Heart Disease; incidence", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Incident events of cardiovascular diseases (CVDs) are heterogenous and may result in different mortality risks. Such evidence may help inform patient and physician decisions in CVD prevention and risk factor management.

Aims

This study aimed to determine the extent to which incident events of common CVD show heterogeneous associations with subsequent mortality risk in the general population.

Methods and results

Based on England-wide linked electronic health records, we established a cohort of 1 310 518 people \u226530 years of age initially free of CVD and followed up for non-fatal events of 12 common CVD and cause-specific mortality. The 12 CVDs were considered as time-varying exposures in Cox's proportional hazards models to estimate hazard rate ratios (HRRs) with 95% confidence intervals (CIs). Over the median follow-up of 4.2 years (2010-16), 81 516 non-fatal CVD, 10 906 cardiovascular deaths, and 40 843 non-cardiovascular deaths occurred. All 12 CVDs were associated with increased risk of cardiovascular mortality, with HRR (95% CI) ranging from 1.67 (1.47-1.89) for stable angina to 7.85 (6.62-9.31) for haemorrhagic stroke. All 12 CVDs were also associated with increased non-cardiovascular and all-cause mortality risk but to a lesser extent: HRR (95% CI) ranged from 1.10 (1.00-1.22) to 4.55 (4.03-5.13) and from 1.24 (1.13-1.35) to 4.92 (4.44-5.46) for transient ischaemic attack and sudden cardiac arrest, respectively.

Conclusion

Incident events of 12 common CVD show significant adverse and markedly differential associations with subsequent cardiovascular, non-cardiovascular, and all-cause mortality risk in the general population.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1093/eurjpc/zwad192" - }, { "id": "37156273", "doi": "https://doi.org/10.1016/j.jad.2023.04.138", @@ -15571,6 +15554,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.jad.2023.04.138; doi:https://doi.org/10.1016/j.jad.2023.04.138" }, + { + "id": "37294923", + "doi": "https://doi.org/10.1093/eurjpc/zwad192", + "title": "Incidence of 12 common cardiovascular diseases and subsequent mortality risk in the general population.", + "authorString": "Prugger C, Perier MC, Gonzalez-Izquierdo A, Hemingway H, Denaxas S, Empana JP.", + "authorAffiliations": "", + "journalTitle": "European journal of preventive cardiology", + "pubYear": "2023", + "date": "2023-10-01", + "isOpenAccess": "N", + "keywords": "Prevention; Survival analysis; Stroke; epidemiology; Coronary Heart Disease; incidence", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Incident events of cardiovascular diseases (CVDs) are heterogenous and may result in different mortality risks. Such evidence may help inform patient and physician decisions in CVD prevention and risk factor management.

Aims

This study aimed to determine the extent to which incident events of common CVD show heterogeneous associations with subsequent mortality risk in the general population.

Methods and results

Based on England-wide linked electronic health records, we established a cohort of 1 310 518 people \u226530 years of age initially free of CVD and followed up for non-fatal events of 12 common CVD and cause-specific mortality. The 12 CVDs were considered as time-varying exposures in Cox's proportional hazards models to estimate hazard rate ratios (HRRs) with 95% confidence intervals (CIs). Over the median follow-up of 4.2 years (2010-16), 81 516 non-fatal CVD, 10 906 cardiovascular deaths, and 40 843 non-cardiovascular deaths occurred. All 12 CVDs were associated with increased risk of cardiovascular mortality, with HRR (95% CI) ranging from 1.67 (1.47-1.89) for stable angina to 7.85 (6.62-9.31) for haemorrhagic stroke. All 12 CVDs were also associated with increased non-cardiovascular and all-cause mortality risk but to a lesser extent: HRR (95% CI) ranged from 1.10 (1.00-1.22) to 4.55 (4.03-5.13) and from 1.24 (1.13-1.35) to 4.92 (4.44-5.46) for transient ischaemic attack and sudden cardiac arrest, respectively.

Conclusion

Incident events of 12 common CVD show significant adverse and markedly differential associations with subsequent cardiovascular, non-cardiovascular, and all-cause mortality risk in the general population.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1093/eurjpc/zwad192" + }, { "id": "36654802", "doi": "https://doi.org/10.1002/lrh2.10315", @@ -16047,23 +16047,6 @@ "laySummary": "", "urls": "pdf:https://www.nature.com/articles/s41588-023-01462-3.pdf; doi:https://doi.org/10.1038/s41588-023-01462-3; html:https://europepmc.org/articles/PMC10484788; pdf:https://europepmc.org/articles/PMC10484788?pdf=render" }, - { - "id": "34481555", - "doi": "https://doi.org/10.1016/s2213-8587(21)00207-2", - "title": "Identifying adults at high-risk for change in weight and BMI in England: a longitudinal, large-scale, population-based cohort study using electronic health records.", - "authorString": "Katsoulis M, Lai AG, Diaz-Ordaz K, Gomes M, Pasea L, Banerjee A, Denaxas S, Tsilidis K, Lagiou P, Misirli G, Bhaskaran K, Wannamethee G, Dobson R, Batterham RL, Kipourou DK, Lumbers RT, Wen L, Wareham N, Langenberg C, Hemingway H.", - "authorAffiliations": "", - "journalTitle": "The lancet. Diabetes & endocrinology", - "pubYear": "2021", - "date": "2021-09-02", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Targeted obesity prevention policies would benefit from the identification of population groups with the highest risk of weight gain. The relative importance of adult age, sex, ethnicity, geographical region, and degree of social deprivation on weight gain is not known. We aimed to identify high-risk groups for changes in weight and BMI using electronic health records (EHR).

Methods

In this longitudinal, population-based cohort study we used linked EHR data from 400 primary care practices (via the Clinical Practice Research Datalink) in England, accessed via the CALIBER programme. Eligible participants were aged 18-74 years, were registered at a general practice clinic, and had BMI and weight measurements recorded between Jan 1, 1998, and June 30, 2016, during the period when they had eligible linked data with at least 1 year of follow-up time. We calculated longitudinal changes in BMI over 1, 5, and 10 years, and investigated the absolute risk and odds ratios (ORs) of transitioning between BMI categories (underweight, normal weight, overweight, obesity class 1 and 2, and severe obesity [class 3]), as defined by WHO. The associations of demographic factors with BMI transitions were estimated by use of logistic regression analysis, adjusting for baseline BMI, family history of cardiovascular disease, use of diuretics, and prevalent chronic conditions.

Findings

We included 2 092 260 eligible individuals with more than 9 million BMI measurements in our study. Young adult age was the strongest risk factor for weight gain at 1, 5, and 10 years of follow-up. Compared with the oldest age group (65-74 years), adults in the youngest age group (18-24 years) had the highest OR (4\u00b722 [95% CI 3\u00b786-4\u00b762]) and greatest absolute risk (37% vs 24%) of transitioning from normal weight to overweight or obesity at 10 years. Likewise, adults in the youngest age group with overweight or obesity at baseline were also at highest risk to transition to a higher BMI category; OR 4\u00b760 (4\u00b706-5\u00b722) and absolute risk (42% vs 18%) of transitioning from overweight to class 1 and 2 obesity, and OR 5\u00b787 (5\u00b723-6\u00b759) and absolute risk (22% vs 5%) of transitioning from class 1 and 2 obesity to class 3 obesity. Other demographic factors were consistently less strongly associated with these transitions; for example, the OR of transitioning from normal weight to overweight or obesity in people living in the most socially deprived versus least deprived areas was 1\u00b723 (1\u00b718-1\u00b727), for men versus women was 1\u00b712 (1\u00b708-1\u00b716), and for Black individuals versus White individuals was 1\u00b713 (1\u00b704-1\u00b724). We provide an open access online risk calculator, and present high-resolution obesity risk charts over a 1-year, 5-year, and 10-year follow-up period.

Interpretation

A radical shift in policy is required to focus on individuals at the highest risk of weight gain (ie, young adults aged 18-24 years) for individual-level and population-level prevention of obesity and its long-term consequences for health and health care.

Funding

The British Hearth Foundation, Health Data Research UK, the UK Medical Research Council, and the National Institute for Health Research.", - "laySummary": "", - "urls": "pdf:http://www.thelancet.com/article/S2213858721002072/pdf; doi:https://doi.org/10.1016/S2213-8587(21)00207-2; html:https://europepmc.org/articles/PMC8440227; pdf:https://europepmc.org/articles/PMC8440227?pdf=render" - }, { "id": "32626822", "doi": "https://doi.org/10.1007/s41109-020-00273-3", @@ -16081,6 +16064,23 @@ "laySummary": "", "urls": "pdf:https://appliednetsci.springeropen.com/track/pdf/10.1007/s41109-020-00273-3; doi:https://doi.org/10.1007/s41109-020-00273-3; html:https://europepmc.org/articles/PMC7319291; pdf:https://europepmc.org/articles/PMC7319291?pdf=render" }, + { + "id": "34481555", + "doi": "https://doi.org/10.1016/s2213-8587(21)00207-2", + "title": "Identifying adults at high-risk for change in weight and BMI in England: a longitudinal, large-scale, population-based cohort study using electronic health records.", + "authorString": "Katsoulis M, Lai AG, Diaz-Ordaz K, Gomes M, Pasea L, Banerjee A, Denaxas S, Tsilidis K, Lagiou P, Misirli G, Bhaskaran K, Wannamethee G, Dobson R, Batterham RL, Kipourou DK, Lumbers RT, Wen L, Wareham N, Langenberg C, Hemingway H.", + "authorAffiliations": "", + "journalTitle": "The lancet. Diabetes & endocrinology", + "pubYear": "2021", + "date": "2021-09-02", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Targeted obesity prevention policies would benefit from the identification of population groups with the highest risk of weight gain. The relative importance of adult age, sex, ethnicity, geographical region, and degree of social deprivation on weight gain is not known. We aimed to identify high-risk groups for changes in weight and BMI using electronic health records (EHR).

Methods

In this longitudinal, population-based cohort study we used linked EHR data from 400 primary care practices (via the Clinical Practice Research Datalink) in England, accessed via the CALIBER programme. Eligible participants were aged 18-74 years, were registered at a general practice clinic, and had BMI and weight measurements recorded between Jan 1, 1998, and June 30, 2016, during the period when they had eligible linked data with at least 1 year of follow-up time. We calculated longitudinal changes in BMI over 1, 5, and 10 years, and investigated the absolute risk and odds ratios (ORs) of transitioning between BMI categories (underweight, normal weight, overweight, obesity class 1 and 2, and severe obesity [class 3]), as defined by WHO. The associations of demographic factors with BMI transitions were estimated by use of logistic regression analysis, adjusting for baseline BMI, family history of cardiovascular disease, use of diuretics, and prevalent chronic conditions.

Findings

We included 2 092 260 eligible individuals with more than 9 million BMI measurements in our study. Young adult age was the strongest risk factor for weight gain at 1, 5, and 10 years of follow-up. Compared with the oldest age group (65-74 years), adults in the youngest age group (18-24 years) had the highest OR (4\u00b722 [95% CI 3\u00b786-4\u00b762]) and greatest absolute risk (37% vs 24%) of transitioning from normal weight to overweight or obesity at 10 years. Likewise, adults in the youngest age group with overweight or obesity at baseline were also at highest risk to transition to a higher BMI category; OR 4\u00b760 (4\u00b706-5\u00b722) and absolute risk (42% vs 18%) of transitioning from overweight to class 1 and 2 obesity, and OR 5\u00b787 (5\u00b723-6\u00b759) and absolute risk (22% vs 5%) of transitioning from class 1 and 2 obesity to class 3 obesity. Other demographic factors were consistently less strongly associated with these transitions; for example, the OR of transitioning from normal weight to overweight or obesity in people living in the most socially deprived versus least deprived areas was 1\u00b723 (1\u00b718-1\u00b727), for men versus women was 1\u00b712 (1\u00b708-1\u00b716), and for Black individuals versus White individuals was 1\u00b713 (1\u00b704-1\u00b724). We provide an open access online risk calculator, and present high-resolution obesity risk charts over a 1-year, 5-year, and 10-year follow-up period.

Interpretation

A radical shift in policy is required to focus on individuals at the highest risk of weight gain (ie, young adults aged 18-24 years) for individual-level and population-level prevention of obesity and its long-term consequences for health and health care.

Funding

The British Hearth Foundation, Health Data Research UK, the UK Medical Research Council, and the National Institute for Health Research.", + "laySummary": "", + "urls": "pdf:http://www.thelancet.com/article/S2213858721002072/pdf; doi:https://doi.org/10.1016/S2213-8587(21)00207-2; html:https://europepmc.org/articles/PMC8440227; pdf:https://europepmc.org/articles/PMC8440227?pdf=render" + }, { "id": "34870259", "doi": "https://doi.org/10.1016/j.xgen.2021.100005", @@ -16489,23 +16489,6 @@ "laySummary": "", "urls": "pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-023-03153-6; doi:https://doi.org/10.1186/s12916-023-03153-6; html:https://europepmc.org/articles/PMC10641987; pdf:https://europepmc.org/articles/PMC10641987?pdf=render" }, - { - "id": "38660461", - "doi": "https://doi.org/10.1089/neur.2023.0116", - "title": "The Australian Traumatic Brain Injury Initiative: Statement of Working Principles and Rapid Review of Methods to Define Data Dictionaries for Neurological Conditions.", - "authorString": "Bagg MK, Hicks AJ, Hellewell SC, Ponsford JL, Lannin NA, O'Brien TJ, Cameron PA, Cooper DJ, Rushworth N, Gabbe BJ, Fitzgerald M.", - "authorAffiliations": "", - "journalTitle": "Neurotrauma reports", - "pubYear": "2024", - "date": "2024-04-11", - "isOpenAccess": "Y", - "keywords": "Brain injuries; Traumatic; Neurology; Common Data Elements; Systematic Review [Publication Type]", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "The Australian Traumatic Brain Injury Initiative (AUS-TBI) aims to develop a health informatics approach to collect data predictive of outcomes for persons with moderate-severe TBI across Australia. Central to this approach is a data dictionary; however, no systematic reviews of methods to define and develop data dictionaries exist to-date. This rapid systematic review aimed to identify and characterize methods for designing data dictionaries to collect outcomes or variables in persons with neurological conditions. Database searches were conducted from inception through October 2021. Records were screened in two stages against set criteria to identify methods to define data dictionaries for neurological conditions (International Classification of Diseases, 11th Revision: 08, 22, and 23). Standardized data were extracted. Processes were checked at each stage by independent review of a random 25% of records. Consensus was reached through discussion where necessary. Thirty-nine initiatives were identified across 29 neurological conditions. No single established or recommended method for defining a data dictionary was identified. Nine initiatives conducted systematic reviews to collate information before implementing a consensus process. Thirty-seven initiatives consulted with end-users. Methods of consultation were \"roundtable\" discussion (n\u2009=\u200930); with facilitation (n\u2009=\u200916); that was iterative (n\u2009=\u200927); and frequently conducted in-person (n\u2009=\u200927). Researcher stakeholders were involved in all initiatives and clinicians in 25. Importantly, only six initiatives involved persons with lived experience of TBI and four involved carers. Methods for defining data dictionaries were variable and reporting is sparse. Our findings are instructive for AUS-TBI and can be used to further development of methods for defining data dictionaries.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1089/neur.2023.0116; html:https://europepmc.org/articles/PMC11040195; pdf:https://europepmc.org/articles/PMC11040195?pdf=render" - }, { "id": "37812323", "doi": "https://doi.org/10.1186/s41687-023-00634-3", @@ -16523,6 +16506,23 @@ "laySummary": "", "urls": "pdf:https://jpro.springeropen.com/counter/pdf/10.1186/s41687-023-00634-3; doi:https://doi.org/10.1186/s41687-023-00634-3; html:https://europepmc.org/articles/PMC10562321; pdf:https://europepmc.org/articles/PMC10562321?pdf=render" }, + { + "id": "38660461", + "doi": "https://doi.org/10.1089/neur.2023.0116", + "title": "The Australian Traumatic Brain Injury Initiative: Statement of Working Principles and Rapid Review of Methods to Define Data Dictionaries for Neurological Conditions.", + "authorString": "Bagg MK, Hicks AJ, Hellewell SC, Ponsford JL, Lannin NA, O'Brien TJ, Cameron PA, Cooper DJ, Rushworth N, Gabbe BJ, Fitzgerald M.", + "authorAffiliations": "", + "journalTitle": "Neurotrauma reports", + "pubYear": "2024", + "date": "2024-04-11", + "isOpenAccess": "Y", + "keywords": "Brain injuries; Traumatic; Neurology; Common Data Elements; Systematic Review [Publication Type]", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "The Australian Traumatic Brain Injury Initiative (AUS-TBI) aims to develop a health informatics approach to collect data predictive of outcomes for persons with moderate-severe TBI across Australia. Central to this approach is a data dictionary; however, no systematic reviews of methods to define and develop data dictionaries exist to-date. This rapid systematic review aimed to identify and characterize methods for designing data dictionaries to collect outcomes or variables in persons with neurological conditions. Database searches were conducted from inception through October 2021. Records were screened in two stages against set criteria to identify methods to define data dictionaries for neurological conditions (International Classification of Diseases, 11th Revision: 08, 22, and 23). Standardized data were extracted. Processes were checked at each stage by independent review of a random 25% of records. Consensus was reached through discussion where necessary. Thirty-nine initiatives were identified across 29 neurological conditions. No single established or recommended method for defining a data dictionary was identified. Nine initiatives conducted systematic reviews to collate information before implementing a consensus process. Thirty-seven initiatives consulted with end-users. Methods of consultation were \"roundtable\" discussion (n\u2009=\u200930); with facilitation (n\u2009=\u200916); that was iterative (n\u2009=\u200927); and frequently conducted in-person (n\u2009=\u200927). Researcher stakeholders were involved in all initiatives and clinicians in 25. Importantly, only six initiatives involved persons with lived experience of TBI and four involved carers. Methods for defining data dictionaries were variable and reporting is sparse. Our findings are instructive for AUS-TBI and can be used to further development of methods for defining data dictionaries.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1089/neur.2023.0116; html:https://europepmc.org/articles/PMC11040195; pdf:https://europepmc.org/articles/PMC11040195?pdf=render" + }, { "id": "35964473", "doi": "https://doi.org/10.1016/j.socscimed.2022.115237", @@ -16557,23 +16557,6 @@ "laySummary": "", "urls": "pdf:https://academic.oup.com/bjd/article-pdf/188/4/460/51790111/ljac132.pdf; doi:https://doi.org/10.1093/bjd/ljac132" }, - { - "id": "36962513", - "doi": "https://doi.org/10.1371/journal.pgph.0000502", - "title": "Association between mobility, non-pharmaceutical interventions, and COVID-19 transmission in Ghana: A modelling study using mobile phone data.", - "authorString": "Gibbs H, Liu Y, Abbott S, Baffoe-Nyarko I, Laryea DO, Akyereko E, Kuma-Aboagye P, Asante IA, Mitj\u00e0 O, LSHTM CMMID COVID-19 Working Group, Ampofo W, Asiedu-Bekoe F, Marks M, Eggo RM.", - "authorAffiliations": "", - "journalTitle": "PLOS global public health", - "pubYear": "2022", - "date": "2022-09-13", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Governments around the world have implemented non-pharmaceutical interventions to limit the transmission of COVID-19. Here we assess if increasing NPI stringency was associated with a reduction in COVID-19 cases in Ghana. While lockdowns and physical distancing have proven effective for reducing COVID-19 transmission, there is still limited understanding of how NPI measures are reflected in indicators of human mobility. Further, there is a lack of understanding about how findings from high-income settings correspond to low and middle-income contexts. In this study, we assess the relationship between indicators of human mobility, NPIs, and estimates of Rt, a real-time measure of the intensity of COVID-19 transmission. We construct a multilevel generalised linear mixed model, combining local disease surveillance data from subnational districts of Ghana with the timing of NPIs and indicators of human mobility from Google and Vodafone Ghana. We observe a relationship between reductions in human mobility and decreases in Rt during the early stages of the COVID-19 epidemic in Ghana. We find that the strength of this relationship varies through time, decreasing after the most stringent period of interventions in the early epidemic. Our findings demonstrate how the association of NPI and mobility indicators with COVID-19 transmission may vary through time. Further, we demonstrate the utility of combining local disease surveillance data with large scale human mobility data to augment existing surveillance capacity to monitor the impact of NPI policies.", - "laySummary": "", - "urls": "pdf:https://journals.plos.org/globalpublichealth/article/file?id=10.1371/journal.pgph.0000502&type=printable; doi:https://doi.org/10.1371/journal.pgph.0000502; html:https://europepmc.org/articles/PMC10021296; pdf:https://europepmc.org/articles/PMC10021296?pdf=render" - }, { "id": "30240446", "doi": "https://doi.org/10.1371/journal.pone.0203896", @@ -16591,6 +16574,23 @@ "laySummary": "", "urls": "pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0203896&type=printable; doi:https://doi.org/10.1371/journal.pone.0203896; html:https://europepmc.org/articles/PMC6150505; pdf:https://europepmc.org/articles/PMC6150505?pdf=render" }, + { + "id": "36962513", + "doi": "https://doi.org/10.1371/journal.pgph.0000502", + "title": "Association between mobility, non-pharmaceutical interventions, and COVID-19 transmission in Ghana: A modelling study using mobile phone data.", + "authorString": "Gibbs H, Liu Y, Abbott S, Baffoe-Nyarko I, Laryea DO, Akyereko E, Kuma-Aboagye P, Asante IA, Mitj\u00e0 O, LSHTM CMMID COVID-19 Working Group, Ampofo W, Asiedu-Bekoe F, Marks M, Eggo RM.", + "authorAffiliations": "", + "journalTitle": "PLOS global public health", + "pubYear": "2022", + "date": "2022-09-13", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Governments around the world have implemented non-pharmaceutical interventions to limit the transmission of COVID-19. Here we assess if increasing NPI stringency was associated with a reduction in COVID-19 cases in Ghana. While lockdowns and physical distancing have proven effective for reducing COVID-19 transmission, there is still limited understanding of how NPI measures are reflected in indicators of human mobility. Further, there is a lack of understanding about how findings from high-income settings correspond to low and middle-income contexts. In this study, we assess the relationship between indicators of human mobility, NPIs, and estimates of Rt, a real-time measure of the intensity of COVID-19 transmission. We construct a multilevel generalised linear mixed model, combining local disease surveillance data from subnational districts of Ghana with the timing of NPIs and indicators of human mobility from Google and Vodafone Ghana. We observe a relationship between reductions in human mobility and decreases in Rt during the early stages of the COVID-19 epidemic in Ghana. We find that the strength of this relationship varies through time, decreasing after the most stringent period of interventions in the early epidemic. Our findings demonstrate how the association of NPI and mobility indicators with COVID-19 transmission may vary through time. Further, we demonstrate the utility of combining local disease surveillance data with large scale human mobility data to augment existing surveillance capacity to monitor the impact of NPI policies.", + "laySummary": "", + "urls": "pdf:https://journals.plos.org/globalpublichealth/article/file?id=10.1371/journal.pgph.0000502&type=printable; doi:https://doi.org/10.1371/journal.pgph.0000502; html:https://europepmc.org/articles/PMC10021296; pdf:https://europepmc.org/articles/PMC10021296?pdf=render" + }, { "id": "35781133", "doi": "https://doi.org/10.3310/zyzc8514", @@ -16676,23 +16676,6 @@ "laySummary": "", "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/1742-6723.14312; doi:https://doi.org/10.1111/1742-6723.14312; html:https://europepmc.org/articles/PMC10952644; pdf:https://europepmc.org/articles/PMC10952644?pdf=render" }, - { - "id": "38581198", - "doi": "https://doi.org/10.1001/jama.2024.4011", - "title": "Prostate-Specific Antigen Screening and 15-Year Prostate Cancer Mortality: A Secondary Analysis of the CAP Randomized Clinical Trial.", - "authorString": "Martin RM, Turner EL, Young GJ, Metcalfe C, Walsh EI, Lane JA, Sterne JAC, Noble S, Holding P, Ben-Shlomo Y, Williams NJ, Pashayan N, Bui MN, Albertsen PC, Seibert TM, Zietman AL, Oxley J, Adolfsson J, Mason MD, Davey Smith G, Neal DE, Hamdy FC, Donovan JL, CAP Trial Group.", - "authorAffiliations": "", - "journalTitle": "JAMA", - "pubYear": "2024", - "date": "2024-05-01", - "isOpenAccess": "N", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Importance

The Cluster Randomized Trial of PSA Testing for Prostate Cancer (CAP) reported no effect of prostate-specific antigen (PSA) screening on prostate cancer mortality at a median 10-year follow-up (primary outcome), but the long-term effects of PSA screening on prostate cancer mortality remain unclear.

Objective

To evaluate the effect of a single invitation for PSA screening on prostate cancer-specific mortality at a median 15-year follow-up compared with no invitation for screening.

Design, setting, and participants

This secondary analysis of the CAP randomized clinical trial included men aged 50 to 69 years identified at 573 primary care practices in England and Wales. Primary care practices were randomized between September 25, 2001, and August 24, 2007, and men were enrolled between January 8, 2002, and January 20, 2009. Follow-up was completed on March 31, 2021.

Intervention

Men received a single invitation for a PSA screening test with subsequent diagnostic tests if the PSA level was 3.0 ng/mL or higher. The control group received standard practice (no invitation).

Main outcomes and measures

The primary outcome was reported previously. Of 8 prespecified secondary outcomes, results of 4 were reported previously. The 4 remaining prespecified secondary outcomes at 15-year follow-up were prostate cancer-specific mortality, all-cause mortality, and prostate cancer stage and Gleason grade at diagnosis.

Results

Of 415\u202f357 eligible men (mean [SD] age, 59.0 [5.6] years), 98% were included in these analyses. Overall, 12\u202f013 and 12\u202f958 men with a prostate cancer diagnosis were in the intervention and control groups, respectively (15-year cumulative risk, 7.08% [95% CI, 6.95%-7.21%] and 6.94% [95% CI, 6.82%-7.06%], respectively). At a median 15-year follow-up, 1199 men in the intervention group (0.69% [95% CI, 0.65%-0.73%]) and 1451 men in the control group (0.78% [95% CI, 0.73%-0.82%]) died of prostate cancer (rate ratio [RR], 0.92 [95% CI, 0.85-0.99]; P\u2009=\u2009.03). Compared with the control, the PSA screening intervention increased detection of low-grade (Gleason score [GS] \u22646: 2.2% vs 1.6%; P\u2009<\u2009.001) and localized (T1/T2: 3.6% vs 3.1%; P\u2009<\u2009.001) disease but not intermediate (GS of 7), high-grade (GS \u22658), locally advanced (T3), or distally advanced (T4/N1/M1) tumors. There were 45\u202f084 all-cause deaths in the intervention group (23.2% [95% CI, 23.0%-23.4%]) and 50\u202f336 deaths in the control group (23.3% [95% CI, 23.1%-23.5%]) (RR, 0.97 [95% CI, 0.94-1.01]; P\u2009=\u2009.11). Eight of the prostate cancer deaths in the intervention group (0.7%) and 7 deaths in the control group (0.5%) were related to a diagnostic biopsy or prostate cancer treatment.

Conclusions and relevance

In this secondary analysis of a randomized clinical trial, a single invitation for PSA screening compared with standard practice without routine screening reduced prostate cancer deaths at a median follow-up of 15 years. However, the absolute reduction in deaths was small.

Trial registration

isrctn.org Identifier: ISRCTN92187251.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1001/jama.2024.4011" - }, { "id": "32460529", "doi": "https://doi.org/10.1161/circimaging.119.010389", @@ -16710,23 +16693,6 @@ "laySummary": "", "urls": "pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCIMAGING.119.010389; doi:https://doi.org/10.1161/CIRCIMAGING.119.010389; html:https://europepmc.org/articles/PMC7610536; pdf:https://europepmc.org/articles/PMC7610536?pdf=render; doi:https://doi.org/10.1161/circimaging.119.010389" }, - { - "id": "36617894", - "doi": "https://doi.org/10.1080/1354750x.2022.2162966", - "title": "Longitudinal profile of circulating endothelial cells in post-acute coronary syndrome patients.", - "authorString": "de Bakker M, Kraan J, Akkerhuis KM, Oemrawsingh R, Asselbergs FW, Hoefer I, Kardys I, Boersma E.", - "authorAffiliations": "", - "journalTitle": "Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals", - "pubYear": "2023", - "date": "2023-01-08", - "isOpenAccess": "N", - "keywords": "Atherosclerosis; Cardiovascular disease; Circulating endothelial cells; acute coronary syndrome; Vascular Injury; Repeated Measurements", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "IntroductionPatients who have experienced an acute coronary syndrome (ACS) are at risk of a recurrent event, but their level of risk varies. Because of their close temporal relationship with vascular injury, longitudinal measurements of circulating endothelial cells (CECs) carry potential to improve individual risk assessment.MethodsWe conducted an explorative nested case-control study within our multicenter, prospective, observational biomarker study (BIOMArCS) of 844 ACS patients. Following an index ACS, high-frequency blood sampling was performed during 1-year follow-up. CECs were identified using flow cytometric analyses in 15 cases with recurrent event, and 30 matched controls.ResultsCases and controls had a median (25th-75thpercentile) age of 64.1 (58.1-75.1) years and 80% were men. During the months preceding the endpoint, the mean (95%CI) CEC concentration in cases was persistently higher than in controls (12.8 [8.2-20.0] versus 10.0 [7.0-14.4] cells/ml), although this difference was non-significant (P\u2009=\u20090.339). In controls, the mean cell concentration was significantly (P\u2009=\u20090.030) lower in post 30-day samples compared to samples collected within one day after index ACS: 10.1 (7.5-13.6) versus 17.0 (10.8-26.6) cells/ml. Similar results were observed for CEC subsets co-expressing CD133 and CD309 (VEGFR-2) or CD106 (VCAM-1).ConclusionDespite their close relation to vascular damage, no increase in cell concentrations were found prior to the occurrence of a secondary adverse cardiac event.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1080/1354750x.2022.2162966; doi:https://doi.org/10.1080/1354750X.2022.2162966" - }, { "id": "31912053", "doi": "https://doi.org/", @@ -16745,21 +16711,38 @@ "urls": "" }, { - "id": "36769754", - "doi": "https://doi.org/10.3390/jcm12031106", - "title": "The Causal Association of Irritable Bowel Syndrome with Multiple Disease Outcomes: A Phenome-Wide Mendelian Randomization Study.", - "authorString": "Li C, Chen Y, Chen Y, Ying Z, Hu Y, Kuang Y, Yang H, Song H, Zeng X.", + "id": "38581198", + "doi": "https://doi.org/10.1001/jama.2024.4011", + "title": "Prostate-Specific Antigen Screening and 15-Year Prostate Cancer Mortality: A Secondary Analysis of the CAP Randomized Clinical Trial.", + "authorString": "Martin RM, Turner EL, Young GJ, Metcalfe C, Walsh EI, Lane JA, Sterne JAC, Noble S, Holding P, Ben-Shlomo Y, Williams NJ, Pashayan N, Bui MN, Albertsen PC, Seibert TM, Zietman AL, Oxley J, Adolfsson J, Mason MD, Davey Smith G, Neal DE, Hamdy FC, Donovan JL, CAP Trial Group.", "authorAffiliations": "", - "journalTitle": "Journal of clinical medicine", + "journalTitle": "JAMA", + "pubYear": "2024", + "date": "2024-05-01", + "isOpenAccess": "N", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Importance

The Cluster Randomized Trial of PSA Testing for Prostate Cancer (CAP) reported no effect of prostate-specific antigen (PSA) screening on prostate cancer mortality at a median 10-year follow-up (primary outcome), but the long-term effects of PSA screening on prostate cancer mortality remain unclear.

Objective

To evaluate the effect of a single invitation for PSA screening on prostate cancer-specific mortality at a median 15-year follow-up compared with no invitation for screening.

Design, setting, and participants

This secondary analysis of the CAP randomized clinical trial included men aged 50 to 69 years identified at 573 primary care practices in England and Wales. Primary care practices were randomized between September 25, 2001, and August 24, 2007, and men were enrolled between January 8, 2002, and January 20, 2009. Follow-up was completed on March 31, 2021.

Intervention

Men received a single invitation for a PSA screening test with subsequent diagnostic tests if the PSA level was 3.0 ng/mL or higher. The control group received standard practice (no invitation).

Main outcomes and measures

The primary outcome was reported previously. Of 8 prespecified secondary outcomes, results of 4 were reported previously. The 4 remaining prespecified secondary outcomes at 15-year follow-up were prostate cancer-specific mortality, all-cause mortality, and prostate cancer stage and Gleason grade at diagnosis.

Results

Of 415\u202f357 eligible men (mean [SD] age, 59.0 [5.6] years), 98% were included in these analyses. Overall, 12\u202f013 and 12\u202f958 men with a prostate cancer diagnosis were in the intervention and control groups, respectively (15-year cumulative risk, 7.08% [95% CI, 6.95%-7.21%] and 6.94% [95% CI, 6.82%-7.06%], respectively). At a median 15-year follow-up, 1199 men in the intervention group (0.69% [95% CI, 0.65%-0.73%]) and 1451 men in the control group (0.78% [95% CI, 0.73%-0.82%]) died of prostate cancer (rate ratio [RR], 0.92 [95% CI, 0.85-0.99]; P\u2009=\u2009.03). Compared with the control, the PSA screening intervention increased detection of low-grade (Gleason score [GS] \u22646: 2.2% vs 1.6%; P\u2009<\u2009.001) and localized (T1/T2: 3.6% vs 3.1%; P\u2009<\u2009.001) disease but not intermediate (GS of 7), high-grade (GS \u22658), locally advanced (T3), or distally advanced (T4/N1/M1) tumors. There were 45\u202f084 all-cause deaths in the intervention group (23.2% [95% CI, 23.0%-23.4%]) and 50\u202f336 deaths in the control group (23.3% [95% CI, 23.1%-23.5%]) (RR, 0.97 [95% CI, 0.94-1.01]; P\u2009=\u2009.11). Eight of the prostate cancer deaths in the intervention group (0.7%) and 7 deaths in the control group (0.5%) were related to a diagnostic biopsy or prostate cancer treatment.

Conclusions and relevance

In this secondary analysis of a randomized clinical trial, a single invitation for PSA screening compared with standard practice without routine screening reduced prostate cancer deaths at a median follow-up of 15 years. However, the absolute reduction in deaths was small.

Trial registration

isrctn.org Identifier: ISRCTN92187251.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1001/jama.2024.4011" + }, + { + "id": "36617894", + "doi": "https://doi.org/10.1080/1354750x.2022.2162966", + "title": "Longitudinal profile of circulating endothelial cells in post-acute coronary syndrome patients.", + "authorString": "de Bakker M, Kraan J, Akkerhuis KM, Oemrawsingh R, Asselbergs FW, Hoefer I, Kardys I, Boersma E.", + "authorAffiliations": "", + "journalTitle": "Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals", "pubYear": "2023", - "date": "2023-01-31", - "isOpenAccess": "Y", - "keywords": "irritable bowel syndrome; Phenome-wide Association Study; Individual-level Mendelian Randomization; Summary-level Mendelian Randomization", + "date": "2023-01-08", + "isOpenAccess": "N", + "keywords": "Atherosclerosis; Cardiovascular disease; Circulating endothelial cells; acute coronary syndrome; Vascular Injury; Repeated Measurements", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Background

This study aimed to identify novel associations between irritable bowel syndrome (IBS) and a broad range of outcomes.

Methods

In total, 346,352 white participants in the U.K. Biobank were randomly divided into two halves, in which a genome-wide association study (GWAS) of IBS and a polygenic risk score (PRS) analysis of IBS using GWAS summary statistics were conducted, respectively. A phenome-wide association study (PheWAS) based on the PRS of IBS was performed to identify disease outcomes associated with IBS. Then, the causalities of these associations were tested by both one-sample (individual-level data in U.K. Biobank) and two-sample (publicly available summary statistics) Mendelian randomization (MR). Sex-stratified PheWAS-MR analyses were performed in male and female, separately.

Results

Our PheWAS identified five diseases associated with genetically predicted IBS. Conventional MR confirmed these causal associations between IBS and depression (OR: 1.07, 95%CI: 1.01-1.14, p = 0.02), diverticular diseases of the intestine (OR: 1.13, 95%CI: 1.08-1.19, p = 3.00 \u00d7 10-6), gastro-esophageal reflux disease (OR: 1.09, 95%CI: 1.05-1.13, p = 3.72 \u00d7 10-5), dyspepsia (OR: 1.21, 95%CI: 1.13-1.30, p = 9.28 \u00d7 10-8), and diaphragmatic hernia (OR: 1.10, 95%CI: 1.05-1.15, p = 2.75 \u00d7 10-5). The causality of these associations was observed in female only, but not men.

Conclusions

Increased risks of IBS is found to cause a series of disease outcomes. Our findings support further investigation on the clinical relevance of increased IBS risks with mental and digestive disorders.", + "abstract": "IntroductionPatients who have experienced an acute coronary syndrome (ACS) are at risk of a recurrent event, but their level of risk varies. Because of their close temporal relationship with vascular injury, longitudinal measurements of circulating endothelial cells (CECs) carry potential to improve individual risk assessment.MethodsWe conducted an explorative nested case-control study within our multicenter, prospective, observational biomarker study (BIOMArCS) of 844 ACS patients. Following an index ACS, high-frequency blood sampling was performed during 1-year follow-up. CECs were identified using flow cytometric analyses in 15 cases with recurrent event, and 30 matched controls.ResultsCases and controls had a median (25th-75thpercentile) age of 64.1 (58.1-75.1) years and 80% were men. During the months preceding the endpoint, the mean (95%CI) CEC concentration in cases was persistently higher than in controls (12.8 [8.2-20.0] versus 10.0 [7.0-14.4] cells/ml), although this difference was non-significant (P\u2009=\u20090.339). In controls, the mean cell concentration was significantly (P\u2009=\u20090.030) lower in post 30-day samples compared to samples collected within one day after index ACS: 10.1 (7.5-13.6) versus 17.0 (10.8-26.6) cells/ml. Similar results were observed for CEC subsets co-expressing CD133 and CD309 (VEGFR-2) or CD106 (VCAM-1).ConclusionDespite their close relation to vascular damage, no increase in cell concentrations were found prior to the occurrence of a secondary adverse cardiac event.", "laySummary": "", - "urls": "doi:https://doi.org/10.3390/jcm12031106; doi:https://doi.org/10.3390/jcm12031106; html:https://europepmc.org/articles/PMC9918111; pdf:https://europepmc.org/articles/PMC9918111?pdf=render" + "urls": "doi:https://doi.org/10.1080/1354750x.2022.2162966; doi:https://doi.org/10.1080/1354750X.2022.2162966" }, { "id": "35297226", @@ -16778,6 +16761,23 @@ "laySummary": "", "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/jcsm.12971; doi:https://doi.org/10.1002/jcsm.12971; html:https://europepmc.org/articles/PMC9178164; pdf:https://europepmc.org/articles/PMC9178164?pdf=render" }, + { + "id": "36769754", + "doi": "https://doi.org/10.3390/jcm12031106", + "title": "The Causal Association of Irritable Bowel Syndrome with Multiple Disease Outcomes: A Phenome-Wide Mendelian Randomization Study.", + "authorString": "Li C, Chen Y, Chen Y, Ying Z, Hu Y, Kuang Y, Yang H, Song H, Zeng X.", + "authorAffiliations": "", + "journalTitle": "Journal of clinical medicine", + "pubYear": "2023", + "date": "2023-01-31", + "isOpenAccess": "Y", + "keywords": "irritable bowel syndrome; Phenome-wide Association Study; Individual-level Mendelian Randomization; Summary-level Mendelian Randomization", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

This study aimed to identify novel associations between irritable bowel syndrome (IBS) and a broad range of outcomes.

Methods

In total, 346,352 white participants in the U.K. Biobank were randomly divided into two halves, in which a genome-wide association study (GWAS) of IBS and a polygenic risk score (PRS) analysis of IBS using GWAS summary statistics were conducted, respectively. A phenome-wide association study (PheWAS) based on the PRS of IBS was performed to identify disease outcomes associated with IBS. Then, the causalities of these associations were tested by both one-sample (individual-level data in U.K. Biobank) and two-sample (publicly available summary statistics) Mendelian randomization (MR). Sex-stratified PheWAS-MR analyses were performed in male and female, separately.

Results

Our PheWAS identified five diseases associated with genetically predicted IBS. Conventional MR confirmed these causal associations between IBS and depression (OR: 1.07, 95%CI: 1.01-1.14, p = 0.02), diverticular diseases of the intestine (OR: 1.13, 95%CI: 1.08-1.19, p = 3.00 \u00d7 10-6), gastro-esophageal reflux disease (OR: 1.09, 95%CI: 1.05-1.13, p = 3.72 \u00d7 10-5), dyspepsia (OR: 1.21, 95%CI: 1.13-1.30, p = 9.28 \u00d7 10-8), and diaphragmatic hernia (OR: 1.10, 95%CI: 1.05-1.15, p = 2.75 \u00d7 10-5). The causality of these associations was observed in female only, but not men.

Conclusions

Increased risks of IBS is found to cause a series of disease outcomes. Our findings support further investigation on the clinical relevance of increased IBS risks with mental and digestive disorders.", + "laySummary": "", + "urls": "doi:https://doi.org/10.3390/jcm12031106; doi:https://doi.org/10.3390/jcm12031106; html:https://europepmc.org/articles/PMC9918111; pdf:https://europepmc.org/articles/PMC9918111?pdf=render" + }, { "id": "34227657", "doi": "https://doi.org/10.1093/bjs/znab183", @@ -16880,23 +16880,6 @@ "laySummary": "", "urls": "pdf:http://www.thelancet.com/article/S2352396423002207/pdf; doi:https://doi.org/10.1016/j.ebiom.2023.104655; html:https://europepmc.org/articles/PMC10279550; pdf:https://europepmc.org/articles/PMC10279550?pdf=render" }, - { - "id": "38040454", - "doi": "https://doi.org/10.1101/cshperspect.a041473", - "title": "Environmental Impacts of Machine Learning Applications in Protein Science.", - "authorString": "Lannelongue L, Inouye M.", - "authorAffiliations": "", - "journalTitle": "Cold Spring Harbor perspectives in biology", - "pubYear": "2023", - "date": "2023-12-01", - "isOpenAccess": "N", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Computing tools and machine learning models play an increasingly important role in biology and are now an essential part of discoveries in protein science. The growing energy needs of modern algorithms have raised concerns in the computational science community in light of the climate emergency. In this work, we summarize the different ways in which protein science can negatively impact the environment and we present the carbon footprint of some popular protein algorithms: molecular simulations, inference of protein-protein interactions, and protein structure prediction. We show that large deep learning models such as AlphaFold and ESMFold can have carbon footprints reaching over 100 tonnes of CO2e in some cases. The magnitude of these impacts highlights the importance of monitoring and mitigating them, and we list actions scientists can take to achieve more sustainable protein computational science.", - "laySummary": "", - "urls": "pdf:http://cshperspectives.cshlp.org/content/15/12/a041473.full.pdf; doi:https://doi.org/10.1101/cshperspect.a041473" - }, { "id": "32616677", "doi": "https://doi.org/10.1212/wnl.0000000000009924", @@ -16914,6 +16897,23 @@ "laySummary": "", "urls": "pdf:https://n.neurology.org/content/neurology/95/6/e697.full.pdf; doi:https://doi.org/10.1212/WNL.0000000000009924; html:https://europepmc.org/articles/PMC7455356; pdf:https://europepmc.org/articles/PMC7455356?pdf=render" }, + { + "id": "38040454", + "doi": "https://doi.org/10.1101/cshperspect.a041473", + "title": "Environmental Impacts of Machine Learning Applications in Protein Science.", + "authorString": "Lannelongue L, Inouye M.", + "authorAffiliations": "", + "journalTitle": "Cold Spring Harbor perspectives in biology", + "pubYear": "2023", + "date": "2023-12-01", + "isOpenAccess": "N", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Computing tools and machine learning models play an increasingly important role in biology and are now an essential part of discoveries in protein science. The growing energy needs of modern algorithms have raised concerns in the computational science community in light of the climate emergency. In this work, we summarize the different ways in which protein science can negatively impact the environment and we present the carbon footprint of some popular protein algorithms: molecular simulations, inference of protein-protein interactions, and protein structure prediction. We show that large deep learning models such as AlphaFold and ESMFold can have carbon footprints reaching over 100 tonnes of CO2e in some cases. The magnitude of these impacts highlights the importance of monitoring and mitigating them, and we list actions scientists can take to achieve more sustainable protein computational science.", + "laySummary": "", + "urls": "pdf:http://cshperspectives.cshlp.org/content/15/12/a041473.full.pdf; doi:https://doi.org/10.1101/cshperspect.a041473" + }, { "id": "34819519", "doi": "https://doi.org/10.1038/s41467-021-27164-0", @@ -16965,6 +16965,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1002/ijc.34279; doi:https://doi.org/10.1002/ijc.34279; html:https://europepmc.org/articles/PMC10086800; pdf:https://europepmc.org/articles/PMC10086800?pdf=render" }, + { + "id": "33306026", + "doi": "https://doi.org/10.2196/23369", + "title": "Engagement With a Behavior Change App for Alcohol Reduction: Data Visualization for Longitudinal Observational Study.", + "authorString": "Bell L, Garnett C, Qian T, Perski O, Williamson E, Potts HW.", + "authorAffiliations": "", + "journalTitle": "Journal of medical Internet research", + "pubYear": "2020", + "date": "2020-12-11", + "isOpenAccess": "Y", + "keywords": "Engagement; Behavior Change; Apps; Mobile Health; Digital Health; Just-in-time Adaptive Interventions; Push Notifications; Micro-randomized Trial; Data Visualizations", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Behavior change apps can develop iteratively, where the app evolves into a complex, dynamic, or personalized intervention through cycles of research, development, and implementation. Understanding how existing users engage with an app (eg, frequency, amount, depth, and duration of use) can help guide further incremental improvements. We aim to explore how simple visualizations can provide a good understanding of temporal patterns of engagement, as usage data are often longitudinal and rich.

Objective

This study aims to visualize behavioral engagement with Drink Less, a behavior change app to help reduce hazardous and harmful alcohol consumption in the general adult population of the United Kingdom.

Methods

We explored behavioral engagement among 19,233 existing users of Drink Less. Users were included in the sample if they were from the United Kingdom; were 18 years or older; were interested in reducing their alcohol consumption; had a baseline Alcohol Use Disorders Identification Test score of 8 or above, indicative of excessive drinking; and had downloaded the app between May 17, 2017, and January 22, 2019 (615 days). Measures of when sessions begin, length of sessions, time to disengagement, and patterns of use were visualized with heat maps, timeline plots, k-modes clustering analyses, and Kaplan-Meier plots.

Results

The daily 11 AM notification is strongly associated with a change in engagement in the following hour; reduction in behavioral engagement over time, with 50.00% (9617/19,233) of users disengaging (defined as no use for 7 or more consecutive days) 22 days after download; identification of 3 distinct trajectories of use, namely engagers (4651/19,233, 24.18% of users), slow disengagers (3679/19,233, 19.13% of users), and fast disengagers (10,903/19,233, 56.68% of users); and limited depth of engagement with 85.076% (7,095,348/8,340,005) of screen views occurring within the Self-monitoring and Feedback module. In addition, a peak of both frequency and amount of time spent per session was observed in the evenings.

Conclusions

Visualizations play an important role in understanding engagement with behavior change apps. Here, we discuss how simple visualizations helped identify important patterns of engagement with Drink Less. Our visualizations of behavioral engagement suggest that the daily notification substantially impacts engagement. Furthermore, the visualizations suggest that a fixed notification policy can be effective for maintaining engagement for some users but ineffective for others. We conclude that optimizing the notification policy to target both effectiveness and engagement is a worthwhile investment. Our future goal is to both understand the causal effect of the notification on engagement and further optimize the notification policy within Drink Less by tailoring to contextual circumstances of individuals over time. Such tailoring will be informed from the findings of our micro-randomized trial (MRT), and these visualizations were useful in both gaining a better understanding of engagement and designing the MRT.", + "laySummary": "", + "urls": "pdf:https://www.jmir.org/2020/12/e23369/PDF; doi:https://doi.org/10.2196/23369; html:https://europepmc.org/articles/PMC7762688" + }, { "id": "35459950", "doi": "https://doi.org/10.1093/intqhc/mzac031", @@ -16983,21 +17000,21 @@ "urls": "pdf:https://academic.oup.com/intqhc/article-pdf/34/2/mzac031/43704475/mzac031.pdf; doi:https://doi.org/10.1093/intqhc/mzac031" }, { - "id": "33306026", - "doi": "https://doi.org/10.2196/23369", - "title": "Engagement With a Behavior Change App for Alcohol Reduction: Data Visualization for Longitudinal Observational Study.", - "authorString": "Bell L, Garnett C, Qian T, Perski O, Williamson E, Potts HW.", + "id": "32103533", + "doi": "https://doi.org/10.1002/sim.8503", + "title": "Propensity scores using missingness pattern information: a practical guide.", + "authorString": "Blake HA, Leyrat C, Mansfield KE, Seaman S, Tomlinson LA, Carpenter J, Williamson EJ.", "authorAffiliations": "", - "journalTitle": "Journal of medical Internet research", + "journalTitle": "Statistics in medicine", "pubYear": "2020", - "date": "2020-12-11", - "isOpenAccess": "Y", - "keywords": "Engagement; Behavior Change; Apps; Mobile Health; Digital Health; Just-in-time Adaptive Interventions; Push Notifications; Micro-randomized Trial; Data Visualizations", + "date": "2020-02-27", + "isOpenAccess": "N", + "keywords": "Electronic Health Records; Propensity Score Analysis; Missingness Pattern; Missing Indicator; Missing Confounder Data", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Background

Behavior change apps can develop iteratively, where the app evolves into a complex, dynamic, or personalized intervention through cycles of research, development, and implementation. Understanding how existing users engage with an app (eg, frequency, amount, depth, and duration of use) can help guide further incremental improvements. We aim to explore how simple visualizations can provide a good understanding of temporal patterns of engagement, as usage data are often longitudinal and rich.

Objective

This study aims to visualize behavioral engagement with Drink Less, a behavior change app to help reduce hazardous and harmful alcohol consumption in the general adult population of the United Kingdom.

Methods

We explored behavioral engagement among 19,233 existing users of Drink Less. Users were included in the sample if they were from the United Kingdom; were 18 years or older; were interested in reducing their alcohol consumption; had a baseline Alcohol Use Disorders Identification Test score of 8 or above, indicative of excessive drinking; and had downloaded the app between May 17, 2017, and January 22, 2019 (615 days). Measures of when sessions begin, length of sessions, time to disengagement, and patterns of use were visualized with heat maps, timeline plots, k-modes clustering analyses, and Kaplan-Meier plots.

Results

The daily 11 AM notification is strongly associated with a change in engagement in the following hour; reduction in behavioral engagement over time, with 50.00% (9617/19,233) of users disengaging (defined as no use for 7 or more consecutive days) 22 days after download; identification of 3 distinct trajectories of use, namely engagers (4651/19,233, 24.18% of users), slow disengagers (3679/19,233, 19.13% of users), and fast disengagers (10,903/19,233, 56.68% of users); and limited depth of engagement with 85.076% (7,095,348/8,340,005) of screen views occurring within the Self-monitoring and Feedback module. In addition, a peak of both frequency and amount of time spent per session was observed in the evenings.

Conclusions

Visualizations play an important role in understanding engagement with behavior change apps. Here, we discuss how simple visualizations helped identify important patterns of engagement with Drink Less. Our visualizations of behavioral engagement suggest that the daily notification substantially impacts engagement. Furthermore, the visualizations suggest that a fixed notification policy can be effective for maintaining engagement for some users but ineffective for others. We conclude that optimizing the notification policy to target both effectiveness and engagement is a worthwhile investment. Our future goal is to both understand the causal effect of the notification on engagement and further optimize the notification policy within Drink Less by tailoring to contextual circumstances of individuals over time. Such tailoring will be informed from the findings of our micro-randomized trial (MRT), and these visualizations were useful in both gaining a better understanding of engagement and designing the MRT.", + "abstract": "Electronic health records are a valuable data source for investigating health-related questions, and propensity score analysis has become an increasingly popular approach to address confounding bias in such investigations. However, because electronic health records are typically routinely recorded as part of standard clinical care, there are often missing values, particularly for potential confounders. In our motivating study-using electronic health records to investigate the effect of renin-angiotensin system blockers on the risk of acute kidney injury-two key confounders, ethnicity and chronic kidney disease stage, have 59% and 53% missing data, respectively. The missingness pattern approach (MPA), a variant of the missing indicator approach, has been proposed as a method for handling partially observed confounders in propensity score analysis. In the MPA, propensity scores are estimated separately for each missingness pattern present in the data. Although the assumptions underlying the validity of the MPA are stated in the literature, it can be difficult in practice to assess their plausibility. In this article, we explore the MPA's underlying assumptions by using causal diagrams to assess their plausibility in a range of simple scenarios, drawing general conclusions about situations in which they are likely to be violated. We present a framework providing practical guidance for assessing whether the MPA's assumptions are plausible in a particular setting and thus deciding when the MPA is appropriate. We apply our framework to our motivating study, showing that the MPA's underlying assumptions appear reasonable, and we demonstrate the application of MPA to this study.", "laySummary": "", - "urls": "pdf:https://www.jmir.org/2020/12/e23369/PDF; doi:https://doi.org/10.2196/23369; html:https://europepmc.org/articles/PMC7762688" + "urls": "pdf:https://researchonline.lshtm.ac.uk/id/eprint/4656008/1/manuscript.pdf; doi:https://doi.org/10.1002/sim.8503; html:https://europepmc.org/articles/PMC7612316; pdf:https://europepmc.org/articles/PMC7612316?pdf=render; doi:https://doi.org/10.1002/sim.8503" }, { "id": "34543272", @@ -17016,23 +17033,6 @@ "laySummary": "", "urls": "pdf:https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1009324&type=printable; doi:https://doi.org/10.1371/journal.pcbi.1009324; html:https://europepmc.org/articles/PMC8452068; pdf:https://europepmc.org/articles/PMC8452068?pdf=render" }, - { - "id": "32103533", - "doi": "https://doi.org/10.1002/sim.8503", - "title": "Propensity scores using missingness pattern information: a practical guide.", - "authorString": "Blake HA, Leyrat C, Mansfield KE, Seaman S, Tomlinson LA, Carpenter J, Williamson EJ.", - "authorAffiliations": "", - "journalTitle": "Statistics in medicine", - "pubYear": "2020", - "date": "2020-02-27", - "isOpenAccess": "N", - "keywords": "Electronic Health Records; Propensity Score Analysis; Missingness Pattern; Missing Indicator; Missing Confounder Data", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Electronic health records are a valuable data source for investigating health-related questions, and propensity score analysis has become an increasingly popular approach to address confounding bias in such investigations. However, because electronic health records are typically routinely recorded as part of standard clinical care, there are often missing values, particularly for potential confounders. In our motivating study-using electronic health records to investigate the effect of renin-angiotensin system blockers on the risk of acute kidney injury-two key confounders, ethnicity and chronic kidney disease stage, have 59% and 53% missing data, respectively. The missingness pattern approach (MPA), a variant of the missing indicator approach, has been proposed as a method for handling partially observed confounders in propensity score analysis. In the MPA, propensity scores are estimated separately for each missingness pattern present in the data. Although the assumptions underlying the validity of the MPA are stated in the literature, it can be difficult in practice to assess their plausibility. In this article, we explore the MPA's underlying assumptions by using causal diagrams to assess their plausibility in a range of simple scenarios, drawing general conclusions about situations in which they are likely to be violated. We present a framework providing practical guidance for assessing whether the MPA's assumptions are plausible in a particular setting and thus deciding when the MPA is appropriate. We apply our framework to our motivating study, showing that the MPA's underlying assumptions appear reasonable, and we demonstrate the application of MPA to this study.", - "laySummary": "", - "urls": "pdf:https://researchonline.lshtm.ac.uk/id/eprint/4656008/1/manuscript.pdf; doi:https://doi.org/10.1002/sim.8503; html:https://europepmc.org/articles/PMC7612316; pdf:https://europepmc.org/articles/PMC7612316?pdf=render; doi:https://doi.org/10.1002/sim.8503" - }, { "id": "32788201", "doi": "https://doi.org/10.1136/archdischild-2020-319027", @@ -17526,23 +17526,6 @@ "laySummary": "", "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/acps.13566; doi:https://doi.org/10.1111/acps.13566; html:https://europepmc.org/articles/PMC10953461; pdf:https://europepmc.org/articles/PMC10953461?pdf=render" }, - { - "id": "37717030", - "doi": "https://doi.org/10.1186/s13756-023-01280-6", - "title": "The impact of the COVID-19 pandemic on the treatment of common infections in primary care and the change to antibiotic prescribing in England.", - "authorString": "Yang YT, Zhong X, Fahmi A, Watts S, Ashcroft DM, Massey J, Fisher L, MacKenna B, Mehrkar A, Bacon SCJ, Goldacre B, Hand K, van Staa T, Palin V.", - "authorAffiliations": "", - "journalTitle": "Antimicrobial resistance and infection control", - "pubYear": "2023", - "date": "2023-09-16", - "isOpenAccess": "Y", - "keywords": "Infection; Antibiotics; Primary Care; Antibiotic Stewardship; Covid-19 Pandemic", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

There is concern that the COVID-19 pandemic altered the management of common infections in primary care. This study aimed to evaluate infection-coded consultation rates and antibiotic use during the pandemic and how any change may have affected clinical outcomes.

Methods

With the approval of NHS England, a retrospective cohort study using the OpenSAFELY platform analysed routinely collected electronic health data from GP practices in England between January 2019 and December 2021. Infection coded consultations and antibiotic prescriptions were used estimate multiple measures over calendar months, including age-sex adjusted prescribing rates, prescribing by infection and antibiotic type, infection consultation rates, coding quality and rate of same-day antibiotic prescribing for COVID-19 infections. Interrupted time series (ITS) estimated the effect of COVID-19 pandemic on infection-coded consultation rates. The impact of the pandemic on non- COVID-19 infection-related hospitalisations was also estimated.

Results

Records from 24 million patients were included. The rate of infection-related consultations fell for all infections (mean reduction of 39% in 2020 compared to 2019 mean rate), except for UTI which remained stable. Modelling infection-related consultation rates highlighted this with an incidence rate ratio of 0.44 (95% CI 0.36-0.53) for incident consultations and 0.43 (95% CI 0.33-0.54) for prevalent consultations. Lower respiratory tract infections (LRTI) saw the largest reduction of 0.11 (95% CI 0.07-0.17). Antibiotic prescribing rates fell with a mean reduction of 118.4 items per 1000 patients in 2020, returning to pre-pandemic rates by summer 2021. Prescribing for LRTI decreased 20% and URTI increased 15.9%. Over 60% of antibiotics were issued without an associated same-day infection code, which increased during the pandemic. Infection-related hospitalisations reduced (by 62%), with the largest reduction observed for pneumonia infections (72.9%). Same-day antibiotic prescribing for COVID-19 infection increased from 1 to 10.5% between the second and third national lockdowns and rose again during 2022.

Conclusions

Changes to consultations and hospital admissions may be driven by reduced transmission of non-COVID-19 infections due to reduced social mixing and lockdowns. Inconsistencies in coding practice emphasises the need for improvement to inform new antibiotic stewardship policies and prevent resistance to novel infections.", - "laySummary": "", - "urls": "pdf:https://aricjournal.biomedcentral.com/counter/pdf/10.1186/s13756-023-01280-6; doi:https://doi.org/10.1186/s13756-023-01280-6; html:https://europepmc.org/articles/PMC10504725; pdf:https://europepmc.org/articles/PMC10504725?pdf=render" - }, { "id": "32790708", "doi": "https://doi.org/10.1371/journal.pone.0237298", @@ -17560,6 +17543,23 @@ "laySummary": "", "urls": "pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0237298&type=printable; doi:https://doi.org/10.1371/journal.pone.0237298; html:https://europepmc.org/articles/PMC7425844; pdf:https://europepmc.org/articles/PMC7425844?pdf=render" }, + { + "id": "37717030", + "doi": "https://doi.org/10.1186/s13756-023-01280-6", + "title": "The impact of the COVID-19 pandemic on the treatment of common infections in primary care and the change to antibiotic prescribing in England.", + "authorString": "Yang YT, Zhong X, Fahmi A, Watts S, Ashcroft DM, Massey J, Fisher L, MacKenna B, Mehrkar A, Bacon SCJ, Goldacre B, Hand K, van Staa T, Palin V.", + "authorAffiliations": "", + "journalTitle": "Antimicrobial resistance and infection control", + "pubYear": "2023", + "date": "2023-09-16", + "isOpenAccess": "Y", + "keywords": "Infection; Antibiotics; Primary Care; Antibiotic Stewardship; Covid-19 Pandemic", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

There is concern that the COVID-19 pandemic altered the management of common infections in primary care. This study aimed to evaluate infection-coded consultation rates and antibiotic use during the pandemic and how any change may have affected clinical outcomes.

Methods

With the approval of NHS England, a retrospective cohort study using the OpenSAFELY platform analysed routinely collected electronic health data from GP practices in England between January 2019 and December 2021. Infection coded consultations and antibiotic prescriptions were used estimate multiple measures over calendar months, including age-sex adjusted prescribing rates, prescribing by infection and antibiotic type, infection consultation rates, coding quality and rate of same-day antibiotic prescribing for COVID-19 infections. Interrupted time series (ITS) estimated the effect of COVID-19 pandemic on infection-coded consultation rates. The impact of the pandemic on non- COVID-19 infection-related hospitalisations was also estimated.

Results

Records from 24 million patients were included. The rate of infection-related consultations fell for all infections (mean reduction of 39% in 2020 compared to 2019 mean rate), except for UTI which remained stable. Modelling infection-related consultation rates highlighted this with an incidence rate ratio of 0.44 (95% CI 0.36-0.53) for incident consultations and 0.43 (95% CI 0.33-0.54) for prevalent consultations. Lower respiratory tract infections (LRTI) saw the largest reduction of 0.11 (95% CI 0.07-0.17). Antibiotic prescribing rates fell with a mean reduction of 118.4 items per 1000 patients in 2020, returning to pre-pandemic rates by summer 2021. Prescribing for LRTI decreased 20% and URTI increased 15.9%. Over 60% of antibiotics were issued without an associated same-day infection code, which increased during the pandemic. Infection-related hospitalisations reduced (by 62%), with the largest reduction observed for pneumonia infections (72.9%). Same-day antibiotic prescribing for COVID-19 infection increased from 1 to 10.5% between the second and third national lockdowns and rose again during 2022.

Conclusions

Changes to consultations and hospital admissions may be driven by reduced transmission of non-COVID-19 infections due to reduced social mixing and lockdowns. Inconsistencies in coding practice emphasises the need for improvement to inform new antibiotic stewardship policies and prevent resistance to novel infections.", + "laySummary": "", + "urls": "pdf:https://aricjournal.biomedcentral.com/counter/pdf/10.1186/s13756-023-01280-6; doi:https://doi.org/10.1186/s13756-023-01280-6; html:https://europepmc.org/articles/PMC10504725; pdf:https://europepmc.org/articles/PMC10504725?pdf=render" + }, { "id": "32864476", "doi": "https://doi.org/10.23889/ijpds.v5i1.1157", @@ -17662,23 +17662,6 @@ "laySummary": "", "urls": "pdf:https://jamanetwork.com/journals/jamadermatology/articlepdf/2778389/jamadermatology_schmidt_2021_oi_210002_1623774349.64965.pdf; doi:https://doi.org/10.1001/jamadermatol.2021.0009; html:https://europepmc.org/articles/PMC8047754" }, - { - "id": "37705832", - "doi": "https://doi.org/10.5837/bjc.2023.003", - "title": "SGLT2 inhibitors in CKD and HFpEF: two new large trials and two new meta-analyses.", - "authorString": "Mayne KJ, Preiss D, Herrington WG.", - "authorAffiliations": "", - "journalTitle": "The British journal of cardiology", - "pubYear": "2023", - "date": "2023-02-21", - "isOpenAccess": "N", - "keywords": "Cardiovascular disease; Heart Failure; Chronic Kidney Disease; Sodium-Glucose Co-Transporter 2 (Sglt2) Inhibitor", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "", - "laySummary": "", - "urls": "doi:https://doi.org/10.5837/bjc.2023.003; html:https://europepmc.org/articles/PMC10495762; pdf:https://europepmc.org/articles/PMC10495762?pdf=render; doi:https://doi.org/10.5837/bjc.2023.003" - }, { "id": "35463778", "doi": "https://doi.org/10.3389/fcvm.2022.859310", @@ -17696,6 +17679,23 @@ "laySummary": "", "urls": "pdf:https://www.frontiersin.org/articles/10.3389/fcvm.2022.859310/pdf; doi:https://doi.org/10.3389/fcvm.2022.859310; html:https://europepmc.org/articles/PMC9021445; pdf:https://europepmc.org/articles/PMC9021445?pdf=render" }, + { + "id": "37705832", + "doi": "https://doi.org/10.5837/bjc.2023.003", + "title": "SGLT2 inhibitors in CKD and HFpEF: two new large trials and two new meta-analyses.", + "authorString": "Mayne KJ, Preiss D, Herrington WG.", + "authorAffiliations": "", + "journalTitle": "The British journal of cardiology", + "pubYear": "2023", + "date": "2023-02-21", + "isOpenAccess": "N", + "keywords": "Cardiovascular disease; Heart Failure; Chronic Kidney Disease; Sodium-Glucose Co-Transporter 2 (Sglt2) Inhibitor", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "", + "laySummary": "", + "urls": "doi:https://doi.org/10.5837/bjc.2023.003; html:https://europepmc.org/articles/PMC10495762; pdf:https://europepmc.org/articles/PMC10495762?pdf=render; doi:https://doi.org/10.5837/bjc.2023.003" + }, { "id": "36834176", "doi": "https://doi.org/10.3390/ijerph20043477", @@ -17713,23 +17713,6 @@ "laySummary": "", "urls": "pdf:https://www.mdpi.com/1660-4601/20/4/3477/pdf?version=1677135187; doi:https://doi.org/10.3390/ijerph20043477; html:https://europepmc.org/articles/PMC9967466; pdf:https://europepmc.org/articles/PMC9967466?pdf=render" }, - { - "id": "37897346", - "doi": "https://doi.org/10.1093/eurheartj/ehad727", - "title": "Five critical quality criteria for artificial intelligence-based prediction models.", - "authorString": "van Royen FS, Asselbergs FW, Alfonso F, Vardas P, van Smeden M.", - "authorAffiliations": "", - "journalTitle": "European heart journal", - "pubYear": "2023", - "date": "2023-12-01", - "isOpenAccess": "Y", - "keywords": "Prediction; Artificial intelligence; Diagnosis; Prognosis; Digital Health", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "To raise the quality of clinical artificial intelligence (AI) prediction modelling studies in the cardiovascular health domain and thereby improve their impact and relevancy, the editors for digital health, innovation, and quality standards of the European Heart Journal propose five minimal quality criteria for AI-based prediction model development and validation studies: complete reporting, carefully defined intended use of the model, rigorous validation, large enough sample size, and openness of code and software.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1093/eurheartj/ehad727; html:https://europepmc.org/articles/PMC10702458; pdf:https://europepmc.org/articles/PMC10702458?pdf=render" - }, { "id": "33497994", "doi": "https://doi.org/10.1016/j.puhe.2020.12.003", @@ -17765,21 +17748,21 @@ "urls": "pdf:http://www.jacionline.org/article/S0091674920317127/pdf; doi:https://doi.org/10.1016/j.jaci.2020.12.001; html:https://europepmc.org/articles/PMC8098860; pdf:https://europepmc.org/articles/PMC8098860?pdf=render" }, { - "id": "37814053", - "doi": "https://doi.org/10.1038/s41588-023-01522-8", - "title": "Age-dependent topic modeling of comorbidities in UK Biobank identifies disease subtypes with differential genetic risk.", - "authorString": "Jiang X, Zhang MJ, Zhang Y, Durvasula A, Inouye M, Holmes C, Price AL, McVean G.", + "id": "37897346", + "doi": "https://doi.org/10.1093/eurheartj/ehad727", + "title": "Five critical quality criteria for artificial intelligence-based prediction models.", + "authorString": "van Royen FS, Asselbergs FW, Alfonso F, Vardas P, van Smeden M.", "authorAffiliations": "", - "journalTitle": "Nature genetics", + "journalTitle": "European heart journal", "pubYear": "2023", - "date": "2023-10-09", + "date": "2023-12-01", "isOpenAccess": "Y", - "keywords": "", + "keywords": "Prediction; Artificial intelligence; Diagnosis; Prognosis; Digital Health", "nationalPriorities": "", "healthCategories": "", - "abstract": "The analysis of longitudinal data from electronic health records (EHRs) has the potential to improve clinical diagnoses and enable personalized medicine, motivating efforts to identify disease subtypes from patient comorbidity information. Here we introduce an age-dependent topic modeling (ATM) method that provides a low-rank representation of longitudinal records of hundreds of distinct diseases in large EHR datasets. We applied ATM to 282,957 UK Biobank samples, identifying 52 diseases with heterogeneous comorbidity profiles; analyses of 211,908 All of Us samples produced concordant results. We defined subtypes of the 52 heterogeneous diseases based on their comorbidity profiles and compared genetic risk across disease subtypes using polygenic risk scores (PRSs), identifying 18 disease subtypes whose PRS differed significantly from other subtypes of the same disease. We further identified specific genetic variants with subtype-dependent effects on disease risk. In conclusion, ATM identifies disease subtypes with differential genome-wide and locus-specific genetic risk profiles.", + "abstract": "To raise the quality of clinical artificial intelligence (AI) prediction modelling studies in the cardiovascular health domain and thereby improve their impact and relevancy, the editors for digital health, innovation, and quality standards of the European Heart Journal propose five minimal quality criteria for AI-based prediction model development and validation studies: complete reporting, carefully defined intended use of the model, rigorous validation, large enough sample size, and openness of code and software.", "laySummary": "", - "urls": "pdf:https://www.nature.com/articles/s41588-023-01522-8.pdf; doi:https://doi.org/10.1038/s41588-023-01522-8; html:https://europepmc.org/articles/PMC10632146; pdf:https://europepmc.org/articles/PMC10632146?pdf=render" + "urls": "doi:https://doi.org/10.1093/eurheartj/ehad727; html:https://europepmc.org/articles/PMC10702458; pdf:https://europepmc.org/articles/PMC10702458?pdf=render" }, { "id": "37008054", @@ -17798,6 +17781,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.14336/ad.2022.0829; doi:https://doi.org/10.14336/AD.2022.0829; html:https://europepmc.org/articles/PMC10017143; pdf:https://europepmc.org/articles/PMC10017143?pdf=render" }, + { + "id": "37814053", + "doi": "https://doi.org/10.1038/s41588-023-01522-8", + "title": "Age-dependent topic modeling of comorbidities in UK Biobank identifies disease subtypes with differential genetic risk.", + "authorString": "Jiang X, Zhang MJ, Zhang Y, Durvasula A, Inouye M, Holmes C, Price AL, McVean G.", + "authorAffiliations": "", + "journalTitle": "Nature genetics", + "pubYear": "2023", + "date": "2023-10-09", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "The analysis of longitudinal data from electronic health records (EHRs) has the potential to improve clinical diagnoses and enable personalized medicine, motivating efforts to identify disease subtypes from patient comorbidity information. Here we introduce an age-dependent topic modeling (ATM) method that provides a low-rank representation of longitudinal records of hundreds of distinct diseases in large EHR datasets. We applied ATM to 282,957 UK Biobank samples, identifying 52 diseases with heterogeneous comorbidity profiles; analyses of 211,908 All of Us samples produced concordant results. We defined subtypes of the 52 heterogeneous diseases based on their comorbidity profiles and compared genetic risk across disease subtypes using polygenic risk scores (PRSs), identifying 18 disease subtypes whose PRS differed significantly from other subtypes of the same disease. We further identified specific genetic variants with subtype-dependent effects on disease risk. In conclusion, ATM identifies disease subtypes with differential genome-wide and locus-specific genetic risk profiles.", + "laySummary": "", + "urls": "pdf:https://www.nature.com/articles/s41588-023-01522-8.pdf; doi:https://doi.org/10.1038/s41588-023-01522-8; html:https://europepmc.org/articles/PMC10632146; pdf:https://europepmc.org/articles/PMC10632146?pdf=render" + }, { "id": "38374065", "doi": "https://doi.org/10.1038/s41467-024-45779-x", @@ -17968,23 +17968,6 @@ "laySummary": "", "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/gps.5627; doi:https://doi.org/10.1002/gps.5627; html:https://europepmc.org/articles/PMC9292841; pdf:https://europepmc.org/articles/PMC9292841?pdf=render" }, - { - "id": "37850214", - "doi": "https://doi.org/10.1183/23120541.00110-2023", - "title": "Mapping inpatient care pathways for patients with COPD: an observational study using routinely collected electronic hospital record data.", - "authorString": "Evison F, Cooper R, Gallier S, Missier P, Sayer AA, Sapey E, Witham MD.", - "authorAffiliations": "", - "journalTitle": "ERJ open research", - "pubYear": "2023", - "date": "2023-09-01", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Introduction

Respiratory specialist ward care is associated with better outcomes for patients with COPD exacerbations. We assessed patient pathways and associated factors for people admitted to hospital with COPD exacerbations.

Methods

We analysed routinely collected electronic health data for patients admitted with COPD exacerbation in 2018 to Queen Elizabeth Hospital, Birmingham, UK. We extracted data on demographics, deprivation index, Elixhauser comorbidities, ward moves, length of stay, and in-hospital and 1-year mortality. We compared care pathways with recommended care pathways (transition from initial assessment area to respiratory wards or discharge). We used Markov state transition models to derive probabilities of following recommended pathways for patient subgroups.

Results

Of 42\u2009555 patients with unplanned admissions during 2018, 571 patients were admitted at least once with an exacerbation of COPD. The mean\u00b1sd age was 51\u00b111 years; 313 (55%) were women, 337 (59%) lived in the most deprived neighbourhoods and 45 (9%) were from non-white ethnic backgrounds. 428 (75.0%) had \u22654 comorbidities. Age >70\u2005years was associated with higher in-hospital and 1-year mortality, more places of care (wards) and longer length of stay; having \u22654 comorbidities was associated with higher mortality and longer length of stay. Older age was associated with a significantly lower probability of following a recommended pathway (>70\u2005years: 0.514, 95% CI 0.458-0.571; \u226470\u2005years: 0.636, 95% CI 0.572-0.696; p=0.004).

Conclusions

Only older age was associated with a lower chance of following recommended hospital pathways of care. Such analyses could help refine appropriate care pathways for patients with COPD exacerbations.", - "laySummary": "", - "urls": "pdf:https://openres.ersjournals.com/content/erjor/early/2023/08/24/23120541.00110-2023.full.pdf; doi:https://doi.org/10.1183/23120541.00110-2023; html:https://europepmc.org/articles/PMC10577591; pdf:https://europepmc.org/articles/PMC10577591?pdf=render" - }, { "id": "32954362", "doi": "https://doi.org/10.1038/s43016-020-0093-y", @@ -18002,6 +17985,23 @@ "laySummary": "", "urls": "html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7497842; doi:https://doi.org/10.1038/s43016-020-0093-y; html:https://europepmc.org/articles/PMC7497842; pdf:https://europepmc.org/articles/PMC7497842?pdf=render; doi:https://doi.org/10.1038/s43016-020-0093-y" }, + { + "id": "37850214", + "doi": "https://doi.org/10.1183/23120541.00110-2023", + "title": "Mapping inpatient care pathways for patients with COPD: an observational study using routinely collected electronic hospital record data.", + "authorString": "Evison F, Cooper R, Gallier S, Missier P, Sayer AA, Sapey E, Witham MD.", + "authorAffiliations": "", + "journalTitle": "ERJ open research", + "pubYear": "2023", + "date": "2023-09-01", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Introduction

Respiratory specialist ward care is associated with better outcomes for patients with COPD exacerbations. We assessed patient pathways and associated factors for people admitted to hospital with COPD exacerbations.

Methods

We analysed routinely collected electronic health data for patients admitted with COPD exacerbation in 2018 to Queen Elizabeth Hospital, Birmingham, UK. We extracted data on demographics, deprivation index, Elixhauser comorbidities, ward moves, length of stay, and in-hospital and 1-year mortality. We compared care pathways with recommended care pathways (transition from initial assessment area to respiratory wards or discharge). We used Markov state transition models to derive probabilities of following recommended pathways for patient subgroups.

Results

Of 42\u2009555 patients with unplanned admissions during 2018, 571 patients were admitted at least once with an exacerbation of COPD. The mean\u00b1sd age was 51\u00b111 years; 313 (55%) were women, 337 (59%) lived in the most deprived neighbourhoods and 45 (9%) were from non-white ethnic backgrounds. 428 (75.0%) had \u22654 comorbidities. Age >70\u2005years was associated with higher in-hospital and 1-year mortality, more places of care (wards) and longer length of stay; having \u22654 comorbidities was associated with higher mortality and longer length of stay. Older age was associated with a significantly lower probability of following a recommended pathway (>70\u2005years: 0.514, 95% CI 0.458-0.571; \u226470\u2005years: 0.636, 95% CI 0.572-0.696; p=0.004).

Conclusions

Only older age was associated with a lower chance of following recommended hospital pathways of care. Such analyses could help refine appropriate care pathways for patients with COPD exacerbations.", + "laySummary": "", + "urls": "pdf:https://openres.ersjournals.com/content/erjor/early/2023/08/24/23120541.00110-2023.full.pdf; doi:https://doi.org/10.1183/23120541.00110-2023; html:https://europepmc.org/articles/PMC10577591; pdf:https://europepmc.org/articles/PMC10577591?pdf=render" + }, { "id": "35130878", "doi": "https://doi.org/10.1186/s12916-022-02234-2", @@ -18070,23 +18070,6 @@ "laySummary": "", "urls": "pdf:https://www.frontiersin.org/articles/10.3389/fsurg.2022.870494/pdf; doi:https://doi.org/10.3389/fsurg.2022.870494; html:https://europepmc.org/articles/PMC9683031; pdf:https://europepmc.org/articles/PMC9683031?pdf=render" }, - { - "id": "38124256", - "doi": "https://doi.org/10.1093/ageing/afad219", - "title": "New Horizons in artificial intelligence in the healthcare of older people.", - "authorString": "Shiwani T, Relton S, Evans R, Kale A, Heaven A, Clegg A, Ageing Data Research Collaborative (Geridata) AI group\n, Todd O.", - "authorAffiliations": "", - "journalTitle": "Age and ageing", - "pubYear": "2023", - "date": "2023-12-01", - "isOpenAccess": "Y", - "keywords": "Artificial intelligence; Technology; Ageing; Health; Older People", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Artificial intelligence (AI) in healthcare describes algorithm-based computational techniques which manage and analyse large datasets to make inferences and predictions. There are many potential applications of AI in the care of older people, from clinical decision support systems that can support identification of delirium from clinical records to wearable devices that can predict the risk of a fall. We held four meetings of older people, clinicians and AI researchers. Three priority areas were identified for AI application in the care of older people. These included: monitoring and early diagnosis of disease, stratified care and care coordination between healthcare providers. However, the meetings also highlighted concerns that AI may exacerbate health inequity for older people through bias within AI models, lack of external validation amongst older people, infringements on privacy and autonomy, insufficient transparency of AI models and lack of safeguarding for errors. Creating effective interventions for older people requires a person-centred approach to account for the needs of older people, as well as sufficient clinical and technological governance to meet standards of generalisability, transparency and effectiveness. Education of clinicians and patients is also needed to ensure appropriate use of AI technologies, with investment in technological infrastructure required to ensure equity of access.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1093/ageing/afad219; html:https://europepmc.org/articles/PMC10733173; pdf:https://europepmc.org/articles/PMC10733173?pdf=render" - }, { "id": "33414147", "doi": "https://doi.org/10.1136/bmjopen-2020-041536", @@ -18104,6 +18087,23 @@ "laySummary": "", "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/11/1/e041536.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-041536; html:https://europepmc.org/articles/PMC7797241; pdf:https://europepmc.org/articles/PMC7797241?pdf=render" }, + { + "id": "38124256", + "doi": "https://doi.org/10.1093/ageing/afad219", + "title": "New Horizons in artificial intelligence in the healthcare of older people.", + "authorString": "Shiwani T, Relton S, Evans R, Kale A, Heaven A, Clegg A, Ageing Data Research Collaborative (Geridata) AI group\n, Todd O.", + "authorAffiliations": "", + "journalTitle": "Age and ageing", + "pubYear": "2023", + "date": "2023-12-01", + "isOpenAccess": "Y", + "keywords": "Artificial intelligence; Technology; Ageing; Health; Older People", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Artificial intelligence (AI) in healthcare describes algorithm-based computational techniques which manage and analyse large datasets to make inferences and predictions. There are many potential applications of AI in the care of older people, from clinical decision support systems that can support identification of delirium from clinical records to wearable devices that can predict the risk of a fall. We held four meetings of older people, clinicians and AI researchers. Three priority areas were identified for AI application in the care of older people. These included: monitoring and early diagnosis of disease, stratified care and care coordination between healthcare providers. However, the meetings also highlighted concerns that AI may exacerbate health inequity for older people through bias within AI models, lack of external validation amongst older people, infringements on privacy and autonomy, insufficient transparency of AI models and lack of safeguarding for errors. Creating effective interventions for older people requires a person-centred approach to account for the needs of older people, as well as sufficient clinical and technological governance to meet standards of generalisability, transparency and effectiveness. Education of clinicians and patients is also needed to ensure appropriate use of AI technologies, with investment in technological infrastructure required to ensure equity of access.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1093/ageing/afad219; html:https://europepmc.org/articles/PMC10733173; pdf:https://europepmc.org/articles/PMC10733173?pdf=render" + }, { "id": "34286192", "doi": "https://doi.org/10.7861/fhj.2021-0083", @@ -18274,23 +18274,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.7554/elife.64827; doi:https://doi.org/10.7554/eLife.64827; html:https://europepmc.org/articles/PMC8064756; pdf:https://europepmc.org/articles/PMC8064756?pdf=render" }, - { - "id": "37140153", - "doi": "https://doi.org/10.1093/ehjci/jead093", - "title": "Determinants of post-operative left ventricular dysfunction in degenerative mitral regurgitation.", - "authorString": "Althunayyan AM, Alborikan S, Badiani S, Wong K, Uppal R, Patel N, Petersen SE, Lloyd G, Bhattacharyya S.", - "authorAffiliations": "", - "journalTitle": "European heart journal. Cardiovascular Imaging", - "pubYear": "2023", - "date": "2023-08-01", - "isOpenAccess": "N", - "keywords": "Surgery; Mitral regurgitation; Mitral Valve Prolapse; Global Longitudinal Strain; Lv Volumes", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Aims

Chronic degenerative mitral regurgitation leads to volume overload causing left ventricular (LV) enlargement and eventually LV impairment. Current guidelines determining thresholds for intervention are based on LV diameters and ejection fraction (LVEF). There are sparse data examining the value of LV volumes and newer markers of LV performance on outcomes of surgery in mitral valve prolapse. The aim of this study is to identify the best marker of LV impairment after mitral valve surgery.

Methods and results

Prospective, observational study of patients with mitral valve prolapse undergoing mitral valve surgery. Pre-operative LV diameters, volumes, LVEF, global longitudinal strain (GLS), and myocardial work measured. Post-operative LV impairment defined as LVEF < 50% at 1 year post-surgery. Eighty-seven patients included. Thirteen percent developed post-operative LV impairment. Patients with post-operative LV dysfunction showed significantly larger indexed LV end-systolic diameters, indexed LV end-systolic volumes (LVESVi), lower LVEF, and more abnormal GLS than patients without post-operative LV dysfunction. In multivariate analysis, LVESVi [odds ratio 1.11 (95% CI 1.01-1.23), P = 0.039] and GLS [odds ratio 1.46 (95% CI 1.00-2.14), P = 0.054] were the only independent predictors of post-operative LV dysfunction. The optimal cut-off of 36.3 mL/m2 for LVESVi had a sensitivity of 82% and specificity of 78% for detection of post-operative LV impairment.

Conclusion

Post-operative LV impairment is common. Indexed LV volumes (36.3 mL/m2) provided the best marker of post-operative LV impairment.", - "laySummary": "", - "urls": "pdf:https://academic.oup.com/ehjcimaging/advance-article-pdf/doi/10.1093/ehjci/jead093/50200028/jead093.pdf; doi:https://doi.org/10.1093/ehjci/jead093" - }, { "id": "35667411", "doi": "https://doi.org/10.1016/j.jamda.2022.05.003", @@ -18308,6 +18291,23 @@ "laySummary": "", "urls": "pdf:https://cronfa.swan.ac.uk/Record/cronfa60151/Download/60151__25104__e0e71818d5bd49acba048a3d98682425.pdf; doi:https://doi.org/10.1016/j.jamda.2022.05.003" }, + { + "id": "37140153", + "doi": "https://doi.org/10.1093/ehjci/jead093", + "title": "Determinants of post-operative left ventricular dysfunction in degenerative mitral regurgitation.", + "authorString": "Althunayyan AM, Alborikan S, Badiani S, Wong K, Uppal R, Patel N, Petersen SE, Lloyd G, Bhattacharyya S.", + "authorAffiliations": "", + "journalTitle": "European heart journal. Cardiovascular Imaging", + "pubYear": "2023", + "date": "2023-08-01", + "isOpenAccess": "N", + "keywords": "Surgery; Mitral regurgitation; Mitral Valve Prolapse; Global Longitudinal Strain; Lv Volumes", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Aims

Chronic degenerative mitral regurgitation leads to volume overload causing left ventricular (LV) enlargement and eventually LV impairment. Current guidelines determining thresholds for intervention are based on LV diameters and ejection fraction (LVEF). There are sparse data examining the value of LV volumes and newer markers of LV performance on outcomes of surgery in mitral valve prolapse. The aim of this study is to identify the best marker of LV impairment after mitral valve surgery.

Methods and results

Prospective, observational study of patients with mitral valve prolapse undergoing mitral valve surgery. Pre-operative LV diameters, volumes, LVEF, global longitudinal strain (GLS), and myocardial work measured. Post-operative LV impairment defined as LVEF < 50% at 1 year post-surgery. Eighty-seven patients included. Thirteen percent developed post-operative LV impairment. Patients with post-operative LV dysfunction showed significantly larger indexed LV end-systolic diameters, indexed LV end-systolic volumes (LVESVi), lower LVEF, and more abnormal GLS than patients without post-operative LV dysfunction. In multivariate analysis, LVESVi [odds ratio 1.11 (95% CI 1.01-1.23), P = 0.039] and GLS [odds ratio 1.46 (95% CI 1.00-2.14), P = 0.054] were the only independent predictors of post-operative LV dysfunction. The optimal cut-off of 36.3 mL/m2 for LVESVi had a sensitivity of 82% and specificity of 78% for detection of post-operative LV impairment.

Conclusion

Post-operative LV impairment is common. Indexed LV volumes (36.3 mL/m2) provided the best marker of post-operative LV impairment.", + "laySummary": "", + "urls": "pdf:https://academic.oup.com/ehjcimaging/advance-article-pdf/doi/10.1093/ehjci/jead093/50200028/jead093.pdf; doi:https://doi.org/10.1093/ehjci/jead093" + }, { "id": "34673925", "doi": "https://doi.org/10.1093/ageing/afab201", @@ -18325,23 +18325,6 @@ "laySummary": "", "urls": "pdf:https://academic.oup.com/ageing/article-pdf/51/1/afab201/42083711/afab201.pdf; doi:https://doi.org/10.1093/ageing/afab201; html:https://europepmc.org/articles/PMC8753038; pdf:https://europepmc.org/articles/PMC8753038?pdf=render" }, - { - "id": "38450564", - "doi": "https://doi.org/10.1089/neu.2023.0462", - "title": "The Australian Traumatic Brain Injury Initiative: Systematic Review and Consensus Process to Determine the Predictive Value of Pre-existing Health Conditions for People with Moderate-Severe Traumatic Brain Injury.", - "authorString": "Antonic-Baker A, Auvrez C, Tao G, Bagg MK, Gadowski A, McKimmie A, Hicks AJ, Hill R, Romero L, Ponsford JL, Lannin NA, Gabbe BJ, Cameron PA, Cooper DJ, Rushworth N, Fitzgerald M, O'Brien TJ.", - "authorAffiliations": "", - "journalTitle": "Journal of neurotrauma", - "pubYear": "2024", - "date": "2024-04-15", - "isOpenAccess": "N", - "keywords": "Health care; Mental health; Comorbidity; Common Data Elements; Multiple Chronic Conditions; Brain Injuries, Traumatic; Outcome Assessment, Systematic Review [Publication Type]", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "The first aim of the Australian Traumatic Brain Injury Initiative (AUS-TBI) encompasses development of a set of measures that comprehensively predict outcomes for people with moderate-severe TBI across Australia. This process engaged diverse stakeholders and information sources across six areas: social, health, and clinical factors; biological markers; treatments; and longer-term outcomes. Here, we report the systematic review of pre-existing health conditions as predictors of outcome for people with moderate-severe TBI. Standardized searches were implemented across databases until March 31, 2022. English-language reports of studies evaluating association between pre-existing health conditions and clinical outcome in at least 10 patients with moderate-severe TBI were included. A predefined algorithm was used to assign a judgement of predictive value to each observed association. The list of identified pre-existing health conditions was then discussed with key stakeholders during a consensus meeting to determine the feasibility of incorporating them into standard care. The searches retrieved 22,217 records, of which 47 articles were included. The process led to identification of 88 unique health predictors (homologized to 21 predictor categories) of 55 outcomes (homologized to 19 outcome categories). Only pre-existing health conditions with high and moderate predictive values were discussed during the consensus meeting. Following the consensus meeting, 5 out of 11 were included (migraine, mental health conditions, \u22654 pre-existing health conditions, osteoporosis, and body mass index [BMI]) as common data elements in the AUS-TBI data dictionary. Upon further discussion, 3 additional pre-existing health conditions were included. These are pre-existing heart disease, frailty score, and previous incidence of TBI.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1089/neu.2023.0462" - }, { "id": "34026049", "doi": "https://doi.org/10.12688/f1000research.25484.2", @@ -18359,6 +18342,23 @@ "laySummary": "", "urls": "pdf:https://f1000research.com/articles/9-1095/v2/pdf; doi:https://doi.org/10.12688/f1000research.25484.2; html:https://europepmc.org/articles/PMC8108552; pdf:https://europepmc.org/articles/PMC8108552?pdf=render" }, + { + "id": "38450564", + "doi": "https://doi.org/10.1089/neu.2023.0462", + "title": "The Australian Traumatic Brain Injury Initiative: Systematic Review and Consensus Process to Determine the Predictive Value of Pre-existing Health Conditions for People with Moderate-Severe Traumatic Brain Injury.", + "authorString": "Antonic-Baker A, Auvrez C, Tao G, Bagg MK, Gadowski A, McKimmie A, Hicks AJ, Hill R, Romero L, Ponsford JL, Lannin NA, Gabbe BJ, Cameron PA, Cooper DJ, Rushworth N, Fitzgerald M, O'Brien TJ.", + "authorAffiliations": "", + "journalTitle": "Journal of neurotrauma", + "pubYear": "2024", + "date": "2024-04-15", + "isOpenAccess": "N", + "keywords": "Health care; Mental health; Comorbidity; Common Data Elements; Multiple Chronic Conditions; Brain Injuries, Traumatic; Outcome Assessment, Systematic Review [Publication Type]", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "The first aim of the Australian Traumatic Brain Injury Initiative (AUS-TBI) encompasses development of a set of measures that comprehensively predict outcomes for people with moderate-severe TBI across Australia. This process engaged diverse stakeholders and information sources across six areas: social, health, and clinical factors; biological markers; treatments; and longer-term outcomes. Here, we report the systematic review of pre-existing health conditions as predictors of outcome for people with moderate-severe TBI. Standardized searches were implemented across databases until March 31, 2022. English-language reports of studies evaluating association between pre-existing health conditions and clinical outcome in at least 10 patients with moderate-severe TBI were included. A predefined algorithm was used to assign a judgement of predictive value to each observed association. The list of identified pre-existing health conditions was then discussed with key stakeholders during a consensus meeting to determine the feasibility of incorporating them into standard care. The searches retrieved 22,217 records, of which 47 articles were included. The process led to identification of 88 unique health predictors (homologized to 21 predictor categories) of 55 outcomes (homologized to 19 outcome categories). Only pre-existing health conditions with high and moderate predictive values were discussed during the consensus meeting. Following the consensus meeting, 5 out of 11 were included (migraine, mental health conditions, \u22654 pre-existing health conditions, osteoporosis, and body mass index [BMI]) as common data elements in the AUS-TBI data dictionary. Upon further discussion, 3 additional pre-existing health conditions were included. These are pre-existing heart disease, frailty score, and previous incidence of TBI.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1089/neu.2023.0462" + }, { "id": "33653161", "doi": "https://doi.org/10.1177/1740774520976617", @@ -18376,23 +18376,6 @@ "laySummary": "", "urls": "pdf:https://journals.sagepub.com/doi/pdf/10.1177/1740774520976617; doi:https://doi.org/10.1177/1740774520976617; html:https://europepmc.org/articles/PMC8174009; pdf:https://europepmc.org/articles/PMC8174009?pdf=render" }, - { - "id": "35634533", - "doi": "https://doi.org/10.12688/wellcomeopenres.17360.1", - "title": "A comprehensive high cost drugs dataset from the NHS in England - An OpenSAFELY-TPP Short Data Report.", - "authorString": "Rowan A, Bates C, Hulme W, Evans D, Davy S, A Kennedy N, Galloway J, E Mansfield K, Bechman K, Matthewman J, Yates M, Brown J, Schultze A, Norton S, J Walker A, E Morton C, Bhaskaran K, T Rentsch C, Williamson E, Croker R, Bacon S, Hickman G, Ward T, Green A, Fisher L, J Curtis H, Tazare J, M Eggo R, Inglesby P, Cockburn J, I McDonald H, Mathur R, Ys Wong A, Forbes H, Parry J, Hester F, Harper S, J Douglas I, Smeeth L, A Tomlinson L, W Lees C, Evans S, Smith C, M Langan S, Mehkar A, MacKenna B, Goldacre B.", - "authorAffiliations": "", - "journalTitle": "Wellcome open research", - "pubYear": "2021", - "date": "2021-12-22", - "isOpenAccess": "Y", - "keywords": "Medications; Biosimilars; Healthcare Administration; Opensafely", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Background: At the outset of the COVID-19 pandemic, there was no routine comprehensive hospital medicines data from the UK available to researchers. These records can be important for many analyses including the effect of certain medicines on the risk of severe COVID-19 outcomes. With the approval of NHS England, we set out to obtain data on one specific group of medicines, \"high-cost drugs\" (HCD) which are typically specialist medicines for the management of long-term conditions, prescribed by hospitals to patients. Additionally, we aimed to make these data available to all approved researchers in OpenSAFELY-TPP. This report is intended to support all studies carried out in OpenSAFELY-TPP, and those elsewhere, working with this dataset or similar data. Methods: Working with the North East Commissioning Support Unit and NHS Digital, we arranged for collation of a single national HCD dataset to help inform responses to the COVID-19 pandemic. The dataset was developed from payment submissions from hospitals to commissioners. Results: In the financial year (FY) 2018/19 there were 2.8 million submissions for 1.1 million unique patient IDs recorded in the HCD. The average number of submissions per patient over the year was 2.6. In FY 2019/20 there were 4.0 million submissions for 1.3 million unique patient IDs. The average number of submissions per patient over the year was 3.1. Of the 21 variables in the dataset, three are now available for analysis in OpenSafely-TPP: Financial year and month of drug being dispensed; drug name; and a description of the drug dispensed. Conclusions: We have described the process for sourcing a national HCD dataset, making these data available for COVID-19-related analysis through OpenSAFELY-TPP and provided information on the variables included in the dataset, data coverage and an initial descriptive analysis.", - "laySummary": "", - "urls": "doi:https://doi.org/10.12688/wellcomeopenres.17360.1; html:https://europepmc.org/articles/PMC9120928; pdf:https://europepmc.org/articles/PMC9120928?pdf=render" - }, { "id": "32665523", "doi": "https://doi.org/10.1097/hjh.0000000000002579", @@ -18410,6 +18393,23 @@ "laySummary": "", "urls": "html:https://journals.lww.com/jhypertension/Fulltext/2020/12000/Association_of_SBP_and_BMI_with_cognitive_and.22.aspx; doi:https://doi.org/10.1097/HJH.0000000000002579" }, + { + "id": "35634533", + "doi": "https://doi.org/10.12688/wellcomeopenres.17360.1", + "title": "A comprehensive high cost drugs dataset from the NHS in England - An OpenSAFELY-TPP Short Data Report.", + "authorString": "Rowan A, Bates C, Hulme W, Evans D, Davy S, A Kennedy N, Galloway J, E Mansfield K, Bechman K, Matthewman J, Yates M, Brown J, Schultze A, Norton S, J Walker A, E Morton C, Bhaskaran K, T Rentsch C, Williamson E, Croker R, Bacon S, Hickman G, Ward T, Green A, Fisher L, J Curtis H, Tazare J, M Eggo R, Inglesby P, Cockburn J, I McDonald H, Mathur R, Ys Wong A, Forbes H, Parry J, Hester F, Harper S, J Douglas I, Smeeth L, A Tomlinson L, W Lees C, Evans S, Smith C, M Langan S, Mehkar A, MacKenna B, Goldacre B.", + "authorAffiliations": "", + "journalTitle": "Wellcome open research", + "pubYear": "2021", + "date": "2021-12-22", + "isOpenAccess": "Y", + "keywords": "Medications; Biosimilars; Healthcare Administration; Opensafely", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Background: At the outset of the COVID-19 pandemic, there was no routine comprehensive hospital medicines data from the UK available to researchers. These records can be important for many analyses including the effect of certain medicines on the risk of severe COVID-19 outcomes. With the approval of NHS England, we set out to obtain data on one specific group of medicines, \"high-cost drugs\" (HCD) which are typically specialist medicines for the management of long-term conditions, prescribed by hospitals to patients. Additionally, we aimed to make these data available to all approved researchers in OpenSAFELY-TPP. This report is intended to support all studies carried out in OpenSAFELY-TPP, and those elsewhere, working with this dataset or similar data. Methods: Working with the North East Commissioning Support Unit and NHS Digital, we arranged for collation of a single national HCD dataset to help inform responses to the COVID-19 pandemic. The dataset was developed from payment submissions from hospitals to commissioners. Results: In the financial year (FY) 2018/19 there were 2.8 million submissions for 1.1 million unique patient IDs recorded in the HCD. The average number of submissions per patient over the year was 2.6. In FY 2019/20 there were 4.0 million submissions for 1.3 million unique patient IDs. The average number of submissions per patient over the year was 3.1. Of the 21 variables in the dataset, three are now available for analysis in OpenSafely-TPP: Financial year and month of drug being dispensed; drug name; and a description of the drug dispensed. Conclusions: We have described the process for sourcing a national HCD dataset, making these data available for COVID-19-related analysis through OpenSAFELY-TPP and provided information on the variables included in the dataset, data coverage and an initial descriptive analysis.", + "laySummary": "", + "urls": "doi:https://doi.org/10.12688/wellcomeopenres.17360.1; html:https://europepmc.org/articles/PMC9120928; pdf:https://europepmc.org/articles/PMC9120928?pdf=render" + }, { "id": "33692093", "doi": "https://doi.org/10.1136/heartjnl-2020-318557", @@ -18444,23 +18444,6 @@ "laySummary": "", "urls": "pdf:https://academic.oup.com/ehjcimaging/article-pdf/22/8/950/39199744/jeaa088.pdf; doi:https://doi.org/10.1093/ehjci/jeaa088; html:https://europepmc.org/articles/PMC8291671; pdf:https://europepmc.org/articles/PMC8291671?pdf=render" }, - { - "id": "37662524", - "doi": "https://doi.org/10.1016/j.eclinm.2023.102172", - "title": "Tafamidis treatment in patients with transthyretin amyloid cardiomyopathy: a systematic review and meta-analysis.", - "authorString": "Wang J, Chen H, Tang Z, Zhang J, Xu Y, Wan K, Hussain K, Gkoutos GV, Han Y, Chen Y.", - "authorAffiliations": "", - "journalTitle": "EClinicalMedicine", - "pubYear": "2023", - "date": "2023-08-24", - "isOpenAccess": "Y", - "keywords": "Prognosis; Tafamidis; Attr; Transthyretin Amyloid Cardiomyopathy", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Previous studies have reported that tafamidis treatment was associated with better outcomes in patients with transthyretin amyloid cardiomyopathy (ATTR-CM) compared with those without tafamidis treatment. Therefore, we aimed to systematically assess the association of tafamidis treatment with outcomes in patients with ATTR-CM.

Methods

The protocol for this systematic review and meta-analysis was registered in the PROSPERO (CRD42022381985). Pubmed, Ovid Embase, Scopus, Cochrane Library, and Web of Science were interrogated to identify studies that evaluated the impact of tafamidis on prognosis in ATTR-CM, from January 1, 2000 to June 1, 2023. A random-effects model was used to determine the pooled risk ratio (RR) for the adverse endpoints. In addition, the main outcomes included all-cause death or heart transplantation, the composite endpoints included all-cause death, heart transplantation, cardiac-assist device implantation, heart failure exacerbations, and hospitalization.

Findings

Fifteen studies comprising 2765 patients (mean age 75.9\u00a0\u00b1\u00a09.3 years; 83.7% male) with a mean follow-up duration of 18.7\u00a0\u00b1\u00a017.1 months were included in the meta-analysis. There was a decrease in left ventricular ejection fraction (LVEF) (standard mean differences (SMD:\u00a0-0.17; 95% confidence interval (CI),\u00a0-0.31 to\u00a0-0.03; P\u00a0=\u00a00.02) but were no significant differences in intraventricular septum (IVS) thickness or global longitudinal strain (GLS) after tafamidis treatment. However, subgroup analysis showed no significant deterioration in LVEF in the patients with wild-type ATTR after tafamidis treatment (SMD:\u00a0-0.11; 95% CI,\u00a0-0.34 to 0.12, P\u00a0=\u00a00.34). In addition, the group with tafamidis treatment had a decreased risk for all-cause death or heart transplantation compared to patients without treatment (the pooled RR, 0.44; 95% CI, 0.31-0.65; P\u00a0<\u00a00.01). Subgroup analysis showed that there was no significant difference of tafamidis on the outcomes in patients with wild-type or hereditary ATTR (RR, 0.44; 95% CI, 0.27-0.73 versus 0.21, 95% CI, 0.11-0.40, P\u00a0=\u00a00.08). Furthermore, tafamidis treatment was associated with a lower risk of the composite endpoint (RR, 0.57; 95% CI, 0.42-0.77; P\u00a0<\u00a00.01).

Interpretation

Our findings suggested that there was no significant deterioration in LVEF in the patients with wild-type ATTR after tafamidis treatment. In addition, tafamidis treatment was associated with a low risk of all-cause death and adverse cardiovascular events.

Funding

This work was supported by grants from the Natural Science Foundation of Sichuan Province [Grant Number: 23NSFSC4589] and the National Natural Science Foundation of China [Grant Number: 82202248].", - "laySummary": "", - "urls": "doi:https://doi.org/10.1016/j.eclinm.2023.102172; html:https://europepmc.org/articles/PMC10474377; pdf:https://europepmc.org/articles/PMC10474377?pdf=render" - }, { "id": "36682888", "doi": "https://doi.org/10.1111/cch.13097", @@ -18478,6 +18461,23 @@ "laySummary": "", "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/cch.13097; doi:https://doi.org/10.1111/cch.13097; html:https://europepmc.org/articles/PMC10946723; pdf:https://europepmc.org/articles/PMC10946723?pdf=render" }, + { + "id": "37662524", + "doi": "https://doi.org/10.1016/j.eclinm.2023.102172", + "title": "Tafamidis treatment in patients with transthyretin amyloid cardiomyopathy: a systematic review and meta-analysis.", + "authorString": "Wang J, Chen H, Tang Z, Zhang J, Xu Y, Wan K, Hussain K, Gkoutos GV, Han Y, Chen Y.", + "authorAffiliations": "", + "journalTitle": "EClinicalMedicine", + "pubYear": "2023", + "date": "2023-08-24", + "isOpenAccess": "Y", + "keywords": "Prognosis; Tafamidis; Attr; Transthyretin Amyloid Cardiomyopathy", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Previous studies have reported that tafamidis treatment was associated with better outcomes in patients with transthyretin amyloid cardiomyopathy (ATTR-CM) compared with those without tafamidis treatment. Therefore, we aimed to systematically assess the association of tafamidis treatment with outcomes in patients with ATTR-CM.

Methods

The protocol for this systematic review and meta-analysis was registered in the PROSPERO (CRD42022381985). Pubmed, Ovid Embase, Scopus, Cochrane Library, and Web of Science were interrogated to identify studies that evaluated the impact of tafamidis on prognosis in ATTR-CM, from January 1, 2000 to June 1, 2023. A random-effects model was used to determine the pooled risk ratio (RR) for the adverse endpoints. In addition, the main outcomes included all-cause death or heart transplantation, the composite endpoints included all-cause death, heart transplantation, cardiac-assist device implantation, heart failure exacerbations, and hospitalization.

Findings

Fifteen studies comprising 2765 patients (mean age 75.9\u00a0\u00b1\u00a09.3 years; 83.7% male) with a mean follow-up duration of 18.7\u00a0\u00b1\u00a017.1 months were included in the meta-analysis. There was a decrease in left ventricular ejection fraction (LVEF) (standard mean differences (SMD:\u00a0-0.17; 95% confidence interval (CI),\u00a0-0.31 to\u00a0-0.03; P\u00a0=\u00a00.02) but were no significant differences in intraventricular septum (IVS) thickness or global longitudinal strain (GLS) after tafamidis treatment. However, subgroup analysis showed no significant deterioration in LVEF in the patients with wild-type ATTR after tafamidis treatment (SMD:\u00a0-0.11; 95% CI,\u00a0-0.34 to 0.12, P\u00a0=\u00a00.34). In addition, the group with tafamidis treatment had a decreased risk for all-cause death or heart transplantation compared to patients without treatment (the pooled RR, 0.44; 95% CI, 0.31-0.65; P\u00a0<\u00a00.01). Subgroup analysis showed that there was no significant difference of tafamidis on the outcomes in patients with wild-type or hereditary ATTR (RR, 0.44; 95% CI, 0.27-0.73 versus 0.21, 95% CI, 0.11-0.40, P\u00a0=\u00a00.08). Furthermore, tafamidis treatment was associated with a lower risk of the composite endpoint (RR, 0.57; 95% CI, 0.42-0.77; P\u00a0<\u00a00.01).

Interpretation

Our findings suggested that there was no significant deterioration in LVEF in the patients with wild-type ATTR after tafamidis treatment. In addition, tafamidis treatment was associated with a low risk of all-cause death and adverse cardiovascular events.

Funding

This work was supported by grants from the Natural Science Foundation of Sichuan Province [Grant Number: 23NSFSC4589] and the National Natural Science Foundation of China [Grant Number: 82202248].", + "laySummary": "", + "urls": "doi:https://doi.org/10.1016/j.eclinm.2023.102172; html:https://europepmc.org/articles/PMC10474377; pdf:https://europepmc.org/articles/PMC10474377?pdf=render" + }, { "id": "32763878", "doi": "https://doi.org/10.2196/18690", @@ -18597,23 +18597,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1093/jamia/ocz105; doi:https://doi.org/10.1093/jamia/ocz105; html:https://europepmc.org/articles/PMC6857510; pdf:https://europepmc.org/articles/PMC6857510?pdf=render" }, - { - "id": "36538350", - "doi": "https://doi.org/10.2196/41200", - "title": "Identifying Patterns of Clinical Interest in Clinicians' Treatment Preferences: Hypothesis-free Data Science Approach to Prioritizing Prescribing Outliers for Clinical Review.", - "authorString": "MacKenna B, Curtis HJ, Hopcroft LEM, Walker AJ, Croker R, Macdonald O, Evans SJW, Inglesby P, Evans D, Morley J, Bacon SCJ, Goldacre B.", - "authorAffiliations": "", - "journalTitle": "JMIR medical informatics", - "pubYear": "2022", - "date": "2022-12-20", - "isOpenAccess": "Y", - "keywords": "Prescribing; Clinical Audit; Antipsychotics; Pericyazine; Data Science; Nhs England; Promazine Hydrochloride", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Data analysis is used to identify signals suggestive of variation in treatment choice or clinical outcome. Analyses to date have generally focused on a hypothesis-driven approach.

Objective

This study aimed to develop a hypothesis-free approach to identify unusual prescribing behavior in primary care data. We aimed to apply this methodology to a national data set in a cross-sectional study to identify chemicals with significant variation in use across Clinical Commissioning Groups (CCGs) for further clinical review, thereby demonstrating proof of concept for prioritization approaches.

Methods

Here we report a new data-driven approach to identify unusual prescribing behaviour in primary care data. This approach first applies a set of filtering steps to identify chemicals with prescribing rate distributions likely to contain outliers, then applies two ranking approaches to identify the most extreme outliers amongst those candidates. This methodology has been applied to three months of national prescribing data (June-August 2017).

Results

Our methodology provides rankings for all chemicals by administrative region. We provide illustrative results for 2 antipsychotic drugs of particular clinical interest: promazine hydrochloride and pericyazine, which rank highly by outlier metrics. Specifically, our method identifies that, while promazine hydrochloride and pericyazine are barely used by most clinicians (with national prescribing rates of 11.1 and 6.2 per 1000 antipsychotic prescriptions, respectively), they make up a substantial proportion of antipsychotic prescribing in 2 small geographic regions in England during the study period (with maximum regional prescribing rates of 298.7 and 241.1 per 1000 antipsychotic prescriptions, respectively).

Conclusions

Our hypothesis-free approach is able to identify candidates for audit and review in clinical practice. To illustrate this, we provide 2 examples of 2 very unusual antipsychotics used disproportionately in 2 small geographic areas of England.", - "laySummary": "", - "urls": "pdf:https://medinform.jmir.org/2022/12/e41200/PDF; doi:https://doi.org/10.2196/41200; html:https://europepmc.org/articles/PMC9812268" - }, { "id": "32946551", "doi": "https://doi.org/10.1093/ageing/afaa158", @@ -18631,6 +18614,23 @@ "laySummary": "", "urls": "pdf:https://academic.oup.com/ageing/article-pdf/49/6/1056/33993322/afaa158.pdf; doi:https://doi.org/10.1093/ageing/afaa158; html:https://europepmc.org/articles/PMC7583515; pdf:https://europepmc.org/articles/PMC7583515?pdf=render" }, + { + "id": "36538350", + "doi": "https://doi.org/10.2196/41200", + "title": "Identifying Patterns of Clinical Interest in Clinicians' Treatment Preferences: Hypothesis-free Data Science Approach to Prioritizing Prescribing Outliers for Clinical Review.", + "authorString": "MacKenna B, Curtis HJ, Hopcroft LEM, Walker AJ, Croker R, Macdonald O, Evans SJW, Inglesby P, Evans D, Morley J, Bacon SCJ, Goldacre B.", + "authorAffiliations": "", + "journalTitle": "JMIR medical informatics", + "pubYear": "2022", + "date": "2022-12-20", + "isOpenAccess": "Y", + "keywords": "Prescribing; Clinical Audit; Antipsychotics; Pericyazine; Data Science; Nhs England; Promazine Hydrochloride", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Data analysis is used to identify signals suggestive of variation in treatment choice or clinical outcome. Analyses to date have generally focused on a hypothesis-driven approach.

Objective

This study aimed to develop a hypothesis-free approach to identify unusual prescribing behavior in primary care data. We aimed to apply this methodology to a national data set in a cross-sectional study to identify chemicals with significant variation in use across Clinical Commissioning Groups (CCGs) for further clinical review, thereby demonstrating proof of concept for prioritization approaches.

Methods

Here we report a new data-driven approach to identify unusual prescribing behaviour in primary care data. This approach first applies a set of filtering steps to identify chemicals with prescribing rate distributions likely to contain outliers, then applies two ranking approaches to identify the most extreme outliers amongst those candidates. This methodology has been applied to three months of national prescribing data (June-August 2017).

Results

Our methodology provides rankings for all chemicals by administrative region. We provide illustrative results for 2 antipsychotic drugs of particular clinical interest: promazine hydrochloride and pericyazine, which rank highly by outlier metrics. Specifically, our method identifies that, while promazine hydrochloride and pericyazine are barely used by most clinicians (with national prescribing rates of 11.1 and 6.2 per 1000 antipsychotic prescriptions, respectively), they make up a substantial proportion of antipsychotic prescribing in 2 small geographic regions in England during the study period (with maximum regional prescribing rates of 298.7 and 241.1 per 1000 antipsychotic prescriptions, respectively).

Conclusions

Our hypothesis-free approach is able to identify candidates for audit and review in clinical practice. To illustrate this, we provide 2 examples of 2 very unusual antipsychotics used disproportionately in 2 small geographic areas of England.", + "laySummary": "", + "urls": "pdf:https://medinform.jmir.org/2022/12/e41200/PDF; doi:https://doi.org/10.2196/41200; html:https://europepmc.org/articles/PMC9812268" + }, { "id": "36942567", "doi": "https://doi.org/10.1161/circep.122.011585", @@ -18733,23 +18733,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1093/ehjdh/ztad049; html:https://europepmc.org/articles/PMC10689918; pdf:https://europepmc.org/articles/PMC10689918?pdf=render" }, - { - "id": "33468531", - "doi": "https://doi.org/10.1136/bmjopen-2020-047101", - "title": "Protocol for the development of the Wales Multimorbidity e-Cohort (WMC): data sources and methods to construct a population-based research platform to investigate multimorbidity.", - "authorString": "Lyons J, Akbari A, Agrawal U, Harper G, Azcoaga-Lorenzo A, Bailey R, Rafferty J, Watkins A, Fry R, McCowan C, Dezateux C, Robson JP, Peek N, Holmes C, Denaxas S, Owen R, Abrams KR, John A, O'Reilly D, Richardson S, Hall M, Gale CP, Davies J, Davies C, Cross L, Gallacher J, Chess J, Brookes AJ, Lyons RA.", - "authorAffiliations": "", - "journalTitle": "BMJ open", - "pubYear": "2021", - "date": "2021-01-19", - "isOpenAccess": "Y", - "keywords": "epidemiology; Public Health; Primary Care; Geriatric Medicine; Health Policy", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Introduction

Multimorbidity is widely recognised as the presence of two or more concurrent long-term conditions, yet remains a poorly understood global issue despite increasing in prevalence.We have created the Wales Multimorbidity e-Cohort (WMC) to provide an accessible research ready data asset to further the understanding of multimorbidity. Our objectives are to create a platform to support research which would help to understand prevalence, trajectories and determinants in multimorbidity, characterise clusters that lead to highest burden on individuals and healthcare services, and evaluate and provide new multimorbidity phenotypes and algorithms to the National Health Service and research communities to support prevention, healthcare planning and the management of individuals with multimorbidity.

Methods and analysis

The WMC has been created and derived from multisourced demographic, administrative and electronic health record data relating to the Welsh population in the Secure Anonymised Information Linkage (SAIL) Databank. The WMC consists of 2.9 million people alive and living in Wales on the 1 January 2000 with follow-up until 31 December 2019, Welsh residency break or death. Published comorbidity indices and phenotype code lists will be used to measure and conceptualise multimorbidity.Study outcomes will include: (1) a description of multimorbidity using published data phenotype algorithms/ontologies, (2) investigation of the associations between baseline demographic factors and multimorbidity, (3) identification of temporal trajectories of clusters of conditions and multimorbidity and (4) investigation of multimorbidity clusters with poor outcomes such as mortality and high healthcare service utilisation.

Ethics and dissemination

The SAIL Databank independent Information Governance Review Panel has approved this study (SAIL Project: 0911). Study findings will be presented to policy groups, public meetings, national and international conferences, and published in peer-reviewed journals.", - "laySummary": "", - "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/11/1/e047101.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-047101; html:https://europepmc.org/articles/PMC7817800; pdf:https://europepmc.org/articles/PMC7817800?pdf=render" - }, { "id": "31398202", "doi": "https://doi.org/10.1371/journal.pone.0220771", @@ -18767,6 +18750,23 @@ "laySummary": "", "urls": "pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0220771&type=printable; doi:https://doi.org/10.1371/journal.pone.0220771; html:https://europepmc.org/articles/PMC6688802; pdf:https://europepmc.org/articles/PMC6688802?pdf=render" }, + { + "id": "33468531", + "doi": "https://doi.org/10.1136/bmjopen-2020-047101", + "title": "Protocol for the development of the Wales Multimorbidity e-Cohort (WMC): data sources and methods to construct a population-based research platform to investigate multimorbidity.", + "authorString": "Lyons J, Akbari A, Agrawal U, Harper G, Azcoaga-Lorenzo A, Bailey R, Rafferty J, Watkins A, Fry R, McCowan C, Dezateux C, Robson JP, Peek N, Holmes C, Denaxas S, Owen R, Abrams KR, John A, O'Reilly D, Richardson S, Hall M, Gale CP, Davies J, Davies C, Cross L, Gallacher J, Chess J, Brookes AJ, Lyons RA.", + "authorAffiliations": "", + "journalTitle": "BMJ open", + "pubYear": "2021", + "date": "2021-01-19", + "isOpenAccess": "Y", + "keywords": "epidemiology; Public Health; Primary Care; Geriatric Medicine; Health Policy", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Introduction

Multimorbidity is widely recognised as the presence of two or more concurrent long-term conditions, yet remains a poorly understood global issue despite increasing in prevalence.We have created the Wales Multimorbidity e-Cohort (WMC) to provide an accessible research ready data asset to further the understanding of multimorbidity. Our objectives are to create a platform to support research which would help to understand prevalence, trajectories and determinants in multimorbidity, characterise clusters that lead to highest burden on individuals and healthcare services, and evaluate and provide new multimorbidity phenotypes and algorithms to the National Health Service and research communities to support prevention, healthcare planning and the management of individuals with multimorbidity.

Methods and analysis

The WMC has been created and derived from multisourced demographic, administrative and electronic health record data relating to the Welsh population in the Secure Anonymised Information Linkage (SAIL) Databank. The WMC consists of 2.9 million people alive and living in Wales on the 1 January 2000 with follow-up until 31 December 2019, Welsh residency break or death. Published comorbidity indices and phenotype code lists will be used to measure and conceptualise multimorbidity.Study outcomes will include: (1) a description of multimorbidity using published data phenotype algorithms/ontologies, (2) investigation of the associations between baseline demographic factors and multimorbidity, (3) identification of temporal trajectories of clusters of conditions and multimorbidity and (4) investigation of multimorbidity clusters with poor outcomes such as mortality and high healthcare service utilisation.

Ethics and dissemination

The SAIL Databank independent Information Governance Review Panel has approved this study (SAIL Project: 0911). Study findings will be presented to policy groups, public meetings, national and international conferences, and published in peer-reviewed journals.", + "laySummary": "", + "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/11/1/e047101.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-047101; html:https://europepmc.org/articles/PMC7817800; pdf:https://europepmc.org/articles/PMC7817800?pdf=render" + }, { "id": "33503030", "doi": "https://doi.org/10.1371/journal.pone.0245636", @@ -18801,6 +18801,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/s2589-7500(22)00151-0; doi:https://doi.org/10.1016/S2589-7500(22)00151-0" }, + { + "id": "34088700", + "doi": "https://doi.org/10.2337/dc20-2518", + "title": "Type 2 Diabetes, Metabolic Traits, and Risk of Heart Failure: A Mendelian Randomization Study.", + "authorString": "Mordi IR, Lumbers RT, Palmer CNA, Pearson ER, Sattar N, Holmes MV, Lang CC, HERMES Consortium.", + "authorAffiliations": "", + "journalTitle": "Diabetes care", + "pubYear": "2021", + "date": "2021-06-04", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Objective

The aim of this study was to use Mendelian randomization (MR) techniques to estimate the causal relationships between genetic liability to type 2 diabetes (T2D), glycemic traits, and risk of heart failure (HF).

Research design and methods

Summary-level data were obtained from genome-wide association studies of T2D, insulin resistance (IR), glycated hemoglobin, fasting insulin and glucose, and HF. MR was conducted using the inverse-variance weighted method. Sensitivity analyses included the MR-Egger method, weighted median and mode methods, and multivariable MR conditioning on potential mediators.

Results

Genetic liability to T2D was causally related to higher risk of HF (odds ratio [OR] 1.13 per 1-log unit higher risk of T2D; 95% CI 1.11-1.14; P < 0.001); however, sensitivity analysis revealed evidence of directional pleiotropy. The relationship between T2D and HF was attenuated when adjusted for coronary disease, BMI, LDL cholesterol, and blood pressure in multivariable MR. Genetically instrumented higher IR was associated with higher risk of HF (OR 1.19 per 1-log unit higher risk of IR; 95% CI 1.00-1.41; P = 0.041). There were no notable associations identified between fasting insulin, glucose, or glycated hemoglobin and risk of HF. Genetic liability to HF was causally linked to higher risk of T2D (OR 1.49; 95% CI 1.01-2.19; P = 0.042), although again with evidence of pleiotropy.

Conclusions

These findings suggest a possible causal role of T2D and IR in HF etiology, although the presence of both bidirectional effects and directional pleiotropy highlights potential sources of bias that must be considered.", + "laySummary": "", + "urls": "pdf:https://diabetesjournals.org/care/article-pdf/44/7/1699/632992/dc202518.pdf; doi:https://doi.org/10.2337/dc20-2518; html:https://europepmc.org/articles/PMC8323186; pdf:https://europepmc.org/articles/PMC8323186?pdf=render" + }, { "id": "38672093", "doi": "https://doi.org/10.3390/biomedicines12040737", @@ -18836,21 +18853,21 @@ "urls": "doi:https://doi.org/10.1016/j.jtha.2023.07.008" }, { - "id": "34088700", - "doi": "https://doi.org/10.2337/dc20-2518", - "title": "Type 2 Diabetes, Metabolic Traits, and Risk of Heart Failure: A Mendelian Randomization Study.", - "authorString": "Mordi IR, Lumbers RT, Palmer CNA, Pearson ER, Sattar N, Holmes MV, Lang CC, HERMES Consortium.", + "id": "37649471", + "doi": "https://doi.org/10.23889/ijpds.v6i3.1705", + "title": "Data linkage can reduce the burden and increase the opportunities in the implementation of Value-Based Health Care policy: a study in patients with ulcerative colitis (PROUD-UC Study).", + "authorString": "Walshe J, Akbari A, Hawthorne AB, Laing H.", "authorAffiliations": "", - "journalTitle": "Diabetes care", + "journalTitle": "International journal of population data science", "pubYear": "2021", - "date": "2021-06-04", + "date": "2021-01-01", "isOpenAccess": "Y", - "keywords": "", + "keywords": "Colitis, ulcerative; Health Policy; Patient Reported Outcome Measure; Routinely Collected Health Data; Data Science; Value-based Health Care", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Objective

The aim of this study was to use Mendelian randomization (MR) techniques to estimate the causal relationships between genetic liability to type 2 diabetes (T2D), glycemic traits, and risk of heart failure (HF).

Research design and methods

Summary-level data were obtained from genome-wide association studies of T2D, insulin resistance (IR), glycated hemoglobin, fasting insulin and glucose, and HF. MR was conducted using the inverse-variance weighted method. Sensitivity analyses included the MR-Egger method, weighted median and mode methods, and multivariable MR conditioning on potential mediators.

Results

Genetic liability to T2D was causally related to higher risk of HF (odds ratio [OR] 1.13 per 1-log unit higher risk of T2D; 95% CI 1.11-1.14; P < 0.001); however, sensitivity analysis revealed evidence of directional pleiotropy. The relationship between T2D and HF was attenuated when adjusted for coronary disease, BMI, LDL cholesterol, and blood pressure in multivariable MR. Genetically instrumented higher IR was associated with higher risk of HF (OR 1.19 per 1-log unit higher risk of IR; 95% CI 1.00-1.41; P = 0.041). There were no notable associations identified between fasting insulin, glucose, or glycated hemoglobin and risk of HF. Genetic liability to HF was causally linked to higher risk of T2D (OR 1.49; 95% CI 1.01-2.19; P = 0.042), although again with evidence of pleiotropy.

Conclusions

These findings suggest a possible causal role of T2D and IR in HF etiology, although the presence of both bidirectional effects and directional pleiotropy highlights potential sources of bias that must be considered.", + "abstract": "

Introduction

Healthcare systems face rising demand and unsustainable cost pressures. In response, health policymakers are adopting Value-Based Health Care (VBHC), targeting available resources to achieve the best possible patient outcomes at the lowest possible cost and actively disinvesting in care of low-value. This requires the evaluation of longitudinal clinical and patient reported outcome measures (PROMs) at an individual-level and population-scale, which can create significant data challenges. Achieving this through routinely collected electronic health record (EHR) data-linkage could facilitate the implementation of VBHC without an unacceptable data burden on patients or health systems and release time for higher-value activities.

Objectives

Our study tested the ability to report an international, patient-centred outcome dataset (ICHOM-IBD) using only anonymised individual-level population-scale linked electronic health record (EHR) data sources, including clinical and patient-reported outcomes, in a cohort of patients with moderate-to-severe ulcerative colitis (UC), receiving biopharmaceutical therapies (\"biologics\") in a single, publicly funded, healthcare system.

Results

We identified a cohort of 17,632 patients with UC in Wales and a cohort from two Health Boards of 447 patients with UC receiving biologics. 112 of these patients had completed 866 condition-specific PROMs during their biologics treatment. 44 out of 59 (74.6%) items in the ICHOM-IBD could be derived from routinely collected data of which a primary care source was essential for eight items and desirable for 21.

Conclusions

We demonstrated that it is possible to report most but not all the ICHOM-IBD outcomes using routinely collected data from multiple sources without additional system burden, potentially supporting Value-Based Health Care implementation with population data science. As digital collection of PROMs and use of condition-specific registries grow, greater utility of this approach can be anticipated. We have identified that the availability of longitudinal primary and secondary care data linked with PROMs is essential for this to be possible.", "laySummary": "", - "urls": "pdf:https://diabetesjournals.org/care/article-pdf/44/7/1699/632992/dc202518.pdf; doi:https://doi.org/10.2337/dc20-2518; html:https://europepmc.org/articles/PMC8323186; pdf:https://europepmc.org/articles/PMC8323186?pdf=render" + "urls": "pdf:https://ijpds.org/article/download/1705/4121; doi:https://doi.org/10.23889/ijpds.v6i3.1705; html:https://europepmc.org/articles/PMC10464864; pdf:https://europepmc.org/articles/PMC10464864?pdf=render" }, { "id": "37440761", @@ -18869,23 +18886,6 @@ "laySummary": "", "urls": "pdf:https://academic.oup.com/ehjcimaging/advance-article-pdf/doi/10.1093/ehjci/jead166/50880139/jead166.pdf; doi:https://doi.org/10.1093/ehjci/jead166; html:https://europepmc.org/articles/PMC10610755; pdf:https://europepmc.org/articles/PMC10610755?pdf=render" }, - { - "id": "37649471", - "doi": "https://doi.org/10.23889/ijpds.v6i3.1705", - "title": "Data linkage can reduce the burden and increase the opportunities in the implementation of Value-Based Health Care policy: a study in patients with ulcerative colitis (PROUD-UC Study).", - "authorString": "Walshe J, Akbari A, Hawthorne AB, Laing H.", - "authorAffiliations": "", - "journalTitle": "International journal of population data science", - "pubYear": "2021", - "date": "2021-01-01", - "isOpenAccess": "Y", - "keywords": "Colitis, ulcerative; Health Policy; Patient Reported Outcome Measure; Routinely Collected Health Data; Data Science; Value-based Health Care", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Introduction

Healthcare systems face rising demand and unsustainable cost pressures. In response, health policymakers are adopting Value-Based Health Care (VBHC), targeting available resources to achieve the best possible patient outcomes at the lowest possible cost and actively disinvesting in care of low-value. This requires the evaluation of longitudinal clinical and patient reported outcome measures (PROMs) at an individual-level and population-scale, which can create significant data challenges. Achieving this through routinely collected electronic health record (EHR) data-linkage could facilitate the implementation of VBHC without an unacceptable data burden on patients or health systems and release time for higher-value activities.

Objectives

Our study tested the ability to report an international, patient-centred outcome dataset (ICHOM-IBD) using only anonymised individual-level population-scale linked electronic health record (EHR) data sources, including clinical and patient-reported outcomes, in a cohort of patients with moderate-to-severe ulcerative colitis (UC), receiving biopharmaceutical therapies (\"biologics\") in a single, publicly funded, healthcare system.

Results

We identified a cohort of 17,632 patients with UC in Wales and a cohort from two Health Boards of 447 patients with UC receiving biologics. 112 of these patients had completed 866 condition-specific PROMs during their biologics treatment. 44 out of 59 (74.6%) items in the ICHOM-IBD could be derived from routinely collected data of which a primary care source was essential for eight items and desirable for 21.

Conclusions

We demonstrated that it is possible to report most but not all the ICHOM-IBD outcomes using routinely collected data from multiple sources without additional system burden, potentially supporting Value-Based Health Care implementation with population data science. As digital collection of PROMs and use of condition-specific registries grow, greater utility of this approach can be anticipated. We have identified that the availability of longitudinal primary and secondary care data linked with PROMs is essential for this to be possible.", - "laySummary": "", - "urls": "pdf:https://ijpds.org/article/download/1705/4121; doi:https://doi.org/10.23889/ijpds.v6i3.1705; html:https://europepmc.org/articles/PMC10464864; pdf:https://europepmc.org/articles/PMC10464864?pdf=render" - }, { "id": "34671274", "doi": "https://doi.org/10.3389/fphys.2021.730736", @@ -19005,23 +19005,6 @@ "laySummary": "", "urls": "pdf:https://link.springer.com/content/pdf/10.1007/s10654-022-00934-w.pdf; doi:https://doi.org/10.1007/s10654-022-00934-w; html:https://europepmc.org/articles/PMC9792414; pdf:https://europepmc.org/articles/PMC9792414?pdf=render" }, - { - "id": "36864090", - "doi": "https://doi.org/10.1038/s41598-023-30369-6", - "title": "Effect of tissue-grouped regulatory variants associated to type 2 diabetes in related secondary outcomes.", - "authorString": "Hemerich D, Smit RAJ, Preuss M, Stalbow L, van der Laan SW, Asselbergs FW, van Setten J, Tragante V.", - "authorAffiliations": "", - "journalTitle": "Scientific reports", - "pubYear": "2023", - "date": "2023-03-02", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Genome-wide association studies have identified over five hundred loci that contribute to variation in type 2 diabetes (T2D), an established risk factor for many diseases. However, the mechanisms and extent through which these loci contribute to subsequent outcomes remain elusive. We hypothesized that combinations of T2D-associated variants acting on tissue-specific regulatory elements might account for greater risk for tissue-specific outcomes, leading to diversity in T2D disease progression. We searched for T2D-associated variants acting on regulatory elements and expression quantitative trait loci (eQTLs) in nine tissues. We used T2D tissue-grouped variant sets as genetic instruments to conduct 2-Sample Mendelian Randomization (MR) in ten related outcomes whose risk is increased by T2D using the FinnGen cohort. We performed PheWAS analysis to investigate whether the T2D tissue-grouped variant sets had specific predicted disease signatures. We identified an average of 176 variants acting in nine tissues implicated in T2D, and an average of 30 variants acting on regulatory elements that are unique to the nine tissues of interest. In 2-Sample MR analyses, all subsets of regulatory variants acting in different tissues were associated with increased risk of the ten secondary outcomes studied on similar levels. No tissue-grouped variant set was associated with an outcome significantly more than other tissue-grouped variant sets. We did not identify different disease progression profiles based on tissue-specific regulatory and transcriptome information. Bigger sample sizes and other layers of regulatory information in critical tissues may help identify subsets of T2D variants that are implicated in certain secondary outcomes, uncovering system-specific disease progression.", - "laySummary": "", - "urls": "pdf:https://www.nature.com/articles/s41598-023-30369-6.pdf; doi:https://doi.org/10.1038/s41598-023-30369-6; html:https://europepmc.org/articles/PMC9981672; pdf:https://europepmc.org/articles/PMC9981672?pdf=render" - }, { "id": "35135774", "doi": "https://doi.org/10.1136/bmjopen-2021-055603", @@ -19039,6 +19022,23 @@ "laySummary": "", "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/12/2/e055603.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-055603; html:https://europepmc.org/articles/PMC8830221; pdf:https://europepmc.org/articles/PMC8830221?pdf=render" }, + { + "id": "36864090", + "doi": "https://doi.org/10.1038/s41598-023-30369-6", + "title": "Effect of tissue-grouped regulatory variants associated to type 2 diabetes in related secondary outcomes.", + "authorString": "Hemerich D, Smit RAJ, Preuss M, Stalbow L, van der Laan SW, Asselbergs FW, van Setten J, Tragante V.", + "authorAffiliations": "", + "journalTitle": "Scientific reports", + "pubYear": "2023", + "date": "2023-03-02", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Genome-wide association studies have identified over five hundred loci that contribute to variation in type 2 diabetes (T2D), an established risk factor for many diseases. However, the mechanisms and extent through which these loci contribute to subsequent outcomes remain elusive. We hypothesized that combinations of T2D-associated variants acting on tissue-specific regulatory elements might account for greater risk for tissue-specific outcomes, leading to diversity in T2D disease progression. We searched for T2D-associated variants acting on regulatory elements and expression quantitative trait loci (eQTLs) in nine tissues. We used T2D tissue-grouped variant sets as genetic instruments to conduct 2-Sample Mendelian Randomization (MR) in ten related outcomes whose risk is increased by T2D using the FinnGen cohort. We performed PheWAS analysis to investigate whether the T2D tissue-grouped variant sets had specific predicted disease signatures. We identified an average of 176 variants acting in nine tissues implicated in T2D, and an average of 30 variants acting on regulatory elements that are unique to the nine tissues of interest. In 2-Sample MR analyses, all subsets of regulatory variants acting in different tissues were associated with increased risk of the ten secondary outcomes studied on similar levels. No tissue-grouped variant set was associated with an outcome significantly more than other tissue-grouped variant sets. We did not identify different disease progression profiles based on tissue-specific regulatory and transcriptome information. Bigger sample sizes and other layers of regulatory information in critical tissues may help identify subsets of T2D variants that are implicated in certain secondary outcomes, uncovering system-specific disease progression.", + "laySummary": "", + "urls": "pdf:https://www.nature.com/articles/s41598-023-30369-6.pdf; doi:https://doi.org/10.1038/s41598-023-30369-6; html:https://europepmc.org/articles/PMC9981672; pdf:https://europepmc.org/articles/PMC9981672?pdf=render" + }, { "id": "34985035", "doi": "https://doi.org/10.1097/htr.0000000000000741", @@ -19090,23 +19090,6 @@ "laySummary": "", "urls": "pdf:https://hrbopenresearch.org/articles/6-10/pdf; doi:https://doi.org/10.12688/hrbopenres.13667.1; html:https://europepmc.org/articles/PMC10345597; pdf:https://europepmc.org/articles/PMC10345597?pdf=render" }, - { - "id": "37293269", - "doi": "https://doi.org/10.1140/epjds/s13688-023-00394-6", - "title": "Do poverty and wealth look the same the world over? A comparative study of 12 cities from five high-income countries using street images.", - "authorString": "Suel E, Muller E, Bennett JE, Blakely T, Doyle Y, Lynch J, Mackenbach JD, Middel A, Mizdrak A, Nathvani R, Brauer M, Ezzati M.", - "authorAffiliations": "", - "journalTitle": "EPJ data science", - "pubYear": "2023", - "date": "2023-06-07", - "isOpenAccess": "Y", - "keywords": "Computer vision; Visual Similarity; Urban Inequalities; Street Images", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Urbanization and inequalities are two of the major policy themes of our time, intersecting in large cities where social and economic inequalities are particularly pronounced. Large scale street-level images are a source of city-wide visual information and allow for comparative analyses of multiple cities. Computer vision methods based on deep learning applied to street images have been shown to successfully measure inequalities in socioeconomic and environmental features, yet existing work has been within specific geographies and have not looked at how visual environments compare across different cities and countries. In this study, we aim to apply existing methods to understand whether, and to what extent, poor and wealthy groups live in visually similar neighborhoods across cities and countries. We present novel insights on similarity of neighborhoods using street-level images and deep learning methods. We analyzed 7.2 million images from 12 cities in five high-income countries, home to more than 85 million people: Auckland (New Zealand), Sydney (Australia), Toronto and Vancouver (Canada), Atlanta, Boston, Chicago, Los Angeles, New York, San Francisco, and Washington D.C. (United States of America), and London (United Kingdom). Visual features associated with neighborhood disadvantage are more distinct and unique to each city than those associated with affluence. For example, from what is visible from street images, high density poor neighborhoods located near the city center (e.g., in London) are visually distinct from poor suburban neighborhoods characterized by lower density and lower accessibility (e.g., in Atlanta). This suggests that differences between two cities is also driven by historical factors, policies, and local geography. Our results also have implications for image-based measures of inequality in cities especially when trained on data from cities that are visually distinct from target cities. We showed that these are more prone to errors for disadvantaged areas especially when transferring across cities, suggesting more attention needs to be paid to improving methods for capturing heterogeneity in poor environment across cities around the world.

Supplementary information

The online version contains supplementary material available at 10.1140/epjds/s13688-023-00394-6.", - "laySummary": "", - "urls": "pdf:https://epjdatascience.springeropen.com/counter/pdf/10.1140/epjds/s13688-023-00394-6; doi:https://doi.org/10.1140/epjds/s13688-023-00394-6; html:https://europepmc.org/articles/PMC10245348; pdf:https://europepmc.org/articles/PMC10245348?pdf=render" - }, { "id": "32728709", "doi": "https://doi.org/10.1093/pubmed/fdaa115", @@ -19125,21 +19108,21 @@ "urls": "pdf:https://discovery.ucl.ac.uk/10110375/1/Syed%20and%20Gilbert%20%282020%29.%20Are%20children%20who%20are%20home%20from%20school%20at%20an%20increased%20risk%20of%20child%20maltreatment.pdf; doi:https://doi.org/10.1093/pubmed/fdaa115" }, { - "id": "37920183", - "doi": "https://doi.org/10.3389/fcvm.2023.1148931", - "title": "Unraveling the relationships between alpha- and beta-adrenergic modulation and the risk of heart failure.", - "authorString": "Baudier C, Fougerousse F, Asselbergs FW, Guedj M, Komajda M, Kotecha D, Thomas Lumbers R, Schmidt AF, Tyl B.", + "id": "37293269", + "doi": "https://doi.org/10.1140/epjds/s13688-023-00394-6", + "title": "Do poverty and wealth look the same the world over? A comparative study of 12 cities from five high-income countries using street images.", + "authorString": "Suel E, Muller E, Bennett JE, Blakely T, Doyle Y, Lynch J, Mackenbach JD, Middel A, Mizdrak A, Nathvani R, Brauer M, Ezzati M.", "authorAffiliations": "", - "journalTitle": "Frontiers in cardiovascular medicine", + "journalTitle": "EPJ data science", "pubYear": "2023", - "date": "2023-10-18", + "date": "2023-06-07", "isOpenAccess": "Y", - "keywords": "adrenergic receptors; Beta-blockers; Mendelian Randomization; Alpha-blockers; Target Validation, Drug", + "keywords": "Computer vision; Visual Similarity; Urban Inequalities; Street Images", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Background

The effects of \u03b1 and \u00df adrenergic receptor modulation on the risk of developing heart failure (HF) remains uncertain due to a lack of randomized controlled trials. This study aimed to estimate the effects of \u03b1 and \u00df adrenergic receptors modulation on the risk of HF and to provide proof of principle for genetic target validation studies in HF.

Methods

Genetic variants within the cis regions encoding the adrenergic receptors \u03b11A, \u03b12B, \u00df1, and \u00df2 associated with blood pressure in a 757,601-participant genome-wide association study (GWAS) were selected as instruments to perform a drug target Mendelian randomization study. Effects of these variants on HF risk were derived from the HERMES GWAS (542,362 controls; 40,805 HF cases).

Results

Lower \u03b11A or \u00df1 activity was associated with reduced HF risk: odds ratio (OR) 0.83 (95% CI 0.74-0.93, P\u2009=\u20090.001) and 0.95 (95% CI 0.93-0.97, P\u2009=\u20098\u2009\u00d7\u200910-6). Conversely, lower \u03b12B activity was associated with increased HF risk: OR 1.09 (95% CI 1.05-1.12, P\u2009=\u20093\u2009\u00d7\u200910-7). No evidence of an effect of lower \u00df2 activity on HF risk was found: OR 0.99 (95% CI 0.92-1.07, P\u2009=\u20090.95). Complementary analyses showed that these effects were consistent with those on left ventricular dimensions and acted independently of any potential effect on coronary artery disease.

Conclusions

This study provides genetic evidence that \u03b11A or \u00df1 receptor inhibition will likely decrease HF risk, while lower \u03b12B activity may increase this risk. Genetic variant analysis can assist with drug development for HF prevention.", + "abstract": "Urbanization and inequalities are two of the major policy themes of our time, intersecting in large cities where social and economic inequalities are particularly pronounced. Large scale street-level images are a source of city-wide visual information and allow for comparative analyses of multiple cities. Computer vision methods based on deep learning applied to street images have been shown to successfully measure inequalities in socioeconomic and environmental features, yet existing work has been within specific geographies and have not looked at how visual environments compare across different cities and countries. In this study, we aim to apply existing methods to understand whether, and to what extent, poor and wealthy groups live in visually similar neighborhoods across cities and countries. We present novel insights on similarity of neighborhoods using street-level images and deep learning methods. We analyzed 7.2 million images from 12 cities in five high-income countries, home to more than 85 million people: Auckland (New Zealand), Sydney (Australia), Toronto and Vancouver (Canada), Atlanta, Boston, Chicago, Los Angeles, New York, San Francisco, and Washington D.C. (United States of America), and London (United Kingdom). Visual features associated with neighborhood disadvantage are more distinct and unique to each city than those associated with affluence. For example, from what is visible from street images, high density poor neighborhoods located near the city center (e.g., in London) are visually distinct from poor suburban neighborhoods characterized by lower density and lower accessibility (e.g., in Atlanta). This suggests that differences between two cities is also driven by historical factors, policies, and local geography. Our results also have implications for image-based measures of inequality in cities especially when trained on data from cities that are visually distinct from target cities. We showed that these are more prone to errors for disadvantaged areas especially when transferring across cities, suggesting more attention needs to be paid to improving methods for capturing heterogeneity in poor environment across cities around the world.

Supplementary information

The online version contains supplementary material available at 10.1140/epjds/s13688-023-00394-6.", "laySummary": "", - "urls": "doi:https://doi.org/10.3389/fcvm.2023.1148931; html:https://europepmc.org/articles/PMC10619754; pdf:https://europepmc.org/articles/PMC10619754?pdf=render" + "urls": "pdf:https://epjdatascience.springeropen.com/counter/pdf/10.1140/epjds/s13688-023-00394-6; doi:https://doi.org/10.1140/epjds/s13688-023-00394-6; html:https://europepmc.org/articles/PMC10245348; pdf:https://europepmc.org/articles/PMC10245348?pdf=render" }, { "id": "34798287", @@ -19158,6 +19141,23 @@ "laySummary": "", "urls": "pdf:http://www.jclinepi.com/article/S0895435621003759/pdf; doi:https://doi.org/10.1016/j.jclinepi.2021.11.023" }, + { + "id": "37920183", + "doi": "https://doi.org/10.3389/fcvm.2023.1148931", + "title": "Unraveling the relationships between alpha- and beta-adrenergic modulation and the risk of heart failure.", + "authorString": "Baudier C, Fougerousse F, Asselbergs FW, Guedj M, Komajda M, Kotecha D, Thomas Lumbers R, Schmidt AF, Tyl B.", + "authorAffiliations": "", + "journalTitle": "Frontiers in cardiovascular medicine", + "pubYear": "2023", + "date": "2023-10-18", + "isOpenAccess": "Y", + "keywords": "adrenergic receptors; Beta-blockers; Mendelian Randomization; Alpha-blockers; Target Validation, Drug", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

The effects of \u03b1 and \u00df adrenergic receptor modulation on the risk of developing heart failure (HF) remains uncertain due to a lack of randomized controlled trials. This study aimed to estimate the effects of \u03b1 and \u00df adrenergic receptors modulation on the risk of HF and to provide proof of principle for genetic target validation studies in HF.

Methods

Genetic variants within the cis regions encoding the adrenergic receptors \u03b11A, \u03b12B, \u00df1, and \u00df2 associated with blood pressure in a 757,601-participant genome-wide association study (GWAS) were selected as instruments to perform a drug target Mendelian randomization study. Effects of these variants on HF risk were derived from the HERMES GWAS (542,362 controls; 40,805 HF cases).

Results

Lower \u03b11A or \u00df1 activity was associated with reduced HF risk: odds ratio (OR) 0.83 (95% CI 0.74-0.93, P\u2009=\u20090.001) and 0.95 (95% CI 0.93-0.97, P\u2009=\u20098\u2009\u00d7\u200910-6). Conversely, lower \u03b12B activity was associated with increased HF risk: OR 1.09 (95% CI 1.05-1.12, P\u2009=\u20093\u2009\u00d7\u200910-7). No evidence of an effect of lower \u00df2 activity on HF risk was found: OR 0.99 (95% CI 0.92-1.07, P\u2009=\u20090.95). Complementary analyses showed that these effects were consistent with those on left ventricular dimensions and acted independently of any potential effect on coronary artery disease.

Conclusions

This study provides genetic evidence that \u03b11A or \u00df1 receptor inhibition will likely decrease HF risk, while lower \u03b12B activity may increase this risk. Genetic variant analysis can assist with drug development for HF prevention.", + "laySummary": "", + "urls": "doi:https://doi.org/10.3389/fcvm.2023.1148931; html:https://europepmc.org/articles/PMC10619754; pdf:https://europepmc.org/articles/PMC10619754?pdf=render" + }, { "id": "36936265", "doi": "https://doi.org/10.1136/bmjmed-2022-000276", @@ -19209,40 +19209,6 @@ "laySummary": "", "urls": "pdf:https://www.mdpi.com/2075-4426/12/8/1230/pdf?version=1659687887; doi:https://doi.org/10.3390/jpm12081230; html:https://europepmc.org/articles/PMC9410389; pdf:https://europepmc.org/articles/PMC9410389?pdf=render" }, - { - "id": "35921096", - "doi": "https://doi.org/10.1001/jamacardio.2022.2333", - "title": "Joint Genetic Inhibition of PCSK9 and CETP and the Association With Coronary Artery Disease: A Factorial Mendelian Randomization Study.", - "authorString": "Cupido AJ, Reeskamp LF, Hingorani AD, Finan C, Asselbergs FW, Hovingh GK, Schmidt AF.", - "authorAffiliations": "", - "journalTitle": "JAMA cardiology", - "pubYear": "2022", - "date": "2022-09-01", - "isOpenAccess": "N", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Importance

Cholesteryl ester transfer protein inhibition (CETP) has been shown to increase levels of high-density lipoprotein cholesterol (HDL-C) and reduce levels of low-density lipoprotein cholesterol (LDL-C). Current LDL-C target attainment is low, and novel phase 3 trials are underway to investigate whether CETP inhibitors result in reduction of cardiovascular disease risk in high-risk patients who may be treated with PCSK9-inhibiting agents.

Objective

To explore the associations of combined reduction of CETP and PCSK9 concentrations with risk of coronary artery disease (CAD) and other clinical and safety outcomes.

Design, setting, and participants

Two-sample 2\u2009\u00d7\u20092 factorial Mendelian randomization study in a general population sample that includes data for UK Biobank participants of European ancestry.

Exposures

Separate genetic scores were constructed for CETP and PCSK9 plasma protein concentrations, which were combined to determine the associations of combined genetically reduced CETP and PCSK9 concentrations with disease.

Main outcomes and measures

Blood lipid and lipoprotein concentrations, blood pressure, CAD, age-related macular degeneration, type 2 diabetes, any stroke and ischemic stroke, Alzheimer disease, vascular dementia, heart failure, atrial fibrillation, chronic kidney disease, asthma, and multiple sclerosis.

Results

Data for 425\u202f354 UKB participants were included; the median (IQR) age was 59 years (51-64), and 229\u202f399 (53.9%) were female. The associations of lower CETP and lower PCSK9 concentrations with CAD are similar when scaled per 10-mg/dL reduction in LDL-C concentrations (CETP: odds ratio [OR], 0.74; 95% CI, 0.67 to 0.81; PCSK9: OR, 0.75; 95% CI, 0.71 to 0.79). Combined exposure to lower CETP and PCSK9 concentrations was associated with an additive magnitude with lipids and all outcomes, and we did not observe any nonadditive interactions, most notably for LDL-C (CETP: effect size, -1.11 mg/dL; 95% CI, -1.40 to -0.82; PCSK9: effect size, -2.13 mg/dL; 95% CI, -2.43 to -1.84; combined: effect size, -3.47 mg/dL; 95% CI, -3.76 to -3.18; P\u2009=\u2009.34 for interaction) and CAD (CETP: OR, 0.96; 95% CI, 0.94 to 1.00; PCSK9: OR, 0.94; 95% CI, 0.91 to 0.97; combined: OR, 0.90; 95% CI, 0.87 to 0.93; P\u2009=\u2009.83 for interaction). In addition, when corrected for multiple testing, lower CETP concentrations were associated with increased age-related macular degeneration (OR, 1.11; 95% CI, 1.04 to 1.19).

Conclusions and relevance

Our results suggest that joint inhibition of CETP and PCSK9 has additive effects on lipid traits and disease risk, including a lower risk of CAD. Further research may explore whether a combination of CETP- and PCSK9-related therapeutics can benefit high-risk patients who are unable to reach treatment targets with existing options.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1001/jamacardio.2022.2333; html:https://europepmc.org/articles/PMC9350849; doi:https://doi.org/10.1001/jamacardio.2022.2333" - }, - { - "id": "38528983", - "doi": "https://doi.org/10.3389/fpsyt.2024.1347100", - "title": "Machine learning in mental health and its relationship with epidemiological practice.", - "authorString": "DelPozo-Banos M, Stewart R, John A.", - "authorAffiliations": "", - "journalTitle": "Frontiers in psychiatry", - "pubYear": "2024", - "date": "2024-03-11", - "isOpenAccess": "Y", - "keywords": "Research methods; Mental health; epidemiology; Machine Learning; Challenges And Opportunities", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "", - "laySummary": "", - "urls": "pdf:https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2024.1347100/pdf; doi:https://doi.org/10.3389/fpsyt.2024.1347100; html:https://europepmc.org/articles/PMC10961376; pdf:https://europepmc.org/articles/PMC10961376?pdf=render" - }, { "id": "31477110", "doi": "https://doi.org/10.1186/s12913-019-4286-8", @@ -19260,6 +19226,23 @@ "laySummary": "", "urls": "pdf:https://bmchealthservres.biomedcentral.com/counter/pdf/10.1186/s12913-019-4286-8; doi:https://doi.org/10.1186/s12913-019-4286-8; html:https://europepmc.org/articles/PMC6720086; pdf:https://europepmc.org/articles/PMC6720086?pdf=render" }, + { + "id": "35921096", + "doi": "https://doi.org/10.1001/jamacardio.2022.2333", + "title": "Joint Genetic Inhibition of PCSK9 and CETP and the Association With Coronary Artery Disease: A Factorial Mendelian Randomization Study.", + "authorString": "Cupido AJ, Reeskamp LF, Hingorani AD, Finan C, Asselbergs FW, Hovingh GK, Schmidt AF.", + "authorAffiliations": "", + "journalTitle": "JAMA cardiology", + "pubYear": "2022", + "date": "2022-09-01", + "isOpenAccess": "N", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Importance

Cholesteryl ester transfer protein inhibition (CETP) has been shown to increase levels of high-density lipoprotein cholesterol (HDL-C) and reduce levels of low-density lipoprotein cholesterol (LDL-C). Current LDL-C target attainment is low, and novel phase 3 trials are underway to investigate whether CETP inhibitors result in reduction of cardiovascular disease risk in high-risk patients who may be treated with PCSK9-inhibiting agents.

Objective

To explore the associations of combined reduction of CETP and PCSK9 concentrations with risk of coronary artery disease (CAD) and other clinical and safety outcomes.

Design, setting, and participants

Two-sample 2\u2009\u00d7\u20092 factorial Mendelian randomization study in a general population sample that includes data for UK Biobank participants of European ancestry.

Exposures

Separate genetic scores were constructed for CETP and PCSK9 plasma protein concentrations, which were combined to determine the associations of combined genetically reduced CETP and PCSK9 concentrations with disease.

Main outcomes and measures

Blood lipid and lipoprotein concentrations, blood pressure, CAD, age-related macular degeneration, type 2 diabetes, any stroke and ischemic stroke, Alzheimer disease, vascular dementia, heart failure, atrial fibrillation, chronic kidney disease, asthma, and multiple sclerosis.

Results

Data for 425\u202f354 UKB participants were included; the median (IQR) age was 59 years (51-64), and 229\u202f399 (53.9%) were female. The associations of lower CETP and lower PCSK9 concentrations with CAD are similar when scaled per 10-mg/dL reduction in LDL-C concentrations (CETP: odds ratio [OR], 0.74; 95% CI, 0.67 to 0.81; PCSK9: OR, 0.75; 95% CI, 0.71 to 0.79). Combined exposure to lower CETP and PCSK9 concentrations was associated with an additive magnitude with lipids and all outcomes, and we did not observe any nonadditive interactions, most notably for LDL-C (CETP: effect size, -1.11 mg/dL; 95% CI, -1.40 to -0.82; PCSK9: effect size, -2.13 mg/dL; 95% CI, -2.43 to -1.84; combined: effect size, -3.47 mg/dL; 95% CI, -3.76 to -3.18; P\u2009=\u2009.34 for interaction) and CAD (CETP: OR, 0.96; 95% CI, 0.94 to 1.00; PCSK9: OR, 0.94; 95% CI, 0.91 to 0.97; combined: OR, 0.90; 95% CI, 0.87 to 0.93; P\u2009=\u2009.83 for interaction). In addition, when corrected for multiple testing, lower CETP concentrations were associated with increased age-related macular degeneration (OR, 1.11; 95% CI, 1.04 to 1.19).

Conclusions and relevance

Our results suggest that joint inhibition of CETP and PCSK9 has additive effects on lipid traits and disease risk, including a lower risk of CAD. Further research may explore whether a combination of CETP- and PCSK9-related therapeutics can benefit high-risk patients who are unable to reach treatment targets with existing options.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1001/jamacardio.2022.2333; html:https://europepmc.org/articles/PMC9350849; doi:https://doi.org/10.1001/jamacardio.2022.2333" + }, { "id": "38206619", "doi": "https://doi.org/10.1093/europace/euad368", @@ -19277,6 +19260,23 @@ "laySummary": "", "urls": "pdf:https://academic.oup.com/europace/article-pdf/26/1/euad368/55443084/euad368.pdf; doi:https://doi.org/10.1093/europace/euad368; html:https://europepmc.org/articles/PMC10783237; pdf:https://europepmc.org/articles/PMC10783237?pdf=render" }, + { + "id": "38528983", + "doi": "https://doi.org/10.3389/fpsyt.2024.1347100", + "title": "Machine learning in mental health and its relationship with epidemiological practice.", + "authorString": "DelPozo-Banos M, Stewart R, John A.", + "authorAffiliations": "", + "journalTitle": "Frontiers in psychiatry", + "pubYear": "2024", + "date": "2024-03-11", + "isOpenAccess": "Y", + "keywords": "Research methods; Mental health; epidemiology; Machine Learning; Challenges And Opportunities", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "", + "laySummary": "", + "urls": "pdf:https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2024.1347100/pdf; doi:https://doi.org/10.3389/fpsyt.2024.1347100; html:https://europepmc.org/articles/PMC10961376; pdf:https://europepmc.org/articles/PMC10961376?pdf=render" + }, { "id": "34435642", "doi": "https://doi.org/10.1093/eurheartj/ehab350", @@ -19328,23 +19328,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1136/emermed-2019-209368" }, - { - "id": "35896705", - "doi": "https://doi.org/10.1038/s41598-022-16639-9", - "title": "Estimation of biological heart age using cardiovascular magnetic resonance radiomics.", - "authorString": "Raisi-Estabragh Z, Salih A, Gkontra P, Atehort\u00faa A, Radeva P, Boscolo Galazzo I, Menegaz G, Harvey NC, Lekadir K, Petersen SE.", - "authorAffiliations": "", - "journalTitle": "Scientific reports", - "pubYear": "2022", - "date": "2022-07-27", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "We developed a novel interpretable biological heart age estimation model using cardiovascular magnetic resonance radiomics measures of ventricular shape and myocardial character. We included 29,996 UK Biobank participants without cardiovascular disease. Images were segmented using an automated analysis pipeline. We extracted 254 radiomics features from the left ventricle, right ventricle, and myocardium of each study. We then used Bayesian ridge regression with tenfold cross-validation to develop a heart age estimation model using the radiomics features as the model input and chronological age as the model output. We examined associations of radiomics features with heart age in men and women, observing sex-differential patterns. We subtracted actual age from model estimated heart age to calculate a \"heart age delta\", which we considered as a measure of heart aging. We performed a phenome-wide association study of 701 exposures with heart age delta. The strongest correlates of heart aging were measures of obesity, adverse serum lipid markers, hypertension, diabetes, heart rate, income, multimorbidity, musculoskeletal health, and respiratory health. This technique provides a new method for phenotypic assessment relating to cardiovascular aging; further studies are required to assess whether it provides incremental risk information over current approaches.", - "laySummary": "", - "urls": "pdf:https://www.nature.com/articles/s41598-022-16639-9.pdf; doi:https://doi.org/10.1038/s41598-022-16639-9; html:https://europepmc.org/articles/PMC9329281; pdf:https://europepmc.org/articles/PMC9329281?pdf=render" - }, { "id": "34427560", "doi": "https://doi.org/10.1684/ejd.2021.4108", @@ -19362,6 +19345,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1684/ejd.2021.4108" }, + { + "id": "35896705", + "doi": "https://doi.org/10.1038/s41598-022-16639-9", + "title": "Estimation of biological heart age using cardiovascular magnetic resonance radiomics.", + "authorString": "Raisi-Estabragh Z, Salih A, Gkontra P, Atehort\u00faa A, Radeva P, Boscolo Galazzo I, Menegaz G, Harvey NC, Lekadir K, Petersen SE.", + "authorAffiliations": "", + "journalTitle": "Scientific reports", + "pubYear": "2022", + "date": "2022-07-27", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "We developed a novel interpretable biological heart age estimation model using cardiovascular magnetic resonance radiomics measures of ventricular shape and myocardial character. We included 29,996 UK Biobank participants without cardiovascular disease. Images were segmented using an automated analysis pipeline. We extracted 254 radiomics features from the left ventricle, right ventricle, and myocardium of each study. We then used Bayesian ridge regression with tenfold cross-validation to develop a heart age estimation model using the radiomics features as the model input and chronological age as the model output. We examined associations of radiomics features with heart age in men and women, observing sex-differential patterns. We subtracted actual age from model estimated heart age to calculate a \"heart age delta\", which we considered as a measure of heart aging. We performed a phenome-wide association study of 701 exposures with heart age delta. The strongest correlates of heart aging were measures of obesity, adverse serum lipid markers, hypertension, diabetes, heart rate, income, multimorbidity, musculoskeletal health, and respiratory health. This technique provides a new method for phenotypic assessment relating to cardiovascular aging; further studies are required to assess whether it provides incremental risk information over current approaches.", + "laySummary": "", + "urls": "pdf:https://www.nature.com/articles/s41598-022-16639-9.pdf; doi:https://doi.org/10.1038/s41598-022-16639-9; html:https://europepmc.org/articles/PMC9329281; pdf:https://europepmc.org/articles/PMC9329281?pdf=render" + }, { "id": "34939031", "doi": "https://doi.org/10.1093/braincomms/fcab241", @@ -19379,6 +19379,23 @@ "laySummary": "", "urls": "pdf:https://academic.oup.com/braincomms/article-pdf/3/4/fcab241/41829863/fcab241.pdf; doi:https://doi.org/10.1093/braincomms/fcab241; html:https://europepmc.org/articles/PMC8688778; pdf:https://europepmc.org/articles/PMC8688778?pdf=render" }, + { + "id": "31748543", + "doi": "https://doi.org/10.1038/s41398-019-0613-4", + "title": "Identification of novel common variants associated with chronic pain using conditional false discovery rate analysis with major depressive disorder and assessment of pleiotropic effects of LRFN5.", + "authorString": "Johnston KJA, Adams MJ, Nicholl BI, Ward J, Strawbridge RJ, McIntosh AM, Smith DJ, Bailey MES.", + "authorAffiliations": "", + "journalTitle": "Translational psychiatry", + "pubYear": "2019", + "date": "2019-11-20", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "Understanding the Causes of Disease", + "healthCategories": "", + "abstract": "Chronic pain is a complex trait that is moderately heritable and genetically, as well as phenotypically, correlated with major depressive disorder (MDD). Use of the conditional false discovery rate (cFDR) approach, which leverages pleiotropy identified from existing GWAS outputs, has been successful in discovering novel associated variants in related phenotypes. Here, genome-wide association study outputs for both von Korff chronic pain grade and for MDD were used to identify variants meeting a cFDR threshold for each outcome phenotype separately, as well as a conjunctional cFDR (ccFDR) threshold for both phenotypes together. Using a moderately conservative threshold, we identified a total of 11 novel single nucleotide polymorphisms (SNPs), six of which were associated with chronic pain grade and nine of which were associated with MDD. Four SNPs on chromosome 14 were associated with both chronic pain grade and MDD. SNPs associated only with chronic pain grade were located within SLC16A7 on chromosome 12. SNPs associated only with MDD were located either in a gene-dense region on chromosome 1 harbouring LINC01360, LRRIQ3, FPGT and FPGT-TNNI3K, or within/close to LRFN5 on chromosome 14. The SNPs associated with both outcomes were also located within LRFN5. Several of the SNPs on chromosomes 1 and 14 were identified as being associated with expression levels of nearby genes in the brain and central nervous system. Overall, using the cFDR approach, we identified several novel genetic loci associated with chronic pain and we describe likely pleiotropic effects of a recently identified MDD locus on chronic pain.", + "laySummary": "This study aimed to identify parts of the genome that cause chronic pain (self-reported as lasting 3+ months), or major depressive disorder (MDD) and to investigate if these two conditions share common genetic causes. They identified 11 different parts of the genome where a specific change (SNP) was linked to chronic pain (6 parts of the genome), MDD (9 parts), or symptoms shared by both conditions (4 parts). The results also suggest that one of parts of the genome that causes chronic pain may influence the development of MDD (but not vice versa), including through lifestyle factors.", + "urls": "pdf:https://www.nature.com/articles/s41398-019-0613-4.pdf; doi:https://doi.org/10.1038/s41398-019-0613-4; html:https://europepmc.org/articles/PMC6868167; pdf:https://europepmc.org/articles/PMC6868167?pdf=render" + }, { "id": "38784722", "doi": "https://doi.org/10.1093/jbmrpl/ziae058", @@ -19413,23 +19430,6 @@ "laySummary": "", "urls": "pdf:https://academic.oup.com/ehjqcco/advance-article-pdf/doi/10.1093/ehjqcco/qcad029/50422842/qcad029.pdf; doi:https://doi.org/10.1093/ehjqcco/qcad029; html:https://europepmc.org/articles/PMC10904726; pdf:https://europepmc.org/articles/PMC10904726?pdf=render" }, - { - "id": "31748543", - "doi": "https://doi.org/10.1038/s41398-019-0613-4", - "title": "Identification of novel common variants associated with chronic pain using conditional false discovery rate analysis with major depressive disorder and assessment of pleiotropic effects of LRFN5.", - "authorString": "Johnston KJA, Adams MJ, Nicholl BI, Ward J, Strawbridge RJ, McIntosh AM, Smith DJ, Bailey MES.", - "authorAffiliations": "", - "journalTitle": "Translational psychiatry", - "pubYear": "2019", - "date": "2019-11-20", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "Understanding the Causes of Disease", - "healthCategories": "", - "abstract": "Chronic pain is a complex trait that is moderately heritable and genetically, as well as phenotypically, correlated with major depressive disorder (MDD). Use of the conditional false discovery rate (cFDR) approach, which leverages pleiotropy identified from existing GWAS outputs, has been successful in discovering novel associated variants in related phenotypes. Here, genome-wide association study outputs for both von Korff chronic pain grade and for MDD were used to identify variants meeting a cFDR threshold for each outcome phenotype separately, as well as a conjunctional cFDR (ccFDR) threshold for both phenotypes together. Using a moderately conservative threshold, we identified a total of 11 novel single nucleotide polymorphisms (SNPs), six of which were associated with chronic pain grade and nine of which were associated with MDD. Four SNPs on chromosome 14 were associated with both chronic pain grade and MDD. SNPs associated only with chronic pain grade were located within SLC16A7 on chromosome 12. SNPs associated only with MDD were located either in a gene-dense region on chromosome 1 harbouring LINC01360, LRRIQ3, FPGT and FPGT-TNNI3K, or within/close to LRFN5 on chromosome 14. The SNPs associated with both outcomes were also located within LRFN5. Several of the SNPs on chromosomes 1 and 14 were identified as being associated with expression levels of nearby genes in the brain and central nervous system. Overall, using the cFDR approach, we identified several novel genetic loci associated with chronic pain and we describe likely pleiotropic effects of a recently identified MDD locus on chronic pain.", - "laySummary": "This study aimed to identify parts of the genome that cause chronic pain (self-reported as lasting 3+ months), or major depressive disorder (MDD) and to investigate if these two conditions share common genetic causes. They identified 11 different parts of the genome where a specific change (SNP) was linked to chronic pain (6 parts of the genome), MDD (9 parts), or symptoms shared by both conditions (4 parts). The results also suggest that one of parts of the genome that causes chronic pain may influence the development of MDD (but not vice versa), including through lifestyle factors.", - "urls": "pdf:https://www.nature.com/articles/s41398-019-0613-4.pdf; doi:https://doi.org/10.1038/s41398-019-0613-4; html:https://europepmc.org/articles/PMC6868167; pdf:https://europepmc.org/articles/PMC6868167?pdf=render" - }, { "id": "37563310", "doi": "https://doi.org/10.1038/s41590-023-01588-w", @@ -19464,23 +19464,6 @@ "laySummary": "", "urls": "pdf:https://bmcmedicine.biomedcentral.com/track/pdf/10.1186/s12916-021-01940-7; doi:https://doi.org/10.1186/s12916-021-01940-7; html:https://europepmc.org/articles/PMC8022365; pdf:https://europepmc.org/articles/PMC8022365?pdf=render" }, - { - "id": "37986130", - "doi": "https://doi.org/10.1186/s41512-023-00159-9", - "title": "An external validation of the Kidney Donor Risk Index in the UK transplant population in the presence of semi-competing events.", - "authorString": "Riley S, Tam K, Tse WY, Connor A, Wei Y.", - "authorAffiliations": "", - "journalTitle": "Diagnostic and prognostic research", - "pubYear": "2023", - "date": "2023-11-21", - "isOpenAccess": "Y", - "keywords": "Survival analysis; Kidney transplantation; Risk Prediction; External Validation; Time-to-event Model; Competing Events", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Transplantation represents the optimal treatment for many patients with end-stage kidney disease. When a donor\u00a0kidney is available to a waitlisted patient, clinicians responsible for the care of the potential recipient must make the decision to accept or decline the offer based upon complex and variable information about the donor, the recipient and the transplant process. A clinical prediction model may be able to support clinicians in their decision-making. The Kidney Donor Risk Index (KDRI) was developed in the United States to predict graft failure following kidney transplantation. The survival process following transplantation consists of semi-competing events where death precludes graft failure, but not vice-versa.

Methods

We externally validated the KDRI in the UK kidney transplant population and assessed whether validation under a semi-competing risks framework impacted predictive performance. Additionally, we explored whether the KDRI requires updating. We included 20,035 adult recipients of first, deceased donor, single, kidney-only transplants between January 1, 2004, and December 31, 2018, collected by the UK Transplant Registry and held by NHS Blood and Transplant. The outcomes of interest were 1- and 5-year graft failure following transplantation. In light of the semi-competing events, recipient death was handled in two ways: censoring patients at the time of death and modelling death as a competing event. Cox proportional hazard models were used to validate the KDRI when censoring graft failure by death, and cause-specific Cox models were used to account for death as a competing event.

Results

The KDRI underestimated event probabilities for those at higher risk of graft failure. For 5-year graft failure, discrimination was poorer in the semi-competing risks model (0.625, 95% CI 0.611 to 0.640;0.611, 95% CI 0.597 to 0.625), but predictions were more accurate (Brier score 0.117, 95% CI 0.112 to 0.121; 0.114, 95% CI 0.109 to 0.118). Calibration plots were similar regardless of whether the death was modelled as a competing event or not. Updating the KDRI worsened calibration, but marginally improved discrimination.

Conclusions

Predictive performance for 1-year graft failure was similar between death-censored and competing event graft failure, but differences appeared when predicting 5-year graft failure. The updated index did not have superior performance and we conclude that updating the KDRI in the present form is not required.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1186/s41512-023-00159-9; html:https://europepmc.org/articles/PMC10662562; pdf:https://europepmc.org/articles/PMC10662562?pdf=render" - }, { "id": "32908284", "doi": "https://doi.org/10.1038/s41591-020-1037-7", @@ -19498,6 +19481,23 @@ "laySummary": "", "urls": "pdf:https://www.nature.com/articles/s41591-020-1037-7.pdf; doi:https://doi.org/10.1038/s41591-020-1037-7; html:https://europepmc.org/articles/PMC7598944; pdf:https://europepmc.org/articles/PMC7598944?pdf=render" }, + { + "id": "37986130", + "doi": "https://doi.org/10.1186/s41512-023-00159-9", + "title": "An external validation of the Kidney Donor Risk Index in the UK transplant population in the presence of semi-competing events.", + "authorString": "Riley S, Tam K, Tse WY, Connor A, Wei Y.", + "authorAffiliations": "", + "journalTitle": "Diagnostic and prognostic research", + "pubYear": "2023", + "date": "2023-11-21", + "isOpenAccess": "Y", + "keywords": "Survival analysis; Kidney transplantation; Risk Prediction; External Validation; Time-to-event Model; Competing Events", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Transplantation represents the optimal treatment for many patients with end-stage kidney disease. When a donor\u00a0kidney is available to a waitlisted patient, clinicians responsible for the care of the potential recipient must make the decision to accept or decline the offer based upon complex and variable information about the donor, the recipient and the transplant process. A clinical prediction model may be able to support clinicians in their decision-making. The Kidney Donor Risk Index (KDRI) was developed in the United States to predict graft failure following kidney transplantation. The survival process following transplantation consists of semi-competing events where death precludes graft failure, but not vice-versa.

Methods

We externally validated the KDRI in the UK kidney transplant population and assessed whether validation under a semi-competing risks framework impacted predictive performance. Additionally, we explored whether the KDRI requires updating. We included 20,035 adult recipients of first, deceased donor, single, kidney-only transplants between January 1, 2004, and December 31, 2018, collected by the UK Transplant Registry and held by NHS Blood and Transplant. The outcomes of interest were 1- and 5-year graft failure following transplantation. In light of the semi-competing events, recipient death was handled in two ways: censoring patients at the time of death and modelling death as a competing event. Cox proportional hazard models were used to validate the KDRI when censoring graft failure by death, and cause-specific Cox models were used to account for death as a competing event.

Results

The KDRI underestimated event probabilities for those at higher risk of graft failure. For 5-year graft failure, discrimination was poorer in the semi-competing risks model (0.625, 95% CI 0.611 to 0.640;0.611, 95% CI 0.597 to 0.625), but predictions were more accurate (Brier score 0.117, 95% CI 0.112 to 0.121; 0.114, 95% CI 0.109 to 0.118). Calibration plots were similar regardless of whether the death was modelled as a competing event or not. Updating the KDRI worsened calibration, but marginally improved discrimination.

Conclusions

Predictive performance for 1-year graft failure was similar between death-censored and competing event graft failure, but differences appeared when predicting 5-year graft failure. The updated index did not have superior performance and we conclude that updating the KDRI in the present form is not required.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1186/s41512-023-00159-9; html:https://europepmc.org/articles/PMC10662562; pdf:https://europepmc.org/articles/PMC10662562?pdf=render" + }, { "id": "32908283", "doi": "https://doi.org/10.1038/s41591-020-1034-x", @@ -19532,23 +19532,6 @@ "laySummary": "", "urls": "pdf:https://openres.ersjournals.com/content/erjor/early/2023/02/16/23120541.00591-2022.full.pdf; doi:https://doi.org/10.1183/23120541.00591-2022; html:https://europepmc.org/articles/PMC10152257; pdf:https://europepmc.org/articles/PMC10152257?pdf=render" }, - { - "id": "37200150", - "doi": "https://doi.org/10.1210/clinem/dgad276", - "title": "Preconception Management of Hyperthyroidism and Thyroid Status in Subsequent Pregnancy: A Population-Based Cohort Study.", - "authorString": "Minassian C, Allen LA, Okosieme O, Vaidya B, Taylor P.", - "authorAffiliations": "", - "journalTitle": "The Journal of clinical endocrinology and metabolism", - "pubYear": "2023", - "date": "2023-10-01", - "isOpenAccess": "Y", - "keywords": "Pregnancy; Thyroxine; Hyperthyroidism; Thyroid stimulating hormone; TSH; Thyroid function; Ft3; Ft4; Carbimazole; Tri-iodothyronine; Ptu; Cprd", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Context

Optimal thyroid status in pregnancy is essential in reducing the risk of adverse outcomes. The management of hyperthyroidism in women of reproductive age poses unique challenges and it is unclear how preconception treatment strategies impact on thyroid status in subsequent pregnancy.

Objective

We aimed to determine trends in the management of hyperthyroidism before and during pregnancy and to assess the impact of different preconception treatment strategies on maternal thyroid status.

Methods

We utilized the Clinical Practice Research Datalink database to evaluate all females aged 15-45 years with a clinical diagnosis of hyperthyroidism and a subsequent pregnancy (January 2000 to December 2017). We compared thyroid status in pregnancy according to preconception treatment, namely, (1) antithyroid drugs up to or beyond pregnancy onset, (2) definitive treatment with thyroidectomy or radioiodine before pregnancy, and (3) no treatment at pregnancy onset.

Results

Our study cohort comprised 4712 pregnancies. Thyrotropin (TSH) was measured in only 53.1% of pregnancies, of which 28.1% showed suboptimal thyroid status (TSH >4.0 mU/L or TSH <0.1 mU/L plus FT4 >reference range). Pregnancies with prior definitive treatment were more likely to have suboptimal thyroid status compared with pregnancies starting during antithyroid drug treatment (odds ratio 4.72, 95% CI 3.50-6.36). A steady decline in the use of definitive treatment before pregnancy was observed from 2000 to 2017. One-third (32.6%) of first trimester carbimazole-exposed pregnancies were switched to propylthiouracil while 6.0% of propylthiouracil-exposed pregnancies switched to carbimazole.

Conclusion

The management of women with hyperthyroidism who become pregnant is suboptimal, particularly in those with preconception definitive treatment, and needs urgent improvement. Better thyroid monitoring and prenatal counseling are needed to optimize thyroid status, reduce teratogenic drug exposure, and ultimately reduce the risk of adverse pregnancy outcomes.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1210/clinem/dgad276; doi:https://doi.org/10.1210/clinem/dgad276; html:https://europepmc.org/articles/PMC10584009" - }, { "id": "35151869", "doi": "https://doi.org/10.1016/j.jbi.2022.104010", @@ -19566,6 +19549,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.jbi.2022.104010; doi:https://doi.org/10.1016/j.jbi.2022.104010; html:https://europepmc.org/articles/PMC8894882" }, + { + "id": "37200150", + "doi": "https://doi.org/10.1210/clinem/dgad276", + "title": "Preconception Management of Hyperthyroidism and Thyroid Status in Subsequent Pregnancy: A Population-Based Cohort Study.", + "authorString": "Minassian C, Allen LA, Okosieme O, Vaidya B, Taylor P.", + "authorAffiliations": "", + "journalTitle": "The Journal of clinical endocrinology and metabolism", + "pubYear": "2023", + "date": "2023-10-01", + "isOpenAccess": "Y", + "keywords": "Pregnancy; Thyroxine; Hyperthyroidism; Thyroid stimulating hormone; TSH; Thyroid function; Ft3; Ft4; Carbimazole; Tri-iodothyronine; Ptu; Cprd", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Context

Optimal thyroid status in pregnancy is essential in reducing the risk of adverse outcomes. The management of hyperthyroidism in women of reproductive age poses unique challenges and it is unclear how preconception treatment strategies impact on thyroid status in subsequent pregnancy.

Objective

We aimed to determine trends in the management of hyperthyroidism before and during pregnancy and to assess the impact of different preconception treatment strategies on maternal thyroid status.

Methods

We utilized the Clinical Practice Research Datalink database to evaluate all females aged 15-45 years with a clinical diagnosis of hyperthyroidism and a subsequent pregnancy (January 2000 to December 2017). We compared thyroid status in pregnancy according to preconception treatment, namely, (1) antithyroid drugs up to or beyond pregnancy onset, (2) definitive treatment with thyroidectomy or radioiodine before pregnancy, and (3) no treatment at pregnancy onset.

Results

Our study cohort comprised 4712 pregnancies. Thyrotropin (TSH) was measured in only 53.1% of pregnancies, of which 28.1% showed suboptimal thyroid status (TSH >4.0 mU/L or TSH <0.1 mU/L plus FT4 >reference range). Pregnancies with prior definitive treatment were more likely to have suboptimal thyroid status compared with pregnancies starting during antithyroid drug treatment (odds ratio 4.72, 95% CI 3.50-6.36). A steady decline in the use of definitive treatment before pregnancy was observed from 2000 to 2017. One-third (32.6%) of first trimester carbimazole-exposed pregnancies were switched to propylthiouracil while 6.0% of propylthiouracil-exposed pregnancies switched to carbimazole.

Conclusion

The management of women with hyperthyroidism who become pregnant is suboptimal, particularly in those with preconception definitive treatment, and needs urgent improvement. Better thyroid monitoring and prenatal counseling are needed to optimize thyroid status, reduce teratogenic drug exposure, and ultimately reduce the risk of adverse pregnancy outcomes.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1210/clinem/dgad276; doi:https://doi.org/10.1210/clinem/dgad276; html:https://europepmc.org/articles/PMC10584009" + }, { "id": "37729117", "doi": "https://doi.org/10.1371/journal.pdig.0000309", @@ -19855,23 +19855,6 @@ "laySummary": "", "urls": "pdf:http://www.jaad.org/article/S0190962219326143/pdf; doi:https://doi.org/10.1016/j.jaad.2019.08.039; html:https://europepmc.org/articles/PMC7704103; pdf:https://europepmc.org/articles/PMC7704103?pdf=render" }, - { - "id": "37703231", - "doi": "https://doi.org/10.1371/journal.pdig.0000334", - "title": "A population-based study exploring phenotypic clusters and clinical outcomes in stroke using unsupervised machine learning approach.", - "authorString": "Akyea RK, Ntaios G, Kontopantelis E, Georgiopoulos G, Soria D, Asselbergs FW, Kai J, Weng SF, Qureshi N.", - "authorAffiliations": "", - "journalTitle": "PLOS digital health", - "pubYear": "2023", - "date": "2023-09-13", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Individuals developing stroke have varying clinical characteristics, demographic, and biochemical profiles. This heterogeneity in phenotypic characteristics can impact on cardiovascular disease (CVD) morbidity and mortality outcomes. This study uses a novel clustering approach to stratify individuals with incident stroke into phenotypic clusters and evaluates the differential burden of recurrent stroke and other cardiovascular outcomes. We used linked clinical data from primary care, hospitalisations, and death records in the UK. A data-driven clustering analysis (kamila algorithm) was used in 48,114 patients aged \u2265 18 years with incident stroke, from 1-Jan-1998 to 31-Dec-2017 and no prior history of serious vascular events. Cox proportional hazards regression was used to estimate hazard ratios (HRs) for subsequent adverse outcomes, for each of the generated clusters. Adverse outcomes included coronary heart disease (CHD), recurrent stroke, peripheral vascular disease (PVD), heart failure, CVD-related and all-cause mortality. Four distinct phenotypes with varying underlying clinical characteristics were identified in patients with incident stroke. Compared with cluster 1 (n = 5,201, 10.8%), the risk of composite recurrent stroke and CVD-related mortality was higher in the other 3 clusters (cluster 2 [n = 18,655, 38.8%]: hazard ratio [HR], 1.07; 95% CI, 1.02-1.12; cluster 3 [n = 10,244, 21.3%]: HR, 1.20; 95% CI, 1.14-1.26; and cluster 4 [n = 14,014, 29.1%]: HR, 1.44; 95% CI: 1.37-1.50). Similar trends in risk were observed for composite recurrent stroke and all-cause mortality outcome, and subsequent recurrent stroke outcome. However, results were not consistent for subsequent risk in CHD, PVD, heart failure, CVD-related mortality, and all-cause mortality. In this proof of principle study, we demonstrated how a heterogenous population of patients with incident stroke can be stratified into four relatively homogenous phenotypes with differential risk of recurrent and major cardiovascular outcomes. This offers an opportunity to revisit the stratification of care for patients with incident stroke to improve patient outcomes.", - "laySummary": "", - "urls": "pdf:https://journals.plos.org/digitalhealth/article/file?id=10.1371/journal.pdig.0000334&type=printable; doi:https://doi.org/10.1371/journal.pdig.0000334; html:https://europepmc.org/articles/PMC10499205; pdf:https://europepmc.org/articles/PMC10499205?pdf=render" - }, { "id": "33655079", "doi": "https://doi.org/10.12688/wellcomeopenres.16304.2", @@ -19889,6 +19872,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.12688/wellcomeopenres.16304.2; html:https://europepmc.org/articles/PMC7890379; pdf:https://europepmc.org/articles/PMC7890379?pdf=render" }, + { + "id": "37703231", + "doi": "https://doi.org/10.1371/journal.pdig.0000334", + "title": "A population-based study exploring phenotypic clusters and clinical outcomes in stroke using unsupervised machine learning approach.", + "authorString": "Akyea RK, Ntaios G, Kontopantelis E, Georgiopoulos G, Soria D, Asselbergs FW, Kai J, Weng SF, Qureshi N.", + "authorAffiliations": "", + "journalTitle": "PLOS digital health", + "pubYear": "2023", + "date": "2023-09-13", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Individuals developing stroke have varying clinical characteristics, demographic, and biochemical profiles. This heterogeneity in phenotypic characteristics can impact on cardiovascular disease (CVD) morbidity and mortality outcomes. This study uses a novel clustering approach to stratify individuals with incident stroke into phenotypic clusters and evaluates the differential burden of recurrent stroke and other cardiovascular outcomes. We used linked clinical data from primary care, hospitalisations, and death records in the UK. A data-driven clustering analysis (kamila algorithm) was used in 48,114 patients aged \u2265 18 years with incident stroke, from 1-Jan-1998 to 31-Dec-2017 and no prior history of serious vascular events. Cox proportional hazards regression was used to estimate hazard ratios (HRs) for subsequent adverse outcomes, for each of the generated clusters. Adverse outcomes included coronary heart disease (CHD), recurrent stroke, peripheral vascular disease (PVD), heart failure, CVD-related and all-cause mortality. Four distinct phenotypes with varying underlying clinical characteristics were identified in patients with incident stroke. Compared with cluster 1 (n = 5,201, 10.8%), the risk of composite recurrent stroke and CVD-related mortality was higher in the other 3 clusters (cluster 2 [n = 18,655, 38.8%]: hazard ratio [HR], 1.07; 95% CI, 1.02-1.12; cluster 3 [n = 10,244, 21.3%]: HR, 1.20; 95% CI, 1.14-1.26; and cluster 4 [n = 14,014, 29.1%]: HR, 1.44; 95% CI: 1.37-1.50). Similar trends in risk were observed for composite recurrent stroke and all-cause mortality outcome, and subsequent recurrent stroke outcome. However, results were not consistent for subsequent risk in CHD, PVD, heart failure, CVD-related mortality, and all-cause mortality. In this proof of principle study, we demonstrated how a heterogenous population of patients with incident stroke can be stratified into four relatively homogenous phenotypes with differential risk of recurrent and major cardiovascular outcomes. This offers an opportunity to revisit the stratification of care for patients with incident stroke to improve patient outcomes.", + "laySummary": "", + "urls": "pdf:https://journals.plos.org/digitalhealth/article/file?id=10.1371/journal.pdig.0000334&type=printable; doi:https://doi.org/10.1371/journal.pdig.0000334; html:https://europepmc.org/articles/PMC10499205; pdf:https://europepmc.org/articles/PMC10499205?pdf=render" + }, { "id": "35987738", "doi": "https://doi.org/10.1016/j.jcmg.2022.06.017", @@ -19991,23 +19991,6 @@ "laySummary": "", "urls": "pdf:https://bmjmedicine.bmj.com/content/bmjmed/2/1/e000245.full.pdf; doi:https://doi.org/10.1136/bmjmed-2022-000245; html:https://europepmc.org/articles/PMC10083523; pdf:https://europepmc.org/articles/PMC10083523?pdf=render" }, - { - "id": "36369983", - "doi": "https://doi.org/10.1093/eurheartj/ehac650", - "title": "Fit for the future: empowering clinical trials with digital technology.", - "authorString": "Kotecha D, DeVore AD, Asselbergs FW.", - "authorAffiliations": "", - "journalTitle": "European heart journal", - "pubYear": "2023", - "date": "2023-01-01", - "isOpenAccess": "N", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "", - "laySummary": "", - "urls": "pdf:https://discovery.ucl.ac.uk/10159909/1/Asselbergs_EHJ%20digital%20viewpoint%202022_final%20accepted.pdf; doi:https://doi.org/10.1093/eurheartj/ehac650" - }, { "id": "35842339", "doi": "https://doi.org/10.1016/j.vaccine.2022.06.080", @@ -20026,21 +20009,21 @@ "urls": "doi:https://doi.org/10.1016/j.vaccine.2022.06.080; doi:https://doi.org/10.1016/j.vaccine.2022.06.080; html:https://europepmc.org/articles/PMC10499753; pdf:https://europepmc.org/articles/PMC10499753?pdf=render" }, { - "id": "37740900", - "doi": "https://doi.org/10.1093/ageing/afad176", - "title": "Interventions for reducing anticholinergic medication burden in older adults-a systematic review and meta-analysis.", - "authorString": "Braithwaite E, Todd OM, Atkin A, Hulatt R, Tadrous R, Alldred DP, Pirmohamed M, Walker L, Lawton R, Clegg A.", + "id": "36369983", + "doi": "https://doi.org/10.1093/eurheartj/ehac650", + "title": "Fit for the future: empowering clinical trials with digital technology.", + "authorString": "Kotecha D, DeVore AD, Asselbergs FW.", "authorAffiliations": "", - "journalTitle": "Age and ageing", + "journalTitle": "European heart journal", "pubYear": "2023", - "date": "2023-09-01", - "isOpenAccess": "Y", - "keywords": "Cognition; Meta-analysis; Systematic review; Falls; Older People; Older Adult; Anticholinergic Medication", + "date": "2023-01-01", + "isOpenAccess": "N", + "keywords": "", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Introduction

Anticholinergic medications block the neurotransmitter acetylcholine in the brain and peripheral nervous system. Many medications have anticholinergic properties, and the cumulative effect of these medications is termed anticholinergic burden. Increased anticholinergic burden can have short-term side effects such as dry mouth, blurred vision and urinary retention as well as long-term effects including dementia, worsening physical function and falls.

Methods

We carried out a systematic review (SR) with meta-analysis (MA) looking at randomised controlled trials addressing interventions to reduce anticholinergic burden in older adults.

Results

We identified seven papers suitable for inclusion in our SR and MA. Interventions included multi-disciplinary involvement in medication reviews and deprescribing of AC medications. Pooled data revealed no significant difference in outcomes between control and intervention group for falls (OR = 0.76, 95% CI: 0.52-1.11, n\u2009=\u2009647), cognition (mean difference = 1.54, 95% CI: -0.04 to 3.13, n\u2009=\u2009405), anticholinergic burden (mean difference = 0.04, 95% CI: -0.11 to 0.18, n\u2009=\u2009710) or quality of life (mean difference = 0.04, 95% CI: -0.04 to 0.12, n\u2009=\u2009461).

Discussion

Overall, there was no significant difference with interventions to reduce anticholinergic burden. As we did not see a significant change in anticholinergic burden scores following interventions, it is likely other outcomes would not change. Short follow-up time and lack of training and support surrounding successful deprescribing may have contributed.", + "abstract": "", "laySummary": "", - "urls": "pdf:https://academic.oup.com/ageing/article-pdf/52/9/afad176/51729004/afad176.pdf; doi:https://doi.org/10.1093/ageing/afad176; html:https://europepmc.org/articles/PMC10517713; pdf:https://europepmc.org/articles/PMC10517713?pdf=render" + "urls": "pdf:https://discovery.ucl.ac.uk/10159909/1/Asselbergs_EHJ%20digital%20viewpoint%202022_final%20accepted.pdf; doi:https://doi.org/10.1093/eurheartj/ehac650" }, { "id": "33328049", @@ -20059,6 +20042,23 @@ "laySummary": "", "urls": "pdf:http://www.thelancet.com/article/S2589750020302193/pdf; doi:https://doi.org/10.1016/S2589-7500(20)30219-3; html:https://europepmc.org/articles/PMC8212701; pdf:https://europepmc.org/articles/PMC8212701?pdf=render" }, + { + "id": "37740900", + "doi": "https://doi.org/10.1093/ageing/afad176", + "title": "Interventions for reducing anticholinergic medication burden in older adults-a systematic review and meta-analysis.", + "authorString": "Braithwaite E, Todd OM, Atkin A, Hulatt R, Tadrous R, Alldred DP, Pirmohamed M, Walker L, Lawton R, Clegg A.", + "authorAffiliations": "", + "journalTitle": "Age and ageing", + "pubYear": "2023", + "date": "2023-09-01", + "isOpenAccess": "Y", + "keywords": "Cognition; Meta-analysis; Systematic review; Falls; Older People; Older Adult; Anticholinergic Medication", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Introduction

Anticholinergic medications block the neurotransmitter acetylcholine in the brain and peripheral nervous system. Many medications have anticholinergic properties, and the cumulative effect of these medications is termed anticholinergic burden. Increased anticholinergic burden can have short-term side effects such as dry mouth, blurred vision and urinary retention as well as long-term effects including dementia, worsening physical function and falls.

Methods

We carried out a systematic review (SR) with meta-analysis (MA) looking at randomised controlled trials addressing interventions to reduce anticholinergic burden in older adults.

Results

We identified seven papers suitable for inclusion in our SR and MA. Interventions included multi-disciplinary involvement in medication reviews and deprescribing of AC medications. Pooled data revealed no significant difference in outcomes between control and intervention group for falls (OR = 0.76, 95% CI: 0.52-1.11, n\u2009=\u2009647), cognition (mean difference = 1.54, 95% CI: -0.04 to 3.13, n\u2009=\u2009405), anticholinergic burden (mean difference = 0.04, 95% CI: -0.11 to 0.18, n\u2009=\u2009710) or quality of life (mean difference = 0.04, 95% CI: -0.04 to 0.12, n\u2009=\u2009461).

Discussion

Overall, there was no significant difference with interventions to reduce anticholinergic burden. As we did not see a significant change in anticholinergic burden scores following interventions, it is likely other outcomes would not change. Short follow-up time and lack of training and support surrounding successful deprescribing may have contributed.", + "laySummary": "", + "urls": "pdf:https://academic.oup.com/ageing/article-pdf/52/9/afad176/51729004/afad176.pdf; doi:https://doi.org/10.1093/ageing/afad176; html:https://europepmc.org/articles/PMC10517713; pdf:https://europepmc.org/articles/PMC10517713?pdf=render" + }, { "id": "34871122", "doi": "https://doi.org/10.1080/09638288.2021.2008526", @@ -20161,23 +20161,6 @@ "laySummary": "", "urls": "pdf:http://www.jprasurg.com/article/S1748681523006769/pdf; doi:https://doi.org/10.1016/j.bjps.2023.10.106" }, - { - "id": "36707908", - "doi": "https://doi.org/10.1186/s13643-023-02173-w", - "title": "A comparison of international modelling methods to evaluate health economics of colorectal cancer screening: a systematic review protocol.", - "authorString": "Adair O, McFerran E, Owen T, McKee C, Lamrock F, Lawler M.", - "authorAffiliations": "", - "journalTitle": "Systematic reviews", - "pubYear": "2023", - "date": "2023-01-27", - "isOpenAccess": "Y", - "keywords": "Screening; Economic evaluation; Colorectal Cancer; Health Economics; Cost-effectiveness Analysis; Quality-adjusted Life Years; Cost-utility; Incremental Cost-effectiveness Ratio; Cost\u2013benefit; Life Years Gained", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Colorectal cancer (CRC) is becoming an increasing health problem worldwide. However, with the help of screening, early diagnosis can reduce incidence and mortality rates. To elevate the economic burden that CRC can cause, cost-effectiveness analysis (CEA) can assist healthcare systems to make screening programmes more cost-effective and prolong survival for early-stage CRC patients. This review aims to identify different CEA modelling methods used internationally to evaluate health economics of CRC screening.

Methods

This review will systematically search electronic databases which include MEDLINE, EMBASE, Web of Science and Scopus. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidance recommendations will design the review, and the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement will be used to extract relevant data from studies retrieved. Two reviewers will screen through the evidence using the PICOS (Participant, Intervention, Comparators, Outcomes, Study Design) framework, with a third reviewer to settle any disagreements. Once data extraction and quality assessment are complete, the results will be presented qualitatively and tabulated using the CHEERS checklist.

Discussion

The results obtained from the systematic review will highlight how different CRC screening programmes around the world utilise and incorporate health economic modelling methods to be more cost-effective. This information can help modellers develop CEA models which can be adapted to suit the specific screening programmes that they are evaluating.

Systematic review registration

PROSPERO CRD42022296113.", - "laySummary": "", - "urls": "pdf:https://systematicreviewsjournal.biomedcentral.com/counter/pdf/10.1186/s13643-023-02173-w; doi:https://doi.org/10.1186/s13643-023-02173-w; html:https://europepmc.org/articles/PMC9883863; pdf:https://europepmc.org/articles/PMC9883863?pdf=render" - }, { "id": "34912046", "doi": "https://doi.org/10.1038/s41366-021-01048-1", @@ -20195,6 +20178,23 @@ "laySummary": "", "urls": "pdf:https://www.nature.com/articles/s41366-021-01048-1.pdf; doi:https://doi.org/10.1038/s41366-021-01048-1; html:https://europepmc.org/articles/PMC8671878; pdf:https://europepmc.org/articles/PMC8671878?pdf=render" }, + { + "id": "36707908", + "doi": "https://doi.org/10.1186/s13643-023-02173-w", + "title": "A comparison of international modelling methods to evaluate health economics of colorectal cancer screening: a systematic review protocol.", + "authorString": "Adair O, McFerran E, Owen T, McKee C, Lamrock F, Lawler M.", + "authorAffiliations": "", + "journalTitle": "Systematic reviews", + "pubYear": "2023", + "date": "2023-01-27", + "isOpenAccess": "Y", + "keywords": "Screening; Economic evaluation; Colorectal Cancer; Health Economics; Cost-effectiveness Analysis; Quality-adjusted Life Years; Cost-utility; Incremental Cost-effectiveness Ratio; Cost\u2013benefit; Life Years Gained", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Colorectal cancer (CRC) is becoming an increasing health problem worldwide. However, with the help of screening, early diagnosis can reduce incidence and mortality rates. To elevate the economic burden that CRC can cause, cost-effectiveness analysis (CEA) can assist healthcare systems to make screening programmes more cost-effective and prolong survival for early-stage CRC patients. This review aims to identify different CEA modelling methods used internationally to evaluate health economics of CRC screening.

Methods

This review will systematically search electronic databases which include MEDLINE, EMBASE, Web of Science and Scopus. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidance recommendations will design the review, and the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement will be used to extract relevant data from studies retrieved. Two reviewers will screen through the evidence using the PICOS (Participant, Intervention, Comparators, Outcomes, Study Design) framework, with a third reviewer to settle any disagreements. Once data extraction and quality assessment are complete, the results will be presented qualitatively and tabulated using the CHEERS checklist.

Discussion

The results obtained from the systematic review will highlight how different CRC screening programmes around the world utilise and incorporate health economic modelling methods to be more cost-effective. This information can help modellers develop CEA models which can be adapted to suit the specific screening programmes that they are evaluating.

Systematic review registration

PROSPERO CRD42022296113.", + "laySummary": "", + "urls": "pdf:https://systematicreviewsjournal.biomedcentral.com/counter/pdf/10.1186/s13643-023-02173-w; doi:https://doi.org/10.1186/s13643-023-02173-w; html:https://europepmc.org/articles/PMC9883863; pdf:https://europepmc.org/articles/PMC9883863?pdf=render" + }, { "id": "37606853", "doi": "https://doi.org/10.1007/s00520-023-07944-8", @@ -20212,23 +20212,6 @@ "laySummary": "", "urls": "pdf:https://link.springer.com/content/pdf/10.1007/s00520-023-07944-8.pdf; doi:https://doi.org/10.1007/s00520-023-07944-8; html:https://europepmc.org/articles/PMC10444652; pdf:https://europepmc.org/articles/PMC10444652?pdf=render" }, - { - "id": "38023948", - "doi": "https://doi.org/10.18332/ejm/171802", - "title": "A qualitative study exploring healthcare workers' lived experiences of the impacts of COVID-19 policies and guidelines on maternal and reproductive healthcare services in the United Kingdom.", - "authorString": "Chaloner J, Qureshi I, Gogoi M, Ekezie WC, Al-Oraibi A, Wobi F, Agbonmwandolor JO, Nellums LB, Pareek M.", - "authorAffiliations": "", - "journalTitle": "European journal of midwifery", - "pubYear": "2023", - "date": "2023-11-08", - "isOpenAccess": "Y", - "keywords": "Healthcare Workers; Vaccine Hesitancy; Redeployment; Infection Controls; Covid-19; Policies And Guidelines", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Introduction

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

Methods

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

Results

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

Conclusions

COVID-19 demonstrated how a global health crisis can impact maternal and reproductive health services, leading to reduced service quality and surgical delays due to staff redeployment policies. Our findings underscore the implications of policy and future health crises preparedness. This includes tailored infection control policies, addressing elective surgery backlogs early and improved dissemination of relevant vaccine information.", - "laySummary": "", - "urls": "pdf:https://www.europeanjournalofmidwifery.eu/pdf-171802-96110?filename=A qualitative study.pdf; doi:https://doi.org/10.18332/ejm/171802; html:https://europepmc.org/articles/PMC10630987; pdf:https://europepmc.org/articles/PMC10630987?pdf=render" - }, { "id": "30659777", "doi": "https://doi.org/10.1111/ijpo.12505", @@ -20246,6 +20229,23 @@ "laySummary": "", "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/ijpo.12505; doi:https://doi.org/10.1111/ijpo.12505; html:https://europepmc.org/articles/PMC6563186; pdf:https://europepmc.org/articles/PMC6563186?pdf=render" }, + { + "id": "38023948", + "doi": "https://doi.org/10.18332/ejm/171802", + "title": "A qualitative study exploring healthcare workers' lived experiences of the impacts of COVID-19 policies and guidelines on maternal and reproductive healthcare services in the United Kingdom.", + "authorString": "Chaloner J, Qureshi I, Gogoi M, Ekezie WC, Al-Oraibi A, Wobi F, Agbonmwandolor JO, Nellums LB, Pareek M.", + "authorAffiliations": "", + "journalTitle": "European journal of midwifery", + "pubYear": "2023", + "date": "2023-11-08", + "isOpenAccess": "Y", + "keywords": "Healthcare Workers; Vaccine Hesitancy; Redeployment; Infection Controls; Covid-19; Policies And Guidelines", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Introduction

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

Methods

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

Results

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

Conclusions

COVID-19 demonstrated how a global health crisis can impact maternal and reproductive health services, leading to reduced service quality and surgical delays due to staff redeployment policies. Our findings underscore the implications of policy and future health crises preparedness. This includes tailored infection control policies, addressing elective surgery backlogs early and improved dissemination of relevant vaccine information.", + "laySummary": "", + "urls": "pdf:https://www.europeanjournalofmidwifery.eu/pdf-171802-96110?filename=A qualitative study.pdf; doi:https://doi.org/10.18332/ejm/171802; html:https://europepmc.org/articles/PMC10630987; pdf:https://europepmc.org/articles/PMC10630987?pdf=render" + }, { "id": "32771960", "doi": "https://doi.org/10.1016/j.ijmedinf.2020.104237", @@ -20280,6 +20280,23 @@ "laySummary": "", "urls": "pdf:https://cronfa.swan.ac.uk/Record/cronfa60128/Download/60128__24479__4d74009536e649b0b17180e2bfd80435.pdf; doi:https://doi.org/10.1111/bjhp.12606; html:https://europepmc.org/articles/PMC9347957; pdf:https://europepmc.org/articles/PMC9347957?pdf=render" }, + { + "id": "32046816", + "doi": "https://doi.org/10.2807/1560-7917.es.2020.25.5.2000080", + "title": "Effectiveness of airport screening at detecting travellers infected with novel coronavirus (2019-nCoV).", + "authorString": "Quilty BJ, Clifford S, CMMID nCoV working group2, Flasche S, Eggo RM.", + "authorAffiliations": "", + "journalTitle": "Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin", + "pubYear": "2020", + "date": "2020-02-01", + "isOpenAccess": "Y", + "keywords": "Surveillance; Effectiveness; Interventions; Emerging Infections; 2019-Ncov; Thermal Scanning; Airport Screening", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "We evaluated effectiveness of thermal passenger screening for 2019-nCoV infection at airport exit and entry to inform public health decision-making. In our baseline scenario, we estimated that 46% (95% confidence interval: 36 to 58) of infected travellers would not be detected, depending on incubation period, sensitivity of exit and entry screening, and proportion of asymptomatic cases. Airport screening is unlikely to detect a sufficient proportion of 2019-nCoV infected travellers to avoid entry of infected travellers.", + "laySummary": "", + "urls": "pdf:https://www.eurosurveillance.org/deliver/fulltext/eurosurveillance/25/5/eurosurv-25-5-2.pdf?itemId=%2Fcontent%2F10.2807%2F1560-7917.ES.2020.25.5.2000080&mimeType=pdf&containerItemId=content/eurosurveillance; doi:https://doi.org/10.2807/1560-7917.ES.2020.25.5.2000080; html:https://europepmc.org/articles/PMC7014668; pdf:https://europepmc.org/articles/PMC7014668?pdf=render" + }, { "id": "36501061", "doi": "https://doi.org/10.3390/nu14235031", @@ -20298,21 +20315,21 @@ "urls": "pdf:https://www.mdpi.com/2072-6643/14/23/5031/pdf?version=1669449806; doi:https://doi.org/10.3390/nu14235031; html:https://europepmc.org/articles/PMC9740080; pdf:https://europepmc.org/articles/PMC9740080?pdf=render" }, { - "id": "32046816", - "doi": "https://doi.org/10.2807/1560-7917.es.2020.25.5.2000080", - "title": "Effectiveness of airport screening at detecting travellers infected with novel coronavirus (2019-nCoV).", - "authorString": "Quilty BJ, Clifford S, CMMID nCoV working group2, Flasche S, Eggo RM.", + "id": "34859617", + "doi": "https://doi.org/10.1002/edm2.309", + "title": "The clinical profile and associated mortality in people with and without diabetes with Coronavirus disease 2019 on admission to acute hospital services.", + "authorString": "Gokhale K, Mostafa SA, Wang J, Tahrani AA, Sainsbury CA, Toulis KA, Thomas GN, Hassan-Smith Z, Sapey E, Gallier S, Adderley NJ, Narendran P, Bellary S, Taverner T, Ghosh S, Nirantharakumar K, Hanif W.", "authorAffiliations": "", - "journalTitle": "Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin", - "pubYear": "2020", - "date": "2020-02-01", + "journalTitle": "Endocrinology, diabetes & metabolism", + "pubYear": "2022", + "date": "2021-12-03", "isOpenAccess": "Y", - "keywords": "Surveillance; Effectiveness; Interventions; Emerging Infections; 2019-Ncov; Thermal Scanning; Airport Screening", + "keywords": "Diabetes; Complications; Covid-19", "nationalPriorities": "", "healthCategories": "", - "abstract": "We evaluated effectiveness of thermal passenger screening for 2019-nCoV infection at airport exit and entry to inform public health decision-making. In our baseline scenario, we estimated that 46% (95% confidence interval: 36 to 58) of infected travellers would not be detected, depending on incubation period, sensitivity of exit and entry screening, and proportion of asymptomatic cases. Airport screening is unlikely to detect a sufficient proportion of 2019-nCoV infected travellers to avoid entry of infected travellers.", + "abstract": "

Introduction

To assess if in adults with COVID-19, whether those with diabetes and complications (DM+C) present with a more severe clinical profile and if that relates to increased mortality, compared to those with diabetes with no complications (DM-NC) and those without diabetes.

Methods

Service-level data was used from 996 adults with laboratory confirmed COVID-19 who presented to the Queen Elizabeth Hospital Birmingham, UK, from March to June 2020. All individuals were categorized into DM+C, DM-NC, and non-diabetes groups. Physiological and laboratory measurements in the first 5 days after admission were collated and compared among groups. Cox proportional hazards regression models were used to evaluate associations between diabetes status and the risk of mortality.

Results

Among the 996 individuals, 104 (10.4%) were DM+C, 295 (29.6%) DM-NC and 597 (59.9%) non-diabetes. There were 309 (31.0%) in-hospital deaths documented, 40 (4.0% of total cohort) were DM+C, 99 (9.9%) DM-NC and 170 (17.0%) non-diabetes. Individuals with DM+C were more likely to present with high anion gap/metabolic acidosis, features of renal impairment, and low albumin/lymphocyte count than those with DM-NC or those without diabetes. There was no significant difference in mortality rates among the groups: compared to individuals without diabetes, the adjusted HRs were 1.39 (95% CI 0.95-2.03, p\u00a0=\u00a00.093) and 1.18 (95% CI 0.90-1.54, p\u00a0=\u00a00.226) in DM+C and DM-C, respectively.

Conclusions

Those with COVID-19 and DM+C presented with a more severe clinical and biochemical profile, but this did not associate with increased mortality in this study.", "laySummary": "", - "urls": "pdf:https://www.eurosurveillance.org/deliver/fulltext/eurosurveillance/25/5/eurosurv-25-5-2.pdf?itemId=%2Fcontent%2F10.2807%2F1560-7917.ES.2020.25.5.2000080&mimeType=pdf&containerItemId=content/eurosurveillance; doi:https://doi.org/10.2807/1560-7917.ES.2020.25.5.2000080; html:https://europepmc.org/articles/PMC7014668; pdf:https://europepmc.org/articles/PMC7014668?pdf=render" + "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/edm2.309; doi:https://doi.org/10.1002/edm2.309; html:https://europepmc.org/articles/PMC8754243; pdf:https://europepmc.org/articles/PMC8754243?pdf=render" }, { "id": "38660106", @@ -20332,21 +20349,21 @@ "urls": "doi:https://doi.org/10.1016/j.jacasi.2024.02.003; html:https://europepmc.org/articles/PMC11035929; pdf:https://europepmc.org/articles/PMC11035929?pdf=render" }, { - "id": "34859617", - "doi": "https://doi.org/10.1002/edm2.309", - "title": "The clinical profile and associated mortality in people with and without diabetes with Coronavirus disease 2019 on admission to acute hospital services.", - "authorString": "Gokhale K, Mostafa SA, Wang J, Tahrani AA, Sainsbury CA, Toulis KA, Thomas GN, Hassan-Smith Z, Sapey E, Gallier S, Adderley NJ, Narendran P, Bellary S, Taverner T, Ghosh S, Nirantharakumar K, Hanif W.", + "id": "32301135", + "doi": "https://doi.org/10.1111/opo.12685", + "title": "Delayed attendance at routine eye examinations is associated with increased probability of general practitioner referral: a record linkage study in Northern Ireland.", + "authorString": "Wright DM, O'Reilly D, Azuara-Blanco A, Curran R, McMullan M, Hogg RE.", "authorAffiliations": "", - "journalTitle": "Endocrinology, diabetes & metabolism", - "pubYear": "2022", - "date": "2021-12-03", - "isOpenAccess": "Y", - "keywords": "Diabetes; Complications; Covid-19", + "journalTitle": "Ophthalmic & physiological optics : the journal of the British College of Ophthalmic Opticians (Optometrists)", + "pubYear": "2020", + "date": "2020-04-16", + "isOpenAccess": "N", + "keywords": "epidemiology; Public Health; Optometry Services", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Introduction

To assess if in adults with COVID-19, whether those with diabetes and complications (DM+C) present with a more severe clinical profile and if that relates to increased mortality, compared to those with diabetes with no complications (DM-NC) and those without diabetes.

Methods

Service-level data was used from 996 adults with laboratory confirmed COVID-19 who presented to the Queen Elizabeth Hospital Birmingham, UK, from March to June 2020. All individuals were categorized into DM+C, DM-NC, and non-diabetes groups. Physiological and laboratory measurements in the first 5 days after admission were collated and compared among groups. Cox proportional hazards regression models were used to evaluate associations between diabetes status and the risk of mortality.

Results

Among the 996 individuals, 104 (10.4%) were DM+C, 295 (29.6%) DM-NC and 597 (59.9%) non-diabetes. There were 309 (31.0%) in-hospital deaths documented, 40 (4.0% of total cohort) were DM+C, 99 (9.9%) DM-NC and 170 (17.0%) non-diabetes. Individuals with DM+C were more likely to present with high anion gap/metabolic acidosis, features of renal impairment, and low albumin/lymphocyte count than those with DM-NC or those without diabetes. There was no significant difference in mortality rates among the groups: compared to individuals without diabetes, the adjusted HRs were 1.39 (95% CI 0.95-2.03, p\u00a0=\u00a00.093) and 1.18 (95% CI 0.90-1.54, p\u00a0=\u00a00.226) in DM+C and DM-C, respectively.

Conclusions

Those with COVID-19 and DM+C presented with a more severe clinical and biochemical profile, but this did not associate with increased mortality in this study.", + "abstract": "

Purpose

To investigate relationships between health and socio-economic status with delayed attendance at routine eye examinations and risk of subsequent general practitioner (GP) referral in Northern Ireland.

Methods

We constructed a cohort of 132\u00a0046 community dwelling individuals aged \u226560\u00a0years, drawing contextual information from the 2011 Northern Ireland Census. Using linked administrative records of routine eye examinations between 2009 and 2014, we calculated 311\u00a0999 examination intervals. Multinomial models were used to estimate associations between contextual factors and examination interval (classified into three groups: early recall, on-time, delayed attendance). Associations between examination interval and referral risk were estimated using logistic regression.

Results

Delayed attendance was recorded for 129\u00a0857 (41.6%) examination intervals, 53\u00a0759 (17.2%) delayed by \u22656\u00a0months. Female sex, poor general or mental health were each associated with delay, as were longer distances to optometry services among those aged \u226570\u00a0years (longest vs shortest: Relative Risk Ratio\u00a0=\u00a01.21 [1.14, 1.28]). Low income and residence in social housing were associated with reduced delay risk. There were 3347 (3.5%) and 11\u00a0401 (5.3%) GP referrals in the 60-69 and \u226570\u00a0years age groups respectively. Delayed attendance was associated with increased referral risk in both groups (Odds Ratios: 60-69\u00a0years\u00a0=\u00a01.30 [1.04, 1.61]; \u226570\u00a0years\u00a0=\u00a01.07 [1.01, 1.13]).

Conclusions

Poor health and longer distances to optometry services were associated with delayed attendance at routine eye examinations but low income was not. Delayed attendance was associated with increased GP referral risk, indicative of missed opportunities to detect potentially serious eye conditions.", "laySummary": "", - "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/edm2.309; doi:https://doi.org/10.1002/edm2.309; html:https://europepmc.org/articles/PMC8754243; pdf:https://europepmc.org/articles/PMC8754243?pdf=render" + "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/opo.12685; doi:https://doi.org/10.1111/opo.12685" }, { "id": "37309807", @@ -20382,23 +20399,6 @@ "laySummary": "", "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ctm2.1291; doi:https://doi.org/10.1002/ctm2.1291; html:https://europepmc.org/articles/PMC10280047; pdf:https://europepmc.org/articles/PMC10280047?pdf=render" }, - { - "id": "32301135", - "doi": "https://doi.org/10.1111/opo.12685", - "title": "Delayed attendance at routine eye examinations is associated with increased probability of general practitioner referral: a record linkage study in Northern Ireland.", - "authorString": "Wright DM, O'Reilly D, Azuara-Blanco A, Curran R, McMullan M, Hogg RE.", - "authorAffiliations": "", - "journalTitle": "Ophthalmic & physiological optics : the journal of the British College of Ophthalmic Opticians (Optometrists)", - "pubYear": "2020", - "date": "2020-04-16", - "isOpenAccess": "N", - "keywords": "epidemiology; Public Health; Optometry Services", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Purpose

To investigate relationships between health and socio-economic status with delayed attendance at routine eye examinations and risk of subsequent general practitioner (GP) referral in Northern Ireland.

Methods

We constructed a cohort of 132\u00a0046 community dwelling individuals aged \u226560\u00a0years, drawing contextual information from the 2011 Northern Ireland Census. Using linked administrative records of routine eye examinations between 2009 and 2014, we calculated 311\u00a0999 examination intervals. Multinomial models were used to estimate associations between contextual factors and examination interval (classified into three groups: early recall, on-time, delayed attendance). Associations between examination interval and referral risk were estimated using logistic regression.

Results

Delayed attendance was recorded for 129\u00a0857 (41.6%) examination intervals, 53\u00a0759 (17.2%) delayed by \u22656\u00a0months. Female sex, poor general or mental health were each associated with delay, as were longer distances to optometry services among those aged \u226570\u00a0years (longest vs shortest: Relative Risk Ratio\u00a0=\u00a01.21 [1.14, 1.28]). Low income and residence in social housing were associated with reduced delay risk. There were 3347 (3.5%) and 11\u00a0401 (5.3%) GP referrals in the 60-69 and \u226570\u00a0years age groups respectively. Delayed attendance was associated with increased referral risk in both groups (Odds Ratios: 60-69\u00a0years\u00a0=\u00a01.30 [1.04, 1.61]; \u226570\u00a0years\u00a0=\u00a01.07 [1.01, 1.13]).

Conclusions

Poor health and longer distances to optometry services were associated with delayed attendance at routine eye examinations but low income was not. Delayed attendance was associated with increased GP referral risk, indicative of missed opportunities to detect potentially serious eye conditions.", - "laySummary": "", - "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/opo.12685; doi:https://doi.org/10.1111/opo.12685" - }, { "id": "31666244", "doi": "https://doi.org/10.1136/archdischild-2019-317271", @@ -20604,21 +20604,21 @@ "urls": "pdf:https://gut.bmj.com/content/gutjnl/71/4/705.full.pdf; doi:https://doi.org/10.1136/gutjnl-2020-323546; html:https://europepmc.org/articles/PMC8921573; pdf:https://europepmc.org/articles/PMC8921573?pdf=render" }, { - "id": "37645022", - "doi": "https://doi.org/10.1183/20734735.0058-2023", - "title": "The impact of poor housing and indoor air quality on respiratory health in children.", - "authorString": "Holden KA, Lee AR, Hawcutt DB, Sinha IP.", + "id": "34230034", + "doi": "https://doi.org/10.1136/bmjresp-2021-000967", + "title": "Increase in recruitment upon integration of trial into a clinical care pathway: an observational study.", + "authorString": "Yip KP, Gompertz S, Snelson C, Willson J, Madathil S, Huq SS, Rauf F, Salmon N, Tengende J, Tracey J, Cooper B, Filby K, Ball S, Parekh D, Dosanjh DPS.", "authorAffiliations": "", - "journalTitle": "Breathe (Sheffield, England)", - "pubYear": "2023", - "date": "2023-06-01", + "journalTitle": "BMJ open respiratory research", + "pubYear": "2021", + "date": "2021-07-01", "isOpenAccess": "Y", - "keywords": "", + "keywords": "Covid-19", "nationalPriorities": "", "healthCategories": "", - "abstract": "It is becoming increasingly apparent that poor housing quality affects indoor air quality, significantly impacting on respiratory health in children and young people. Exposure to damp and/or mould in the home, cold homes and the presence of pests and pollutants all have a significant detrimental impact on child respiratory health. There is a complex relationship between features of poor-quality housing, such as being in a state of disrepair, poor ventilation, overcrowding and being cold, that favour an environment resulting in poor indoor air quality. Children living in rented (private or public) housing are more likely to come from lower-income backgrounds and are most at risk of living in substandard housing posing a serious threat to respiratory health. Children have the right to safe and adequate housing, and research has shown that either rehousing or making modifications to poor-quality housing to improve indoor air quality results in improved respiratory health. Urgent action is needed to address this threat to health. All stakeholders should understand the relationship between poor-quality housing and respiratory health in children and act, working with families, to redress this modifiable risk factor.

Educational aims

The reader should understand how housing quality and indoor air quality affect respiratory health in children.The reader should understand which children are at most risk of living in poor-quality housing.The reader should understand what policy recommendations have been made and what actions need to be undertaken to improve housing quality and respiratory health in children and young people.", + "abstract": "

Introduction

Many respiratory clinical trials fail to reach their recruitment target and this problem exacerbates existing funding issues. Integration of the clinical trial recruitment process into a clinical care pathway (CCP) may represent an effective way to significantly increase recruitment numbers.

Methods

A respiratory support unit and a CCP for escalation of patients with severe COVID-19 were established on 11 January 2021. The recruitment process for the Randomised Evaluation of COVID-19 Therapy-Respiratory Support trial was integrated into the CCP on the same date. Recruitment data for the trial were collected before and after integration into the CCP.

Results

On integration of the recruitment process into a CCP, there was a significant increase in recruitment numbers. Fifty patients were recruited over 266 days before this process occurred whereas 108 patients were recruited over 49 days after this process. There was a statistically significant increase in both the proportion of recruited patients relative to the number of COVID-19 hospital admissions (change from 2.8% to 9.1%, p<0.0001) and intensive therapy unit admissions (change from 17.8% to 50.2%, p<0.001) over the same period, showing that this increase in recruitment was independent of COVID-19 prevalence.

Discussion

Integrating the trial recruitment process into a CCP can significantly boost recruitment numbers. This represents an innovative model that can be used to maximise recruitment without impacting on the financial and labour costs associated with the running of a respiratory clinical trial.", "laySummary": "", - "urls": "doi:https://doi.org/10.1183/20734735.0058-2023; html:https://europepmc.org/articles/PMC10461733; pdf:https://europepmc.org/articles/PMC10461733?pdf=render" + "urls": "pdf:https://bmjopenrespres.bmj.com/content/bmjresp/8/1/e000967.full.pdf; doi:https://doi.org/10.1136/bmjresp-2021-000967; html:https://europepmc.org/articles/PMC8261886; pdf:https://europepmc.org/articles/PMC8261886?pdf=render" }, { "id": "35589356", @@ -20638,21 +20638,21 @@ "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/12/5/e057343.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-057343; html:https://europepmc.org/articles/PMC9121475; pdf:https://europepmc.org/articles/PMC9121475?pdf=render" }, { - "id": "34230034", - "doi": "https://doi.org/10.1136/bmjresp-2021-000967", - "title": "Increase in recruitment upon integration of trial into a clinical care pathway: an observational study.", - "authorString": "Yip KP, Gompertz S, Snelson C, Willson J, Madathil S, Huq SS, Rauf F, Salmon N, Tengende J, Tracey J, Cooper B, Filby K, Ball S, Parekh D, Dosanjh DPS.", + "id": "37645022", + "doi": "https://doi.org/10.1183/20734735.0058-2023", + "title": "The impact of poor housing and indoor air quality on respiratory health in children.", + "authorString": "Holden KA, Lee AR, Hawcutt DB, Sinha IP.", "authorAffiliations": "", - "journalTitle": "BMJ open respiratory research", - "pubYear": "2021", - "date": "2021-07-01", + "journalTitle": "Breathe (Sheffield, England)", + "pubYear": "2023", + "date": "2023-06-01", "isOpenAccess": "Y", - "keywords": "Covid-19", + "keywords": "", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Introduction

Many respiratory clinical trials fail to reach their recruitment target and this problem exacerbates existing funding issues. Integration of the clinical trial recruitment process into a clinical care pathway (CCP) may represent an effective way to significantly increase recruitment numbers.

Methods

A respiratory support unit and a CCP for escalation of patients with severe COVID-19 were established on 11 January 2021. The recruitment process for the Randomised Evaluation of COVID-19 Therapy-Respiratory Support trial was integrated into the CCP on the same date. Recruitment data for the trial were collected before and after integration into the CCP.

Results

On integration of the recruitment process into a CCP, there was a significant increase in recruitment numbers. Fifty patients were recruited over 266 days before this process occurred whereas 108 patients were recruited over 49 days after this process. There was a statistically significant increase in both the proportion of recruited patients relative to the number of COVID-19 hospital admissions (change from 2.8% to 9.1%, p<0.0001) and intensive therapy unit admissions (change from 17.8% to 50.2%, p<0.001) over the same period, showing that this increase in recruitment was independent of COVID-19 prevalence.

Discussion

Integrating the trial recruitment process into a CCP can significantly boost recruitment numbers. This represents an innovative model that can be used to maximise recruitment without impacting on the financial and labour costs associated with the running of a respiratory clinical trial.", + "abstract": "It is becoming increasingly apparent that poor housing quality affects indoor air quality, significantly impacting on respiratory health in children and young people. Exposure to damp and/or mould in the home, cold homes and the presence of pests and pollutants all have a significant detrimental impact on child respiratory health. There is a complex relationship between features of poor-quality housing, such as being in a state of disrepair, poor ventilation, overcrowding and being cold, that favour an environment resulting in poor indoor air quality. Children living in rented (private or public) housing are more likely to come from lower-income backgrounds and are most at risk of living in substandard housing posing a serious threat to respiratory health. Children have the right to safe and adequate housing, and research has shown that either rehousing or making modifications to poor-quality housing to improve indoor air quality results in improved respiratory health. Urgent action is needed to address this threat to health. All stakeholders should understand the relationship between poor-quality housing and respiratory health in children and act, working with families, to redress this modifiable risk factor.

Educational aims

The reader should understand how housing quality and indoor air quality affect respiratory health in children.The reader should understand which children are at most risk of living in poor-quality housing.The reader should understand what policy recommendations have been made and what actions need to be undertaken to improve housing quality and respiratory health in children and young people.", "laySummary": "", - "urls": "pdf:https://bmjopenrespres.bmj.com/content/bmjresp/8/1/e000967.full.pdf; doi:https://doi.org/10.1136/bmjresp-2021-000967; html:https://europepmc.org/articles/PMC8261886; pdf:https://europepmc.org/articles/PMC8261886?pdf=render" + "urls": "doi:https://doi.org/10.1183/20734735.0058-2023; html:https://europepmc.org/articles/PMC10461733; pdf:https://europepmc.org/articles/PMC10461733?pdf=render" }, { "id": "38355192", @@ -20790,23 +20790,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1186/s12891-024-07446-6; html:https://europepmc.org/articles/PMC11031996; pdf:https://europepmc.org/articles/PMC11031996?pdf=render" }, - { - "id": "37516479", - "doi": "https://doi.org/10.1016/s2468-2667(23)00126-3", - "title": "Insights from linking police domestic abuse data and health data in South Wales, UK: a linked routine data analysis using decision tree classification.", - "authorString": "Kennedy N, Win TL, Bandyopadhyay A, Kennedy J, Rowe B, McNerney C, Evans J, Hughes K, Bellis MA, Jones A, Harrington K, Moore S, Brophy S.", - "authorAffiliations": "", - "journalTitle": "The Lancet. Public health", - "pubYear": "2023", - "date": "2023-08-01", - "isOpenAccess": "N", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Exposure to domestic abuse can lead to long-term negative impacts on the victim's physical and psychological wellbeing. The 1998 Crime and Disorder Act requires agencies to collaborate on crime reduction strategies, including data sharing. Although data sharing is feasible for individuals, rarely are whole-agency data linked. This study aimed to examine the knowledge obtained by integrating information from police and health-care datasets through data linkage and analyse associated risk factor clusters.

Methods

This retrospective cohort study analyses data from residents of South Wales who were victims of domestic abuse resulting in a Public Protection Notification (PPN) submission between Aug 12, 2015 and March 31, 2020. The study links these data with the victims' health records, collated within the Secure Anonymised Information Linkage databank, to examine factors associated with the outcome of an Emergency Department attendance, emergency hospital admission, or death within 12 months of the PPN submission. To assess the time to outcome for domestic abuse victims after the index PPN submission, we used Kaplan-Meier survival analysis. We used multivariable Cox regression models to identify which factors contributed the highest risk of experiencing an outcome after the index PPN submission. Finally, we created decision trees to describe specific groups of individuals who are at risk of experiencing a domestic abuse incident and subsequent outcome.

Findings

After excluding individuals with multiple PPN records, duplicates, and records with a poor matching score or missing fields, the resulting clean dataset consisted of 8709 domestic abuse victims, of whom 6257 (71\u00b78%) were female. Within a year of a domestic abuse incident, 3650 (41\u00b79%) individuals had an outcome. Factors associated with experiencing an outcome within 12 months of the PPN included younger victim age (hazard ratio 1\u00b7183 [95% CI 1\u00b7053-1\u00b7329], p=0\u00b70048), further PPN submissions after the initial referral (1\u00b7383 [1\u00b7295-1\u00b7476]; p<0\u00b70001), injury at the scene (1\u00b7484 [1\u00b7368-1\u00b7609]; p<0\u00b70001), assessed high risk (1\u00b7600 [1\u00b7444-1\u00b7773]; p<0\u00b70001), referral to other agencies (1\u00b7518 [1\u00b7358-1\u00b7697]; p<0\u00b70001), history of violence (1\u00b7229 [1\u00b7134-1\u00b7333]; p<0\u00b70001), attempted strangulation (1\u00b7311 [1\u00b7148-1\u00b7497]; p<0\u00b70001), and pregnancy (1\u00b7372 [1\u00b7142-1\u00b7648]; p=0\u00b70007). Health-care data before the index PPN established that previous Emergency Department and hospital admissions, smoking, smoking cessation advice, obstetric codes, and prescription of antidepressants and antibiotics were associated with having a future outcome following a domestic abuse incident.

Interpretation

The results indicate that vulnerable individuals are detectable in multiple datasets before and after involvement of the police. Operationalising these findings could reduce police callouts and future Emergency Department or hospital admissions, and improve outcomes for those who are vulnerable. Strategies include querying previous Emergency Department and hospital admissions, giving a high-risk assessment for a pregnant victim, and facilitating data linkage to identify vulnerable individuals.

Funding

National Institute for Health Research.", - "laySummary": "", - "urls": "pdf:http://www.thelancet.com/article/S2468266723001263/pdf; doi:https://doi.org/10.1016/S2468-2667(23)00126-3" - }, { "id": "33475522", "doi": "https://doi.org/10.2196/18229", @@ -20841,6 +20824,23 @@ "laySummary": "A phenotyping algorithm is presented to monitor bleeding in primary and hospital care. Model is well presented in the document and has potential to be scalable and applied to other conditions.", "urls": "pdf:https://bmcmedicine.biomedcentral.com/track/pdf/10.1186/s12916-019-1438-y; doi:https://doi.org/10.1186/s12916-019-1438-y; html:https://europepmc.org/articles/PMC6864929; pdf:https://europepmc.org/articles/PMC6864929?pdf=render" }, + { + "id": "37516479", + "doi": "https://doi.org/10.1016/s2468-2667(23)00126-3", + "title": "Insights from linking police domestic abuse data and health data in South Wales, UK: a linked routine data analysis using decision tree classification.", + "authorString": "Kennedy N, Win TL, Bandyopadhyay A, Kennedy J, Rowe B, McNerney C, Evans J, Hughes K, Bellis MA, Jones A, Harrington K, Moore S, Brophy S.", + "authorAffiliations": "", + "journalTitle": "The Lancet. Public health", + "pubYear": "2023", + "date": "2023-08-01", + "isOpenAccess": "N", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Exposure to domestic abuse can lead to long-term negative impacts on the victim's physical and psychological wellbeing. The 1998 Crime and Disorder Act requires agencies to collaborate on crime reduction strategies, including data sharing. Although data sharing is feasible for individuals, rarely are whole-agency data linked. This study aimed to examine the knowledge obtained by integrating information from police and health-care datasets through data linkage and analyse associated risk factor clusters.

Methods

This retrospective cohort study analyses data from residents of South Wales who were victims of domestic abuse resulting in a Public Protection Notification (PPN) submission between Aug 12, 2015 and March 31, 2020. The study links these data with the victims' health records, collated within the Secure Anonymised Information Linkage databank, to examine factors associated with the outcome of an Emergency Department attendance, emergency hospital admission, or death within 12 months of the PPN submission. To assess the time to outcome for domestic abuse victims after the index PPN submission, we used Kaplan-Meier survival analysis. We used multivariable Cox regression models to identify which factors contributed the highest risk of experiencing an outcome after the index PPN submission. Finally, we created decision trees to describe specific groups of individuals who are at risk of experiencing a domestic abuse incident and subsequent outcome.

Findings

After excluding individuals with multiple PPN records, duplicates, and records with a poor matching score or missing fields, the resulting clean dataset consisted of 8709 domestic abuse victims, of whom 6257 (71\u00b78%) were female. Within a year of a domestic abuse incident, 3650 (41\u00b79%) individuals had an outcome. Factors associated with experiencing an outcome within 12 months of the PPN included younger victim age (hazard ratio 1\u00b7183 [95% CI 1\u00b7053-1\u00b7329], p=0\u00b70048), further PPN submissions after the initial referral (1\u00b7383 [1\u00b7295-1\u00b7476]; p<0\u00b70001), injury at the scene (1\u00b7484 [1\u00b7368-1\u00b7609]; p<0\u00b70001), assessed high risk (1\u00b7600 [1\u00b7444-1\u00b7773]; p<0\u00b70001), referral to other agencies (1\u00b7518 [1\u00b7358-1\u00b7697]; p<0\u00b70001), history of violence (1\u00b7229 [1\u00b7134-1\u00b7333]; p<0\u00b70001), attempted strangulation (1\u00b7311 [1\u00b7148-1\u00b7497]; p<0\u00b70001), and pregnancy (1\u00b7372 [1\u00b7142-1\u00b7648]; p=0\u00b70007). Health-care data before the index PPN established that previous Emergency Department and hospital admissions, smoking, smoking cessation advice, obstetric codes, and prescription of antidepressants and antibiotics were associated with having a future outcome following a domestic abuse incident.

Interpretation

The results indicate that vulnerable individuals are detectable in multiple datasets before and after involvement of the police. Operationalising these findings could reduce police callouts and future Emergency Department or hospital admissions, and improve outcomes for those who are vulnerable. Strategies include querying previous Emergency Department and hospital admissions, giving a high-risk assessment for a pregnant victim, and facilitating data linkage to identify vulnerable individuals.

Funding

National Institute for Health Research.", + "laySummary": "", + "urls": "pdf:http://www.thelancet.com/article/S2468266723001263/pdf; doi:https://doi.org/10.1016/S2468-2667(23)00126-3" + }, { "id": "35616501", "doi": "https://doi.org/10.1177/14791641221088824", @@ -21028,23 +21028,6 @@ "laySummary": "", "urls": "pdf:https://mhealth.jmir.org/2022/10/e40667/PDF; doi:https://doi.org/10.2196/40667; html:https://europepmc.org/articles/PMC9579931" }, - { - "id": "37751239", - "doi": "https://doi.org/10.2196/49438", - "title": "Design and Evaluation of an Intensive Care Unit Dashboard Built in Response to the COVID-19 Pandemic: Semistructured Interview Study.", - "authorString": "Wac M, Craddock I, Chantziara S, Campbell T, Santos-Rodriguez R, Davidson B, McWilliams C.", - "authorAffiliations": "", - "journalTitle": "JMIR human factors", - "pubYear": "2023", - "date": "2023-09-26", - "isOpenAccess": "Y", - "keywords": "Design; Health; ICU; EPR; intensive care unit; Interview; Intensive Care; Critical Care; Electronic Patient Record; Participatory Design; Ehr; Electronic Health Record; Software Engineering; Clinical Information System; Cis; Thematic Analysis; Dashboard; Human-centered Design; Covid-19; Interactive Display", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Dashboards and interactive displays are becoming increasingly prevalent in most health care settings and have the potential to streamline access to information, consolidate disparate data sources and deliver new insights. Our research focuses on intensive care units (ICUs) which are heavily instrumented, critical care environments that generate vast amounts of data and frequently require individualized support for each patient. Consequently, clinicians experience a high cognitive load, which can translate to suboptimal performance. The global COVID-19 pandemic exacerbated this problem by generating a large number of additional hospitalizations, which necessitated a new tool that would help manage ICUs' census. In a previous study, we interviewed clinicians at the University Hospitals Bristol and Weston National Health Service Foundation Trust to capture the requirements for bespoke dashboards that would alleviate this problem.

Objective

This study aims to design, implement, and evaluate an ICU dashboard to allow for monitoring of the high volume of patients in need of critical care, particularly tailored to high-demand situations, such as those seen during the COVID-19 pandemic.

Methods

Building upon the previously gathered requirements, we developed a dashboard, integrated it within the ICU of a National Health Service trust, and allowed all staff to access our tool. For evaluation purposes, participants were recruited and interviewed following a 25-day period during which they were able to use the dashboard clinically. The semistructured interviews followed a topic guide aimed at capturing the usability of the dashboard, supplemented with additional questions asked post hoc to probe themes established during the interview. Interview transcripts were analyzed using a thematic analysis framework that combined inductive and deductive approaches and integrated the Technology Acceptance Model.

Results

A total of 10 participants with 4 different roles in the ICU (6 consultants, 2 junior doctors, 1 nurse, and 1 advanced clinical practitioner) participated in the interviews. Our analysis generated 4 key topics that prevailed across the data: our dashboard met the usability requirements of the participants and was found useful and intuitive; participants perceived that it impacted their delivery of patient care by improving the access to the information and better equipping them to do their job; the tool was used in a variety of ways and for different reasons and tasks; and there were barriers to integration of our dashboard into practice, including familiarity with existing systems, which stifled the adoption of our tool.

Conclusions

Our findings show that the perceived utility of the dashboard had a positive impact on the clinicians' workflows in the ICU. Improving access to information translated into more efficient patient care and transformed some of the existing processes. The introduction of our tool was met with positive reception, but its integration during the COVID-19 pandemic limited its adoption into practice.", - "laySummary": "", - "urls": "doi:https://doi.org/10.2196/49438; doi:https://doi.org/10.2196/49438; html:https://europepmc.org/articles/PMC10565627" - }, { "id": "32518842", "doi": "https://doi.org/10.12688/wellcomeopenres.15786.1", @@ -21062,6 +21045,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.12688/wellcomeopenres.15786.1; html:https://europepmc.org/articles/PMC7255910; pdf:https://europepmc.org/articles/PMC7255910?pdf=render" }, + { + "id": "37751239", + "doi": "https://doi.org/10.2196/49438", + "title": "Design and Evaluation of an Intensive Care Unit Dashboard Built in Response to the COVID-19 Pandemic: Semistructured Interview Study.", + "authorString": "Wac M, Craddock I, Chantziara S, Campbell T, Santos-Rodriguez R, Davidson B, McWilliams C.", + "authorAffiliations": "", + "journalTitle": "JMIR human factors", + "pubYear": "2023", + "date": "2023-09-26", + "isOpenAccess": "Y", + "keywords": "Design; Health; ICU; EPR; intensive care unit; Interview; Intensive Care; Critical Care; Electronic Patient Record; Participatory Design; Ehr; Electronic Health Record; Software Engineering; Clinical Information System; Cis; Thematic Analysis; Dashboard; Human-centered Design; Covid-19; Interactive Display", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Dashboards and interactive displays are becoming increasingly prevalent in most health care settings and have the potential to streamline access to information, consolidate disparate data sources and deliver new insights. Our research focuses on intensive care units (ICUs) which are heavily instrumented, critical care environments that generate vast amounts of data and frequently require individualized support for each patient. Consequently, clinicians experience a high cognitive load, which can translate to suboptimal performance. The global COVID-19 pandemic exacerbated this problem by generating a large number of additional hospitalizations, which necessitated a new tool that would help manage ICUs' census. In a previous study, we interviewed clinicians at the University Hospitals Bristol and Weston National Health Service Foundation Trust to capture the requirements for bespoke dashboards that would alleviate this problem.

Objective

This study aims to design, implement, and evaluate an ICU dashboard to allow for monitoring of the high volume of patients in need of critical care, particularly tailored to high-demand situations, such as those seen during the COVID-19 pandemic.

Methods

Building upon the previously gathered requirements, we developed a dashboard, integrated it within the ICU of a National Health Service trust, and allowed all staff to access our tool. For evaluation purposes, participants were recruited and interviewed following a 25-day period during which they were able to use the dashboard clinically. The semistructured interviews followed a topic guide aimed at capturing the usability of the dashboard, supplemented with additional questions asked post hoc to probe themes established during the interview. Interview transcripts were analyzed using a thematic analysis framework that combined inductive and deductive approaches and integrated the Technology Acceptance Model.

Results

A total of 10 participants with 4 different roles in the ICU (6 consultants, 2 junior doctors, 1 nurse, and 1 advanced clinical practitioner) participated in the interviews. Our analysis generated 4 key topics that prevailed across the data: our dashboard met the usability requirements of the participants and was found useful and intuitive; participants perceived that it impacted their delivery of patient care by improving the access to the information and better equipping them to do their job; the tool was used in a variety of ways and for different reasons and tasks; and there were barriers to integration of our dashboard into practice, including familiarity with existing systems, which stifled the adoption of our tool.

Conclusions

Our findings show that the perceived utility of the dashboard had a positive impact on the clinicians' workflows in the ICU. Improving access to information translated into more efficient patient care and transformed some of the existing processes. The introduction of our tool was met with positive reception, but its integration during the COVID-19 pandemic limited its adoption into practice.", + "laySummary": "", + "urls": "doi:https://doi.org/10.2196/49438; doi:https://doi.org/10.2196/49438; html:https://europepmc.org/articles/PMC10565627" + }, { "id": "30969971", "doi": "https://doi.org/10.1371/journal.pone.0213435", @@ -21164,23 +21164,6 @@ "laySummary": "", "urls": "pdf:https://pubs.acs.org/doi/pdf/10.1021/acs.jproteome.7b00879; doi:https://doi.org/10.1021/acs.jproteome.7b00879; html:https://europepmc.org/articles/PMC5891819; pdf:https://europepmc.org/articles/PMC5891819?pdf=render" }, - { - "id": "37389932", - "doi": "https://doi.org/10.2196/44126", - "title": "Barriers to and Facilitators of Using Remote Measurement Technology in the Long-Term Monitoring of Individuals With ADHD: Interview Study.", - "authorString": "Denyer H, Deng Q, Adanijo A, Asherson P, Bilbow A, Folarin A, Groom MJ, Hollis C, Wykes T, Dobson RJ, Kuntsi J, Simblett S.", - "authorAffiliations": "", - "journalTitle": "JMIR formative research", - "pubYear": "2023", - "date": "2023-06-30", - "isOpenAccess": "Y", - "keywords": "Mobile phone; ADHD; Qualitative analysis; Engagement; Attention-deficit/hyperactivity Disorder; Barriers And Facilitators; Remote Measurement Technology", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Remote measurement technology (RMT) has the potential to address current research and clinical challenges of attention-deficit/hyperactivity disorder (ADHD) symptoms and its co-occurring mental health problems. Despite research using RMT already being successfully applied to other populations, adherence and attrition are potential obstacles when applying RMT to a disorder such as ADHD. Hypothetical views and attitudes toward using RMT in a population with ADHD have previously been explored; however, to our knowledge, there is no previous research that has used qualitative methods to understand the barriers to and facilitators of using RMT in individuals with ADHD following participation in a remote monitoring period.

Objective

We aimed to evaluate the barriers to and facilitators of using RMT in individuals with ADHD compared with a group of people who did not have a diagnosis of ADHD. We also aimed to explore participants' views on using RMT for 1 or 2 years in future studies.

Methods

In total, 20 individuals with ADHD and 20 individuals without ADHD were followed up for 10 weeks using RMT that involved active (questionnaires and cognitive tasks) and passive (smartphone sensors and wearable devices) monitoring; 10 adolescents and adults with ADHD and 12 individuals in a comparison group completed semistructured qualitative interviews at the end of the study period. The interviews focused on potential barriers to and facilitators of using RMT in adults with ADHD. A framework methodology was used to explore the data qualitatively.

Results

Barriers to and facilitators of using RMT were categorized as health-related, user-related, and technology-related factors across both participant groups. When comparing themes that emerged across the participant groups, both individuals with and without ADHD experienced similar barriers and facilitators in using RMT. The participants agreed that RMT can provide useful objective data. However, slight differences between the participant groups were identified as barriers to RMT across all major themes. Individuals with ADHD described the impact that their ADHD symptoms had on participating (health-related theme), commented on the perceived cost of completing the cognitive tasks (user-related theme), and described more technical challenges (technology-related theme) than individuals without ADHD. Hypothetical views on future studies using RMT in individuals with ADHD for 1 or 2 years were positive.

Conclusions

Individuals with ADHD agreed that RMT, which uses repeated measurements with ongoing active and passive monitoring, can provide useful objective data. Although themes overlapped with previous research on barriers to and facilitators of engagement with RMT (eg, depression and epilepsy) and with a comparison group, there are unique considerations for people with ADHD, for example, understanding the impact that ADHD symptoms may have on engaging with RMT. Researchers need to continue working with people with ADHD to develop future RMT studies for longer periods.", - "laySummary": "", - "urls": "pdf:https://formative.jmir.org/2023/1/e44126/PDF; doi:https://doi.org/10.2196/44126; html:https://europepmc.org/articles/PMC10365629; pdf:https://europepmc.org/articles/PMC10365629?pdf=render" - }, { "id": "35471746", "doi": "https://doi.org/10.1186/s13613-022-01011-x", @@ -21198,6 +21181,23 @@ "laySummary": "", "urls": "pdf:https://annalsofintensivecare.springeropen.com/track/pdf/10.1186/s13613-022-01011-x; doi:https://doi.org/10.1186/s13613-022-01011-x; html:https://europepmc.org/articles/PMC9038989; pdf:https://europepmc.org/articles/PMC9038989?pdf=render" }, + { + "id": "37389932", + "doi": "https://doi.org/10.2196/44126", + "title": "Barriers to and Facilitators of Using Remote Measurement Technology in the Long-Term Monitoring of Individuals With ADHD: Interview Study.", + "authorString": "Denyer H, Deng Q, Adanijo A, Asherson P, Bilbow A, Folarin A, Groom MJ, Hollis C, Wykes T, Dobson RJ, Kuntsi J, Simblett S.", + "authorAffiliations": "", + "journalTitle": "JMIR formative research", + "pubYear": "2023", + "date": "2023-06-30", + "isOpenAccess": "Y", + "keywords": "Mobile phone; ADHD; Qualitative analysis; Engagement; Attention-deficit/hyperactivity Disorder; Barriers And Facilitators; Remote Measurement Technology", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Remote measurement technology (RMT) has the potential to address current research and clinical challenges of attention-deficit/hyperactivity disorder (ADHD) symptoms and its co-occurring mental health problems. Despite research using RMT already being successfully applied to other populations, adherence and attrition are potential obstacles when applying RMT to a disorder such as ADHD. Hypothetical views and attitudes toward using RMT in a population with ADHD have previously been explored; however, to our knowledge, there is no previous research that has used qualitative methods to understand the barriers to and facilitators of using RMT in individuals with ADHD following participation in a remote monitoring period.

Objective

We aimed to evaluate the barriers to and facilitators of using RMT in individuals with ADHD compared with a group of people who did not have a diagnosis of ADHD. We also aimed to explore participants' views on using RMT for 1 or 2 years in future studies.

Methods

In total, 20 individuals with ADHD and 20 individuals without ADHD were followed up for 10 weeks using RMT that involved active (questionnaires and cognitive tasks) and passive (smartphone sensors and wearable devices) monitoring; 10 adolescents and adults with ADHD and 12 individuals in a comparison group completed semistructured qualitative interviews at the end of the study period. The interviews focused on potential barriers to and facilitators of using RMT in adults with ADHD. A framework methodology was used to explore the data qualitatively.

Results

Barriers to and facilitators of using RMT were categorized as health-related, user-related, and technology-related factors across both participant groups. When comparing themes that emerged across the participant groups, both individuals with and without ADHD experienced similar barriers and facilitators in using RMT. The participants agreed that RMT can provide useful objective data. However, slight differences between the participant groups were identified as barriers to RMT across all major themes. Individuals with ADHD described the impact that their ADHD symptoms had on participating (health-related theme), commented on the perceived cost of completing the cognitive tasks (user-related theme), and described more technical challenges (technology-related theme) than individuals without ADHD. Hypothetical views on future studies using RMT in individuals with ADHD for 1 or 2 years were positive.

Conclusions

Individuals with ADHD agreed that RMT, which uses repeated measurements with ongoing active and passive monitoring, can provide useful objective data. Although themes overlapped with previous research on barriers to and facilitators of engagement with RMT (eg, depression and epilepsy) and with a comparison group, there are unique considerations for people with ADHD, for example, understanding the impact that ADHD symptoms may have on engaging with RMT. Researchers need to continue working with people with ADHD to develop future RMT studies for longer periods.", + "laySummary": "", + "urls": "pdf:https://formative.jmir.org/2023/1/e44126/PDF; doi:https://doi.org/10.2196/44126; html:https://europepmc.org/articles/PMC10365629; pdf:https://europepmc.org/articles/PMC10365629?pdf=render" + }, { "id": "38346686", "doi": "https://doi.org/10.1093/ageing/afae004", @@ -21266,23 +21266,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.3390/ijerph181910156; html:https://europepmc.org/articles/PMC8507627; pdf:https://europepmc.org/articles/PMC8507627?pdf=render" }, - { - "id": "38388919", - "doi": "https://doi.org/10.1186/s12913-024-10716-7", - "title": "Spatio-temporal modelling of referrals to outpatient respiratory clinics in the integrated care system of the Morecambe Bay area, England.", - "authorString": "Mountain R, Knight J, Heys K, Giorgi E, Gatheral T.", - "authorAffiliations": "", - "journalTitle": "BMC health services research", - "pubYear": "2024", - "date": "2024-02-22", - "isOpenAccess": "Y", - "keywords": "Spatio-temporal; Integrated Care; Chronic Respiratory Disease; Routinely Collected Data; Outpatient Referrals", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Promoting integrated care is a key goal of the NHS Long Term Plan to improve population respiratory health, yet there is limited data-driven evidence of its effectiveness. The Morecambe Bay Respiratory Network is an integrated care initiative operating in the North-West of England since 2017. A key target area has been reducing referrals to outpatient respiratory clinics by upskilling primary care teams. This study aims to explore space-time patterns in referrals from general practice in the Morecambe Bay area to evaluate the impact of the initiative.

Methods

Data on referrals to outpatient clinics and chronic respiratory disease patient counts between 2012-2020 were obtained from the Morecambe Bay Community Data Warehouse, a large store of routinely collected healthcare data. For analysis, the data is aggregated by year and small area geography. The methodology comprises of two parts. The first explores the issues that can arise when using routinely collected primary care data for space-time analysis and applies spatio-temporal conditional autoregressive modelling to adjust for data complexities. The second part models the rate of outpatient referral via a Poisson generalised linear mixed model that adjusts for changes in demographic factors and number of respiratory disease patients.

Results

The first year of the Morecambe Bay Respiratory Network was not associated with a significant difference in referral rate. However, the second and third years saw significant reductions in areas that had received intervention, with full intervention associated with a 31.8% (95% CI 17.0-43.9) and 40.5% (95% CI 27.5-50.9) decrease in referral rate in 2018 and 2019, respectively.

Conclusions

Routinely collected data can be used to robustly evaluate key outcome measures of integrated care. The results demonstrate that effective integrated care has real potential to ease the burden on respiratory outpatient services by reducing the need for an onward referral. This is of great relevance given the current pressure on outpatient services globally, particularly long waiting lists following the COVID-19 pandemic and the need for more innovative models of care.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1186/s12913-024-10716-7; html:https://europepmc.org/articles/PMC10882730; pdf:https://europepmc.org/articles/PMC10882730?pdf=render" - }, { "id": "30999919", "doi": "https://doi.org/10.1186/s12911-019-0805-0", @@ -21300,6 +21283,23 @@ "laySummary": "", "urls": "pdf:https://bmcmedinformdecismak.biomedcentral.com/track/pdf/10.1186/s12911-019-0805-0; doi:https://doi.org/10.1186/s12911-019-0805-0; html:https://europepmc.org/articles/PMC6472089; pdf:https://europepmc.org/articles/PMC6472089?pdf=render" }, + { + "id": "38388919", + "doi": "https://doi.org/10.1186/s12913-024-10716-7", + "title": "Spatio-temporal modelling of referrals to outpatient respiratory clinics in the integrated care system of the Morecambe Bay area, England.", + "authorString": "Mountain R, Knight J, Heys K, Giorgi E, Gatheral T.", + "authorAffiliations": "", + "journalTitle": "BMC health services research", + "pubYear": "2024", + "date": "2024-02-22", + "isOpenAccess": "Y", + "keywords": "Spatio-temporal; Integrated Care; Chronic Respiratory Disease; Routinely Collected Data; Outpatient Referrals", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Promoting integrated care is a key goal of the NHS Long Term Plan to improve population respiratory health, yet there is limited data-driven evidence of its effectiveness. The Morecambe Bay Respiratory Network is an integrated care initiative operating in the North-West of England since 2017. A key target area has been reducing referrals to outpatient respiratory clinics by upskilling primary care teams. This study aims to explore space-time patterns in referrals from general practice in the Morecambe Bay area to evaluate the impact of the initiative.

Methods

Data on referrals to outpatient clinics and chronic respiratory disease patient counts between 2012-2020 were obtained from the Morecambe Bay Community Data Warehouse, a large store of routinely collected healthcare data. For analysis, the data is aggregated by year and small area geography. The methodology comprises of two parts. The first explores the issues that can arise when using routinely collected primary care data for space-time analysis and applies spatio-temporal conditional autoregressive modelling to adjust for data complexities. The second part models the rate of outpatient referral via a Poisson generalised linear mixed model that adjusts for changes in demographic factors and number of respiratory disease patients.

Results

The first year of the Morecambe Bay Respiratory Network was not associated with a significant difference in referral rate. However, the second and third years saw significant reductions in areas that had received intervention, with full intervention associated with a 31.8% (95% CI 17.0-43.9) and 40.5% (95% CI 27.5-50.9) decrease in referral rate in 2018 and 2019, respectively.

Conclusions

Routinely collected data can be used to robustly evaluate key outcome measures of integrated care. The results demonstrate that effective integrated care has real potential to ease the burden on respiratory outpatient services by reducing the need for an onward referral. This is of great relevance given the current pressure on outpatient services globally, particularly long waiting lists following the COVID-19 pandemic and the need for more innovative models of care.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1186/s12913-024-10716-7; html:https://europepmc.org/articles/PMC10882730; pdf:https://europepmc.org/articles/PMC10882730?pdf=render" + }, { "id": "36932161", "doi": "https://doi.org/10.1038/s41433-023-02478-z", @@ -21657,23 +21657,6 @@ "laySummary": "", "urls": "pdf:https://www.nature.com/articles/s41541-024-00878-0.pdf; doi:https://doi.org/10.1038/s41541-024-00878-0; html:https://europepmc.org/articles/PMC11111746; pdf:https://europepmc.org/articles/PMC11111746?pdf=render" }, - { - "id": "36660920", - "doi": "https://doi.org/10.1093/ehjci/jeac270", - "title": "The role of obesity-related cardiovascular remodelling in mediating incident cardiovascular outcomes: a population-based observational study.", - "authorString": "Szabo L, McCracken C, Cooper J, Rider OJ, Vago H, Merkely B, Harvey NC, Neubauer S, Petersen SE, Raisi-Estabragh Z.", - "authorAffiliations": "", - "journalTitle": "European heart journal. Cardiovascular Imaging", - "pubYear": "2023", - "date": "2023-06-01", - "isOpenAccess": "Y", - "keywords": "Obesity; body mass index; Mediation; Cardiac Magnetic Resonance Imaging; Cardiovascular Remodelling; Waist-to-hip Ratio; Disease Mechanisms; Incident Cardiovascular Outcomes", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Aims

We examined associations of obesity with incident cardiovascular outcomes and cardiovascular magnetic resonance (CMR) phenotypes, integrating information from body mass index (BMI) and waist-to-hip ratio (WHR). Then, we used multiple mediation to define the role of obesity-related cardiac remodelling in driving obesity-outcome associations, independent of cardiometabolic diseases.

Methods and results

In 491 606 UK Biobank participants, using Cox proportional hazard models, greater obesity (higher WHR, higher BMI) was linked to significantly greater risk of incident ischaemic heart disease, atrial fibrillation (AF), heart failure (HF), all-cause mortality, and cardiovascular disease (CVD) mortality. In combined stratification by BMI and WHR thresholds, elevated WHR was associated with greater risk of adverse outcomes at any BMI level. Individuals with overweight BMI but normal WHR had weaker disease associations. In the subset of participants with CMR (n = 31 107), using linear regression, greater obesity was associated with higher left ventricular (LV) mass, greater LV concentricity, poorer LV systolic function, lower myocardial native T1, larger left atrial (LA) volumes, poorer LA function, and lower aortic distensibility. Of note, higher BMI was linked to higher, whilst greater WHR was linked to lower LV end-diastolic volume (LVEDV). In Cox models, greater LVEDV and LV mass (LVM) were linked to increased risk of CVD, most importantly HF and an increased LA maximal volume was the key predictive measure of new-onset AF. In multiple mediation analyses, hypertension and adverse LV remodelling (higher LVM, greater concentricity) were major independent mediators of the obesity-outcome associations. Atrial remodelling and native T1 were additional mediators in the associations of obesity with AF and HF, respectively.

Conclusions

We demonstrate associations of obesity with adverse cardiovascular phenotypes and their significant independent role in mediating obesity-outcome relationships. In addition, our findings support the integrated use of BMI and WHR to evaluate obesity-related cardiovascular risk.", - "laySummary": "", - "urls": "pdf:https://academic.oup.com/ehjcimaging/advance-article-pdf/doi/10.1093/ehjci/jeac270/48798234/jeac270.pdf; doi:https://doi.org/10.1093/ehjci/jeac270; html:https://europepmc.org/articles/PMC10284050; pdf:https://europepmc.org/articles/PMC10284050?pdf=render" - }, { "id": "33655501", "doi": "https://doi.org/10.1111/bjd.19885", @@ -21691,6 +21674,23 @@ "laySummary": "", "urls": "pdf:https://researchonline.lshtm.ac.uk/id/eprint/4660846/7/Mulick_etal_2021_Four-childhood-atopic-dermatitis-subtypes.pdf; doi:https://doi.org/10.1111/bjd.19885; html:https://europepmc.org/articles/PMC8410876; pdf:https://europepmc.org/articles/PMC8410876?pdf=render; doi:https://doi.org/10.1111/bjd.19885" }, + { + "id": "36660920", + "doi": "https://doi.org/10.1093/ehjci/jeac270", + "title": "The role of obesity-related cardiovascular remodelling in mediating incident cardiovascular outcomes: a population-based observational study.", + "authorString": "Szabo L, McCracken C, Cooper J, Rider OJ, Vago H, Merkely B, Harvey NC, Neubauer S, Petersen SE, Raisi-Estabragh Z.", + "authorAffiliations": "", + "journalTitle": "European heart journal. Cardiovascular Imaging", + "pubYear": "2023", + "date": "2023-06-01", + "isOpenAccess": "Y", + "keywords": "Obesity; body mass index; Mediation; Cardiac Magnetic Resonance Imaging; Cardiovascular Remodelling; Waist-to-hip Ratio; Disease Mechanisms; Incident Cardiovascular Outcomes", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Aims

We examined associations of obesity with incident cardiovascular outcomes and cardiovascular magnetic resonance (CMR) phenotypes, integrating information from body mass index (BMI) and waist-to-hip ratio (WHR). Then, we used multiple mediation to define the role of obesity-related cardiac remodelling in driving obesity-outcome associations, independent of cardiometabolic diseases.

Methods and results

In 491 606 UK Biobank participants, using Cox proportional hazard models, greater obesity (higher WHR, higher BMI) was linked to significantly greater risk of incident ischaemic heart disease, atrial fibrillation (AF), heart failure (HF), all-cause mortality, and cardiovascular disease (CVD) mortality. In combined stratification by BMI and WHR thresholds, elevated WHR was associated with greater risk of adverse outcomes at any BMI level. Individuals with overweight BMI but normal WHR had weaker disease associations. In the subset of participants with CMR (n = 31 107), using linear regression, greater obesity was associated with higher left ventricular (LV) mass, greater LV concentricity, poorer LV systolic function, lower myocardial native T1, larger left atrial (LA) volumes, poorer LA function, and lower aortic distensibility. Of note, higher BMI was linked to higher, whilst greater WHR was linked to lower LV end-diastolic volume (LVEDV). In Cox models, greater LVEDV and LV mass (LVM) were linked to increased risk of CVD, most importantly HF and an increased LA maximal volume was the key predictive measure of new-onset AF. In multiple mediation analyses, hypertension and adverse LV remodelling (higher LVM, greater concentricity) were major independent mediators of the obesity-outcome associations. Atrial remodelling and native T1 were additional mediators in the associations of obesity with AF and HF, respectively.

Conclusions

We demonstrate associations of obesity with adverse cardiovascular phenotypes and their significant independent role in mediating obesity-outcome relationships. In addition, our findings support the integrated use of BMI and WHR to evaluate obesity-related cardiovascular risk.", + "laySummary": "", + "urls": "pdf:https://academic.oup.com/ehjcimaging/advance-article-pdf/doi/10.1093/ehjci/jeac270/48798234/jeac270.pdf; doi:https://doi.org/10.1093/ehjci/jeac270; html:https://europepmc.org/articles/PMC10284050; pdf:https://europepmc.org/articles/PMC10284050?pdf=render" + }, { "id": "35038301", "doi": "https://doi.org/10.2196/30523", @@ -21844,6 +21844,23 @@ "laySummary": "", "urls": "pdf:https://www.nature.com/articles/s41398-018-0236-1.pdf; doi:https://doi.org/10.1038/s41398-018-0236-1; html:https://europepmc.org/articles/PMC6123450; pdf:https://europepmc.org/articles/PMC6123450?pdf=render" }, + { + "id": "35595677", + "doi": "https://doi.org/10.1016/s2589-7500(22)00061-9", + "title": "Identifying adverse childhood experiences with electronic health records of linked mothers and children in England: a multistage development and validation study.", + "authorString": "Syed S, Gonzalez-Izquierdo A, Allister J, Feder G, Li L, Gilbert R.", + "authorAffiliations": "", + "journalTitle": "The Lancet. Digital health", + "pubYear": "2022", + "date": "2022-05-17", + "isOpenAccess": "N", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Electronic health records (EHRs) of mothers and children provide an opportunity to identify adverse childhood experiences (ACEs) during crucial periods of childhood development, yet well developed indicators of ACEs remain scarce. We aimed to develop clinically relevant indicators of ACEs for linked EHRs of mothers and children using a multistage prediction model of child maltreatment and maternal intimate partner violence (IPV).

Methods

In this multistage development and validation study, we developed a representative population-based birth cohort of mothers and children in England, followed from up to 2 years before birth to up to 5 years after birth across the Clinical Practice Research Datalink (CPRD) GOLD (primary care), Hospital Episode Statistics (secondary care), and the Office for National Statistics mortality register. We included livebirths in England between July 1, 2004, and June 30, 2016, to mothers aged 16-55 years, who had registered with a general practitioner (GP) that met CPRD quality standards before 21 weeks of gestation. The primary outcome (reference standard) was any child maltreatment or maternal IPV in either the mother's or child's record from 2 years before birth (maternal IPV only) to 5 years after birth. We used seven prediction models, combined with expert ratings, to systematically develop indicators. We validated the final indicators by integrating results from machine learning models, survival analyses, and clustering analyses in the validation cohort.

Findings

We included data collected between July 1, 2002, and June 27, 2018. Of 376\u2009006 eligible births, we included 211\u2009393 mother-child pairs (422\u2009786 patients) from 400 practices, of whom 126\u2009837 mother-child pairs (60\u00b70%; 240 practices) were randomly assigned to a derivation cohort and 84\u2009556 pairs (40\u00b70%; 160 practices) to a validation cohort. We included 63 indicators in six ACE domains: maternal mental health problems, maternal substance misuse, adverse family environments, child maltreatment, maternal IPV, and high-risk presentations of child maltreatment. Excluding the seven indicators in the reference standard, 56 indicators showed high discriminative validity for the reference standard of any child maltreatment or maternal IPV between 2 years before and 5 years after birth (validation cohort, area under the receiver operating characteristic curve 0\u00b785 [95% CI 0\u00b784-0\u00b786]). During the 2 years before birth and 5 years after birth, the overall period prevalence of maternal IPV and child maltreatment (reference standard) was 2\u00b73% (2876 of 126\u2009837 pairs) in the derivation cohort and 2\u00b73% (1916 of 84\u2009556 pairs) in the validation cohort. During the 2 years before and after birth, the period prevalence was 39\u00b71% (95% CI 38\u00b77-39\u00b75; 34\u2009773 pairs) for any of the 63 ACE indicators, 22\u00b72% (21\u00b78-22\u00b75%; 20\u2009122 pairs) for maternal mental health problems, 15\u00b77% (15\u00b74-16\u00b70%; 14\u2009549 pairs) for adverse family environments, 8\u00b71% (7\u00b78-8\u00b73%; 6808 pairs) for high-risk presentations of child maltreatment, 6\u00b79% (6\u00b77-7\u00b72%; 7856 pairs) for maternal substance misuse, and 3\u00b70% (2\u00b79-3\u00b72%; 2540 pairs) for any child maltreatment (2\u00b74% [2\u00b73-5\u00b76%; 2051 pairs]) and maternal IPV (1\u00b70% [0\u00b78-1\u00b70%; 875 pairs]). 62\u00b76% (21\u2009785 of 34\u2009773 pairs) of ACEs were recorded in primary care only, and 72\u00b73% (25\u2009140 cases) were recorded in the maternal record only.

Interpretation

We developed clinically relevant indicators for identifying ACEs using the EHRs of mothers and children presenting to general practices and hospital admissions. Over 70% of ACEs were identified via maternal records and were recorded in primary care by GPs within 2 years of birth, reinforcing the importance of reviewing parental and carer records to inform clinical responses to children. ACE indicators can contribute to longitudinal surveillance informing public health policy and resource allocation. Further evaluation is required to determine how ACE indicators can be used in clinical practice.

Funding

None.", + "laySummary": "", + "urls": "pdf:http://www.thelancet.com/article/S2589750022000619/pdf; doi:https://doi.org/10.1016/S2589-7500(22)00061-9" + }, { "id": "37489768", "doi": "https://doi.org/10.1161/jaha.122.029296", @@ -21862,21 +21879,21 @@ "urls": "pdf:https://www.ahajournals.org/doi/pdf/10.1161/JAHA.122.029296; doi:https://doi.org/10.1161/JAHA.122.029296; html:https://europepmc.org/articles/PMC7614905; pdf:https://europepmc.org/articles/PMC7614905?pdf=render" }, { - "id": "35595677", - "doi": "https://doi.org/10.1016/s2589-7500(22)00061-9", - "title": "Identifying adverse childhood experiences with electronic health records of linked mothers and children in England: a multistage development and validation study.", - "authorString": "Syed S, Gonzalez-Izquierdo A, Allister J, Feder G, Li L, Gilbert R.", + "id": "34137744", + "doi": "https://doi.org/10.1097/ta.0000000000003317", + "title": "Association between type 2 diabetes and long-term outcomes in middle-aged and older trauma patients.", + "authorString": "Daly SL, Gabbe BJ, Climie RE, Ekegren CL.", "authorAffiliations": "", - "journalTitle": "The Lancet. Digital health", + "journalTitle": "The journal of trauma and acute care surgery", "pubYear": "2022", - "date": "2022-05-17", + "date": "2022-01-01", "isOpenAccess": "N", "keywords": "", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Background

Electronic health records (EHRs) of mothers and children provide an opportunity to identify adverse childhood experiences (ACEs) during crucial periods of childhood development, yet well developed indicators of ACEs remain scarce. We aimed to develop clinically relevant indicators of ACEs for linked EHRs of mothers and children using a multistage prediction model of child maltreatment and maternal intimate partner violence (IPV).

Methods

In this multistage development and validation study, we developed a representative population-based birth cohort of mothers and children in England, followed from up to 2 years before birth to up to 5 years after birth across the Clinical Practice Research Datalink (CPRD) GOLD (primary care), Hospital Episode Statistics (secondary care), and the Office for National Statistics mortality register. We included livebirths in England between July 1, 2004, and June 30, 2016, to mothers aged 16-55 years, who had registered with a general practitioner (GP) that met CPRD quality standards before 21 weeks of gestation. The primary outcome (reference standard) was any child maltreatment or maternal IPV in either the mother's or child's record from 2 years before birth (maternal IPV only) to 5 years after birth. We used seven prediction models, combined with expert ratings, to systematically develop indicators. We validated the final indicators by integrating results from machine learning models, survival analyses, and clustering analyses in the validation cohort.

Findings

We included data collected between July 1, 2002, and June 27, 2018. Of 376\u2009006 eligible births, we included 211\u2009393 mother-child pairs (422\u2009786 patients) from 400 practices, of whom 126\u2009837 mother-child pairs (60\u00b70%; 240 practices) were randomly assigned to a derivation cohort and 84\u2009556 pairs (40\u00b70%; 160 practices) to a validation cohort. We included 63 indicators in six ACE domains: maternal mental health problems, maternal substance misuse, adverse family environments, child maltreatment, maternal IPV, and high-risk presentations of child maltreatment. Excluding the seven indicators in the reference standard, 56 indicators showed high discriminative validity for the reference standard of any child maltreatment or maternal IPV between 2 years before and 5 years after birth (validation cohort, area under the receiver operating characteristic curve 0\u00b785 [95% CI 0\u00b784-0\u00b786]). During the 2 years before birth and 5 years after birth, the overall period prevalence of maternal IPV and child maltreatment (reference standard) was 2\u00b73% (2876 of 126\u2009837 pairs) in the derivation cohort and 2\u00b73% (1916 of 84\u2009556 pairs) in the validation cohort. During the 2 years before and after birth, the period prevalence was 39\u00b71% (95% CI 38\u00b77-39\u00b75; 34\u2009773 pairs) for any of the 63 ACE indicators, 22\u00b72% (21\u00b78-22\u00b75%; 20\u2009122 pairs) for maternal mental health problems, 15\u00b77% (15\u00b74-16\u00b70%; 14\u2009549 pairs) for adverse family environments, 8\u00b71% (7\u00b78-8\u00b73%; 6808 pairs) for high-risk presentations of child maltreatment, 6\u00b79% (6\u00b77-7\u00b72%; 7856 pairs) for maternal substance misuse, and 3\u00b70% (2\u00b79-3\u00b72%; 2540 pairs) for any child maltreatment (2\u00b74% [2\u00b73-5\u00b76%; 2051 pairs]) and maternal IPV (1\u00b70% [0\u00b78-1\u00b70%; 875 pairs]). 62\u00b76% (21\u2009785 of 34\u2009773 pairs) of ACEs were recorded in primary care only, and 72\u00b73% (25\u2009140 cases) were recorded in the maternal record only.

Interpretation

We developed clinically relevant indicators for identifying ACEs using the EHRs of mothers and children presenting to general practices and hospital admissions. Over 70% of ACEs were identified via maternal records and were recorded in primary care by GPs within 2 years of birth, reinforcing the importance of reviewing parental and carer records to inform clinical responses to children. ACE indicators can contribute to longitudinal surveillance informing public health policy and resource allocation. Further evaluation is required to determine how ACE indicators can be used in clinical practice.

Funding

None.", + "abstract": "

Background

Diabetes is associated with increased hospital complications and mortality following trauma. However, there is limited research on the longer-term recovery of trauma patients with diabetes. The aim of this study was to explore the association between type 2 diabetes (T2D) and in-hospital and 24-month outcomes in major trauma patients.

Methods

In this cohort study using the Victorian State Trauma Registry, middle-aged and older adults (\u226545 years) with major trauma were followed up at 24 months postinjury. Logistic regression (univariable and multivariable) analyses were used to determine the association between diabetes status and 24-month patient-reported outcomes. In-hospital outcomes were compared between groups using \u03c72 tests.

Results

Of the 11,490 participants who survived to hospital discharge, 8,493 survived to 24 months postinjury and were followed up at that time point: 953 people (11%) with and 7540 (89%) without T2D. People with T2D had a higher in-hospital death rate (19%) compared with people without T2D (16%; p < 0.001). After adjusting for confounders, people with T2D had poorer outcomes 24 months postinjury than people without T2D, with respect to functional recovery (Glasgow Outcome Scale Extended) (adjusted odds ratio [AOR], 0.58; 95% confidence interval [CI], 0.48-0.69) and return to work/study (AOR, 0.51; 95% CI, 0.37-0.71]). People with T2D experienced higher odds of problems with mobility (AOR, 1.92; 95% CI, 1.60-2.30), self-care (AOR, 1.94; 95% CI, 1.64, 2.29), usual activities (AOR, 1.50; 95% CI, 1.26-1.79), pain and discomfort (AOR, 1.75; 95% CI, 1.49-2.07), anxiety and depression (AOR, 1.45; 95% CI, 1.24, 1.70), and self-reported disability (AOR, 1.51; 95% CI, 1.28-1.79) than people without T2D.

Conclusion

Major trauma patients with T2D have a poorer prognosis than patients without T2D, both during their hospital admission and 24 months postinjury. Patients with T2D may need additional health care and support following trauma to reach their recovery potential.

Level of evidence

Prognostic, level III.", "laySummary": "", - "urls": "pdf:http://www.thelancet.com/article/S2589750022000619/pdf; doi:https://doi.org/10.1016/S2589-7500(22)00061-9" + "urls": "doi:https://doi.org/10.1097/TA.0000000000003317" }, { "id": "37679551", @@ -21895,23 +21912,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1038/s41590-023-01635-6; html:https://europepmc.org/articles/PMC10602847; pdf:https://europepmc.org/articles/PMC10602847?pdf=render" }, - { - "id": "34137744", - "doi": "https://doi.org/10.1097/ta.0000000000003317", - "title": "Association between type 2 diabetes and long-term outcomes in middle-aged and older trauma patients.", - "authorString": "Daly SL, Gabbe BJ, Climie RE, Ekegren CL.", - "authorAffiliations": "", - "journalTitle": "The journal of trauma and acute care surgery", - "pubYear": "2022", - "date": "2022-01-01", - "isOpenAccess": "N", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Diabetes is associated with increased hospital complications and mortality following trauma. However, there is limited research on the longer-term recovery of trauma patients with diabetes. The aim of this study was to explore the association between type 2 diabetes (T2D) and in-hospital and 24-month outcomes in major trauma patients.

Methods

In this cohort study using the Victorian State Trauma Registry, middle-aged and older adults (\u226545 years) with major trauma were followed up at 24 months postinjury. Logistic regression (univariable and multivariable) analyses were used to determine the association between diabetes status and 24-month patient-reported outcomes. In-hospital outcomes were compared between groups using \u03c72 tests.

Results

Of the 11,490 participants who survived to hospital discharge, 8,493 survived to 24 months postinjury and were followed up at that time point: 953 people (11%) with and 7540 (89%) without T2D. People with T2D had a higher in-hospital death rate (19%) compared with people without T2D (16%; p < 0.001). After adjusting for confounders, people with T2D had poorer outcomes 24 months postinjury than people without T2D, with respect to functional recovery (Glasgow Outcome Scale Extended) (adjusted odds ratio [AOR], 0.58; 95% confidence interval [CI], 0.48-0.69) and return to work/study (AOR, 0.51; 95% CI, 0.37-0.71]). People with T2D experienced higher odds of problems with mobility (AOR, 1.92; 95% CI, 1.60-2.30), self-care (AOR, 1.94; 95% CI, 1.64, 2.29), usual activities (AOR, 1.50; 95% CI, 1.26-1.79), pain and discomfort (AOR, 1.75; 95% CI, 1.49-2.07), anxiety and depression (AOR, 1.45; 95% CI, 1.24, 1.70), and self-reported disability (AOR, 1.51; 95% CI, 1.28-1.79) than people without T2D.

Conclusion

Major trauma patients with T2D have a poorer prognosis than patients without T2D, both during their hospital admission and 24 months postinjury. Patients with T2D may need additional health care and support following trauma to reach their recovery potential.

Level of evidence

Prognostic, level III.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1097/TA.0000000000003317" - }, { "id": "35025917", "doi": "https://doi.org/10.1371/journal.pone.0261142", @@ -21929,23 +21929,6 @@ "laySummary": "", "urls": "pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0261142&type=printable; doi:https://doi.org/10.1371/journal.pone.0261142; html:https://europepmc.org/articles/PMC8757902; pdf:https://europepmc.org/articles/PMC8757902?pdf=render" }, - { - "id": "37750555", - "doi": "https://doi.org/10.1161/jaha.123.030766", - "title": "Impact of New Cardiovascular Events on Quality of Life and Hospital Costs in People With Cardiovascular Disease in the United Kingdom and United States.", - "authorString": "Lui JNM, Williams C, Keng MJ, Hopewell JC, Sammons E, Chen F, Gray A, Bowman L, Landray SMJ, Mihaylova B, REVEAL Collaborative Group.", - "authorAffiliations": "", - "journalTitle": "Journal of the American Heart Association", - "pubYear": "2023", - "date": "2023-09-26", - "isOpenAccess": "Y", - "keywords": "Cardiovascular diseases; Quality of life; United States; United Kingdom; Secondary Prevention; Health Care Costs", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Despite optimized risk factor control, people with prior cardiovascular disease remain at high cardiovascular disease risk. We assess the immediate- and longer-term impacts of new vascular and nonvascular events on quality of life (QoL) and hospital costs among participants in the REVEAL (Randomized Evaluation of the Effects of Anacetrapib Through Lipid Modification) trial in secondary prevention.

Methods and results

Data on demographic and clinical characteristics, health-related quality of life (QoL: EuroQoL 5-Dimension-5-Level), adverse events, and hospital admissions during the 4-year follow-up of the 21\u2009820 participants recruited in Europe and North America informed assessments of the impacts of new adverse events on QoL and hospital costs from the UK and US health systems' perspectives using generalized linear regression models. Reductions in QoL were estimated in the years of event occurrence for nonhemorrhagic stroke (-0.067 [United Kingdom], -0.069 [US]), heart failure admission (-0.072 [United Kingdom], -0.103 [US]), incident cancer (-0.064 [United Kingdom], -0.068 [US]), and noncoronary revascularization (-0.071 [United Kingdom], -0.061 [US]), as well as in subsequent years following these events. Myocardial infarction and coronary revascularization (CRV) procedures were not found to affect QoL. All adverse events were associated with additional hospital costs in the years of events and in subsequent years, with the highest additional costs in the years of noncoronary revascularization (\u00a35830 [United Kingdom], $14\u2009133 [US Medicare]), of myocardial infarction with urgent CRV procedure (\u00a35614, $24722), and of urgent/nonurgent CRV procedure without myocardial infarction (\u00a34674/\u00a34651 and $15\u2009251/$17\u2009539).

Conclusions

Stroke, heart failure, and noncoronary revascularization procedures substantially reduce QoL, and all cardiovascular disease events increase hospital costs. These estimates are useful in informing cost-effectiveness of interventions to reduce cardiovascular disease risk in secondary prevention.

Registration

URL: https://www.clinicaltrials.gov; Unique identifier: NCT01252953; https://www.Isrctn.com. Unique identifier: ISRCTN48678192; https://www.clinicaltrialsregister.eu. Unique identifier: 2010-023467-18.", - "laySummary": "", - "urls": "pdf:https://www.ahajournals.org/doi/pdf/10.1161/JAHA.123.030766; doi:https://doi.org/10.1161/JAHA.123.030766; html:https://europepmc.org/articles/PMC7615160; pdf:https://europepmc.org/articles/PMC7615160?pdf=render" - }, { "id": "37124165", "doi": "https://doi.org/10.1016/j.ufug.2023.127934", @@ -21963,6 +21946,23 @@ "laySummary": "", "urls": "html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10088280; doi:https://doi.org/10.1016/j.ufug.2023.127934; html:https://europepmc.org/articles/PMC10088280; pdf:https://europepmc.org/articles/PMC10088280?pdf=render" }, + { + "id": "37750555", + "doi": "https://doi.org/10.1161/jaha.123.030766", + "title": "Impact of New Cardiovascular Events on Quality of Life and Hospital Costs in People With Cardiovascular Disease in the United Kingdom and United States.", + "authorString": "Lui JNM, Williams C, Keng MJ, Hopewell JC, Sammons E, Chen F, Gray A, Bowman L, Landray SMJ, Mihaylova B, REVEAL Collaborative Group.", + "authorAffiliations": "", + "journalTitle": "Journal of the American Heart Association", + "pubYear": "2023", + "date": "2023-09-26", + "isOpenAccess": "Y", + "keywords": "Cardiovascular diseases; Quality of life; United States; United Kingdom; Secondary Prevention; Health Care Costs", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Despite optimized risk factor control, people with prior cardiovascular disease remain at high cardiovascular disease risk. We assess the immediate- and longer-term impacts of new vascular and nonvascular events on quality of life (QoL) and hospital costs among participants in the REVEAL (Randomized Evaluation of the Effects of Anacetrapib Through Lipid Modification) trial in secondary prevention.

Methods and results

Data on demographic and clinical characteristics, health-related quality of life (QoL: EuroQoL 5-Dimension-5-Level), adverse events, and hospital admissions during the 4-year follow-up of the 21\u2009820 participants recruited in Europe and North America informed assessments of the impacts of new adverse events on QoL and hospital costs from the UK and US health systems' perspectives using generalized linear regression models. Reductions in QoL were estimated in the years of event occurrence for nonhemorrhagic stroke (-0.067 [United Kingdom], -0.069 [US]), heart failure admission (-0.072 [United Kingdom], -0.103 [US]), incident cancer (-0.064 [United Kingdom], -0.068 [US]), and noncoronary revascularization (-0.071 [United Kingdom], -0.061 [US]), as well as in subsequent years following these events. Myocardial infarction and coronary revascularization (CRV) procedures were not found to affect QoL. All adverse events were associated with additional hospital costs in the years of events and in subsequent years, with the highest additional costs in the years of noncoronary revascularization (\u00a35830 [United Kingdom], $14\u2009133 [US Medicare]), of myocardial infarction with urgent CRV procedure (\u00a35614, $24722), and of urgent/nonurgent CRV procedure without myocardial infarction (\u00a34674/\u00a34651 and $15\u2009251/$17\u2009539).

Conclusions

Stroke, heart failure, and noncoronary revascularization procedures substantially reduce QoL, and all cardiovascular disease events increase hospital costs. These estimates are useful in informing cost-effectiveness of interventions to reduce cardiovascular disease risk in secondary prevention.

Registration

URL: https://www.clinicaltrials.gov; Unique identifier: NCT01252953; https://www.Isrctn.com. Unique identifier: ISRCTN48678192; https://www.clinicaltrialsregister.eu. Unique identifier: 2010-023467-18.", + "laySummary": "", + "urls": "pdf:https://www.ahajournals.org/doi/pdf/10.1161/JAHA.123.030766; doi:https://doi.org/10.1161/JAHA.123.030766; html:https://europepmc.org/articles/PMC7615160; pdf:https://europepmc.org/articles/PMC7615160?pdf=render" + }, { "id": "36713101", "doi": "https://doi.org/10.1093/ehjdh/ztab082", @@ -22218,23 +22218,6 @@ "laySummary": "", "urls": "pdf:https://www.pnas.org/content/pnas/117/18/9787.full.pdf; doi:https://doi.org/10.1073/pnas.1912957117; html:https://europepmc.org/articles/PMC7211961; pdf:https://europepmc.org/articles/PMC7211961?pdf=render" }, - { - "id": "38552911", - "doi": "https://doi.org/10.1016/j.jad.2024.03.106", - "title": "Identifying depression-related topics in smartphone-collected free-response speech recordings using an automatic speech recognition system and a deep learning topic model.", - "authorString": "Zhang Y, Folarin AA, Dineley J, Conde P, de Angel V, Sun S, Ranjan Y, Rashid Z, Stewart C, Laiou P, Sankesara H, Qian L, Matcham F, White K, Oetzmann C, Lamers F, Siddi S, Simblett S, Schuller BW, Vairavan S, Wykes T, Haro JM, Penninx BWJH, Narayan VA, Hotopf M, Dobson RJB, Cummins N, RADAR-CNS consortium.", - "authorAffiliations": "", - "journalTitle": "Journal of affective disorders", - "pubYear": "2024", - "date": "2024-03-27", - "isOpenAccess": "N", - "keywords": "Depression; Speech; Smartphone; Automatic Speech Recognition; Topic Modeling", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Prior research has associated spoken language use with depression, yet studies often involve small or non-clinical samples and face challenges in the manual transcription of speech. This paper aimed to automatically identify depression-related topics in speech recordings collected from clinical samples.

Methods

The data included 3919 English free-response speech recordings collected via smartphones from 265 participants with a depression history. We transcribed speech recordings via automatic speech recognition (Whisper tool, OpenAI) and identified principal topics from transcriptions using a deep learning topic model (BERTopic). To identify depression risk topics and understand the context, we compared participants' depression severity and behavioral (extracted from wearable devices) and linguistic (extracted from transcribed texts) characteristics across identified topics.

Results

From the 29 topics identified, we identified 6 risk topics for depression: 'No Expectations', 'Sleep', 'Mental Therapy', 'Haircut', 'Studying', and 'Coursework'. Participants mentioning depression risk topics exhibited higher sleep variability, later sleep onset, and fewer daily steps and used fewer words, more negative language, and fewer leisure-related words in their speech recordings.

Limitations

Our findings were derived from a depressed cohort with a specific speech task, potentially limiting the generalizability to non-clinical populations or other speech tasks. Additionally, some topics had small sample sizes, necessitating further validation in larger datasets.

Conclusion

This study demonstrates that specific speech topics can indicate depression severity. The employed data-driven workflow provides a practical approach for analyzing large-scale speech data collected from real-world settings.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1016/j.jad.2024.03.106" - }, { "id": "36587850", "doi": "https://doi.org/10.1016/j.jaci.2022.12.810", @@ -22253,21 +22236,21 @@ "urls": "doi:https://doi.org/10.1016/j.jaci.2022.12.810; doi:https://doi.org/10.1016/j.jaci.2022.12.810; html:https://europepmc.org/articles/PMC10109092; pdf:https://europepmc.org/articles/PMC10109092?pdf=render" }, { - "id": "37964568", - "doi": "https://doi.org/10.1192/bjo.2023.547", - "title": "The association of anxiety disorders and depression with facial scarring: population-based, data linkage, matched cohort analysis of 358 158 patients.", - "authorString": "Gibson JAG, Dobbs TD, Griffiths R, Song J, Akbari A, Bodger O, Hutchings HA, Lyons RA, John A, Whitaker IS.", + "id": "38552911", + "doi": "https://doi.org/10.1016/j.jad.2024.03.106", + "title": "Identifying depression-related topics in smartphone-collected free-response speech recordings using an automatic speech recognition system and a deep learning topic model.", + "authorString": "Zhang Y, Folarin AA, Dineley J, Conde P, de Angel V, Sun S, Ranjan Y, Rashid Z, Stewart C, Laiou P, Sankesara H, Qian L, Matcham F, White K, Oetzmann C, Lamers F, Siddi S, Simblett S, Schuller BW, Vairavan S, Wykes T, Haro JM, Penninx BWJH, Narayan VA, Hotopf M, Dobson RJB, Cummins N, RADAR-CNS consortium.", "authorAffiliations": "", - "journalTitle": "BJPsych open", - "pubYear": "2023", - "date": "2023-11-15", - "isOpenAccess": "Y", - "keywords": "epidemiology; risk assessment; Depressive Disorders; Trauma And Stressor-related Disorders; Anxiety Or Fear-related Disorders", + "journalTitle": "Journal of affective disorders", + "pubYear": "2024", + "date": "2024-03-27", + "isOpenAccess": "N", + "keywords": "Depression; Speech; Smartphone; Automatic Speech Recognition; Topic Modeling", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Background

Estimates suggest that 1 in 100 people in the UK live with facial scarring. Despite this incidence, psychological support is limited.

Aims

The aim of this study was to strengthen the case for improving such support by determining the incidence and risk factors for anxiety and depression disorders in patients with facial scarring.

Method

A matched cohort study was performed. Patients were identified via secondary care data sources, using clinical codes for conditions resulting in facial scarring. A diagnosis of anxiety or depression was determined by linkage with the patient's primary care general practice data. Incidence was calculated per 1000 person-years at risk (PYAR). Logistic regression was used to determine risk factors.

Results

Between 2009 and 2018, 179 079 patients met the study criteria and were identified as having a facial scar, and matched to 179 079 controls. The incidence of anxiety in the facial scarring group was 10.05 per 1000 PYAR compared with 7.48 per 1000 PYAR for controls. The incidence of depression in the facial scarring group was 16.28 per 1000 PYAR compared with 9.56 per 1000 PYAR for controls. Age at the time of scarring, previous history of anxiety or depression, female gender, socioeconomic status and classification of scarring increased the risk of both anxiety disorders and depression.

Conclusions

There is a high burden of anxiety disorders and depression in this patient group. Risk of these mental health disorders is very much determined by factors apparent at the time of injury, supporting the need for psychological support.", + "abstract": "

Background

Prior research has associated spoken language use with depression, yet studies often involve small or non-clinical samples and face challenges in the manual transcription of speech. This paper aimed to automatically identify depression-related topics in speech recordings collected from clinical samples.

Methods

The data included 3919 English free-response speech recordings collected via smartphones from 265 participants with a depression history. We transcribed speech recordings via automatic speech recognition (Whisper tool, OpenAI) and identified principal topics from transcriptions using a deep learning topic model (BERTopic). To identify depression risk topics and understand the context, we compared participants' depression severity and behavioral (extracted from wearable devices) and linguistic (extracted from transcribed texts) characteristics across identified topics.

Results

From the 29 topics identified, we identified 6 risk topics for depression: 'No Expectations', 'Sleep', 'Mental Therapy', 'Haircut', 'Studying', and 'Coursework'. Participants mentioning depression risk topics exhibited higher sleep variability, later sleep onset, and fewer daily steps and used fewer words, more negative language, and fewer leisure-related words in their speech recordings.

Limitations

Our findings were derived from a depressed cohort with a specific speech task, potentially limiting the generalizability to non-clinical populations or other speech tasks. Additionally, some topics had small sample sizes, necessitating further validation in larger datasets.

Conclusion

This study demonstrates that specific speech topics can indicate depression severity. The employed data-driven workflow provides a practical approach for analyzing large-scale speech data collected from real-world settings.", "laySummary": "", - "urls": "pdf:https://www.cambridge.org/core/services/aop-cambridge-core/content/view/269D54BC172655C337E4E02E05E0A4FB/S2056472423005471a.pdf/div-class-title-the-association-of-anxiety-disorders-and-depression-with-facial-scarring-population-based-data-linkage-matched-cohort-analysis-of-358-158-patients-div.pdf; doi:https://doi.org/10.1192/bjo.2023.547; html:https://europepmc.org/articles/PMC10753955; pdf:https://europepmc.org/articles/PMC10753955?pdf=render" + "urls": "doi:https://doi.org/10.1016/j.jad.2024.03.106" }, { "id": "32895316", @@ -22286,6 +22269,23 @@ "laySummary": "", "urls": "pdf:https://thorax.bmj.com/content/thoraxjnl/75/10/826.full.pdf; doi:https://doi.org/10.1136/thoraxjnl-2020-215566" }, + { + "id": "37964568", + "doi": "https://doi.org/10.1192/bjo.2023.547", + "title": "The association of anxiety disorders and depression with facial scarring: population-based, data linkage, matched cohort analysis of 358 158 patients.", + "authorString": "Gibson JAG, Dobbs TD, Griffiths R, Song J, Akbari A, Bodger O, Hutchings HA, Lyons RA, John A, Whitaker IS.", + "authorAffiliations": "", + "journalTitle": "BJPsych open", + "pubYear": "2023", + "date": "2023-11-15", + "isOpenAccess": "Y", + "keywords": "epidemiology; risk assessment; Depressive Disorders; Trauma And Stressor-related Disorders; Anxiety Or Fear-related Disorders", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Estimates suggest that 1 in 100 people in the UK live with facial scarring. Despite this incidence, psychological support is limited.

Aims

The aim of this study was to strengthen the case for improving such support by determining the incidence and risk factors for anxiety and depression disorders in patients with facial scarring.

Method

A matched cohort study was performed. Patients were identified via secondary care data sources, using clinical codes for conditions resulting in facial scarring. A diagnosis of anxiety or depression was determined by linkage with the patient's primary care general practice data. Incidence was calculated per 1000 person-years at risk (PYAR). Logistic regression was used to determine risk factors.

Results

Between 2009 and 2018, 179 079 patients met the study criteria and were identified as having a facial scar, and matched to 179 079 controls. The incidence of anxiety in the facial scarring group was 10.05 per 1000 PYAR compared with 7.48 per 1000 PYAR for controls. The incidence of depression in the facial scarring group was 16.28 per 1000 PYAR compared with 9.56 per 1000 PYAR for controls. Age at the time of scarring, previous history of anxiety or depression, female gender, socioeconomic status and classification of scarring increased the risk of both anxiety disorders and depression.

Conclusions

There is a high burden of anxiety disorders and depression in this patient group. Risk of these mental health disorders is very much determined by factors apparent at the time of injury, supporting the need for psychological support.", + "laySummary": "", + "urls": "pdf:https://www.cambridge.org/core/services/aop-cambridge-core/content/view/269D54BC172655C337E4E02E05E0A4FB/S2056472423005471a.pdf/div-class-title-the-association-of-anxiety-disorders-and-depression-with-facial-scarring-population-based-data-linkage-matched-cohort-analysis-of-358-158-patients-div.pdf; doi:https://doi.org/10.1192/bjo.2023.547; html:https://europepmc.org/articles/PMC10753955; pdf:https://europepmc.org/articles/PMC10753955?pdf=render" + }, { "id": "33644414", "doi": "https://doi.org/10.23889/ijpds.v5i3.1371", @@ -22575,23 +22575,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1093/ije/dyaa216; doi:https://doi.org/10.1093/ije/dyaa216; html:https://europepmc.org/articles/PMC8271202; pdf:https://europepmc.org/articles/PMC8271202?pdf=render" }, - { - "id": "37987834", - "doi": "https://doi.org/10.1007/s00330-023-10311-0", - "title": "Radiomics of pericardial fat: a new frontier in heart failure discrimination and prediction.", - "authorString": "Szabo L, Salih A, Pujadas ER, Bard A, McCracken C, Ardissino M, Antoniades C, Vago H, Maurovich-Horvat P, Merkely B, Neubauer S, Lekadir K, Petersen SE, Raisi-Estabragh Z.", - "authorAffiliations": "", - "journalTitle": "European radiology", - "pubYear": "2023", - "date": "2023-11-21", - "isOpenAccess": "N", - "keywords": "Pericardium; Adipose tissue; Magnetic Resonance Imaging; Machine Learning; Radiomics", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Objectives

To use pericardial adipose tissue (PAT) radiomics phenotyping to differentiate existing and predict future heart failure (HF) cases in the UK Biobank.

Methods

PAT segmentations were derived from cardiovascular magnetic resonance (CMR) studies using an automated quality-controlled model to define the region-of-interest for radiomics analysis. Prevalent (present at time of imaging) and incident (first occurrence after imaging) HF were ascertained using health record linkage. We created balanced cohorts of non-HF individuals for comparison. PyRadiomics was utilised to extract 104 radiomics features, of which 28 were chosen after excluding highly correlated ones (0.8). These features, plus sex and age, served as predictors in binary classification models trained separately to detect (1) prevalent and (2) incident HF. We tested seven modeling methods using tenfold nested cross-validation and examined feature importance with explainability methods.

Results

We studied 1204 participants in total, 297 participants with prevalent (60\u2009\u00b1\u20097\u00a0years, 21% female) and 305 with incident (61\u2009\u00b1\u20096\u00a0years, 32% female) HF, and an equal number of non-HF comparators. We achieved good discriminative performance for both prevalent (voting classifier; AUC: 0.76; F1 score: 0.70) and incident (light gradient boosting machine: AUC: 0.74; F1 score: 0.68) HF. Our radiomics models showed marginally better performance compared to PAT area alone. Increased PAT size (maximum 2D diameter in a given column or slice) and texture heterogeneity (sum entropy) were important features for prevalent and incident HF classification models.

Conclusions

The amount and character of PAT discriminate individuals with prevalent HF and predict incidence of future HF.

Clinical relevance statement

This study presents an innovative application of pericardial adipose tissue (PAT) radiomics phenotyping as a predictive tool for heart failure (HF), a major public health concern. By leveraging advanced machine learning methods, the research uncovers that the quantity and characteristics of PAT can be used to identify existing cases of HF and predict future occurrences. The enhanced performance of these radiomics models over PAT area alone supports the potential for better personalised care through earlier detection and prevention of HF.

Key points

\u2022PAT radiomics applied to CMR was used for the first time to derive binary machine learning classifiers to develop models for discrimination of prevalence and prediction of incident heart failure. \u2022Models using PAT area provided acceptable discrimination between cases of prevalent or incident heart failure and comparator groups. \u2022An increased PAT volume (increased diameter using shape features) and greater texture heterogeneity captured by radiomics texture features (increased sum entropy) can be used as an additional classifier marker for heart failure.", - "laySummary": "", - "urls": "pdf:https://link.springer.com/content/pdf/10.1007/s00330-023-10311-0.pdf; doi:https://doi.org/10.1007/s00330-023-10311-0" - }, { "id": "37285143", "doi": "https://doi.org/10.1001/jamacardio.2023.1290", @@ -22626,6 +22609,23 @@ "laySummary": "", "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/camh.12571; doi:https://doi.org/10.1111/camh.12571; html:https://europepmc.org/articles/PMC10083915; pdf:https://europepmc.org/articles/PMC10083915?pdf=render" }, + { + "id": "37987834", + "doi": "https://doi.org/10.1007/s00330-023-10311-0", + "title": "Radiomics of pericardial fat: a new frontier in heart failure discrimination and prediction.", + "authorString": "Szabo L, Salih A, Pujadas ER, Bard A, McCracken C, Ardissino M, Antoniades C, Vago H, Maurovich-Horvat P, Merkely B, Neubauer S, Lekadir K, Petersen SE, Raisi-Estabragh Z.", + "authorAffiliations": "", + "journalTitle": "European radiology", + "pubYear": "2023", + "date": "2023-11-21", + "isOpenAccess": "N", + "keywords": "Pericardium; Adipose tissue; Magnetic Resonance Imaging; Machine Learning; Radiomics", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Objectives

To use pericardial adipose tissue (PAT) radiomics phenotyping to differentiate existing and predict future heart failure (HF) cases in the UK Biobank.

Methods

PAT segmentations were derived from cardiovascular magnetic resonance (CMR) studies using an automated quality-controlled model to define the region-of-interest for radiomics analysis. Prevalent (present at time of imaging) and incident (first occurrence after imaging) HF were ascertained using health record linkage. We created balanced cohorts of non-HF individuals for comparison. PyRadiomics was utilised to extract 104 radiomics features, of which 28 were chosen after excluding highly correlated ones (0.8). These features, plus sex and age, served as predictors in binary classification models trained separately to detect (1) prevalent and (2) incident HF. We tested seven modeling methods using tenfold nested cross-validation and examined feature importance with explainability methods.

Results

We studied 1204 participants in total, 297 participants with prevalent (60\u2009\u00b1\u20097\u00a0years, 21% female) and 305 with incident (61\u2009\u00b1\u20096\u00a0years, 32% female) HF, and an equal number of non-HF comparators. We achieved good discriminative performance for both prevalent (voting classifier; AUC: 0.76; F1 score: 0.70) and incident (light gradient boosting machine: AUC: 0.74; F1 score: 0.68) HF. Our radiomics models showed marginally better performance compared to PAT area alone. Increased PAT size (maximum 2D diameter in a given column or slice) and texture heterogeneity (sum entropy) were important features for prevalent and incident HF classification models.

Conclusions

The amount and character of PAT discriminate individuals with prevalent HF and predict incidence of future HF.

Clinical relevance statement

This study presents an innovative application of pericardial adipose tissue (PAT) radiomics phenotyping as a predictive tool for heart failure (HF), a major public health concern. By leveraging advanced machine learning methods, the research uncovers that the quantity and characteristics of PAT can be used to identify existing cases of HF and predict future occurrences. The enhanced performance of these radiomics models over PAT area alone supports the potential for better personalised care through earlier detection and prevention of HF.

Key points

\u2022PAT radiomics applied to CMR was used for the first time to derive binary machine learning classifiers to develop models for discrimination of prevalence and prediction of incident heart failure. \u2022Models using PAT area provided acceptable discrimination between cases of prevalent or incident heart failure and comparator groups. \u2022An increased PAT volume (increased diameter using shape features) and greater texture heterogeneity captured by radiomics texture features (increased sum entropy) can be used as an additional classifier marker for heart failure.", + "laySummary": "", + "urls": "pdf:https://link.springer.com/content/pdf/10.1007/s00330-023-10311-0.pdf; doi:https://doi.org/10.1007/s00330-023-10311-0" + }, { "id": "36264615", "doi": "https://doi.org/10.1161/circgen.122.003704", @@ -22660,23 +22660,6 @@ "laySummary": "", "urls": "pdf:https://trialsjournal.biomedcentral.com/counter/pdf/10.1186/s13063-023-07763-6; doi:https://doi.org/10.1186/s13063-023-07763-6; html:https://europepmc.org/articles/PMC10664262; pdf:https://europepmc.org/articles/PMC10664262?pdf=render" }, - { - "id": "37706486", - "doi": "https://doi.org/10.1080/09638288.2023.2254235", - "title": "Stepped collaborative care for pain and posttraumatic stress disorder after major trauma: a randomized controlled feasibility trial.", - "authorString": "Giummarra MJ, Reeder S, Williams S, Devlin A, Knol R, Ponsford J, Arnold CA, Konstantatos A, Gabbe BJ, Clarke H, Katz J, Mitchell F, Robinson E, Zatzick D.", - "authorAffiliations": "", - "journalTitle": "Disability and rehabilitation", - "pubYear": "2023", - "date": "2023-09-14", - "isOpenAccess": "N", - "keywords": "Trauma; Injury; Recovery; Pain; Hospitalization; Ptsd; Brief Intervention", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Purpose

To examine feasibility and acceptability of providing stepped collaborative care case management targeting posttraumatic stress disorder (PTSD) and pain symptoms after major traumatic injury.

Materials and methods

Participants were major trauma survivors in Victoria, Australia, at risk of persistent pain or PTSD with high baseline symptoms. Participants were block-randomized, stratified by compensation-status, to the usual care (n\u2009=\u200915) or intervention (n\u2009=\u200917) group (46% of eligible patients). The intervention was adapted from existing stepped collaborative care interventions with input from interdisciplinary experts and people with lived experience in trauma and disability. The proactive case management intervention targeted PTSD and pain management for 6-months using motivational interviewing, cognitive behavioral therapy strategies, and collaborative care. Qualitative interviews explored intervention acceptability.

Results

Intervention participants received a median of 7\u2009h case manager contact and reported that they valued the supportive and non-judgmental listening, and timely access to effective strategies, resources, and treatments post-injury from the case manager. Participants reported few disadvantages from participation, and positive impacts on symptoms and recovery outcomes consistent with the reduction in PTSD and pain symptoms measured at 1-, 3- and 6-months.

Conclusions

Stepped collaborative care was low-cost, feasible, and acceptable to people at risk of PTSD or pain after major trauma.IMPLICATIONS FOR REHABILITATIONAfter hospitalization for injury, people can experience difficulty accessing timely support to manage posttraumatic stress, pain and other concerns.Stepped case management-based interventions that provide individualized support and collaborative care have reduced posttraumatic stress symptom severity for patients admitted to American trauma centers.We showed that this model of care could be adapted to target pain and mental health in the trauma system in Victoria, Australia.The intervention was low cost, acceptable and highly valued by most participants who perceived that it helped them use strategies to better manage post-traumatic symptoms, and to access clinicians and treatments relevant to their needs.", - "laySummary": "", - "urls": "pdf:https://www.tandfonline.com/doi/pdf/10.1080/09638288.2023.2254235?needAccess=true; doi:https://doi.org/10.1080/09638288.2023.2254235" - }, { "id": "33382071", "doi": "https://doi.org/10.1093/schbul/sbaa176", @@ -22694,6 +22677,23 @@ "laySummary": "", "urls": "pdf:https://academic.oup.com/schizophreniabulletin/article-pdf/47/2/575/36620724/sbaa176.pdf; doi:https://doi.org/10.1093/schbul/sbaa176; html:https://europepmc.org/articles/PMC7965055; pdf:https://europepmc.org/articles/PMC7965055?pdf=render; doi:https://doi.org/10.1093/schbul/sbaa176" }, + { + "id": "37706486", + "doi": "https://doi.org/10.1080/09638288.2023.2254235", + "title": "Stepped collaborative care for pain and posttraumatic stress disorder after major trauma: a randomized controlled feasibility trial.", + "authorString": "Giummarra MJ, Reeder S, Williams S, Devlin A, Knol R, Ponsford J, Arnold CA, Konstantatos A, Gabbe BJ, Clarke H, Katz J, Mitchell F, Robinson E, Zatzick D.", + "authorAffiliations": "", + "journalTitle": "Disability and rehabilitation", + "pubYear": "2023", + "date": "2023-09-14", + "isOpenAccess": "N", + "keywords": "Trauma; Injury; Recovery; Pain; Hospitalization; Ptsd; Brief Intervention", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Purpose

To examine feasibility and acceptability of providing stepped collaborative care case management targeting posttraumatic stress disorder (PTSD) and pain symptoms after major traumatic injury.

Materials and methods

Participants were major trauma survivors in Victoria, Australia, at risk of persistent pain or PTSD with high baseline symptoms. Participants were block-randomized, stratified by compensation-status, to the usual care (n\u2009=\u200915) or intervention (n\u2009=\u200917) group (46% of eligible patients). The intervention was adapted from existing stepped collaborative care interventions with input from interdisciplinary experts and people with lived experience in trauma and disability. The proactive case management intervention targeted PTSD and pain management for 6-months using motivational interviewing, cognitive behavioral therapy strategies, and collaborative care. Qualitative interviews explored intervention acceptability.

Results

Intervention participants received a median of 7\u2009h case manager contact and reported that they valued the supportive and non-judgmental listening, and timely access to effective strategies, resources, and treatments post-injury from the case manager. Participants reported few disadvantages from participation, and positive impacts on symptoms and recovery outcomes consistent with the reduction in PTSD and pain symptoms measured at 1-, 3- and 6-months.

Conclusions

Stepped collaborative care was low-cost, feasible, and acceptable to people at risk of PTSD or pain after major trauma.IMPLICATIONS FOR REHABILITATIONAfter hospitalization for injury, people can experience difficulty accessing timely support to manage posttraumatic stress, pain and other concerns.Stepped case management-based interventions that provide individualized support and collaborative care have reduced posttraumatic stress symptom severity for patients admitted to American trauma centers.We showed that this model of care could be adapted to target pain and mental health in the trauma system in Victoria, Australia.The intervention was low cost, acceptable and highly valued by most participants who perceived that it helped them use strategies to better manage post-traumatic symptoms, and to access clinicians and treatments relevant to their needs.", + "laySummary": "", + "urls": "pdf:https://www.tandfonline.com/doi/pdf/10.1080/09638288.2023.2254235?needAccess=true; doi:https://doi.org/10.1080/09638288.2023.2254235" + }, { "id": "31529100", "doi": "https://doi.org/10.1093/pm/pnz209", @@ -22830,23 +22830,6 @@ "laySummary": "", "urls": "pdf:https://www.frontiersin.org/articles/10.3389/fdgth.2022.833912/pdf; doi:https://doi.org/10.3389/fdgth.2022.833912; html:https://europepmc.org/articles/PMC8825497; pdf:https://europepmc.org/articles/PMC8825497?pdf=render" }, - { - "id": "35022215", - "doi": "https://doi.org/10.1136/bmj-2021-067519", - "title": "Indirect effects of the covid-19 pandemic on childhood infection in England: population based observational study.", - "authorString": "Kadambari S, Goldacre R, Morris E, Goldacre MJ, Pollard AJ.", - "authorAffiliations": "", - "journalTitle": "BMJ (Clinical research ed.)", - "pubYear": "2022", - "date": "2022-01-12", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Objective

To assess the impact of the covid-19 pandemic on hospital admission rates and mortality outcomes for childhood respiratory infections, severe invasive infections, and vaccine preventable disease in England.

Design

Population based observational study of 19 common childhood respiratory, severe invasive, and vaccine preventable infections, comparing hospital admission rates and mortality outcomes before and after the onset of the pandemic in England.

Setting

Hospital admission data from every NHS hospital in England from 1 March 2017 to 30 June 2021 with record linkage to national mortality data.

Population

Children aged 0-14 years admitted to an NHS hospital with a selected childhood infection from 1 March 2017 to 30 June 2021.

Main outcome measures

For each infection, numbers of hospital admissions every month from 1 March 2017 to 30 June 2021, percentage changes in the number of hospital admissions before and after 1 March 2020, and adjusted odds ratios to compare 60 day case fatality outcomes before and after 1 March 2020.

Results

After 1 March 2020, substantial and sustained reductions in hospital admissions were found for all but one of the 19 infective conditions studied. Among the respiratory infections, the greatest percentage reductions were for influenza (mean annual number admitted between 1 March 2017 and 29 February 2020 was 5379 and number of children admitted from 1 March 2020 to 28 February 2021 was 304, 94% reduction, 95% confidence interval 89% to 97%), and bronchiolitis (from 51\u2009655 to 9423, 82% reduction, 95% confidence interval 79% to 84%). Among the severe invasive infections, the greatest reduction was for meningitis (50% reduction, 47% to 52%). For the vaccine preventable infections, reductions ranged from 53% (32% to 68%) for mumps to 90% (80% to 95%) for measles. Reductions were seen across all demographic subgroups and in children with underlying comorbidities. Corresponding decreases were also found for the absolute numbers of 60 day case fatalities, although the proportion of children admitted for pneumonia who died within 60 days increased (age-sex adjusted odds ratio 1.71, 95% confidence interval 1.43 to 2.05). More recent data indicate that some respiratory infections increased to higher levels than usual after May 2021.

Conclusions

During the covid-19 pandemic, a range of behavioural changes (adoption of non-pharmacological interventions) and societal strategies (school closures, lockdowns, and restricted travel) were used to reduce transmission of SARS-CoV-2, which also reduced admissions for common and severe childhood infections. Continued monitoring of these infections is required as social restrictions evolve.", - "laySummary": "", - "urls": "pdf:https://www.bmj.com/content/bmj/376/bmj-2021-067519.full.pdf; doi:https://doi.org/10.1136/bmj-2021-067519; html:https://europepmc.org/articles/PMC8753487; pdf:https://europepmc.org/articles/PMC8753487?pdf=render" - }, { "id": "34356044", "doi": "https://doi.org/10.3390/genes12071029", @@ -22864,6 +22847,23 @@ "laySummary": "", "urls": "pdf:https://www.mdpi.com/2073-4425/12/7/1029/pdf?version=1625724795; doi:https://doi.org/10.3390/genes12071029; html:https://europepmc.org/articles/PMC8303793; pdf:https://europepmc.org/articles/PMC8303793?pdf=render" }, + { + "id": "35022215", + "doi": "https://doi.org/10.1136/bmj-2021-067519", + "title": "Indirect effects of the covid-19 pandemic on childhood infection in England: population based observational study.", + "authorString": "Kadambari S, Goldacre R, Morris E, Goldacre MJ, Pollard AJ.", + "authorAffiliations": "", + "journalTitle": "BMJ (Clinical research ed.)", + "pubYear": "2022", + "date": "2022-01-12", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Objective

To assess the impact of the covid-19 pandemic on hospital admission rates and mortality outcomes for childhood respiratory infections, severe invasive infections, and vaccine preventable disease in England.

Design

Population based observational study of 19 common childhood respiratory, severe invasive, and vaccine preventable infections, comparing hospital admission rates and mortality outcomes before and after the onset of the pandemic in England.

Setting

Hospital admission data from every NHS hospital in England from 1 March 2017 to 30 June 2021 with record linkage to national mortality data.

Population

Children aged 0-14 years admitted to an NHS hospital with a selected childhood infection from 1 March 2017 to 30 June 2021.

Main outcome measures

For each infection, numbers of hospital admissions every month from 1 March 2017 to 30 June 2021, percentage changes in the number of hospital admissions before and after 1 March 2020, and adjusted odds ratios to compare 60 day case fatality outcomes before and after 1 March 2020.

Results

After 1 March 2020, substantial and sustained reductions in hospital admissions were found for all but one of the 19 infective conditions studied. Among the respiratory infections, the greatest percentage reductions were for influenza (mean annual number admitted between 1 March 2017 and 29 February 2020 was 5379 and number of children admitted from 1 March 2020 to 28 February 2021 was 304, 94% reduction, 95% confidence interval 89% to 97%), and bronchiolitis (from 51\u2009655 to 9423, 82% reduction, 95% confidence interval 79% to 84%). Among the severe invasive infections, the greatest reduction was for meningitis (50% reduction, 47% to 52%). For the vaccine preventable infections, reductions ranged from 53% (32% to 68%) for mumps to 90% (80% to 95%) for measles. Reductions were seen across all demographic subgroups and in children with underlying comorbidities. Corresponding decreases were also found for the absolute numbers of 60 day case fatalities, although the proportion of children admitted for pneumonia who died within 60 days increased (age-sex adjusted odds ratio 1.71, 95% confidence interval 1.43 to 2.05). More recent data indicate that some respiratory infections increased to higher levels than usual after May 2021.

Conclusions

During the covid-19 pandemic, a range of behavioural changes (adoption of non-pharmacological interventions) and societal strategies (school closures, lockdowns, and restricted travel) were used to reduce transmission of SARS-CoV-2, which also reduced admissions for common and severe childhood infections. Continued monitoring of these infections is required as social restrictions evolve.", + "laySummary": "", + "urls": "pdf:https://www.bmj.com/content/bmj/376/bmj-2021-067519.full.pdf; doi:https://doi.org/10.1136/bmj-2021-067519; html:https://europepmc.org/articles/PMC8753487; pdf:https://europepmc.org/articles/PMC8753487?pdf=render" + }, { "id": "31827124", "doi": "https://doi.org/10.1038/s41598-019-54849-w", @@ -22898,23 +22898,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1093/cvr/cvaa233; doi:https://doi.org/10.1093/cvr/cvaa233; html:https://europepmc.org/articles/PMC8152696; pdf:https://europepmc.org/articles/PMC8152696?pdf=render" }, - { - "id": "33652931", - "doi": "https://doi.org/10.3390/jcm10050921", - "title": "Diagnosis and Risk Prediction of Dilated Cardiomyopathy in the Era of Big Data and Genomics.", - "authorString": "Sammani A, Baas AF, Asselbergs FW, Te Riele ASJM.", - "authorAffiliations": "", - "journalTitle": "Journal of clinical medicine", - "pubYear": "2021", - "date": "2021-02-26", - "isOpenAccess": "Y", - "keywords": "Artificial intelligence; Diagnosis; Prognosis; Genetic; Dilated cardiomyopathy; Big Data; Deep Learning", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Dilated cardiomyopathy (DCM) is a leading cause of heart failure and life-threatening ventricular arrhythmias (LTVA). Work-up and risk stratification of DCM is clinically challenging, as there is great heterogeneity in phenotype and genotype. Throughout the last decade, improved genetic testing of patients has identified genotype-phenotype associations and enhanced evaluation of at-risk relatives leading to better patient prognosis. The field is now ripe to explore opportunities to improve personalised risk assessments. Multivariable risk models presented as \"risk calculators\" can incorporate a multitude of clinical variables and predict outcome (such as heart failure hospitalisations or LTVA). In addition, genetic risk scores derived from genome/exome-wide association studies can estimate an individual's lifetime genetic risk of developing DCM. The use of clinically granular investigations, such as late gadolinium enhancement on cardiac magnetic resonance imaging, is warranted in order to increase predictive performance. To this end, constructing big data infrastructures improves accessibility of data by using electronic health records, existing research databases, and disease registries. By applying methods such as machine and deep learning, we can model complex interactions, identify new phenotype clusters, and perform prognostic modelling. This review aims to provide an overview of the evolution of DCM definitions as well as its clinical work-up and considerations in the era of genomics. In addition, we present exciting examples in the field of big data infrastructures, personalised prognostic assessment, and artificial intelligence.", - "laySummary": "", - "urls": "pdf:https://www.mdpi.com/2077-0383/10/5/921/pdf?version=1615467325; doi:https://doi.org/10.3390/jcm10050921; html:https://europepmc.org/articles/PMC7956169; pdf:https://europepmc.org/articles/PMC7956169?pdf=render" - }, { "id": "31349307", "doi": "https://doi.org/10.3233/shti190058", @@ -22932,6 +22915,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.3233/SHTI190058" }, + { + "id": "33652931", + "doi": "https://doi.org/10.3390/jcm10050921", + "title": "Diagnosis and Risk Prediction of Dilated Cardiomyopathy in the Era of Big Data and Genomics.", + "authorString": "Sammani A, Baas AF, Asselbergs FW, Te Riele ASJM.", + "authorAffiliations": "", + "journalTitle": "Journal of clinical medicine", + "pubYear": "2021", + "date": "2021-02-26", + "isOpenAccess": "Y", + "keywords": "Artificial intelligence; Diagnosis; Prognosis; Genetic; Dilated cardiomyopathy; Big Data; Deep Learning", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Dilated cardiomyopathy (DCM) is a leading cause of heart failure and life-threatening ventricular arrhythmias (LTVA). Work-up and risk stratification of DCM is clinically challenging, as there is great heterogeneity in phenotype and genotype. Throughout the last decade, improved genetic testing of patients has identified genotype-phenotype associations and enhanced evaluation of at-risk relatives leading to better patient prognosis. The field is now ripe to explore opportunities to improve personalised risk assessments. Multivariable risk models presented as \"risk calculators\" can incorporate a multitude of clinical variables and predict outcome (such as heart failure hospitalisations or LTVA). In addition, genetic risk scores derived from genome/exome-wide association studies can estimate an individual's lifetime genetic risk of developing DCM. The use of clinically granular investigations, such as late gadolinium enhancement on cardiac magnetic resonance imaging, is warranted in order to increase predictive performance. To this end, constructing big data infrastructures improves accessibility of data by using electronic health records, existing research databases, and disease registries. By applying methods such as machine and deep learning, we can model complex interactions, identify new phenotype clusters, and perform prognostic modelling. This review aims to provide an overview of the evolution of DCM definitions as well as its clinical work-up and considerations in the era of genomics. In addition, we present exciting examples in the field of big data infrastructures, personalised prognostic assessment, and artificial intelligence.", + "laySummary": "", + "urls": "pdf:https://www.mdpi.com/2077-0383/10/5/921/pdf?version=1615467325; doi:https://doi.org/10.3390/jcm10050921; html:https://europepmc.org/articles/PMC7956169; pdf:https://europepmc.org/articles/PMC7956169?pdf=render" + }, { "id": "36810251", "doi": "https://doi.org/10.1172/jci.insight.156643", @@ -22949,23 +22949,6 @@ "laySummary": "", "urls": "pdf:http://insight.jci.org/articles/view/156643/files/pdf; doi:https://doi.org/10.1172/jci.insight.156643; html:https://europepmc.org/articles/PMC9977494; pdf:https://europepmc.org/articles/PMC9977494?pdf=render" }, - { - "id": "36721180", - "doi": "https://doi.org/10.1186/s12961-022-00956-6", - "title": "Tracking health system performance in times of crisis using routine health data: lessons learned from a multicountry consortium.", - "authorString": "Turcotte-Tremblay AM, Leerapan B, Akweongo P, Amponsah F, Aryal A, Asai D, Awoonor-Williams JK, Ayele W, Bauhoff S, Doubova SV, Gadeka DD, Dulal M, Gage A, Gordon-Strachan G, Haile-Mariam D, Joseph JP, Kaewkamjornchai P, Kapoor NR, Gelaw SK, Kim MK, Kruk ME, Kubota S, Margozzini P, Mehata S, Mthethwa L, Nega A, Oh J, Park SK, Passi-Solar A, Perez Cuevas RE, Reddy T, Rittiphairoj T, Sapag JC, Thermidor R, Tlou B, Arsenault C.", - "authorAffiliations": "", - "journalTitle": "Health research policy and systems", - "pubYear": "2023", - "date": "2023-01-31", - "isOpenAccess": "Y", - "keywords": "Quality Of Care; Health Systems; Routine Health Information Systems; Covid-19", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "COVID-19 has prompted the use of readily available administrative data to track health system performance in times of crisis and to monitor disruptions in essential healthcare services. In this commentary we describe our experience working with these data and lessons learned across countries. Since April 2020, the Quality Evidence for Health System Transformation (QuEST) network has used administrative data and routine health information systems (RHIS) to assess health system performance during COVID-19 in Chile, Ethiopia, Ghana, Haiti, Lao People's Democratic Republic, Mexico, Nepal, South Africa, Republic of Korea and Thailand. We compiled a large set of indicators related to common health conditions for the purpose of multicountry comparisons. The study compiled 73 indicators. A total of 43% of the indicators compiled pertained to reproductive, maternal, newborn and child health (RMNCH). Only 12% of the indicators were related to hypertension, diabetes or cancer care. We also found few indicators related to mental health services and outcomes within these data systems. Moreover, 72% of the indicators compiled were related to volume of services delivered, 18% to health outcomes and only 10% to the quality of processes of care. While several datasets were complete or near-complete censuses of all health facilities in the country, others excluded some facility types or population groups. In some countries, RHIS did not capture services delivered through non-visit or nonconventional care during COVID-19, such as telemedicine. We propose the following recommendations to improve the analysis of administrative and RHIS data to track health system performance in times of crisis: ensure the scope of health conditions covered is aligned with the burden of disease, increase the number of indicators related to quality of care and health outcomes; incorporate data on nonconventional care such as telehealth; continue improving data quality and expand reporting from private sector facilities; move towards collecting patient-level data through electronic health records to facilitate quality-of-care assessment and equity analyses; implement more resilient and standardized health information technologies; reduce delays and loosen restrictions for researchers to access the data; complement routine data with patient-reported data; and\u00a0employ mixed methods to better understand the underlying causes of service disruptions.", - "laySummary": "", - "urls": "pdf:https://health-policy-systems.biomedcentral.com/counter/pdf/10.1186/s12961-022-00956-6; doi:https://doi.org/10.1186/s12961-022-00956-6; html:https://europepmc.org/articles/PMC9888332; pdf:https://europepmc.org/articles/PMC9888332?pdf=render" - }, { "id": "31446406", "doi": "https://doi.org/10.1136/bmjopen-2018-027577", @@ -22984,21 +22967,21 @@ "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/9/8/e027577.full.pdf; doi:https://doi.org/10.1136/bmjopen-2018-027577; html:https://europepmc.org/articles/PMC6720244; pdf:https://europepmc.org/articles/PMC6720244?pdf=render" }, { - "id": "35396183", - "doi": "https://doi.org/10.1016/s2589-7500(22)00003-6", - "title": "The medical algorithmic audit.", - "authorString": "Liu X, Glocker B, McCradden MM, Ghassemi M, Denniston AK, Oakden-Rayner L.", + "id": "36721180", + "doi": "https://doi.org/10.1186/s12961-022-00956-6", + "title": "Tracking health system performance in times of crisis using routine health data: lessons learned from a multicountry consortium.", + "authorString": "Turcotte-Tremblay AM, Leerapan B, Akweongo P, Amponsah F, Aryal A, Asai D, Awoonor-Williams JK, Ayele W, Bauhoff S, Doubova SV, Gadeka DD, Dulal M, Gage A, Gordon-Strachan G, Haile-Mariam D, Joseph JP, Kaewkamjornchai P, Kapoor NR, Gelaw SK, Kim MK, Kruk ME, Kubota S, Margozzini P, Mehata S, Mthethwa L, Nega A, Oh J, Park SK, Passi-Solar A, Perez Cuevas RE, Reddy T, Rittiphairoj T, Sapag JC, Thermidor R, Tlou B, Arsenault C.", "authorAffiliations": "", - "journalTitle": "The Lancet. Digital health", - "pubYear": "2022", - "date": "2022-04-05", - "isOpenAccess": "N", - "keywords": "", + "journalTitle": "Health research policy and systems", + "pubYear": "2023", + "date": "2023-01-31", + "isOpenAccess": "Y", + "keywords": "Quality Of Care; Health Systems; Routine Health Information Systems; Covid-19", "nationalPriorities": "", "healthCategories": "", - "abstract": "Artificial intelligence systems for health care, like any other medical device, have the potential to fail. However, specific qualities of artificial intelligence systems, such as the tendency to learn spurious correlates in training data, poor generalisability to new deployment settings, and a paucity of reliable explainability mechanisms, mean they can yield unpredictable errors that might be entirely missed without proactive investigation. We propose a medical algorithmic audit framework that guides the auditor through a process of considering potential algorithmic errors in the context of a clinical task, mapping the components that might contribute to the occurrence of errors, and anticipating their potential consequences. We suggest several approaches for testing algorithmic errors, including exploratory error analysis, subgroup testing, and adversarial testing, and provide examples from our own work and previous studies. The medical algorithmic audit is a tool that can be used to better understand the weaknesses of an artificial intelligence system and put in place mechanisms to mitigate their impact. We propose that safety monitoring and medical algorithmic auditing should be a joint responsibility between users and developers, and encourage the use of feedback mechanisms between these groups to promote learning and maintain safe deployment of artificial intelligence systems.", + "abstract": "COVID-19 has prompted the use of readily available administrative data to track health system performance in times of crisis and to monitor disruptions in essential healthcare services. In this commentary we describe our experience working with these data and lessons learned across countries. Since April 2020, the Quality Evidence for Health System Transformation (QuEST) network has used administrative data and routine health information systems (RHIS) to assess health system performance during COVID-19 in Chile, Ethiopia, Ghana, Haiti, Lao People's Democratic Republic, Mexico, Nepal, South Africa, Republic of Korea and Thailand. We compiled a large set of indicators related to common health conditions for the purpose of multicountry comparisons. The study compiled 73 indicators. A total of 43% of the indicators compiled pertained to reproductive, maternal, newborn and child health (RMNCH). Only 12% of the indicators were related to hypertension, diabetes or cancer care. We also found few indicators related to mental health services and outcomes within these data systems. Moreover, 72% of the indicators compiled were related to volume of services delivered, 18% to health outcomes and only 10% to the quality of processes of care. While several datasets were complete or near-complete censuses of all health facilities in the country, others excluded some facility types or population groups. In some countries, RHIS did not capture services delivered through non-visit or nonconventional care during COVID-19, such as telemedicine. We propose the following recommendations to improve the analysis of administrative and RHIS data to track health system performance in times of crisis: ensure the scope of health conditions covered is aligned with the burden of disease, increase the number of indicators related to quality of care and health outcomes; incorporate data on nonconventional care such as telehealth; continue improving data quality and expand reporting from private sector facilities; move towards collecting patient-level data through electronic health records to facilitate quality-of-care assessment and equity analyses; implement more resilient and standardized health information technologies; reduce delays and loosen restrictions for researchers to access the data; complement routine data with patient-reported data; and\u00a0employ mixed methods to better understand the underlying causes of service disruptions.", "laySummary": "", - "urls": "pdf:http://www.thelancet.com/article/S2589750022000036/pdf; doi:https://doi.org/10.1016/S2589-7500(22)00003-6" + "urls": "pdf:https://health-policy-systems.biomedcentral.com/counter/pdf/10.1186/s12961-022-00956-6; doi:https://doi.org/10.1186/s12961-022-00956-6; html:https://europepmc.org/articles/PMC9888332; pdf:https://europepmc.org/articles/PMC9888332?pdf=render" }, { "id": "34751629", @@ -23017,6 +23000,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1080/09638288.2021.1998671" }, + { + "id": "35396183", + "doi": "https://doi.org/10.1016/s2589-7500(22)00003-6", + "title": "The medical algorithmic audit.", + "authorString": "Liu X, Glocker B, McCradden MM, Ghassemi M, Denniston AK, Oakden-Rayner L.", + "authorAffiliations": "", + "journalTitle": "The Lancet. Digital health", + "pubYear": "2022", + "date": "2022-04-05", + "isOpenAccess": "N", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Artificial intelligence systems for health care, like any other medical device, have the potential to fail. However, specific qualities of artificial intelligence systems, such as the tendency to learn spurious correlates in training data, poor generalisability to new deployment settings, and a paucity of reliable explainability mechanisms, mean they can yield unpredictable errors that might be entirely missed without proactive investigation. We propose a medical algorithmic audit framework that guides the auditor through a process of considering potential algorithmic errors in the context of a clinical task, mapping the components that might contribute to the occurrence of errors, and anticipating their potential consequences. We suggest several approaches for testing algorithmic errors, including exploratory error analysis, subgroup testing, and adversarial testing, and provide examples from our own work and previous studies. The medical algorithmic audit is a tool that can be used to better understand the weaknesses of an artificial intelligence system and put in place mechanisms to mitigate their impact. We propose that safety monitoring and medical algorithmic auditing should be a joint responsibility between users and developers, and encourage the use of feedback mechanisms between these groups to promote learning and maintain safe deployment of artificial intelligence systems.", + "laySummary": "", + "urls": "pdf:http://www.thelancet.com/article/S2589750022000036/pdf; doi:https://doi.org/10.1016/S2589-7500(22)00003-6" + }, { "id": "34139439", "doi": "https://doi.org/10.1016/j.compbiomed.2021.104542", @@ -23085,23 +23085,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1186/s12864-023-09663-0; html:https://europepmc.org/articles/PMC10559536; pdf:https://europepmc.org/articles/PMC10559536?pdf=render" }, - { - "id": "38383544", - "doi": "https://doi.org/10.1038/s41467-024-45761-7", - "title": "The plasmidome associated with Gram-negative bloodstream infections: A large-scale observational study using complete plasmid assemblies.", - "authorString": "Lipworth S, Matlock W, Shaw L, Vihta KD, Rodger G, Chau K, Barker L, George S, Kavanagh J, Davies T, Vaughan A, Andersson M, Jeffery K, Oakley S, Morgan M, Hopkins S, Peto T, Crook D, Walker AS, Stoesser N.", - "authorAffiliations": "", - "journalTitle": "Nature communications", - "pubYear": "2024", - "date": "2024-02-22", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Plasmids carry genes conferring antimicrobial resistance and other clinically important traits, and contribute to the rapid dissemination of such genes. Previous studies using complete plasmid assemblies, which are essential for reliable inference, have been small and/or limited to plasmids carrying antimicrobial resistance genes (ARGs). In this study, we sequenced 1,880 complete plasmids from 738 isolates from bloodstream infections in Oxfordshire, UK. The bacteria had been originally isolated in 2009 (194 isolates) and 2018 (368 isolates), plus a stratified selection from intervening years (176 isolates). We demonstrate that plasmids are largely, but not entirely, constrained to a single host species, although there is substantial overlap between species of plasmid gene-repertoire. Most ARGs are carried by a relatively small number of plasmid groups with biological features that are predictable. Plasmids carrying ARGs (including those encoding carbapenemases) share a putative 'backbone' of core genes with those carrying no such genes. These findings suggest that future surveillance should, in addition to tracking plasmids currently associated with clinically important genes, focus on identifying and monitoring the dissemination of high-risk plasmid groups with the potential to rapidly acquire and disseminate these genes.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1038/s41467-024-45761-7; html:https://europepmc.org/articles/PMC10881496; pdf:https://europepmc.org/articles/PMC10881496?pdf=render" - }, { "id": "34598995", "doi": "https://doi.org/10.1136/bmjopen-2021-055219", @@ -23119,6 +23102,23 @@ "laySummary": "", "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/11/10/e055219.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-055219; html:https://europepmc.org/articles/PMC8488707; pdf:https://europepmc.org/articles/PMC8488707?pdf=render" }, + { + "id": "38383544", + "doi": "https://doi.org/10.1038/s41467-024-45761-7", + "title": "The plasmidome associated with Gram-negative bloodstream infections: A large-scale observational study using complete plasmid assemblies.", + "authorString": "Lipworth S, Matlock W, Shaw L, Vihta KD, Rodger G, Chau K, Barker L, George S, Kavanagh J, Davies T, Vaughan A, Andersson M, Jeffery K, Oakley S, Morgan M, Hopkins S, Peto T, Crook D, Walker AS, Stoesser N.", + "authorAffiliations": "", + "journalTitle": "Nature communications", + "pubYear": "2024", + "date": "2024-02-22", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Plasmids carry genes conferring antimicrobial resistance and other clinically important traits, and contribute to the rapid dissemination of such genes. Previous studies using complete plasmid assemblies, which are essential for reliable inference, have been small and/or limited to plasmids carrying antimicrobial resistance genes (ARGs). In this study, we sequenced 1,880 complete plasmids from 738 isolates from bloodstream infections in Oxfordshire, UK. The bacteria had been originally isolated in 2009 (194 isolates) and 2018 (368 isolates), plus a stratified selection from intervening years (176 isolates). We demonstrate that plasmids are largely, but not entirely, constrained to a single host species, although there is substantial overlap between species of plasmid gene-repertoire. Most ARGs are carried by a relatively small number of plasmid groups with biological features that are predictable. Plasmids carrying ARGs (including those encoding carbapenemases) share a putative 'backbone' of core genes with those carrying no such genes. These findings suggest that future surveillance should, in addition to tracking plasmids currently associated with clinically important genes, focus on identifying and monitoring the dissemination of high-risk plasmid groups with the potential to rapidly acquire and disseminate these genes.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1038/s41467-024-45761-7; html:https://europepmc.org/articles/PMC10881496; pdf:https://europepmc.org/articles/PMC10881496?pdf=render" + }, { "id": "30183734", "doi": "https://doi.org/10.1371/journal.pone.0202359", @@ -23136,23 +23136,6 @@ "laySummary": "", "urls": "pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0202359&type=printable; doi:https://doi.org/10.1371/journal.pone.0202359; html:https://europepmc.org/articles/PMC6124703; pdf:https://europepmc.org/articles/PMC6124703?pdf=render" }, - { - "id": "36835444", - "doi": "https://doi.org/10.3390/ijms24044031", - "title": "Untargeted Metabolomics Identifies Potential Hypertrophic Cardiomyopathy Biomarkers in Carriers of MYBPC3 Founder Variants.", - "authorString": "Jansen M, Schuldt M, van Driel BO, Schmidt AF, Christiaans I, van der Crabben SN, Hoedemaekers YM, Dooijes D, Jongbloed JDH, Boven LG, Deprez RHL, Wilde AAM, Jans JJM, van der Velden J, de Boer RA, van Tintelen JP, Asselbergs FW, Baas AF.", - "authorAffiliations": "", - "journalTitle": "International journal of molecular sciences", - "pubYear": "2023", - "date": "2023-02-17", - "isOpenAccess": "Y", - "keywords": "Biomarkers; hypertrophic cardiomyopathy; Metabolomics; Mybpc3", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Hypertrophic cardiomyopathy (HCM) is the most prevalent monogenic heart disease, commonly caused by pathogenic MYBPC3 variants, and a significant cause of sudden cardiac death. Severity is highly variable, with incomplete penetrance among genotype-positive family members. Previous studies demonstrated metabolic changes in HCM. We aimed to identify metabolite profiles associated with disease severity in carriers of MYBPC3 founder variants using direct-infusion high-resolution mass spectrometry in plasma of 30 carriers with a severe phenotype (maximum wall thickness \u226520 mm, septal reduction therapy, congestive heart failure, left ventricular ejection fraction <50%, or malignant ventricular arrhythmia) and 30 age- and sex-matched carriers with no or a mild phenotype. Of the top 25 mass spectrometry peaks selected by sparse partial least squares discriminant analysis, XGBoost gradient boosted trees, and Lasso logistic regression (42 total), 36 associated with severe HCM at a p < 0.05, 20 at p < 0.01, and 3 at p < 0.001. These peaks could be clustered to several metabolic pathways, including acylcarnitine, histidine, lysine, purine and steroid hormone metabolism, and proteolysis. In conclusion, this exploratory case-control study identified metabolites associated with severe phenotypes in MYBPC3 founder variant carriers. Future studies should assess whether these biomarkers contribute to HCM pathogenesis and evaluate their contribution to risk stratification.", - "laySummary": "", - "urls": "pdf:https://www.mdpi.com/1422-0067/24/4/4031/pdf?version=1676950066; doi:https://doi.org/10.3390/ijms24044031; html:https://europepmc.org/articles/PMC9961357; pdf:https://europepmc.org/articles/PMC9961357?pdf=render" - }, { "id": "32282926", "doi": "https://doi.org/10.1111/bjd.19122", @@ -23170,6 +23153,23 @@ "laySummary": "", "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/bjd.19122; doi:https://doi.org/10.1111/bjd.19122" }, + { + "id": "36835444", + "doi": "https://doi.org/10.3390/ijms24044031", + "title": "Untargeted Metabolomics Identifies Potential Hypertrophic Cardiomyopathy Biomarkers in Carriers of MYBPC3 Founder Variants.", + "authorString": "Jansen M, Schuldt M, van Driel BO, Schmidt AF, Christiaans I, van der Crabben SN, Hoedemaekers YM, Dooijes D, Jongbloed JDH, Boven LG, Deprez RHL, Wilde AAM, Jans JJM, van der Velden J, de Boer RA, van Tintelen JP, Asselbergs FW, Baas AF.", + "authorAffiliations": "", + "journalTitle": "International journal of molecular sciences", + "pubYear": "2023", + "date": "2023-02-17", + "isOpenAccess": "Y", + "keywords": "Biomarkers; hypertrophic cardiomyopathy; Metabolomics; Mybpc3", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Hypertrophic cardiomyopathy (HCM) is the most prevalent monogenic heart disease, commonly caused by pathogenic MYBPC3 variants, and a significant cause of sudden cardiac death. Severity is highly variable, with incomplete penetrance among genotype-positive family members. Previous studies demonstrated metabolic changes in HCM. We aimed to identify metabolite profiles associated with disease severity in carriers of MYBPC3 founder variants using direct-infusion high-resolution mass spectrometry in plasma of 30 carriers with a severe phenotype (maximum wall thickness \u226520 mm, septal reduction therapy, congestive heart failure, left ventricular ejection fraction <50%, or malignant ventricular arrhythmia) and 30 age- and sex-matched carriers with no or a mild phenotype. Of the top 25 mass spectrometry peaks selected by sparse partial least squares discriminant analysis, XGBoost gradient boosted trees, and Lasso logistic regression (42 total), 36 associated with severe HCM at a p < 0.05, 20 at p < 0.01, and 3 at p < 0.001. These peaks could be clustered to several metabolic pathways, including acylcarnitine, histidine, lysine, purine and steroid hormone metabolism, and proteolysis. In conclusion, this exploratory case-control study identified metabolites associated with severe phenotypes in MYBPC3 founder variant carriers. Future studies should assess whether these biomarkers contribute to HCM pathogenesis and evaluate their contribution to risk stratification.", + "laySummary": "", + "urls": "pdf:https://www.mdpi.com/1422-0067/24/4/4031/pdf?version=1676950066; doi:https://doi.org/10.3390/ijms24044031; html:https://europepmc.org/articles/PMC9961357; pdf:https://europepmc.org/articles/PMC9961357?pdf=render" + }, { "id": "33180769", "doi": "https://doi.org/10.1371/journal.pone.0240902", @@ -23306,6 +23306,23 @@ "laySummary": "", "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/12/4/e052514.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-052514; html:https://europepmc.org/articles/PMC9019828; pdf:https://europepmc.org/articles/PMC9019828?pdf=render" }, + { + "id": "32861307", + "doi": "https://doi.org/10.1016/s0140-6736(20)30930-2", + "title": "Invasive versus non-invasive management of older patients with non-ST elevation myocardial infarction (SENIOR-NSTEMI): a cohort study based on routine clinical data.", + "authorString": "Kaura A, Sterne JAC, Trickey A, Abbott S, Mulla A, Glampson B, Panoulas V, Davies J, Woods K, Omigie J, Shah AD, Channon KM, Weber JN, Thursz MR, Elliott P, Hemingway H, Williams B, Asselbergs FW, O'Sullivan M, Lord GM, Melikian N, Johnson T, Francis DP, Shah AM, Perera D, Kharbanda R, Patel RS, Mayet J.", + "authorAffiliations": "", + "journalTitle": "Lancet (London, England)", + "pubYear": "2020", + "date": "2020-08-01", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Previous trials suggest lower long-term risk of mortality after invasive rather than non-invasive management of patients with non-ST elevation myocardial infarction (NSTEMI), but the trials excluded very elderly patients. We aimed to estimate the effect of invasive versus non-invasive management within 3 days of peak troponin concentration on the survival of patients aged 80 years or older with NSTEMI.

Methods

Routine clinical data for this study were obtained from five collaborating hospitals hosting NIHR Biomedical Research Centres in the UK (all tertiary centres with emergency departments). Eligible patients were 80 years old or older when they underwent troponin measurements and were diagnosed with NSTEMI between 2010 (2008 for University College Hospital) and 2017. Propensity scores (patients' estimated probability of receiving invasive management) based on pretreatment variables were derived using logistic regression; patients with high probabilities of non-invasive or invasive management were excluded. Patients who died within 3 days of peak troponin concentration without receiving invasive management were assigned to the invasive or non-invasive management groups based on their propensity scores, to mitigate immortal time bias. We estimated mortality hazard ratios comparing invasive with non-invasive management, and compared the rate of hospital admissions for heart failure.

Findings

Of the 1976 patients with NSTEMI, 101 died within 3 days of their peak troponin concentration and 375 were excluded because of extreme propensity scores. The remaining 1500 patients had a median age of 86 (IQR 82-89) years of whom (845 [56%] received non-invasive management. During median follow-up of 3\u00b70 (IQR 1\u00b72-4\u00b78) years, 613 (41%) patients died. The adjusted cumulative 5-year mortality was 36% in the invasive management group and 55% in the non-invasive management group (adjusted hazard ratio 0\u00b768, 95% CI 0\u00b755-0\u00b784). Invasive management was associated with lower incidence of hospital admissions for heart failure (adjusted rate ratio compared with non-invasive management 0\u00b767, 95% CI 0\u00b748-0\u00b793).

Interpretation

The survival advantage of invasive compared with non-invasive management appears to extend to patients with NSTEMI who are aged 80 years or older.

Funding

NIHR Imperial Biomedical Research Centre, as part of the NIHR Health Informatics Collaborative.", + "laySummary": "", + "urls": "pdf:http://www.thelancet.com/article/S0140673620309302/pdf; doi:https://doi.org/10.1016/S0140-6736(20)30930-2; html:https://europepmc.org/articles/PMC7456783; pdf:https://europepmc.org/articles/PMC7456783?pdf=render" + }, { "id": "36285341", "doi": "https://doi.org/10.1080/17434440.2022.2132147", @@ -23324,21 +23341,21 @@ "urls": "doi:https://doi.org/10.1080/17434440.2022.2132147; doi:https://doi.org/10.1080/17434440.2022.2132147" }, { - "id": "32861307", - "doi": "https://doi.org/10.1016/s0140-6736(20)30930-2", - "title": "Invasive versus non-invasive management of older patients with non-ST elevation myocardial infarction (SENIOR-NSTEMI): a cohort study based on routine clinical data.", - "authorString": "Kaura A, Sterne JAC, Trickey A, Abbott S, Mulla A, Glampson B, Panoulas V, Davies J, Woods K, Omigie J, Shah AD, Channon KM, Weber JN, Thursz MR, Elliott P, Hemingway H, Williams B, Asselbergs FW, O'Sullivan M, Lord GM, Melikian N, Johnson T, Francis DP, Shah AM, Perera D, Kharbanda R, Patel RS, Mayet J.", + "id": "36576811", + "doi": "https://doi.org/10.1001/jamacardio.2022.4466", + "title": "Predictive Utility of a Coronary Artery Disease Polygenic Risk Score in Primary Prevention.", + "authorString": "Marston NA, Pirruccello JP, Melloni GEM, Koyama S, Kamanu FK, Weng LC, Roselli C, Kamatani Y, Komuro I, Aragam KG, Butterworth AS, Ito K, Lubitz SA, Ellinor PT, Sabatine MS, Ruff CT.", "authorAffiliations": "", - "journalTitle": "Lancet (London, England)", - "pubYear": "2020", - "date": "2020-08-01", - "isOpenAccess": "Y", + "journalTitle": "JAMA cardiology", + "pubYear": "2023", + "date": "2023-02-01", + "isOpenAccess": "N", "keywords": "", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Background

Previous trials suggest lower long-term risk of mortality after invasive rather than non-invasive management of patients with non-ST elevation myocardial infarction (NSTEMI), but the trials excluded very elderly patients. We aimed to estimate the effect of invasive versus non-invasive management within 3 days of peak troponin concentration on the survival of patients aged 80 years or older with NSTEMI.

Methods

Routine clinical data for this study were obtained from five collaborating hospitals hosting NIHR Biomedical Research Centres in the UK (all tertiary centres with emergency departments). Eligible patients were 80 years old or older when they underwent troponin measurements and were diagnosed with NSTEMI between 2010 (2008 for University College Hospital) and 2017. Propensity scores (patients' estimated probability of receiving invasive management) based on pretreatment variables were derived using logistic regression; patients with high probabilities of non-invasive or invasive management were excluded. Patients who died within 3 days of peak troponin concentration without receiving invasive management were assigned to the invasive or non-invasive management groups based on their propensity scores, to mitigate immortal time bias. We estimated mortality hazard ratios comparing invasive with non-invasive management, and compared the rate of hospital admissions for heart failure.

Findings

Of the 1976 patients with NSTEMI, 101 died within 3 days of their peak troponin concentration and 375 were excluded because of extreme propensity scores. The remaining 1500 patients had a median age of 86 (IQR 82-89) years of whom (845 [56%] received non-invasive management. During median follow-up of 3\u00b70 (IQR 1\u00b72-4\u00b78) years, 613 (41%) patients died. The adjusted cumulative 5-year mortality was 36% in the invasive management group and 55% in the non-invasive management group (adjusted hazard ratio 0\u00b768, 95% CI 0\u00b755-0\u00b784). Invasive management was associated with lower incidence of hospital admissions for heart failure (adjusted rate ratio compared with non-invasive management 0\u00b767, 95% CI 0\u00b748-0\u00b793).

Interpretation

The survival advantage of invasive compared with non-invasive management appears to extend to patients with NSTEMI who are aged 80 years or older.

Funding

NIHR Imperial Biomedical Research Centre, as part of the NIHR Health Informatics Collaborative.", + "abstract": "

Importance

The clinical utility of polygenic risk scores (PRS) for coronary artery disease (CAD) has not yet been established.

Objective

To investigate the ability of a CAD PRS to potentially guide statin initiation in primary prevention after accounting for age and clinical risk.

Design, setting, and participants

This was a longitudinal cohort study with enrollment starting on January 1, 2006, and ending on December 31, 2010, with data updated to mid-2021, using data from the UK Biobank, a long-term population study of UK citizens. A replication analysis was performed in Biobank Japan. The analysis included all patients without a history of CAD and who were not taking lipid-lowering therapy. Data were analyzed from January 1 to June 30, 2022.

Exposures

Polygenic risk for CAD was defined as low (bottom 20%), intermediate, and high (top 20%) using a CAD PRS including 241 genome-wide significant single-nucleotide variations (SNVs). The pooled cohort equations were used to estimate 10-year atherosclerotic cardiovascular disease (ASCVD) risk and classify individuals as low (<5%), borderline (5-<7.5%), intermediate (7.5-<20%), or high risk (\u226520%).

Main outcomes and measures

Myocardial infarction (MI) and ASCVD events (defined as incident clinical CAD [including MI], stroke, or CV death).

Results

A total of 330\u202f201 patients (median [IQR] age, 57 [40-74] years; 189\u202f107 female individuals [57%]) were included from the UK Biobank. Over the 10-year follow-up, 4454 individuals had an MI. The CAD PRS was significantly associated with the risk of MI in all age groups but had significantly stronger risk prediction at younger ages (age <50 years: hazard ratio [HR] per 1 SD of PRS, 1.72; 95% CI, 1.56-1.89; age 50-60 years: HR, 1.46; 95% CI, 1.38-1.53; age >60 years: HR, 1.42; 95% CI, 1.37-1.48; P for interaction <.001). In patients younger than 50 years, those with high PRS had a 3- to 4-fold increased associated risk of MI compared with those in the low PRS category. A significant interaction between CAD PRS and age was replicated in Biobank Japan. When CAD PRS testing was added to the clinical ASCVD risk score in individuals younger than 50 years, 591 of 4373 patients (20%) with borderline risk were risk stratified into intermediate risk, warranting initiation of statin therapy and 3198 of 7477 patients (20%) with both borderline or intermediate risk were stratified as low risk, thus not warranting therapy.

Conclusions and relevance

Results of this cohort study suggest that the predictive ability of a CAD PRS was greater in younger individuals and can be used to better identify patients with borderline and intermediate clinical risk who should initiate statin therapy.", "laySummary": "", - "urls": "pdf:http://www.thelancet.com/article/S0140673620309302/pdf; doi:https://doi.org/10.1016/S0140-6736(20)30930-2; html:https://europepmc.org/articles/PMC7456783; pdf:https://europepmc.org/articles/PMC7456783?pdf=render" + "urls": "doi:https://doi.org/10.1001/jamacardio.2022.4466; html:https://europepmc.org/articles/PMC9857431; doi:https://doi.org/10.1001/jamacardio.2022.4466" }, { "id": "38692709", @@ -23357,23 +23374,6 @@ "laySummary": "", "urls": "pdf:https://bmjopenrespres.bmj.com/content/bmjresp/11/1/e001746.full.pdf; doi:https://doi.org/10.1136/bmjresp-2023-001746; html:https://europepmc.org/articles/PMC11086188; pdf:https://europepmc.org/articles/PMC11086188?pdf=render" }, - { - "id": "36576811", - "doi": "https://doi.org/10.1001/jamacardio.2022.4466", - "title": "Predictive Utility of a Coronary Artery Disease Polygenic Risk Score in Primary Prevention.", - "authorString": "Marston NA, Pirruccello JP, Melloni GEM, Koyama S, Kamanu FK, Weng LC, Roselli C, Kamatani Y, Komuro I, Aragam KG, Butterworth AS, Ito K, Lubitz SA, Ellinor PT, Sabatine MS, Ruff CT.", - "authorAffiliations": "", - "journalTitle": "JAMA cardiology", - "pubYear": "2023", - "date": "2023-02-01", - "isOpenAccess": "N", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Importance

The clinical utility of polygenic risk scores (PRS) for coronary artery disease (CAD) has not yet been established.

Objective

To investigate the ability of a CAD PRS to potentially guide statin initiation in primary prevention after accounting for age and clinical risk.

Design, setting, and participants

This was a longitudinal cohort study with enrollment starting on January 1, 2006, and ending on December 31, 2010, with data updated to mid-2021, using data from the UK Biobank, a long-term population study of UK citizens. A replication analysis was performed in Biobank Japan. The analysis included all patients without a history of CAD and who were not taking lipid-lowering therapy. Data were analyzed from January 1 to June 30, 2022.

Exposures

Polygenic risk for CAD was defined as low (bottom 20%), intermediate, and high (top 20%) using a CAD PRS including 241 genome-wide significant single-nucleotide variations (SNVs). The pooled cohort equations were used to estimate 10-year atherosclerotic cardiovascular disease (ASCVD) risk and classify individuals as low (<5%), borderline (5-<7.5%), intermediate (7.5-<20%), or high risk (\u226520%).

Main outcomes and measures

Myocardial infarction (MI) and ASCVD events (defined as incident clinical CAD [including MI], stroke, or CV death).

Results

A total of 330\u202f201 patients (median [IQR] age, 57 [40-74] years; 189\u202f107 female individuals [57%]) were included from the UK Biobank. Over the 10-year follow-up, 4454 individuals had an MI. The CAD PRS was significantly associated with the risk of MI in all age groups but had significantly stronger risk prediction at younger ages (age <50 years: hazard ratio [HR] per 1 SD of PRS, 1.72; 95% CI, 1.56-1.89; age 50-60 years: HR, 1.46; 95% CI, 1.38-1.53; age >60 years: HR, 1.42; 95% CI, 1.37-1.48; P for interaction <.001). In patients younger than 50 years, those with high PRS had a 3- to 4-fold increased associated risk of MI compared with those in the low PRS category. A significant interaction between CAD PRS and age was replicated in Biobank Japan. When CAD PRS testing was added to the clinical ASCVD risk score in individuals younger than 50 years, 591 of 4373 patients (20%) with borderline risk were risk stratified into intermediate risk, warranting initiation of statin therapy and 3198 of 7477 patients (20%) with both borderline or intermediate risk were stratified as low risk, thus not warranting therapy.

Conclusions and relevance

Results of this cohort study suggest that the predictive ability of a CAD PRS was greater in younger individuals and can be used to better identify patients with borderline and intermediate clinical risk who should initiate statin therapy.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1001/jamacardio.2022.4466; html:https://europepmc.org/articles/PMC9857431; doi:https://doi.org/10.1001/jamacardio.2022.4466" - }, { "id": "37101398", "doi": "https://doi.org/10.1002/ejhf.2868", @@ -23425,23 +23425,6 @@ "laySummary": "", "urls": "pdf:https://www.researchprotocols.org/2023/1/e42965/PDF; doi:https://doi.org/10.2196/42965; html:https://europepmc.org/articles/PMC9936366" }, - { - "id": "35103964", - "doi": "https://doi.org/10.1007/978-1-0716-2140-0_6", - "title": "Chromatin Immunoprecipitation Sequencing (ChIP-seq) Protocol for Small Amounts of Frozen Biobanked Cardiac Tissue.", - "authorString": "Pei J, van den Dungen NAM, Asselbergs FW, Mokry M, Harakalova M.", - "authorAffiliations": "", - "journalTitle": "Methods in molecular biology (Clifton, N.J.)", - "pubYear": "2022", - "date": "2022-01-01", - "isOpenAccess": "N", - "keywords": "Sequencing; Antibody; Promoters; Cardiac Tissues; Chromatin Immunoprecipitation; Enhancers; Small Biopsy", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Chromatin immunoprecipitation and sequencing (ChIP-seq) is a well-established method to study the epigenetic profile at the genome-wide scale, including histone modifications and DNA-protein interactions. It provides valuable insights to better understand disease mechanisms. Here we present an optimized ChIP-seq protocol suitable for human cardiac tissues, especially the frozen biobanked small biopsy samples.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1007/978-1-0716-2140-0_6" - }, { "id": "33328048", "doi": "https://doi.org/10.1016/s2589-7500(20)30218-1", @@ -23459,6 +23442,23 @@ "laySummary": "", "urls": "pdf:http://www.thelancet.com/article/S2589750020302181/pdf; doi:https://doi.org/10.1016/S2589-7500(20)30218-1; html:https://europepmc.org/articles/PMC8183333; pdf:https://europepmc.org/articles/PMC8183333?pdf=render; doi:https://doi.org/10.1016/s2589-7500(20)30218-1" }, + { + "id": "35103964", + "doi": "https://doi.org/10.1007/978-1-0716-2140-0_6", + "title": "Chromatin Immunoprecipitation Sequencing (ChIP-seq) Protocol for Small Amounts of Frozen Biobanked Cardiac Tissue.", + "authorString": "Pei J, van den Dungen NAM, Asselbergs FW, Mokry M, Harakalova M.", + "authorAffiliations": "", + "journalTitle": "Methods in molecular biology (Clifton, N.J.)", + "pubYear": "2022", + "date": "2022-01-01", + "isOpenAccess": "N", + "keywords": "Sequencing; Antibody; Promoters; Cardiac Tissues; Chromatin Immunoprecipitation; Enhancers; Small Biopsy", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Chromatin immunoprecipitation and sequencing (ChIP-seq) is a well-established method to study the epigenetic profile at the genome-wide scale, including histone modifications and DNA-protein interactions. It provides valuable insights to better understand disease mechanisms. Here we present an optimized ChIP-seq protocol suitable for human cardiac tissues, especially the frozen biobanked small biopsy samples.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1007/978-1-0716-2140-0_6" + }, { "id": "32929109", "doi": "https://doi.org/10.1038/s41598-020-72060-0", @@ -23527,23 +23527,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.jchf.2019.03.009" }, - { - "id": "37563721", - "doi": "https://doi.org/10.1186/s13063-023-07473-z", - "title": "Evaluation of interventions to prevent vasovagal reactions among whole blood donors: rationale and design of a large cluster randomised trial.", - "authorString": "McMahon A, Kaptoge S, Walker M, Mehenny S, Gilchrist PT, Sambrook J, Akhtar N, Sweeting M, Wood AM, Stirrups K, Chung R, Fahle S, Johnson E, Cullen D, Godfrey R, Duthie S, Allen L, Harvey P, Berkson M, Allen E, Watkins NA, Bradley JR, Kingston N, Miflin G, Armitage J, Roberts DJ, Danesh J, Di Angelantonio E.", - "authorAffiliations": "", - "journalTitle": "Trials", - "pubYear": "2023", - "date": "2023-08-10", - "isOpenAccess": "Y", - "keywords": "Cross-over; Blood donors; Blood Donation; Factorial Design; Vasovagal Reactions; Cluster Randomised Trial; Stepped-wedge", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Vasovagal reactions (VVRs) are the most common acute complications of blood donation. Responsible for substantial morbidity, they also reduce the likelihood of repeated donations and are disruptive and costly for blood services. Although blood establishments worldwide have adopted different strategies to prevent VVRs (including water loading and applied muscle tension [AMT]), robust evidence is limited. The Strategies to Improve Donor Experiences (STRIDES) trial aims to reliably assess the impact of four different interventions to prevent VVRs among blood donors.

Methods

STRIDES is a cluster-randomised cross-over/stepped-wedge factorial trial of four interventions to reduce VVRs involving about 1.4 million whole blood donors enrolled from all 73 blood donation sites (mobile teams and donor centres) of National Health Service Blood and Transplant (NHSBT) in England. Each site (\"cluster\") has been randomly allocated to receive one or more interventions during a 36-month period, using principles of cross-over, stepped-wedge and factorial trial design to assign the sequence of interventions. Each of the four interventions is compared to NHSBT's current practices: (i) 500-ml isotonic drink before donation (vs current 500-ml plain water); (ii) 3-min rest on donation chair after donation (vs current 2 min); (iii) new modified AMT (vs current practice of AMT); and (iv) psychosocial intervention using preparatory materials (vs current practice of nothing). The primary outcome is the number of in-session VVRs with loss of consciousness (i.e. episodes involving loss of consciousness of any duration, with or without additional complications). Secondary outcomes include all in-session VVRs (i.e. with and without loss of consciousness), all delayed VVRs (i.e. those occurring after leaving the venue) and any in-session non-VVR adverse events or reactions.

Discussion

The STRIDES trial should yield novel information about interventions, singly and in combination, for the prevention of VVRs, with the aim of generating policy-shaping evidence to help inform blood services to improve donor health, donor experience, and service efficiency.

Trial registration

ISRCTN: 10412338. Registration date: October 24, 2019.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1186/s13063-023-07473-z; html:https://europepmc.org/articles/PMC10413586; pdf:https://europepmc.org/articles/PMC10413586?pdf=render" - }, { "id": "35242820", "doi": "https://doi.org/10.3389/fcvm.2021.816985", @@ -23561,6 +23544,23 @@ "laySummary": "", "urls": "pdf:https://www.frontiersin.org/articles/10.3389/fcvm.2021.816985/pdf; doi:https://doi.org/10.3389/fcvm.2021.816985; html:https://europepmc.org/articles/PMC8886212; pdf:https://europepmc.org/articles/PMC8886212?pdf=render" }, + { + "id": "37563721", + "doi": "https://doi.org/10.1186/s13063-023-07473-z", + "title": "Evaluation of interventions to prevent vasovagal reactions among whole blood donors: rationale and design of a large cluster randomised trial.", + "authorString": "McMahon A, Kaptoge S, Walker M, Mehenny S, Gilchrist PT, Sambrook J, Akhtar N, Sweeting M, Wood AM, Stirrups K, Chung R, Fahle S, Johnson E, Cullen D, Godfrey R, Duthie S, Allen L, Harvey P, Berkson M, Allen E, Watkins NA, Bradley JR, Kingston N, Miflin G, Armitage J, Roberts DJ, Danesh J, Di Angelantonio E.", + "authorAffiliations": "", + "journalTitle": "Trials", + "pubYear": "2023", + "date": "2023-08-10", + "isOpenAccess": "Y", + "keywords": "Cross-over; Blood donors; Blood Donation; Factorial Design; Vasovagal Reactions; Cluster Randomised Trial; Stepped-wedge", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Vasovagal reactions (VVRs) are the most common acute complications of blood donation. Responsible for substantial morbidity, they also reduce the likelihood of repeated donations and are disruptive and costly for blood services. Although blood establishments worldwide have adopted different strategies to prevent VVRs (including water loading and applied muscle tension [AMT]), robust evidence is limited. The Strategies to Improve Donor Experiences (STRIDES) trial aims to reliably assess the impact of four different interventions to prevent VVRs among blood donors.

Methods

STRIDES is a cluster-randomised cross-over/stepped-wedge factorial trial of four interventions to reduce VVRs involving about 1.4 million whole blood donors enrolled from all 73 blood donation sites (mobile teams and donor centres) of National Health Service Blood and Transplant (NHSBT) in England. Each site (\"cluster\") has been randomly allocated to receive one or more interventions during a 36-month period, using principles of cross-over, stepped-wedge and factorial trial design to assign the sequence of interventions. Each of the four interventions is compared to NHSBT's current practices: (i) 500-ml isotonic drink before donation (vs current 500-ml plain water); (ii) 3-min rest on donation chair after donation (vs current 2 min); (iii) new modified AMT (vs current practice of AMT); and (iv) psychosocial intervention using preparatory materials (vs current practice of nothing). The primary outcome is the number of in-session VVRs with loss of consciousness (i.e. episodes involving loss of consciousness of any duration, with or without additional complications). Secondary outcomes include all in-session VVRs (i.e. with and without loss of consciousness), all delayed VVRs (i.e. those occurring after leaving the venue) and any in-session non-VVR adverse events or reactions.

Discussion

The STRIDES trial should yield novel information about interventions, singly and in combination, for the prevention of VVRs, with the aim of generating policy-shaping evidence to help inform blood services to improve donor health, donor experience, and service efficiency.

Trial registration

ISRCTN: 10412338. Registration date: October 24, 2019.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1186/s13063-023-07473-z; html:https://europepmc.org/articles/PMC10413586; pdf:https://europepmc.org/articles/PMC10413586?pdf=render" + }, { "id": "36243582", "doi": "https://doi.org/10.1016/j.injury.2022.09.052", @@ -23765,23 +23765,6 @@ "laySummary": "", "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/jdv.17450; doi:https://doi.org/10.1111/jdv.17450; html:https://europepmc.org/articles/PMC8447018; pdf:https://europepmc.org/articles/PMC8447018?pdf=render" }, - { - "id": "37884627", - "doi": "https://doi.org/10.1038/s41591-023-02608-w", - "title": "The value of standards for health datasets in artificial intelligence-based applications.", - "authorString": "Arora A, Alderman JE, Palmer J, Ganapathi S, Laws E, McCradden MD, Oakden-Rayner L, Pfohl SR, Ghassemi M, McKay F, Treanor D, Rostamzadeh N, Mateen B, Gath J, Adebajo AO, Kuku S, Matin R, Heller K, Sapey E, Sebire NJ, Cole-Lewis H, Calvert M, Denniston A, Liu X.", - "authorAffiliations": "", - "journalTitle": "Nature medicine", - "pubYear": "2023", - "date": "2023-10-26", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Artificial intelligence as a medical device is increasingly being applied to healthcare for diagnosis, risk stratification and resource allocation. However, a growing body of evidence has highlighted the risk of algorithmic bias, which may perpetuate existing health inequity. This problem arises in part because of systemic inequalities in dataset curation, unequal opportunity to participate in research and inequalities of access. This study aims to explore existing standards, frameworks and best practices for ensuring adequate data diversity in health datasets. Exploring the body of existing literature and expert views is an important step towards the development of consensus-based guidelines. The study comprises two parts: a systematic review of existing standards, frameworks and best practices for healthcare datasets; and a survey and thematic analysis of stakeholder views of bias, health equity and best practices for artificial intelligence as a medical device. We found that the need for dataset diversity was well described in literature, and experts generally favored the development of a robust set of guidelines, but there were mixed views about how these could be implemented practically. The outputs of this study will be used to inform the development of standards for transparency of data diversity in health datasets (the STANDING Together initiative).", - "laySummary": "", - "urls": "pdf:https://www.nature.com/articles/s41591-023-02608-w.pdf; doi:https://doi.org/10.1038/s41591-023-02608-w; html:https://europepmc.org/articles/PMC10667100; pdf:https://europepmc.org/articles/PMC10667100?pdf=render" - }, { "id": "34642218", "doi": "https://doi.org/10.1136/bcr-2021-243424", @@ -23799,6 +23782,23 @@ "laySummary": "", "urls": "pdf:https://casereports.bmj.com/content/bmjcr/14/10/e243424.full.pdf; doi:https://doi.org/10.1136/bcr-2021-243424; html:https://europepmc.org/articles/PMC8513217; pdf:https://europepmc.org/articles/PMC8513217?pdf=render" }, + { + "id": "37884627", + "doi": "https://doi.org/10.1038/s41591-023-02608-w", + "title": "The value of standards for health datasets in artificial intelligence-based applications.", + "authorString": "Arora A, Alderman JE, Palmer J, Ganapathi S, Laws E, McCradden MD, Oakden-Rayner L, Pfohl SR, Ghassemi M, McKay F, Treanor D, Rostamzadeh N, Mateen B, Gath J, Adebajo AO, Kuku S, Matin R, Heller K, Sapey E, Sebire NJ, Cole-Lewis H, Calvert M, Denniston A, Liu X.", + "authorAffiliations": "", + "journalTitle": "Nature medicine", + "pubYear": "2023", + "date": "2023-10-26", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Artificial intelligence as a medical device is increasingly being applied to healthcare for diagnosis, risk stratification and resource allocation. However, a growing body of evidence has highlighted the risk of algorithmic bias, which may perpetuate existing health inequity. This problem arises in part because of systemic inequalities in dataset curation, unequal opportunity to participate in research and inequalities of access. This study aims to explore existing standards, frameworks and best practices for ensuring adequate data diversity in health datasets. Exploring the body of existing literature and expert views is an important step towards the development of consensus-based guidelines. The study comprises two parts: a systematic review of existing standards, frameworks and best practices for healthcare datasets; and a survey and thematic analysis of stakeholder views of bias, health equity and best practices for artificial intelligence as a medical device. We found that the need for dataset diversity was well described in literature, and experts generally favored the development of a robust set of guidelines, but there were mixed views about how these could be implemented practically. The outputs of this study will be used to inform the development of standards for transparency of data diversity in health datasets (the STANDING Together initiative).", + "laySummary": "", + "urls": "pdf:https://www.nature.com/articles/s41591-023-02608-w.pdf; doi:https://doi.org/10.1038/s41591-023-02608-w; html:https://europepmc.org/articles/PMC10667100; pdf:https://europepmc.org/articles/PMC10667100?pdf=render" + }, { "id": "34143303", "doi": "https://doi.org/10.1007/s00787-021-01817-3", @@ -23833,23 +23833,6 @@ "laySummary": "\"Been and Sheikh\u2019s editorial about COVID-19, outlines the importance of two natural experiments: a- how different countries responded to the pandemic and its effects and b- impact of improvements in air quality on human and planetary health.\"", "urls": "doi:https://doi.org/10.7189/jogh.10.010104; doi:https://doi.org/10.7189/jogh.10.010104; html:https://europepmc.org/articles/PMC7179980; pdf:https://europepmc.org/articles/PMC7179980?pdf=render" }, - { - "id": "35048949", - "doi": "https://doi.org/10.1093/eurjpc/zwac008", - "title": "Light to moderate coffee consumption is associated with lower risk of death: a UK Biobank study.", - "authorString": "Simon J, Fung K, Raisi-Estabragh Z, Aung N, Khanji MY, Kolossv\u00e1ry M, Merkely B, Munroe PB, Harvey NC, Piechnik SK, Neubauer S, Petersen SE, Maurovich-Horvat P.", - "authorAffiliations": "", - "journalTitle": "European journal of preventive cardiology", - "pubYear": "2022", - "date": "2022-05-01", - "isOpenAccess": "N", - "keywords": "Cardiac Magnetic Resonance; Cardiovascular Health; Coffee Consumption", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Aims

To study the association of daily coffee consumption with all-cause and cardiovascular (CV) mortality and major CV outcomes. In a subgroup of participants who underwent cardiovascular magnetic resonance (CMR) imaging, we evaluated the association between regular coffee intake and cardiac structure and function.

Methods and results

UK Biobank participants without clinically manifested heart disease at the time of recruitment were included. Regular coffee intake was categorized into three groups: zero, light-to-moderate (0.5-3 cups/day), and high (>3 cups/day). In the multivariate analysis, we adjusted for the main CV risk factors. We included 468\u00a0629 individuals (56.2\u2009\u00b1\u20098.1\u2009years, 44.2% male), of whom 22.1% did not consume coffee regularly, 58.4% had 0.5-3 cups per day, and 19.5% had >3 cups per day. Compared to non-coffee drinkers, light-to-moderate (0.5-3 cups per day) coffee drinking was associated with lower risk of all-cause mortality [multivariate hazard ratio (HR)\u2009=\u20090.88, 95% confidence interval (CI): 0.83-0.92; P\u2009<\u20090.001] and CV mortality (multivariate HR\u2009=\u20090.83, 95% CI: 0.74-0.94; P\u2009=\u20090.006), and incident stroke (multivariate HR\u2009=\u20090.79, 95% CI: 0.63-0.99 P\u2009=\u20090.037) after a median follow-up of 11\u2009years. CMR data were available in 30\u00a0650 participants. Both light-to-moderate and high coffee consuming categories were associated with dose-dependent increased left and right ventricular end-diastolic, end-systolic and stroke volumes, and greater left ventricular mass.

Conclusion

Coffee consumption of up to three cups per day was associated with favourable CV outcomes. Regular coffee consumption was also associated with a likely healthy pattern of CMR metrics in keeping with the reverse of age-related cardiac alterations.", - "laySummary": "", - "urls": "pdf:https://academic.oup.com/eurjpc/article-pdf/29/6/982/43589594/zwac008.pdf; doi:https://doi.org/10.1093/eurjpc/zwac008" - }, { "id": "34306597", "doi": "https://doi.org/10.1155/2021/6663884", @@ -23867,6 +23850,23 @@ "laySummary": "", "urls": "pdf:https://downloads.hindawi.com/journals/jhe/2021/6663884.pdf; doi:https://doi.org/10.1155/2021/6663884; html:https://europepmc.org/articles/PMC8285182; pdf:https://europepmc.org/articles/PMC8285182?pdf=render" }, + { + "id": "35048949", + "doi": "https://doi.org/10.1093/eurjpc/zwac008", + "title": "Light to moderate coffee consumption is associated with lower risk of death: a UK Biobank study.", + "authorString": "Simon J, Fung K, Raisi-Estabragh Z, Aung N, Khanji MY, Kolossv\u00e1ry M, Merkely B, Munroe PB, Harvey NC, Piechnik SK, Neubauer S, Petersen SE, Maurovich-Horvat P.", + "authorAffiliations": "", + "journalTitle": "European journal of preventive cardiology", + "pubYear": "2022", + "date": "2022-05-01", + "isOpenAccess": "N", + "keywords": "Cardiac Magnetic Resonance; Cardiovascular Health; Coffee Consumption", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Aims

To study the association of daily coffee consumption with all-cause and cardiovascular (CV) mortality and major CV outcomes. In a subgroup of participants who underwent cardiovascular magnetic resonance (CMR) imaging, we evaluated the association between regular coffee intake and cardiac structure and function.

Methods and results

UK Biobank participants without clinically manifested heart disease at the time of recruitment were included. Regular coffee intake was categorized into three groups: zero, light-to-moderate (0.5-3 cups/day), and high (>3 cups/day). In the multivariate analysis, we adjusted for the main CV risk factors. We included 468\u00a0629 individuals (56.2\u2009\u00b1\u20098.1\u2009years, 44.2% male), of whom 22.1% did not consume coffee regularly, 58.4% had 0.5-3 cups per day, and 19.5% had >3 cups per day. Compared to non-coffee drinkers, light-to-moderate (0.5-3 cups per day) coffee drinking was associated with lower risk of all-cause mortality [multivariate hazard ratio (HR)\u2009=\u20090.88, 95% confidence interval (CI): 0.83-0.92; P\u2009<\u20090.001] and CV mortality (multivariate HR\u2009=\u20090.83, 95% CI: 0.74-0.94; P\u2009=\u20090.006), and incident stroke (multivariate HR\u2009=\u20090.79, 95% CI: 0.63-0.99 P\u2009=\u20090.037) after a median follow-up of 11\u2009years. CMR data were available in 30\u00a0650 participants. Both light-to-moderate and high coffee consuming categories were associated with dose-dependent increased left and right ventricular end-diastolic, end-systolic and stroke volumes, and greater left ventricular mass.

Conclusion

Coffee consumption of up to three cups per day was associated with favourable CV outcomes. Regular coffee consumption was also associated with a likely healthy pattern of CMR metrics in keeping with the reverse of age-related cardiac alterations.", + "laySummary": "", + "urls": "pdf:https://academic.oup.com/eurjpc/article-pdf/29/6/982/43589594/zwac008.pdf; doi:https://doi.org/10.1093/eurjpc/zwac008" + }, { "id": "37408046", "doi": "https://doi.org/10.1186/s40545-023-00590-9", @@ -23884,23 +23884,6 @@ "laySummary": "", "urls": "pdf:https://joppp.biomedcentral.com/counter/pdf/10.1186/s40545-023-00590-9; doi:https://doi.org/10.1186/s40545-023-00590-9; html:https://europepmc.org/articles/PMC10320864; pdf:https://europepmc.org/articles/PMC10320864?pdf=render" }, - { - "id": "38279797", - "doi": "https://doi.org/10.1089/neu.2023.0465", - "title": "The Australian Traumatic Brain Injury Initiative: Systematic Review of the Effect of Acute Interventions on Outcome for People With Moderate-Severe Traumatic Brain Injury.", - "authorString": "Keeves J, Gadowski A, McKimmie A, Bagg MK, Antonic-Baker A, Hicks AJ, Clarke N, Brown A, McNamara R, Reeder S, Roman C, Jeffcote T, Romero L, Hill R, Ponsford JL, Lannin NA, O'Brien TJ, Cameron PA, Rushworth N, Fitzgerald M, Gabbe BJ, Cooper DJ.", - "authorAffiliations": "", - "journalTitle": "Journal of neurotrauma", - "pubYear": "2024", - "date": "2024-04-08", - "isOpenAccess": "N", - "keywords": "Common Data Elements; Brain Injuries, Traumatic; Outcome Assessment, Health Care; Systematic Review [Publication Type]; Emergency Medical Services, Critical Care, Early Medical Intervention", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "The Australian Traumatic Brain Injury Initiative (AUS-TBI) is developing a data resource to enable improved outcome prediction for people with moderate-severe TBI (msTBI) across Australia. Fundamental to this resource is the collaboratively designed data dictionary. This systematic review and consultation aimed to identify acute interventions with potential to modify clinical outcomes for people after msTBI, for inclusion in a data dictionary. Standardized searches were implemented across bibliographic databases from inception through April 2022. English-language reports of randomized controlled trials (RCTs) evaluating any association between any acute intervention and clinical outcome in at least 100 patients with msTBI, were included. A predefined algorithm was used to assign a value to each observed association. Consultation with AUS-TBI clinicians and researchers formed the consensus process for interventions to be included in a single data dictionary. Searches retrieved 14,455 records, of which 124 full-length RCTs were screened, with 35 studies included. These studies evaluated 26 unique acute interventions across 21 unique clinical outcomes. Only 4 interventions were considered to have medium modifying value for any outcome from the review, with an additional 8 interventions agreed upon through the consensus process. The interventions with medium value were tranexamic acid and phenytoin, which had a positive effect on an outcome; and decompressive craniectomy surgery and hypothermia, which negatively affected outcomes. From the systematic review and consensus process, 12 interventions were identified as potential modifiers to be included in the AUS-TBI national data resource.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1089/neu.2023.0465" - }, { "id": "37190768", "doi": "https://doi.org/10.1017/s2045796023000276", @@ -23918,6 +23901,23 @@ "laySummary": "", "urls": "pdf:https://www.cambridge.org/core/services/aop-cambridge-core/content/view/A60E6D761449A937DCE08F3A075B236D/S2045796023000276a.pdf/div-class-title-the-mental-health-of-all-children-in-contact-with-social-services-a-population-wide-record-linkage-study-in-northern-ireland-div.pdf; doi:https://doi.org/10.1017/S2045796023000276; html:https://europepmc.org/articles/PMC10227534; pdf:https://europepmc.org/articles/PMC10227534?pdf=render" }, + { + "id": "38279797", + "doi": "https://doi.org/10.1089/neu.2023.0465", + "title": "The Australian Traumatic Brain Injury Initiative: Systematic Review of the Effect of Acute Interventions on Outcome for People With Moderate-Severe Traumatic Brain Injury.", + "authorString": "Keeves J, Gadowski A, McKimmie A, Bagg MK, Antonic-Baker A, Hicks AJ, Clarke N, Brown A, McNamara R, Reeder S, Roman C, Jeffcote T, Romero L, Hill R, Ponsford JL, Lannin NA, O'Brien TJ, Cameron PA, Rushworth N, Fitzgerald M, Gabbe BJ, Cooper DJ.", + "authorAffiliations": "", + "journalTitle": "Journal of neurotrauma", + "pubYear": "2024", + "date": "2024-04-08", + "isOpenAccess": "N", + "keywords": "Common Data Elements; Brain Injuries, Traumatic; Outcome Assessment, Health Care; Systematic Review [Publication Type]; Emergency Medical Services, Critical Care, Early Medical Intervention", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "The Australian Traumatic Brain Injury Initiative (AUS-TBI) is developing a data resource to enable improved outcome prediction for people with moderate-severe TBI (msTBI) across Australia. Fundamental to this resource is the collaboratively designed data dictionary. This systematic review and consultation aimed to identify acute interventions with potential to modify clinical outcomes for people after msTBI, for inclusion in a data dictionary. Standardized searches were implemented across bibliographic databases from inception through April 2022. English-language reports of randomized controlled trials (RCTs) evaluating any association between any acute intervention and clinical outcome in at least 100 patients with msTBI, were included. A predefined algorithm was used to assign a value to each observed association. Consultation with AUS-TBI clinicians and researchers formed the consensus process for interventions to be included in a single data dictionary. Searches retrieved 14,455 records, of which 124 full-length RCTs were screened, with 35 studies included. These studies evaluated 26 unique acute interventions across 21 unique clinical outcomes. Only 4 interventions were considered to have medium modifying value for any outcome from the review, with an additional 8 interventions agreed upon through the consensus process. The interventions with medium value were tranexamic acid and phenytoin, which had a positive effect on an outcome; and decompressive craniectomy surgery and hypothermia, which negatively affected outcomes. From the systematic review and consensus process, 12 interventions were identified as potential modifiers to be included in the AUS-TBI national data resource.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1089/neu.2023.0465" + }, { "id": "36198485", "doi": "https://doi.org/10.1136/jech-2021-217986", @@ -24037,23 +24037,6 @@ "laySummary": "", "urls": "html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9796319; doi:https://doi.org/10.1111/1747-0080.12746; html:https://europepmc.org/articles/PMC9796319; pdf:https://europepmc.org/articles/PMC9796319?pdf=render" }, - { - "id": "34849869", - "doi": "https://doi.org/10.1093/gigascience/giab076", - "title": "An overview of the National COVID-19 Chest Imaging Database: data quality and cohort analysis.", - "authorString": "Cushnan D, Bennett O, Berka R, Bertolli O, Chopra A, Dorgham S, Favaro A, Ganepola T, Halling-Brown M, Imreh G, Jacob J, Jefferson E, Lemarchand F, Schofield D, Wyatt JC, NCCID Collaborative.", - "authorAffiliations": "", - "journalTitle": "GigaScience", - "pubYear": "2021", - "date": "2021-11-01", - "isOpenAccess": "Y", - "keywords": "Medical imaging; Machine Learning; Thoracic Imaging; Covid-19; Sars-cov2", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

The National COVID-19 Chest Imaging Database (NCCID) is a centralized database containing mainly chest X-rays and computed tomography scans from patients across the UK. The objective of the initiative is to support a better understanding of the coronavirus SARS-CoV-2 disease (COVID-19) and the development of machine learning technologies that will improve care for patients hospitalized with a severe COVID-19 infection. This article introduces the training dataset, including a snapshot analysis covering the completeness of clinical data, and availability of image data for the various use-cases (diagnosis, prognosis, longitudinal risk). An additional cohort analysis measures how well the NCCID represents the wider COVID-19-affected UK population in terms of geographic, demographic, and temporal coverage.

Findings

The NCCID offers high-quality DICOM images acquired across a variety of imaging machinery; multiple time points including historical images are available for a subset of patients. This volume and variety make the database well suited to development of diagnostic/prognostic models for COVID-associated respiratory conditions. Historical images and clinical data may aid long-term risk stratification, particularly as availability of comorbidity data increases through linkage to other resources. The cohort analysis revealed good alignment to general UK COVID-19 statistics for some categories, e.g., sex, whilst identifying areas for improvements to data collection methods, particularly geographic coverage.

Conclusion

The NCCID is a growing resource that provides researchers with a large, high-quality database that can be leveraged both to support the response to the COVID-19 pandemic and as a test bed for building clinically viable medical imaging models.", - "laySummary": "", - "urls": "pdf:https://academic.oup.com/gigascience/article-pdf/10/11/giab076/41395024/giab076.pdf; doi:https://doi.org/10.1093/gigascience/giab076; html:https://europepmc.org/articles/PMC8633457; pdf:https://europepmc.org/articles/PMC8633457?pdf=render" - }, { "id": "33560181", "doi": "https://doi.org/10.1177/0272989x21994035", @@ -24071,6 +24054,23 @@ "laySummary": "", "urls": "pdf:https://journals.sagepub.com/doi/pdf/10.1177/0272989X21994035; doi:https://doi.org/10.1177/0272989X21994035" }, + { + "id": "34849869", + "doi": "https://doi.org/10.1093/gigascience/giab076", + "title": "An overview of the National COVID-19 Chest Imaging Database: data quality and cohort analysis.", + "authorString": "Cushnan D, Bennett O, Berka R, Bertolli O, Chopra A, Dorgham S, Favaro A, Ganepola T, Halling-Brown M, Imreh G, Jacob J, Jefferson E, Lemarchand F, Schofield D, Wyatt JC, NCCID Collaborative.", + "authorAffiliations": "", + "journalTitle": "GigaScience", + "pubYear": "2021", + "date": "2021-11-01", + "isOpenAccess": "Y", + "keywords": "Medical imaging; Machine Learning; Thoracic Imaging; Covid-19; Sars-cov2", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

The National COVID-19 Chest Imaging Database (NCCID) is a centralized database containing mainly chest X-rays and computed tomography scans from patients across the UK. The objective of the initiative is to support a better understanding of the coronavirus SARS-CoV-2 disease (COVID-19) and the development of machine learning technologies that will improve care for patients hospitalized with a severe COVID-19 infection. This article introduces the training dataset, including a snapshot analysis covering the completeness of clinical data, and availability of image data for the various use-cases (diagnosis, prognosis, longitudinal risk). An additional cohort analysis measures how well the NCCID represents the wider COVID-19-affected UK population in terms of geographic, demographic, and temporal coverage.

Findings

The NCCID offers high-quality DICOM images acquired across a variety of imaging machinery; multiple time points including historical images are available for a subset of patients. This volume and variety make the database well suited to development of diagnostic/prognostic models for COVID-associated respiratory conditions. Historical images and clinical data may aid long-term risk stratification, particularly as availability of comorbidity data increases through linkage to other resources. The cohort analysis revealed good alignment to general UK COVID-19 statistics for some categories, e.g., sex, whilst identifying areas for improvements to data collection methods, particularly geographic coverage.

Conclusion

The NCCID is a growing resource that provides researchers with a large, high-quality database that can be leveraged both to support the response to the COVID-19 pandemic and as a test bed for building clinically viable medical imaging models.", + "laySummary": "", + "urls": "pdf:https://academic.oup.com/gigascience/article-pdf/10/11/giab076/41395024/giab076.pdf; doi:https://doi.org/10.1093/gigascience/giab076; html:https://europepmc.org/articles/PMC8633457; pdf:https://europepmc.org/articles/PMC8633457?pdf=render" + }, { "id": "35028631", "doi": "https://doi.org/10.1016/s2666-7568(21)00281-6", @@ -24088,23 +24088,6 @@ "laySummary": "", "urls": "pdf:http://www.thelancet.com/article/S2666756821002816/pdf; doi:https://doi.org/10.1016/S2666-7568(21)00281-6; html:https://europepmc.org/articles/PMC8732286" }, - { - "id": "37217302", - "doi": "https://doi.org/10.1136/emermed-2022-212827", - "title": "External validation of triage tools for adults with suspected COVID-19 in a middle-income setting: an observational cohort study.", - "authorString": "Marincowitz C, Sbaffi L, Hasan M, Hodkinson P, McAlpine D, Fuller G, Goodacre S, Bath PA, Bath PA, Omer Y, Wallis LA.", - "authorAffiliations": "", - "journalTitle": "Emergency medicine journal : EMJ", - "pubYear": "2023", - "date": "2023-05-22", - "isOpenAccess": "Y", - "keywords": "risk management; Triage; Covid-19", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Tools proposed to triage ED acuity in suspected COVID-19 were derived and validated in higher income settings during early waves of the pandemic. We estimated the accuracy of seven risk-stratification tools recommended to predict severe illness in the Western Cape, South Africa.

Methods

An observational cohort study using routinely collected data from EDs across the Western Cape, from 27 August 2020 to 11 March 2022, was conducted to assess the performance of the PRIEST (Pandemic Respiratory Infection Emergency System Triage) tool, NEWS2 (National Early Warning Score, version 2), TEWS (Triage Early Warning Score), the WHO algorithm, CRB-65, Quick COVID-19 Severity Index and PMEWS (Pandemic Medical Early Warning Score) in suspected COVID-19. The primary outcome was intubation or non-invasive ventilation, death or intensive care unit admission at 30 days.

Results

Of the 446\u2009084 patients, 15\u2009397 (3.45%, 95% CI 34% to 35.1%) experienced the primary outcome. Clinical decision-making for inpatient admission achieved a sensitivity of 0.77 (95% CI 0.76 to 0.78), specificity of 0.88 (95% CI 0.87 to 0.88) and the negative predictive value (NPV) of 0.99 (95% CI 0.99 to 0.99). NEWS2, PMEWS and PRIEST scores achieved good estimated discrimination (C-statistic 0.79 to 0.82) and identified patients at risk of adverse outcomes at recommended cut-offs with moderate sensitivity (>0.8) and specificity ranging from 0.41 to 0.64. Use of the tools at recommended thresholds would have more than doubled admissions, with only a 0.01% reduction in false negative triage.

Conclusion

No risk score outperformed existing clinical decision-making in determining the need for inpatient admission based on prediction of the primary outcome in this setting. Use of the PRIEST score at a threshold of one point higher than the previously recommended best approximated existing clinical accuracy.", - "laySummary": "", - "urls": "pdf:https://emj.bmj.com/content/emermed/early/2023/05/22/emermed-2022-212827.full.pdf; doi:https://doi.org/10.1136/emermed-2022-212827; html:https://europepmc.org/articles/PMC10359554; pdf:https://europepmc.org/articles/PMC10359554?pdf=render" - }, { "id": "33289226", "doi": "https://doi.org/10.1111/ans.16426", @@ -24139,6 +24122,23 @@ "laySummary": "", "urls": "pdf:https://ijpds.org/article/download/1134/2643; doi:https://doi.org/10.23889/ijpds.v4i2.1134; html:https://europepmc.org/articles/PMC8142954; pdf:https://europepmc.org/articles/PMC8142954?pdf=render" }, + { + "id": "37217302", + "doi": "https://doi.org/10.1136/emermed-2022-212827", + "title": "External validation of triage tools for adults with suspected COVID-19 in a middle-income setting: an observational cohort study.", + "authorString": "Marincowitz C, Sbaffi L, Hasan M, Hodkinson P, McAlpine D, Fuller G, Goodacre S, Bath PA, Bath PA, Omer Y, Wallis LA.", + "authorAffiliations": "", + "journalTitle": "Emergency medicine journal : EMJ", + "pubYear": "2023", + "date": "2023-05-22", + "isOpenAccess": "Y", + "keywords": "risk management; Triage; Covid-19", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Tools proposed to triage ED acuity in suspected COVID-19 were derived and validated in higher income settings during early waves of the pandemic. We estimated the accuracy of seven risk-stratification tools recommended to predict severe illness in the Western Cape, South Africa.

Methods

An observational cohort study using routinely collected data from EDs across the Western Cape, from 27 August 2020 to 11 March 2022, was conducted to assess the performance of the PRIEST (Pandemic Respiratory Infection Emergency System Triage) tool, NEWS2 (National Early Warning Score, version 2), TEWS (Triage Early Warning Score), the WHO algorithm, CRB-65, Quick COVID-19 Severity Index and PMEWS (Pandemic Medical Early Warning Score) in suspected COVID-19. The primary outcome was intubation or non-invasive ventilation, death or intensive care unit admission at 30 days.

Results

Of the 446\u2009084 patients, 15\u2009397 (3.45%, 95% CI 34% to 35.1%) experienced the primary outcome. Clinical decision-making for inpatient admission achieved a sensitivity of 0.77 (95% CI 0.76 to 0.78), specificity of 0.88 (95% CI 0.87 to 0.88) and the negative predictive value (NPV) of 0.99 (95% CI 0.99 to 0.99). NEWS2, PMEWS and PRIEST scores achieved good estimated discrimination (C-statistic 0.79 to 0.82) and identified patients at risk of adverse outcomes at recommended cut-offs with moderate sensitivity (>0.8) and specificity ranging from 0.41 to 0.64. Use of the tools at recommended thresholds would have more than doubled admissions, with only a 0.01% reduction in false negative triage.

Conclusion

No risk score outperformed existing clinical decision-making in determining the need for inpatient admission based on prediction of the primary outcome in this setting. Use of the PRIEST score at a threshold of one point higher than the previously recommended best approximated existing clinical accuracy.", + "laySummary": "", + "urls": "pdf:https://emj.bmj.com/content/emermed/early/2023/05/22/emermed-2022-212827.full.pdf; doi:https://doi.org/10.1136/emermed-2022-212827; html:https://europepmc.org/articles/PMC10359554; pdf:https://europepmc.org/articles/PMC10359554?pdf=render" + }, { "id": "38746859", "doi": "https://doi.org/10.1183/23120541.00430-2023", @@ -24241,23 +24241,6 @@ "laySummary": "", "urls": "html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9691043; doi:https://doi.org/10.1016/S0140-6736(22)02235-8; html:https://europepmc.org/articles/PMC9691043; pdf:https://europepmc.org/articles/PMC9691043?pdf=render" }, - { - "id": "38345865", - "doi": "https://doi.org/10.1113/jp284597", - "title": "Reduced plakoglobin increases the risk of sodium current defects and atrial conduction abnormalities in response to androgenic anabolic steroid abuse.", - "authorString": "Sommerfeld LC, Holmes AP, Yu TY, O'Shea C, Kavanagh DM, Pike JM, Wright T, Syeda F, Aljehani A, Kew T, Cardoso VR, Kabir SN, Hepburn C, Menon PR, Broadway-Stringer S, O'Reilly M, Witten A, Fortmueller L, Lutz S, Kulle A, Gkoutos GV, Pavlovic D, Arlt W, Lavery GG, Steeds R, Gehmlich K, Stoll M, Kirchhof P, Fabritz L.", - "authorAffiliations": "", - "journalTitle": "The Journal of physiology", - "pubYear": "2024", - "date": "2024-02-12", - "isOpenAccess": "N", - "keywords": "Testosterone; Conduction velocity; Nav1.5; Desmosome; Arrhythmogenic Right Ventricular Cardiomyopathy; Cardiac Atria", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Androgenic anabolic steroids (AAS) are commonly abused by young men. Male sex and increased AAS levels are associated with earlier and more severe manifestation of common cardiac conditions, such as atrial fibrillation, and rare ones, such as arrhythmogenic right ventricular cardiomyopathy (ARVC). Clinical observations suggest a potential atrial involvement in ARVC. Arrhythmogenic right ventricular cardiomyopathy is caused by desmosomal gene defects, including reduced plakoglobin expression. Here, we analysed clinical records from 146 ARVC patients to identify that ARVC is more common in males than females. Patients with ARVC also had an increased incidence of atrial arrhythmias and P\u00a0wave changes. To study desmosomal vulnerability and the effects of AAS on the atria, young adult male mice, heterozygously deficient for plakoglobin (Plako+/- ), and wild type (WT) littermates were chronically exposed to 5\u03b1-dihydrotestosterone (DHT) or placebo. The DHT increased atrial expression of pro-hypertrophic, fibrotic and inflammatory transcripts. In mice with reduced plakoglobin, DHT exaggerated P\u00a0wave abnormalities, atrial conduction slowing, sodium current depletion, action potential amplitude reduction and the fall in action potential depolarization rate. Super-resolution microscopy revealed a decrease in NaV 1.5\u00a0membrane clustering in Plako+/- atrial cardiomyocytes after DHT exposure. In summary, AAS combined with plakoglobin deficiency cause pathological atrial electrical remodelling in young male hearts. Male sex is likely to increase the risk of atrial arrhythmia, particularly in those with desmosomal gene variants. This risk is likely to be exaggerated further by AAS use. KEY POINTS: Androgenic male sex hormones, such as testosterone,\u00a0might increase the risk of atrial fibrillation in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC), which is often caused by desmosomal gene defects (e.g. reduced plakoglobin expression). In this study, we observed a significantly higher proportion of males who had ARVC compared with females, and atrial arrhythmias and P\u00a0wave changes represented a common observation in advanced ARVC stages. In mice with reduced plakoglobin expression, chronic administration of 5\u03b1-dihydrotestosterone led to P\u00a0wave abnormalities, atrial conduction slowing, sodium current depletion and a decrease in membrane-localized NaV 1.5 clusters. 5\u03b1-Dihydrotestosterone, therefore, represents a stimulus aggravating the pro-arrhythmic phenotype in carriers of desmosomal mutations and can affect atrial electrical function.", - "laySummary": "", - "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1113/JP284597; doi:https://doi.org/10.1113/JP284597" - }, { "id": "33728815", "doi": "https://doi.org/10.1002/art.41709", @@ -24275,6 +24258,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1002/art.41709; doi:https://doi.org/10.1002/art.41709" }, + { + "id": "38345865", + "doi": "https://doi.org/10.1113/jp284597", + "title": "Reduced plakoglobin increases the risk of sodium current defects and atrial conduction abnormalities in response to androgenic anabolic steroid abuse.", + "authorString": "Sommerfeld LC, Holmes AP, Yu TY, O'Shea C, Kavanagh DM, Pike JM, Wright T, Syeda F, Aljehani A, Kew T, Cardoso VR, Kabir SN, Hepburn C, Menon PR, Broadway-Stringer S, O'Reilly M, Witten A, Fortmueller L, Lutz S, Kulle A, Gkoutos GV, Pavlovic D, Arlt W, Lavery GG, Steeds R, Gehmlich K, Stoll M, Kirchhof P, Fabritz L.", + "authorAffiliations": "", + "journalTitle": "The Journal of physiology", + "pubYear": "2024", + "date": "2024-02-12", + "isOpenAccess": "N", + "keywords": "Testosterone; Conduction velocity; Nav1.5; Desmosome; Arrhythmogenic Right Ventricular Cardiomyopathy; Cardiac Atria", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Androgenic anabolic steroids (AAS) are commonly abused by young men. Male sex and increased AAS levels are associated with earlier and more severe manifestation of common cardiac conditions, such as atrial fibrillation, and rare ones, such as arrhythmogenic right ventricular cardiomyopathy (ARVC). Clinical observations suggest a potential atrial involvement in ARVC. Arrhythmogenic right ventricular cardiomyopathy is caused by desmosomal gene defects, including reduced plakoglobin expression. Here, we analysed clinical records from 146 ARVC patients to identify that ARVC is more common in males than females. Patients with ARVC also had an increased incidence of atrial arrhythmias and P\u00a0wave changes. To study desmosomal vulnerability and the effects of AAS on the atria, young adult male mice, heterozygously deficient for plakoglobin (Plako+/- ), and wild type (WT) littermates were chronically exposed to 5\u03b1-dihydrotestosterone (DHT) or placebo. The DHT increased atrial expression of pro-hypertrophic, fibrotic and inflammatory transcripts. In mice with reduced plakoglobin, DHT exaggerated P\u00a0wave abnormalities, atrial conduction slowing, sodium current depletion, action potential amplitude reduction and the fall in action potential depolarization rate. Super-resolution microscopy revealed a decrease in NaV 1.5\u00a0membrane clustering in Plako+/- atrial cardiomyocytes after DHT exposure. In summary, AAS combined with plakoglobin deficiency cause pathological atrial electrical remodelling in young male hearts. Male sex is likely to increase the risk of atrial arrhythmia, particularly in those with desmosomal gene variants. This risk is likely to be exaggerated further by AAS use. KEY POINTS: Androgenic male sex hormones, such as testosterone,\u00a0might increase the risk of atrial fibrillation in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC), which is often caused by desmosomal gene defects (e.g. reduced plakoglobin expression). In this study, we observed a significantly higher proportion of males who had ARVC compared with females, and atrial arrhythmias and P\u00a0wave changes represented a common observation in advanced ARVC stages. In mice with reduced plakoglobin expression, chronic administration of 5\u03b1-dihydrotestosterone led to P\u00a0wave abnormalities, atrial conduction slowing, sodium current depletion and a decrease in membrane-localized NaV 1.5 clusters. 5\u03b1-Dihydrotestosterone, therefore, represents a stimulus aggravating the pro-arrhythmic phenotype in carriers of desmosomal mutations and can affect atrial electrical function.", + "laySummary": "", + "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1113/JP284597; doi:https://doi.org/10.1113/JP284597" + }, { "id": "34948912", "doi": "https://doi.org/10.3390/ijerph182413304", @@ -24360,23 +24360,6 @@ "laySummary": "", "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/13/1/e064364.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-064364; html:https://europepmc.org/articles/PMC9872487; pdf:https://europepmc.org/articles/PMC9872487?pdf=render" }, - { - "id": "36828608", - "doi": "https://doi.org/10.1016/s2589-7500(22)00249-7", - "title": "The role of patient-reported outcome measures in trials of artificial intelligence health technologies: a systematic evaluation of ClinicalTrials.gov records (1997-2022).", - "authorString": "Pearce FJ, Cruz Rivera S, Liu X, Manna E, Denniston AK, Calvert MJ.", - "authorAffiliations": "", - "journalTitle": "The Lancet. Digital health", - "pubYear": "2023", - "date": "2023-03-01", - "isOpenAccess": "N", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "The extent to which patient-reported outcome measures (PROMs) are used in clinical trials for artificial intelligence (AI) technologies is unknown. In this systematic evaluation, we aim to establish how PROMs are being used to assess AI health technologies. We searched ClinicalTrials.gov for interventional trials registered from inception to Sept 20, 2022, and included trials that tested an AI health technology. We excluded observational studies, patient registries, and expanded access reports. We extracted data regarding the form, function, and intended use population of the AI health technology, in addition to the PROMs used and whether PROMs were incorporated as an input or output in the AI model. The search identified 2958 trials, of which 627 were included in the analysis. 152 (24%) of the included trials used one or more PROM, visual analogue scale, patient-reported experience measure, or usability measure as a trial endpoint. The type of AI health technologies used by these trials included AI-enabled smart devices, clinical decision support systems, and chatbots. The number of clinical trials of AI health technologies registered on ClinicalTrials.gov and the proportion of trials that used PROMs increased from registry inception to 2022. The most common clinical areas AI health technologies were designed for were digestive system health for non-PROM trials and musculoskeletal health (followed by mental and behavioural health) for PROM trials, with PROMs commonly used in clinical areas for which assessment of health-related quality of life and symptom burden is particularly important. Additionally, AI-enabled smart devices were the most common applications tested in trials that used at least one PROM. 24 trials tested AI models that captured PROM data as an input for the AI model. PROM use in clinical trials of AI health technologies falls behind PROM use in all clinical trials. Trial records having inadequate detail regarding the PROMs used or the type of AI health technology tested was a limitation of this systematic evaluation and might have contributed to inaccuracies in the data synthesised. Overall, the use of PROMs in the function and assessment of AI health technologies is not only possible, but is a powerful way of showing that, even in the most technologically advanced health-care systems, patients' perspectives remain central.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1016/s2589-7500(22)00249-7; doi:https://doi.org/10.1016/S2589-7500(22)00249-7" - }, { "id": "35144240", "doi": "https://doi.org/10.2196/32543", @@ -24394,6 +24377,23 @@ "laySummary": "", "urls": "pdf:https://publichealth.jmir.org/2022/5/e32543/PDF; doi:https://doi.org/10.2196/32543; html:https://europepmc.org/articles/PMC9150729" }, + { + "id": "36828608", + "doi": "https://doi.org/10.1016/s2589-7500(22)00249-7", + "title": "The role of patient-reported outcome measures in trials of artificial intelligence health technologies: a systematic evaluation of ClinicalTrials.gov records (1997-2022).", + "authorString": "Pearce FJ, Cruz Rivera S, Liu X, Manna E, Denniston AK, Calvert MJ.", + "authorAffiliations": "", + "journalTitle": "The Lancet. Digital health", + "pubYear": "2023", + "date": "2023-03-01", + "isOpenAccess": "N", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "The extent to which patient-reported outcome measures (PROMs) are used in clinical trials for artificial intelligence (AI) technologies is unknown. In this systematic evaluation, we aim to establish how PROMs are being used to assess AI health technologies. We searched ClinicalTrials.gov for interventional trials registered from inception to Sept 20, 2022, and included trials that tested an AI health technology. We excluded observational studies, patient registries, and expanded access reports. We extracted data regarding the form, function, and intended use population of the AI health technology, in addition to the PROMs used and whether PROMs were incorporated as an input or output in the AI model. The search identified 2958 trials, of which 627 were included in the analysis. 152 (24%) of the included trials used one or more PROM, visual analogue scale, patient-reported experience measure, or usability measure as a trial endpoint. The type of AI health technologies used by these trials included AI-enabled smart devices, clinical decision support systems, and chatbots. The number of clinical trials of AI health technologies registered on ClinicalTrials.gov and the proportion of trials that used PROMs increased from registry inception to 2022. The most common clinical areas AI health technologies were designed for were digestive system health for non-PROM trials and musculoskeletal health (followed by mental and behavioural health) for PROM trials, with PROMs commonly used in clinical areas for which assessment of health-related quality of life and symptom burden is particularly important. Additionally, AI-enabled smart devices were the most common applications tested in trials that used at least one PROM. 24 trials tested AI models that captured PROM data as an input for the AI model. PROM use in clinical trials of AI health technologies falls behind PROM use in all clinical trials. Trial records having inadequate detail regarding the PROMs used or the type of AI health technology tested was a limitation of this systematic evaluation and might have contributed to inaccuracies in the data synthesised. Overall, the use of PROMs in the function and assessment of AI health technologies is not only possible, but is a powerful way of showing that, even in the most technologically advanced health-care systems, patients' perspectives remain central.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1016/s2589-7500(22)00249-7; doi:https://doi.org/10.1016/S2589-7500(22)00249-7" + }, { "id": "36854461", "doi": "https://doi.org/10.1136/bmj-2022-073149", @@ -24445,23 +24445,6 @@ "laySummary": "", "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/11/1/e042945.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-042945; html:https://europepmc.org/articles/PMC7843315; pdf:https://europepmc.org/articles/PMC7843315?pdf=render" }, - { - "id": "37813531", - "doi": "https://doi.org/10.1136/bmjopen-2023-073162", - "title": "Detection and evaluation of signals associated with exposure to individual and combination of medications in pregnancy: a signal detection study protocol.", - "authorString": "Subramanian A, Lee SI, Hemali Sudasinghe SPB, Wambua S, Phillips K, Singh M, Azcoaga-Lorenzo A, Cockburn N, Wang J, Fagbamigbe A, Usman M, Damase-Michel C, Yau C, Kent L, McCowan C, OReilly D, Santorelli G, Hope H, Kennedy J, Mhereeg M, Abel KM, Eastwood KA, Black M, Loane M, Moss N, Brophy S, Brocklehurst P, Dolk H, Nelson-Piercy C, Nirantharakumar K, MuM-PreDiCT Group.", - "authorAffiliations": "", - "journalTitle": "BMJ open", - "pubYear": "2023", - "date": "2023-10-09", - "isOpenAccess": "Y", - "keywords": "Obstetrics; epidemiology; Maternal Medicine", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Introduction

Considering the high prevalence of polypharmacy in pregnant women and the knowledge gap in the risk-benefit safety profile of their often-complex treatment plan, more research is needed to optimise prescribing. In this study, we aim to detect adverse and protective effect signals of exposure to individual and pairwise combinations of medications during pregnancy.

Methods and analysis

Using a range of real-world data sources from the UK, we aim to conduct a pharmacovigilance study to assess the safety of medications prescribed during the preconception period (3\u2009months prior to conception) and first trimester of pregnancy. Women aged between 15 and 49 years with a record of pregnancy within the Clinical Practice Research Datalink (CPRD) Pregnancy Register, the Welsh Secure Anonymised Information Linkage (SAIL), the Scottish Morbidity Record (SMR) data sets and the Northern Ireland Maternity System (NIMATS) will be included. A series of case control studies will be conducted to estimate measures of disproportionality, detecting signals of association between a range of pregnancy outcomes and exposure to individual and combinations of medications. A multidisciplinary expert team will be invited to a signal detection workshop. By employing a structured framework, signals will be transparently assessed by each member of the team using a questionnaire appraising the signals on aspects of temporality, selection, time and measurement-related biases and confounding by underlying disease or comedications. Through group discussion, the expert team will reach consensus on each of the medication exposure-outcome signal, thereby excluding spurious signals, leaving signals suggestive of causal associations for further evaluation.

Ethics and dissemination

Ethical approval has been obtained from the Independent Scientific Advisory Committee, SAIL Information Governance Review Panel, University of St. Andrews Teaching and Research Ethics Committee and Office for Research Ethics Committees Northern Ireland (ORECNI) for access and use of CPRD, SAIL, SMR and NIMATS data, respectively.", - "laySummary": "", - "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/13/10/e073162.full.pdf; doi:https://doi.org/10.1136/bmjopen-2023-073162; html:https://europepmc.org/articles/PMC10565241; pdf:https://europepmc.org/articles/PMC10565241?pdf=render" - }, { "id": "34734970", "doi": "https://doi.org/10.1001/jamaophthalmol.2021.4601", @@ -24480,21 +24463,21 @@ "urls": "pdf:https://jamanetwork.com/journals/jamaophthalmology/articlepdf/2785704/jamaophthalmology_kuan_2021_oi_210068_1639510445.31311.pdf; doi:https://doi.org/10.1001/jamaophthalmol.2021.4601; html:https://europepmc.org/articles/PMC8569599" }, { - "id": "35869974", - "doi": "https://doi.org/10.1093/ndt/gfac224", - "title": "Care processes and outcomes of deprivation across the clinical course of kidney disease: findings from a high-income country with universal healthcare.", - "authorString": "Sawhney S, Blakeman T, Blana D, Boyers D, Fluck N, Nath M, Methven S, Rzewuska M, Black C.", + "id": "37813531", + "doi": "https://doi.org/10.1136/bmjopen-2023-073162", + "title": "Detection and evaluation of signals associated with exposure to individual and combination of medications in pregnancy: a signal detection study protocol.", + "authorString": "Subramanian A, Lee SI, Hemali Sudasinghe SPB, Wambua S, Phillips K, Singh M, Azcoaga-Lorenzo A, Cockburn N, Wang J, Fagbamigbe A, Usman M, Damase-Michel C, Yau C, Kent L, McCowan C, OReilly D, Santorelli G, Hope H, Kennedy J, Mhereeg M, Abel KM, Eastwood KA, Black M, Loane M, Moss N, Brophy S, Brocklehurst P, Dolk H, Nelson-Piercy C, Nirantharakumar K, MuM-PreDiCT Group.", "authorAffiliations": "", - "journalTitle": "Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association", + "journalTitle": "BMJ open", "pubYear": "2023", - "date": "2023-05-01", + "date": "2023-10-09", "isOpenAccess": "Y", - "keywords": "Prognosis; epidemiology; Health Inequalities; Ckd; Aki; Care Processes", + "keywords": "Obstetrics; epidemiology; Maternal Medicine", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Background

No single study contrasts the extent and consequences of inequity of kidney care across the clinical course of kidney disease.

Methods

This population study of Grampian (UK) followed incident presentations of acute kidney injury (AKI) and incident estimated glomerular filtration rate (eGFR) thresholds of <60, <45 and <30\u00a0mL/min/1.73\u00a0m2 in separate cohorts (2011-2021). The key exposure was area-level deprivation (lowest quintile of the Scottish Index of Multiple Deprivation). Outcomes were care processes (monitoring, prescribing, appointments, unscheduled care), long-term mortality and kidney failure. Modelling involved multivariable logistic regression, negative binomial regression and cause-specific Cox models with and without adjustment of comorbidities.

Results

There were 41\u00a0313, 51\u00a0190, 32\u00a0171 and 17\u00a0781 new presentations of AKI and eGFR thresholds <60, <45 and <30 \u00a0mL/min/1.73\u00a0m2. A total of 6.1-7.8% of the population was from deprived areas and (versus all others) presented on average 5\u00a0years younger, with more diabetes and pulmonary and liver disease. Those from deprived areas were more likely to present initially in hospital, less likely to receive community monitoring, less likely to attend appointments and more likely to have an unplanned emergency department or hospital admission episode. Deprivation had the greatest association with long-term kidney failure at the eGFR <60\u00a0mL/min/1.73\u00a0m2 threshold {adjusted hazard ratio [HR] 1.48 [95% confidence interval (CI) 1.17-1.87]} and this association decreased with advancing disease severity [HR 1.09 (95% CI 0.93-1.28) at eGFR <30\u00a0mL/min/1.73\u00a0m2), with a similar pattern for mortality. Across all analyses the most detrimental associations of deprivation were an eGFR threshold <60\u00a0mL/min/1.73\u00a0m2, AKI, males and those <65\u00a0years of age.

Conclusions

Even in a high-income country with universal healthcare, serious and consistent inequities in kidney care exist. The poorer care and outcomes with area-level deprivation were greater earlier in the disease course.", + "abstract": "

Introduction

Considering the high prevalence of polypharmacy in pregnant women and the knowledge gap in the risk-benefit safety profile of their often-complex treatment plan, more research is needed to optimise prescribing. In this study, we aim to detect adverse and protective effect signals of exposure to individual and pairwise combinations of medications during pregnancy.

Methods and analysis

Using a range of real-world data sources from the UK, we aim to conduct a pharmacovigilance study to assess the safety of medications prescribed during the preconception period (3\u2009months prior to conception) and first trimester of pregnancy. Women aged between 15 and 49 years with a record of pregnancy within the Clinical Practice Research Datalink (CPRD) Pregnancy Register, the Welsh Secure Anonymised Information Linkage (SAIL), the Scottish Morbidity Record (SMR) data sets and the Northern Ireland Maternity System (NIMATS) will be included. A series of case control studies will be conducted to estimate measures of disproportionality, detecting signals of association between a range of pregnancy outcomes and exposure to individual and combinations of medications. A multidisciplinary expert team will be invited to a signal detection workshop. By employing a structured framework, signals will be transparently assessed by each member of the team using a questionnaire appraising the signals on aspects of temporality, selection, time and measurement-related biases and confounding by underlying disease or comedications. Through group discussion, the expert team will reach consensus on each of the medication exposure-outcome signal, thereby excluding spurious signals, leaving signals suggestive of causal associations for further evaluation.

Ethics and dissemination

Ethical approval has been obtained from the Independent Scientific Advisory Committee, SAIL Information Governance Review Panel, University of St. Andrews Teaching and Research Ethics Committee and Office for Research Ethics Committees Northern Ireland (ORECNI) for access and use of CPRD, SAIL, SMR and NIMATS data, respectively.", "laySummary": "", - "urls": "pdf:https://academic.oup.com/ndt/advance-article-pdf/doi/10.1093/ndt/gfac224/45505736/gfac224.pdf; doi:https://doi.org/10.1093/ndt/gfac224; html:https://europepmc.org/articles/PMC10157789; pdf:https://europepmc.org/articles/PMC10157789?pdf=render" + "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/13/10/e073162.full.pdf; doi:https://doi.org/10.1136/bmjopen-2023-073162; html:https://europepmc.org/articles/PMC10565241; pdf:https://europepmc.org/articles/PMC10565241?pdf=render" }, { "id": "31361079", @@ -24514,21 +24497,38 @@ "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/1742-6723.13361; doi:https://doi.org/10.1111/1742-6723.13361" }, { - "id": "35435219", - "doi": "https://doi.org/10.1093/ehjqcco/qcac016", - "title": "Temporal trends in disease-specific causes of cardiovascular mortality amongst patients with cancer in the USA between 1999 and 2019.", - "authorString": "Raisi-Estabragh Z, Kobo O, Freeman P, Petersen SE, Kolman L, Miller RJH, Roguin A, Van Spall HGC, Vuong J, Yang EH, Mamas MA.", + "id": "32119825", + "doi": "https://doi.org/10.1016/s2214-109x(20)30074-7", + "title": "Feasibility of controlling COVID-19 outbreaks by isolation of cases and contacts.", + "authorString": "Hellewell J, Abbott S, Gimma A, Bosse NI, Jarvis CI, Russell TW, Munday JD, Kucharski AJ, Edmunds WJ, Centre for the Mathematical Modelling of Infectious Diseases COVID-19 Working Group, Funk S, Eggo RM.", "authorAffiliations": "", - "journalTitle": "European heart journal. Quality of care & clinical outcomes", - "pubYear": "2022", - "date": "2022-12-01", + "journalTitle": "The Lancet. Global health", + "pubYear": "2020", + "date": "2020-02-28", "isOpenAccess": "Y", - "keywords": "Cancer; Cardiovascular disease; epidemiology; Cardiovascular Mortality; Mortality Trends; Cardio-oncology", + "keywords": "", + "nationalPriorities": "Improving Public Health", + "healthCategories": "COVID-19", + "abstract": "

Background

Isolation of cases and contact tracing is used to control outbreaks of infectious diseases, and has been used for coronavirus disease 2019 (COVID-19). Whether this strategy will achieve control depends on characteristics of both the pathogen and the response. Here we use a mathematical model to assess if isolation and contact tracing are able to control onwards transmission from imported cases of COVID-19.

Methods

We developed a stochastic transmission model, parameterised to the COVID-19 outbreak. We used the model to quantify the potential effectiveness of contact tracing and isolation of cases at controlling a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-like pathogen. We considered scenarios that varied in the number of initial cases, the basic reproduction number (R0), the delay from symptom onset to isolation, the probability that contacts were traced, the proportion of transmission that occurred before symptom onset, and the proportion of subclinical infections. We assumed isolation prevented all further transmission in the model. Outbreaks were deemed controlled if transmission ended within 12 weeks or before 5000 cases in total. We measured the success of controlling outbreaks using isolation and contact tracing, and quantified the weekly maximum number of cases traced to measure feasibility of public health effort.

Findings

Simulated outbreaks starting with five initial cases, an R0 of 1\u00b75, and 0% transmission before symptom onset could be controlled even with low contact tracing probability; however, the probability of controlling an outbreak decreased with the number of initial cases, when R0 was 2\u00b75 or 3\u00b75 and with more transmission before symptom onset. Across different initial numbers of cases, the majority of scenarios with an R0 of 1\u00b75 were controllable with less than 50% of contacts successfully traced. To control the majority of outbreaks, for R0 of 2\u00b75 more than 70% of contacts had to be traced, and for an R0 of 3\u00b75 more than 90% of contacts had to be traced. The delay between symptom onset and isolation had the largest role in determining whether an outbreak was controllable when R0 was 1\u00b75. For R0 values of 2\u00b75 or 3\u00b75, if there were 40 initial cases, contact tracing and isolation were only potentially feasible when less than 1% of transmission occurred before symptom onset.

Interpretation

In most scenarios, highly effective contact tracing and case isolation is enough to control a new outbreak of COVID-19 within 3 months. The probability of control decreases with long delays from symptom onset to isolation, fewer cases ascertained by contact tracing, and increasing transmission before symptoms. This model can be modified to reflect updated transmission characteristics and more specific definitions of outbreak control to assess the potential success of local response efforts.

Funding

Wellcome Trust, Global Challenges Research Fund, and Health Data Research UK.", + "laySummary": "", + "urls": "pdf:http://www.thelancet.com/article/S2214109X20300747/pdf; doi:https://doi.org/10.1016/S2214-109X(20)30074-7; html:https://europepmc.org/articles/PMC7097845; pdf:https://europepmc.org/articles/PMC7097845?pdf=render" + }, + { + "id": "35869974", + "doi": "https://doi.org/10.1093/ndt/gfac224", + "title": "Care processes and outcomes of deprivation across the clinical course of kidney disease: findings from a high-income country with universal healthcare.", + "authorString": "Sawhney S, Blakeman T, Blana D, Boyers D, Fluck N, Nath M, Methven S, Rzewuska M, Black C.", + "authorAffiliations": "", + "journalTitle": "Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association", + "pubYear": "2023", + "date": "2023-05-01", + "isOpenAccess": "Y", + "keywords": "Prognosis; epidemiology; Health Inequalities; Ckd; Aki; Care Processes", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Aims

We report disease-specific cardiovascular causes of mortality among cancer patients in the USA between 1999 and 2019, considering temporal trends by age, sex, and cancer site.

Methods and results

We used the Multiple Cause of Death database, accessed through the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research resource. We included 629\u00a0308 decedents with cardiovascular disease (CVD) recorded as the primary cause of death and active malignancy listed as a contributing cause of death. We created disease-specific CVD categories and grouped cancers by site. We calculated the proportion of CVD deaths attributed to each disease category stratified by sex, age, and cancer site. We also examined disease-specific temporal trends by cancer site. Ischaemic heart disease (IHD) was the most common cardiovascular cause of death across all cancer types (55.6%), being more common in men (59.8%), older ages, and in those with lung (67.8%) and prostate (58.3%) cancers. Cerebrovascular disease (12.9%) and hypertensive diseases (7.6%) were other common causes of death. The proportion of deaths due to heart failure was greatest in haematological (7.7%) and breast (6.3%) cancers. There was a decreasing temporal trend in the proportion of cardiovascular deaths attributed to IHD across all cancer types. The proportion of deaths due to hypertensive diseases showed the greatest percentage increase, with the largest change in breast cancer patients (+191.1%).

Conclusion

We demonstrate differential cardiovascular mortality risk by cancer site and demographics, providing insight into the evolving healthcare needs of this growing high-cardiovascular risk population.", + "abstract": "

Background

No single study contrasts the extent and consequences of inequity of kidney care across the clinical course of kidney disease.

Methods

This population study of Grampian (UK) followed incident presentations of acute kidney injury (AKI) and incident estimated glomerular filtration rate (eGFR) thresholds of <60, <45 and <30\u00a0mL/min/1.73\u00a0m2 in separate cohorts (2011-2021). The key exposure was area-level deprivation (lowest quintile of the Scottish Index of Multiple Deprivation). Outcomes were care processes (monitoring, prescribing, appointments, unscheduled care), long-term mortality and kidney failure. Modelling involved multivariable logistic regression, negative binomial regression and cause-specific Cox models with and without adjustment of comorbidities.

Results

There were 41\u00a0313, 51\u00a0190, 32\u00a0171 and 17\u00a0781 new presentations of AKI and eGFR thresholds <60, <45 and <30 \u00a0mL/min/1.73\u00a0m2. A total of 6.1-7.8% of the population was from deprived areas and (versus all others) presented on average 5\u00a0years younger, with more diabetes and pulmonary and liver disease. Those from deprived areas were more likely to present initially in hospital, less likely to receive community monitoring, less likely to attend appointments and more likely to have an unplanned emergency department or hospital admission episode. Deprivation had the greatest association with long-term kidney failure at the eGFR <60\u00a0mL/min/1.73\u00a0m2 threshold {adjusted hazard ratio [HR] 1.48 [95% confidence interval (CI) 1.17-1.87]} and this association decreased with advancing disease severity [HR 1.09 (95% CI 0.93-1.28) at eGFR <30\u00a0mL/min/1.73\u00a0m2), with a similar pattern for mortality. Across all analyses the most detrimental associations of deprivation were an eGFR threshold <60\u00a0mL/min/1.73\u00a0m2, AKI, males and those <65\u00a0years of age.

Conclusions

Even in a high-income country with universal healthcare, serious and consistent inequities in kidney care exist. The poorer care and outcomes with area-level deprivation were greater earlier in the disease course.", "laySummary": "", - "urls": "pdf:https://academic.oup.com/ehjqcco/advance-article-pdf/doi/10.1093/ehjqcco/qcac016/43887262/qcac016.pdf; doi:https://doi.org/10.1093/ehjqcco/qcac016; html:https://europepmc.org/articles/PMC9745666; pdf:https://europepmc.org/articles/PMC9745666?pdf=render" + "urls": "pdf:https://academic.oup.com/ndt/advance-article-pdf/doi/10.1093/ndt/gfac224/45505736/gfac224.pdf; doi:https://doi.org/10.1093/ndt/gfac224; html:https://europepmc.org/articles/PMC10157789; pdf:https://europepmc.org/articles/PMC10157789?pdf=render" }, { "id": "34127232", @@ -24547,23 +24547,6 @@ "laySummary": "", "urls": "pdf:http://arxiv.org/pdf/2010.01165; doi:https://doi.org/10.1016/j.artmed.2021.102083" }, - { - "id": "32119825", - "doi": "https://doi.org/10.1016/s2214-109x(20)30074-7", - "title": "Feasibility of controlling COVID-19 outbreaks by isolation of cases and contacts.", - "authorString": "Hellewell J, Abbott S, Gimma A, Bosse NI, Jarvis CI, Russell TW, Munday JD, Kucharski AJ, Edmunds WJ, Centre for the Mathematical Modelling of Infectious Diseases COVID-19 Working Group, Funk S, Eggo RM.", - "authorAffiliations": "", - "journalTitle": "The Lancet. Global health", - "pubYear": "2020", - "date": "2020-02-28", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "Improving Public Health", - "healthCategories": "COVID-19", - "abstract": "

Background

Isolation of cases and contact tracing is used to control outbreaks of infectious diseases, and has been used for coronavirus disease 2019 (COVID-19). Whether this strategy will achieve control depends on characteristics of both the pathogen and the response. Here we use a mathematical model to assess if isolation and contact tracing are able to control onwards transmission from imported cases of COVID-19.

Methods

We developed a stochastic transmission model, parameterised to the COVID-19 outbreak. We used the model to quantify the potential effectiveness of contact tracing and isolation of cases at controlling a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-like pathogen. We considered scenarios that varied in the number of initial cases, the basic reproduction number (R0), the delay from symptom onset to isolation, the probability that contacts were traced, the proportion of transmission that occurred before symptom onset, and the proportion of subclinical infections. We assumed isolation prevented all further transmission in the model. Outbreaks were deemed controlled if transmission ended within 12 weeks or before 5000 cases in total. We measured the success of controlling outbreaks using isolation and contact tracing, and quantified the weekly maximum number of cases traced to measure feasibility of public health effort.

Findings

Simulated outbreaks starting with five initial cases, an R0 of 1\u00b75, and 0% transmission before symptom onset could be controlled even with low contact tracing probability; however, the probability of controlling an outbreak decreased with the number of initial cases, when R0 was 2\u00b75 or 3\u00b75 and with more transmission before symptom onset. Across different initial numbers of cases, the majority of scenarios with an R0 of 1\u00b75 were controllable with less than 50% of contacts successfully traced. To control the majority of outbreaks, for R0 of 2\u00b75 more than 70% of contacts had to be traced, and for an R0 of 3\u00b75 more than 90% of contacts had to be traced. The delay between symptom onset and isolation had the largest role in determining whether an outbreak was controllable when R0 was 1\u00b75. For R0 values of 2\u00b75 or 3\u00b75, if there were 40 initial cases, contact tracing and isolation were only potentially feasible when less than 1% of transmission occurred before symptom onset.

Interpretation

In most scenarios, highly effective contact tracing and case isolation is enough to control a new outbreak of COVID-19 within 3 months. The probability of control decreases with long delays from symptom onset to isolation, fewer cases ascertained by contact tracing, and increasing transmission before symptoms. This model can be modified to reflect updated transmission characteristics and more specific definitions of outbreak control to assess the potential success of local response efforts.

Funding

Wellcome Trust, Global Challenges Research Fund, and Health Data Research UK.", - "laySummary": "", - "urls": "pdf:http://www.thelancet.com/article/S2214109X20300747/pdf; doi:https://doi.org/10.1016/S2214-109X(20)30074-7; html:https://europepmc.org/articles/PMC7097845; pdf:https://europepmc.org/articles/PMC7097845?pdf=render" - }, { "id": "33749694", "doi": "https://doi.org/", @@ -24581,6 +24564,23 @@ "laySummary": "", "urls": "" }, + { + "id": "35435219", + "doi": "https://doi.org/10.1093/ehjqcco/qcac016", + "title": "Temporal trends in disease-specific causes of cardiovascular mortality amongst patients with cancer in the USA between 1999 and 2019.", + "authorString": "Raisi-Estabragh Z, Kobo O, Freeman P, Petersen SE, Kolman L, Miller RJH, Roguin A, Van Spall HGC, Vuong J, Yang EH, Mamas MA.", + "authorAffiliations": "", + "journalTitle": "European heart journal. Quality of care & clinical outcomes", + "pubYear": "2022", + "date": "2022-12-01", + "isOpenAccess": "Y", + "keywords": "Cancer; Cardiovascular disease; epidemiology; Cardiovascular Mortality; Mortality Trends; Cardio-oncology", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Aims

We report disease-specific cardiovascular causes of mortality among cancer patients in the USA between 1999 and 2019, considering temporal trends by age, sex, and cancer site.

Methods and results

We used the Multiple Cause of Death database, accessed through the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research resource. We included 629\u00a0308 decedents with cardiovascular disease (CVD) recorded as the primary cause of death and active malignancy listed as a contributing cause of death. We created disease-specific CVD categories and grouped cancers by site. We calculated the proportion of CVD deaths attributed to each disease category stratified by sex, age, and cancer site. We also examined disease-specific temporal trends by cancer site. Ischaemic heart disease (IHD) was the most common cardiovascular cause of death across all cancer types (55.6%), being more common in men (59.8%), older ages, and in those with lung (67.8%) and prostate (58.3%) cancers. Cerebrovascular disease (12.9%) and hypertensive diseases (7.6%) were other common causes of death. The proportion of deaths due to heart failure was greatest in haematological (7.7%) and breast (6.3%) cancers. There was a decreasing temporal trend in the proportion of cardiovascular deaths attributed to IHD across all cancer types. The proportion of deaths due to hypertensive diseases showed the greatest percentage increase, with the largest change in breast cancer patients (+191.1%).

Conclusion

We demonstrate differential cardiovascular mortality risk by cancer site and demographics, providing insight into the evolving healthcare needs of this growing high-cardiovascular risk population.", + "laySummary": "", + "urls": "pdf:https://academic.oup.com/ehjqcco/advance-article-pdf/doi/10.1093/ehjqcco/qcac016/43887262/qcac016.pdf; doi:https://doi.org/10.1093/ehjqcco/qcac016; html:https://europepmc.org/articles/PMC9745666; pdf:https://europepmc.org/articles/PMC9745666?pdf=render" + }, { "id": "30972781", "doi": "https://doi.org/10.1111/apt.15232", @@ -24870,23 +24870,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.jacc.2023.05.065" }, - { - "id": "38170504", - "doi": "https://doi.org/10.1001/jamacardio.2023.4994", - "title": "Genetic Associations of Circulating Cardiovascular Proteins With Gestational Hypertension and Preeclampsia.", - "authorString": "Schuermans A, Truong B, Ardissino M, Bhukar R, Slob EAW, Nakao T, Dron JS, Small AM, Cho SMJ, Yu Z, Hornsby W, Antoine T, Lannery K, Postupaka D, Gray KJ, Yan Q, Butterworth AS, Burgess S, Wood MJ, Scott NS, Harrington CM, Sarma AA, Lau ES, Roh JD, Januzzi JL, Natarajan P, Honigberg MC.", - "authorAffiliations": "", - "journalTitle": "JAMA cardiology", - "pubYear": "2024", - "date": "2024-03-01", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Importance

Hypertensive disorders of pregnancy (HDPs), including gestational hypertension and preeclampsia, are important contributors to maternal morbidity and mortality worldwide. In addition, women with HDPs face an elevated long-term risk of cardiovascular disease.

Objective

To identify proteins in the circulation associated with HDPs.

Design, setting, and participants

Two-sample mendelian randomization (MR) tested the associations of genetic instruments for cardiovascular disease-related proteins with gestational hypertension and preeclampsia. In downstream analyses, a systematic review of observational data was conducted to evaluate the identified proteins' dynamics across gestation in hypertensive vs normotensive pregnancies, and phenome-wide MR analyses were performed to identify potential non-HDP-related effects associated with the prioritized proteins. Genetic association data for cardiovascular disease-related proteins were obtained from the Systematic and Combined Analysis of Olink Proteins (SCALLOP) consortium. Genetic association data for the HDPs were obtained from recent European-ancestry genome-wide association study meta-analyses for gestational hypertension and preeclampsia. Study data were analyzed October 2022 to October 2023.

Exposures

Genetic instruments for 90 candidate proteins implicated in cardiovascular diseases, constructed using cis-protein quantitative trait loci (cis-pQTLs).

Main outcomes and measures

Gestational hypertension and preeclampsia.

Results

Genetic association data for cardiovascular disease-related proteins were obtained from 21\u202f758 participants from the SCALLOP consortium. Genetic association data for the HDPs were obtained from 393\u202f238 female individuals (8636 cases and 384\u202f602 controls) for gestational hypertension and 606\u202f903 female individuals (16\u202f032 cases and 590\u202f871 controls) for preeclampsia. Seventy-five of 90 proteins (83.3%) had at least 1 valid cis-pQTL. Of those, 10 proteins (13.3%) were significantly associated with HDPs. Four were robust to sensitivity analyses for gestational hypertension (cluster of differentiation 40, eosinophil cationic protein [ECP], galectin 3, N-terminal pro-brain natriuretic peptide [NT-proBNP]), and 2 were robust for preeclampsia (cystatin B, heat shock protein 27 [HSP27]). Consistent with the MR findings, observational data revealed that lower NT-proBNP (0.76- to 0.88-fold difference vs no HDPs) and higher HSP27 (2.40-fold difference vs no HDPs) levels during the first trimester of pregnancy were associated with increased risk of HDPs, as were higher levels of ECP (1.60-fold difference vs no HDPs). Phenome-wide MR analyses identified 37 unique non-HDP-related protein-disease associations, suggesting potential on-target effects associated with interventions lowering HDP risk through the identified proteins.

Conclusions and relevance

Study findings suggest genetic associations of 4 cardiovascular disease-related proteins with gestational hypertension and 2 associated with preeclampsia. Future studies are required to test the efficacy of targeting the corresponding pathways to reduce HDP risk.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1001/jamacardio.2023.4994; html:https://europepmc.org/articles/PMC10765315; pdf:https://europepmc.org/articles/PMC10765315?pdf=render" - }, { "id": "34772649", "doi": "https://doi.org/10.1016/s2589-7500(21)00252-1", @@ -24904,6 +24887,23 @@ "laySummary": "", "urls": "pdf:http://www.thelancet.com/article/S2589750021002521/pdf; doi:https://doi.org/10.1016/S2589-7500(21)00252-1" }, + { + "id": "38170504", + "doi": "https://doi.org/10.1001/jamacardio.2023.4994", + "title": "Genetic Associations of Circulating Cardiovascular Proteins With Gestational Hypertension and Preeclampsia.", + "authorString": "Schuermans A, Truong B, Ardissino M, Bhukar R, Slob EAW, Nakao T, Dron JS, Small AM, Cho SMJ, Yu Z, Hornsby W, Antoine T, Lannery K, Postupaka D, Gray KJ, Yan Q, Butterworth AS, Burgess S, Wood MJ, Scott NS, Harrington CM, Sarma AA, Lau ES, Roh JD, Januzzi JL, Natarajan P, Honigberg MC.", + "authorAffiliations": "", + "journalTitle": "JAMA cardiology", + "pubYear": "2024", + "date": "2024-03-01", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Importance

Hypertensive disorders of pregnancy (HDPs), including gestational hypertension and preeclampsia, are important contributors to maternal morbidity and mortality worldwide. In addition, women with HDPs face an elevated long-term risk of cardiovascular disease.

Objective

To identify proteins in the circulation associated with HDPs.

Design, setting, and participants

Two-sample mendelian randomization (MR) tested the associations of genetic instruments for cardiovascular disease-related proteins with gestational hypertension and preeclampsia. In downstream analyses, a systematic review of observational data was conducted to evaluate the identified proteins' dynamics across gestation in hypertensive vs normotensive pregnancies, and phenome-wide MR analyses were performed to identify potential non-HDP-related effects associated with the prioritized proteins. Genetic association data for cardiovascular disease-related proteins were obtained from the Systematic and Combined Analysis of Olink Proteins (SCALLOP) consortium. Genetic association data for the HDPs were obtained from recent European-ancestry genome-wide association study meta-analyses for gestational hypertension and preeclampsia. Study data were analyzed October 2022 to October 2023.

Exposures

Genetic instruments for 90 candidate proteins implicated in cardiovascular diseases, constructed using cis-protein quantitative trait loci (cis-pQTLs).

Main outcomes and measures

Gestational hypertension and preeclampsia.

Results

Genetic association data for cardiovascular disease-related proteins were obtained from 21\u202f758 participants from the SCALLOP consortium. Genetic association data for the HDPs were obtained from 393\u202f238 female individuals (8636 cases and 384\u202f602 controls) for gestational hypertension and 606\u202f903 female individuals (16\u202f032 cases and 590\u202f871 controls) for preeclampsia. Seventy-five of 90 proteins (83.3%) had at least 1 valid cis-pQTL. Of those, 10 proteins (13.3%) were significantly associated with HDPs. Four were robust to sensitivity analyses for gestational hypertension (cluster of differentiation 40, eosinophil cationic protein [ECP], galectin 3, N-terminal pro-brain natriuretic peptide [NT-proBNP]), and 2 were robust for preeclampsia (cystatin B, heat shock protein 27 [HSP27]). Consistent with the MR findings, observational data revealed that lower NT-proBNP (0.76- to 0.88-fold difference vs no HDPs) and higher HSP27 (2.40-fold difference vs no HDPs) levels during the first trimester of pregnancy were associated with increased risk of HDPs, as were higher levels of ECP (1.60-fold difference vs no HDPs). Phenome-wide MR analyses identified 37 unique non-HDP-related protein-disease associations, suggesting potential on-target effects associated with interventions lowering HDP risk through the identified proteins.

Conclusions and relevance

Study findings suggest genetic associations of 4 cardiovascular disease-related proteins with gestational hypertension and 2 associated with preeclampsia. Future studies are required to test the efficacy of targeting the corresponding pathways to reduce HDP risk.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1001/jamacardio.2023.4994; html:https://europepmc.org/articles/PMC10765315; pdf:https://europepmc.org/articles/PMC10765315?pdf=render" + }, { "id": "37477360", "doi": "https://doi.org/10.1097/ypg.0000000000000349", @@ -25074,23 +25074,6 @@ "laySummary": "", "urls": "pdf:https://bjgpopen.org/content/bjgpoa/4/5/bjgpopen20X101109.full.pdf; doi:https://doi.org/10.3399/bjgpopen20X101109; html:https://europepmc.org/articles/PMC7880177; pdf:https://europepmc.org/articles/PMC7880177?pdf=render" }, - { - "id": "36082669", - "doi": "https://doi.org/10.1161/hypertensionaha.122.19354", - "title": "Determining the Relationship Between Blood Pressure, Kidney Function, and Chronic Kidney Disease: Insights From Genetic Epidemiology.", - "authorString": "Staplin N, Herrington WG, Murgia F, Ibrahim M, Bull KR, Judge PK, Ng SYA, Turner M, Zhu D, Emberson J, Landray MJ, Baigent C, Haynes R, Hopewell JC.", - "authorAffiliations": "", - "journalTitle": "Hypertension (Dallas, Tex. : 1979)", - "pubYear": "2022", - "date": "2022-09-09", - "isOpenAccess": "Y", - "keywords": "Blood pressure; Chronic; creatinine; epidemiology; Renal Insufficiency", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

It is well established that decreased kidney function can increase blood pressure (BP), but it is unproven whether moderately elevated BP causes chronic kidney disease (CKD) or glomerular hyperfiltration.

Methods

311 119 White British UK Biobank participants were included in logistic regression analyses to estimate the odds of CKD (defined as long-term kidney replacement therapy, estimated glomerular filtration rate [eGFR]< 60mL/min/1.73m2, or urinary albumin:creatinine ratio \u22653 mg/mmol) associated with higher genetically predicted BP using genetic risk scores comprising 219 systolic and 223 diastolic BP loci. Analyses estimating associations with clinical categories of eGFR and urinary albumin:creatinine ratio were also conducted, with an eGFR \u2265120 mL (min\u00b71.73m2) considered evidence of glomerular hyperfiltration.

Results

21 623 participants had CKD: 7781 with reduced eGFR and 15\u2009500 with albuminuria. 1828 participants had an eGFR \u2265120 mL/min/1.73m2. Each genetically predicted 10 mmHg higher systolic BP and 5 mmHg higher diastolic BP were associated with a 37% (95% CI, 1.29-1.45) and 19% (1.14-1.25) higher odds of CKD, respectively. Associations were evident for both the reduced eGFR and albuminuria components of the CKD outcome. The odds of hyperfiltration (versus an eGFR \u226560 and <90 mL/min/1.73m2 were 49% higher (95% CI, 1.21-1.84) for each genetically predicted 10 mmHg higher systolic BP. Associations with CKD and hyperfiltration were similar irrespective of preexisting diabetes, vascular disease, or different levels of adiposity.

Conclusions

In this general population, genetic epidemiological evidence supports a causal role of life-long differences in BP for decreased kidney function, glomerular hyperfiltration, and albuminuria. Physiological autoregulation may not afford complete renal protection against the moderate BP elevations.", - "laySummary": "", - "urls": "pdf:https://ora.ox.ac.uk/objects/uuid:aefe90da-8a81-4cfa-981a-bb36eca6faa3/files/r6w924c60k; doi:https://doi.org/10.1161/HYPERTENSIONAHA.122.19354; html:https://europepmc.org/articles/PMC9640248; pdf:https://europepmc.org/articles/PMC9640248?pdf=render" - }, { "id": "30648344", "doi": "https://doi.org/10.1002/cnm.3180", @@ -25108,6 +25091,23 @@ "laySummary": "", "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/cnm.3180; doi:https://doi.org/10.1002/cnm.3180; html:https://europepmc.org/articles/PMC6593817; pdf:https://europepmc.org/articles/PMC6593817?pdf=render" }, + { + "id": "36082669", + "doi": "https://doi.org/10.1161/hypertensionaha.122.19354", + "title": "Determining the Relationship Between Blood Pressure, Kidney Function, and Chronic Kidney Disease: Insights From Genetic Epidemiology.", + "authorString": "Staplin N, Herrington WG, Murgia F, Ibrahim M, Bull KR, Judge PK, Ng SYA, Turner M, Zhu D, Emberson J, Landray MJ, Baigent C, Haynes R, Hopewell JC.", + "authorAffiliations": "", + "journalTitle": "Hypertension (Dallas, Tex. : 1979)", + "pubYear": "2022", + "date": "2022-09-09", + "isOpenAccess": "Y", + "keywords": "Blood pressure; Chronic; creatinine; epidemiology; Renal Insufficiency", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

It is well established that decreased kidney function can increase blood pressure (BP), but it is unproven whether moderately elevated BP causes chronic kidney disease (CKD) or glomerular hyperfiltration.

Methods

311 119 White British UK Biobank participants were included in logistic regression analyses to estimate the odds of CKD (defined as long-term kidney replacement therapy, estimated glomerular filtration rate [eGFR]< 60mL/min/1.73m2, or urinary albumin:creatinine ratio \u22653 mg/mmol) associated with higher genetically predicted BP using genetic risk scores comprising 219 systolic and 223 diastolic BP loci. Analyses estimating associations with clinical categories of eGFR and urinary albumin:creatinine ratio were also conducted, with an eGFR \u2265120 mL (min\u00b71.73m2) considered evidence of glomerular hyperfiltration.

Results

21 623 participants had CKD: 7781 with reduced eGFR and 15\u2009500 with albuminuria. 1828 participants had an eGFR \u2265120 mL/min/1.73m2. Each genetically predicted 10 mmHg higher systolic BP and 5 mmHg higher diastolic BP were associated with a 37% (95% CI, 1.29-1.45) and 19% (1.14-1.25) higher odds of CKD, respectively. Associations were evident for both the reduced eGFR and albuminuria components of the CKD outcome. The odds of hyperfiltration (versus an eGFR \u226560 and <90 mL/min/1.73m2 were 49% higher (95% CI, 1.21-1.84) for each genetically predicted 10 mmHg higher systolic BP. Associations with CKD and hyperfiltration were similar irrespective of preexisting diabetes, vascular disease, or different levels of adiposity.

Conclusions

In this general population, genetic epidemiological evidence supports a causal role of life-long differences in BP for decreased kidney function, glomerular hyperfiltration, and albuminuria. Physiological autoregulation may not afford complete renal protection against the moderate BP elevations.", + "laySummary": "", + "urls": "pdf:https://ora.ox.ac.uk/objects/uuid:aefe90da-8a81-4cfa-981a-bb36eca6faa3/files/r6w924c60k; doi:https://doi.org/10.1161/HYPERTENSIONAHA.122.19354; html:https://europepmc.org/articles/PMC9640248; pdf:https://europepmc.org/articles/PMC9640248?pdf=render" + }, { "id": "34095527", "doi": "https://doi.org/10.23889/ijpds.v4i1.581", @@ -25125,6 +25125,23 @@ "laySummary": "", "urls": "pdf:https://ijpds.org/article/download/581/2923; doi:https://doi.org/10.23889/ijpds.v4i1.581; html:https://europepmc.org/articles/PMC8142962; pdf:https://europepmc.org/articles/PMC8142962?pdf=render" }, + { + "id": "34275648", + "doi": "https://doi.org/10.1016/j.injury.2021.06.037", + "title": "Patterns and predictors of personal responsibility attributions after major trauma.", + "authorString": "Lau G, Gabbe BJ, Giummarra MJ.", + "authorAffiliations": "", + "journalTitle": "Injury", + "pubYear": "2021", + "date": "2021-07-06", + "isOpenAccess": "N", + "keywords": "wounds and injuries; Insurance, Accident; Violence; Guilt; Accidental Injuries; Liability, Legal", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

External responsibility attributions after injury are associated with worse recovery. However, there remains limited understanding of who accepts personal responsibilityfor their injury and whether or how responsibility attributions change over time.

Methods

This prospective cohort study included patients who received care from recovery co-ordinators following serious injury and admission to a major trauma centre in Victoria, Australia (n=850). Self-reported personal responsibility attributions (totally, partially, not responsible, or did not know) were collected at three timepoints (admission, discharge, and six months post-injury) and linked to demographic, injury and clinical characteristics from the Victorian State Trauma Registry.

Results

Mixed effects multinomial analyses revealed that female sex (adjusted relative risk ratio, aRRR=3.11-4.66) and compensable injury (aRRR=7.83-15.27) were associated with reporting lower personal responsibility relative to total responsibility. Falls and motorcyclists had decreased risk of reporting lower personal responsibility than non-drivers (motor vehicle/motorcycle passengers, cyclists and pedestrians) (aRRR=0.11-0.19). More than one-third of participants changed their personal responsibility attribution within six months post-injury. Kappa analyses revealed fair to moderate agreement between the three timepoints (kappa=0.38-0.59), and Stuart-Maxwell tests showed unidirectional bias towards reporting lower levels of personal responsibility between admission and discharge (p<0.001). No demographic, health or injury characteristics predicted a change in responsibility attributions in logistic regression analyses.

Conclusions

Personal responsibility attributions often change over time. Therefore, responsibility attributions should not be considered static, and attributions made at different times post-injury should not be used interchangeably in research or clinical settings. Given that external responsibility attributions are associated with worse post-injury outcomes, potential interventions to optimise recovery should be prioritised for patients who predominantly report lower levels of personal responsibility, especially women and people with compensable injuries. Meanwhile, factors associated with high levels of personal responsibility highlight opportunities to implement targeted injury prevention strategies.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1016/j.injury.2021.06.037" + }, { "id": "38763167", "doi": "https://doi.org/10.1164/rccm.202312-2289oc", @@ -25143,21 +25160,21 @@ "urls": "doi:https://doi.org/10.1164/rccm.202312-2289OC" }, { - "id": "34275648", - "doi": "https://doi.org/10.1016/j.injury.2021.06.037", - "title": "Patterns and predictors of personal responsibility attributions after major trauma.", - "authorString": "Lau G, Gabbe BJ, Giummarra MJ.", + "id": "35796550", + "doi": "https://doi.org/10.1093/hmg/ddac153", + "title": "The impact of fatty acids biosynthesis on the risk of cardiovascular diseases in Europeans and East Asians: a Mendelian randomization study.", + "authorString": "Borges MC, Haycock P, Zheng J, Hemani G, Howe LJ, Schmidt AF, Staley JR, Lumbers RT, Henry A, Lemaitre RN, Gaunt TR, Holmes MV, Davey Smith G, Hingorani AD, Lawlor DA.", "authorAffiliations": "", - "journalTitle": "Injury", - "pubYear": "2021", - "date": "2021-07-06", + "journalTitle": "Human molecular genetics", + "pubYear": "2022", + "date": "2022-11-01", "isOpenAccess": "N", - "keywords": "wounds and injuries; Insurance, Accident; Violence; Guilt; Accidental Injuries; Liability, Legal", + "keywords": "", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Background

External responsibility attributions after injury are associated with worse recovery. However, there remains limited understanding of who accepts personal responsibilityfor their injury and whether or how responsibility attributions change over time.

Methods

This prospective cohort study included patients who received care from recovery co-ordinators following serious injury and admission to a major trauma centre in Victoria, Australia (n=850). Self-reported personal responsibility attributions (totally, partially, not responsible, or did not know) were collected at three timepoints (admission, discharge, and six months post-injury) and linked to demographic, injury and clinical characteristics from the Victorian State Trauma Registry.

Results

Mixed effects multinomial analyses revealed that female sex (adjusted relative risk ratio, aRRR=3.11-4.66) and compensable injury (aRRR=7.83-15.27) were associated with reporting lower personal responsibility relative to total responsibility. Falls and motorcyclists had decreased risk of reporting lower personal responsibility than non-drivers (motor vehicle/motorcycle passengers, cyclists and pedestrians) (aRRR=0.11-0.19). More than one-third of participants changed their personal responsibility attribution within six months post-injury. Kappa analyses revealed fair to moderate agreement between the three timepoints (kappa=0.38-0.59), and Stuart-Maxwell tests showed unidirectional bias towards reporting lower levels of personal responsibility between admission and discharge (p<0.001). No demographic, health or injury characteristics predicted a change in responsibility attributions in logistic regression analyses.

Conclusions

Personal responsibility attributions often change over time. Therefore, responsibility attributions should not be considered static, and attributions made at different times post-injury should not be used interchangeably in research or clinical settings. Given that external responsibility attributions are associated with worse post-injury outcomes, potential interventions to optimise recovery should be prioritised for patients who predominantly report lower levels of personal responsibility, especially women and people with compensable injuries. Meanwhile, factors associated with high levels of personal responsibility highlight opportunities to implement targeted injury prevention strategies.", + "abstract": "Despite early interest, the evidence linking fatty acids to cardiovascular diseases (CVDs) remains controversial. We used Mendelian randomization to explore the involvement of polyunsaturated (PUFA) and monounsaturated (MUFA) fatty acids biosynthesis in the etiology of several CVD endpoints in up to 1\u2009153\u2009768 European (maximum 123\u2009668 cases) and 212\u2009453 East Asian (maximum 29\u2009319 cases) ancestry individuals. As instruments, we selected single nucleotide polymorphisms mapping to genes with well-known roles in PUFA (i.e. FADS1/2 and ELOVL2) and MUFA (i.e. SCD) biosynthesis. Our findings suggest that higher PUFA biosynthesis rate (proxied by rs174576 near FADS1/2) is related to higher odds of multiple CVDs, particularly ischemic stroke, peripheral artery disease and venous thromboembolism, whereas higher MUFA biosynthesis rate (proxied by rs603424 near SCD) is related to lower odds of coronary artery disease among Europeans. Results were unclear for East Asians as most effect estimates were imprecise. By triangulating multiple approaches (i.e. uni-/multi-variable Mendelian randomization, a phenome-wide scan, genetic colocalization and within-sibling analyses), our results are compatible with higher low-density lipoprotein (LDL) cholesterol (and possibly glucose) being a downstream effect of higher PUFA biosynthesis rate. Our findings indicate that PUFA and MUFA biosynthesis are involved in the etiology of CVDs and suggest LDL cholesterol as a potential mediating trait between PUFA biosynthesis and CVDs risk.", "laySummary": "", - "urls": "doi:https://doi.org/10.1016/j.injury.2021.06.037" + "urls": "pdf:https://academic.oup.com/hmg/advance-article-pdf/doi/10.1093/hmg/ddac153/45277324/ddac153.pdf; doi:https://doi.org/10.1093/hmg/ddac153" }, { "id": "37477803", @@ -25176,23 +25193,6 @@ "laySummary": "", "urls": "pdf:https://link.springer.com/content/pdf/10.1007/s11897-023-00615-z.pdf; doi:https://doi.org/10.1007/s11897-023-00615-z; html:https://europepmc.org/articles/PMC10589200; pdf:https://europepmc.org/articles/PMC10589200?pdf=render" }, - { - "id": "35796550", - "doi": "https://doi.org/10.1093/hmg/ddac153", - "title": "The impact of fatty acids biosynthesis on the risk of cardiovascular diseases in Europeans and East Asians: a Mendelian randomization study.", - "authorString": "Borges MC, Haycock P, Zheng J, Hemani G, Howe LJ, Schmidt AF, Staley JR, Lumbers RT, Henry A, Lemaitre RN, Gaunt TR, Holmes MV, Davey Smith G, Hingorani AD, Lawlor DA.", - "authorAffiliations": "", - "journalTitle": "Human molecular genetics", - "pubYear": "2022", - "date": "2022-11-01", - "isOpenAccess": "N", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Despite early interest, the evidence linking fatty acids to cardiovascular diseases (CVDs) remains controversial. We used Mendelian randomization to explore the involvement of polyunsaturated (PUFA) and monounsaturated (MUFA) fatty acids biosynthesis in the etiology of several CVD endpoints in up to 1\u2009153\u2009768 European (maximum 123\u2009668 cases) and 212\u2009453 East Asian (maximum 29\u2009319 cases) ancestry individuals. As instruments, we selected single nucleotide polymorphisms mapping to genes with well-known roles in PUFA (i.e. FADS1/2 and ELOVL2) and MUFA (i.e. SCD) biosynthesis. Our findings suggest that higher PUFA biosynthesis rate (proxied by rs174576 near FADS1/2) is related to higher odds of multiple CVDs, particularly ischemic stroke, peripheral artery disease and venous thromboembolism, whereas higher MUFA biosynthesis rate (proxied by rs603424 near SCD) is related to lower odds of coronary artery disease among Europeans. Results were unclear for East Asians as most effect estimates were imprecise. By triangulating multiple approaches (i.e. uni-/multi-variable Mendelian randomization, a phenome-wide scan, genetic colocalization and within-sibling analyses), our results are compatible with higher low-density lipoprotein (LDL) cholesterol (and possibly glucose) being a downstream effect of higher PUFA biosynthesis rate. Our findings indicate that PUFA and MUFA biosynthesis are involved in the etiology of CVDs and suggest LDL cholesterol as a potential mediating trait between PUFA biosynthesis and CVDs risk.", - "laySummary": "", - "urls": "pdf:https://academic.oup.com/hmg/advance-article-pdf/doi/10.1093/hmg/ddac153/45277324/ddac153.pdf; doi:https://doi.org/10.1093/hmg/ddac153" - }, { "id": "35089148", "doi": "https://doi.org/10.2196/28095", @@ -25261,23 +25261,6 @@ "laySummary": "", "urls": "pdf:https://www.nature.com/articles/s41467-023-43434-5.pdf; doi:https://doi.org/10.1038/s41467-023-43434-5; html:https://europepmc.org/articles/PMC10665349; pdf:https://europepmc.org/articles/PMC10665349?pdf=render" }, - { - "id": "37538742", - "doi": "https://doi.org/10.1098/rsos.221469", - "title": "Bayesian inference of polymerase dynamics over the exclusion process.", - "authorString": "Cavallaro M, Wang Y, Hebenstreit D, Dutta R.", - "authorAffiliations": "", - "journalTitle": "Royal Society open science", - "pubYear": "2023", - "date": "2023-08-02", - "isOpenAccess": "Y", - "keywords": "Gene Expression; Bayesian Statistics; Particle Transport; Non-equilbrium Physics", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Transcription is a complex phenomenon that permits the conversion of genetic information into phenotype by means of an enzyme called RNA polymerase, which erratically moves along and scans the DNA template. We perform Bayesian inference over a paradigmatic mechanistic model of non-equilibrium statistical physics, i.e. the asymmetric exclusion processes in the hydrodynamic limit, assuming a Gaussian process prior for the polymerase progression rate as a latent variable. Our framework allows us to infer the speed of polymerases during transcription given their spatial distribution, while avoiding the explicit inversion of the system's dynamics. The results, which show processing rates strongly varying with genomic position and minor role of traffic-like congestion, may have strong implications for the understanding of gene expression.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1098/rsos.221469; doi:https://doi.org/10.1098/rsos.221469; html:https://europepmc.org/articles/PMC10394410; pdf:https://europepmc.org/articles/PMC10394410?pdf=render" - }, { "id": "31822919", "doi": "https://doi.org/10.1093/pubmed/fdz172", @@ -25295,6 +25278,23 @@ "laySummary": "", "urls": "pdf:https://academic.oup.com/jpubhealth/article-pdf/42/4/e516/34469316/fdz172.pdf; doi:https://doi.org/10.1093/pubmed/fdz172" }, + { + "id": "37538742", + "doi": "https://doi.org/10.1098/rsos.221469", + "title": "Bayesian inference of polymerase dynamics over the exclusion process.", + "authorString": "Cavallaro M, Wang Y, Hebenstreit D, Dutta R.", + "authorAffiliations": "", + "journalTitle": "Royal Society open science", + "pubYear": "2023", + "date": "2023-08-02", + "isOpenAccess": "Y", + "keywords": "Gene Expression; Bayesian Statistics; Particle Transport; Non-equilbrium Physics", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Transcription is a complex phenomenon that permits the conversion of genetic information into phenotype by means of an enzyme called RNA polymerase, which erratically moves along and scans the DNA template. We perform Bayesian inference over a paradigmatic mechanistic model of non-equilibrium statistical physics, i.e. the asymmetric exclusion processes in the hydrodynamic limit, assuming a Gaussian process prior for the polymerase progression rate as a latent variable. Our framework allows us to infer the speed of polymerases during transcription given their spatial distribution, while avoiding the explicit inversion of the system's dynamics. The results, which show processing rates strongly varying with genomic position and minor role of traffic-like congestion, may have strong implications for the understanding of gene expression.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1098/rsos.221469; doi:https://doi.org/10.1098/rsos.221469; html:https://europepmc.org/articles/PMC10394410; pdf:https://europepmc.org/articles/PMC10394410?pdf=render" + }, { "id": "32651323", "doi": "https://doi.org/10.3233/jad-200338", @@ -25346,23 +25346,6 @@ "laySummary": "", "urls": "pdf:https://academic.oup.com/ije/advance-article-pdf/doi/10.1093/ije/dyac130/44245961/dyac130.pdf; doi:https://doi.org/10.1093/ije/dyac130; html:https://europepmc.org/articles/PMC9908066; pdf:https://europepmc.org/articles/PMC9908066?pdf=render" }, - { - "id": "36701266", - "doi": "https://doi.org/10.1371/journal.pmed.1004036", - "title": "Gestational age at birth and body size from infancy through adolescence: An individual participant data meta-analysis on 253,810 singletons in 16 birth cohort studies.", - "authorString": "Vinther JL, Cadman T, Avraam D, Ekstr\u00f8m CT, S\u00f8rensen TIA, Elhakeem A, Santos AC, Pinot de Moira A, Heude B, I\u00f1iguez C, Pizzi C, Simons E, Voerman E, Corpeleijn E, Zariouh F, Santorelli G, Inskip HM, Barros H, Carson J, Harris JR, Nader JL, Ronkainen J, Strandberg-Larsen K, Santa-Marina L, Calas L, Cederkvist L, Popovic M, Charles MA, Welten M, Vrijheid M, Azad M, Subbarao P, Burton P, Mandhane PJ, Huang RC, Wilson RC, Haakma S, Fern\u00e1ndez-Barr\u00e9s S, Turvey S, Santos S, Tough SC, Tough SC, Sebert S, Moraes TJ, Salika T, Jaddoe VWV, Lawlor DA, Nybo Andersen AM.", - "authorAffiliations": "", - "journalTitle": "PLoS medicine", - "pubYear": "2023", - "date": "2023-01-26", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Preterm birth is the leading cause of perinatal morbidity and mortality and is associated with adverse developmental and long-term health outcomes, including several cardiometabolic risk factors and outcomes. However, evidence about the association of preterm birth with later body size derives mainly from studies using birth weight as a proxy of prematurity rather than an actual length of gestation. We investigated the association of gestational age (GA) at birth with body size from infancy through adolescence.

Methods and findings

We conducted a two-stage individual participant data (IPD) meta-analysis using data from 253,810 mother-child dyads from 16 general population-based cohort studies in Europe (Denmark, Finland, France, Italy, Norway, Portugal, Spain, the Netherlands, United Kingdom), North America (Canada), and Australasia (Australia) to estimate the association of GA with body mass index (BMI) and overweight (including obesity) adjusted for the following maternal characteristics as potential confounders: education, height, prepregnancy BMI, ethnic background, parity, smoking during pregnancy, age at child's birth, gestational diabetes and hypertension, and preeclampsia. Pregnancy and birth cohort studies from the LifeCycle and the EUCAN-Connect projects were invited and were eligible for inclusion if they had information on GA and minimum one measurement of BMI between infancy and adolescence. Using a federated analytical tool (DataSHIELD), we fitted linear and logistic regression models in each cohort separately with a complete-case approach and combined the regression estimates and standard errors through random-effects study-level meta-analysis providing an overall effect estimate at early infancy (>0.0 to 0.5 years), late infancy (>0.5 to 2.0 years), early childhood (>2.0 to 5.0 years), mid-childhood (>5.0 to 9.0 years), late childhood (>9.0 to 14.0 years), and adolescence (>14.0 to 19.0 years). GA was positively associated with BMI in the first decade of life, with the greatest increase in mean BMI z-score during early infancy (0.02, 95% confidence interval (CI): 0.00; 0.05, p < 0.05) per week of increase in GA, while in adolescence, preterm individuals reached similar levels of BMI (0.00, 95% CI: -0.01; 0.01, p 0.9) as term counterparts. The association between GA and overweight revealed a similar pattern of association with an increase in odds ratio (OR) of overweight from late infancy through mid-childhood (OR 1.01 to 1.02) per week increase in GA. By adolescence, however, GA was slightly negatively associated with the risk of overweight (OR 0.98 [95% CI: 0.97; 1.00], p 0.1) per week of increase in GA. Although based on only four cohorts (n = 32,089) that reached the age of adolescence, data suggest that individuals born very preterm may be at increased odds of overweight (OR 1.46 [95% CI: 1.03; 2.08], p < 0.05) compared with term counterparts. Findings were consistent across cohorts and sensitivity analyses despite considerable heterogeneity in cohort characteristics. However, residual confounding may be a limitation in this study, while findings may be less generalisable to settings in low- and middle-income countries.

Conclusions

This study based on data from infancy through adolescence from 16 cohort studies found that GA may be important for body size in infancy, but the strength of association attenuates consistently with age. By adolescence, preterm individuals have on average a similar mean BMI to peers born at term.", - "laySummary": "", - "urls": "pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1004036&type=printable; doi:https://doi.org/10.1371/journal.pmed.1004036; html:https://europepmc.org/articles/PMC9879424; pdf:https://europepmc.org/articles/PMC9879424?pdf=render" - }, { "id": "32142356", "doi": "https://doi.org/10.1164/rccm.201902-0286oc", @@ -25397,6 +25380,23 @@ "laySummary": "", "urls": "pdf:http://www.thelancet.com/article/S2352396419300775/pdf; doi:https://doi.org/10.1016/j.ebiom.2019.02.005; html:https://europepmc.org/articles/PMC6442001; pdf:https://europepmc.org/articles/PMC6442001?pdf=render" }, + { + "id": "36701266", + "doi": "https://doi.org/10.1371/journal.pmed.1004036", + "title": "Gestational age at birth and body size from infancy through adolescence: An individual participant data meta-analysis on 253,810 singletons in 16 birth cohort studies.", + "authorString": "Vinther JL, Cadman T, Avraam D, Ekstr\u00f8m CT, S\u00f8rensen TIA, Elhakeem A, Santos AC, Pinot de Moira A, Heude B, I\u00f1iguez C, Pizzi C, Simons E, Voerman E, Corpeleijn E, Zariouh F, Santorelli G, Inskip HM, Barros H, Carson J, Harris JR, Nader JL, Ronkainen J, Strandberg-Larsen K, Santa-Marina L, Calas L, Cederkvist L, Popovic M, Charles MA, Welten M, Vrijheid M, Azad M, Subbarao P, Burton P, Mandhane PJ, Huang RC, Wilson RC, Haakma S, Fern\u00e1ndez-Barr\u00e9s S, Turvey S, Santos S, Tough SC, Tough SC, Sebert S, Moraes TJ, Salika T, Jaddoe VWV, Lawlor DA, Nybo Andersen AM.", + "authorAffiliations": "", + "journalTitle": "PLoS medicine", + "pubYear": "2023", + "date": "2023-01-26", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Preterm birth is the leading cause of perinatal morbidity and mortality and is associated with adverse developmental and long-term health outcomes, including several cardiometabolic risk factors and outcomes. However, evidence about the association of preterm birth with later body size derives mainly from studies using birth weight as a proxy of prematurity rather than an actual length of gestation. We investigated the association of gestational age (GA) at birth with body size from infancy through adolescence.

Methods and findings

We conducted a two-stage individual participant data (IPD) meta-analysis using data from 253,810 mother-child dyads from 16 general population-based cohort studies in Europe (Denmark, Finland, France, Italy, Norway, Portugal, Spain, the Netherlands, United Kingdom), North America (Canada), and Australasia (Australia) to estimate the association of GA with body mass index (BMI) and overweight (including obesity) adjusted for the following maternal characteristics as potential confounders: education, height, prepregnancy BMI, ethnic background, parity, smoking during pregnancy, age at child's birth, gestational diabetes and hypertension, and preeclampsia. Pregnancy and birth cohort studies from the LifeCycle and the EUCAN-Connect projects were invited and were eligible for inclusion if they had information on GA and minimum one measurement of BMI between infancy and adolescence. Using a federated analytical tool (DataSHIELD), we fitted linear and logistic regression models in each cohort separately with a complete-case approach and combined the regression estimates and standard errors through random-effects study-level meta-analysis providing an overall effect estimate at early infancy (>0.0 to 0.5 years), late infancy (>0.5 to 2.0 years), early childhood (>2.0 to 5.0 years), mid-childhood (>5.0 to 9.0 years), late childhood (>9.0 to 14.0 years), and adolescence (>14.0 to 19.0 years). GA was positively associated with BMI in the first decade of life, with the greatest increase in mean BMI z-score during early infancy (0.02, 95% confidence interval (CI): 0.00; 0.05, p < 0.05) per week of increase in GA, while in adolescence, preterm individuals reached similar levels of BMI (0.00, 95% CI: -0.01; 0.01, p 0.9) as term counterparts. The association between GA and overweight revealed a similar pattern of association with an increase in odds ratio (OR) of overweight from late infancy through mid-childhood (OR 1.01 to 1.02) per week increase in GA. By adolescence, however, GA was slightly negatively associated with the risk of overweight (OR 0.98 [95% CI: 0.97; 1.00], p 0.1) per week of increase in GA. Although based on only four cohorts (n = 32,089) that reached the age of adolescence, data suggest that individuals born very preterm may be at increased odds of overweight (OR 1.46 [95% CI: 1.03; 2.08], p < 0.05) compared with term counterparts. Findings were consistent across cohorts and sensitivity analyses despite considerable heterogeneity in cohort characteristics. However, residual confounding may be a limitation in this study, while findings may be less generalisable to settings in low- and middle-income countries.

Conclusions

This study based on data from infancy through adolescence from 16 cohort studies found that GA may be important for body size in infancy, but the strength of association attenuates consistently with age. By adolescence, preterm individuals have on average a similar mean BMI to peers born at term.", + "laySummary": "", + "urls": "pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1004036&type=printable; doi:https://doi.org/10.1371/journal.pmed.1004036; html:https://europepmc.org/articles/PMC9879424; pdf:https://europepmc.org/articles/PMC9879424?pdf=render" + }, { "id": "37735103", "doi": "https://doi.org/10.1136/bmjresp-2023-001895", @@ -25465,23 +25465,6 @@ "laySummary": "", "urls": "pdf:https://www.mdpi.com/2075-4426/12/6/958/pdf?version=1655284846; doi:https://doi.org/10.3390/jpm12060958; html:https://europepmc.org/articles/PMC9225330; pdf:https://europepmc.org/articles/PMC9225330?pdf=render" }, - { - "id": "36469091", - "doi": "https://doi.org/10.1093/ageing/afac252", - "title": "Prevalence and outcomes of atrial fibrillation in older people living in care homes in Wales: a routine data linkage study 2003-2018.", - "authorString": "Ritchie LA, Harrison SL, Penson PE, Akbari A, Torabi F, Hollinghurst J, Harris D, Oke OB, Akpan A, Halcox JP, Rodgers SE, Lip GYH, Lane DA.", - "authorAffiliations": "", - "journalTitle": "Age and ageing", - "pubYear": "2022", - "date": "2022-12-01", - "isOpenAccess": "N", - "keywords": "Prevalence; Atrial fibrillation; Stroke; Older People; Care Homes; Health Outcomes", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Objective

To determine atrial fibrillation (AF) prevalence and temporal trends, and examine associations between AF and risk of adverse health outcomes in older care home residents.

Methods

Retrospective cohort study using anonymised linked data from the Secure Anonymised Information Linkage Databank on CARE home residents in Wales with AF (SAIL CARE-AF) between 2003 and 2018. Fine-Gray competing risk models were used to estimate the risk of health outcomes with mortality as a competing risk. Cox regression analyses were used to estimate the risk of mortality.

Results

There were 86,602 older care home residents (median age 86.0\u00a0years [interquartile range 80.8-90.6]) who entered a care home between 2003 and 2018. When the pre-care home entry data extraction was standardised, the overall prevalence of AF was 17.4% (95% confidence interval 17.1-17.8) between 2010 and 2018. There was no significant change in the age- and sex-standardised prevalence of AF from 16.8% (15.9-17.9) in 2010 to 17.0% (16.1-18.0) in 2018. Residents with AF had a significantly higher risk of cardiovascular mortality (adjusted hazard ratio [HR] 1.27 [1.17-1.37], P\u00a0<\u20090.001), all-cause mortality (adjusted HR 1.14 [1.11-1.17], P\u00a0<\u20090.001), ischaemic stroke (adjusted sub-distribution HR 1.55 [1.36-1.76], P\u00a0<\u20090.001) and cardiovascular hospitalisation (adjusted sub-distribution HR 1.28 [1.22-1.34], P\u00a0<\u20090.001).

Conclusions

Older care home residents with AF have an increased risk of adverse health outcomes, even when higher mortality rates and other confounders are accounted for. This re-iterates the need for appropriate oral anticoagulant prescription and optimal management of cardiovascular co-morbidities, irrespective of frailty status and predicted life expectancy.", - "laySummary": "", - "urls": "pdf:https://academic.oup.com/ageing/article-pdf/51/12/afac252/47589319/afac252.pdf; doi:https://doi.org/10.1093/ageing/afac252" - }, { "id": "30940752", "doi": "https://doi.org/10.1136/bmjopen-2018-023232", @@ -25499,6 +25482,23 @@ "laySummary": "", "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/9/4/e023232.full.pdf; doi:https://doi.org/10.1136/bmjopen-2018-023232; html:https://europepmc.org/articles/PMC6500195; pdf:https://europepmc.org/articles/PMC6500195?pdf=render" }, + { + "id": "36469091", + "doi": "https://doi.org/10.1093/ageing/afac252", + "title": "Prevalence and outcomes of atrial fibrillation in older people living in care homes in Wales: a routine data linkage study 2003-2018.", + "authorString": "Ritchie LA, Harrison SL, Penson PE, Akbari A, Torabi F, Hollinghurst J, Harris D, Oke OB, Akpan A, Halcox JP, Rodgers SE, Lip GYH, Lane DA.", + "authorAffiliations": "", + "journalTitle": "Age and ageing", + "pubYear": "2022", + "date": "2022-12-01", + "isOpenAccess": "N", + "keywords": "Prevalence; Atrial fibrillation; Stroke; Older People; Care Homes; Health Outcomes", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Objective

To determine atrial fibrillation (AF) prevalence and temporal trends, and examine associations between AF and risk of adverse health outcomes in older care home residents.

Methods

Retrospective cohort study using anonymised linked data from the Secure Anonymised Information Linkage Databank on CARE home residents in Wales with AF (SAIL CARE-AF) between 2003 and 2018. Fine-Gray competing risk models were used to estimate the risk of health outcomes with mortality as a competing risk. Cox regression analyses were used to estimate the risk of mortality.

Results

There were 86,602 older care home residents (median age 86.0\u00a0years [interquartile range 80.8-90.6]) who entered a care home between 2003 and 2018. When the pre-care home entry data extraction was standardised, the overall prevalence of AF was 17.4% (95% confidence interval 17.1-17.8) between 2010 and 2018. There was no significant change in the age- and sex-standardised prevalence of AF from 16.8% (15.9-17.9) in 2010 to 17.0% (16.1-18.0) in 2018. Residents with AF had a significantly higher risk of cardiovascular mortality (adjusted hazard ratio [HR] 1.27 [1.17-1.37], P\u00a0<\u20090.001), all-cause mortality (adjusted HR 1.14 [1.11-1.17], P\u00a0<\u20090.001), ischaemic stroke (adjusted sub-distribution HR 1.55 [1.36-1.76], P\u00a0<\u20090.001) and cardiovascular hospitalisation (adjusted sub-distribution HR 1.28 [1.22-1.34], P\u00a0<\u20090.001).

Conclusions

Older care home residents with AF have an increased risk of adverse health outcomes, even when higher mortality rates and other confounders are accounted for. This re-iterates the need for appropriate oral anticoagulant prescription and optimal management of cardiovascular co-morbidities, irrespective of frailty status and predicted life expectancy.", + "laySummary": "", + "urls": "pdf:https://academic.oup.com/ageing/article-pdf/51/12/afac252/47589319/afac252.pdf; doi:https://doi.org/10.1093/ageing/afac252" + }, { "id": "32524641", "doi": "https://doi.org/10.1002/sim.8556", @@ -25669,23 +25669,6 @@ "laySummary": "", "urls": "pdf:https://www.nature.com/articles/s41467-020-19996-z.pdf; doi:https://doi.org/10.1038/s41467-020-19996-z; html:https://europepmc.org/articles/PMC7744536; pdf:https://europepmc.org/articles/PMC7744536?pdf=render" }, - { - "id": "37419925", - "doi": "https://doi.org/10.1038/s41467-023-38930-7", - "title": "Optimal strategies for learning multi-ancestry polygenic scores vary across traits.", - "authorString": "Lehmann B, Mackintosh M, McVean G, Holmes C.", - "authorAffiliations": "", - "journalTitle": "Nature communications", - "pubYear": "2023", - "date": "2023-07-07", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Polygenic scores (PGSs) are individual-level measures that aggregate the genome-wide genetic predisposition to a given trait. As PGS have predominantly been developed using European-ancestry samples, trait prediction using such European ancestry-derived PGS is less accurate in non-European ancestry individuals. Although there has been recent progress in combining multiple PGS trained on distinct populations, the problem of how to maximize performance given a multiple-ancestry cohort is largely unexplored. Here, we investigate the effect of sample size and ancestry composition on PGS performance for fifteen traits in UK Biobank. For some traits, PGS estimated using a relatively small African-ancestry training set outperformed, on an African-ancestry test set, PGS estimated using a much larger European-ancestry only training set. We observe similar, but not identical, results when considering other minority-ancestry groups within UK Biobank. Our results emphasise the importance of targeted data collection from underrepresented groups in order to address existing disparities in PGS performance.", - "laySummary": "", - "urls": "pdf:https://www.nature.com/articles/s41467-023-38930-7.pdf; doi:https://doi.org/10.1038/s41467-023-38930-7; html:https://europepmc.org/articles/PMC10328935; pdf:https://europepmc.org/articles/PMC10328935?pdf=render" - }, { "id": "31711543", "doi": "https://doi.org/10.1186/s13326-019-0214-4", @@ -25720,6 +25703,23 @@ "laySummary": "", "urls": "pdf:https://erj.ersjournals.com/content/erj/54/5/1900476.full.pdf; doi:https://doi.org/10.1183/13993003.00476-2019" }, + { + "id": "37419925", + "doi": "https://doi.org/10.1038/s41467-023-38930-7", + "title": "Optimal strategies for learning multi-ancestry polygenic scores vary across traits.", + "authorString": "Lehmann B, Mackintosh M, McVean G, Holmes C.", + "authorAffiliations": "", + "journalTitle": "Nature communications", + "pubYear": "2023", + "date": "2023-07-07", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Polygenic scores (PGSs) are individual-level measures that aggregate the genome-wide genetic predisposition to a given trait. As PGS have predominantly been developed using European-ancestry samples, trait prediction using such European ancestry-derived PGS is less accurate in non-European ancestry individuals. Although there has been recent progress in combining multiple PGS trained on distinct populations, the problem of how to maximize performance given a multiple-ancestry cohort is largely unexplored. Here, we investigate the effect of sample size and ancestry composition on PGS performance for fifteen traits in UK Biobank. For some traits, PGS estimated using a relatively small African-ancestry training set outperformed, on an African-ancestry test set, PGS estimated using a much larger European-ancestry only training set. We observe similar, but not identical, results when considering other minority-ancestry groups within UK Biobank. Our results emphasise the importance of targeted data collection from underrepresented groups in order to address existing disparities in PGS performance.", + "laySummary": "", + "urls": "pdf:https://www.nature.com/articles/s41467-023-38930-7.pdf; doi:https://doi.org/10.1038/s41467-023-38930-7; html:https://europepmc.org/articles/PMC10328935; pdf:https://europepmc.org/articles/PMC10328935?pdf=render" + }, { "id": "33719753", "doi": "https://doi.org/10.1080/13607863.2021.1893270", @@ -25771,23 +25771,6 @@ "laySummary": "", "urls": "pdf:https://n.neurology.org/content/neurology/95/4/e353.full.pdf; doi:https://doi.org/10.1212/WNL.0000000000009814; html:https://europepmc.org/articles/PMC7455321; pdf:https://europepmc.org/articles/PMC7455321?pdf=render" }, - { - "id": "38416429", - "doi": "https://doi.org/10.1056/nejmoa2311330", - "title": "Cognition and Memory after Covid-19 in a Large Community Sample.", - "authorString": "Hampshire A, Azor A, Atchison C, Trender W, Hellyer PJ, Giunchiglia V, Husain M, Cooke GS, Cooper E, Lound A, Donnelly CA, Chadeau-Hyam M, Ward H, Elliott P.", - "authorAffiliations": "", - "journalTitle": "The New England journal of medicine", - "pubYear": "2024", - "date": "2024-02-01", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Cognitive symptoms after coronavirus disease 2019 (Covid-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are well-recognized. Whether objectively measurable cognitive deficits exist and how long they persist are unclear.

Methods

We invited 800,000 adults in a study in England to complete an online assessment of cognitive function. We estimated a global cognitive score across eight tasks. We hypothesized that participants with persistent symptoms (lasting \u226512 weeks) after infection onset would have objectively measurable global cognitive deficits and that impairments in executive functioning and memory would be observed in such participants, especially in those who reported recent poor memory or difficulty thinking or concentrating (\"brain fog\").

Results

Of the 141,583 participants who started the online cognitive assessment, 112,964 completed it. In a multiple regression analysis, participants who had recovered from Covid-19 in whom symptoms had resolved in less than 4 weeks or at least 12 weeks had similar small deficits in global cognition as compared with those in the no-Covid-19 group, who had not been infected with SARS-CoV-2 or had unconfirmed infection (-0.23 SD [95% confidence interval {CI}, -0.33 to -0.13] and -0.24 SD [95% CI, -0.36 to -0.12], respectively); larger deficits as compared with the no-Covid-19 group were seen in participants with unresolved persistent symptoms (-0.42 SD; 95% CI, -0.53 to -0.31). Larger deficits were seen in participants who had SARS-CoV-2 infection during periods in which the original virus or the B.1.1.7 variant was predominant than in those infected with later variants (e.g., -0.17 SD for the B.1.1.7 variant vs. the B.1.1.529 variant; 95% CI, -0.20 to -0.13) and in participants who had been hospitalized than in those who had not been hospitalized (e.g., intensive care unit admission, -0.35 SD; 95% CI, -0.49 to -0.20). Results of the analyses were similar to those of propensity-score-matching analyses. In a comparison of the group that had unresolved persistent symptoms with the no-Covid-19 group, memory, reasoning, and executive function tasks were associated with the largest deficits (-0.33 to -0.20 SD); these tasks correlated weakly with recent symptoms, including poor memory and brain fog. No adverse events were reported.

Conclusions

Participants with resolved persistent symptoms after Covid-19 had objectively measured cognitive function similar to that in participants with shorter-duration symptoms, although short-duration Covid-19 was still associated with small cognitive deficits after recovery. Longer-term persistence of cognitive deficits and any clinical implications remain uncertain. (Funded by the National Institute for Health and Care Research and others.).", - "laySummary": "", - "urls": "pdf:https://www.nejm.org/doi/pdf/10.1056/NEJMoa2311330?articleTools=true; doi:https://doi.org/10.1056/NEJMoa2311330; html:https://europepmc.org/articles/PMC7615803; pdf:https://europepmc.org/articles/PMC7615803?pdf=render" - }, { "id": "35259281", "doi": "https://doi.org/10.1111/acel.13524", @@ -25822,6 +25805,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.chiabu.2020.104760; doi:https://doi.org/10.1016/j.chiabu.2020.104760; html:https://europepmc.org/articles/PMC7718112" }, + { + "id": "38416429", + "doi": "https://doi.org/10.1056/nejmoa2311330", + "title": "Cognition and Memory after Covid-19 in a Large Community Sample.", + "authorString": "Hampshire A, Azor A, Atchison C, Trender W, Hellyer PJ, Giunchiglia V, Husain M, Cooke GS, Cooper E, Lound A, Donnelly CA, Chadeau-Hyam M, Ward H, Elliott P.", + "authorAffiliations": "", + "journalTitle": "The New England journal of medicine", + "pubYear": "2024", + "date": "2024-02-01", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Cognitive symptoms after coronavirus disease 2019 (Covid-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are well-recognized. Whether objectively measurable cognitive deficits exist and how long they persist are unclear.

Methods

We invited 800,000 adults in a study in England to complete an online assessment of cognitive function. We estimated a global cognitive score across eight tasks. We hypothesized that participants with persistent symptoms (lasting \u226512 weeks) after infection onset would have objectively measurable global cognitive deficits and that impairments in executive functioning and memory would be observed in such participants, especially in those who reported recent poor memory or difficulty thinking or concentrating (\"brain fog\").

Results

Of the 141,583 participants who started the online cognitive assessment, 112,964 completed it. In a multiple regression analysis, participants who had recovered from Covid-19 in whom symptoms had resolved in less than 4 weeks or at least 12 weeks had similar small deficits in global cognition as compared with those in the no-Covid-19 group, who had not been infected with SARS-CoV-2 or had unconfirmed infection (-0.23 SD [95% confidence interval {CI}, -0.33 to -0.13] and -0.24 SD [95% CI, -0.36 to -0.12], respectively); larger deficits as compared with the no-Covid-19 group were seen in participants with unresolved persistent symptoms (-0.42 SD; 95% CI, -0.53 to -0.31). Larger deficits were seen in participants who had SARS-CoV-2 infection during periods in which the original virus or the B.1.1.7 variant was predominant than in those infected with later variants (e.g., -0.17 SD for the B.1.1.7 variant vs. the B.1.1.529 variant; 95% CI, -0.20 to -0.13) and in participants who had been hospitalized than in those who had not been hospitalized (e.g., intensive care unit admission, -0.35 SD; 95% CI, -0.49 to -0.20). Results of the analyses were similar to those of propensity-score-matching analyses. In a comparison of the group that had unresolved persistent symptoms with the no-Covid-19 group, memory, reasoning, and executive function tasks were associated with the largest deficits (-0.33 to -0.20 SD); these tasks correlated weakly with recent symptoms, including poor memory and brain fog. No adverse events were reported.

Conclusions

Participants with resolved persistent symptoms after Covid-19 had objectively measured cognitive function similar to that in participants with shorter-duration symptoms, although short-duration Covid-19 was still associated with small cognitive deficits after recovery. Longer-term persistence of cognitive deficits and any clinical implications remain uncertain. (Funded by the National Institute for Health and Care Research and others.).", + "laySummary": "", + "urls": "pdf:https://www.nejm.org/doi/pdf/10.1056/NEJMoa2311330?articleTools=true; doi:https://doi.org/10.1056/NEJMoa2311330; html:https://europepmc.org/articles/PMC7615803; pdf:https://europepmc.org/articles/PMC7615803?pdf=render" + }, { "id": "33824583", "doi": "https://doi.org/10.2147/copd.s298585", @@ -25924,23 +25924,6 @@ "laySummary": "", "urls": "pdf:https://ijpds.org/article/download/2113/4170; doi:https://doi.org/10.23889/ijpds.v8i1.2113; html:https://europepmc.org/articles/PMC10476150; pdf:https://europepmc.org/articles/PMC10476150?pdf=render" }, - { - "id": "38663408", - "doi": "https://doi.org/10.1016/j.xgen.2024.100541", - "title": "Characterization of the genetic determinants of context-specific DNA methylation in primary monocytes.", - "authorString": "Gilchrist JJ, Fang H, Danielli S, Tomkova M, Nassiri I, Ng E, Tong O, Taylor C, Muldoon D, Cohen LRZ, Al-Mossawi H, Lau E, Neville M, Schuster-Boeckler B, Knight JC, Fairfax BP.", - "authorAffiliations": "", - "journalTitle": "Cell genomics", - "pubYear": "2024", - "date": "2024-04-24", - "isOpenAccess": "Y", - "keywords": "Genetics; Monocytes; Cancer; LPS; DNA methylation; Innate Immune Activation; Mqtl; Epigenetic Aging", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "To better understand inter-individual variation in sensitivity of DNA methylation (DNAm) to immune activity, we characterized effects of inflammatory stimuli on primary monocyte DNAm (n\u00a0= 190). We find that monocyte DNAm is site-dependently sensitive to lipopolysaccharide (LPS), with LPS-induced demethylation occurring following hydroxymethylation. We identify 7,359 high-confidence immune-modulated CpGs (imCpGs) that differ in genomic localization and transcription factor usage according to whether they represent a gain or loss in DNAm. Demethylated imCpGs are profoundly enriched for enhancers and colocalize to genes enriched for disease associations, especially cancer. DNAm is age associated, and we find that 24-h LPS exposure triggers approximately 6\u00a0months of gain in epigenetic age, directly linking epigenetic aging with innate immune activity. By integrating LPS-induced changes in DNAm with genetic variation, we identify 234 imCpGs under local genetic control. Exploring shared causal loci between LPS-induced DNAm responses and human disease traits highlights examples of disease-associated loci that modulate imCpG formation.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1016/j.xgen.2024.100541; html:https://europepmc.org/articles/PMC11099345; pdf:https://europepmc.org/articles/PMC11099345?pdf=render" - }, { "id": "36828609", "doi": "https://doi.org/10.1016/s2589-7500(22)00252-7", @@ -25958,23 +25941,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/s2589-7500(22)00252-7; doi:https://doi.org/10.1016/S2589-7500(22)00252-7" }, - { - "id": "37563195", - "doi": "https://doi.org/10.1038/s41598-023-38880-6", - "title": "Locational memory of macrovessel vascular cells is transcriptionally imprinted.", - "authorString": "Spanjersberg TCF, Oosterhoff LA, Kruitwagen HS, van den Dungen NAM, Vernooij JCM, Asselbergs FW, Mokry M, Spee B, Harakalova M, van Steenbeek FG.", - "authorAffiliations": "", - "journalTitle": "Scientific reports", - "pubYear": "2023", - "date": "2023-08-10", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Vascular pathologies show locational predisposition throughout the body; further insights into the transcriptomics basis of this vascular heterogeneity are needed. We analyzed transcriptomes from cultured endothelial cells and vascular smooth muscle cells from nine adult canine macrovessels: the aorta, coronary artery, vena cava, portal vein, femoral artery, femoral vein, saphenous vein, pulmonary vein, and pulmonary artery. We observed that organ-specific expression patterns persist in vitro, indicating that these genes are not regulated by blood flow or surrounding cell types but are likely fixed in the epigenetic memory. We further demonstrated the preserved location-specific expression of GATA4 protein in cultured cells and in the primary adult vessel. On a functional level, arterial and venous endothelial cells differed in vascular network morphology as the arterial networks maintained a higher complexity. Our findings prompt the rethinking of the extrapolation of results from single-origin endothelial cell systems.", - "laySummary": "", - "urls": "pdf:https://www.nature.com/articles/s41598-023-38880-6.pdf; doi:https://doi.org/10.1038/s41598-023-38880-6; html:https://europepmc.org/articles/PMC10415317; pdf:https://europepmc.org/articles/PMC10415317?pdf=render" - }, { "id": "35504525", "doi": "https://doi.org/10.1016/j.jclinepi.2022.04.025", @@ -25992,6 +25958,40 @@ "laySummary": "", "urls": "pdf:https://discovery.ucl.ac.uk/10160730/1/JCEPI-D-21-01101_R2-2%2022-40.pdf; doi:https://doi.org/10.1016/j.jclinepi.2022.04.025" }, + { + "id": "38663408", + "doi": "https://doi.org/10.1016/j.xgen.2024.100541", + "title": "Characterization of the genetic determinants of context-specific DNA methylation in primary monocytes.", + "authorString": "Gilchrist JJ, Fang H, Danielli S, Tomkova M, Nassiri I, Ng E, Tong O, Taylor C, Muldoon D, Cohen LRZ, Al-Mossawi H, Lau E, Neville M, Schuster-Boeckler B, Knight JC, Fairfax BP.", + "authorAffiliations": "", + "journalTitle": "Cell genomics", + "pubYear": "2024", + "date": "2024-04-24", + "isOpenAccess": "Y", + "keywords": "Genetics; Monocytes; Cancer; LPS; DNA methylation; Innate Immune Activation; Mqtl; Epigenetic Aging", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "To better understand inter-individual variation in sensitivity of DNA methylation (DNAm) to immune activity, we characterized effects of inflammatory stimuli on primary monocyte DNAm (n\u00a0= 190). We find that monocyte DNAm is site-dependently sensitive to lipopolysaccharide (LPS), with LPS-induced demethylation occurring following hydroxymethylation. We identify 7,359 high-confidence immune-modulated CpGs (imCpGs) that differ in genomic localization and transcription factor usage according to whether they represent a gain or loss in DNAm. Demethylated imCpGs are profoundly enriched for enhancers and colocalize to genes enriched for disease associations, especially cancer. DNAm is age associated, and we find that 24-h LPS exposure triggers approximately 6\u00a0months of gain in epigenetic age, directly linking epigenetic aging with innate immune activity. By integrating LPS-induced changes in DNAm with genetic variation, we identify 234 imCpGs under local genetic control. Exploring shared causal loci between LPS-induced DNAm responses and human disease traits highlights examples of disease-associated loci that modulate imCpG formation.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1016/j.xgen.2024.100541; html:https://europepmc.org/articles/PMC11099345; pdf:https://europepmc.org/articles/PMC11099345?pdf=render" + }, + { + "id": "37563195", + "doi": "https://doi.org/10.1038/s41598-023-38880-6", + "title": "Locational memory of macrovessel vascular cells is transcriptionally imprinted.", + "authorString": "Spanjersberg TCF, Oosterhoff LA, Kruitwagen HS, van den Dungen NAM, Vernooij JCM, Asselbergs FW, Mokry M, Spee B, Harakalova M, van Steenbeek FG.", + "authorAffiliations": "", + "journalTitle": "Scientific reports", + "pubYear": "2023", + "date": "2023-08-10", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Vascular pathologies show locational predisposition throughout the body; further insights into the transcriptomics basis of this vascular heterogeneity are needed. We analyzed transcriptomes from cultured endothelial cells and vascular smooth muscle cells from nine adult canine macrovessels: the aorta, coronary artery, vena cava, portal vein, femoral artery, femoral vein, saphenous vein, pulmonary vein, and pulmonary artery. We observed that organ-specific expression patterns persist in vitro, indicating that these genes are not regulated by blood flow or surrounding cell types but are likely fixed in the epigenetic memory. We further demonstrated the preserved location-specific expression of GATA4 protein in cultured cells and in the primary adult vessel. On a functional level, arterial and venous endothelial cells differed in vascular network morphology as the arterial networks maintained a higher complexity. Our findings prompt the rethinking of the extrapolation of results from single-origin endothelial cell systems.", + "laySummary": "", + "urls": "pdf:https://www.nature.com/articles/s41598-023-38880-6.pdf; doi:https://doi.org/10.1038/s41598-023-38880-6; html:https://europepmc.org/articles/PMC10415317; pdf:https://europepmc.org/articles/PMC10415317?pdf=render" + }, { "id": "34364665", "doi": "https://doi.org/10.1016/j.cardfail.2021.05.012", @@ -26367,21 +26367,21 @@ "urls": "pdf:https://ora.ox.ac.uk/objects/uuid:f91f9722-f207-4d97-aa64-58636b323acc/files/r6969z144v; doi:https://doi.org/10.1056/NEJMoa2204233; html:https://europepmc.org/articles/PMC7614055; pdf:https://europepmc.org/articles/PMC7614055?pdf=render" }, { - "id": "38190103", - "doi": "https://doi.org/10.1016/j.xgen.2023.100469", - "title": "Genome-wide classification of epigenetic activity reveals regions of enriched heritability in immune-related traits.", - "authorString": "Stricker M, Zhang W, Cheng WY, Gazal S, Dendrou C, Nahkuri S, Palamara PF.", + "id": "32017129", + "doi": "https://doi.org/10.5694/mja2.50485", + "title": "Discharge destination and patient-reported outcomes after inpatient treatment for isolated lower limb fractures.", + "authorString": "Kimmel LA, Simpson PM, Holland AE, Edwards ER, Cameron PA, de Steiger RS, Page RS, Hau R, Bucknill A, Kasza J, Gabbe BJ.", "authorAffiliations": "", - "journalTitle": "Cell genomics", - "pubYear": "2024", - "date": "2023-12-28", - "isOpenAccess": "Y", - "keywords": "Immune system; Heritability; Epigenetics; Machine Learning", + "journalTitle": "The Medical journal of Australia", + "pubYear": "2020", + "date": "2020-02-04", + "isOpenAccess": "N", + "keywords": "Rehabilitation; Treatment outcome; Orthopedic Procedures; Fractures, Bone; Trauma Surgery", "nationalPriorities": "", "healthCategories": "", - "abstract": "Epigenetics underpins the regulation of genes known to play a key role in the adaptive and innate immune system (AIIS). We developed a method, EpiNN, that leverages epigenetic data to detect AIIS-relevant genomic regions and used it to detect 2,765 putative AIIS loci. Experimental validation of one of these loci, DNMT1, provided evidence for a novel AIIS-specific transcription start site. We built a genome-wide AIIS\u00a0annotation and used linkage disequilibrium (LD) score regression to test whether it predicts regional heritability using association statistics for 176 traits. We detected significant heritability effects (average |\u03c4\u2217|=1.65) for 20 out of 26 immune-relevant traits. In a meta-analysis, immune-relevant traits and diseases were 4.45\u00d7 more enriched for heritability than other traits. The EpiNN annotation was also depleted of trans-ancestry genetic correlation, indicating ancestry-specific effects. These results underscore the effectiveness of leveraging supervised learning algorithms and epigenetic data to detect loci implicated in specific classes of traits and diseases.", + "abstract": "

Objectives

To examine the association between discharge destination (home or inpatient rehabilitation) for adult patients treated in hospital for isolated lower limb fractures and patient-reported outcomes.

Design

Review of prospectively collected Victorian Orthopaedic Trauma Outcomes Registry (VOTOR) data.

Setting, participants

Adults (18-64 years old) treated for isolated lower limb fractures at four Melbourne trauma hospitals that contribute data to the VOTOR, 1 March 2007 - 31 March 2016.

Main outcome measures

Return to work and functional recovery (assessed with the extended Glasgow Outcomes Scale, GOS-E); propensity score analysis of association between discharge destination and outcome.

Results

Of 7961 eligible patients, 1432 (18%) were discharged to inpatient rehabilitation, and 6775 (85%) were followed up 12 months after their injuries. After propensity score adjustment, the odds of better functional recovery were 56% lower for patients discharged to inpatient rehabilitation than for those discharged directly home (odds ratio, 0.44; 95% CI, 0.37-0.51); for the 5057 people working before their accident, the odds of return to work were reduced by 66% (odds ratio, 0.34; 95% CI, 0.26-0.46). Propensity score analysis improved matching of the discharge destination groups, but imbalances in funding source remained for both outcome analyses, and for also for site and cause of injury in the GOS-E analysis (standardised differences, 10-16%).

Conclusions

Discharge to inpatient rehabilitation after treatment for isolated lower limb fractures was associated with poorer outcomes than discharge home. Factors that remained unbalanced after propensity score analysis could be assessed in controlled trials.", "laySummary": "", - "urls": "doi:https://doi.org/10.1016/j.xgen.2023.100469; html:https://europepmc.org/articles/PMC10794845; pdf:https://europepmc.org/articles/PMC10794845?pdf=render" + "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.5694/mja2.50485; doi:https://doi.org/10.5694/mja2.50485" }, { "id": "35275087", @@ -26401,21 +26401,21 @@ "urls": "pdf:https://mental.jmir.org/2022/3/e34898/PDF; doi:https://doi.org/10.2196/34898; html:https://europepmc.org/articles/PMC8957008" }, { - "id": "32017129", - "doi": "https://doi.org/10.5694/mja2.50485", - "title": "Discharge destination and patient-reported outcomes after inpatient treatment for isolated lower limb fractures.", - "authorString": "Kimmel LA, Simpson PM, Holland AE, Edwards ER, Cameron PA, de Steiger RS, Page RS, Hau R, Bucknill A, Kasza J, Gabbe BJ.", + "id": "38190103", + "doi": "https://doi.org/10.1016/j.xgen.2023.100469", + "title": "Genome-wide classification of epigenetic activity reveals regions of enriched heritability in immune-related traits.", + "authorString": "Stricker M, Zhang W, Cheng WY, Gazal S, Dendrou C, Nahkuri S, Palamara PF.", "authorAffiliations": "", - "journalTitle": "The Medical journal of Australia", - "pubYear": "2020", - "date": "2020-02-04", - "isOpenAccess": "N", - "keywords": "Rehabilitation; Treatment outcome; Orthopedic Procedures; Fractures, Bone; Trauma Surgery", + "journalTitle": "Cell genomics", + "pubYear": "2024", + "date": "2023-12-28", + "isOpenAccess": "Y", + "keywords": "Immune system; Heritability; Epigenetics; Machine Learning", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Objectives

To examine the association between discharge destination (home or inpatient rehabilitation) for adult patients treated in hospital for isolated lower limb fractures and patient-reported outcomes.

Design

Review of prospectively collected Victorian Orthopaedic Trauma Outcomes Registry (VOTOR) data.

Setting, participants

Adults (18-64 years old) treated for isolated lower limb fractures at four Melbourne trauma hospitals that contribute data to the VOTOR, 1 March 2007 - 31 March 2016.

Main outcome measures

Return to work and functional recovery (assessed with the extended Glasgow Outcomes Scale, GOS-E); propensity score analysis of association between discharge destination and outcome.

Results

Of 7961 eligible patients, 1432 (18%) were discharged to inpatient rehabilitation, and 6775 (85%) were followed up 12 months after their injuries. After propensity score adjustment, the odds of better functional recovery were 56% lower for patients discharged to inpatient rehabilitation than for those discharged directly home (odds ratio, 0.44; 95% CI, 0.37-0.51); for the 5057 people working before their accident, the odds of return to work were reduced by 66% (odds ratio, 0.34; 95% CI, 0.26-0.46). Propensity score analysis improved matching of the discharge destination groups, but imbalances in funding source remained for both outcome analyses, and for also for site and cause of injury in the GOS-E analysis (standardised differences, 10-16%).

Conclusions

Discharge to inpatient rehabilitation after treatment for isolated lower limb fractures was associated with poorer outcomes than discharge home. Factors that remained unbalanced after propensity score analysis could be assessed in controlled trials.", + "abstract": "Epigenetics underpins the regulation of genes known to play a key role in the adaptive and innate immune system (AIIS). We developed a method, EpiNN, that leverages epigenetic data to detect AIIS-relevant genomic regions and used it to detect 2,765 putative AIIS loci. Experimental validation of one of these loci, DNMT1, provided evidence for a novel AIIS-specific transcription start site. We built a genome-wide AIIS\u00a0annotation and used linkage disequilibrium (LD) score regression to test whether it predicts regional heritability using association statistics for 176 traits. We detected significant heritability effects (average |\u03c4\u2217|=1.65) for 20 out of 26 immune-relevant traits. In a meta-analysis, immune-relevant traits and diseases were 4.45\u00d7 more enriched for heritability than other traits. The EpiNN annotation was also depleted of trans-ancestry genetic correlation, indicating ancestry-specific effects. These results underscore the effectiveness of leveraging supervised learning algorithms and epigenetic data to detect loci implicated in specific classes of traits and diseases.", "laySummary": "", - "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.5694/mja2.50485; doi:https://doi.org/10.5694/mja2.50485" + "urls": "doi:https://doi.org/10.1016/j.xgen.2023.100469; html:https://europepmc.org/articles/PMC10794845; pdf:https://europepmc.org/articles/PMC10794845?pdf=render" }, { "id": "35355205", @@ -26468,23 +26468,6 @@ "laySummary": "", "urls": "pdf:https://www.repository.cam.ac.uk/bitstreams/bb5465bd-c08f-4c3d-ab0e-87fee39fc92b/download; doi:https://doi.org/10.1016/S2214-109X(22)00358-8; html:https://europepmc.org/articles/PMC9573849" }, - { - "id": "37046260", - "doi": "https://doi.org/10.1186/s12913-023-09363-1", - "title": "Associations between the stringency of COVID-19 containment policies and health service disruptions in 10 countries.", - "authorString": "Reddy T, Kapoor NR, Kubota S, Doubova SV, Asai D, Mariam DH, Ayele W, Mebratie AD, Thermidor R, Sapag JC, Bedregal P, Passi-Solar \u00c1, Gordon-Strachan G, Dulal M, Gadeka DD, Mehata S, Margozzini P, Leerapan B, Rittiphairoj T, Kaewkamjornchai P, Nega A, Awoonor-Williams JK, Kruk ME, Arsenault C.", - "authorAffiliations": "", - "journalTitle": "BMC health services research", - "pubYear": "2023", - "date": "2023-04-12", - "isOpenAccess": "Y", - "keywords": "Health Services; Health Systems; Pandemic Response; Health System Resilience; Covid-19 Restrictions; Health Care Disruptions", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Disruptions in essential health services during the COVID-19 pandemic have been reported in several countries. Yet, patterns in health service disruption according to country responses remain unclear.\u00a0In this paper, we investigate associations between the stringency of COVID-19 containment policies and disruptions in 31 health services in 10 low- middle- and high-income countries in 2020.

Methods

Using routine health information systems and administrative data from 10 countries (Chile, Ethiopia, Ghana, Haiti, Lao People's Democratic Republic, Mexico, Nepal, South Africa, South Korea, and Thailand) we estimated health service disruptions for the period of April to December 2020 by dividing monthly service provision at national levels by the average service provision in the 15\u00a0months pre-COVID (January 2019-March 2020). We used the\u00a0Oxford COVID-19 Government Response Tracker (OxCGRT) index and\u00a0multi-level linear regression analyses to assess associations between the stringency of restrictions and health service disruptions over nine months. We extended the analysis by examining associations between 11 individual containment or closure policies and health service disruptions. Models were adjusted for COVID caseload, health service category and country GDP and included robust standard errors.

Findings

Chronic disease care was among the most affected services. Regression analyses revealed that a 10% increase in the mean stringency index was associated with a 3.3 percentage-point (95% CI -3.9, -2.7) reduction in relative service volumes. Among individual policies, curfews, and the presence of a state of emergency, had the largest coefficients and were associated with 14.1 (95% CI -19.6, 8.7) and 10.7 (95% CI -12.7, -8.7) percentage-point lower relative service volumes, respectively. In contrast, number of COVID-19 cases in 2020 was not associated with health service disruptions in any model.

Conclusions

Although containment policies were crucial in reducing COVID-19 mortality in many contexts, it is important to consider the indirect effects of these restrictions. Strategies to improve the resilience of health systems should be designed to ensure that populations can continue accessing essential health care despite the presence of containment policies during future infectious disease outbreaks.", - "laySummary": "", - "urls": "pdf:https://bmchealthservres.biomedcentral.com/counter/pdf/10.1186/s12913-023-09363-1; doi:https://doi.org/10.1186/s12913-023-09363-1; html:https://europepmc.org/articles/PMC10096103; pdf:https://europepmc.org/articles/PMC10096103?pdf=render" - }, { "id": "31984563", "doi": "https://doi.org/10.1111/jce.14368", @@ -26503,21 +26486,38 @@ "urls": "doi:https://doi.org/10.1111/jce.14368" }, { - "id": "37180793", - "doi": "https://doi.org/10.3389/fcvm.2023.1136764", - "title": "Diabetes and heart failure associations in women and men: Results from the MORGAM consortium.", - "authorString": "Chadalavada S, Reinikainen J, Andersson J, Di Castelnuovo A, Iacoviello L, Jousilahti P, K\u00e5rhus LL, Linneberg A, S\u00f6derberg S, Tunstall-Pedoe H, Lekadir K, Aung N, Jensen MT, Kuulasmaa K, Niiranen TJ, Petersen SE.", + "id": "37046260", + "doi": "https://doi.org/10.1186/s12913-023-09363-1", + "title": "Associations between the stringency of COVID-19 containment policies and health service disruptions in 10 countries.", + "authorString": "Reddy T, Kapoor NR, Kubota S, Doubova SV, Asai D, Mariam DH, Ayele W, Mebratie AD, Thermidor R, Sapag JC, Bedregal P, Passi-Solar \u00c1, Gordon-Strachan G, Dulal M, Gadeka DD, Mehata S, Margozzini P, Leerapan B, Rittiphairoj T, Kaewkamjornchai P, Nega A, Awoonor-Williams JK, Kruk ME, Arsenault C.", "authorAffiliations": "", - "journalTitle": "Frontiers in cardiovascular medicine", + "journalTitle": "BMC health services research", "pubYear": "2023", - "date": "2023-04-25", + "date": "2023-04-12", "isOpenAccess": "Y", - "keywords": "Diabetes; Sex differences; epidemiology; Heart Failure; Morgam", + "keywords": "Health Services; Health Systems; Pandemic Response; Health System Resilience; Covid-19 Restrictions; Health Care Disruptions", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Background

Diabetes and its cardiovascular complications are a growing concern worldwide. Recently, some studies have demonstrated that relative risk of heart failure (HF) is higher in women with type 1 diabetes (T1DM) than in men. This study aims to validate these findings in cohorts representing five countries across Europe.

Methods

This study includes 88,559 (51.8% women) participants, 3,281 (46.3% women) of whom had diabetes at baseline. Survival analysis was performed with the outcomes of interest being death and HF with a follow-up time of 12 years. Sub-group analysis according to sex and type of diabetes was also performed for the HF outcome.

Results

6,460 deaths were recorded, of which 567 were amongst those with diabetes. Additionally, HF was diagnosed in 2,772 individuals (446 with diabetes). A multivariable Cox proportional hazard analysis showed that there was an increased risk of death and HF (hazard ratio (HR) of 1.73 [1.58-1.89] and 2.12 [1.91-2.36], respectively) when comparing those with diabetes and those without. The HR for HF was 6.72 [2.75-16.41] for women with T1DM vs. 5.80 [2.72-12.37] for men with T1DM, but the interaction term for sex differences was insignificant (p for interaction 0.45). There was no significant difference in the relative risk of HF between men and women when both types of diabetes were combined (HR 2.22 [1.93-2.54] vs. 1.99 [1.67-2.38] respectively, p for interaction 0.80).

Conclusion

Diabetes is associated with increased risks of death and heart failure, and there was no difference in relative risk according to sex.", + "abstract": "

Background

Disruptions in essential health services during the COVID-19 pandemic have been reported in several countries. Yet, patterns in health service disruption according to country responses remain unclear.\u00a0In this paper, we investigate associations between the stringency of COVID-19 containment policies and disruptions in 31 health services in 10 low- middle- and high-income countries in 2020.

Methods

Using routine health information systems and administrative data from 10 countries (Chile, Ethiopia, Ghana, Haiti, Lao People's Democratic Republic, Mexico, Nepal, South Africa, South Korea, and Thailand) we estimated health service disruptions for the period of April to December 2020 by dividing monthly service provision at national levels by the average service provision in the 15\u00a0months pre-COVID (January 2019-March 2020). We used the\u00a0Oxford COVID-19 Government Response Tracker (OxCGRT) index and\u00a0multi-level linear regression analyses to assess associations between the stringency of restrictions and health service disruptions over nine months. We extended the analysis by examining associations between 11 individual containment or closure policies and health service disruptions. Models were adjusted for COVID caseload, health service category and country GDP and included robust standard errors.

Findings

Chronic disease care was among the most affected services. Regression analyses revealed that a 10% increase in the mean stringency index was associated with a 3.3 percentage-point (95% CI -3.9, -2.7) reduction in relative service volumes. Among individual policies, curfews, and the presence of a state of emergency, had the largest coefficients and were associated with 14.1 (95% CI -19.6, 8.7) and 10.7 (95% CI -12.7, -8.7) percentage-point lower relative service volumes, respectively. In contrast, number of COVID-19 cases in 2020 was not associated with health service disruptions in any model.

Conclusions

Although containment policies were crucial in reducing COVID-19 mortality in many contexts, it is important to consider the indirect effects of these restrictions. Strategies to improve the resilience of health systems should be designed to ensure that populations can continue accessing essential health care despite the presence of containment policies during future infectious disease outbreaks.", "laySummary": "", - "urls": "pdf:https://www.frontiersin.org/articles/10.3389/fcvm.2023.1136764/pdf; doi:https://doi.org/10.3389/fcvm.2023.1136764; html:https://europepmc.org/articles/PMC10167048; pdf:https://europepmc.org/articles/PMC10167048?pdf=render" + "urls": "pdf:https://bmchealthservres.biomedcentral.com/counter/pdf/10.1186/s12913-023-09363-1; doi:https://doi.org/10.1186/s12913-023-09363-1; html:https://europepmc.org/articles/PMC10096103; pdf:https://europepmc.org/articles/PMC10096103?pdf=render" + }, + { + "id": "31109684", + "doi": "https://doi.org/10.1016/j.injury.2019.05.004", + "title": "Agreement between medical record and administrative coding of common comorbidities in orthopaedic trauma patients.", + "authorString": "Daly S, Nguyen TQ, Gabbe BJ, Braaf S, Simpson P, Ekegren CL.", + "authorAffiliations": "", + "journalTitle": "Injury", + "pubYear": "2019", + "date": "2019-05-08", + "isOpenAccess": "N", + "keywords": "Trauma; Comorbidity; Agreement; Orthopaedic; Icd-10-am", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Objective

To i) quantify the agreement between comorbidities documented within medical records and an orthopaedic trauma dataset; and ii) compare agreement between these sources before and after the introduction of new comorbidity coding rules in Australian hospitals.

Study design and setting

A random sample of adult (\u2265 16 years) orthopaedic trauma patients (n\u2009=\u2009400) were extracted from the Victorian Orthopaedic Trauma Outcomes Registry (VOTOR). Diagnoses of obesity, arthritis, diabetes and cardiac conditions documented within patients' medical records were compared to ICD-10-AM comorbidity codes (provided by hospitals) for the same admission. Agreement was calculated (Cohen's kappa) before and after the introduction of new coding rules.

Results

All comorbidities had the same or higher prevalence in medical record data compared to coded data. Kappa values ranged from <0.001 (poor agreement) for coronary artery disease to 0.94 (excellent agreement) for type 2 diabetes. There was improvement in agreement between sources for most conditions following the introduction of new coding rules.

Conclusion

There has been improvement in the coding of certain comorbidities since the introduction of new coding rules, suggesting that, since 2015, administrative data has improved capacity to capture patients' comorbidity profiles. Consideration must be taken when using the ICD-10-AM data due to its limitations.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1016/j.injury.2019.05.004" }, { "id": "PMC8718341", @@ -26537,21 +26537,21 @@ "urls": "html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8718341/?tool=EBI; pdf:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8718341/pdf/?tool=EBI; html:https://europepmc.org/articles/PMC8718341; pdf:https://europepmc.org/articles/PMC8718341?pdf=render" }, { - "id": "31109684", - "doi": "https://doi.org/10.1016/j.injury.2019.05.004", - "title": "Agreement between medical record and administrative coding of common comorbidities in orthopaedic trauma patients.", - "authorString": "Daly S, Nguyen TQ, Gabbe BJ, Braaf S, Simpson P, Ekegren CL.", + "id": "37180793", + "doi": "https://doi.org/10.3389/fcvm.2023.1136764", + "title": "Diabetes and heart failure associations in women and men: Results from the MORGAM consortium.", + "authorString": "Chadalavada S, Reinikainen J, Andersson J, Di Castelnuovo A, Iacoviello L, Jousilahti P, K\u00e5rhus LL, Linneberg A, S\u00f6derberg S, Tunstall-Pedoe H, Lekadir K, Aung N, Jensen MT, Kuulasmaa K, Niiranen TJ, Petersen SE.", "authorAffiliations": "", - "journalTitle": "Injury", - "pubYear": "2019", - "date": "2019-05-08", - "isOpenAccess": "N", - "keywords": "Trauma; Comorbidity; Agreement; Orthopaedic; Icd-10-am", + "journalTitle": "Frontiers in cardiovascular medicine", + "pubYear": "2023", + "date": "2023-04-25", + "isOpenAccess": "Y", + "keywords": "Diabetes; Sex differences; epidemiology; Heart Failure; Morgam", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Objective

To i) quantify the agreement between comorbidities documented within medical records and an orthopaedic trauma dataset; and ii) compare agreement between these sources before and after the introduction of new comorbidity coding rules in Australian hospitals.

Study design and setting

A random sample of adult (\u2265 16 years) orthopaedic trauma patients (n\u2009=\u2009400) were extracted from the Victorian Orthopaedic Trauma Outcomes Registry (VOTOR). Diagnoses of obesity, arthritis, diabetes and cardiac conditions documented within patients' medical records were compared to ICD-10-AM comorbidity codes (provided by hospitals) for the same admission. Agreement was calculated (Cohen's kappa) before and after the introduction of new coding rules.

Results

All comorbidities had the same or higher prevalence in medical record data compared to coded data. Kappa values ranged from <0.001 (poor agreement) for coronary artery disease to 0.94 (excellent agreement) for type 2 diabetes. There was improvement in agreement between sources for most conditions following the introduction of new coding rules.

Conclusion

There has been improvement in the coding of certain comorbidities since the introduction of new coding rules, suggesting that, since 2015, administrative data has improved capacity to capture patients' comorbidity profiles. Consideration must be taken when using the ICD-10-AM data due to its limitations.", + "abstract": "

Background

Diabetes and its cardiovascular complications are a growing concern worldwide. Recently, some studies have demonstrated that relative risk of heart failure (HF) is higher in women with type 1 diabetes (T1DM) than in men. This study aims to validate these findings in cohorts representing five countries across Europe.

Methods

This study includes 88,559 (51.8% women) participants, 3,281 (46.3% women) of whom had diabetes at baseline. Survival analysis was performed with the outcomes of interest being death and HF with a follow-up time of 12 years. Sub-group analysis according to sex and type of diabetes was also performed for the HF outcome.

Results

6,460 deaths were recorded, of which 567 were amongst those with diabetes. Additionally, HF was diagnosed in 2,772 individuals (446 with diabetes). A multivariable Cox proportional hazard analysis showed that there was an increased risk of death and HF (hazard ratio (HR) of 1.73 [1.58-1.89] and 2.12 [1.91-2.36], respectively) when comparing those with diabetes and those without. The HR for HF was 6.72 [2.75-16.41] for women with T1DM vs. 5.80 [2.72-12.37] for men with T1DM, but the interaction term for sex differences was insignificant (p for interaction 0.45). There was no significant difference in the relative risk of HF between men and women when both types of diabetes were combined (HR 2.22 [1.93-2.54] vs. 1.99 [1.67-2.38] respectively, p for interaction 0.80).

Conclusion

Diabetes is associated with increased risks of death and heart failure, and there was no difference in relative risk according to sex.", "laySummary": "", - "urls": "doi:https://doi.org/10.1016/j.injury.2019.05.004" + "urls": "pdf:https://www.frontiersin.org/articles/10.3389/fcvm.2023.1136764/pdf; doi:https://doi.org/10.3389/fcvm.2023.1136764; html:https://europepmc.org/articles/PMC10167048; pdf:https://europepmc.org/articles/PMC10167048?pdf=render" }, { "id": "31747863", @@ -26672,23 +26672,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.lanepe.2021.100267; doi:https://doi.org/10.1016/j.lanepe.2021.100267; html:https://europepmc.org/articles/PMC8629724; pdf:https://europepmc.org/articles/PMC8629724?pdf=render" }, - { - "id": "38479550", - "doi": "https://doi.org/10.1016/j.ajcnut.2024.03.006", - "title": "Dietary intake of plant- and animal-derived protein and incident cardiovascular diseases: the pan-European EPIC-CVD case-cohort study.", - "authorString": "Zheng JS, Steur M, Imamura F, Freisling H, Johnson L, van der Schouw YT, Tong TY, Weiderpass E, Bajracharya R, Crous-Bou M, Dahm CC, Heath AK, Ibsen DB, Jannasch F, Katzke V, Masala G, Moreno-Iribas C, Sacerdote C, Schulze MB, Sieri S, Wareham NJ, Danesh J, Butterworth AS, Forouhi NG.", - "authorAffiliations": "", - "journalTitle": "The American journal of clinical nutrition", - "pubYear": "2024", - "date": "2024-03-11", - "isOpenAccess": "Y", - "keywords": "Cardiovascular disease; Stroke; ischemic heart disease; Plant-derived Protein; Animal-derived Protein", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Epidemiological evidence suggests that a potential association between dietary protein intake and cardiovascular disease (CVD) may depend on the protein source, that is, plant- or animal-derived, but past research was limited and inconclusive.

Objectives

To evaluate the association of dietary plant- or animal-derived protein consumption with risk of CVD, and its components ischemic heart disease (IHD) and stroke.

Methods

This analysis in the European Prospective Investigation into Cancer and Nutrition (EPIC)-CVD case-cohort study included 16,244 incident CVD cases (10,784 IHD and 6423 stroke cases) and 15,141 subcohort members from 7 European countries. We investigated the association of estimated dietary protein intake with CVD, IHD, and stroke (total, fatal, and nonfatal) using multivariable-adjusted Prentice-weighted Cox regression. We estimated isocaloric substitutions of replacing fats and carbohydrates with plant- or animal-derived protein and replacing food-specific animal protein with plant protein. Multiplicative interactions between dietary protein and prespecified variables were tested.

Results

Neither plant- nor animal-derived protein intake was associated with incident CVD, IHD, or stroke in adjusted analyses without or with macronutrient-specified substitution analyses. Higher plant-derived protein intake was associated with 22% lower total stroke incidence among never smokers [HR 0.78, 95% confidence intervals (CI): 0.62, 0.99], but not among current smokers (HR 1.08, 95% CI: 0.83, 1.40, P-interaction = 0.004). Moreover, higher plant-derived protein (per 3% total energy) when replacing red meat protein (HR 0.52, 95% CI: 0.31, 0.88), processed meat protein (HR 0.39, 95% CI: 0.17, 0.90), and dairy protein (HR 0.54, 95% CI: 0.30, 0.98) was associated with lower incidence of fatal stroke.

Conclusion

Plant- or animal-derived protein intake was not associated with overall CVD. However, the association of plant-derived protein consumption with lower total stroke incidence among nonsmokers, and with lower incidence of fatal stroke highlights the importance of investigating CVD subtypes and potential interactions. These observations warrant further investigation in diverse populations with varying macronutrient intakes and dietary patterns.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1016/j.ajcnut.2024.03.006; doi:https://doi.org/10.1016/j.ajcnut.2024.03.006; html:https://europepmc.org/articles/PMC11130694; pdf:https://europepmc.org/articles/PMC11130694?pdf=render" - }, { "id": "35477354", "doi": "https://doi.org/10.1186/s12877-022-03077-5", @@ -26706,6 +26689,23 @@ "laySummary": "", "urls": "pdf:https://bmcgeriatr.biomedcentral.com/track/pdf/10.1186/s12877-022-03077-5; doi:https://doi.org/10.1186/s12877-022-03077-5; html:https://europepmc.org/articles/PMC9043890; pdf:https://europepmc.org/articles/PMC9043890?pdf=render" }, + { + "id": "38479550", + "doi": "https://doi.org/10.1016/j.ajcnut.2024.03.006", + "title": "Dietary intake of plant- and animal-derived protein and incident cardiovascular diseases: the pan-European EPIC-CVD case-cohort study.", + "authorString": "Zheng JS, Steur M, Imamura F, Freisling H, Johnson L, van der Schouw YT, Tong TY, Weiderpass E, Bajracharya R, Crous-Bou M, Dahm CC, Heath AK, Ibsen DB, Jannasch F, Katzke V, Masala G, Moreno-Iribas C, Sacerdote C, Schulze MB, Sieri S, Wareham NJ, Danesh J, Butterworth AS, Forouhi NG.", + "authorAffiliations": "", + "journalTitle": "The American journal of clinical nutrition", + "pubYear": "2024", + "date": "2024-03-11", + "isOpenAccess": "Y", + "keywords": "Cardiovascular disease; Stroke; ischemic heart disease; Plant-derived Protein; Animal-derived Protein", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Epidemiological evidence suggests that a potential association between dietary protein intake and cardiovascular disease (CVD) may depend on the protein source, that is, plant- or animal-derived, but past research was limited and inconclusive.

Objectives

To evaluate the association of dietary plant- or animal-derived protein consumption with risk of CVD, and its components ischemic heart disease (IHD) and stroke.

Methods

This analysis in the European Prospective Investigation into Cancer and Nutrition (EPIC)-CVD case-cohort study included 16,244 incident CVD cases (10,784 IHD and 6423 stroke cases) and 15,141 subcohort members from 7 European countries. We investigated the association of estimated dietary protein intake with CVD, IHD, and stroke (total, fatal, and nonfatal) using multivariable-adjusted Prentice-weighted Cox regression. We estimated isocaloric substitutions of replacing fats and carbohydrates with plant- or animal-derived protein and replacing food-specific animal protein with plant protein. Multiplicative interactions between dietary protein and prespecified variables were tested.

Results

Neither plant- nor animal-derived protein intake was associated with incident CVD, IHD, or stroke in adjusted analyses without or with macronutrient-specified substitution analyses. Higher plant-derived protein intake was associated with 22% lower total stroke incidence among never smokers [HR 0.78, 95% confidence intervals (CI): 0.62, 0.99], but not among current smokers (HR 1.08, 95% CI: 0.83, 1.40, P-interaction = 0.004). Moreover, higher plant-derived protein (per 3% total energy) when replacing red meat protein (HR 0.52, 95% CI: 0.31, 0.88), processed meat protein (HR 0.39, 95% CI: 0.17, 0.90), and dairy protein (HR 0.54, 95% CI: 0.30, 0.98) was associated with lower incidence of fatal stroke.

Conclusion

Plant- or animal-derived protein intake was not associated with overall CVD. However, the association of plant-derived protein consumption with lower total stroke incidence among nonsmokers, and with lower incidence of fatal stroke highlights the importance of investigating CVD subtypes and potential interactions. These observations warrant further investigation in diverse populations with varying macronutrient intakes and dietary patterns.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1016/j.ajcnut.2024.03.006; doi:https://doi.org/10.1016/j.ajcnut.2024.03.006; html:https://europepmc.org/articles/PMC11130694; pdf:https://europepmc.org/articles/PMC11130694?pdf=render" + }, { "id": "36722341", "doi": "https://doi.org/10.1093/cei/uxad008", @@ -26757,23 +26757,6 @@ "laySummary": "", "urls": "pdf:http://www.annalsofglobalhealth.org/articles/10.5334/aogh.3465/galley/3414/download/; doi:https://doi.org/10.5334/aogh.3465; html:https://europepmc.org/articles/PMC8757382; pdf:https://europepmc.org/articles/PMC8757382?pdf=render" }, - { - "id": "37422075", - "doi": "https://doi.org/10.1016/j.jval.2023.06.019", - "title": "Perspectives on Patient-Reported Outcome Data After Treatment Discontinuation in Cancer Clinical Trials.", - "authorString": "King-Kallimanis BL, Calvert M, Cella D, Cocks K, Coens C, Fairclough D, Howie L, Jonsson P, Mahendraratnam N, Maues J, Sarac S, Shaw J, Stigger N, Trask P, Wieseler B.", - "authorAffiliations": "", - "journalTitle": "Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research", - "pubYear": "2023", - "date": "2023-07-06", - "isOpenAccess": "N", - "keywords": "Oncology; Clinical Trials; Patient-reported Outcomes; Multistakeholder Perspective", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Objectives

Patient-reported outcome (PRO) data are critical in understanding treatments from the patient perspective in cancer clinical trials. The potential benefits and methodological approaches to the collection of PRO data after treatment discontinuation (eg, because of progressive disease or unacceptable drug toxicity) are less clear. The purpose of this article is to describe the Food and Drug Administration's Oncology Center of Excellence and the Critical Path Institute cosponsored 2-hour virtual roundtable, held in 2020, to discuss this specific issue.

Methods

We summarize key points from this discussion with 16 stakeholders representing academia, clinical practice, patients, international regulatory agencies, health technology assessment bodies/payers, industry, and PRO instrument development.

Results

Stakeholders recognized that any PRO data collection after treatment discontinuation should have clearly defined objectives to ensure that data can be analyzed and reported.

Conclusions

Data collection after discontinuation without a justification for its use wastes patients' time and effort and is unethical.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1016/j.jval.2023.06.019" - }, { "id": "32234121", "doi": "https://doi.org/10.2807/1560-7917.es.2020.25.12.2000256", @@ -26791,6 +26774,23 @@ "laySummary": "", "urls": "pdf:https://www.eurosurveillance.org/deliver/fulltext/eurosurveillance/25/12/eurosurv-25-12-3.pdf?itemId=%2Fcontent%2F10.2807%2F1560-7917.ES.2020.25.12.2000256&mimeType=pdf&containerItemId=content/eurosurveillance; doi:https://doi.org/10.2807/1560-7917.ES.2020.25.12.2000256; html:https://europepmc.org/articles/PMC7118348; pdf:https://europepmc.org/articles/PMC7118348?pdf=render" }, + { + "id": "37422075", + "doi": "https://doi.org/10.1016/j.jval.2023.06.019", + "title": "Perspectives on Patient-Reported Outcome Data After Treatment Discontinuation in Cancer Clinical Trials.", + "authorString": "King-Kallimanis BL, Calvert M, Cella D, Cocks K, Coens C, Fairclough D, Howie L, Jonsson P, Mahendraratnam N, Maues J, Sarac S, Shaw J, Stigger N, Trask P, Wieseler B.", + "authorAffiliations": "", + "journalTitle": "Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research", + "pubYear": "2023", + "date": "2023-07-06", + "isOpenAccess": "N", + "keywords": "Oncology; Clinical Trials; Patient-reported Outcomes; Multistakeholder Perspective", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Objectives

Patient-reported outcome (PRO) data are critical in understanding treatments from the patient perspective in cancer clinical trials. The potential benefits and methodological approaches to the collection of PRO data after treatment discontinuation (eg, because of progressive disease or unacceptable drug toxicity) are less clear. The purpose of this article is to describe the Food and Drug Administration's Oncology Center of Excellence and the Critical Path Institute cosponsored 2-hour virtual roundtable, held in 2020, to discuss this specific issue.

Methods

We summarize key points from this discussion with 16 stakeholders representing academia, clinical practice, patients, international regulatory agencies, health technology assessment bodies/payers, industry, and PRO instrument development.

Results

Stakeholders recognized that any PRO data collection after treatment discontinuation should have clearly defined objectives to ensure that data can be analyzed and reported.

Conclusions

Data collection after discontinuation without a justification for its use wastes patients' time and effort and is unethical.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1016/j.jval.2023.06.019" + }, { "id": "32814581", "doi": "https://doi.org/10.1186/s12916-020-01687-7", @@ -26893,23 +26893,6 @@ "laySummary": "", "urls": "pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1003815&type=printable; doi:https://doi.org/10.1371/journal.pmed.1003815; html:https://europepmc.org/articles/PMC8523052; pdf:https://europepmc.org/articles/PMC8523052?pdf=render" }, - { - "id": "35410933", - "doi": "https://doi.org/10.1136/bmjopen-2021-057885", - "title": "Non-pharmacological therapies for postviral syndromes, including Long COVID: a systematic review and meta-analysis protocol.", - "authorString": "Chandan JS, Brown K, Simms-Williams N, Camaradou J, Bashir N, Heining D, Aiyegbusi OL, Turner G, Cruz Rivera S, Hotham R, Nirantharakumar K, Sivan M, Khunti K, Raindi D, Marwaha S, Hughes SE, McMullan C, Calvert M, Haroon S.", - "authorAffiliations": "", - "journalTitle": "BMJ open", - "pubYear": "2022", - "date": "2022-04-11", - "isOpenAccess": "Y", - "keywords": "Infectious diseases; Rehabilitation Medicine; Covid-19", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Introduction

Postviral syndromes (PVS) describe the sustained presence of symptoms following an acute viral infection, for months or even years. Exposure to the SARS-CoV-2 virus and subsequent development of COVID-19 has shown to have similar effects with individuals continuing to exhibit symptoms for greater than 12 weeks. The sustained presence of symptoms is variably referred to as 'post COVID-19 syndrome', 'post-COVID condition' or more commonly 'Long COVID'. Knowledge of the long-term health impacts and treatments for Long COVID are evolving. To minimise overlap with existing work in the field exploring treatments of Long COVID, we have only chosen to focus on non-pharmacological treatments.

Aims

This review aims to summarise the effectiveness of non-pharmacological treatments for PVS, including Long COVID. A secondary aim is to summarise the symptoms and health impacts associated with PVS in individuals recruited to treatment studies.

Methods and analysis

Primary electronic searches will be performed in bibliographic databases including: Embase, MEDLINE, PyscINFO, CINAHL and MedRxiv from 1 January 2001 to 29 October 2021. At least two independent reviewers will screen each study for inclusion and data will be extracted from all eligible studies onto a data extraction form. The quality of all included studies will be assessed using Cochrane risk of bias tools and the Newcastle-Ottawa grading system. Non-pharmacological treatments for PVS and Long COVID will be narratively summarised and effect estimates will be pooled using random effects meta-analysis where there is sufficient methodological homogeneity. The symptoms and health impacts reported in the included studies on non-pharmacological interventions will be extracted and narratively reported.

Ethics and dissemination

This systematic review does not require ethical approval. The findings from this study will be submitted for peer-reviewed publication, shared at conference presentations and disseminated to both clinical and patient groups.

Prospero registration number

The review will adhere to this protocol which has also been registered with PROSPERO (CRD42021282074).", - "laySummary": "", - "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/12/4/e057885.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-057885; html:https://europepmc.org/articles/PMC9002258; pdf:https://europepmc.org/articles/PMC9002258?pdf=render" - }, { "id": "31671849", "doi": "https://doi.org/10.3390/ijerph16214178", @@ -26928,21 +26911,21 @@ "urls": "pdf:https://www.mdpi.com/1660-4601/16/21/4178/pdf?version=1573119054; doi:https://doi.org/10.3390/ijerph16214178; html:https://europepmc.org/articles/PMC6862192; pdf:https://europepmc.org/articles/PMC6862192?pdf=render" }, { - "id": "38106559", - "doi": "https://doi.org/10.1016/j.eclinm.2023.102251", - "title": "Long-term symptom profiles after COVID-19 vs other acute respiratory infections: an analysis of data from the COVIDENCE UK study.", - "authorString": "Vivaldi G, Pfeffer PE, Talaei M, Basera TJ, Shaheen SO, Martineau AR.", + "id": "35410933", + "doi": "https://doi.org/10.1136/bmjopen-2021-057885", + "title": "Non-pharmacological therapies for postviral syndromes, including Long COVID: a systematic review and meta-analysis protocol.", + "authorString": "Chandan JS, Brown K, Simms-Williams N, Camaradou J, Bashir N, Heining D, Aiyegbusi OL, Turner G, Cruz Rivera S, Hotham R, Nirantharakumar K, Sivan M, Khunti K, Raindi D, Marwaha S, Hughes SE, McMullan C, Calvert M, Haroon S.", "authorAffiliations": "", - "journalTitle": "EClinicalMedicine", - "pubYear": "2023", - "date": "2023-10-06", + "journalTitle": "BMJ open", + "pubYear": "2022", + "date": "2022-04-11", "isOpenAccess": "Y", - "keywords": "Acute respiratory infections; Sars-cov-2; Long Covid; Post-acute Sequelae", + "keywords": "Infectious diseases; Rehabilitation Medicine; Covid-19", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Background

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

Methods

COVIDENCE UK is a prospective, population-based UK study of ARIs in adults. We analysed data for 16\u00a0potential long COVID symptoms and health-related quality of life (HRQoL), reported between January 21 and February 15, 2021, by participants unvaccinated against SARS-CoV-2. We classified participants as having previous SARS-CoV-2 infection or previous non-COVID-19 ARI (\u22654 weeks prior) or no reported ARI. We compared symptoms by infection status using logistic and fractional regression, and identified symptom clusters using latent class analysis (LCA). This study is registered with ClinicalTrials.gov, NCT04330599.

Findings

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

Interpretation

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

Funding

Barts Charity.", + "abstract": "

Introduction

Postviral syndromes (PVS) describe the sustained presence of symptoms following an acute viral infection, for months or even years. Exposure to the SARS-CoV-2 virus and subsequent development of COVID-19 has shown to have similar effects with individuals continuing to exhibit symptoms for greater than 12 weeks. The sustained presence of symptoms is variably referred to as 'post COVID-19 syndrome', 'post-COVID condition' or more commonly 'Long COVID'. Knowledge of the long-term health impacts and treatments for Long COVID are evolving. To minimise overlap with existing work in the field exploring treatments of Long COVID, we have only chosen to focus on non-pharmacological treatments.

Aims

This review aims to summarise the effectiveness of non-pharmacological treatments for PVS, including Long COVID. A secondary aim is to summarise the symptoms and health impacts associated with PVS in individuals recruited to treatment studies.

Methods and analysis

Primary electronic searches will be performed in bibliographic databases including: Embase, MEDLINE, PyscINFO, CINAHL and MedRxiv from 1 January 2001 to 29 October 2021. At least two independent reviewers will screen each study for inclusion and data will be extracted from all eligible studies onto a data extraction form. The quality of all included studies will be assessed using Cochrane risk of bias tools and the Newcastle-Ottawa grading system. Non-pharmacological treatments for PVS and Long COVID will be narratively summarised and effect estimates will be pooled using random effects meta-analysis where there is sufficient methodological homogeneity. The symptoms and health impacts reported in the included studies on non-pharmacological interventions will be extracted and narratively reported.

Ethics and dissemination

This systematic review does not require ethical approval. The findings from this study will be submitted for peer-reviewed publication, shared at conference presentations and disseminated to both clinical and patient groups.

Prospero registration number

The review will adhere to this protocol which has also been registered with PROSPERO (CRD42021282074).", "laySummary": "", - "urls": "doi:https://doi.org/10.1016/j.eclinm.2023.102251; html:https://europepmc.org/articles/PMC10721552; pdf:https://europepmc.org/articles/PMC10721552?pdf=render" + "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/12/4/e057885.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-057885; html:https://europepmc.org/articles/PMC9002258; pdf:https://europepmc.org/articles/PMC9002258?pdf=render" }, { "id": "35585575", @@ -26961,6 +26944,23 @@ "laySummary": "", "urls": "pdf:https://bmcpublichealth.biomedcentral.com/track/pdf/10.1186/s12889-022-13219-4; doi:https://doi.org/10.1186/s12889-022-13219-4; html:https://europepmc.org/articles/PMC9115545; pdf:https://europepmc.org/articles/PMC9115545?pdf=render" }, + { + "id": "38106559", + "doi": "https://doi.org/10.1016/j.eclinm.2023.102251", + "title": "Long-term symptom profiles after COVID-19 vs other acute respiratory infections: an analysis of data from the COVIDENCE UK study.", + "authorString": "Vivaldi G, Pfeffer PE, Talaei M, Basera TJ, Shaheen SO, Martineau AR.", + "authorAffiliations": "", + "journalTitle": "EClinicalMedicine", + "pubYear": "2023", + "date": "2023-10-06", + "isOpenAccess": "Y", + "keywords": "Acute respiratory infections; Sars-cov-2; Long Covid; Post-acute Sequelae", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

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

Methods

COVIDENCE UK is a prospective, population-based UK study of ARIs in adults. We analysed data for 16\u00a0potential long COVID symptoms and health-related quality of life (HRQoL), reported between January 21 and February 15, 2021, by participants unvaccinated against SARS-CoV-2. We classified participants as having previous SARS-CoV-2 infection or previous non-COVID-19 ARI (\u22654 weeks prior) or no reported ARI. We compared symptoms by infection status using logistic and fractional regression, and identified symptom clusters using latent class analysis (LCA). This study is registered with ClinicalTrials.gov, NCT04330599.

Findings

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

Interpretation

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

Funding

Barts Charity.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1016/j.eclinm.2023.102251; html:https://europepmc.org/articles/PMC10721552; pdf:https://europepmc.org/articles/PMC10721552?pdf=render" + }, { "id": "33588321", "doi": "https://doi.org/10.1016/j.retram.2021.103276", @@ -27301,6 +27301,23 @@ "laySummary": "", "urls": "pdf:https://www.nature.com/articles/s41588-021-00991-z.pdf; doi:https://doi.org/10.1038/s41588-021-00991-z; html:https://europepmc.org/articles/PMC9883041; pdf:https://europepmc.org/articles/PMC9883041?pdf=render; doi:https://doi.org/10.1038/s41588-021-00991-z" }, + { + "id": "35866236", + "doi": "https://doi.org/10.7189/jogh.12.05033", + "title": "The road to recovery: an interrupted time series analysis of policy intervention to restore essential health services in Mexico during the COVID-19 pandemic.", + "authorString": "Doubova SV, Arsenault C, Contreras-S\u00e1nchez SE, Borrayo-S\u00e1nchez G, Leslie HH.", + "authorAffiliations": "", + "journalTitle": "Journal of global health", + "pubYear": "2022", + "date": "2022-07-23", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Recovery of health services disrupted by the COVID-19 pandemic represents a significant challenge in low- and middle-income countries. In April 2021, the Mexican Institute of Social Security (IMSS), which provides health care to 68.5 million people, launched the National Strategy for Health Services Recovery (Recovery policy). The study objective was to evaluate whether the Recovery policy addressed COVID-related declines in maternal, child health, and non-communicable diseases (NCDs) services.

Methods

We analysed the data of 35 IMSS delegations from January 2019 to November 2021 on contraceptive visits, antenatal care consultations, deliveries, caesarean sections, sick children's consultations, child vaccination, breast and cervical cancer screening, diabetes and hypertension consultations, and control. We focused on the period before (April 2020 - March 2021) and during (April 2021 - November 2021) the Recovery policy and used an interrupted time series design and Poisson Generalized Estimating Equation models to estimate the association of this policy with service use and outcomes and change in their trends.

Results

Despite the third wave of the pandemic in 2021, service utilization increased in the Recovery period, reaching (at minimum) 49% of pre-pandemic levels for sick children's consultations and (at maximum) 106% of pre-pandemic levels for breast cancer screenings. Evidence for the Recovery policy role was mixed: the policy was associated with increased facility deliveries (IRR\u2009=\u20091.15, 95%CI\u2009=\u20091.11-1.19) with a growing trend over time (IRR\u2009=\u20091.04, 95%CI\u2009=\u20091.03-1.05); antenatal care and child health services saw strong level effects but decrease over time. Additionally, the Recovery policy was associated with diabetes and hypertension control. Services recovery varied across delegations.

Conclusions

Health service utilization and NCDs control demonstrated important gains in 2021, but evidence suggests the policy had inconsistent effects across services and decreasing impact over time. Further efforts to strengthen essential health services and ensure consistent recovery across delegations are warranted.", + "laySummary": "", + "urls": "pdf:https://jogh.org/wp-content/uploads/2022/07/jogh-12-05033.pdf; doi:https://doi.org/10.7189/jogh.12.05033; html:https://europepmc.org/articles/PMC9304921; pdf:https://europepmc.org/articles/PMC9304921?pdf=render" + }, { "id": "38642613", "doi": "https://doi.org/10.1016/j.clinme.2024.100209", @@ -27335,23 +27352,6 @@ "laySummary": "", "urls": "html:https://journals.lww.com/jaids/fulltext/2024/01011/estimation_of_improvements_in_mortality_in.10.aspx; doi:https://doi.org/10.1097/QAI.0000000000003326; html:https://europepmc.org/articles/PMC10769170; pdf:https://europepmc.org/articles/PMC10769170?pdf=render" }, - { - "id": "35866236", - "doi": "https://doi.org/10.7189/jogh.12.05033", - "title": "The road to recovery: an interrupted time series analysis of policy intervention to restore essential health services in Mexico during the COVID-19 pandemic.", - "authorString": "Doubova SV, Arsenault C, Contreras-S\u00e1nchez SE, Borrayo-S\u00e1nchez G, Leslie HH.", - "authorAffiliations": "", - "journalTitle": "Journal of global health", - "pubYear": "2022", - "date": "2022-07-23", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Recovery of health services disrupted by the COVID-19 pandemic represents a significant challenge in low- and middle-income countries. In April 2021, the Mexican Institute of Social Security (IMSS), which provides health care to 68.5 million people, launched the National Strategy for Health Services Recovery (Recovery policy). The study objective was to evaluate whether the Recovery policy addressed COVID-related declines in maternal, child health, and non-communicable diseases (NCDs) services.

Methods

We analysed the data of 35 IMSS delegations from January 2019 to November 2021 on contraceptive visits, antenatal care consultations, deliveries, caesarean sections, sick children's consultations, child vaccination, breast and cervical cancer screening, diabetes and hypertension consultations, and control. We focused on the period before (April 2020 - March 2021) and during (April 2021 - November 2021) the Recovery policy and used an interrupted time series design and Poisson Generalized Estimating Equation models to estimate the association of this policy with service use and outcomes and change in their trends.

Results

Despite the third wave of the pandemic in 2021, service utilization increased in the Recovery period, reaching (at minimum) 49% of pre-pandemic levels for sick children's consultations and (at maximum) 106% of pre-pandemic levels for breast cancer screenings. Evidence for the Recovery policy role was mixed: the policy was associated with increased facility deliveries (IRR\u2009=\u20091.15, 95%CI\u2009=\u20091.11-1.19) with a growing trend over time (IRR\u2009=\u20091.04, 95%CI\u2009=\u20091.03-1.05); antenatal care and child health services saw strong level effects but decrease over time. Additionally, the Recovery policy was associated with diabetes and hypertension control. Services recovery varied across delegations.

Conclusions

Health service utilization and NCDs control demonstrated important gains in 2021, but evidence suggests the policy had inconsistent effects across services and decreasing impact over time. Further efforts to strengthen essential health services and ensure consistent recovery across delegations are warranted.", - "laySummary": "", - "urls": "pdf:https://jogh.org/wp-content/uploads/2022/07/jogh-12-05033.pdf; doi:https://doi.org/10.7189/jogh.12.05033; html:https://europepmc.org/articles/PMC9304921; pdf:https://europepmc.org/articles/PMC9304921?pdf=render" - }, { "id": "31282950", "doi": "https://doi.org/10.1001/jamaneurol.2019.1812", @@ -27421,21 +27421,21 @@ "urls": "html:https://journals.lww.com/epidem/Fulltext/2021/09000/Weight_Change_and_the_Onset_of_Cardiovascular.19.aspx; doi:https://doi.org/10.1097/EDE.0000000000001393; html:https://europepmc.org/articles/PMC8318567; pdf:https://europepmc.org/articles/PMC8318567?pdf=render" }, { - "id": "37777287", - "doi": "https://doi.org/10.1016/s2468-2667(23)00178-0", - "title": "All-cause hospitalisation among people living with HIV according to gender, mode of HIV acquisition, ethnicity, and geographical origin in Europe and North America: findings from the ART-CC cohort collaboration.", - "authorString": "Rein SM, Lampe FC, Ingle SM, Sterne JAC, Trickey A, Gill MJ, Papastamopoulos V, Wittkop L, van der Valk M, Kitchen M, Guest JL, Satre DD, Wandeler G, Galindo P, Castilho J, Crane HM, Smith CJ.", + "id": "33591280", + "doi": "https://doi.org/10.2196/16348", + "title": "A Social Media Campaign (#datasaveslives) to Promote the Benefits of Using Health Data for Research Purposes: Mixed Methods Analysis.", + "authorString": "Hassan L, Nenadic G, Tully MP.", "authorAffiliations": "", - "journalTitle": "The Lancet. Public health", - "pubYear": "2023", - "date": "2023-10-01", + "journalTitle": "Journal of medical Internet research", + "pubYear": "2021", + "date": "2021-02-16", "isOpenAccess": "Y", - "keywords": "", + "keywords": "Medical research; Public Engagement; Social Network Analysis; Social Media", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Background

Understanding demographic disparities in hospitalisation is crucial for the identification of vulnerable populations, interventions, and resource planning.

Methods

Data were from the Antiretroviral Therapy Cohort Collaboration (ART-CC) on people living with HIV in Europe and North America, followed up between January, 2007 and December, 2020. We investigated differences in all-cause hospitalisation according to gender and mode of HIV acquisition, ethnicity, and combined geographical origin and ethnicity, in people living with HIV on modern combination antiretroviral therapy (cART). Analyses were performed separately for European and North American cohorts. Hospitalisation rates were assessed using negative binomial multilevel regression, adjusted for age, time since cART intitiaion, and calendar year.

Findings

Among 23\u2008594 people living with HIV in Europe and 9612 in North America, hospitalisation rates per 100 person-years were 16\u00b72 (95% CI 16\u00b70-16\u00b74) and 13\u00b71 (12\u00b78-13\u00b75). Compared with gay, bisexual, and other men who have sex with men, rates were higher for heterosexual men and women, and much higher for men and women who acquired HIV through injection drug use (adjusted incidence rate ratios ranged from 1\u00b72 to 2\u00b75 in Europe and from 1\u00b72 to 3\u00b73 in North America). In both regions, individuals with geographical origin other than the region of study generally had lower hospitalisation rates compared with those with geographical origin of the study country. In North America, Indigenous people and Black or African American individuals had higher rates than White individuals (adjusted incidence rate ratios 1\u00b79 and 1\u00b72), whereas Asian and Hispanic people living with HIV had somewhat lower rates. In Europe there was a lower rate in Asian individuals compared with White individuals.

Interpretation

Substantial disparities exist in all-cause hospitalisation between demographic groups of people living with HIV in the current cART era in high-income settings, highlighting the need for targeted support.

Funding

Royal Free Charity and the National Institute on Alcohol Abuse and Alcoholism.", + "abstract": "

Background

Social media provides the potential to engage a wide audience about scientific research, including the public. However, little empirical research exists to guide health scientists regarding what works and how to optimize impact. We examined the social media campaign #datasaveslives established in 2014 to highlight positive examples of the use and reuse of health data in research.

Objective

This study aims to examine how the #datasaveslives hashtag was used on social media, how often, and by whom; thus, we aim to provide insights into the impact of a major social media campaign in the UK health informatics research community and further afield.

Methods

We analyzed all publicly available posts (tweets) that included the hashtag #datasaveslives (N=13,895) on the microblogging platform Twitter between September 1, 2016, and August 31, 2017. Using a combination of qualitative and quantitative analyses, we determined the frequency and purpose of tweets. Social network analysis was used to analyze and visualize tweet sharing (retweet) networks among hashtag users.

Results

Overall, we found 4175 original posts and 9720 retweets featuring #datasaveslives by 3649 unique Twitter users. In total, 66.01% (2756/4175) of the original posts were retweeted at least once. Higher frequencies of tweets were observed during the weeks of prominent policy publications, popular conferences, and public engagement events. Cluster analysis based on retweet relationships revealed an interconnected series of groups of #datasaveslives users in academia, health services and policy, and charities and patient networks. Thematic analysis of tweets showed that #datasaveslives was used for a broader range of purposes than indexing information, including event reporting, encouraging participation and action, and showing personal support for data sharing.

Conclusions

This study shows that a hashtag-based social media campaign was effective in encouraging a wide audience of stakeholders to disseminate positive examples of health research. Furthermore, the findings suggest that the campaign supported community building and bridging practices within and between the interdisciplinary sectors related to the field of health data science and encouraged individuals to demonstrate personal support for sharing health data.", "laySummary": "", - "urls": "pdf:http://www.thelancet.com/article/S2468266723001780/pdf; doi:https://doi.org/10.1016/S2468-2667(23)00178-0; html:https://europepmc.org/articles/PMC10851157; pdf:https://europepmc.org/articles/PMC10851157?pdf=render" + "urls": "pdf:https://www.jmir.org/2021/2/e16348/PDF; doi:https://doi.org/10.2196/16348; html:https://europepmc.org/articles/PMC7925154" }, { "id": "36689332", @@ -27455,21 +27455,21 @@ "urls": "pdf:https://academic.oup.com/neuro-oncology/advance-article-pdf/doi/10.1093/neuonc/noad021/49522012/noad021.pdf; doi:https://doi.org/10.1093/neuonc/noad021; html:https://europepmc.org/articles/PMC10326489; pdf:https://europepmc.org/articles/PMC10326489?pdf=render" }, { - "id": "33591280", - "doi": "https://doi.org/10.2196/16348", - "title": "A Social Media Campaign (#datasaveslives) to Promote the Benefits of Using Health Data for Research Purposes: Mixed Methods Analysis.", - "authorString": "Hassan L, Nenadic G, Tully MP.", + "id": "37777287", + "doi": "https://doi.org/10.1016/s2468-2667(23)00178-0", + "title": "All-cause hospitalisation among people living with HIV according to gender, mode of HIV acquisition, ethnicity, and geographical origin in Europe and North America: findings from the ART-CC cohort collaboration.", + "authorString": "Rein SM, Lampe FC, Ingle SM, Sterne JAC, Trickey A, Gill MJ, Papastamopoulos V, Wittkop L, van der Valk M, Kitchen M, Guest JL, Satre DD, Wandeler G, Galindo P, Castilho J, Crane HM, Smith CJ.", "authorAffiliations": "", - "journalTitle": "Journal of medical Internet research", - "pubYear": "2021", - "date": "2021-02-16", + "journalTitle": "The Lancet. Public health", + "pubYear": "2023", + "date": "2023-10-01", "isOpenAccess": "Y", - "keywords": "Medical research; Public Engagement; Social Network Analysis; Social Media", + "keywords": "", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Background

Social media provides the potential to engage a wide audience about scientific research, including the public. However, little empirical research exists to guide health scientists regarding what works and how to optimize impact. We examined the social media campaign #datasaveslives established in 2014 to highlight positive examples of the use and reuse of health data in research.

Objective

This study aims to examine how the #datasaveslives hashtag was used on social media, how often, and by whom; thus, we aim to provide insights into the impact of a major social media campaign in the UK health informatics research community and further afield.

Methods

We analyzed all publicly available posts (tweets) that included the hashtag #datasaveslives (N=13,895) on the microblogging platform Twitter between September 1, 2016, and August 31, 2017. Using a combination of qualitative and quantitative analyses, we determined the frequency and purpose of tweets. Social network analysis was used to analyze and visualize tweet sharing (retweet) networks among hashtag users.

Results

Overall, we found 4175 original posts and 9720 retweets featuring #datasaveslives by 3649 unique Twitter users. In total, 66.01% (2756/4175) of the original posts were retweeted at least once. Higher frequencies of tweets were observed during the weeks of prominent policy publications, popular conferences, and public engagement events. Cluster analysis based on retweet relationships revealed an interconnected series of groups of #datasaveslives users in academia, health services and policy, and charities and patient networks. Thematic analysis of tweets showed that #datasaveslives was used for a broader range of purposes than indexing information, including event reporting, encouraging participation and action, and showing personal support for data sharing.

Conclusions

This study shows that a hashtag-based social media campaign was effective in encouraging a wide audience of stakeholders to disseminate positive examples of health research. Furthermore, the findings suggest that the campaign supported community building and bridging practices within and between the interdisciplinary sectors related to the field of health data science and encouraged individuals to demonstrate personal support for sharing health data.", + "abstract": "

Background

Understanding demographic disparities in hospitalisation is crucial for the identification of vulnerable populations, interventions, and resource planning.

Methods

Data were from the Antiretroviral Therapy Cohort Collaboration (ART-CC) on people living with HIV in Europe and North America, followed up between January, 2007 and December, 2020. We investigated differences in all-cause hospitalisation according to gender and mode of HIV acquisition, ethnicity, and combined geographical origin and ethnicity, in people living with HIV on modern combination antiretroviral therapy (cART). Analyses were performed separately for European and North American cohorts. Hospitalisation rates were assessed using negative binomial multilevel regression, adjusted for age, time since cART intitiaion, and calendar year.

Findings

Among 23\u2008594 people living with HIV in Europe and 9612 in North America, hospitalisation rates per 100 person-years were 16\u00b72 (95% CI 16\u00b70-16\u00b74) and 13\u00b71 (12\u00b78-13\u00b75). Compared with gay, bisexual, and other men who have sex with men, rates were higher for heterosexual men and women, and much higher for men and women who acquired HIV through injection drug use (adjusted incidence rate ratios ranged from 1\u00b72 to 2\u00b75 in Europe and from 1\u00b72 to 3\u00b73 in North America). In both regions, individuals with geographical origin other than the region of study generally had lower hospitalisation rates compared with those with geographical origin of the study country. In North America, Indigenous people and Black or African American individuals had higher rates than White individuals (adjusted incidence rate ratios 1\u00b79 and 1\u00b72), whereas Asian and Hispanic people living with HIV had somewhat lower rates. In Europe there was a lower rate in Asian individuals compared with White individuals.

Interpretation

Substantial disparities exist in all-cause hospitalisation between demographic groups of people living with HIV in the current cART era in high-income settings, highlighting the need for targeted support.

Funding

Royal Free Charity and the National Institute on Alcohol Abuse and Alcoholism.", "laySummary": "", - "urls": "pdf:https://www.jmir.org/2021/2/e16348/PDF; doi:https://doi.org/10.2196/16348; html:https://europepmc.org/articles/PMC7925154" + "urls": "pdf:http://www.thelancet.com/article/S2468266723001780/pdf; doi:https://doi.org/10.1016/S2468-2667(23)00178-0; html:https://europepmc.org/articles/PMC10851157; pdf:https://europepmc.org/articles/PMC10851157?pdf=render" }, { "id": "37264679", @@ -27845,23 +27845,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.neuroimage.2022.119779; doi:https://doi.org/10.1016/j.neuroimage.2022.119779; html:https://europepmc.org/articles/PMC10933815; pdf:https://europepmc.org/articles/PMC10933815?pdf=render" }, - { - "id": "37722858", - "doi": "https://doi.org/10.3399/bjgp.2023.0077", - "title": "Inequities in hypertension management: observational cross-sectional study in North East London using electronic health records.", - "authorString": "Rison S, Redfern O, Dostal I, Carvalho C, Mathur R, Raisi-Estabragh Z, Robson J.", - "authorAffiliations": "", - "journalTitle": "The British journal of general practice : the journal of the Royal College of General Practitioners", - "pubYear": "2023", - "date": "2023-10-26", - "isOpenAccess": "Y", - "keywords": "Hypertension; Cardiovascular diseases; Blood pressure; General Practice; Antihypertensives; Health Inequities", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Hypertension is a key modifiable risk factor for cardiovascular disease - the leading cause of death in the UK. Good blood pressure (BP) control reduces mortality. However, health inequities may lead to variability in hypertension monitoring and control.

Aim

To investigate health inequities related to ethnicity, sex, age, and socioeconomic status in the monitoring, treatment, and control of BP in a large cohort of adult patients with hypertension.

Design and setting

A cross-sectional cohort study of adults with hypertension registered with general practices in North East London on 1 April 2019.

Method

Multivariable logistic regression was used to estimate associations of demographics and treatment intensity for the following hypertension management indicators: a) BP recording in past 12 months; b) BP on age- adjusted target; and c) BP on age-adjusted target and BP recorded in past 12 months.

Results

In total, 156 296 adults were included. The Black ethnicity group was less likely to have controlled BP than the White ethnicity group (odds ratio [OR] 0.87, 95% [confidence interval] CI = 0.84 to 0.91). The Asian ethnicity group was more likely to have controlled BP (OR 1.28, 95% CI = 1.23 to 1.32). Ethnicity differences in control could not be explained by the likelihood of having a recent BP recording, nor by treatment intensity differences. Older adults (aged \u226550 years) were more likely to have controlled hypertension than younger patients.

Conclusion

Individuals of Black ethnicity and younger people are less likely to have controlled hypertension and may warrant targeted interventions. Possible explanations for these findings are presented but further research is needed about reasons for ethnic differences.", - "laySummary": "", - "urls": "doi:https://doi.org/10.3399/BJGP.2023.0077; html:https://europepmc.org/articles/PMC10523336; pdf:https://europepmc.org/articles/PMC10523336?pdf=render" - }, { "id": "32400358", "doi": "https://doi.org/10.2807/1560-7917.es.2020.25.18.2000632", @@ -27879,6 +27862,23 @@ "laySummary": "The authors of this paper estimate the number of cases and spread of COVID-19 using data on critical care admissions within the UK, from a period of February to March 2020. Their results suggest that the UK had hundreds of thousands of COVID-19 cases by the time the national lockdown was implemented. They highlight the usefulness of surveilling critical care data to better understand the dynamics of the epidemic and better inform the response measures.", "urls": "pdf:https://www.eurosurveillance.org/deliver/fulltext/eurosurveillance/25/18/eurosurv-25-18-2.pdf?itemId=%2Fcontent%2F10.2807%2F1560-7917.ES.2020.25.18.2000632&mimeType=pdf&containerItemId=content/eurosurveillance; doi:https://doi.org/10.2807/1560-7917.ES.2020.25.18.2000632; html:https://europepmc.org/articles/PMC7219029; pdf:https://europepmc.org/articles/PMC7219029?pdf=render" }, + { + "id": "37722858", + "doi": "https://doi.org/10.3399/bjgp.2023.0077", + "title": "Inequities in hypertension management: observational cross-sectional study in North East London using electronic health records.", + "authorString": "Rison S, Redfern O, Dostal I, Carvalho C, Mathur R, Raisi-Estabragh Z, Robson J.", + "authorAffiliations": "", + "journalTitle": "The British journal of general practice : the journal of the Royal College of General Practitioners", + "pubYear": "2023", + "date": "2023-10-26", + "isOpenAccess": "Y", + "keywords": "Hypertension; Cardiovascular diseases; Blood pressure; General Practice; Antihypertensives; Health Inequities", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Hypertension is a key modifiable risk factor for cardiovascular disease - the leading cause of death in the UK. Good blood pressure (BP) control reduces mortality. However, health inequities may lead to variability in hypertension monitoring and control.

Aim

To investigate health inequities related to ethnicity, sex, age, and socioeconomic status in the monitoring, treatment, and control of BP in a large cohort of adult patients with hypertension.

Design and setting

A cross-sectional cohort study of adults with hypertension registered with general practices in North East London on 1 April 2019.

Method

Multivariable logistic regression was used to estimate associations of demographics and treatment intensity for the following hypertension management indicators: a) BP recording in past 12 months; b) BP on age- adjusted target; and c) BP on age-adjusted target and BP recorded in past 12 months.

Results

In total, 156 296 adults were included. The Black ethnicity group was less likely to have controlled BP than the White ethnicity group (odds ratio [OR] 0.87, 95% [confidence interval] CI = 0.84 to 0.91). The Asian ethnicity group was more likely to have controlled BP (OR 1.28, 95% CI = 1.23 to 1.32). Ethnicity differences in control could not be explained by the likelihood of having a recent BP recording, nor by treatment intensity differences. Older adults (aged \u226550 years) were more likely to have controlled hypertension than younger patients.

Conclusion

Individuals of Black ethnicity and younger people are less likely to have controlled hypertension and may warrant targeted interventions. Possible explanations for these findings are presented but further research is needed about reasons for ethnic differences.", + "laySummary": "", + "urls": "doi:https://doi.org/10.3399/BJGP.2023.0077; html:https://europepmc.org/articles/PMC10523336; pdf:https://europepmc.org/articles/PMC10523336?pdf=render" + }, { "id": "36060542", "doi": "https://doi.org/10.3389/fdgth.2022.939292", @@ -27947,23 +27947,6 @@ "laySummary": "", "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ejp.1750; doi:https://doi.org/10.1002/ejp.1750" }, - { - "id": "38597854", - "doi": "https://doi.org/10.1016/j.jcmg.2024.03.001", - "title": "Noninvasive Techniques for Tracking\u00a0Biological Aging of the Cardiovascular System: JACC Family Series.", - "authorString": "Raisi-Estabragh Z, Szabo L, Schuermans A, Salih AM, Chin CWL, V\u00e1g\u00f3 H, Altmann A, Ng FS, Garg P, Pavanello S, Marwick TH, Petersen SE.", - "authorAffiliations": "", - "journalTitle": "JACC. Cardiovascular imaging", - "pubYear": "2024", - "date": "2024-04-08", - "isOpenAccess": "N", - "keywords": "Molecular markers; Echocardiography; Cardiac Computed Tomography; Healthy Aging; Cardiac Magnetic Resonance; Multimodality Cardiovascular Imaging; Biological Heart Age", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Population aging is one of the most important demographic transformations of our time. Increasing the \"health span\"-the proportion of life spent in good health-is a global priority. Biological aging comprises molecular and cellular modifications over many years, which culminate in gradual physiological decline across multiple organ systems and predispose to age-related illnesses. Cardiovascular disease is a major cause of ill health and premature death in older people. The rate at\u00a0which biological aging occurs varies across individuals of the same age and is influenced by a wide range of genetic and\u00a0environmental exposures. The authors review the hallmarks of biological cardiovascular aging and their capture using\u00a0imaging and other noninvasive techniques and examine how this information may be used to understand aging trajectories, with the aim of guiding individual- and population-level interventions to promote healthy aging.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1016/j.jcmg.2024.03.001" - }, { "id": "36960327", "doi": "https://doi.org/10.2147/clep.s384605", @@ -27981,23 +27964,6 @@ "laySummary": "", "urls": "pdf:https://www.dovepress.com/getfile.php?fileID=88236; doi:https://doi.org/10.2147/CLEP.S384605; html:https://europepmc.org/articles/PMC10030004; pdf:https://europepmc.org/articles/PMC10030004?pdf=render" }, - { - "id": "37751444", - "doi": "https://doi.org/10.1371/journal.pone.0290583", - "title": "Long Covid symptoms and diagnosis in primary care: A cohort study using structured and unstructured data in The Health Improvement Network primary care database.", - "authorString": "Shah AD, Subramanian A, Lewis J, Dhalla S, Ford E, Haroon S, Kuan V, Nirantharakumar K.", - "authorAffiliations": "", - "journalTitle": "PloS one", - "pubYear": "2023", - "date": "2023-09-26", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Long Covid is a widely recognised consequence of COVID-19 infection, but little is known about the burden of symptoms that patients present with in primary care, as these are typically recorded only in free text clinical notes.

Aims

To compare symptoms in patients with and without a history of COVID-19, and investigate symptoms associated with a Long Covid diagnosis.

Methods

We used primary care electronic health record data until the end of December 2020 from The Health Improvement Network (THIN), a Cegedim database. We included adults registered with participating practices in England, Scotland or Wales. We extracted information about 89 symptoms and 'Long Covid' diagnoses from free text using natural language processing. We calculated hazard ratios (adjusted for age, sex, baseline medical conditions and prior symptoms) for each symptom from 12 weeks after the COVID-19 diagnosis.

Results

We compared 11,015 patients with confirmed COVID-19 and 18,098 unexposed controls. Only 20% of symptom records were coded, with 80% in free text. A wide range of symptoms were associated with COVID-19 at least 12 weeks post-infection, with strongest associations for fatigue (adjusted hazard ratio (aHR) 3.46, 95% confidence interval (CI) 2.87, 4.17), shortness of breath (aHR 2.89, 95% CI 2.48, 3.36), palpitations (aHR 2.59, 95% CI 1.86, 3.60), and phlegm (aHR 2.43, 95% CI 1.65, 3.59). However, a limited subset of symptoms were recorded within 7 days prior to a Long Covid diagnosis in more than 20% of cases: shortness of breath, chest pain, pain, fatigue, cough, and anxiety / depression.

Conclusions

Numerous symptoms are reported to primary care at least 12 weeks after COVID-19 infection, but only a subset are commonly associated with a GP diagnosis of Long Covid.", - "laySummary": "", - "urls": "pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0290583&type=printable; doi:https://doi.org/10.1371/journal.pone.0290583; html:https://europepmc.org/articles/PMC10521988; pdf:https://europepmc.org/articles/PMC10521988?pdf=render" - }, { "id": "32735830", "doi": "https://doi.org/10.1016/s2352-3026(20)30228-3", @@ -28032,6 +27998,40 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.xpro.2021.100334; doi:https://doi.org/10.1016/j.xpro.2021.100334; html:https://europepmc.org/articles/PMC7881265; pdf:https://europepmc.org/articles/PMC7881265?pdf=render" }, + { + "id": "38597854", + "doi": "https://doi.org/10.1016/j.jcmg.2024.03.001", + "title": "Noninvasive Techniques for Tracking\u00a0Biological Aging of the Cardiovascular System: JACC Family Series.", + "authorString": "Raisi-Estabragh Z, Szabo L, Schuermans A, Salih AM, Chin CWL, V\u00e1g\u00f3 H, Altmann A, Ng FS, Garg P, Pavanello S, Marwick TH, Petersen SE.", + "authorAffiliations": "", + "journalTitle": "JACC. Cardiovascular imaging", + "pubYear": "2024", + "date": "2024-04-08", + "isOpenAccess": "N", + "keywords": "Molecular markers; Echocardiography; Cardiac Computed Tomography; Healthy Aging; Cardiac Magnetic Resonance; Multimodality Cardiovascular Imaging; Biological Heart Age", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Population aging is one of the most important demographic transformations of our time. Increasing the \"health span\"-the proportion of life spent in good health-is a global priority. Biological aging comprises molecular and cellular modifications over many years, which culminate in gradual physiological decline across multiple organ systems and predispose to age-related illnesses. Cardiovascular disease is a major cause of ill health and premature death in older people. The rate at\u00a0which biological aging occurs varies across individuals of the same age and is influenced by a wide range of genetic and\u00a0environmental exposures. The authors review the hallmarks of biological cardiovascular aging and their capture using\u00a0imaging and other noninvasive techniques and examine how this information may be used to understand aging trajectories, with the aim of guiding individual- and population-level interventions to promote healthy aging.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1016/j.jcmg.2024.03.001" + }, + { + "id": "37751444", + "doi": "https://doi.org/10.1371/journal.pone.0290583", + "title": "Long Covid symptoms and diagnosis in primary care: A cohort study using structured and unstructured data in The Health Improvement Network primary care database.", + "authorString": "Shah AD, Subramanian A, Lewis J, Dhalla S, Ford E, Haroon S, Kuan V, Nirantharakumar K.", + "authorAffiliations": "", + "journalTitle": "PloS one", + "pubYear": "2023", + "date": "2023-09-26", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Long Covid is a widely recognised consequence of COVID-19 infection, but little is known about the burden of symptoms that patients present with in primary care, as these are typically recorded only in free text clinical notes.

Aims

To compare symptoms in patients with and without a history of COVID-19, and investigate symptoms associated with a Long Covid diagnosis.

Methods

We used primary care electronic health record data until the end of December 2020 from The Health Improvement Network (THIN), a Cegedim database. We included adults registered with participating practices in England, Scotland or Wales. We extracted information about 89 symptoms and 'Long Covid' diagnoses from free text using natural language processing. We calculated hazard ratios (adjusted for age, sex, baseline medical conditions and prior symptoms) for each symptom from 12 weeks after the COVID-19 diagnosis.

Results

We compared 11,015 patients with confirmed COVID-19 and 18,098 unexposed controls. Only 20% of symptom records were coded, with 80% in free text. A wide range of symptoms were associated with COVID-19 at least 12 weeks post-infection, with strongest associations for fatigue (adjusted hazard ratio (aHR) 3.46, 95% confidence interval (CI) 2.87, 4.17), shortness of breath (aHR 2.89, 95% CI 2.48, 3.36), palpitations (aHR 2.59, 95% CI 1.86, 3.60), and phlegm (aHR 2.43, 95% CI 1.65, 3.59). However, a limited subset of symptoms were recorded within 7 days prior to a Long Covid diagnosis in more than 20% of cases: shortness of breath, chest pain, pain, fatigue, cough, and anxiety / depression.

Conclusions

Numerous symptoms are reported to primary care at least 12 weeks after COVID-19 infection, but only a subset are commonly associated with a GP diagnosis of Long Covid.", + "laySummary": "", + "urls": "pdf:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0290583&type=printable; doi:https://doi.org/10.1371/journal.pone.0290583; html:https://europepmc.org/articles/PMC10521988; pdf:https://europepmc.org/articles/PMC10521988?pdf=render" + }, { "id": "32023934", "doi": "https://doi.org/10.3390/ijerph17030892", @@ -28134,6 +28134,23 @@ "laySummary": "", "urls": "pdf:https://www.frontiersin.org/articles/10.3389/fpubh.2022.1017337/pdf; doi:https://doi.org/10.3389/fpubh.2022.1017337; html:https://europepmc.org/articles/PMC9706255; pdf:https://europepmc.org/articles/PMC9706255?pdf=render" }, + { + "id": "31756303", + "doi": "https://doi.org/10.1161/circgen.119.002711", + "title": "Genetic Determinants of Lipids and Cardiovascular Disease Outcomes: A Wide-Angled Mendelian Randomization Investigation.", + "authorString": "Allara E, Morani G, Carter P, Gkatzionis A, Zuber V, Foley CN, Rees JMB, Mason AM, Bell S, Gill D, Lindstr\u00f6m S, Butterworth AS, Di Angelantonio E, Peters J, Burgess S, INVENT consortium.", + "authorAffiliations": "", + "journalTitle": "Circulation. Genomic and precision medicine", + "pubYear": "2019", + "date": "2019-11-22", + "isOpenAccess": "Y", + "keywords": "Lipids; Aortic valve stenosis; epidemiology; Venous Thromboembolism; Mendelian Randomization", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Evidence from randomized trials has shown that therapies that lower LDL (low-density lipoprotein)-cholesterol and triglycerides reduce coronary artery disease (CAD) risk. However, there is still uncertainty about their effects on other cardiovascular outcomes. We therefore performed a systematic investigation of causal relationships between circulating lipids and cardiovascular outcomes using a Mendelian randomization approach.

Methods

In the primary analysis, we performed 2-sample multivariable Mendelian randomization using data from participants of European ancestry. We also conducted univariable analyses using inverse-variance weighted and robust methods, and gene-specific analyses using variants that can be considered as proxies for specific lipid-lowering medications. We obtained associations with lipid fractions from the Global Lipids Genetics Consortium, a meta-analysis of 188\u2009577 participants, and genetic associations with cardiovascular outcomes from 367\u2009703 participants in UK Biobank.

Results

For LDL-cholesterol, in addition to the expected positive associations with CAD risk (odds ratio [OR] per 1 SD increase, 1.45 [95% CI, 1.35-1.57]) and other atheromatous outcomes (ischemic cerebrovascular disease and peripheral vascular disease), we found independent associations of genetically predicted LDL-cholesterol with abdominal aortic aneurysm (OR, 1.75 [95% CI, 1.40-2.17]) and aortic valve stenosis (OR, 1.46 [95% CI, 1.25-1.70]). Genetically predicted triglyceride levels were positively associated with CAD (OR, 1.25 [95% CI, 1.12-1.40]), aortic valve stenosis (OR, 1.29 [95% CI, 1.04-1.61]), and hypertension (OR, 1.17 [95% CI, 1.07-1.27]), but inversely associated with venous thromboembolism (OR, 0.79 [95% CI, 0.67-0.93]) and hemorrhagic stroke (OR, 0.78 [95% CI, 0.62-0.98]). We also found positive associations of genetically predicted LDL-cholesterol and triglycerides with heart failure that appeared to be mediated by CAD.

Conclusions

Lowering LDL-cholesterol is likely to prevent abdominal aortic aneurysm and aortic stenosis, in addition to CAD and other atheromatous cardiovascular outcomes. Lowering triglycerides is likely to prevent CAD and aortic valve stenosis but may increase thromboembolic risk.", + "laySummary": "", + "urls": "pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCGEN.119.002711; doi:https://doi.org/10.1161/CIRCGEN.119.002711; html:https://europepmc.org/articles/PMC6922071; pdf:https://europepmc.org/articles/PMC6922071?pdf=render" + }, { "id": "38246848", "doi": "https://doi.org/10.1016/j.tim.2023.12.004", @@ -28151,23 +28168,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.tim.2023.12.004" }, - { - "id": "36958365", - "doi": "https://doi.org/10.1016/s2352-3018(23)00028-0", - "title": "Life expectancy after 2015 of adults with HIV on long-term antiretroviral therapy in Europe and North America: a collaborative analysis of cohort studies.", - "authorString": "Trickey A, Sabin CA, Burkholder G, Crane H, d'Arminio Monforte A, Egger M, Gill MJ, Grabar S, Guest JL, Jarrin I, Lampe FC, Obel N, Reyes JM, Stephan C, Sterling TR, Teira R, Touloumi G, Wasmuth JC, Wit F, Wittkop L, Zangerle R, Silverberg MJ, Justice A, Sterne JAC.", - "authorAffiliations": "", - "journalTitle": "The lancet. HIV", - "pubYear": "2023", - "date": "2023-03-20", - "isOpenAccess": "N", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

The life expectancy of people with HIV taking antiretroviral therapy (ART) has increased substantially over the past 25 years. Most previous studies of life expectancy were based on data from the first few years after starting ART, when mortality is highest. However, many people with HIV have been successfully treated with ART for many years, and up-to-date prognosis data are needed. We aimed to estimate life expectancy in adults with HIV on ART for at least 1 year in Europe and North America from 2015 onwards.

Methods

We used data for people with HIV taking ART from the Antiretroviral Therapy Cohort Collaboration and the UK Collaborative HIV Cohort Study. Included participants started ART between 1996 and 2014 and had been on ART for at least 1 year by 2015, or started ART between 2015 and 2019 and survived for at least 1 year; all participants were aged at least 16 years at ART initiation. We used Poisson models to estimate the associations between mortality and demographic and clinical characteristics, including CD4 cell count at the start of follow-up. We also estimated the remaining years of life left for people with HIV aged 40 years who were taking ART, and stratified these estimates by variables associated with mortality. These estimates were compared with estimates for years of life remaining in a corresponding multi-country general population.

Findings

Among 206 891 people with HIV included, 5780 deaths were recorded since 2015. We estimated that women with HIV at age 40 years had 35\u00b78 years (95% CI 35\u00b72-36\u00b74) of life left if they started ART before 2015, and 39\u00b70 years (38\u00b75-39\u00b75) left if they started ART after 2015. For men with HIV, the corresponding estimates were 34\u00b75 years (33\u00b78-35\u00b72) and 37\u00b70 (36\u00b75-37\u00b76). Women with CD4 counts of fewer than 49 cells per \u03bcL at the start of follow-up had an estimated 19\u00b74 years (18\u00b72-20\u00b75) of life left at age 40 years if they started ART before 2015 and 24\u00b79 years (23\u00b79-25\u00b79) left if they started ART after 2015. The corresponding estimates for men were 18\u00b72 years (17\u00b71-19\u00b74) and 23\u00b77 years (22\u00b77-24\u00b78). Women with CD4 counts of at least 500 cells per \u03bcL at the start of follow-up had an estimated 40\u00b72 years (39\u00b77-40\u00b76) of life left at age 40 years if they started ART before 2015 and 42\u00b70 years (41\u00b77-42\u00b73) left if they started ART after 2015. The corresponding estimates for men were 38\u00b70 years (37\u00b75-38\u00b75) and 39\u00b72 years (38\u00b77-39\u00b77).

Interpretation

For people with HIV on ART and with high CD4 cell counts who survived to 2015 or started ART after 2015, life expectancy was only a few years lower than that in the general population, irrespective of when ART was started. However, for people with low CD4 counts at the start of follow-up, life-expectancy estimates were substantially lower, emphasising the continuing importance of early diagnosis and sustained treatment of HIV.

Funding

US National Institute on Alcohol Abuse and Alcoholism and UK Medical Research Council.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1016/s2352-3018(23)00028-0; doi:https://doi.org/10.1016/S2352-3018(23)00028-0; html:https://europepmc.org/articles/PMC10288029; pdf:https://europepmc.org/articles/PMC10288029?pdf=render; doi:https://doi.org/10.1016/s2352-3018(23)00028-0" - }, { "id": "34931349", "doi": "https://doi.org/10.1111/bcp.15191", @@ -28186,21 +28186,21 @@ "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/bcp.15191; doi:https://doi.org/10.1111/bcp.15191; html:https://europepmc.org/articles/PMC9303316; pdf:https://europepmc.org/articles/PMC9303316?pdf=render" }, { - "id": "31756303", - "doi": "https://doi.org/10.1161/circgen.119.002711", - "title": "Genetic Determinants of Lipids and Cardiovascular Disease Outcomes: A Wide-Angled Mendelian Randomization Investigation.", - "authorString": "Allara E, Morani G, Carter P, Gkatzionis A, Zuber V, Foley CN, Rees JMB, Mason AM, Bell S, Gill D, Lindstr\u00f6m S, Butterworth AS, Di Angelantonio E, Peters J, Burgess S, INVENT consortium.", + "id": "36958365", + "doi": "https://doi.org/10.1016/s2352-3018(23)00028-0", + "title": "Life expectancy after 2015 of adults with HIV on long-term antiretroviral therapy in Europe and North America: a collaborative analysis of cohort studies.", + "authorString": "Trickey A, Sabin CA, Burkholder G, Crane H, d'Arminio Monforte A, Egger M, Gill MJ, Grabar S, Guest JL, Jarrin I, Lampe FC, Obel N, Reyes JM, Stephan C, Sterling TR, Teira R, Touloumi G, Wasmuth JC, Wit F, Wittkop L, Zangerle R, Silverberg MJ, Justice A, Sterne JAC.", "authorAffiliations": "", - "journalTitle": "Circulation. Genomic and precision medicine", - "pubYear": "2019", - "date": "2019-11-22", - "isOpenAccess": "Y", - "keywords": "Lipids; Aortic valve stenosis; epidemiology; Venous Thromboembolism; Mendelian Randomization", + "journalTitle": "The lancet. HIV", + "pubYear": "2023", + "date": "2023-03-20", + "isOpenAccess": "N", + "keywords": "", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Background

Evidence from randomized trials has shown that therapies that lower LDL (low-density lipoprotein)-cholesterol and triglycerides reduce coronary artery disease (CAD) risk. However, there is still uncertainty about their effects on other cardiovascular outcomes. We therefore performed a systematic investigation of causal relationships between circulating lipids and cardiovascular outcomes using a Mendelian randomization approach.

Methods

In the primary analysis, we performed 2-sample multivariable Mendelian randomization using data from participants of European ancestry. We also conducted univariable analyses using inverse-variance weighted and robust methods, and gene-specific analyses using variants that can be considered as proxies for specific lipid-lowering medications. We obtained associations with lipid fractions from the Global Lipids Genetics Consortium, a meta-analysis of 188\u2009577 participants, and genetic associations with cardiovascular outcomes from 367\u2009703 participants in UK Biobank.

Results

For LDL-cholesterol, in addition to the expected positive associations with CAD risk (odds ratio [OR] per 1 SD increase, 1.45 [95% CI, 1.35-1.57]) and other atheromatous outcomes (ischemic cerebrovascular disease and peripheral vascular disease), we found independent associations of genetically predicted LDL-cholesterol with abdominal aortic aneurysm (OR, 1.75 [95% CI, 1.40-2.17]) and aortic valve stenosis (OR, 1.46 [95% CI, 1.25-1.70]). Genetically predicted triglyceride levels were positively associated with CAD (OR, 1.25 [95% CI, 1.12-1.40]), aortic valve stenosis (OR, 1.29 [95% CI, 1.04-1.61]), and hypertension (OR, 1.17 [95% CI, 1.07-1.27]), but inversely associated with venous thromboembolism (OR, 0.79 [95% CI, 0.67-0.93]) and hemorrhagic stroke (OR, 0.78 [95% CI, 0.62-0.98]). We also found positive associations of genetically predicted LDL-cholesterol and triglycerides with heart failure that appeared to be mediated by CAD.

Conclusions

Lowering LDL-cholesterol is likely to prevent abdominal aortic aneurysm and aortic stenosis, in addition to CAD and other atheromatous cardiovascular outcomes. Lowering triglycerides is likely to prevent CAD and aortic valve stenosis but may increase thromboembolic risk.", + "abstract": "

Background

The life expectancy of people with HIV taking antiretroviral therapy (ART) has increased substantially over the past 25 years. Most previous studies of life expectancy were based on data from the first few years after starting ART, when mortality is highest. However, many people with HIV have been successfully treated with ART for many years, and up-to-date prognosis data are needed. We aimed to estimate life expectancy in adults with HIV on ART for at least 1 year in Europe and North America from 2015 onwards.

Methods

We used data for people with HIV taking ART from the Antiretroviral Therapy Cohort Collaboration and the UK Collaborative HIV Cohort Study. Included participants started ART between 1996 and 2014 and had been on ART for at least 1 year by 2015, or started ART between 2015 and 2019 and survived for at least 1 year; all participants were aged at least 16 years at ART initiation. We used Poisson models to estimate the associations between mortality and demographic and clinical characteristics, including CD4 cell count at the start of follow-up. We also estimated the remaining years of life left for people with HIV aged 40 years who were taking ART, and stratified these estimates by variables associated with mortality. These estimates were compared with estimates for years of life remaining in a corresponding multi-country general population.

Findings

Among 206 891 people with HIV included, 5780 deaths were recorded since 2015. We estimated that women with HIV at age 40 years had 35\u00b78 years (95% CI 35\u00b72-36\u00b74) of life left if they started ART before 2015, and 39\u00b70 years (38\u00b75-39\u00b75) left if they started ART after 2015. For men with HIV, the corresponding estimates were 34\u00b75 years (33\u00b78-35\u00b72) and 37\u00b70 (36\u00b75-37\u00b76). Women with CD4 counts of fewer than 49 cells per \u03bcL at the start of follow-up had an estimated 19\u00b74 years (18\u00b72-20\u00b75) of life left at age 40 years if they started ART before 2015 and 24\u00b79 years (23\u00b79-25\u00b79) left if they started ART after 2015. The corresponding estimates for men were 18\u00b72 years (17\u00b71-19\u00b74) and 23\u00b77 years (22\u00b77-24\u00b78). Women with CD4 counts of at least 500 cells per \u03bcL at the start of follow-up had an estimated 40\u00b72 years (39\u00b77-40\u00b76) of life left at age 40 years if they started ART before 2015 and 42\u00b70 years (41\u00b77-42\u00b73) left if they started ART after 2015. The corresponding estimates for men were 38\u00b70 years (37\u00b75-38\u00b75) and 39\u00b72 years (38\u00b77-39\u00b77).

Interpretation

For people with HIV on ART and with high CD4 cell counts who survived to 2015 or started ART after 2015, life expectancy was only a few years lower than that in the general population, irrespective of when ART was started. However, for people with low CD4 counts at the start of follow-up, life-expectancy estimates were substantially lower, emphasising the continuing importance of early diagnosis and sustained treatment of HIV.

Funding

US National Institute on Alcohol Abuse and Alcoholism and UK Medical Research Council.", "laySummary": "", - "urls": "pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCGEN.119.002711; doi:https://doi.org/10.1161/CIRCGEN.119.002711; html:https://europepmc.org/articles/PMC6922071; pdf:https://europepmc.org/articles/PMC6922071?pdf=render" + "urls": "doi:https://doi.org/10.1016/s2352-3018(23)00028-0; doi:https://doi.org/10.1016/S2352-3018(23)00028-0; html:https://europepmc.org/articles/PMC10288029; pdf:https://europepmc.org/articles/PMC10288029?pdf=render; doi:https://doi.org/10.1016/s2352-3018(23)00028-0" }, { "id": "37671353", @@ -28236,23 +28236,6 @@ "laySummary": "", "urls": "pdf:https://bmcfampract.biomedcentral.com/track/pdf/10.1186/s12875-021-01384-1; doi:https://doi.org/10.1186/s12875-021-01384-1; html:https://europepmc.org/articles/PMC7927406; pdf:https://europepmc.org/articles/PMC7927406?pdf=render" }, - { - "id": "38233595", - "doi": "https://doi.org/10.1038/s41588-023-01638-x", - "title": "Inherited polygenic effects on common hematological traits influence clonal selection on JAK2V617F and the development of myeloproliferative neoplasms.", - "authorString": "Guo J, Walter K, Quiros PM, Gu M, Baxter EJ, Danesh J, Di Angelantonio E, Roberts D, Guglielmelli P, Harrison CN, Godfrey AL, Green AR, Vassiliou GS, Vuckovic D, Nangalia J, Soranzo N.", - "authorAffiliations": "", - "journalTitle": "Nature genetics", - "pubYear": "2024", - "date": "2024-01-17", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Myeloproliferative neoplasms (MPNs) are chronic cancers characterized by overproduction of mature blood cells. Their causative somatic mutations, for example, JAK2V617F, are common in the population, yet only a minority of carriers develop MPN. Here we show that the inherited polygenic loci that underlie common hematological traits influence JAK2V617F clonal expansion. We identify polygenic risk scores (PGSs) for monocyte count and plateletcrit as new risk factors for JAK2V617F positivity. PGSs for several hematological traits influenced the risk of different MPN subtypes, with low PGSs for two platelet traits also showing protective effects in JAK2V617F carriers, making them two to three times less likely to have essential thrombocythemia than carriers with high PGSs. We observed that extreme hematological PGSs may contribute to an MPN diagnosis in the absence of somatic driver mutations. Our study showcases how polygenic backgrounds underlying common hematological traits influence both clonal selection on somatic mutations and the subsequent phenotype of cancer.", - "laySummary": "", - "urls": "pdf:https://www.nature.com/articles/s41588-023-01638-x.pdf; doi:https://doi.org/10.1038/s41588-023-01638-x; html:https://europepmc.org/articles/PMC10864174; pdf:https://europepmc.org/articles/PMC10864174?pdf=render" - }, { "id": "36732776", "doi": "https://doi.org/10.1186/s13040-023-00321-5", @@ -28271,21 +28254,21 @@ "urls": "pdf:https://biodatamining.biomedcentral.com/counter/pdf/10.1186/s13040-023-00321-5; doi:https://doi.org/10.1186/s13040-023-00321-5; html:https://europepmc.org/articles/PMC9893534; pdf:https://europepmc.org/articles/PMC9893534?pdf=render" }, { - "id": "38115598", - "doi": "https://doi.org/10.1089/neu.2023.0461", - "title": "The Australian Traumatic Brain Injury Initiative: Systematic Review and Consensus Process to Determine the Predictive Value of Demographic, Injury Event, and Social Characteristics on Outcomes for People With Moderate-Severe Traumatic Brain Injury.", - "authorString": "Gabbe BJ, Keeves J, McKimmie A, Gadowski AM, Holland AJ, Semple BD, Young JT, Crowe L, Ownsworth T, Bagg MK, Antonic-Baker A, Hicks AJ, Hill R, Curtis K, Romero L, Ponsford JL, Lannin NA, O'Brien TJ, Cameron PA, Cooper DJ, Rushworth N, Fitzgerald M.", + "id": "38233595", + "doi": "https://doi.org/10.1038/s41588-023-01638-x", + "title": "Inherited polygenic effects on common hematological traits influence clonal selection on JAK2V617F and the development of myeloproliferative neoplasms.", + "authorString": "Guo J, Walter K, Quiros PM, Gu M, Baxter EJ, Danesh J, Di Angelantonio E, Roberts D, Guglielmelli P, Harrison CN, Godfrey AL, Green AR, Vassiliou GS, Vuckovic D, Nangalia J, Soranzo N.", "authorAffiliations": "", - "journalTitle": "Journal of neurotrauma", + "journalTitle": "Nature genetics", "pubYear": "2024", - "date": "2024-04-01", - "isOpenAccess": "N", - "keywords": "Traumatic; Demography; Common Data Elements; Social Factors; Outcome Assessment, Health Care; Systematic Review [Publication Type]; Brain Injuries, Culture", + "date": "2024-01-17", + "isOpenAccess": "Y", + "keywords": "", "nationalPriorities": "", "healthCategories": "", - "abstract": "The objective of the Australian Traumatic Brain Injury (AUS-TBI) Initiative is to develop a data dictionary to inform data collection and facilitate prediction of outcomes of people who experience moderate-severe TBI in Australia. The aim of this systematic review was to summarize the evidence of the association between demographic, injury event, and social characteristics with outcomes, in people with moderate-severe TBI, to identify potentially predictive indicators. Standardized searches were implemented across bibliographic databases to March 31, 2022. English-language reports, excluding case series, which evaluated the association between demographic, injury event, and social characteristics, and any clinical outcome in at least 10 patients with moderate-severe TBI were included. Abstracts and full text records were independently screened by at least two reviewers in Covidence. A pre-defined algorithm was used to assign a judgement of predictive value to each observed association. The review findings were discussed with an expert panel to determine the feasibility of incorporation of routine measurement into standard care. The search strategy retrieved 16,685 records; 867 full-length records were screened, and 111 studies included. Twenty-two predictors of 32 different outcomes were identified; 7 were classified as high-level (age, sex, ethnicity, employment, insurance, education, and living situation at the time of injury). After discussion with an expert consensus group, 15 were recommended for inclusion in the data dictionary. This review identified numerous predictors capable of enabling early identification of those at risk for poor outcomes and improved personalization of care through inclusion in routine data collection.", + "abstract": "Myeloproliferative neoplasms (MPNs) are chronic cancers characterized by overproduction of mature blood cells. Their causative somatic mutations, for example, JAK2V617F, are common in the population, yet only a minority of carriers develop MPN. Here we show that the inherited polygenic loci that underlie common hematological traits influence JAK2V617F clonal expansion. We identify polygenic risk scores (PGSs) for monocyte count and plateletcrit as new risk factors for JAK2V617F positivity. PGSs for several hematological traits influenced the risk of different MPN subtypes, with low PGSs for two platelet traits also showing protective effects in JAK2V617F carriers, making them two to three times less likely to have essential thrombocythemia than carriers with high PGSs. We observed that extreme hematological PGSs may contribute to an MPN diagnosis in the absence of somatic driver mutations. Our study showcases how polygenic backgrounds underlying common hematological traits influence both clonal selection on somatic mutations and the subsequent phenotype of cancer.", "laySummary": "", - "urls": "doi:https://doi.org/10.1089/neu.2023.0461" + "urls": "pdf:https://www.nature.com/articles/s41588-023-01638-x.pdf; doi:https://doi.org/10.1038/s41588-023-01638-x; html:https://europepmc.org/articles/PMC10864174; pdf:https://europepmc.org/articles/PMC10864174?pdf=render" }, { "id": "34982094", @@ -28304,6 +28287,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1167/tvst.11.1.3; doi:https://doi.org/10.1167/tvst.11.1.3; html:https://europepmc.org/articles/PMC8742534; pdf:https://europepmc.org/articles/PMC8742534?pdf=render" }, + { + "id": "38115598", + "doi": "https://doi.org/10.1089/neu.2023.0461", + "title": "The Australian Traumatic Brain Injury Initiative: Systematic Review and Consensus Process to Determine the Predictive Value of Demographic, Injury Event, and Social Characteristics on Outcomes for People With Moderate-Severe Traumatic Brain Injury.", + "authorString": "Gabbe BJ, Keeves J, McKimmie A, Gadowski AM, Holland AJ, Semple BD, Young JT, Crowe L, Ownsworth T, Bagg MK, Antonic-Baker A, Hicks AJ, Hill R, Curtis K, Romero L, Ponsford JL, Lannin NA, O'Brien TJ, Cameron PA, Cooper DJ, Rushworth N, Fitzgerald M.", + "authorAffiliations": "", + "journalTitle": "Journal of neurotrauma", + "pubYear": "2024", + "date": "2024-04-01", + "isOpenAccess": "N", + "keywords": "Traumatic; Demography; Common Data Elements; Social Factors; Outcome Assessment, Health Care; Systematic Review [Publication Type]; Brain Injuries, Culture", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "The objective of the Australian Traumatic Brain Injury (AUS-TBI) Initiative is to develop a data dictionary to inform data collection and facilitate prediction of outcomes of people who experience moderate-severe TBI in Australia. The aim of this systematic review was to summarize the evidence of the association between demographic, injury event, and social characteristics with outcomes, in people with moderate-severe TBI, to identify potentially predictive indicators. Standardized searches were implemented across bibliographic databases to March 31, 2022. English-language reports, excluding case series, which evaluated the association between demographic, injury event, and social characteristics, and any clinical outcome in at least 10 patients with moderate-severe TBI were included. Abstracts and full text records were independently screened by at least two reviewers in Covidence. A pre-defined algorithm was used to assign a judgement of predictive value to each observed association. The review findings were discussed with an expert panel to determine the feasibility of incorporation of routine measurement into standard care. The search strategy retrieved 16,685 records; 867 full-length records were screened, and 111 studies included. Twenty-two predictors of 32 different outcomes were identified; 7 were classified as high-level (age, sex, ethnicity, employment, insurance, education, and living situation at the time of injury). After discussion with an expert consensus group, 15 were recommended for inclusion in the data dictionary. This review identified numerous predictors capable of enabling early identification of those at risk for poor outcomes and improved personalization of care through inclusion in routine data collection.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1089/neu.2023.0461" + }, { "id": "35983770", "doi": "https://doi.org/10.2807/1560-7917.es.2022.27.33.2100885", @@ -28423,23 +28423,6 @@ "laySummary": "", "urls": "pdf:https://njl-admin.nihr.ac.uk/document/download/2034745; html:http://europepmc.org/books/NBK563908; doi:https://doi.org/10.3310/hta24570" }, - { - "id": "37814896", - "doi": "https://doi.org/10.1161/circgen.123.004181", - "title": "Cardiovascular Disease Knowledge Portal: A Community Resource for Cardiovascular Disease Research.", - "authorString": "Costanzo MC, Roselli C, Brandes M, Duby M, Hoang Q, Jang D, Koesterer R, Kudtarkar P, Moriondo A, Nguyen T, Ruebenacker O, Smadbeck P, Sun Y, Butterworth AS, Aragam KG, Lumbers RT, Khera AV, Lubitz SA, Ellinor PT, Gaulton KJ, Flannick J, Burtt NP.", - "authorAffiliations": "", - "journalTitle": "Circulation. Genomic and precision medicine", - "pubYear": "2023", - "date": "2023-10-10", - "isOpenAccess": "N", - "keywords": "Cardiovascular diseases; Database; Phenotype; Myocardial infarction; Biomarkers; epigenomics", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "", - "laySummary": "", - "urls": "doi:https://doi.org/10.1161/CIRCGEN.123.004181" - }, { "id": "36814324", "doi": "https://doi.org/10.1186/s13195-023-01184-y", @@ -28457,6 +28440,23 @@ "laySummary": "", "urls": "pdf:https://alzres.biomedcentral.com/counter/pdf/10.1186/s13195-023-01184-y; doi:https://doi.org/10.1186/s13195-023-01184-y; html:https://europepmc.org/articles/PMC9945600; pdf:https://europepmc.org/articles/PMC9945600?pdf=render" }, + { + "id": "37814896", + "doi": "https://doi.org/10.1161/circgen.123.004181", + "title": "Cardiovascular Disease Knowledge Portal: A Community Resource for Cardiovascular Disease Research.", + "authorString": "Costanzo MC, Roselli C, Brandes M, Duby M, Hoang Q, Jang D, Koesterer R, Kudtarkar P, Moriondo A, Nguyen T, Ruebenacker O, Smadbeck P, Sun Y, Butterworth AS, Aragam KG, Lumbers RT, Khera AV, Lubitz SA, Ellinor PT, Gaulton KJ, Flannick J, Burtt NP.", + "authorAffiliations": "", + "journalTitle": "Circulation. Genomic and precision medicine", + "pubYear": "2023", + "date": "2023-10-10", + "isOpenAccess": "N", + "keywords": "Cardiovascular diseases; Database; Phenotype; Myocardial infarction; Biomarkers; epigenomics", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "", + "laySummary": "", + "urls": "doi:https://doi.org/10.1161/CIRCGEN.123.004181" + }, { "id": "38198570", "doi": "https://doi.org/10.1126/scitranslmed.adf4428", @@ -28967,23 +28967,6 @@ "laySummary": "", "urls": "pdf:https://www.bmj.com/content/bmj/370/bmj.m3210.full.pdf; doi:https://doi.org/10.1136/bmj.m3210; html:https://europepmc.org/articles/PMC7490785" }, - { - "id": "38115587", - "doi": "https://doi.org/10.1089/neu.2023.0464", - "title": "The Australian Traumatic Brain Injury Initiative: Systematic Review of Predictive Value of Biological Markers for People With Moderate-Severe Traumatic Brain Injury.", - "authorString": "Bagg MK, Hellewell SC, Keeves J, Antonic-Baker A, McKimmie A, Hicks AJ, Gadowski A, Newcombe VFJ, Barlow KM, Balogh ZJ, Ross JP, Law M, Caeyenberghs K, Parizel PM, Thorne J, Papini M, Gill G, Jefferson A, Ponsford JL, Lannin NA, O'Brien TJ, Cameron PA, Cooper DJ, Rushworth N, Gabbe BJ, Fitzgerald M.", - "authorAffiliations": "", - "journalTitle": "Journal of neurotrauma", - "pubYear": "2024", - "date": "2024-03-08", - "isOpenAccess": "N", - "keywords": "Tomography, X-ray computed; Tissues; Biomarkers; Magnetic Resonance Imaging; Body Fluids; Common Data Elements; Brain Injuries, Traumatic; Systematic Review [Publication Type]", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "The Australian Traumatic Brain Injury Initiative (AUS-TBI) aims to co-design a data resource to predict outcomes for people with moderate-severe traumatic brain injury (TBI) across Australia. Fundamental to this resource is the data dictionary, which is an ontology of data items. Here, we report the systematic review and consensus process for inclusion of biological markers in the data dictionary. Standardized database searches were implemented from inception through April 2022. English-language studies evaluating association between a fluid, tissue, or imaging marker and any clinical outcome in at least 10 patients with moderate-severe TBI were included. Records were screened using a prioritization algorithm and saturation threshold in Research Screener. Full-length records were then screened in Covidence. A pre-defined algorithm was used to assign a judgement of predictive value to each observed association, and high-value predictors were discussed in a consensus process. Searches retrieved 106,593 records; 1,417 full-length records were screened, resulting in 546 included records. Two hundred thirty-nine individual markers were extracted, evaluated against 101 outcomes. Forty-one markers were judged to be high-value predictors of 15 outcomes. Fluid markers retained following the consensus process included ubiquitin C-terminal hydrolase L1 (UCH-L1), S100, and glial fibrillary acidic protein (GFAP). Imaging markers included computed tomography (CT) scores (e.g., Marshall scores), pathological observations (e.g., hemorrhage, midline shift), and magnetic resonance imaging (MRI) classification (e.g., diffuse axonal injury). Clinical context and time of sampling of potential predictive indicators are important considerations for utility. This systematic review and consensus process has identified fluid and imaging biomarkers with high predictive value of clinical and long-term outcomes following moderate-severe TBI.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1089/neu.2023.0464" - }, { "id": "32900377", "doi": "https://doi.org/10.1186/s12916-020-01754-z", @@ -29001,6 +28984,23 @@ "laySummary": "", "urls": "pdf:https://bmcmedicine.biomedcentral.com/track/pdf/10.1186/s12916-020-01754-z; doi:https://doi.org/10.1186/s12916-020-01754-z; html:https://europepmc.org/articles/PMC7487816; pdf:https://europepmc.org/articles/PMC7487816?pdf=render" }, + { + "id": "38115587", + "doi": "https://doi.org/10.1089/neu.2023.0464", + "title": "The Australian Traumatic Brain Injury Initiative: Systematic Review of Predictive Value of Biological Markers for People With Moderate-Severe Traumatic Brain Injury.", + "authorString": "Bagg MK, Hellewell SC, Keeves J, Antonic-Baker A, McKimmie A, Hicks AJ, Gadowski A, Newcombe VFJ, Barlow KM, Balogh ZJ, Ross JP, Law M, Caeyenberghs K, Parizel PM, Thorne J, Papini M, Gill G, Jefferson A, Ponsford JL, Lannin NA, O'Brien TJ, Cameron PA, Cooper DJ, Rushworth N, Gabbe BJ, Fitzgerald M.", + "authorAffiliations": "", + "journalTitle": "Journal of neurotrauma", + "pubYear": "2024", + "date": "2024-03-08", + "isOpenAccess": "N", + "keywords": "Tomography, X-ray computed; Tissues; Biomarkers; Magnetic Resonance Imaging; Body Fluids; Common Data Elements; Brain Injuries, Traumatic; Systematic Review [Publication Type]", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "The Australian Traumatic Brain Injury Initiative (AUS-TBI) aims to co-design a data resource to predict outcomes for people with moderate-severe traumatic brain injury (TBI) across Australia. Fundamental to this resource is the data dictionary, which is an ontology of data items. Here, we report the systematic review and consensus process for inclusion of biological markers in the data dictionary. Standardized database searches were implemented from inception through April 2022. English-language studies evaluating association between a fluid, tissue, or imaging marker and any clinical outcome in at least 10 patients with moderate-severe TBI were included. Records were screened using a prioritization algorithm and saturation threshold in Research Screener. Full-length records were then screened in Covidence. A pre-defined algorithm was used to assign a judgement of predictive value to each observed association, and high-value predictors were discussed in a consensus process. Searches retrieved 106,593 records; 1,417 full-length records were screened, resulting in 546 included records. Two hundred thirty-nine individual markers were extracted, evaluated against 101 outcomes. Forty-one markers were judged to be high-value predictors of 15 outcomes. Fluid markers retained following the consensus process included ubiquitin C-terminal hydrolase L1 (UCH-L1), S100, and glial fibrillary acidic protein (GFAP). Imaging markers included computed tomography (CT) scores (e.g., Marshall scores), pathological observations (e.g., hemorrhage, midline shift), and magnetic resonance imaging (MRI) classification (e.g., diffuse axonal injury). Clinical context and time of sampling of potential predictive indicators are important considerations for utility. This systematic review and consensus process has identified fluid and imaging biomarkers with high predictive value of clinical and long-term outcomes following moderate-severe TBI.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1089/neu.2023.0464" + }, { "id": "34535985", "doi": "https://doi.org/10.1002/hep4.1805", @@ -29103,23 +29103,6 @@ "laySummary": "", "urls": "pdf:https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1010726&type=printable; doi:https://doi.org/10.1371/journal.pcbi.1010726; html:https://europepmc.org/articles/PMC9744322; pdf:https://europepmc.org/articles/PMC9744322?pdf=render" }, - { - "id": "36512045", - "doi": "https://doi.org/10.1007/s00330-022-09323-z", - "title": "Prediction of incident cardiovascular events using machine learning and CMR radiomics.", - "authorString": "Pujadas ER, Raisi-Estabragh Z, Szabo L, McCracken C, Morcillo CI, Campello VM, Mart\u00edn-Isla C, Atehortua AM, Vago H, Merkely B, Maurovich-Horvat P, Harvey NC, Neubauer S, Petersen SE, Lekadir K.", - "authorAffiliations": "", - "journalTitle": "European radiology", - "pubYear": "2023", - "date": "2022-12-13", - "isOpenAccess": "Y", - "keywords": "Atrial fibrillation; Heart Failure; Preventive Medicine; Machine Learning; Radiomics", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Objectives

Evaluation of the feasibility of using cardiovascular magnetic resonance (CMR) radiomics in the prediction of incident atrial fibrillation (AF), heart failure (HF), myocardial infarction\u00a0(MI), and stroke using machine learning techniques.

Methods

We identified participants from the UK Biobank who experienced incident AF, HF, MI, or stroke during the continuous longitudinal follow-up. The CMR indices and the vascular risk factors (VRFs) as well as the CMR images were obtained for each participant. Three-segmented regions of interest (ROIs) were computed: right ventricle cavity, left ventricle (LV) cavity, and LV myocardium in end-systole and end-diastole phases. Radiomics features were extracted from the 3D volumes of the ROIs. Seven integrative models were built for each incident cardiovascular disease (CVD) as an outcome. Each model was built with VRF, CMR indices, and radiomics features and a combination of them. Support vector machine was used for classification. To assess the model performance, the accuracy, sensitivity, specificity, and AUC were reported.

Results

AF prediction model using the VRF+CMR+Rad model (accuracy: 0.71, AUC 0.76) obtained the best result. However, the AUC was similar to the VRF+Rad model. HF showed the most significant improvement with the inclusion of CMR metrics (VRF+CMR+Rad: 0.79, AUC 0.84). Moreover, adding only the radiomics features to the VRF reached an almost similarly good performance (VRF+Rad: accuracy 0.77, AUC 0.83). Prediction models looking into incident MI and stroke reached slightly smaller improvement.

Conclusions

Radiomics features may provide incremental predictive value over VRF and CMR indices in the prediction of incident CVDs.

Key points

\u2022 Prediction of incident atrial fibrillation, heart failure, stroke, and myocardial infarction using machine learning techniques. \u2022 CMR radiomics, vascular risk factors, and standard CMR indices will be considered in the machine learning models. \u2022 The experiments show that radiomics features can provide incremental predictive value over VRF and CMR indices in the prediction of incident cardiovascular diseases.", - "laySummary": "", - "urls": "pdf:https://link.springer.com/content/pdf/10.1007/s00330-022-09323-z.pdf; doi:https://doi.org/10.1007/s00330-022-09323-z; html:https://europepmc.org/articles/PMC10121487; pdf:https://europepmc.org/articles/PMC10121487?pdf=render" - }, { "id": "30848519", "doi": "https://doi.org/10.1111/dme.13945", @@ -29137,6 +29120,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1111/dme.13945" }, + { + "id": "36512045", + "doi": "https://doi.org/10.1007/s00330-022-09323-z", + "title": "Prediction of incident cardiovascular events using machine learning and CMR radiomics.", + "authorString": "Pujadas ER, Raisi-Estabragh Z, Szabo L, McCracken C, Morcillo CI, Campello VM, Mart\u00edn-Isla C, Atehortua AM, Vago H, Merkely B, Maurovich-Horvat P, Harvey NC, Neubauer S, Petersen SE, Lekadir K.", + "authorAffiliations": "", + "journalTitle": "European radiology", + "pubYear": "2023", + "date": "2022-12-13", + "isOpenAccess": "Y", + "keywords": "Atrial fibrillation; Heart Failure; Preventive Medicine; Machine Learning; Radiomics", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Objectives

Evaluation of the feasibility of using cardiovascular magnetic resonance (CMR) radiomics in the prediction of incident atrial fibrillation (AF), heart failure (HF), myocardial infarction\u00a0(MI), and stroke using machine learning techniques.

Methods

We identified participants from the UK Biobank who experienced incident AF, HF, MI, or stroke during the continuous longitudinal follow-up. The CMR indices and the vascular risk factors (VRFs) as well as the CMR images were obtained for each participant. Three-segmented regions of interest (ROIs) were computed: right ventricle cavity, left ventricle (LV) cavity, and LV myocardium in end-systole and end-diastole phases. Radiomics features were extracted from the 3D volumes of the ROIs. Seven integrative models were built for each incident cardiovascular disease (CVD) as an outcome. Each model was built with VRF, CMR indices, and radiomics features and a combination of them. Support vector machine was used for classification. To assess the model performance, the accuracy, sensitivity, specificity, and AUC were reported.

Results

AF prediction model using the VRF+CMR+Rad model (accuracy: 0.71, AUC 0.76) obtained the best result. However, the AUC was similar to the VRF+Rad model. HF showed the most significant improvement with the inclusion of CMR metrics (VRF+CMR+Rad: 0.79, AUC 0.84). Moreover, adding only the radiomics features to the VRF reached an almost similarly good performance (VRF+Rad: accuracy 0.77, AUC 0.83). Prediction models looking into incident MI and stroke reached slightly smaller improvement.

Conclusions

Radiomics features may provide incremental predictive value over VRF and CMR indices in the prediction of incident CVDs.

Key points

\u2022 Prediction of incident atrial fibrillation, heart failure, stroke, and myocardial infarction using machine learning techniques. \u2022 CMR radiomics, vascular risk factors, and standard CMR indices will be considered in the machine learning models. \u2022 The experiments show that radiomics features can provide incremental predictive value over VRF and CMR indices in the prediction of incident cardiovascular diseases.", + "laySummary": "", + "urls": "pdf:https://link.springer.com/content/pdf/10.1007/s00330-022-09323-z.pdf; doi:https://doi.org/10.1007/s00330-022-09323-z; html:https://europepmc.org/articles/PMC10121487; pdf:https://europepmc.org/articles/PMC10121487?pdf=render" + }, { "id": "34596018", "doi": "https://doi.org/10.2807/1560-7917.es.2021.26.39.2001440", @@ -29375,6 +29375,23 @@ "laySummary": "", "urls": "html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8081749; doi:https://doi.org/10.1016/j.jinf.2021.04.027; html:https://europepmc.org/articles/PMC8081749; pdf:https://europepmc.org/articles/PMC8081749?pdf=render" }, + { + "id": "30444743", + "doi": "https://doi.org/10.1097/ccm.0000000000003424", + "title": "Risk Factors for 1-Year Mortality and Hospital Utilization Patterns in Critical Care Survivors: A Retrospective, Observational, Population-Based Data Linkage Study.", + "authorString": "Szakmany T, Walters AM, Pugh R, Battle C, Berridge DM, Lyons RA.", + "authorAffiliations": "", + "journalTitle": "Critical care medicine", + "pubYear": "2019", + "date": "2019-01-01", + "isOpenAccess": "N", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Objectives

Clear understanding of the long-term consequences of critical care survivorship is essential. We investigated the care process and individual factors associated with long-term mortality among ICU survivors and explored hospital use in this group.

Design

Population-based data linkage study using the Secure Anonymised Information Linkage databank.

Setting

All ICUs between 2006 and 2013 in Wales, United Kingdom.

Patients

We identified 40,631 patients discharged alive from Welsh adult ICUs.

Interventions

None.

Measurements and main results

Primary outcome was 365-day survival. The secondary outcomes were 30- and 90-day survival and hospital utilization in the 365 days following ICU discharge. Kaplan-Meier curves were plotted to compare survival rates. Cox proportional hazards regression models were used to determine risk factors of mortality. Seven-thousand eight-hundred eighty-three patients (19.4%) died during the 1-year follow-up period. In the multivariable Cox regression analysis, advanced age and comorbidities were significant determinants of long-term mortality. Expedited discharge due to ICU bed shortage was associated with higher risk. The rate of hospitalization in the year prior to the critical care admission was 28 hospitalized days/1,000 d; post critical care was 88 hospitalized days/1,000 d for those who were still alive; and 57 hospitalized days/1,000 d and 412 hospitalized days/1,000 d for those who died by the end of the study, respectively.

Conclusions

One in five ICU survivors die within 1 year, with advanced age and comorbidity being significant predictors of outcome, leading to high resource use. Care process factors indicating high system stress were associated with increased risk. More detailed understanding is needed on the effects of the potentially modifiable factors to optimize service delivery and improve long-term outcomes of the critically ill.", + "laySummary": "", + "urls": "pdf:https://europepmc.org/articles/pmc6330072?pdf=render; doi:https://doi.org/10.1097/CCM.0000000000003424; html:https://europepmc.org/articles/PMC6330072; pdf:https://europepmc.org/articles/PMC6330072?pdf=render; doi:https://doi.org/10.1097/ccm.0000000000003424" + }, { "id": "34040552", "doi": "https://doi.org/10.3389/fpsyt.2021.627996", @@ -29410,21 +29427,21 @@ "urls": "pdf:https://bjgp.org/content/bjgp/71/707/e441.full.pdf; doi:https://doi.org/10.3399/bjgp20X714161; html:https://europepmc.org/articles/PMC8041293; pdf:https://europepmc.org/articles/PMC8041293?pdf=render" }, { - "id": "30444743", - "doi": "https://doi.org/10.1097/ccm.0000000000003424", - "title": "Risk Factors for 1-Year Mortality and Hospital Utilization Patterns in Critical Care Survivors: A Retrospective, Observational, Population-Based Data Linkage Study.", - "authorString": "Szakmany T, Walters AM, Pugh R, Battle C, Berridge DM, Lyons RA.", + "id": "33036417", + "doi": "https://doi.org/10.3390/ijerph17197320", + "title": "Prognostic Role of Demographic, Injury and Claim Factors in Disabling Pain and Mental Health Conditions 12 Months after Compensable Injury.", + "authorString": "Nguyen TL, Baker KS, Ioannou L, Hassani-Mahmooei B, Gibson SJ, Collie A, Ponsford J, Cameron PA, Gabbe BJ, Giummarra MJ.", "authorAffiliations": "", - "journalTitle": "Critical care medicine", - "pubYear": "2019", - "date": "2019-01-01", - "isOpenAccess": "N", - "keywords": "", + "journalTitle": "International journal of environmental research and public health", + "pubYear": "2020", + "date": "2020-10-07", + "isOpenAccess": "Y", + "keywords": "Injury; Pain; Compensation; Mental health; Insurance; Disability; Traumatic Injury", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Objectives

Clear understanding of the long-term consequences of critical care survivorship is essential. We investigated the care process and individual factors associated with long-term mortality among ICU survivors and explored hospital use in this group.

Design

Population-based data linkage study using the Secure Anonymised Information Linkage databank.

Setting

All ICUs between 2006 and 2013 in Wales, United Kingdom.

Patients

We identified 40,631 patients discharged alive from Welsh adult ICUs.

Interventions

None.

Measurements and main results

Primary outcome was 365-day survival. The secondary outcomes were 30- and 90-day survival and hospital utilization in the 365 days following ICU discharge. Kaplan-Meier curves were plotted to compare survival rates. Cox proportional hazards regression models were used to determine risk factors of mortality. Seven-thousand eight-hundred eighty-three patients (19.4%) died during the 1-year follow-up period. In the multivariable Cox regression analysis, advanced age and comorbidities were significant determinants of long-term mortality. Expedited discharge due to ICU bed shortage was associated with higher risk. The rate of hospitalization in the year prior to the critical care admission was 28 hospitalized days/1,000 d; post critical care was 88 hospitalized days/1,000 d for those who were still alive; and 57 hospitalized days/1,000 d and 412 hospitalized days/1,000 d for those who died by the end of the study, respectively.

Conclusions

One in five ICU survivors die within 1 year, with advanced age and comorbidity being significant predictors of outcome, leading to high resource use. Care process factors indicating high system stress were associated with increased risk. More detailed understanding is needed on the effects of the potentially modifiable factors to optimize service delivery and improve long-term outcomes of the critically ill.", + "abstract": "Identifying who might develop disabling pain or poor mental health after injury is a high priority so that healthcare providers can provide targeted preventive interventions. This retrospective cohort study aimed to identify predictors of disabling pain or probable mental health conditions at 12 months post-injury. Participants were recruited 12-months after admission to a major trauma service for a compensable transport or workplace injury (n = 157). Injury, compensation claim, health services and medication information were obtained from the Victorian Orthopaedic Trauma Outcome Registry, Victorian State Trauma Registry and Compensation Research Database. Participants completed questionnaires about pain, and mental health (anxiety, depression, posttraumatic stress disorder) at 12 months post-injury. One third had disabling pain, one third had at least one probable mental health condition and more than one in five had both disabling pain and a mental health condition at 12 months post-injury. Multivariable logistic regression found mental health treatment 3-6 months post-injury, persistent work disability and opioid use at 6-12 months predicted disabling pain at 12 months post-injury. The presence of opioid use at 3-6 months, work disability and psychotropic medications at 6-12 months predicted a mental health condition at 12 months post-injury. These factors could be used to identify at risk of developing disabling pain who could benefit from timely interventions to better manage both pain and mental health post-injury. Implications for healthcare and compensation system are discussed.", "laySummary": "", - "urls": "pdf:https://europepmc.org/articles/pmc6330072?pdf=render; doi:https://doi.org/10.1097/CCM.0000000000003424; html:https://europepmc.org/articles/PMC6330072; pdf:https://europepmc.org/articles/PMC6330072?pdf=render; doi:https://doi.org/10.1097/ccm.0000000000003424" + "urls": "pdf:https://www.mdpi.com/1660-4601/17/19/7320/pdf?version=1602228180; doi:https://doi.org/10.3390/ijerph17197320; html:https://europepmc.org/articles/PMC7579145; pdf:https://europepmc.org/articles/PMC7579145?pdf=render" }, { "id": "38082486", @@ -29443,23 +29460,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1681/ASN.0000000000000271; html:https://europepmc.org/articles/PMC7615589; pdf:https://europepmc.org/articles/PMC7615589?pdf=render" }, - { - "id": "33036417", - "doi": "https://doi.org/10.3390/ijerph17197320", - "title": "Prognostic Role of Demographic, Injury and Claim Factors in Disabling Pain and Mental Health Conditions 12 Months after Compensable Injury.", - "authorString": "Nguyen TL, Baker KS, Ioannou L, Hassani-Mahmooei B, Gibson SJ, Collie A, Ponsford J, Cameron PA, Gabbe BJ, Giummarra MJ.", - "authorAffiliations": "", - "journalTitle": "International journal of environmental research and public health", - "pubYear": "2020", - "date": "2020-10-07", - "isOpenAccess": "Y", - "keywords": "Injury; Pain; Compensation; Mental health; Insurance; Disability; Traumatic Injury", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Identifying who might develop disabling pain or poor mental health after injury is a high priority so that healthcare providers can provide targeted preventive interventions. This retrospective cohort study aimed to identify predictors of disabling pain or probable mental health conditions at 12 months post-injury. Participants were recruited 12-months after admission to a major trauma service for a compensable transport or workplace injury (n = 157). Injury, compensation claim, health services and medication information were obtained from the Victorian Orthopaedic Trauma Outcome Registry, Victorian State Trauma Registry and Compensation Research Database. Participants completed questionnaires about pain, and mental health (anxiety, depression, posttraumatic stress disorder) at 12 months post-injury. One third had disabling pain, one third had at least one probable mental health condition and more than one in five had both disabling pain and a mental health condition at 12 months post-injury. Multivariable logistic regression found mental health treatment 3-6 months post-injury, persistent work disability and opioid use at 6-12 months predicted disabling pain at 12 months post-injury. The presence of opioid use at 3-6 months, work disability and psychotropic medications at 6-12 months predicted a mental health condition at 12 months post-injury. These factors could be used to identify at risk of developing disabling pain who could benefit from timely interventions to better manage both pain and mental health post-injury. Implications for healthcare and compensation system are discussed.", - "laySummary": "", - "urls": "pdf:https://www.mdpi.com/1660-4601/17/19/7320/pdf?version=1602228180; doi:https://doi.org/10.3390/ijerph17197320; html:https://europepmc.org/articles/PMC7579145; pdf:https://europepmc.org/articles/PMC7579145?pdf=render" - }, { "id": "33605084", "doi": "https://doi.org/10.1111/jcmm.16388", @@ -29494,23 +29494,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.burns.2021.07.025" }, - { - "id": "37817277", - "doi": "https://doi.org/10.1186/s13063-023-07656-8", - "title": "e-Consent in UK academic-led clinical trials: current practice, challenges and the need for more evidence.", - "authorString": "Mitchell EJ, Appelbe D, Bravery A, Culliford L, Evans H, Farrin AJ, Gillies K, Hood K, Love SB, Sydes MR, Williamson PR, Wakefield N, as part of the e-Consent collaborative group.", - "authorAffiliations": "", - "journalTitle": "Trials", - "pubYear": "2023", - "date": "2023-10-10", - "isOpenAccess": "Y", - "keywords": "Consent; Clinical Trial; E-consent", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

During the COVID-19 pandemic, in-person healthcare visits were reduced. Consequently, trial teams needed to consider implementing remote methods for conducting clinical trials, including e-Consent. Although some clinical trials may have implemented e-Consent prior to the pandemic, anecdotes of uptake for this method increased within academic-led trials. When the increased use of this process emerged, representatives from several large academic clinical trial groups within the UK collaborated to discuss ways in which trialists can learn from one another when implementing e-Consent.

Methods

A survey of UKCRC-registered Clinical Trials Units (CTUs) was undertaken in April-June 2021 to understand the implementation of and their views on the use of e-Consent and experiences from the perspectives of systems programmers and quality assurance staff on the use of e-Consent. CTUs not using e-Consent were asked to provide any reasons/barriers (including no suitable trials) and any plans for implementing it in the future. Two events for trialists and patient and public involvement (PPI) representatives were then held to disseminate findings, foster discussion, share experiences and aid in the identification of areas that the academic CTU community felt required more research.

Results

Thirty-four (64%) of 53 CTUs responded to the survey, with good geographical representation across the UK. Twenty-one (62%) of the responding CTUs had implemented e-Consent in at least one of their trials, across different types of trials, including CTIMPs (Clinical Trial of Investigational Medicinal Product), ATIMPs (Advanced Therapy Medicinal Products) and non-CTIMPs. One hundred ninety-seven participants attended the two workshops for wide-ranging discussions.

Conclusion

e-Consent is increasingly used in academic-led trials, yet uncertainties remain amongst trialists, patients and members of the public. Uncertainties include a lack of formal, practical guidance and a lack of evidence to demonstrate optimal or appropriate methods to use. We strongly encourage trialists to continue to share their own experiences of the implementation of e-Consent.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1186/s13063-023-07656-8; html:https://europepmc.org/articles/PMC10565982; pdf:https://europepmc.org/articles/PMC10565982?pdf=render" - }, { "id": "31481394", "doi": "https://doi.org/10.1136/bmj.l4892", @@ -29528,6 +29511,23 @@ "laySummary": "", "urls": "pdf:https://www.bmj.com/content/bmj/366/bmj.l4892.full.pdf; doi:https://doi.org/10.1136/bmj.l4892; html:https://europepmc.org/articles/PMC6719286" }, + { + "id": "37817277", + "doi": "https://doi.org/10.1186/s13063-023-07656-8", + "title": "e-Consent in UK academic-led clinical trials: current practice, challenges and the need for more evidence.", + "authorString": "Mitchell EJ, Appelbe D, Bravery A, Culliford L, Evans H, Farrin AJ, Gillies K, Hood K, Love SB, Sydes MR, Williamson PR, Wakefield N, as part of the e-Consent collaborative group.", + "authorAffiliations": "", + "journalTitle": "Trials", + "pubYear": "2023", + "date": "2023-10-10", + "isOpenAccess": "Y", + "keywords": "Consent; Clinical Trial; E-consent", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

During the COVID-19 pandemic, in-person healthcare visits were reduced. Consequently, trial teams needed to consider implementing remote methods for conducting clinical trials, including e-Consent. Although some clinical trials may have implemented e-Consent prior to the pandemic, anecdotes of uptake for this method increased within academic-led trials. When the increased use of this process emerged, representatives from several large academic clinical trial groups within the UK collaborated to discuss ways in which trialists can learn from one another when implementing e-Consent.

Methods

A survey of UKCRC-registered Clinical Trials Units (CTUs) was undertaken in April-June 2021 to understand the implementation of and their views on the use of e-Consent and experiences from the perspectives of systems programmers and quality assurance staff on the use of e-Consent. CTUs not using e-Consent were asked to provide any reasons/barriers (including no suitable trials) and any plans for implementing it in the future. Two events for trialists and patient and public involvement (PPI) representatives were then held to disseminate findings, foster discussion, share experiences and aid in the identification of areas that the academic CTU community felt required more research.

Results

Thirty-four (64%) of 53 CTUs responded to the survey, with good geographical representation across the UK. Twenty-one (62%) of the responding CTUs had implemented e-Consent in at least one of their trials, across different types of trials, including CTIMPs (Clinical Trial of Investigational Medicinal Product), ATIMPs (Advanced Therapy Medicinal Products) and non-CTIMPs. One hundred ninety-seven participants attended the two workshops for wide-ranging discussions.

Conclusion

e-Consent is increasingly used in academic-led trials, yet uncertainties remain amongst trialists, patients and members of the public. Uncertainties include a lack of formal, practical guidance and a lack of evidence to demonstrate optimal or appropriate methods to use. We strongly encourage trialists to continue to share their own experiences of the implementation of e-Consent.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1186/s13063-023-07656-8; html:https://europepmc.org/articles/PMC10565982; pdf:https://europepmc.org/articles/PMC10565982?pdf=render" + }, { "id": "31964672", "doi": "https://doi.org/10.1136/bmjopen-2019-033318", @@ -29562,23 +29562,6 @@ "laySummary": "", "urls": "pdf:https://www.frontiersin.org/articles/10.3389/fimmu.2022.1032331/pdf; doi:https://doi.org/10.3389/fimmu.2022.1032331; html:https://europepmc.org/articles/PMC9624227; pdf:https://europepmc.org/articles/PMC9624227?pdf=render" }, - { - "id": "37339333", - "doi": "https://doi.org/10.1002/jia2.26104", - "title": "COVID-19 among adults living with HIV: correlates of mortality among public sector healthcare users in Western Cape, South Africa.", - "authorString": "Kassanjee R, Davies MA, Ngwenya O, Osei-Yeboah R, Jacobs T, Morden E, Timmerman V, Britz S, Mendelson M, Taljaard J, Riou J, Boulle A, Tiffin N, Zinyakatira N.", - "authorAffiliations": "", - "journalTitle": "Journal of the International AIDS Society", - "pubYear": "2023", - "date": "2023-06-01", - "isOpenAccess": "Y", - "keywords": "Mortality; HIV; South Africa; Cd4 Count; Covid-19; Sars-cov-2", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Introduction

While a large proportion of people with HIV (PWH) have experienced SARS-CoV-2 infections, there is uncertainty about the role of HIV disease severity on COVID-19 outcomes, especially in lower-income settings. We studied the association of mortality with characteristics of HIV severity and management, and vaccination, among adult PWH.

Methods

We analysed observational cohort data on all PWH aged \u226515 years experiencing a diagnosed SARS-CoV-2 infection (until March 2022), who accessed public sector healthcare in the Western Cape province of South Africa. Logistic regression was used to study the association of mortality with evidence of antiretroviral therapy (ART) collection, time since first HIV evidence, CD4 cell count, viral load (among those with evidence of ART collection) and COVID-19 vaccination, adjusting for demographic characteristics, comorbidities, admission pressure, location and time period.

Results

Mortality occurred in 5.7% (95% CI: 5.3,6.0) of 17,831 first-diagnosed infections. Higher mortality was associated with lower recent CD4, no evidence of ART collection, high or unknown recent viral load and recent first HIV evidence, differentially by age. Vaccination was protective. The burden of comorbidities was high, and tuberculosis (especially more recent episodes of tuberculosis), chronic kidney disease, diabetes and hypertension were associated with higher mortality, more strongly in younger adults.

Conclusions

Mortality was strongly associated with suboptimal HIV control, and the prevalence of these risk factors increased in later COVID-19 waves. It remains a public health priority to ensure PWH are on suppressive ART and vaccinated, and manage any disruptions in care that occurred during the pandemic. The diagnosis and management of comorbidities, including for tuberculosis, should be optimized.", - "laySummary": "", - "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/jia2.26104; doi:https://doi.org/10.1002/jia2.26104; html:https://europepmc.org/articles/PMC10281639; pdf:https://europepmc.org/articles/PMC10281639?pdf=render" - }, { "id": "32401709", "doi": "https://doi.org/10.1016/s2468-2667(20)30112-2", @@ -29596,6 +29579,23 @@ "laySummary": "Chandan et al. comment on the effect the covid pandemic may have on domestic violence and propose surveillance for domestic violence is needed. ", "urls": "pdf:http://www.thelancet.com/article/S2468266720301122/pdf; doi:https://doi.org/10.1016/S2468-2667(20)30112-2; html:https://europepmc.org/articles/PMC7252171; pdf:https://europepmc.org/articles/PMC7252171?pdf=render" }, + { + "id": "37339333", + "doi": "https://doi.org/10.1002/jia2.26104", + "title": "COVID-19 among adults living with HIV: correlates of mortality among public sector healthcare users in Western Cape, South Africa.", + "authorString": "Kassanjee R, Davies MA, Ngwenya O, Osei-Yeboah R, Jacobs T, Morden E, Timmerman V, Britz S, Mendelson M, Taljaard J, Riou J, Boulle A, Tiffin N, Zinyakatira N.", + "authorAffiliations": "", + "journalTitle": "Journal of the International AIDS Society", + "pubYear": "2023", + "date": "2023-06-01", + "isOpenAccess": "Y", + "keywords": "Mortality; HIV; South Africa; Cd4 Count; Covid-19; Sars-cov-2", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Introduction

While a large proportion of people with HIV (PWH) have experienced SARS-CoV-2 infections, there is uncertainty about the role of HIV disease severity on COVID-19 outcomes, especially in lower-income settings. We studied the association of mortality with characteristics of HIV severity and management, and vaccination, among adult PWH.

Methods

We analysed observational cohort data on all PWH aged \u226515 years experiencing a diagnosed SARS-CoV-2 infection (until March 2022), who accessed public sector healthcare in the Western Cape province of South Africa. Logistic regression was used to study the association of mortality with evidence of antiretroviral therapy (ART) collection, time since first HIV evidence, CD4 cell count, viral load (among those with evidence of ART collection) and COVID-19 vaccination, adjusting for demographic characteristics, comorbidities, admission pressure, location and time period.

Results

Mortality occurred in 5.7% (95% CI: 5.3,6.0) of 17,831 first-diagnosed infections. Higher mortality was associated with lower recent CD4, no evidence of ART collection, high or unknown recent viral load and recent first HIV evidence, differentially by age. Vaccination was protective. The burden of comorbidities was high, and tuberculosis (especially more recent episodes of tuberculosis), chronic kidney disease, diabetes and hypertension were associated with higher mortality, more strongly in younger adults.

Conclusions

Mortality was strongly associated with suboptimal HIV control, and the prevalence of these risk factors increased in later COVID-19 waves. It remains a public health priority to ensure PWH are on suppressive ART and vaccinated, and manage any disruptions in care that occurred during the pandemic. The diagnosis and management of comorbidities, including for tuberculosis, should be optimized.", + "laySummary": "", + "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/jia2.26104; doi:https://doi.org/10.1002/jia2.26104; html:https://europepmc.org/articles/PMC10281639; pdf:https://europepmc.org/articles/PMC10281639?pdf=render" + }, { "id": "36482104", "doi": "https://doi.org/10.1038/s41591-022-02100-x", @@ -29732,6 +29732,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1038/s41590-024-01754-8; doi:https://doi.org/10.1038/s41590-024-01754-8; html:https://europepmc.org/articles/PMC10907301; pdf:https://europepmc.org/articles/PMC10907301?pdf=render" }, + { + "id": "31220083", + "doi": "https://doi.org/10.1371/journal.pmed.1002833", + "title": "Associations of genetically determined iron status across the phenome: A mendelian randomization study.", + "authorString": "Gill D, Benyamin B, Moore LSP, Monori G, Zhou A, Koskeridis F, Evangelou E, Laffan M, Walker AP, Tsilidis KK, Dehghan A, Elliott P, Hypp\u00f6nen E, Tzoulaki I.", + "authorAffiliations": "", + "journalTitle": "PLoS medicine", + "pubYear": "2019", + "date": "2019-06-20", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "Understanding the Causes of Disease", + "healthCategories": "", + "abstract": "

Background

Iron is integral to many physiological processes, and variations in its levels, even within the normal range, can have implications for health. The objective of this study was to explore the broad clinical effects of varying iron status.

Methods and findings

Genome-wide association study (GWAS) summary data obtained from 48,972 European individuals (55% female) across 19 cohorts in the Genetics of Iron Status Consortium were used to identify 3 genetic variants (rs1800562 and rs1799945 in the hemochromatosis gene [HFE] and rs855791 in the transmembrane protease serine 6 gene [TMPRSS6]) that associate with increased serum iron, ferritin, and transferrin saturation and decreased transferrin levels, thus serving as instruments for systemic iron status. Phenome-wide association study (PheWAS) of these instruments was performed on 424,439 European individuals (54% female) in the UK Biobank who were aged 40-69 years when recruited from 2006 to 2010, with their genetic data linked to Hospital Episode Statistics (HES) from April, 1995 to March, 2016. Two-sample summary data mendelian randomization (MR) analysis was performed to investigate the effect of varying iron status on outcomes across the human phenome. MR-PheWAS analysis for the 3 iron status genetic instruments was performed separately and then pooled by meta-analysis. Correction was made for testing of multiple correlated phenotypes using a 5% false discovery rate (FDR) threshold. Heterogeneity between MR estimates for different instruments was used to indicate possible bias due to effects of the genetic variants through pathways unrelated to iron status. There were 904 distinct phenotypes included in the MR-PheWAS analyses. After correcting for multiple testing, the 3 genetic instruments for systemic iron status demonstrated consistent evidence of a causal effect of higher iron status on decreasing risk of traits related to anemia (iron deficiency anemia: odds ratio [OR] scaled to a standard deviation [SD] increase in genetically determined serum iron levels 0.72, 95% confidence interval [CI] 0.64-0.81, P = 4 \u00d7 10-8) and hypercholesterolemia (hypercholesterolemia: OR 0.88, 95% CI 0.83-0.93, P = 2 \u00d7 10-5) and increasing risk of traits related to infection of the skin and related structures (cellulitis and abscess of the leg: OR 1.25, 95% CI 1.10-1.42, P = 6 \u00d7 10-4). The main limitations of this study relate to possible bias from pleiotropic effects of the considered genetic variants and misclassification of diagnoses in the HES data. Furthermore, this work only investigated participants with European ancestry, and the findings may not be applicable to other ethnic groups.

Conclusions

Our findings offer novel, to our knowledge, insight into previously unreported effects of iron status, highlighting a potential protective effect of higher iron status on hypercholesterolemia and a detrimental role on risk of skin and skin structure infections. Given the modifiable and variable nature of iron status, these findings warrant further investigation.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1371/journal.pmed.1002833; doi:https://doi.org/10.1371/journal.pmed.1002833; html:https://europepmc.org/articles/PMC6586257; pdf:https://europepmc.org/articles/PMC6586257?pdf=render" + }, { "id": "38594327", "doi": "https://doi.org/10.1038/s41698-024-00580-3", @@ -29766,23 +29783,6 @@ "laySummary": "", "urls": "pdf:https://academic.oup.com/eurheartj/article-pdf/43/31/2921/45333809/ehac238.pdf; doi:https://doi.org/10.1093/eurheartj/ehac238; html:https://europepmc.org/articles/PMC9443991; pdf:https://europepmc.org/articles/PMC9443991?pdf=render" }, - { - "id": "31220083", - "doi": "https://doi.org/10.1371/journal.pmed.1002833", - "title": "Associations of genetically determined iron status across the phenome: A mendelian randomization study.", - "authorString": "Gill D, Benyamin B, Moore LSP, Monori G, Zhou A, Koskeridis F, Evangelou E, Laffan M, Walker AP, Tsilidis KK, Dehghan A, Elliott P, Hypp\u00f6nen E, Tzoulaki I.", - "authorAffiliations": "", - "journalTitle": "PLoS medicine", - "pubYear": "2019", - "date": "2019-06-20", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "Understanding the Causes of Disease", - "healthCategories": "", - "abstract": "

Background

Iron is integral to many physiological processes, and variations in its levels, even within the normal range, can have implications for health. The objective of this study was to explore the broad clinical effects of varying iron status.

Methods and findings

Genome-wide association study (GWAS) summary data obtained from 48,972 European individuals (55% female) across 19 cohorts in the Genetics of Iron Status Consortium were used to identify 3 genetic variants (rs1800562 and rs1799945 in the hemochromatosis gene [HFE] and rs855791 in the transmembrane protease serine 6 gene [TMPRSS6]) that associate with increased serum iron, ferritin, and transferrin saturation and decreased transferrin levels, thus serving as instruments for systemic iron status. Phenome-wide association study (PheWAS) of these instruments was performed on 424,439 European individuals (54% female) in the UK Biobank who were aged 40-69 years when recruited from 2006 to 2010, with their genetic data linked to Hospital Episode Statistics (HES) from April, 1995 to March, 2016. Two-sample summary data mendelian randomization (MR) analysis was performed to investigate the effect of varying iron status on outcomes across the human phenome. MR-PheWAS analysis for the 3 iron status genetic instruments was performed separately and then pooled by meta-analysis. Correction was made for testing of multiple correlated phenotypes using a 5% false discovery rate (FDR) threshold. Heterogeneity between MR estimates for different instruments was used to indicate possible bias due to effects of the genetic variants through pathways unrelated to iron status. There were 904 distinct phenotypes included in the MR-PheWAS analyses. After correcting for multiple testing, the 3 genetic instruments for systemic iron status demonstrated consistent evidence of a causal effect of higher iron status on decreasing risk of traits related to anemia (iron deficiency anemia: odds ratio [OR] scaled to a standard deviation [SD] increase in genetically determined serum iron levels 0.72, 95% confidence interval [CI] 0.64-0.81, P = 4 \u00d7 10-8) and hypercholesterolemia (hypercholesterolemia: OR 0.88, 95% CI 0.83-0.93, P = 2 \u00d7 10-5) and increasing risk of traits related to infection of the skin and related structures (cellulitis and abscess of the leg: OR 1.25, 95% CI 1.10-1.42, P = 6 \u00d7 10-4). The main limitations of this study relate to possible bias from pleiotropic effects of the considered genetic variants and misclassification of diagnoses in the HES data. Furthermore, this work only investigated participants with European ancestry, and the findings may not be applicable to other ethnic groups.

Conclusions

Our findings offer novel, to our knowledge, insight into previously unreported effects of iron status, highlighting a potential protective effect of higher iron status on hypercholesterolemia and a detrimental role on risk of skin and skin structure infections. Given the modifiable and variable nature of iron status, these findings warrant further investigation.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1371/journal.pmed.1002833; doi:https://doi.org/10.1371/journal.pmed.1002833; html:https://europepmc.org/articles/PMC6586257; pdf:https://europepmc.org/articles/PMC6586257?pdf=render" - }, { "id": "31242963", "doi": "https://doi.org/10.1016/j.vaccine.2019.06.019", @@ -29953,23 +29953,6 @@ "laySummary": "", "urls": "pdf:https://academic.oup.com/mbe/advance-article-pdf/doi/10.1093/molbev/msad070/49594873/msad070.pdf; doi:https://doi.org/10.1093/molbev/msad070; html:https://europepmc.org/articles/PMC10118308; pdf:https://europepmc.org/articles/PMC10118308?pdf=render" }, - { - "id": "37699620", - "doi": "https://doi.org/10.1136/bmjopen-2023-074626", - "title": "Development of the TrAnsparent ReportinG of observational studies Emulating a Target trial (TARGET) guideline.", - "authorString": "Hansford HJ, Cashin AG, Jones MD, Swanson SA, Islam N, Dahabreh IJ, Dickerman BA, Egger M, Garcia-Albeniz X, Golub RM, Lodi S, Moreno-Betancur M, Pearson SA, Schneeweiss S, Sterne J, Sharp MK, Stuart EA, Hernan MA, Lee H, McAuley JH.", - "authorAffiliations": "", - "journalTitle": "BMJ open", - "pubYear": "2023", - "date": "2023-09-12", - "isOpenAccess": "Y", - "keywords": "Retrospective studies; epidemiology; Statistics & Research Methods", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Observational studies are increasingly used to inform health decision-making when randomised trials are not feasible, ethical or timely. The target trial approach provides a framework to help minimise common biases in observational studies that aim to estimate the causal effect of interventions. Incomplete reporting of studies using the target trial framework limits the ability for clinicians, researchers, patients and other decision-makers to appraise, synthesise and interpret findings to inform clinical and public health practice and policy. This paper describes the methods that we will use to develop the TrAnsparent ReportinG of observational studies Emulating a Target trial (TARGET) reporting guideline.

Methods/design

The TARGET reporting guideline will be developed in five stages following recommended guidance. The first stage will identify target trial reporting practices by systematically reviewing published studies that explicitly emulated a target trial. The second stage will identify and refine items to be considered for inclusion in the TARGET guideline by consulting content experts using sequential online surveys. The third stage will prioritise and consolidate key items to be included in the TARGET guideline at an in-person consensus meeting of TARGET investigators. The fourth stage will produce and pilot-test both the TARGET guideline and explanation and elaboration document with relevant stakeholders. The fifth stage will disseminate the TARGET guideline and resources via journals, conferences and courses.

Ethics and dissemination

Ethical approval for the survey has been attained (HC220536). The TARGET guideline will be disseminated widely in partnership with stakeholders to maximise adoption and improve reporting of these studies.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1136/bmjopen-2023-074626; html:https://europepmc.org/articles/PMC10503363; pdf:https://europepmc.org/articles/PMC10503363?pdf=render" - }, { "id": "32679111", "doi": "https://doi.org/10.1016/s0140-6736(20)31356-8", @@ -29987,6 +29970,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/s0140-6736(20)31356-8; doi:https://doi.org/10.1016/S0140-6736(20)31356-8; html:https://europepmc.org/articles/PMC7429983; pdf:https://europepmc.org/articles/PMC7429983?pdf=render" }, + { + "id": "37699620", + "doi": "https://doi.org/10.1136/bmjopen-2023-074626", + "title": "Development of the TrAnsparent ReportinG of observational studies Emulating a Target trial (TARGET) guideline.", + "authorString": "Hansford HJ, Cashin AG, Jones MD, Swanson SA, Islam N, Dahabreh IJ, Dickerman BA, Egger M, Garcia-Albeniz X, Golub RM, Lodi S, Moreno-Betancur M, Pearson SA, Schneeweiss S, Sterne J, Sharp MK, Stuart EA, Hernan MA, Lee H, McAuley JH.", + "authorAffiliations": "", + "journalTitle": "BMJ open", + "pubYear": "2023", + "date": "2023-09-12", + "isOpenAccess": "Y", + "keywords": "Retrospective studies; epidemiology; Statistics & Research Methods", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Observational studies are increasingly used to inform health decision-making when randomised trials are not feasible, ethical or timely. The target trial approach provides a framework to help minimise common biases in observational studies that aim to estimate the causal effect of interventions. Incomplete reporting of studies using the target trial framework limits the ability for clinicians, researchers, patients and other decision-makers to appraise, synthesise and interpret findings to inform clinical and public health practice and policy. This paper describes the methods that we will use to develop the TrAnsparent ReportinG of observational studies Emulating a Target trial (TARGET) reporting guideline.

Methods/design

The TARGET reporting guideline will be developed in five stages following recommended guidance. The first stage will identify target trial reporting practices by systematically reviewing published studies that explicitly emulated a target trial. The second stage will identify and refine items to be considered for inclusion in the TARGET guideline by consulting content experts using sequential online surveys. The third stage will prioritise and consolidate key items to be included in the TARGET guideline at an in-person consensus meeting of TARGET investigators. The fourth stage will produce and pilot-test both the TARGET guideline and explanation and elaboration document with relevant stakeholders. The fifth stage will disseminate the TARGET guideline and resources via journals, conferences and courses.

Ethics and dissemination

Ethical approval for the survey has been attained (HC220536). The TARGET guideline will be disseminated widely in partnership with stakeholders to maximise adoption and improve reporting of these studies.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1136/bmjopen-2023-074626; html:https://europepmc.org/articles/PMC10503363; pdf:https://europepmc.org/articles/PMC10503363?pdf=render" + }, { "id": "35047183", "doi": "https://doi.org/10.7189/jogh.11.01011", @@ -30038,23 +30038,6 @@ "laySummary": "", "urls": "pdf:https://ijpds.org/article/download/1383/2566; doi:https://doi.org/10.23889/ijpds.v5i2.1383; html:https://europepmc.org/articles/PMC7473253; pdf:https://europepmc.org/articles/PMC7473253?pdf=render" }, - { - "id": "38280393", - "doi": "https://doi.org/10.1016/s2352-3018(23)00272-2", - "title": "Longitudinal trends in causes of death among adults with HIV on antiretroviral therapy in Europe and North America from 1996 to 2020: a collaboration of cohort studies.", - "authorString": "Trickey A, McGinnis K, Gill MJ, Abgrall S, Berenguer J, Wyen C, Hessamfar M, Reiss P, Kusejko K, Silverberg MJ, Imaz A, Teira R, d'Arminio Monforte A, Zangerle R, Guest JL, Papastamopoulos V, Crane H, Sterling TR, Grabar S, Ingle SM, Sterne JAC.", - "authorAffiliations": "", - "journalTitle": "The lancet. HIV", - "pubYear": "2024", - "date": "2024-01-24", - "isOpenAccess": "N", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Mortality rates among people with HIV have fallen since 1996 following the widespread availability of effective antiretroviral therapy (ART). Patterns of cause-specific mortality are evolving as the population with HIV ages. We aimed to investigate longitudinal trends in cause-specific mortality among people with HIV starting ART in Europe and North America.

Methods

In this collaborative observational cohort study, we used data from 17 European and North American HIV cohorts contributing data to the Antiretroviral Therapy Cohort Collaboration. We included data for people with HIV who started ART between 1996 and 2020 at the age of 16 years or older. Causes of death were classified into a single cause by both a clinician and an algorithm if International Classification of Diseases, Ninth Revision or Tenth Revision data were available, or independently by two clinicians. Disagreements were resolved through panel discussion. We used Poisson models to compare cause-specific mortality rates during the calendar periods 1996-99, 2000-03, 2004-07, 2008-11, 2012-15, and 2016-20, adjusted for time-updated age, CD4 count, and whether the individual was ART-naive at the start of each period.

Findings

Among 189\u2009301 people with HIV included in this study, 16\u2009832 (8\u00b79%) deaths were recorded during 1 519\u2009200 person-years of follow-up. 13\u2009180 (78\u00b73%) deaths were classified by cause: the most common causes were AIDS (4203 deaths; 25\u00b70%), non-AIDS non-hepatitis malignancy (2311; 13\u00b77%), and cardiovascular or heart-related (1403; 8\u00b73%) mortality. The proportion of deaths due to AIDS declined from 49% during 1996-99 to 16% during 2016-20. Rates of all-cause mortality per 1000 person-years decreased from 16\u00b78 deaths (95% CI 15\u00b74-18\u00b74) during 1996-99 to 7\u00b79 deaths (7\u00b76-8\u00b72) during 2016-20. Rates of all-cause mortality declined with time: the average adjusted mortality rate ratio per calendar period was 0\u00b785 (95% CI 0\u00b784-0\u00b786). Rates of cause-specific mortality also declined: the most pronounced reduction was for AIDS-related mortality (0\u00b781; 0\u00b779-0\u00b783). There were also reductions in rates of cardiovascular-related (0\u00b783, 0\u00b779-0\u00b787), liver-related (0\u00b788, 0\u00b784-0\u00b793), non-AIDS infection-related (0\u00b791, 0\u00b786-0\u00b796), non-AIDS-non-hepatocellular carcinoma malignancy-related (0\u00b794, 0\u00b790-0\u00b797), and suicide or accident-related mortality (0\u00b789, 0\u00b782-0\u00b795). Mortality rates among people who acquired HIV through injecting drug use increased in women (1\u00b707, 1\u00b700-1\u00b714) and decreased slightly in men (0\u00b796, 0\u00b793-0\u00b799).

Interpretation

Reductions of most major causes of death, particularly AIDS-related deaths among people with HIV on ART, were not seen for all subgroups. Interventions targeted at high-risk groups, substance use, and comorbidities might further increase life expectancy in people with HIV towards that in the general population.

Funding

US National Institute on Alcohol Abuse and Alcoholism.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1016/S2352-3018(23)00272-2" - }, { "id": "32909959", "doi": "https://doi.org/10.1136/bmj.m3164", @@ -30089,6 +30072,23 @@ "laySummary": "", "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/12/11/e063159.full.pdf; doi:https://doi.org/10.1136/bmjopen-2022-063159; html:https://europepmc.org/articles/PMC9644078; pdf:https://europepmc.org/articles/PMC9644078?pdf=render" }, + { + "id": "38280393", + "doi": "https://doi.org/10.1016/s2352-3018(23)00272-2", + "title": "Longitudinal trends in causes of death among adults with HIV on antiretroviral therapy in Europe and North America from 1996 to 2020: a collaboration of cohort studies.", + "authorString": "Trickey A, McGinnis K, Gill MJ, Abgrall S, Berenguer J, Wyen C, Hessamfar M, Reiss P, Kusejko K, Silverberg MJ, Imaz A, Teira R, d'Arminio Monforte A, Zangerle R, Guest JL, Papastamopoulos V, Crane H, Sterling TR, Grabar S, Ingle SM, Sterne JAC.", + "authorAffiliations": "", + "journalTitle": "The lancet. HIV", + "pubYear": "2024", + "date": "2024-01-24", + "isOpenAccess": "N", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Mortality rates among people with HIV have fallen since 1996 following the widespread availability of effective antiretroviral therapy (ART). Patterns of cause-specific mortality are evolving as the population with HIV ages. We aimed to investigate longitudinal trends in cause-specific mortality among people with HIV starting ART in Europe and North America.

Methods

In this collaborative observational cohort study, we used data from 17 European and North American HIV cohorts contributing data to the Antiretroviral Therapy Cohort Collaboration. We included data for people with HIV who started ART between 1996 and 2020 at the age of 16 years or older. Causes of death were classified into a single cause by both a clinician and an algorithm if International Classification of Diseases, Ninth Revision or Tenth Revision data were available, or independently by two clinicians. Disagreements were resolved through panel discussion. We used Poisson models to compare cause-specific mortality rates during the calendar periods 1996-99, 2000-03, 2004-07, 2008-11, 2012-15, and 2016-20, adjusted for time-updated age, CD4 count, and whether the individual was ART-naive at the start of each period.

Findings

Among 189\u2009301 people with HIV included in this study, 16\u2009832 (8\u00b79%) deaths were recorded during 1 519\u2009200 person-years of follow-up. 13\u2009180 (78\u00b73%) deaths were classified by cause: the most common causes were AIDS (4203 deaths; 25\u00b70%), non-AIDS non-hepatitis malignancy (2311; 13\u00b77%), and cardiovascular or heart-related (1403; 8\u00b73%) mortality. The proportion of deaths due to AIDS declined from 49% during 1996-99 to 16% during 2016-20. Rates of all-cause mortality per 1000 person-years decreased from 16\u00b78 deaths (95% CI 15\u00b74-18\u00b74) during 1996-99 to 7\u00b79 deaths (7\u00b76-8\u00b72) during 2016-20. Rates of all-cause mortality declined with time: the average adjusted mortality rate ratio per calendar period was 0\u00b785 (95% CI 0\u00b784-0\u00b786). Rates of cause-specific mortality also declined: the most pronounced reduction was for AIDS-related mortality (0\u00b781; 0\u00b779-0\u00b783). There were also reductions in rates of cardiovascular-related (0\u00b783, 0\u00b779-0\u00b787), liver-related (0\u00b788, 0\u00b784-0\u00b793), non-AIDS infection-related (0\u00b791, 0\u00b786-0\u00b796), non-AIDS-non-hepatocellular carcinoma malignancy-related (0\u00b794, 0\u00b790-0\u00b797), and suicide or accident-related mortality (0\u00b789, 0\u00b782-0\u00b795). Mortality rates among people who acquired HIV through injecting drug use increased in women (1\u00b707, 1\u00b700-1\u00b714) and decreased slightly in men (0\u00b796, 0\u00b793-0\u00b799).

Interpretation

Reductions of most major causes of death, particularly AIDS-related deaths among people with HIV on ART, were not seen for all subgroups. Interventions targeted at high-risk groups, substance use, and comorbidities might further increase life expectancy in people with HIV towards that in the general population.

Funding

US National Institute on Alcohol Abuse and Alcoholism.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1016/S2352-3018(23)00272-2" + }, { "id": "32371477", "doi": "https://doi.org/10.1126/science.abc0473", @@ -30157,23 +30157,6 @@ "laySummary": "", "urls": "pdf:https://bmcpublichealth.biomedcentral.com/track/pdf/10.1186/s12889-022-13069-0; doi:https://doi.org/10.1186/s12889-022-13069-0; html:https://europepmc.org/articles/PMC8996221; pdf:https://europepmc.org/articles/PMC8996221?pdf=render" }, - { - "id": "33048945", - "doi": "https://doi.org/10.1371/journal.pmed.1003290", - "title": "Neurodevelopmental multimorbidity and educational outcomes of Scottish schoolchildren: A population-based record linkage cohort study.", - "authorString": "Fleming M, Salim EE, Mackay DF, Henderson A, Kinnear D, Clark D, King A, McLay JS, Cooper SA, Pell JP.", - "authorAffiliations": "", - "journalTitle": "PLoS medicine", - "pubYear": "2020", - "date": "2020-10-13", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Neurodevelopmental conditions commonly coexist in children, but compared to adults, childhood multimorbidity attracts less attention in research and clinical practice. We previously reported that children treated for attention deficit hyperactivity disorder (ADHD) and depression have more school absences and exclusions, additional support needs, poorer attainment, and increased unemployment. They are also more likely to have coexisting conditions, including autism and intellectual disability. We investigated prevalence of neurodevelopmental multimorbidity (\u22652 conditions) among Scottish schoolchildren and their educational outcomes compared to peers.

Methods and findings

We retrospectively linked 6 Scotland-wide databases to analyse 766,244 children (390,290 [50.9%] boys; 375,954 [49.1%] girls) aged 4 to 19 years (mean = 10.9) attending Scottish schools between 2009 and 2013. Children were distributed across all deprivation quintiles (most to least deprived: 22.7%, 20.1%, 19.3%, 19.5%, 18.4%). The majority (96.2%) were white ethnicity. We ascertained autism spectrum disorder (ASD) and intellectual disabilities from records of additional support needs and ADHD and depression through relevant encashed prescriptions. We identified neurodevelopmental multimorbidity (\u22652 of these conditions) in 4,789 (0.6%) children, with ASD and intellectual disability the most common combination. On adjusting for sociodemographic (sex, age, ethnicity, deprivation) and maternity (maternal age, maternal smoking, sex-gestation-specific birth weight centile, gestational age, 5-minute Apgar score, mode of delivery, parity) factors, multimorbidity was associated with increased school absenteeism and exclusion, unemployment, and poorer exam attainment. Significant dose relationships were evident between number of conditions (0, 1, \u22652) and the last 3 outcomes. Compared to children with no conditions, children with 1 condition, and children with 2 or more conditions, had more absenteeism (1 condition adjusted incidence rate ratio [IRR] 1.28, 95% CI 1.27-1.30, p < 0.001 and 2 or more conditions adjusted IRR 1.23, 95% CI 1.20-1.28, p < 0.001), greater exclusion (adjusted IRR 2.37, 95% CI 2.25-2.48, p < 0.001 and adjusted IRR 3.04, 95% CI 2.74-3.38, p < 0.001), poorer attainment (adjusted odds ratio [OR] 3.92, 95% CI 3.63-4.23, p < 0.001 and adjusted OR 12.07, 95% CI 9.15-15.94, p < 0.001), and increased unemployment (adjusted OR 1.57, 95% CI 1.49-1.66, p < 0.001 and adjusted OR 2.11, 95% CI 1.83-2.45, p < 0.001). Associations remained after further adjustment for comorbid physical conditions and additional support needs. Coexisting depression was the strongest driver of absenteeism and coexisting ADHD the strongest driver of exclusion. Absence of formal primary care diagnoses was a limitation since ascertaining depression and ADHD from prescriptions omitted affected children receiving alternative or no treatment and some antidepressants can be prescribed for other indications.

Conclusions

Structuring clinical practice and training around single conditions may disadvantage children with neurodevelopmental multimorbidity, who we observed had significantly poorer educational outcomes compared to children with 1 condition and no conditions.", - "laySummary": "", - "urls": "pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1003290&type=printable; doi:https://doi.org/10.1371/journal.pmed.1003290; html:https://europepmc.org/articles/PMC7553326; pdf:https://europepmc.org/articles/PMC7553326?pdf=render" - }, { "id": "30993728", "doi": "https://doi.org/10.1111/cen.13990", @@ -30191,6 +30174,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1111/cen.13990" }, + { + "id": "33048945", + "doi": "https://doi.org/10.1371/journal.pmed.1003290", + "title": "Neurodevelopmental multimorbidity and educational outcomes of Scottish schoolchildren: A population-based record linkage cohort study.", + "authorString": "Fleming M, Salim EE, Mackay DF, Henderson A, Kinnear D, Clark D, King A, McLay JS, Cooper SA, Pell JP.", + "authorAffiliations": "", + "journalTitle": "PLoS medicine", + "pubYear": "2020", + "date": "2020-10-13", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Neurodevelopmental conditions commonly coexist in children, but compared to adults, childhood multimorbidity attracts less attention in research and clinical practice. We previously reported that children treated for attention deficit hyperactivity disorder (ADHD) and depression have more school absences and exclusions, additional support needs, poorer attainment, and increased unemployment. They are also more likely to have coexisting conditions, including autism and intellectual disability. We investigated prevalence of neurodevelopmental multimorbidity (\u22652 conditions) among Scottish schoolchildren and their educational outcomes compared to peers.

Methods and findings

We retrospectively linked 6 Scotland-wide databases to analyse 766,244 children (390,290 [50.9%] boys; 375,954 [49.1%] girls) aged 4 to 19 years (mean = 10.9) attending Scottish schools between 2009 and 2013. Children were distributed across all deprivation quintiles (most to least deprived: 22.7%, 20.1%, 19.3%, 19.5%, 18.4%). The majority (96.2%) were white ethnicity. We ascertained autism spectrum disorder (ASD) and intellectual disabilities from records of additional support needs and ADHD and depression through relevant encashed prescriptions. We identified neurodevelopmental multimorbidity (\u22652 of these conditions) in 4,789 (0.6%) children, with ASD and intellectual disability the most common combination. On adjusting for sociodemographic (sex, age, ethnicity, deprivation) and maternity (maternal age, maternal smoking, sex-gestation-specific birth weight centile, gestational age, 5-minute Apgar score, mode of delivery, parity) factors, multimorbidity was associated with increased school absenteeism and exclusion, unemployment, and poorer exam attainment. Significant dose relationships were evident between number of conditions (0, 1, \u22652) and the last 3 outcomes. Compared to children with no conditions, children with 1 condition, and children with 2 or more conditions, had more absenteeism (1 condition adjusted incidence rate ratio [IRR] 1.28, 95% CI 1.27-1.30, p < 0.001 and 2 or more conditions adjusted IRR 1.23, 95% CI 1.20-1.28, p < 0.001), greater exclusion (adjusted IRR 2.37, 95% CI 2.25-2.48, p < 0.001 and adjusted IRR 3.04, 95% CI 2.74-3.38, p < 0.001), poorer attainment (adjusted odds ratio [OR] 3.92, 95% CI 3.63-4.23, p < 0.001 and adjusted OR 12.07, 95% CI 9.15-15.94, p < 0.001), and increased unemployment (adjusted OR 1.57, 95% CI 1.49-1.66, p < 0.001 and adjusted OR 2.11, 95% CI 1.83-2.45, p < 0.001). Associations remained after further adjustment for comorbid physical conditions and additional support needs. Coexisting depression was the strongest driver of absenteeism and coexisting ADHD the strongest driver of exclusion. Absence of formal primary care diagnoses was a limitation since ascertaining depression and ADHD from prescriptions omitted affected children receiving alternative or no treatment and some antidepressants can be prescribed for other indications.

Conclusions

Structuring clinical practice and training around single conditions may disadvantage children with neurodevelopmental multimorbidity, who we observed had significantly poorer educational outcomes compared to children with 1 condition and no conditions.", + "laySummary": "", + "urls": "pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1003290&type=printable; doi:https://doi.org/10.1371/journal.pmed.1003290; html:https://europepmc.org/articles/PMC7553326; pdf:https://europepmc.org/articles/PMC7553326?pdf=render" + }, { "id": "33306713", "doi": "https://doi.org/10.1371/journal.pone.0243383", @@ -30225,23 +30225,6 @@ "laySummary": "", "urls": "pdf:http://www.cell.com/article/S2589004222013517/pdf; doi:https://doi.org/10.1016/j.isci.2022.105079; html:https://europepmc.org/articles/PMC9441477; pdf:https://europepmc.org/articles/PMC9441477?pdf=render" }, - { - "id": "37719788", - "doi": "https://doi.org/10.1093/noajnl/vdad096", - "title": "Development of a core outcome set for use in adult primary glioma phase III interventional trials: A mixed methods study.", - "authorString": "Retzer A, Baddeley E, Sivell S, Scott H, Nelson A, Bulbeck H, Seddon K, Grant R, Adams R, Watts C, Aiyegbusi OL, Kearns P, Rivera SC, Dirven L, Calvert M, Byrne A.", - "authorAffiliations": "", - "journalTitle": "Neuro-oncology advances", - "pubYear": "2023", - "date": "2023-01-01", - "isOpenAccess": "Y", - "keywords": "trials; Outcomes; Neuro-oncology; Delphi; Primary Glioma", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Glioma interventional studies should collect data aligned with patient priorities, enabling treatment benefit assessment and informed decision-making. This requires effective data synthesis and meta-analyses, underpinned by consistent trial outcome measurement, analysis, and reporting. Development of a core outcome set (COS) may contribute to a solution.

Methods

A 5-stage process was used to develop a COS for glioma trials from the UK perspective. Outcome lists were generated in stages 1: a trial registry review and systematic review of qualitative studies and 2: interviews with glioma patients and caregivers. In stage 3, the outcome lists were de-duplicated with accessible terminology, in stage 4 outcomes were rated via a 2-round Delphi process, and stage 5 comprised a consensus meeting to finalize the COS. Patient-reportable COS outcomes were identified.

Results

In Delphi round 1, 96 participants rated 35 outcomes identified in stages 1 and 2, to which a further 10 were added. Participants (77/96) rated the resulting 45 outcomes in round 2. Of these, 22 outcomes met a priori threshold for inclusion in the COS. After further review, a COS consisting of 19 outcomes grouped into 7 outcome domains (survival, adverse events, activities of daily living, health-related quality of life, seizure activity, cognitive function, and physical function) was finalized by 13 participants at the consensus meeting.

Conclusions

A COS for glioma trials was developed, comprising 7 outcome domains. Additional research will identify appropriate measurement tools and further validate this COS.", - "laySummary": "", - "urls": "pdf:https://academic.oup.com/noa/advance-article-pdf/doi/10.1093/noajnl/vdad096/51026152/vdad096.pdf; doi:https://doi.org/10.1093/noajnl/vdad096; html:https://europepmc.org/articles/PMC10503650; pdf:https://europepmc.org/articles/PMC10503650?pdf=render" - }, { "id": "34112101", "doi": "https://doi.org/10.1186/s12872-021-02020-7", @@ -30259,6 +30242,23 @@ "laySummary": "", "urls": "pdf:https://bmccardiovascdisord.biomedcentral.com/counter/pdf/10.1186/s12872-021-02020-7; doi:https://doi.org/10.1186/s12872-021-02020-7; html:https://europepmc.org/articles/PMC8191101; pdf:https://europepmc.org/articles/PMC8191101?pdf=render" }, + { + "id": "37719788", + "doi": "https://doi.org/10.1093/noajnl/vdad096", + "title": "Development of a core outcome set for use in adult primary glioma phase III interventional trials: A mixed methods study.", + "authorString": "Retzer A, Baddeley E, Sivell S, Scott H, Nelson A, Bulbeck H, Seddon K, Grant R, Adams R, Watts C, Aiyegbusi OL, Kearns P, Rivera SC, Dirven L, Calvert M, Byrne A.", + "authorAffiliations": "", + "journalTitle": "Neuro-oncology advances", + "pubYear": "2023", + "date": "2023-01-01", + "isOpenAccess": "Y", + "keywords": "trials; Outcomes; Neuro-oncology; Delphi; Primary Glioma", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Glioma interventional studies should collect data aligned with patient priorities, enabling treatment benefit assessment and informed decision-making. This requires effective data synthesis and meta-analyses, underpinned by consistent trial outcome measurement, analysis, and reporting. Development of a core outcome set (COS) may contribute to a solution.

Methods

A 5-stage process was used to develop a COS for glioma trials from the UK perspective. Outcome lists were generated in stages 1: a trial registry review and systematic review of qualitative studies and 2: interviews with glioma patients and caregivers. In stage 3, the outcome lists were de-duplicated with accessible terminology, in stage 4 outcomes were rated via a 2-round Delphi process, and stage 5 comprised a consensus meeting to finalize the COS. Patient-reportable COS outcomes were identified.

Results

In Delphi round 1, 96 participants rated 35 outcomes identified in stages 1 and 2, to which a further 10 were added. Participants (77/96) rated the resulting 45 outcomes in round 2. Of these, 22 outcomes met a priori threshold for inclusion in the COS. After further review, a COS consisting of 19 outcomes grouped into 7 outcome domains (survival, adverse events, activities of daily living, health-related quality of life, seizure activity, cognitive function, and physical function) was finalized by 13 participants at the consensus meeting.

Conclusions

A COS for glioma trials was developed, comprising 7 outcome domains. Additional research will identify appropriate measurement tools and further validate this COS.", + "laySummary": "", + "urls": "pdf:https://academic.oup.com/noa/advance-article-pdf/doi/10.1093/noajnl/vdad096/51026152/vdad096.pdf; doi:https://doi.org/10.1093/noajnl/vdad096; html:https://europepmc.org/articles/PMC10503650; pdf:https://europepmc.org/articles/PMC10503650?pdf=render" + }, { "id": "35210596", "doi": "https://doi.org/10.1038/s41591-022-01736-z", @@ -30617,21 +30617,21 @@ "urls": "doi:https://doi.org/10.1098/rspb.2020.1405; doi:https://doi.org/10.1098/rspb.2020.1405; html:https://europepmc.org/articles/PMC7575516; pdf:https://europepmc.org/articles/PMC7575516?pdf=render" }, { - "id": "37025302", - "doi": "https://doi.org/10.1093/jacamr/dlad039", - "title": "Inclusion of minor alleles improves catalogue-based prediction of fluoroquinolone resistance in Mycobacterium tuberculosis.", - "authorString": "Brankin AE, Fowler PW.", + "id": "35165324", + "doi": "https://doi.org/10.1038/s41598-022-06315-3", + "title": "Improving robustness of automatic cardiac function quantification from cine magnetic resonance imaging using synthetic image data.", + "authorString": "Gheorghi\u021b\u0103 BA, Itu LM, Sharma P, Suciu C, Wetzl J, Geppert C, Ali MAA, Lee AM, Piechnik SK, Neubauer S, Petersen SE, Schulz-Menger J, Chi\u021biboi T.", "authorAffiliations": "", - "journalTitle": "JAC-antimicrobial resistance", - "pubYear": "2023", - "date": "2023-04-04", + "journalTitle": "Scientific reports", + "pubYear": "2022", + "date": "2022-02-14", "isOpenAccess": "Y", "keywords": "", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Objectives

Fluoroquinolone resistance poses a threat to the successful treatment of tuberculosis. WGS, and the subsequent detection of catalogued resistance-associated mutations, offers an attractive solution to fluoroquinolone susceptibility testing but sensitivities are often less than 90%. We hypothesize that this is partly because the bioinformatic pipelines used usually mask the recognition of minor alleles that have been implicated in fluoroquinolone resistance.

Methods

We analysed the Comprehensive Resistance Prediction for Tuberculosis: an International Consortium (CRyPTIC) dataset of globally diverse WGS Mycobacterium tuberculosis isolates, with matched MICs for two fluoroquinolone drugs and allowed putative minor alleles to contribute to resistance prediction.

Results

Detecting minor alleles increased the sensitivity of WGS for moxifloxacin resistance prediction from 85.4% to 94.0%, without significantly reducing specificity. We also found no correlation between the proportion of an M. tuberculosis population containing a resistance-conferring allele and the magnitude of resistance.

Conclusions

Together our results highlight the importance of detecting minor resistance-conferring alleles when using WGS, or indeed any sequencing-based approach, to diagnose fluoroquinolone resistance.", + "abstract": "Although having been the subject of intense research over the years, cardiac function quantification from MRI is still not a fully automatic process in the clinical practice. This is partly due to the shortage of training data covering all relevant cardiovascular disease phenotypes. We propose to synthetically generate short axis CINE MRI using a generative adversarial model to expand the available data sets that consist of predominantly healthy subjects to include more cases with reduced ejection fraction. We introduce a deep learning convolutional neural network (CNN) to predict the end-diastolic volume, end-systolic volume, and implicitly the ejection fraction from cardiac MRI without explicit segmentation. The left ventricle volume predictions were compared to the ground truth values, showing superior accuracy compared to state-of-the-art segmentation methods. We show that using synthetic data generated for pre-training a CNN significantly improves the prediction compared to only using the limited amount of available data, when the training set is imbalanced.", "laySummary": "", - "urls": "pdf:https://academic.oup.com/jacamr/article-pdf/5/2/dlad039/49747584/dlad039.pdf; doi:https://doi.org/10.1093/jacamr/dlad039; html:https://europepmc.org/articles/PMC10072237; pdf:https://europepmc.org/articles/PMC10072237?pdf=render" + "urls": "pdf:https://www.nature.com/articles/s41598-022-06315-3.pdf; doi:https://doi.org/10.1038/s41598-022-06315-3; html:https://europepmc.org/articles/PMC8844403; pdf:https://europepmc.org/articles/PMC8844403?pdf=render" }, { "id": "36423925", @@ -30651,38 +30651,21 @@ "urls": "pdf:https://thorax.bmj.com/content/thoraxjnl/early/2022/12/29/thorax-2022-219591.full.pdf; doi:https://doi.org/10.1136/thorax-2022-219591; html:https://europepmc.org/articles/PMC10359556; pdf:https://europepmc.org/articles/PMC10359556?pdf=render" }, { - "id": "35165324", - "doi": "https://doi.org/10.1038/s41598-022-06315-3", - "title": "Improving robustness of automatic cardiac function quantification from cine magnetic resonance imaging using synthetic image data.", - "authorString": "Gheorghi\u021b\u0103 BA, Itu LM, Sharma P, Suciu C, Wetzl J, Geppert C, Ali MAA, Lee AM, Piechnik SK, Neubauer S, Petersen SE, Schulz-Menger J, Chi\u021biboi T.", - "authorAffiliations": "", - "journalTitle": "Scientific reports", - "pubYear": "2022", - "date": "2022-02-14", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Although having been the subject of intense research over the years, cardiac function quantification from MRI is still not a fully automatic process in the clinical practice. This is partly due to the shortage of training data covering all relevant cardiovascular disease phenotypes. We propose to synthetically generate short axis CINE MRI using a generative adversarial model to expand the available data sets that consist of predominantly healthy subjects to include more cases with reduced ejection fraction. We introduce a deep learning convolutional neural network (CNN) to predict the end-diastolic volume, end-systolic volume, and implicitly the ejection fraction from cardiac MRI without explicit segmentation. The left ventricle volume predictions were compared to the ground truth values, showing superior accuracy compared to state-of-the-art segmentation methods. We show that using synthetic data generated for pre-training a CNN significantly improves the prediction compared to only using the limited amount of available data, when the training set is imbalanced.", - "laySummary": "", - "urls": "pdf:https://www.nature.com/articles/s41598-022-06315-3.pdf; doi:https://doi.org/10.1038/s41598-022-06315-3; html:https://europepmc.org/articles/PMC8844403; pdf:https://europepmc.org/articles/PMC8844403?pdf=render" - }, - { - "id": "37865101", - "doi": "https://doi.org/10.1016/s2213-8587(23)00253-x", - "title": "Empagliflozin in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial.", - "authorString": "RECOVERY Collaborative Group.", + "id": "37025302", + "doi": "https://doi.org/10.1093/jacamr/dlad039", + "title": "Inclusion of minor alleles improves catalogue-based prediction of fluoroquinolone resistance in Mycobacterium tuberculosis.", + "authorString": "Brankin AE, Fowler PW.", "authorAffiliations": "", - "journalTitle": "The lancet. Diabetes & endocrinology", + "journalTitle": "JAC-antimicrobial resistance", "pubYear": "2023", - "date": "2023-10-18", + "date": "2023-04-04", "isOpenAccess": "Y", "keywords": "", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Background

Empagliflozin has been proposed as a treatment for COVID-19 on the basis of its anti-inflammatory, metabolic, and haemodynamic effects. The RECOVERY trial aimed to assess its safety and efficacy in patients admitted to hospital with COVID-19.

Methods

In the randomised, controlled, open-label RECOVERY trial, several possible treatments are compared with usual care in patients hospitalised with COVID-19. In this analysis, we assess eligible and consenting adults who were randomly allocated in a 1:1 ratio to either usual standard of care alone or usual standard of care plus oral empagliflozin 10 mg once daily for 28 days or until discharge (whichever came first) using web-based simple (unstratified) randomisation with allocation concealment. The primary outcome was 28-day mortality; secondary outcomes were duration of hospitalisation and (among participants not on invasive mechanical ventilation at baseline) the composite of invasive mechanical ventilation or death. On March 3, 2023 the independent data monitoring committee recommended that the investigators review the data and recruitment was consequently stopped on March 7, 2023. The ongoing RECOVERY trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936).

Findings

Between July 28, 2021 and March 6, 2023, 4271 patients were randomly allocated to receive either empagliflozin (2113 patients) or usual care alone (2158 patients). Primary and secondary outcome data were known for greater than 99% of randomly assigned patients. Overall, 289 (14%) of 2113 patients allocated to empagliflozin and 307 (14%) of 2158 patients allocated to usual care died within 28 days (rate ratio 0\u00b796 [95% CI 0\u00b782-1\u00b713]; p=0\u00b764). There was no evidence of significant differences in duration of hospitalisation (median 8 days for both groups) or the proportion of patients discharged from hospital alive within 28 days (1678 [79%] in the empagliflozin group vs 1677 [78%] in the usual care group; rate ratio 1\u00b703 [95% CI 0\u00b796-1\u00b710]; p=0\u00b744). Among those not on invasive mechanical ventilation at baseline, there was no evidence of a significant difference in the proportion meeting the composite endpoint of invasive mechanical ventilation or death (338 [16%] of 2084 vs 371 [17%] of 2143; risk ratio 0\u00b795 [95% CI 0\u00b784-1\u00b708]; p=0\u00b744). Two serious adverse events believed to be related to empagliflozin were reported: both were ketosis without acidosis.

Interpretation

In adults hospitalised with COVID-19, empagliflozin was not associated with reductions in 28-day mortality, duration of hospital stay, or risk of progressing to invasive mechanical ventilation or death so is not indicated for the treatment of such patients unless there is an established indication due to a different condition such as diabetes.

Funding

UK Research and Innovation (Medical Research Council) and National Institute of Health Research (MC_PC_19056), and Wellcome Trust (222406/Z/20/Z).

Translations

For the Nepali, Hindi, Indonesian (Bahasa) and Vietnamese translations of the abstract see Supplementary Materials section.", + "abstract": "

Objectives

Fluoroquinolone resistance poses a threat to the successful treatment of tuberculosis. WGS, and the subsequent detection of catalogued resistance-associated mutations, offers an attractive solution to fluoroquinolone susceptibility testing but sensitivities are often less than 90%. We hypothesize that this is partly because the bioinformatic pipelines used usually mask the recognition of minor alleles that have been implicated in fluoroquinolone resistance.

Methods

We analysed the Comprehensive Resistance Prediction for Tuberculosis: an International Consortium (CRyPTIC) dataset of globally diverse WGS Mycobacterium tuberculosis isolates, with matched MICs for two fluoroquinolone drugs and allowed putative minor alleles to contribute to resistance prediction.

Results

Detecting minor alleles increased the sensitivity of WGS for moxifloxacin resistance prediction from 85.4% to 94.0%, without significantly reducing specificity. We also found no correlation between the proportion of an M. tuberculosis population containing a resistance-conferring allele and the magnitude of resistance.

Conclusions

Together our results highlight the importance of detecting minor resistance-conferring alleles when using WGS, or indeed any sequencing-based approach, to diagnose fluoroquinolone resistance.", "laySummary": "", - "urls": "doi:https://doi.org/10.1016/S2213-8587(23)00253-X; html:https://europepmc.org/articles/PMC10957483; pdf:https://europepmc.org/articles/PMC10957483?pdf=render" + "urls": "pdf:https://academic.oup.com/jacamr/article-pdf/5/2/dlad039/49747584/dlad039.pdf; doi:https://doi.org/10.1093/jacamr/dlad039; html:https://europepmc.org/articles/PMC10072237; pdf:https://europepmc.org/articles/PMC10072237?pdf=render" }, { "id": "32637892", @@ -30701,6 +30684,23 @@ "laySummary": "", "urls": "pdf:http://www.thelancet.com/article/S258953702030136X/pdf; doi:https://doi.org/10.1016/j.eclinm.2020.100392; html:https://europepmc.org/articles/PMC7329705; pdf:https://europepmc.org/articles/PMC7329705?pdf=render" }, + { + "id": "37865101", + "doi": "https://doi.org/10.1016/s2213-8587(23)00253-x", + "title": "Empagliflozin in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial.", + "authorString": "RECOVERY Collaborative Group.", + "authorAffiliations": "", + "journalTitle": "The lancet. Diabetes & endocrinology", + "pubYear": "2023", + "date": "2023-10-18", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Empagliflozin has been proposed as a treatment for COVID-19 on the basis of its anti-inflammatory, metabolic, and haemodynamic effects. The RECOVERY trial aimed to assess its safety and efficacy in patients admitted to hospital with COVID-19.

Methods

In the randomised, controlled, open-label RECOVERY trial, several possible treatments are compared with usual care in patients hospitalised with COVID-19. In this analysis, we assess eligible and consenting adults who were randomly allocated in a 1:1 ratio to either usual standard of care alone or usual standard of care plus oral empagliflozin 10 mg once daily for 28 days or until discharge (whichever came first) using web-based simple (unstratified) randomisation with allocation concealment. The primary outcome was 28-day mortality; secondary outcomes were duration of hospitalisation and (among participants not on invasive mechanical ventilation at baseline) the composite of invasive mechanical ventilation or death. On March 3, 2023 the independent data monitoring committee recommended that the investigators review the data and recruitment was consequently stopped on March 7, 2023. The ongoing RECOVERY trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936).

Findings

Between July 28, 2021 and March 6, 2023, 4271 patients were randomly allocated to receive either empagliflozin (2113 patients) or usual care alone (2158 patients). Primary and secondary outcome data were known for greater than 99% of randomly assigned patients. Overall, 289 (14%) of 2113 patients allocated to empagliflozin and 307 (14%) of 2158 patients allocated to usual care died within 28 days (rate ratio 0\u00b796 [95% CI 0\u00b782-1\u00b713]; p=0\u00b764). There was no evidence of significant differences in duration of hospitalisation (median 8 days for both groups) or the proportion of patients discharged from hospital alive within 28 days (1678 [79%] in the empagliflozin group vs 1677 [78%] in the usual care group; rate ratio 1\u00b703 [95% CI 0\u00b796-1\u00b710]; p=0\u00b744). Among those not on invasive mechanical ventilation at baseline, there was no evidence of a significant difference in the proportion meeting the composite endpoint of invasive mechanical ventilation or death (338 [16%] of 2084 vs 371 [17%] of 2143; risk ratio 0\u00b795 [95% CI 0\u00b784-1\u00b708]; p=0\u00b744). Two serious adverse events believed to be related to empagliflozin were reported: both were ketosis without acidosis.

Interpretation

In adults hospitalised with COVID-19, empagliflozin was not associated with reductions in 28-day mortality, duration of hospital stay, or risk of progressing to invasive mechanical ventilation or death so is not indicated for the treatment of such patients unless there is an established indication due to a different condition such as diabetes.

Funding

UK Research and Innovation (Medical Research Council) and National Institute of Health Research (MC_PC_19056), and Wellcome Trust (222406/Z/20/Z).

Translations

For the Nepali, Hindi, Indonesian (Bahasa) and Vietnamese translations of the abstract see Supplementary Materials section.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1016/S2213-8587(23)00253-X; html:https://europepmc.org/articles/PMC10957483; pdf:https://europepmc.org/articles/PMC10957483?pdf=render" + }, { "id": "32170038", "doi": "https://doi.org/10.1136/heartjnl-2019-316088", @@ -31075,23 +31075,6 @@ "laySummary": "", "urls": "html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7614871; doi:https://doi.org/10.1016/j.ekir.2023.05.008; html:https://europepmc.org/articles/PMC7614871; pdf:https://europepmc.org/articles/PMC7614871?pdf=render" }, - { - "id": "38553074", - "doi": "https://doi.org/10.1136/bmjopen-2024-085392", - "title": "Protocol for a mixed-methods study to develop and feasibility test a digital system for the capture of patient-reported outcomes (PROs) in patients receiving chimeric antigen receptor T-cell (CAR-T) therapies (the PRO-CAR-T study).", - "authorString": "Hughes SE, McMullan C, Aiyegbusi OL, Shaw K, Kinsella F, Ferguson P, Khatsuria F, Burns D, Pyatt L, Ansell J, Chakera E, Richardson-Abraham J, Denniston AK, Davies EH, Craddock C, Calvert M.", - "authorAffiliations": "", - "journalTitle": "BMJ open", - "pubYear": "2024", - "date": "2024-03-29", - "isOpenAccess": "Y", - "keywords": "Gene therapy; Quality of life; Haematology; Patient-centered Care; Ehealth; Patient Reported Outcome Measures", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Introduction

Chimeric antigen receptor (CAR) T-cell therapies are novel, potentially curative therapies for haematological malignancies. CAR T-cell therapies are associated with severe toxicities, meaning patients require monitoring during acute and postacute treatment phases. Electronic patient-reported outcomes (ePROs), self-reports of health status provided via online questionnaires, can complement clinician observation with potential to improve patient outcomes. This study will develop and evaluate feasibility of a new ePRO system for CAR-T patients in routine care.

Methods and analysis

Multiphase, mixed-methods study involving multiple stakeholder groups (patients, family members, carers, clinicians, academics/researchers and policy-makers). The intervention development phase comprises a Delphi study to select PRO measures for the digital system, a codesign workshop and consensus meetings to establish thresholds for notifications to the clinical team if a patient reports severe symptoms or side effects. Usability testing will evaluate how users interact with the digital system and, lastly, we will evaluate ePRO system feasibility with 30 CAR-T patients (adults aged 18+ years) when used in addition to usual care. Feasibility study participants will use the ePRO system to submit self-reports of symptoms, treatment tolerability and quality of life at specific time points. The CAR-T clinical team will respond to system notifications triggered by patients' submitted responses with actions in line with standard clinical practice. Feasibility measures will be collected at prespecified time points following CAR T-cell infusion. A qualitative substudy involving patients and clinical team members will explore acceptability of the ePRO system.

Ethics and dissemination

Favourable ethical opinion was granted by the Health and Social Care Research Ethics Committee B(HSC REC B) (ref: 23/NI/0104) on 28 September 2023. Findings will be submitted for publication in high-quality, peer-reviewed journals. Summaries of results, codeveloped with the Blood and Transplant Research Unit Patient and Public Involvement and Engagement group, will be disseminated to all interested groups.

Trial registration number

ISCTRN11232653.", - "laySummary": "", - "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/14/3/e085392.full.pdf; doi:https://doi.org/10.1136/bmjopen-2024-085392; html:https://europepmc.org/articles/PMC10982800; pdf:https://europepmc.org/articles/PMC10982800?pdf=render" - }, { "id": "36936592", "doi": "https://doi.org/10.1136/bmjmed-2022-000151", @@ -31109,6 +31092,23 @@ "laySummary": "", "urls": "pdf:https://bmjmedicine.bmj.com/content/bmjmed/1/1/e000151.full.pdf; doi:https://doi.org/10.1136/bmjmed-2022-000151; html:https://europepmc.org/articles/PMC9951363; pdf:https://europepmc.org/articles/PMC9951363?pdf=render" }, + { + "id": "38553074", + "doi": "https://doi.org/10.1136/bmjopen-2024-085392", + "title": "Protocol for a mixed-methods study to develop and feasibility test a digital system for the capture of patient-reported outcomes (PROs) in patients receiving chimeric antigen receptor T-cell (CAR-T) therapies (the PRO-CAR-T study).", + "authorString": "Hughes SE, McMullan C, Aiyegbusi OL, Shaw K, Kinsella F, Ferguson P, Khatsuria F, Burns D, Pyatt L, Ansell J, Chakera E, Richardson-Abraham J, Denniston AK, Davies EH, Craddock C, Calvert M.", + "authorAffiliations": "", + "journalTitle": "BMJ open", + "pubYear": "2024", + "date": "2024-03-29", + "isOpenAccess": "Y", + "keywords": "Gene therapy; Quality of life; Haematology; Patient-centered Care; Ehealth; Patient Reported Outcome Measures", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Introduction

Chimeric antigen receptor (CAR) T-cell therapies are novel, potentially curative therapies for haematological malignancies. CAR T-cell therapies are associated with severe toxicities, meaning patients require monitoring during acute and postacute treatment phases. Electronic patient-reported outcomes (ePROs), self-reports of health status provided via online questionnaires, can complement clinician observation with potential to improve patient outcomes. This study will develop and evaluate feasibility of a new ePRO system for CAR-T patients in routine care.

Methods and analysis

Multiphase, mixed-methods study involving multiple stakeholder groups (patients, family members, carers, clinicians, academics/researchers and policy-makers). The intervention development phase comprises a Delphi study to select PRO measures for the digital system, a codesign workshop and consensus meetings to establish thresholds for notifications to the clinical team if a patient reports severe symptoms or side effects. Usability testing will evaluate how users interact with the digital system and, lastly, we will evaluate ePRO system feasibility with 30 CAR-T patients (adults aged 18+ years) when used in addition to usual care. Feasibility study participants will use the ePRO system to submit self-reports of symptoms, treatment tolerability and quality of life at specific time points. The CAR-T clinical team will respond to system notifications triggered by patients' submitted responses with actions in line with standard clinical practice. Feasibility measures will be collected at prespecified time points following CAR T-cell infusion. A qualitative substudy involving patients and clinical team members will explore acceptability of the ePRO system.

Ethics and dissemination

Favourable ethical opinion was granted by the Health and Social Care Research Ethics Committee B(HSC REC B) (ref: 23/NI/0104) on 28 September 2023. Findings will be submitted for publication in high-quality, peer-reviewed journals. Summaries of results, codeveloped with the Blood and Transplant Research Unit Patient and Public Involvement and Engagement group, will be disseminated to all interested groups.

Trial registration number

ISCTRN11232653.", + "laySummary": "", + "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/14/3/e085392.full.pdf; doi:https://doi.org/10.1136/bmjopen-2024-085392; html:https://europepmc.org/articles/PMC10982800; pdf:https://europepmc.org/articles/PMC10982800?pdf=render" + }, { "id": "36058413", "doi": "https://doi.org/10.1016/j.jinf.2022.08.030", @@ -31160,23 +31160,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.bbih.2021.100286; doi:https://doi.org/10.1016/j.bbih.2021.100286; html:https://europepmc.org/articles/PMC8261829; pdf:https://europepmc.org/articles/PMC8261829?pdf=render" }, - { - "id": "36335192", - "doi": "https://doi.org/10.1038/s41598-022-22218-9", - "title": "Genetic insights into smoking behaviours in 10,558 men of African ancestry from continental Africa and the UK.", - "authorString": "Piga NN, Boua PR, Soremekun C, Shrine N, Coley K, Brandenburg JT, Tobin MD, Ramsay M, Fatumo S, Choudhury A, Batini C.", - "authorAffiliations": "", - "journalTitle": "Scientific reports", - "pubYear": "2022", - "date": "2022-11-05", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Smoking is a leading risk factor for many of the top ten causes of death worldwide. Of the 1.3 billion smokers globally, 80% live in low- and middle-income countries, where the number of deaths due to tobacco use is expected to double in the next decade according to the World Health Organization. Genetic studies have helped to identify biological pathways for smoking behaviours, but have mostly focussed on individuals of European ancestry or living in either North America or Europe. We performed a genome-wide association study of two smoking behaviour traits in 10,558 men of African ancestry living in five African countries and the UK. Eight independent variants were associated with either smoking initiation or cessation at P-value\u2009<\u20095\u2009\u00d7\u200910-6, four being monomorphic or rare in European populations. Gene prioritisation strategy highlighted five genes, including SEMA6D, previously described as associated with several smoking behaviour traits. These results confirm the importance of analysing underrepresented populations in genetic epidemiology, and the urgent need for larger genomic studies to boost discovery power to better understand smoking behaviours, as well as many other traits.", - "laySummary": "", - "urls": "pdf:https://www.nature.com/articles/s41598-022-22218-9.pdf; doi:https://doi.org/10.1038/s41598-022-22218-9; html:https://europepmc.org/articles/PMC9637114; pdf:https://europepmc.org/articles/PMC9637114?pdf=render" - }, { "id": "35212847", "doi": "https://doi.org/10.1007/s00455-022-10425-5", @@ -31194,6 +31177,23 @@ "laySummary": "", "urls": "pdf:https://link.springer.com/content/pdf/10.1007/s00455-022-10425-5.pdf; doi:https://doi.org/10.1007/s00455-022-10425-5; html:https://europepmc.org/articles/PMC9643178; pdf:https://europepmc.org/articles/PMC9643178?pdf=render" }, + { + "id": "36335192", + "doi": "https://doi.org/10.1038/s41598-022-22218-9", + "title": "Genetic insights into smoking behaviours in 10,558 men of African ancestry from continental Africa and the UK.", + "authorString": "Piga NN, Boua PR, Soremekun C, Shrine N, Coley K, Brandenburg JT, Tobin MD, Ramsay M, Fatumo S, Choudhury A, Batini C.", + "authorAffiliations": "", + "journalTitle": "Scientific reports", + "pubYear": "2022", + "date": "2022-11-05", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Smoking is a leading risk factor for many of the top ten causes of death worldwide. Of the 1.3 billion smokers globally, 80% live in low- and middle-income countries, where the number of deaths due to tobacco use is expected to double in the next decade according to the World Health Organization. Genetic studies have helped to identify biological pathways for smoking behaviours, but have mostly focussed on individuals of European ancestry or living in either North America or Europe. We performed a genome-wide association study of two smoking behaviour traits in 10,558 men of African ancestry living in five African countries and the UK. Eight independent variants were associated with either smoking initiation or cessation at P-value\u2009<\u20095\u2009\u00d7\u200910-6, four being monomorphic or rare in European populations. Gene prioritisation strategy highlighted five genes, including SEMA6D, previously described as associated with several smoking behaviour traits. These results confirm the importance of analysing underrepresented populations in genetic epidemiology, and the urgent need for larger genomic studies to boost discovery power to better understand smoking behaviours, as well as many other traits.", + "laySummary": "", + "urls": "pdf:https://www.nature.com/articles/s41598-022-22218-9.pdf; doi:https://doi.org/10.1038/s41598-022-22218-9; html:https://europepmc.org/articles/PMC9637114; pdf:https://europepmc.org/articles/PMC9637114?pdf=render" + }, { "id": "37981722", "doi": "https://doi.org/10.1093/aje/kwad232", @@ -31245,23 +31245,6 @@ "laySummary": "", "urls": "pdf:https://www.karger.com/Article/Pdf/517521; doi:https://doi.org/10.1159/000517521" }, - { - "id": "37474660", - "doi": "https://doi.org/10.1038/s41591-023-02445-x", - "title": "Considerations for patient and public involvement and engagement in health research.", - "authorString": "Aiyegbusi OL, McMullan C, Hughes SE, Turner GM, Subramanian A, Hotham R, Davies EH, Frost C, Alder Y, Agyen L, Buckland L, Camaradou J, Chong A, Jeyes F, Kumar S, Matthews KL, Moore P, Ormerod J, Price G, Saint-Cricq M, Stanton D, Walker A, Haroon S, Denniston AK, Calvert MJ, TLC Study Group.", - "authorAffiliations": "", - "journalTitle": "Nature medicine", - "pubYear": "2023", - "date": "2023-07-20", - "isOpenAccess": "N", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Patient and public involvement and engagement (PPIE) can provide valuable insights into the experiences of those living with and affected by a disease or health condition. Inclusive collaboration between patients, the public and researchers can lead to productive relationships, ensuring that health research addresses patient needs. Guidelines are available to support effective PPIE; however, evaluation of the impact of PPIE strategies in health research is limited. In this Review, we evaluate the impact of PPIE in the 'Therapies for Long COVID in non-hospitalised individuals' (TLC) Study, using a combination of group discussions and interviews with patient partners and researchers. We identify areas of good practice and reflect on areas for improvement. Using these insights and the results of a survey, we synthesize two checklists of considerations for PPIE, and we propose that research teams use these checklists to optimize the impact of PPIE for both patients and researchers in future studies.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1038/s41591-023-02445-x" - }, { "id": "35434685", "doi": "https://doi.org/10.1016/j.lanepe.2022.100381", @@ -31279,6 +31262,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.lanepe.2022.100381; doi:https://doi.org/10.1016/j.lanepe.2022.100381; html:https://europepmc.org/articles/PMC8996067; pdf:https://europepmc.org/articles/PMC8996067?pdf=render" }, + { + "id": "37474660", + "doi": "https://doi.org/10.1038/s41591-023-02445-x", + "title": "Considerations for patient and public involvement and engagement in health research.", + "authorString": "Aiyegbusi OL, McMullan C, Hughes SE, Turner GM, Subramanian A, Hotham R, Davies EH, Frost C, Alder Y, Agyen L, Buckland L, Camaradou J, Chong A, Jeyes F, Kumar S, Matthews KL, Moore P, Ormerod J, Price G, Saint-Cricq M, Stanton D, Walker A, Haroon S, Denniston AK, Calvert MJ, TLC Study Group.", + "authorAffiliations": "", + "journalTitle": "Nature medicine", + "pubYear": "2023", + "date": "2023-07-20", + "isOpenAccess": "N", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Patient and public involvement and engagement (PPIE) can provide valuable insights into the experiences of those living with and affected by a disease or health condition. Inclusive collaboration between patients, the public and researchers can lead to productive relationships, ensuring that health research addresses patient needs. Guidelines are available to support effective PPIE; however, evaluation of the impact of PPIE strategies in health research is limited. In this Review, we evaluate the impact of PPIE in the 'Therapies for Long COVID in non-hospitalised individuals' (TLC) Study, using a combination of group discussions and interviews with patient partners and researchers. We identify areas of good practice and reflect on areas for improvement. Using these insights and the results of a survey, we synthesize two checklists of considerations for PPIE, and we propose that research teams use these checklists to optimize the impact of PPIE for both patients and researchers in future studies.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1038/s41591-023-02445-x" + }, { "id": "37730620", "doi": "https://doi.org/10.1186/s13643-023-02333-y", @@ -31330,23 +31330,6 @@ "laySummary": "", "urls": "pdf:http://www.thelancet.com/article/S2468125321000054/pdf; doi:https://doi.org/10.1016/S2468-1253(21)00005-4; html:https://europepmc.org/articles/PMC7808901; pdf:https://europepmc.org/articles/PMC7808901?pdf=render" }, - { - "id": "37872160", - "doi": "https://doi.org/10.1038/s41467-023-42284-5", - "title": "Genome-wide association study of thyroid-stimulating hormone highlights new genes, pathways and associations with thyroid disease.", - "authorString": "Williams AT, Chen J, Coley K, Batini C, Izquierdo A, Packer R, Abner E, Kanoni S, Shepherd DJ, Free RC, Hollox EJ, Brunskill NJ, Ntalla I, Reeve N, Brightling CE, Venn L, Adams E, Bee C, Wallace SE, Pareek M, Hansell AL, Esko T, Estonian Biobank Research Team, Stow D, Jacobs BM, van Heel DA, Genes & Health Research Team, Hennah W, Rao BS, Dudbridge F, Wain LV, Shrine N, Tobin MD, John C.", - "authorAffiliations": "", - "journalTitle": "Nature communications", - "pubYear": "2023", - "date": "2023-10-23", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Thyroid hormones play a critical role in regulation of multiple physiological functions and thyroid dysfunction is associated with substantial morbidity. Here, we use electronic health records to undertake a genome-wide association study of thyroid-stimulating hormone (TSH) levels, with a total sample size of 247,107. We identify 158 novel genetic associations, more than doubling the number of known associations with TSH, and implicate 112 putative causal genes, of which 76 are not previously implicated. A polygenic score for TSH is associated with TSH levels in African, South Asian, East Asian, Middle Eastern and admixed American ancestries, and associated with hypothyroidism and other thyroid disease in South Asians. In Europeans, the TSH polygenic score is associated with thyroid disease, including thyroid cancer and age-of-onset of hypothyroidism and hyperthyroidism. We develop pathway-specific genetic risk scores for TSH levels and use these in phenome-wide association studies to identify potential consequences of pathway perturbation. Together, these findings demonstrate the potential utility of genetic associations to inform future therapeutics and risk prediction for thyroid diseases.", - "laySummary": "", - "urls": "pdf:https://www.nature.com/articles/s41467-023-42284-5.pdf; doi:https://doi.org/10.1038/s41467-023-42284-5; html:https://europepmc.org/articles/PMC10593800; pdf:https://europepmc.org/articles/PMC10593800?pdf=render" - }, { "id": "32619549", "doi": "https://doi.org/10.1016/j.cels.2020.05.012", @@ -31381,6 +31364,23 @@ "laySummary": "", "urls": "pdf:https://www.ahajournals.org/doi/pdf/10.1161/JAHA.119.013684; doi:https://doi.org/10.1161/JAHA.119.013684; html:https://europepmc.org/articles/PMC7428631; pdf:https://europepmc.org/articles/PMC7428631?pdf=render" }, + { + "id": "37872160", + "doi": "https://doi.org/10.1038/s41467-023-42284-5", + "title": "Genome-wide association study of thyroid-stimulating hormone highlights new genes, pathways and associations with thyroid disease.", + "authorString": "Williams AT, Chen J, Coley K, Batini C, Izquierdo A, Packer R, Abner E, Kanoni S, Shepherd DJ, Free RC, Hollox EJ, Brunskill NJ, Ntalla I, Reeve N, Brightling CE, Venn L, Adams E, Bee C, Wallace SE, Pareek M, Hansell AL, Esko T, Estonian Biobank Research Team, Stow D, Jacobs BM, van Heel DA, Genes & Health Research Team, Hennah W, Rao BS, Dudbridge F, Wain LV, Shrine N, Tobin MD, John C.", + "authorAffiliations": "", + "journalTitle": "Nature communications", + "pubYear": "2023", + "date": "2023-10-23", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Thyroid hormones play a critical role in regulation of multiple physiological functions and thyroid dysfunction is associated with substantial morbidity. Here, we use electronic health records to undertake a genome-wide association study of thyroid-stimulating hormone (TSH) levels, with a total sample size of 247,107. We identify 158 novel genetic associations, more than doubling the number of known associations with TSH, and implicate 112 putative causal genes, of which 76 are not previously implicated. A polygenic score for TSH is associated with TSH levels in African, South Asian, East Asian, Middle Eastern and admixed American ancestries, and associated with hypothyroidism and other thyroid disease in South Asians. In Europeans, the TSH polygenic score is associated with thyroid disease, including thyroid cancer and age-of-onset of hypothyroidism and hyperthyroidism. We develop pathway-specific genetic risk scores for TSH levels and use these in phenome-wide association studies to identify potential consequences of pathway perturbation. Together, these findings demonstrate the potential utility of genetic associations to inform future therapeutics and risk prediction for thyroid diseases.", + "laySummary": "", + "urls": "pdf:https://www.nature.com/articles/s41467-023-42284-5.pdf; doi:https://doi.org/10.1038/s41467-023-42284-5; html:https://europepmc.org/articles/PMC10593800; pdf:https://europepmc.org/articles/PMC10593800?pdf=render" + }, { "id": "33928785", "doi": "https://doi.org/10.1161/circulationaha.120.049844", @@ -31619,23 +31619,6 @@ "laySummary": "", "urls": "pdf:https://formative.jmir.org/2022/1/e21341/PDF; doi:https://doi.org/10.2196/21341; html:https://europepmc.org/articles/PMC8845013; pdf:https://europepmc.org/articles/PMC8845013?pdf=render" }, - { - "id": "35861818", - "doi": "https://doi.org/10.1161/jaha.121.025473", - "title": "Interatrial Block Predicts Life-Threatening Arrhythmias in Dilated Cardiomyopathy.", - "authorString": "Henkens MTHM, L\u00f3pez Mart\u00ednez H, Weerts J, Sammani A, Raafs AG, Verdonschot JAJ, van de Leur RR, Sikking MA, Stroeks S, van Empel VPM, Brunner-La Rocca HP, van Stipdonk AMW, Farmakis D, Hazebroek MR, Vernooy K, Bay\u00e9s-de-Luna A, Asselbergs FW, Bay\u00e9s-Gen\u00eds A, Heymans SRB.", - "authorAffiliations": "", - "journalTitle": "Journal of the American Heart Association", - "pubYear": "2022", - "date": "2022-07-15", - "isOpenAccess": "Y", - "keywords": "Electrocardiography; Dilated cardiomyopathy; Sudden Cardiac Death; Interatrial Block; Non\u2010ischemic Cardiomyopathy; Life\u2010threatening Arrhythmias", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Background Interatrial block (IAB) has been associated with supraventricular arrhythmias and stroke, and even with sudden cardiac death in the general population. Whether IAB is associated with life-threatening arrhythmias (LTA) and sudden cardiac death in dilated cardiomyopathy (DCM) remains unknown. This study aimed to determine the association between IAB and LTA in ambulant patients with DCM. Methods and Results A derivation cohort (Maastricht Dilated Cardiomyopathy Registry; N=469) and an external validation cohort (Utrecht Cardiomyopathy Cohort; N=321) were used for this study. The presence of IAB (P-wave duration>120\u00a0milliseconds) or atrial fibrillation (AF) was determined using digital calipers by physicians blinded to the study data. In the derivation cohort, IAB and AF were present in 291 (62%) and 70 (15%) patients with DCM, respectively. LTA (defined as sudden cardiac death, justified shock from implantable cardioverter-defibrillator or anti-tachypacing, or hemodynamic unstable ventricular fibrillation/tachycardia) occurred in 49 patients (3 with no IAB, 35 with IAB, and 11 patients with AF, respectively; median follow-up, 4.4\u00a0years [2.1; 7.4]). The LTA-free survival distribution significantly differed between IAB or AF versus no IAB (both P<0.01), but not between IAB versus AF (P=0.999). This association remained statistically significant in the multivariable model (IAB: HR, 4.8 (1.4-16.1), P=0.013; AF: HR, 6.4 (1.7-24.0), P=0.007). In the external validation cohort, the survival distribution was also significantly worse for IAB or AF versus no IAB (P=0.037; P=0.005), but not for IAB versus AF (P=0.836). Conclusions IAB is an easy to assess, widely applicable marker associated with LTA in DCM. IAB and AF seem to confer similar risk of LTA. Further research on IAB in DCM, and on the management of IAB in DCM is warranted.", - "laySummary": "", - "urls": "pdf:https://www.ahajournals.org/doi/pdf/10.1161/JAHA.121.025473; doi:https://doi.org/10.1161/JAHA.121.025473; html:https://europepmc.org/articles/PMC9707810; pdf:https://europepmc.org/articles/PMC9707810?pdf=render" - }, { "id": "33184391", "doi": "https://doi.org/10.1038/s41598-020-76816-6", @@ -31653,6 +31636,23 @@ "laySummary": "", "urls": "pdf:https://www.nature.com/articles/s41598-020-76816-6.pdf; doi:https://doi.org/10.1038/s41598-020-76816-6; html:https://europepmc.org/articles/PMC7661535; pdf:https://europepmc.org/articles/PMC7661535?pdf=render" }, + { + "id": "35861818", + "doi": "https://doi.org/10.1161/jaha.121.025473", + "title": "Interatrial Block Predicts Life-Threatening Arrhythmias in Dilated Cardiomyopathy.", + "authorString": "Henkens MTHM, L\u00f3pez Mart\u00ednez H, Weerts J, Sammani A, Raafs AG, Verdonschot JAJ, van de Leur RR, Sikking MA, Stroeks S, van Empel VPM, Brunner-La Rocca HP, van Stipdonk AMW, Farmakis D, Hazebroek MR, Vernooy K, Bay\u00e9s-de-Luna A, Asselbergs FW, Bay\u00e9s-Gen\u00eds A, Heymans SRB.", + "authorAffiliations": "", + "journalTitle": "Journal of the American Heart Association", + "pubYear": "2022", + "date": "2022-07-15", + "isOpenAccess": "Y", + "keywords": "Electrocardiography; Dilated cardiomyopathy; Sudden Cardiac Death; Interatrial Block; Non\u2010ischemic Cardiomyopathy; Life\u2010threatening Arrhythmias", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Background Interatrial block (IAB) has been associated with supraventricular arrhythmias and stroke, and even with sudden cardiac death in the general population. Whether IAB is associated with life-threatening arrhythmias (LTA) and sudden cardiac death in dilated cardiomyopathy (DCM) remains unknown. This study aimed to determine the association between IAB and LTA in ambulant patients with DCM. Methods and Results A derivation cohort (Maastricht Dilated Cardiomyopathy Registry; N=469) and an external validation cohort (Utrecht Cardiomyopathy Cohort; N=321) were used for this study. The presence of IAB (P-wave duration>120\u00a0milliseconds) or atrial fibrillation (AF) was determined using digital calipers by physicians blinded to the study data. In the derivation cohort, IAB and AF were present in 291 (62%) and 70 (15%) patients with DCM, respectively. LTA (defined as sudden cardiac death, justified shock from implantable cardioverter-defibrillator or anti-tachypacing, or hemodynamic unstable ventricular fibrillation/tachycardia) occurred in 49 patients (3 with no IAB, 35 with IAB, and 11 patients with AF, respectively; median follow-up, 4.4\u00a0years [2.1; 7.4]). The LTA-free survival distribution significantly differed between IAB or AF versus no IAB (both P<0.01), but not between IAB versus AF (P=0.999). This association remained statistically significant in the multivariable model (IAB: HR, 4.8 (1.4-16.1), P=0.013; AF: HR, 6.4 (1.7-24.0), P=0.007). In the external validation cohort, the survival distribution was also significantly worse for IAB or AF versus no IAB (P=0.037; P=0.005), but not for IAB versus AF (P=0.836). Conclusions IAB is an easy to assess, widely applicable marker associated with LTA in DCM. IAB and AF seem to confer similar risk of LTA. Further research on IAB in DCM, and on the management of IAB in DCM is warranted.", + "laySummary": "", + "urls": "pdf:https://www.ahajournals.org/doi/pdf/10.1161/JAHA.121.025473; doi:https://doi.org/10.1161/JAHA.121.025473; html:https://europepmc.org/articles/PMC9707810; pdf:https://europepmc.org/articles/PMC9707810?pdf=render" + }, { "id": "36688706", "doi": "https://doi.org/10.1093/rheumatology/kead038", @@ -31704,40 +31704,6 @@ "laySummary": "", "urls": "pdf:https://www.jmir.org/2021/4/e26627/PDF; doi:https://doi.org/10.2196/26627; html:https://europepmc.org/articles/PMC8023383" }, - { - "id": "37391266", - "doi": "https://doi.org/10.1016/s2589-7500(23)00087-0", - "title": "Wearable technology and the cardiovascular system: the future of patient assessment.", - "authorString": "Williams GJ, Al-Baraikan A, Rademakers FE, Ciravegna F, van de Vosse FN, Lawrie A, Rothman A, Ashley EA, Wilkins MR, Lawford PV, Omholt SW, Wisl\u00f8ff U, Hose DR, Chico TJA, Gunn JP, Morris PD.", - "authorAffiliations": "", - "journalTitle": "The Lancet. Digital health", - "pubYear": "2023", - "date": "2023-07-01", - "isOpenAccess": "N", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "The past decade has seen a dramatic rise in consumer technologies able to monitor a variety of cardiovascular parameters. Such devices initially recorded markers of exercise, but now include physiological and health-care focused measurements. The public are keen to adopt these devices in the belief that they are useful to identify and monitor cardiovascular disease. Clinicians are therefore often presented with health app data accompanied by a diverse range of concerns and queries. Herein, we assess whether these devices are accurate, their outputs validated, and whether they are suitable for professionals to make management decisions. We review underpinning methods and technologies and explore the evidence supporting the use of these devices as diagnostic and monitoring tools in hypertension, arrhythmia, heart failure, coronary artery disease, pulmonary hypertension, and valvular heart disease. Used correctly, they might improve health care and support research.", - "laySummary": "", - "urls": "pdf:http://www.thelancet.com/article/S2589750023000870/pdf; doi:https://doi.org/10.1016/S2589-7500(23)00087-0" - }, - { - "id": "37096818", - "doi": "https://doi.org/10.1093/ehjacc/zuad042", - "title": "Serially measured high-sensitivity cardiac troponin T, N-terminal-pro-B-type natriuretic peptide, high-sensitivity C-reactive protein, and growth differentiation factor 15 for risk assessment after acute coronary syndrome: the BIOMArCS cohort.", - "authorString": "G\u00fcrg\u00f6ze MT, Akkerhuis KM, Oemrawsingh RM, Umans VAWM, Kietselaer B, Schotborgh CE, Ronner E, Lenderink T, Aksoy I, van der Harst P, Asselbergs FW, Maas AC, Oude Ophuis AJ, Krenning B, de Winter RJ, The SHK, Wardeh AJ, Hermans WRM, Cramer GE, van Gorp I, de Rijke YB, van Schaik RHN, Boersma E.", - "authorAffiliations": "", - "journalTitle": "European heart journal. Acute cardiovascular care", - "pubYear": "2023", - "date": "2023-07-01", - "isOpenAccess": "Y", - "keywords": "Prognosis; Biomarkers; acute coronary syndrome; risk assessment; Repeated Measurements", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Aims

Evidence regarding the role of serial measurements of biomarkers for risk assessment in post-acute coronary syndrome (ACS) patients is limited. The aim was to explore the prognostic value of four, serially measured biomarkers in a large, real-world cohort of post-ACS patients.

Methods and results

BIOMArCS is a prospective, multi-centre, observational study in 844 post-ACS patients in whom 12 218 blood samples (median 17 per patient) were obtained during 1-year follow-up. The longitudinal patterns of high-sensitivity cardiac troponin T (hs-cTnT), N-terminal-pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein (hs-CRP), and growth differentiation factor 15 (GDF-15) were analysed in relation to the primary endpoint (PE) of cardiovascular mortality and recurrent ACS using multivariable joint models. Median age was 63 years, 78% were men and the PE was reached by 45 patients. The average biomarker levels were systematically higher in PE compared with PE-free patients. After adjustment for 6-month post-discharge Global Registry of Acute Coronary Events score, 1 standard deviation increase in log[hs-cTnT] was associated with a 61% increased risk of the PE [hazard ratio (HR) 1.61, 95% confidence interval (CI) 1.02-2.44, P = 0.045], while for log[GDF-15] this was 81% (HR 1.81, 95% CI 1.28-2.70, P = 0.001). These associations remained significant after multivariable adjustment, while NT-proBNP and hs-CRP were not. Furthermore, GDF-15 level showed an increasing trend prior to the PE (Structured Graphical Abstract).

Conclusion

Longitudinally measured hs-cTnT and GDF-15 concentrations provide prognostic value in the risk assessment of clinically stabilized patients post-ACS.

Clinical trial registration

The Netherlands Trial Register. Currently available at URL https://trialsearch.who.int/; Unique Identifiers: NTR1698 and NTR1106.", - "laySummary": "", - "urls": "pdf:https://academic.oup.com/ehjacc/advance-article-pdf/doi/10.1093/ehjacc/zuad042/50087609/zuad042.pdf; doi:https://doi.org/10.1093/ehjacc/zuad042; html:https://europepmc.org/articles/PMC10328437; pdf:https://europepmc.org/articles/PMC10328437?pdf=render" - }, { "id": "32685697", "doi": "https://doi.org/10.12688/wellcomeopenres.15788.1", @@ -31790,21 +31756,38 @@ "urls": "pdf:https://discovery.ucl.ac.uk/10097154/3/Solebo_Liu%20AC%20Flare%20SR%20290919.pdf; doi:https://doi.org/10.1080/09273948.2019.1709650" }, { - "id": "33782080", - "doi": "https://doi.org/10.1136/thoraxjnl-2020-216512", - "title": "Impact of COVID-19 national lockdown on asthma exacerbations: interrupted time-series analysis of English primary care data.", - "authorString": "Shah SA, Quint JK, Nwaru BI, Sheikh A.", + "id": "37391266", + "doi": "https://doi.org/10.1016/s2589-7500(23)00087-0", + "title": "Wearable technology and the cardiovascular system: the future of patient assessment.", + "authorString": "Williams GJ, Al-Baraikan A, Rademakers FE, Ciravegna F, van de Vosse FN, Lawrie A, Rothman A, Ashley EA, Wilkins MR, Lawford PV, Omholt SW, Wisl\u00f8ff U, Hose DR, Chico TJA, Gunn JP, Morris PD.", "authorAffiliations": "", - "journalTitle": "Thorax", - "pubYear": "2021", - "date": "2021-03-29", + "journalTitle": "The Lancet. Digital health", + "pubYear": "2023", + "date": "2023-07-01", + "isOpenAccess": "N", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "The past decade has seen a dramatic rise in consumer technologies able to monitor a variety of cardiovascular parameters. Such devices initially recorded markers of exercise, but now include physiological and health-care focused measurements. The public are keen to adopt these devices in the belief that they are useful to identify and monitor cardiovascular disease. Clinicians are therefore often presented with health app data accompanied by a diverse range of concerns and queries. Herein, we assess whether these devices are accurate, their outputs validated, and whether they are suitable for professionals to make management decisions. We review underpinning methods and technologies and explore the evidence supporting the use of these devices as diagnostic and monitoring tools in hypertension, arrhythmia, heart failure, coronary artery disease, pulmonary hypertension, and valvular heart disease. Used correctly, they might improve health care and support research.", + "laySummary": "", + "urls": "pdf:http://www.thelancet.com/article/S2589750023000870/pdf; doi:https://doi.org/10.1016/S2589-7500(23)00087-0" + }, + { + "id": "37096818", + "doi": "https://doi.org/10.1093/ehjacc/zuad042", + "title": "Serially measured high-sensitivity cardiac troponin T, N-terminal-pro-B-type natriuretic peptide, high-sensitivity C-reactive protein, and growth differentiation factor 15 for risk assessment after acute coronary syndrome: the BIOMArCS cohort.", + "authorString": "G\u00fcrg\u00f6ze MT, Akkerhuis KM, Oemrawsingh RM, Umans VAWM, Kietselaer B, Schotborgh CE, Ronner E, Lenderink T, Aksoy I, van der Harst P, Asselbergs FW, Maas AC, Oude Ophuis AJ, Krenning B, de Winter RJ, The SHK, Wardeh AJ, Hermans WRM, Cramer GE, van Gorp I, de Rijke YB, van Schaik RHN, Boersma E.", + "authorAffiliations": "", + "journalTitle": "European heart journal. Acute cardiovascular care", + "pubYear": "2023", + "date": "2023-07-01", "isOpenAccess": "Y", - "keywords": "Asthma; Asthma Epidemiology; Covid-19", + "keywords": "Prognosis; Biomarkers; acute coronary syndrome; risk assessment; Repeated Measurements", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Background

The impact of COVID-19 and ensuing national lockdown on asthma exacerbations is unclear.

Methods

We conducted an interrupted time-series (lockdown on 23 March 2020 as point of interruption) analysis in asthma cohort identified using a validated algorithm from a national-level primary care database, the Optimum Patient Care Database. We derived asthma exacerbation rates for every week and compared exacerbation rates in the period: January to August 2020 with a pre-COVID-19 period and January to August 2016-2019. Exacerbations were defined as asthma-related hospital attendance/admission (including accident and emergency visit), or an acute course of oral corticosteroids with evidence of respiratory review, as recorded in primary care. We used a generalised least squares modelling approach and stratified the analyses by age, sex, English region and healthcare setting.

Results

From a database of 9 949 387 patients, there were 100 165 patients with asthma who experienced at least one exacerbation during 2016-2020. Of 278 996 exacerbation episodes, 49 938 (17.9%) required hospital visit. Comparing pre-lockdown to post-lockdown period, we observed a statistically significant reduction in the level (-0.196 episodes per person-year; p<0.001; almost 20 episodes for every 100 patients with asthma per year) of exacerbation rates across all patients. The reductions in level in stratified analyses were: 0.005-0.244 (healthcare setting, only those without hospital attendance/admission were significant), 0.210-0.277 (sex), 0.159-0.367 (age), 0.068-0.590 (region).

Conclusions

There has been a significant reduction in attendance to primary care for asthma exacerbations during the pandemic. This reduction was observed in all age groups, both sexes and across most regions in England.", + "abstract": "

Aims

Evidence regarding the role of serial measurements of biomarkers for risk assessment in post-acute coronary syndrome (ACS) patients is limited. The aim was to explore the prognostic value of four, serially measured biomarkers in a large, real-world cohort of post-ACS patients.

Methods and results

BIOMArCS is a prospective, multi-centre, observational study in 844 post-ACS patients in whom 12 218 blood samples (median 17 per patient) were obtained during 1-year follow-up. The longitudinal patterns of high-sensitivity cardiac troponin T (hs-cTnT), N-terminal-pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein (hs-CRP), and growth differentiation factor 15 (GDF-15) were analysed in relation to the primary endpoint (PE) of cardiovascular mortality and recurrent ACS using multivariable joint models. Median age was 63 years, 78% were men and the PE was reached by 45 patients. The average biomarker levels were systematically higher in PE compared with PE-free patients. After adjustment for 6-month post-discharge Global Registry of Acute Coronary Events score, 1 standard deviation increase in log[hs-cTnT] was associated with a 61% increased risk of the PE [hazard ratio (HR) 1.61, 95% confidence interval (CI) 1.02-2.44, P = 0.045], while for log[GDF-15] this was 81% (HR 1.81, 95% CI 1.28-2.70, P = 0.001). These associations remained significant after multivariable adjustment, while NT-proBNP and hs-CRP were not. Furthermore, GDF-15 level showed an increasing trend prior to the PE (Structured Graphical Abstract).

Conclusion

Longitudinally measured hs-cTnT and GDF-15 concentrations provide prognostic value in the risk assessment of clinically stabilized patients post-ACS.

Clinical trial registration

The Netherlands Trial Register. Currently available at URL https://trialsearch.who.int/; Unique Identifiers: NTR1698 and NTR1106.", "laySummary": "", - "urls": "pdf:https://thorax.bmj.com/content/thoraxjnl/76/9/860.full.pdf; doi:https://doi.org/10.1136/thoraxjnl-2020-216512; html:https://europepmc.org/articles/PMC8011425; pdf:https://europepmc.org/articles/PMC8011425?pdf=render" + "urls": "pdf:https://academic.oup.com/ehjacc/advance-article-pdf/doi/10.1093/ehjacc/zuad042/50087609/zuad042.pdf; doi:https://doi.org/10.1093/ehjacc/zuad042; html:https://europepmc.org/articles/PMC10328437; pdf:https://europepmc.org/articles/PMC10328437?pdf=render" }, { "id": "31145509", @@ -31824,21 +31807,21 @@ "urls": "pdf:https://pure.rug.nl/ws/files/89611268/Manduchi_et_al_2019_Genetic_Epidemiology.pdf; doi:https://doi.org/10.1002/gepi.22215; html:https://europepmc.org/articles/PMC6687530; pdf:https://europepmc.org/articles/PMC6687530?pdf=render; doi:https://doi.org/10.1002/gepi.22215" }, { - "id": "36357634", - "doi": "https://doi.org/10.1007/s00467-022-05789-7", - "title": "Shared genetic risk across different presentations of gene test-negative idiopathic nephrotic syndrome.", - "authorString": "Downie ML, Gupta S, Chan MMY, Sadeghi-Alavijeh O, Cao J, Parekh RS, Diz CB, Bierzynska A, Levine AP, Pepper RJ, Stanescu H, Saleem MA, Kleta R, Bockenhauer D, Koziell AB, Gale DP.", + "id": "33782080", + "doi": "https://doi.org/10.1136/thoraxjnl-2020-216512", + "title": "Impact of COVID-19 national lockdown on asthma exacerbations: interrupted time-series analysis of English primary care data.", + "authorString": "Shah SA, Quint JK, Nwaru BI, Sheikh A.", "authorAffiliations": "", - "journalTitle": "Pediatric nephrology (Berlin, Germany)", - "pubYear": "2023", - "date": "2022-11-10", + "journalTitle": "Thorax", + "pubYear": "2021", + "date": "2021-03-29", "isOpenAccess": "Y", - "keywords": "Paediatrics; Minimal Change Disease; Focal Segmental Glomerulosclerosis; Monogenic; Genetic Risk Score; Steroid-resistant Nephrotic Syndrome; Steroid-sensitive Nephrotic Syndrome", + "keywords": "Asthma; Asthma Epidemiology; Covid-19", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Background

Idiop athic nephrotic syndrome (INS) is classified in children according to response to initial corticosteroid therapy into steroid-sensitive (SSNS) and steroid-resistant nephrotic syndrome (SRNS), and in adults according to histology into minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS). However, there is well-recognised phenotypic overlap between these entities. Genome-wide association studies (GWAS) have shown a strong association between SSNS and variation at HLA, suggesting an underlying immunological basis. We sought to determine whether a risk score generated from genetic variants associated with SSNS could be used to gain insight into the pathophysiology of INS presenting in other ways.

Methods

We developed an SSNS genetic risk score (SSNS-GRS) from the five variants independently associated with childhood SSNS in a previous European GWAS. We quantified SSNS-GRS in independent cohorts of European individuals with childhood SSNS, non-monogenic SRNS, MCD, and FSGS, and contrasted them with SSNS-GRS quantified in individuals with monogenic SRNS, membranous nephropathy (a different immune-mediated disease-causing nephrotic syndrome), and healthy controls.

Results

The SSNS-GRS was significantly elevated in cohorts with SSNS, non-monogenic SRNS, MCD, and FSGS compared to healthy participants and those with membranous nephropathy. The SSNS-GRS in all cohorts with non-monogenic INS were also significantly elevated compared to those with monogenic SRNS.

Conclusions

The shared genetic risk factors among patients with different presentations of INS strongly suggests a shared autoimmune pathogenesis when monogenic causes are excluded. Use of the SSNS-GRS, in addition to testing for monogenic causes, may help to classify patients presenting with INS. A higher resolution version of the Graphical abstract is available as Supplementary information.", + "abstract": "

Background

The impact of COVID-19 and ensuing national lockdown on asthma exacerbations is unclear.

Methods

We conducted an interrupted time-series (lockdown on 23 March 2020 as point of interruption) analysis in asthma cohort identified using a validated algorithm from a national-level primary care database, the Optimum Patient Care Database. We derived asthma exacerbation rates for every week and compared exacerbation rates in the period: January to August 2020 with a pre-COVID-19 period and January to August 2016-2019. Exacerbations were defined as asthma-related hospital attendance/admission (including accident and emergency visit), or an acute course of oral corticosteroids with evidence of respiratory review, as recorded in primary care. We used a generalised least squares modelling approach and stratified the analyses by age, sex, English region and healthcare setting.

Results

From a database of 9 949 387 patients, there were 100 165 patients with asthma who experienced at least one exacerbation during 2016-2020. Of 278 996 exacerbation episodes, 49 938 (17.9%) required hospital visit. Comparing pre-lockdown to post-lockdown period, we observed a statistically significant reduction in the level (-0.196 episodes per person-year; p<0.001; almost 20 episodes for every 100 patients with asthma per year) of exacerbation rates across all patients. The reductions in level in stratified analyses were: 0.005-0.244 (healthcare setting, only those without hospital attendance/admission were significant), 0.210-0.277 (sex), 0.159-0.367 (age), 0.068-0.590 (region).

Conclusions

There has been a significant reduction in attendance to primary care for asthma exacerbations during the pandemic. This reduction was observed in all age groups, both sexes and across most regions in England.", "laySummary": "", - "urls": "pdf:https://link.springer.com/content/pdf/10.1007/s00467-022-05789-7.pdf; doi:https://doi.org/10.1007/s00467-022-05789-7; html:https://europepmc.org/articles/PMC10154254; pdf:https://europepmc.org/articles/PMC10154254?pdf=render" + "urls": "pdf:https://thorax.bmj.com/content/thoraxjnl/76/9/860.full.pdf; doi:https://doi.org/10.1136/thoraxjnl-2020-216512; html:https://europepmc.org/articles/PMC8011425; pdf:https://europepmc.org/articles/PMC8011425?pdf=render" }, { "id": "33560344", @@ -31858,21 +31841,21 @@ "urls": "pdf:https://academic.oup.com/jcem/article-pdf/106/5/1255/41848481/dgab067.pdf; doi:https://doi.org/10.1210/clinem/dgab067; html:https://europepmc.org/articles/PMC7928949" }, { - "id": "36210800", - "doi": "https://doi.org/10.1038/s43856-022-00189-2", - "title": "Feasibility and ethics of using data from the Scottish newborn blood spot archive for research.", - "authorString": "Cunningham-Burley S, McCartney DL, Campbell A, Flaig R, Orange CEL, Porteous C, Aitken M, Mulholland C, Davidson S, McCafferty SM, Murphy L, Wrobel N, McCafferty S, Wallace K, StClair D, Kerr S, Hayward C, McIntosh AM, Sudlow C, Marioni RE, Pell J, Miedzybrodzka Z, Porteous DJ.", + "id": "36357634", + "doi": "https://doi.org/10.1007/s00467-022-05789-7", + "title": "Shared genetic risk across different presentations of gene test-negative idiopathic nephrotic syndrome.", + "authorString": "Downie ML, Gupta S, Chan MMY, Sadeghi-Alavijeh O, Cao J, Parekh RS, Diz CB, Bierzynska A, Levine AP, Pepper RJ, Stanescu H, Saleem MA, Kleta R, Bockenhauer D, Koziell AB, Gale DP.", "authorAffiliations": "", - "journalTitle": "Communications medicine", - "pubYear": "2022", - "date": "2022-10-06", + "journalTitle": "Pediatric nephrology (Berlin, Germany)", + "pubYear": "2023", + "date": "2022-11-10", "isOpenAccess": "Y", - "keywords": "epigenomics; epidemiology", + "keywords": "Paediatrics; Minimal Change Disease; Focal Segmental Glomerulosclerosis; Monogenic; Genetic Risk Score; Steroid-resistant Nephrotic Syndrome; Steroid-sensitive Nephrotic Syndrome", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Background

Newborn heel prick blood spots are routinely used to screen for inborn errors of metabolism and life-limiting inherited disorders. The potential value of secondary data from newborn blood spot archives merits ethical consideration and assessment of feasibility for public benefit. Early life exposures and behaviours set health trajectories in childhood and later life. The newborn blood spot is potentially well placed to create an unbiased and cost-effective population-level retrospective birth cohort study. Scotland has retained newborn blood spots for all children born since 1965, around 3 million in total. However, a moratorium on research access is currently in place, pending public consultation.

Methods

We conducted a Citizens' Jury as a first step to explore whether research use of newborn blood spots was in the public interest. We also assessed the feasibility and value of extracting research data from dried blood spots for predictive medicine.

Results

Jurors delivered an agreed verdict that conditional research access to the newborn blood spots was in the public interest. The Chief Medical Officer for Scotland authorised restricted lifting of the current research moratorium to allow a feasibility study. Newborn blood spots from consented Generation Scotland volunteers were retrieved and their potential for both epidemiological and biological research demonstrated.

Conclusions

Through the Citizens' Jury, we have begun to identify under what conditions, if any, should researchers in Scotland be granted access to the archive. Through the feasibility study, we have demonstrated the potential value of research access for health data science and predictive medicine.", + "abstract": "

Background

Idiop athic nephrotic syndrome (INS) is classified in children according to response to initial corticosteroid therapy into steroid-sensitive (SSNS) and steroid-resistant nephrotic syndrome (SRNS), and in adults according to histology into minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS). However, there is well-recognised phenotypic overlap between these entities. Genome-wide association studies (GWAS) have shown a strong association between SSNS and variation at HLA, suggesting an underlying immunological basis. We sought to determine whether a risk score generated from genetic variants associated with SSNS could be used to gain insight into the pathophysiology of INS presenting in other ways.

Methods

We developed an SSNS genetic risk score (SSNS-GRS) from the five variants independently associated with childhood SSNS in a previous European GWAS. We quantified SSNS-GRS in independent cohorts of European individuals with childhood SSNS, non-monogenic SRNS, MCD, and FSGS, and contrasted them with SSNS-GRS quantified in individuals with monogenic SRNS, membranous nephropathy (a different immune-mediated disease-causing nephrotic syndrome), and healthy controls.

Results

The SSNS-GRS was significantly elevated in cohorts with SSNS, non-monogenic SRNS, MCD, and FSGS compared to healthy participants and those with membranous nephropathy. The SSNS-GRS in all cohorts with non-monogenic INS were also significantly elevated compared to those with monogenic SRNS.

Conclusions

The shared genetic risk factors among patients with different presentations of INS strongly suggests a shared autoimmune pathogenesis when monogenic causes are excluded. Use of the SSNS-GRS, in addition to testing for monogenic causes, may help to classify patients presenting with INS. A higher resolution version of the Graphical abstract is available as Supplementary information.", "laySummary": "", - "urls": "pdf:https://www.nature.com/articles/s43856-022-00189-2.pdf; doi:https://doi.org/10.1038/s43856-022-00189-2; html:https://europepmc.org/articles/PMC9537278; pdf:https://europepmc.org/articles/PMC9537278?pdf=render" + "urls": "pdf:https://link.springer.com/content/pdf/10.1007/s00467-022-05789-7.pdf; doi:https://doi.org/10.1007/s00467-022-05789-7; html:https://europepmc.org/articles/PMC10154254; pdf:https://europepmc.org/articles/PMC10154254?pdf=render" }, { "id": "31055854", @@ -31891,6 +31874,23 @@ "laySummary": "", "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.5694/mja2.50143; doi:https://doi.org/10.5694/mja2.50143" }, + { + "id": "36210800", + "doi": "https://doi.org/10.1038/s43856-022-00189-2", + "title": "Feasibility and ethics of using data from the Scottish newborn blood spot archive for research.", + "authorString": "Cunningham-Burley S, McCartney DL, Campbell A, Flaig R, Orange CEL, Porteous C, Aitken M, Mulholland C, Davidson S, McCafferty SM, Murphy L, Wrobel N, McCafferty S, Wallace K, StClair D, Kerr S, Hayward C, McIntosh AM, Sudlow C, Marioni RE, Pell J, Miedzybrodzka Z, Porteous DJ.", + "authorAffiliations": "", + "journalTitle": "Communications medicine", + "pubYear": "2022", + "date": "2022-10-06", + "isOpenAccess": "Y", + "keywords": "epigenomics; epidemiology", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Newborn heel prick blood spots are routinely used to screen for inborn errors of metabolism and life-limiting inherited disorders. The potential value of secondary data from newborn blood spot archives merits ethical consideration and assessment of feasibility for public benefit. Early life exposures and behaviours set health trajectories in childhood and later life. The newborn blood spot is potentially well placed to create an unbiased and cost-effective population-level retrospective birth cohort study. Scotland has retained newborn blood spots for all children born since 1965, around 3 million in total. However, a moratorium on research access is currently in place, pending public consultation.

Methods

We conducted a Citizens' Jury as a first step to explore whether research use of newborn blood spots was in the public interest. We also assessed the feasibility and value of extracting research data from dried blood spots for predictive medicine.

Results

Jurors delivered an agreed verdict that conditional research access to the newborn blood spots was in the public interest. The Chief Medical Officer for Scotland authorised restricted lifting of the current research moratorium to allow a feasibility study. Newborn blood spots from consented Generation Scotland volunteers were retrieved and their potential for both epidemiological and biological research demonstrated.

Conclusions

Through the Citizens' Jury, we have begun to identify under what conditions, if any, should researchers in Scotland be granted access to the archive. Through the feasibility study, we have demonstrated the potential value of research access for health data science and predictive medicine.", + "laySummary": "", + "urls": "pdf:https://www.nature.com/articles/s43856-022-00189-2.pdf; doi:https://doi.org/10.1038/s43856-022-00189-2; html:https://europepmc.org/articles/PMC9537278; pdf:https://europepmc.org/articles/PMC9537278?pdf=render" + }, { "id": "35238940", "doi": "https://doi.org/10.1093/ndt/gfac040", @@ -31925,23 +31925,6 @@ "laySummary": "", "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/jvh.13863; doi:https://doi.org/10.1111/jvh.13863; html:https://europepmc.org/articles/PMC10526649; pdf:https://europepmc.org/articles/PMC10526649?pdf=render" }, - { - "id": "36256701", - "doi": "https://doi.org/10.1093/eurjcn/zvac098", - "title": "Bed rest duration and complications after transfemoral cardiac catheterization: a network meta-analysis.", - "authorString": "Busca E, Airoldi C, Bertoncini F, Buratti G, Casarotto R, Gaboardi S, Faggiano F, Barisone M, White IR, Allara E, Dal Molin A.", - "authorAffiliations": "", - "journalTitle": "European journal of cardiovascular nursing", - "pubYear": "2023", - "date": "2023-07-01", - "isOpenAccess": "Y", - "keywords": "Cardiac catheterization; Percutaneous coronary intervention; Systematic review; Network Meta-analysis; Femoral Access", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Aims

To assess the effects of bed rest duration on short-term complications following transfemoral catheterization.

Methods and results

A systematic search was carried out in MEDLINE, Embase, CINAHL, Cochrane Database of Systematic Reviews, Scopus, SciELO and in five registries of grey literature. Randomized controlled trials and quasi-experimental studies comparing different durations of bed rest after transfemoral catheterization were included. Primary outcomes were haematoma and bleeding near the access site. Secondary outcomes were arteriovenous fistula, pseudoaneurysm, back pain, general patient discomfort and urinary discomfort. Study findings were summarized using a network meta-analysis (NMA). Twenty-eight studies and 9217 participants were included (mean age 60.4 years). In NMA, bed rest duration was not consistently associated with either primary outcome, and this was confirmed in sensitivity analyses. There was no evidence of associations with secondary outcomes, except for two effects related to back pain. A bed rest duration of 2-2.9 h was associated with lower risk of back pain [risk ratio (RR) 0.33, 95% confidence interval (CI) 0.17-0.62] and a duration over 12 h with greater risk of back pain (RR 1.94, 95% CI 1.16-3.24), when compared with the 4-5.9 h interval. Post hoc analysis revealed an increased risk of back pain per hour of bed rest (RR 1.08, 95% CI 1.04-1.11).

Conclusion

A short bed rest was not associated with complications in patients undergoing transfemoral catheterization; the greater the duration of bed rest, the more likely the patients were to experience back pain. Ambulation as early as 2 h after transfemoral catheterization can be safely implemented.

Registration

PROSPERO: CRD42014014222.", - "laySummary": "", - "urls": "pdf:https://academic.oup.com/eurjcn/advance-article-pdf/doi/10.1093/eurjcn/zvac098/47022353/zvac098.pdf; doi:https://doi.org/10.1093/eurjcn/zvac098; html:https://europepmc.org/articles/PMC10353909; pdf:https://europepmc.org/articles/PMC10353909?pdf=render" - }, { "id": "33323251", "doi": "https://doi.org/10.1016/s2589-7500(19)30123-2", @@ -31959,6 +31942,23 @@ "laySummary": "", "urls": "pdf:http://www.thelancet.com/article/S2589750019301232/pdf; doi:https://doi.org/10.1016/S2589-7500(19)30123-2" }, + { + "id": "36256701", + "doi": "https://doi.org/10.1093/eurjcn/zvac098", + "title": "Bed rest duration and complications after transfemoral cardiac catheterization: a network meta-analysis.", + "authorString": "Busca E, Airoldi C, Bertoncini F, Buratti G, Casarotto R, Gaboardi S, Faggiano F, Barisone M, White IR, Allara E, Dal Molin A.", + "authorAffiliations": "", + "journalTitle": "European journal of cardiovascular nursing", + "pubYear": "2023", + "date": "2023-07-01", + "isOpenAccess": "Y", + "keywords": "Cardiac catheterization; Percutaneous coronary intervention; Systematic review; Network Meta-analysis; Femoral Access", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Aims

To assess the effects of bed rest duration on short-term complications following transfemoral catheterization.

Methods and results

A systematic search was carried out in MEDLINE, Embase, CINAHL, Cochrane Database of Systematic Reviews, Scopus, SciELO and in five registries of grey literature. Randomized controlled trials and quasi-experimental studies comparing different durations of bed rest after transfemoral catheterization were included. Primary outcomes were haematoma and bleeding near the access site. Secondary outcomes were arteriovenous fistula, pseudoaneurysm, back pain, general patient discomfort and urinary discomfort. Study findings were summarized using a network meta-analysis (NMA). Twenty-eight studies and 9217 participants were included (mean age 60.4 years). In NMA, bed rest duration was not consistently associated with either primary outcome, and this was confirmed in sensitivity analyses. There was no evidence of associations with secondary outcomes, except for two effects related to back pain. A bed rest duration of 2-2.9 h was associated with lower risk of back pain [risk ratio (RR) 0.33, 95% confidence interval (CI) 0.17-0.62] and a duration over 12 h with greater risk of back pain (RR 1.94, 95% CI 1.16-3.24), when compared with the 4-5.9 h interval. Post hoc analysis revealed an increased risk of back pain per hour of bed rest (RR 1.08, 95% CI 1.04-1.11).

Conclusion

A short bed rest was not associated with complications in patients undergoing transfemoral catheterization; the greater the duration of bed rest, the more likely the patients were to experience back pain. Ambulation as early as 2 h after transfemoral catheterization can be safely implemented.

Registration

PROSPERO: CRD42014014222.", + "laySummary": "", + "urls": "pdf:https://academic.oup.com/eurjcn/advance-article-pdf/doi/10.1093/eurjcn/zvac098/47022353/zvac098.pdf; doi:https://doi.org/10.1093/eurjcn/zvac098; html:https://europepmc.org/articles/PMC10353909; pdf:https://europepmc.org/articles/PMC10353909?pdf=render" + }, { "id": "36048760", "doi": "https://doi.org/10.1371/journal.pgen.1010294", @@ -32214,23 +32214,6 @@ "laySummary": "", "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/9/9/e032165.full.pdf; doi:https://doi.org/10.1136/bmjopen-2019-032165; html:https://europepmc.org/articles/PMC6731819; pdf:https://europepmc.org/articles/PMC6731819?pdf=render" }, - { - "id": "37104291", - "doi": "https://doi.org/10.1371/journal.pmed.1004221", - "title": "A nutritional biomarker score of the Mediterranean diet and incident type 2 diabetes: Integrated analysis of data from the MedLey randomised controlled trial and the EPIC-InterAct case-cohort study.", - "authorString": "Sobiecki JG, Imamura F, Davis CR, Sharp SJ, Koulman A, Hodgson JM, Guevara M, Schulze MB, Zheng JS, Agnoli C, Bonet C, Colorado-Yohar SM, Fagherazzi G, Franks PW, Gundersen TE, Jannasch F, Kaaks R, Katzke V, Molina-Montes E, Nilsson PM, Palli D, Panico S, Papier K, Rolandsson O, Sacerdote C, Tj\u00f8nneland A, Tong TYN, van der Schouw YT, Danesh J, Butterworth AS, Riboli E, Murphy KJ, Wareham NJ, Forouhi NG.", - "authorAffiliations": "", - "journalTitle": "PLoS medicine", - "pubYear": "2023", - "date": "2023-04-27", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Self-reported adherence to the Mediterranean diet has been modestly inversely associated with incidence of type 2 diabetes (T2D) in cohort studies. There is uncertainty about the validity and magnitude of this association due to subjective reporting of diet. The association has not been evaluated using an objectively measured biomarker of the Mediterranean diet.

Methods and findings

We derived a biomarker score based on 5 circulating carotenoids and 24 fatty acids that discriminated between the Mediterranean or habitual diet arms of a parallel design, 6-month partial-feeding randomised controlled trial (RCT) conducted between 2013 and 2014, the MedLey trial (128 participants out of 166 randomised). We applied this biomarker score in an observational study, the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study, to assess the association of the score with T2D incidence over an average of 9.7 years of follow-up since the baseline (1991 to 1998). We included 22,202 participants, of whom 9,453 were T2D cases, with relevant biomarkers from an original case-cohort of 27,779 participants sampled from a cohort of 340,234 people. As a secondary measure of the Mediterranean diet, we used a score estimated from dietary-self report. Within the trial, the biomarker score discriminated well between the 2 arms; the cross-validated C-statistic was 0.88 (95% confidence interval (CI) 0.82 to 0.94). The score was inversely associated with incident T2D in EPIC-InterAct: the hazard ratio (HR) per standard deviation of the score was 0.71 (95% CI: 0.65 to 0.77) following adjustment for sociodemographic, lifestyle and medical factors, and adiposity. In comparison, the HR per standard deviation of the self-reported Mediterranean diet was 0.90 (95% CI: 0.86 to 0.95). Assuming the score was causally associated with T2D, higher adherence to the Mediterranean diet in Western European adults by 10 percentiles of the score was estimated to reduce the incidence of T2D by 11% (95% CI: 7% to 14%). The study limitations included potential measurement error in nutritional biomarkers, unclear specificity of the biomarker score to the Mediterranean diet, and possible residual confounding.

Conclusions

These findings suggest that objectively assessed adherence to the Mediterranean diet is associated with lower risk of T2D and that even modestly higher adherence may have the potential to reduce the population burden of T2D meaningfully.

Trial registration

Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12613000602729 https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=363860.", - "laySummary": "", - "urls": "pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1004221&type=printable; doi:https://doi.org/10.1371/journal.pmed.1004221; html:https://europepmc.org/articles/PMC10138823; pdf:https://europepmc.org/articles/PMC10138823?pdf=render" - }, { "id": "34661196", "doi": "https://doi.org/10.1093/ehjopen/oeab019", @@ -32248,6 +32231,23 @@ "laySummary": "", "urls": "pdf:https://academic.oup.com/ehjopen/article-pdf/1/2/oeab019/41727950/oeab019.pdf; doi:https://doi.org/10.1093/ehjopen/oeab019; html:https://europepmc.org/articles/PMC8508012; pdf:https://europepmc.org/articles/PMC8508012?pdf=render" }, + { + "id": "37104291", + "doi": "https://doi.org/10.1371/journal.pmed.1004221", + "title": "A nutritional biomarker score of the Mediterranean diet and incident type 2 diabetes: Integrated analysis of data from the MedLey randomised controlled trial and the EPIC-InterAct case-cohort study.", + "authorString": "Sobiecki JG, Imamura F, Davis CR, Sharp SJ, Koulman A, Hodgson JM, Guevara M, Schulze MB, Zheng JS, Agnoli C, Bonet C, Colorado-Yohar SM, Fagherazzi G, Franks PW, Gundersen TE, Jannasch F, Kaaks R, Katzke V, Molina-Montes E, Nilsson PM, Palli D, Panico S, Papier K, Rolandsson O, Sacerdote C, Tj\u00f8nneland A, Tong TYN, van der Schouw YT, Danesh J, Butterworth AS, Riboli E, Murphy KJ, Wareham NJ, Forouhi NG.", + "authorAffiliations": "", + "journalTitle": "PLoS medicine", + "pubYear": "2023", + "date": "2023-04-27", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Self-reported adherence to the Mediterranean diet has been modestly inversely associated with incidence of type 2 diabetes (T2D) in cohort studies. There is uncertainty about the validity and magnitude of this association due to subjective reporting of diet. The association has not been evaluated using an objectively measured biomarker of the Mediterranean diet.

Methods and findings

We derived a biomarker score based on 5 circulating carotenoids and 24 fatty acids that discriminated between the Mediterranean or habitual diet arms of a parallel design, 6-month partial-feeding randomised controlled trial (RCT) conducted between 2013 and 2014, the MedLey trial (128 participants out of 166 randomised). We applied this biomarker score in an observational study, the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study, to assess the association of the score with T2D incidence over an average of 9.7 years of follow-up since the baseline (1991 to 1998). We included 22,202 participants, of whom 9,453 were T2D cases, with relevant biomarkers from an original case-cohort of 27,779 participants sampled from a cohort of 340,234 people. As a secondary measure of the Mediterranean diet, we used a score estimated from dietary-self report. Within the trial, the biomarker score discriminated well between the 2 arms; the cross-validated C-statistic was 0.88 (95% confidence interval (CI) 0.82 to 0.94). The score was inversely associated with incident T2D in EPIC-InterAct: the hazard ratio (HR) per standard deviation of the score was 0.71 (95% CI: 0.65 to 0.77) following adjustment for sociodemographic, lifestyle and medical factors, and adiposity. In comparison, the HR per standard deviation of the self-reported Mediterranean diet was 0.90 (95% CI: 0.86 to 0.95). Assuming the score was causally associated with T2D, higher adherence to the Mediterranean diet in Western European adults by 10 percentiles of the score was estimated to reduce the incidence of T2D by 11% (95% CI: 7% to 14%). The study limitations included potential measurement error in nutritional biomarkers, unclear specificity of the biomarker score to the Mediterranean diet, and possible residual confounding.

Conclusions

These findings suggest that objectively assessed adherence to the Mediterranean diet is associated with lower risk of T2D and that even modestly higher adherence may have the potential to reduce the population burden of T2D meaningfully.

Trial registration

Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12613000602729 https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=363860.", + "laySummary": "", + "urls": "pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1004221&type=printable; doi:https://doi.org/10.1371/journal.pmed.1004221; html:https://europepmc.org/articles/PMC10138823; pdf:https://europepmc.org/articles/PMC10138823?pdf=render" + }, { "id": "34632432", "doi": "https://doi.org/10.1016/s2666-5247(21)00128-2", @@ -32452,23 +32452,6 @@ "laySummary": "", "urls": "pdf:https://www.nature.com/articles/s41746-021-00404-9.pdf; doi:https://doi.org/10.1038/s41746-021-00404-9; html:https://europepmc.org/articles/PMC7910461; pdf:https://europepmc.org/articles/PMC7910461?pdf=render" }, - { - "id": "33941991", - "doi": "https://doi.org/10.1016/j.rse.2021.112339", - "title": "Multimodal deep learning from satellite and street-level imagery for measuring income, overcrowding, and environmental deprivation in urban areas.", - "authorString": "Suel E, Bhatt S, Brauer M, Flaxman S, Ezzati M.", - "authorAffiliations": "", - "journalTitle": "Remote sensing of environment", - "pubYear": "2021", - "date": "2021-05-01", - "isOpenAccess": "Y", - "keywords": "Segmentation; Satellite Images; Convolutional Neural Networks; Street-Level Images; Urban Measurements", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Data collected at large scale and low cost (e.g. satellite and street level imagery) have the potential to substantially improve resolution, spatial coverage, and temporal frequency of measurement of urban inequalities. Multiple types of data from different sources are often available for a given geographic area. Yet, most studies utilize a single type of input data when making measurements due to methodological difficulties in their joint use. We propose two deep learning-based methods for jointly utilizing satellite and street level imagery for measuring urban inequalities. We use London as a case study for three selected outputs, each measured in decile classes: income, overcrowding, and environmental deprivation. We compare the performances of our proposed multimodal models to corresponding unimodal ones using mean absolute error (MAE). First, satellite tiles are appended to street level imagery to enhance predictions at locations where street images are available leading to improvements in accuracy by 20, 10, and 9% in units of decile classes for income, overcrowding, and living environment. The second approach, novel to the best of our knowledge, uses a U-Net architecture to make predictions for all grid cells in a city at high spatial resolution (e.g. for 3\u00a0m\u00a0\u00d7\u00a03\u00a0m pixels in London in our experiments). It can utilize city wide availability of satellite images as well as more sparse information from street-level images where they are available leading to improvements in accuracy by 6, 10, and 11%. We also show examples of prediction maps from both approaches to visually highlight performance differences.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1016/j.rse.2021.112339; doi:https://doi.org/10.1016/j.rse.2021.112339; html:https://europepmc.org/articles/PMC7985619; pdf:https://europepmc.org/articles/PMC7985619?pdf=render" - }, { "id": "33493433", "doi": "https://doi.org/10.1016/s1470-2045(20)30743-9", @@ -32486,6 +32469,23 @@ "laySummary": "", "urls": "pdf:http://www.thelancet.com/article/S1470204520307439/pdf; doi:https://doi.org/10.1016/S1470-2045(20)30743-9; html:https://europepmc.org/articles/PMC7825861; pdf:https://europepmc.org/articles/PMC7825861?pdf=render" }, + { + "id": "33941991", + "doi": "https://doi.org/10.1016/j.rse.2021.112339", + "title": "Multimodal deep learning from satellite and street-level imagery for measuring income, overcrowding, and environmental deprivation in urban areas.", + "authorString": "Suel E, Bhatt S, Brauer M, Flaxman S, Ezzati M.", + "authorAffiliations": "", + "journalTitle": "Remote sensing of environment", + "pubYear": "2021", + "date": "2021-05-01", + "isOpenAccess": "Y", + "keywords": "Segmentation; Satellite Images; Convolutional Neural Networks; Street-Level Images; Urban Measurements", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Data collected at large scale and low cost (e.g. satellite and street level imagery) have the potential to substantially improve resolution, spatial coverage, and temporal frequency of measurement of urban inequalities. Multiple types of data from different sources are often available for a given geographic area. Yet, most studies utilize a single type of input data when making measurements due to methodological difficulties in their joint use. We propose two deep learning-based methods for jointly utilizing satellite and street level imagery for measuring urban inequalities. We use London as a case study for three selected outputs, each measured in decile classes: income, overcrowding, and environmental deprivation. We compare the performances of our proposed multimodal models to corresponding unimodal ones using mean absolute error (MAE). First, satellite tiles are appended to street level imagery to enhance predictions at locations where street images are available leading to improvements in accuracy by 20, 10, and 9% in units of decile classes for income, overcrowding, and living environment. The second approach, novel to the best of our knowledge, uses a U-Net architecture to make predictions for all grid cells in a city at high spatial resolution (e.g. for 3\u00a0m\u00a0\u00d7\u00a03\u00a0m pixels in London in our experiments). It can utilize city wide availability of satellite images as well as more sparse information from street-level images where they are available leading to improvements in accuracy by 6, 10, and 11%. We also show examples of prediction maps from both approaches to visually highlight performance differences.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1016/j.rse.2021.112339; doi:https://doi.org/10.1016/j.rse.2021.112339; html:https://europepmc.org/articles/PMC7985619; pdf:https://europepmc.org/articles/PMC7985619?pdf=render" + }, { "id": "35144751", "doi": "https://doi.org/10.1016/j.jacc.2021.11.045", @@ -32775,23 +32775,6 @@ "laySummary": "", "urls": "html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7612925; doi:https://doi.org/10.1038/s41588-020-00751-5; html:https://europepmc.org/articles/PMC7612925; pdf:https://europepmc.org/articles/PMC7612925?pdf=render; doi:https://doi.org/10.1038/s41588-020-00751-5" }, - { - "id": "38388497", - "doi": "https://doi.org/10.1038/s41467-024-45355-3", - "title": "Concordance of randomised controlled trials for artificial intelligence interventions with the CONSORT-AI reporting guidelines.", - "authorString": "Martindale APL, Ng B, Ngai V, Kale AU, Ferrante di Ruffano L, Golub RM, Collins GS, Moher D, McCradden MD, Oakden-Rayner L, Rivera SC, Calvert M, Kelly CJ, Lee CS, Yau C, Chan AW, Keane PA, Beam AL, Denniston AK, Liu X.", - "authorAffiliations": "", - "journalTitle": "Nature communications", - "pubYear": "2024", - "date": "2024-02-22", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "The Consolidated Standards of Reporting Trials extension for Artificial Intelligence interventions (CONSORT-AI) was published in September 2020. Since its publication, several randomised controlled trials (RCTs) of AI interventions have been published but their completeness and transparency of reporting is unknown. This systematic review assesses the completeness of reporting of AI RCTs following publication of CONSORT-AI and provides a comprehensive summary of RCTs published in recent years. 65 RCTs were identified, mostly conducted in China (37%) and USA (18%). Median concordance with CONSORT-AI reporting was 90% (IQR 77-94%), although only 10 RCTs explicitly reported its use. Several items were consistently under-reported, including algorithm version, accessibility of the AI intervention or code, and references to a study protocol. Only 3 of 52 included journals explicitly endorsed or mandated CONSORT-AI. Despite a generally high concordance amongst recent AI RCTs, some AI-specific considerations remain systematically poorly reported. Further encouragement of CONSORT-AI adoption by journals and funders may enable more complete adoption of the full CONSORT-AI guidelines.", - "laySummary": "", - "urls": "pdf:https://www.nature.com/articles/s41467-024-45355-3.pdf; doi:https://doi.org/10.1038/s41467-024-45355-3; html:https://europepmc.org/articles/PMC10883966; pdf:https://europepmc.org/articles/PMC10883966?pdf=render" - }, { "id": "33391794", "doi": "https://doi.org/10.1098/rsos.200958", @@ -32809,6 +32792,23 @@ "laySummary": "", "urls": "pdf:https://royalsocietypublishing.org/doi/pdf/10.1098/rsos.200958; doi:https://doi.org/10.1098/rsos.200958; html:https://europepmc.org/articles/PMC7735342; pdf:https://europepmc.org/articles/PMC7735342?pdf=render" }, + { + "id": "38388497", + "doi": "https://doi.org/10.1038/s41467-024-45355-3", + "title": "Concordance of randomised controlled trials for artificial intelligence interventions with the CONSORT-AI reporting guidelines.", + "authorString": "Martindale APL, Ng B, Ngai V, Kale AU, Ferrante di Ruffano L, Golub RM, Collins GS, Moher D, McCradden MD, Oakden-Rayner L, Rivera SC, Calvert M, Kelly CJ, Lee CS, Yau C, Chan AW, Keane PA, Beam AL, Denniston AK, Liu X.", + "authorAffiliations": "", + "journalTitle": "Nature communications", + "pubYear": "2024", + "date": "2024-02-22", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "The Consolidated Standards of Reporting Trials extension for Artificial Intelligence interventions (CONSORT-AI) was published in September 2020. Since its publication, several randomised controlled trials (RCTs) of AI interventions have been published but their completeness and transparency of reporting is unknown. This systematic review assesses the completeness of reporting of AI RCTs following publication of CONSORT-AI and provides a comprehensive summary of RCTs published in recent years. 65 RCTs were identified, mostly conducted in China (37%) and USA (18%). Median concordance with CONSORT-AI reporting was 90% (IQR 77-94%), although only 10 RCTs explicitly reported its use. Several items were consistently under-reported, including algorithm version, accessibility of the AI intervention or code, and references to a study protocol. Only 3 of 52 included journals explicitly endorsed or mandated CONSORT-AI. Despite a generally high concordance amongst recent AI RCTs, some AI-specific considerations remain systematically poorly reported. Further encouragement of CONSORT-AI adoption by journals and funders may enable more complete adoption of the full CONSORT-AI guidelines.", + "laySummary": "", + "urls": "pdf:https://www.nature.com/articles/s41467-024-45355-3.pdf; doi:https://doi.org/10.1038/s41467-024-45355-3; html:https://europepmc.org/articles/PMC10883966; pdf:https://europepmc.org/articles/PMC10883966?pdf=render" + }, { "id": "32040531", "doi": "https://doi.org/10.1371/journal.pone.0228940", @@ -32843,23 +32843,6 @@ "laySummary": "", "urls": "pdf:https://www.ahajournals.org/doi/pdf/10.1161/JAHA.120.021115; doi:https://doi.org/10.1161/JAHA.120.021115; html:https://europepmc.org/articles/PMC8649290; pdf:https://europepmc.org/articles/PMC8649290?pdf=render" }, - { - "id": "37808344", - "doi": "https://doi.org/10.1016/j.jacadv.2023.100573", - "title": "CYP2C19 Genotype Prevalence and Association With Recurrent Myocardial Infarction in British-South Asians Treated With\u00a0Clopidogrel.", - "authorString": "Magavern EF, Jacobs B, Warren H, Finocchiaro G, Finer S, van Heel DA, Genes & Health Research Team, Smedley D, Caulfield MJ.", - "authorAffiliations": "", - "journalTitle": "JACC. Advances", - "pubYear": "2023", - "date": "2023-09-01", - "isOpenAccess": "Y", - "keywords": "Pharmacogenomics; ischemic heart disease; Pharmacotherapy; Preventive Cardiology", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Cytochrome P450 family 2 subfamily C member 19 (CYP2C19) is a hepatic enzyme involved in the metabolism of clopidogrel from a prodrug to its active metabolite. Prior studies of genetic polymorphisms in CYP2C19 and their relationship with clinical efficacy have not included South Asian populations.

Objectives

The objective of this study was to assess prevalence of common CYP2C19 genotype polymorphisms in a British-South Asian population and correlate these with recurrent myocardial infarction risk in participants prescribed clopidogrel.

Methods

The Genes & Health cohort of British Bangladeshi and Pakistani ancestry participants were studied. CYP2C19 diplotypes were assessed using array data. Multivariable logistic regression was used to test for association between genetically inferred CYP2C19 metabolizer status and recurrent myocardial infarction, controlling for known cardiovascular disease risk factors, percutaneous coronary intervention, age, sex, and population stratification.

Results

Genes & Health cohort participants (N\u00a0=\u00a044,396) have a high prevalence (57%) of intermediate or poor CYP2C19 metabolizers, with at least 1 loss-of-function CYP2C19 allele. The prevalence of poor metabolizers carrying 2\u00a0CYP2C19 loss-of-function alleles is 13%, which is higher than that in previously studied European (2.4%) and Central/South Asian populations (8.2%). Sixty-nine percent of the cohort who were diagnosed with an acute myocardial infarction were prescribed clopidogrel. Poor metabolizers were significantly more likely to have a recurrent myocardial infarction (OR: 3.1; P\u00a0=\u00a00.019).

Conclusions

A pharmacogenomic-driven approach to clopidogrel prescribing has the potential to impact significantly on clinical management and outcomes in individuals of Bangladeshi and Pakistani ancestry.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1016/j.jacadv.2023.100573; html:https://europepmc.org/articles/PMC10550831; pdf:https://europepmc.org/articles/PMC10550831?pdf=render" - }, { "id": "33947203", "doi": "https://doi.org/10.1161/circulationaha.120.053033", @@ -32877,6 +32860,23 @@ "laySummary": "", "urls": "pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCULATIONAHA.120.053033; doi:https://doi.org/10.1161/CIRCULATIONAHA.120.053033; html:https://europepmc.org/articles/PMC8247549; pdf:https://europepmc.org/articles/PMC8247549?pdf=render" }, + { + "id": "37808344", + "doi": "https://doi.org/10.1016/j.jacadv.2023.100573", + "title": "CYP2C19 Genotype Prevalence and Association With Recurrent Myocardial Infarction in British-South Asians Treated With\u00a0Clopidogrel.", + "authorString": "Magavern EF, Jacobs B, Warren H, Finocchiaro G, Finer S, van Heel DA, Genes & Health Research Team, Smedley D, Caulfield MJ.", + "authorAffiliations": "", + "journalTitle": "JACC. Advances", + "pubYear": "2023", + "date": "2023-09-01", + "isOpenAccess": "Y", + "keywords": "Pharmacogenomics; ischemic heart disease; Pharmacotherapy; Preventive Cardiology", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Cytochrome P450 family 2 subfamily C member 19 (CYP2C19) is a hepatic enzyme involved in the metabolism of clopidogrel from a prodrug to its active metabolite. Prior studies of genetic polymorphisms in CYP2C19 and their relationship with clinical efficacy have not included South Asian populations.

Objectives

The objective of this study was to assess prevalence of common CYP2C19 genotype polymorphisms in a British-South Asian population and correlate these with recurrent myocardial infarction risk in participants prescribed clopidogrel.

Methods

The Genes & Health cohort of British Bangladeshi and Pakistani ancestry participants were studied. CYP2C19 diplotypes were assessed using array data. Multivariable logistic regression was used to test for association between genetically inferred CYP2C19 metabolizer status and recurrent myocardial infarction, controlling for known cardiovascular disease risk factors, percutaneous coronary intervention, age, sex, and population stratification.

Results

Genes & Health cohort participants (N\u00a0=\u00a044,396) have a high prevalence (57%) of intermediate or poor CYP2C19 metabolizers, with at least 1 loss-of-function CYP2C19 allele. The prevalence of poor metabolizers carrying 2\u00a0CYP2C19 loss-of-function alleles is 13%, which is higher than that in previously studied European (2.4%) and Central/South Asian populations (8.2%). Sixty-nine percent of the cohort who were diagnosed with an acute myocardial infarction were prescribed clopidogrel. Poor metabolizers were significantly more likely to have a recurrent myocardial infarction (OR: 3.1; P\u00a0=\u00a00.019).

Conclusions

A pharmacogenomic-driven approach to clopidogrel prescribing has the potential to impact significantly on clinical management and outcomes in individuals of Bangladeshi and Pakistani ancestry.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1016/j.jacadv.2023.100573; html:https://europepmc.org/articles/PMC10550831; pdf:https://europepmc.org/articles/PMC10550831?pdf=render" + }, { "id": "34053260", "doi": "https://doi.org/10.1098/rstb.2020.0283", @@ -32928,23 +32928,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.23889/ijpds.v6i1.1718; html:https://europepmc.org/articles/PMC9052961; pdf:https://europepmc.org/articles/PMC9052961?pdf=render" }, - { - "id": "38381822", - "doi": "https://doi.org/10.1126/sciadv.adi9379", - "title": "Spontaneous, persistent, T cell-dependent IFN-\u03b3 release in patients who progress to Long Covid.", - "authorString": "Krishna BA, Lim EY, Metaxaki M, Jackson S, Mactavous L, NIHR BioResource, Lyons PA, Doffinger R, Bradley JR, Smith KGC, Sinclair J, Matheson NJ, Lehner PJ, Sithole N, Wills MR.", - "authorAffiliations": "", - "journalTitle": "Science advances", - "pubYear": "2024", - "date": "2024-02-21", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "After acute infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a proportion of patients experience persistent symptoms beyond 12 weeks, termed Long Covid. Understanding the mechanisms that cause this debilitating disease and identifying biomarkers for diagnostic, therapeutic, and monitoring purposes are urgently required. We detected persistently high levels of interferon-\u03b3 (IFN-\u03b3) from peripheral blood mononuclear cells of patients with Long Covid using highly sensitive FluoroSpot assays. This IFN-\u03b3 release was seen in the absence of ex vivo peptide stimulation and remains persistently elevated in patients with Long Covid, unlike the resolution seen in patients recovering from acute SARS-CoV-2 infection. The IFN-\u03b3 release was CD8+ T cell-mediated and dependent on antigen presentation by CD14+ cells. Longitudinal follow-up of our study cohort showed that symptom improvement and resolution correlated with a decrease in IFN-\u03b3 production to baseline levels. Our study highlights a potential mechanism underlying Long Covid, enabling the search for biomarkers and therapeutics in patients with Long Covid.", - "laySummary": "", - "urls": "pdf:https://www.science.org/doi/pdf/10.1126/sciadv.adi9379?download=true; doi:https://doi.org/10.1126/sciadv.adi9379; html:https://europepmc.org/articles/PMC10881041; pdf:https://europepmc.org/articles/PMC10881041?pdf=render" - }, { "id": "35751107", "doi": "https://doi.org/10.1186/s13059-022-02702-1", @@ -32979,6 +32962,23 @@ "laySummary": "", "urls": "pdf:https://biblio.ugent.be/publication/01GTEZMFA3PQ4FR2HWVVMJE1PP/file/01GTEZP5YQ68PC7TFPP52TS6QR.pdf; doi:https://doi.org/10.1093/ehjqcco/qcac045; html:https://europepmc.org/articles/PMC9603542; pdf:https://europepmc.org/articles/PMC9603542?pdf=render; doi:https://doi.org/10.1093/ehjqcco/qcac045" }, + { + "id": "38381822", + "doi": "https://doi.org/10.1126/sciadv.adi9379", + "title": "Spontaneous, persistent, T cell-dependent IFN-\u03b3 release in patients who progress to Long Covid.", + "authorString": "Krishna BA, Lim EY, Metaxaki M, Jackson S, Mactavous L, NIHR BioResource, Lyons PA, Doffinger R, Bradley JR, Smith KGC, Sinclair J, Matheson NJ, Lehner PJ, Sithole N, Wills MR.", + "authorAffiliations": "", + "journalTitle": "Science advances", + "pubYear": "2024", + "date": "2024-02-21", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "After acute infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a proportion of patients experience persistent symptoms beyond 12 weeks, termed Long Covid. Understanding the mechanisms that cause this debilitating disease and identifying biomarkers for diagnostic, therapeutic, and monitoring purposes are urgently required. We detected persistently high levels of interferon-\u03b3 (IFN-\u03b3) from peripheral blood mononuclear cells of patients with Long Covid using highly sensitive FluoroSpot assays. This IFN-\u03b3 release was seen in the absence of ex vivo peptide stimulation and remains persistently elevated in patients with Long Covid, unlike the resolution seen in patients recovering from acute SARS-CoV-2 infection. The IFN-\u03b3 release was CD8+ T cell-mediated and dependent on antigen presentation by CD14+ cells. Longitudinal follow-up of our study cohort showed that symptom improvement and resolution correlated with a decrease in IFN-\u03b3 production to baseline levels. Our study highlights a potential mechanism underlying Long Covid, enabling the search for biomarkers and therapeutics in patients with Long Covid.", + "laySummary": "", + "urls": "pdf:https://www.science.org/doi/pdf/10.1126/sciadv.adi9379?download=true; doi:https://doi.org/10.1126/sciadv.adi9379; html:https://europepmc.org/articles/PMC10881041; pdf:https://europepmc.org/articles/PMC10881041?pdf=render" + }, { "id": "34870142", "doi": "https://doi.org/10.1016/j.infpip.2021.100192", @@ -33540,23 +33540,6 @@ "laySummary": "", "urls": "pdf:https://academic.oup.com/braincomms/article-pdf/5/2/fcad041/49521070/fcad041.pdf; doi:https://doi.org/10.1093/braincomms/fcad041; html:https://europepmc.org/articles/PMC10053643; pdf:https://europepmc.org/articles/PMC10053643?pdf=render" }, - { - "id": "36998408", - "doi": "https://doi.org/10.3389/fmicb.2023.1070340", - "title": "A longitudinal study reveals persistence of antimicrobial resistance on livestock farms is not due to antimicrobial usage alone.", - "authorString": "Smith RP, May HE, AbuOun M, Stubberfield E, Gilson D, Chau KK, Crook DW, Shaw LP, Read DS, Stoesser N, Vilar MJ, Anjum MF.", - "authorAffiliations": "", - "journalTitle": "Frontiers in microbiology", - "pubYear": "2023", - "date": "2023-03-14", - "isOpenAccess": "Y", - "keywords": "Sheep; Cattle; Pigs; Antimicrobial resistance; Longitudinal; Antimicrobial Usage", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Introduction

There are concerns that antimicrobial usage (AMU) is driving an increase in multi-drug resistant (MDR) bacteria so treatment of microbial infections is becoming harder in humans and animals. The aim of this study was to evaluate factors, including usage, that affect antimicrobial resistance (AMR) on farm over time.

Methods

A population of 14 cattle, sheep and pig farms within a defined area of England were sampled three times over a year to collect data on AMR in faecal Enterobacterales flora; AMU; and husbandry or management practices. Ten pooled samples were collected at each visit, with each comprising of 10 pinches of fresh faeces. Up to 14 isolates per visit were whole genome sequenced to determine presence of AMR genes.

Results

Sheep farms had very low AMU in comparison to the other species and very few sheep isolates were genotypically resistant at any time point. AMR genes were detected persistently across pig farms at all visits, even on farms with low AMU, whereas AMR bacteria was consistently lower on cattle farms than pigs, even for those with comparably high AMU. MDR bacteria was also more commonly detected on pig farms than any other livestock species.

Discussion

The results may be explained by a complex combination of factors on pig farms including historic AMU; co-selection of AMR bacteria; variation in amounts of antimicrobials used between visits; potential persistence in environmental reservoirs of AMR bacteria; or importation of pigs with AMR microbiota from supplying farms. Pig farms may also be at increased risk of AMR due to the greater use of oral routes of group antimicrobial treatment, which were less targeted than cattle treatments; the latter mostly administered to individual animals. Also, farms which exhibited either increasing or decreasing trends of AMR across the study did not have corresponding trends in their AMU. Therefore, our results suggest that factors other than AMU on individual farms are important for persistence of AMR bacteria on farms, which may be operating at the farm and livestock species level.", - "laySummary": "", - "urls": "pdf:https://www.frontiersin.org/articles/10.3389/fmicb.2023.1070340/pdf; doi:https://doi.org/10.3389/fmicb.2023.1070340; html:https://europepmc.org/articles/PMC10043416; pdf:https://europepmc.org/articles/PMC10043416?pdf=render" - }, { "id": "33325834", "doi": "https://doi.org/10.2196/23530", @@ -33591,6 +33574,40 @@ "laySummary": "", "urls": "pdf:http://www.journal-of-hepatology.eu/article/S0168827820336035/pdf; doi:https://doi.org/10.1016/j.jhep.2020.08.030; html:https://europepmc.org/articles/PMC8055539; pdf:https://europepmc.org/articles/PMC8055539?pdf=render" }, + { + "id": "36998408", + "doi": "https://doi.org/10.3389/fmicb.2023.1070340", + "title": "A longitudinal study reveals persistence of antimicrobial resistance on livestock farms is not due to antimicrobial usage alone.", + "authorString": "Smith RP, May HE, AbuOun M, Stubberfield E, Gilson D, Chau KK, Crook DW, Shaw LP, Read DS, Stoesser N, Vilar MJ, Anjum MF.", + "authorAffiliations": "", + "journalTitle": "Frontiers in microbiology", + "pubYear": "2023", + "date": "2023-03-14", + "isOpenAccess": "Y", + "keywords": "Sheep; Cattle; Pigs; Antimicrobial resistance; Longitudinal; Antimicrobial Usage", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Introduction

There are concerns that antimicrobial usage (AMU) is driving an increase in multi-drug resistant (MDR) bacteria so treatment of microbial infections is becoming harder in humans and animals. The aim of this study was to evaluate factors, including usage, that affect antimicrobial resistance (AMR) on farm over time.

Methods

A population of 14 cattle, sheep and pig farms within a defined area of England were sampled three times over a year to collect data on AMR in faecal Enterobacterales flora; AMU; and husbandry or management practices. Ten pooled samples were collected at each visit, with each comprising of 10 pinches of fresh faeces. Up to 14 isolates per visit were whole genome sequenced to determine presence of AMR genes.

Results

Sheep farms had very low AMU in comparison to the other species and very few sheep isolates were genotypically resistant at any time point. AMR genes were detected persistently across pig farms at all visits, even on farms with low AMU, whereas AMR bacteria was consistently lower on cattle farms than pigs, even for those with comparably high AMU. MDR bacteria was also more commonly detected on pig farms than any other livestock species.

Discussion

The results may be explained by a complex combination of factors on pig farms including historic AMU; co-selection of AMR bacteria; variation in amounts of antimicrobials used between visits; potential persistence in environmental reservoirs of AMR bacteria; or importation of pigs with AMR microbiota from supplying farms. Pig farms may also be at increased risk of AMR due to the greater use of oral routes of group antimicrobial treatment, which were less targeted than cattle treatments; the latter mostly administered to individual animals. Also, farms which exhibited either increasing or decreasing trends of AMR across the study did not have corresponding trends in their AMU. Therefore, our results suggest that factors other than AMU on individual farms are important for persistence of AMR bacteria on farms, which may be operating at the farm and livestock species level.", + "laySummary": "", + "urls": "pdf:https://www.frontiersin.org/articles/10.3389/fmicb.2023.1070340/pdf; doi:https://doi.org/10.3389/fmicb.2023.1070340; html:https://europepmc.org/articles/PMC10043416; pdf:https://europepmc.org/articles/PMC10043416?pdf=render" + }, + { + "id": "30649175", + "doi": "https://doi.org/10.1001/jamacardio.2018.4537", + "title": "Cardiovascular Risk Factors Associated With Venous Thromboembolism.", + "authorString": "Gregson J, Kaptoge S, Bolton T, Pennells L, Willeit P, Burgess S, Bell S, Sweeting M, Rimm EB, Kabrhel C, Z\u00f6ller B, Assmann G, Gudnason V, Folsom AR, Arndt V, Fletcher A, Norman PE, Nordestgaard BG, Kitamura A, Mahmoodi BK, Whincup PH, Knuiman M, Salomaa V, Meisinger C, Koenig W, Kavousi M, V\u00f6lzke H, Cooper JA, Ninomiya T, Casiglia E, Rodriguez B, Ben-Shlomo Y, Despr\u00e9s JP, Simons L, Barrett-Connor E, Bj\u00f6rkelund C, Notdurfter M, Kromhout D, Price J, Sutherland SE, Sundstr\u00f6m J, Kauhanen J, Gallacher J, Beulens JWJ, Dankner R, Cooper C, Giampaoli S, Deen JF, G\u00f3mez de la C\u00e1mara A, Kuller LH, Rosengren A, Svensson PJ, Nagel D, Crespo CJ, Brenner H, Albertorio-Diaz JR, Atkins R, Brunner EJ, Shipley M, Nj\u00f8lstad I, Lawlor DA, van der Schouw YT, Selmer RM, Trevisan M, Verschuren WMM, Greenland P, Wassertheil-Smoller S, Lowe GDO, Wood AM, Butterworth AS, Thompson SG, Danesh J, Di Angelantonio E, Meade T, Emerging Risk Factors Collaboration.", + "authorAffiliations": "", + "journalTitle": "JAMA cardiology", + "pubYear": "2019", + "date": "2019-02-01", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "Understanding the Causes of Disease", + "healthCategories": "", + "abstract": "

Importance

It is uncertain to what extent established cardiovascular risk factors are associated with venous thromboembolism (VTE).

Objective

To estimate the associations of major cardiovascular risk factors with VTE, ie, deep vein thrombosis and pulmonary embolism.

Design, setting, and participants

This study included individual participant data mostly from essentially population-based cohort studies from the Emerging Risk Factors Collaboration (ERFC; 731\u202f728 participants; 75 cohorts; years of baseline surveys, February 1960 to June 2008; latest date of follow-up, December 2015) and the UK Biobank (421\u202f537 participants; years of baseline surveys, March 2006 to September 2010; latest date of follow-up, February 2016). Participants without cardiovascular disease at baseline were included. Data were analyzed from June 2017 to September 2018.

Exposures

A panel of several established cardiovascular risk factors.

Main outcomes and measures

Hazard ratios (HRs) per 1-SD higher usual risk factor levels (or presence/absence). Incident fatal outcomes in ERFC (VTE,\u20091041; coronary heart disease [CHD], 25\u202f131) and incident fatal/nonfatal outcomes in UK Biobank (VTE, 2321; CHD, 3385). Hazard ratios were adjusted for age, sex, smoking status, diabetes, and body mass index (BMI).

Results

Of the 731\u202f728 participants from the ERFC, 403\u202f396 (55.1%) were female, and the mean (SD) age at the time of the survey was 51.9 (9.0) years; of the 421\u202f537 participants from the UK Biobank, 233\u202f699 (55.4%) were female, and the mean (SD) age at the time of the survey was 56.4 (8.1) years. Risk factors for VTE included older age (ERFC: HR per decade, 2.67; 95% CI, 2.45-2.91; UK Biobank: HR, 1.81; 95% CI, 1.71-1.92), current smoking (ERFC: HR, 1.38; 95% CI, 1.20-1.58; UK Biobank: HR, 1.23; 95% CI, 1.08-1.40), and BMI (ERFC: HR per 1-SD higher BMI, 1.43; 95% CI, 1.35-1.50; UK Biobank: HR, 1.37; 95% CI, 1.32-1.41). For these factors, there were similar HRs for pulmonary embolism and deep vein thrombosis in UK Biobank (except adiposity was more strongly associated with pulmonary embolism) and similar HRs for unprovoked vs provoked VTE. Apart from adiposity, these risk factors were less strongly associated with VTE than CHD. There were inconsistent associations of VTEs with diabetes and blood pressure across ERFC and UK Biobank, and there was limited ability to study lipid and inflammation markers.

Conclusions and relevance

Older age, smoking, and adiposity were consistently associated with higher VTE risk.", + "laySummary": "", + "urls": "pdf:https://pdxscholar.library.pdx.edu/cgi/viewcontent.cgi?article=1451&context=sph_facpub; doi:https://doi.org/10.1001/jamacardio.2018.4537; html:https://europepmc.org/articles/PMC6386140" + }, { "id": "34965929", "doi": "https://doi.org/10.1136/bmj-2021-065834", @@ -33626,21 +33643,21 @@ "urls": "doi:https://doi.org/10.1038/s41598-023-33391-w; doi:https://doi.org/10.1038/s41598-023-33391-w; html:https://europepmc.org/articles/PMC10199085; pdf:https://europepmc.org/articles/PMC10199085?pdf=render" }, { - "id": "30649175", - "doi": "https://doi.org/10.1001/jamacardio.2018.4537", - "title": "Cardiovascular Risk Factors Associated With Venous Thromboembolism.", - "authorString": "Gregson J, Kaptoge S, Bolton T, Pennells L, Willeit P, Burgess S, Bell S, Sweeting M, Rimm EB, Kabrhel C, Z\u00f6ller B, Assmann G, Gudnason V, Folsom AR, Arndt V, Fletcher A, Norman PE, Nordestgaard BG, Kitamura A, Mahmoodi BK, Whincup PH, Knuiman M, Salomaa V, Meisinger C, Koenig W, Kavousi M, V\u00f6lzke H, Cooper JA, Ninomiya T, Casiglia E, Rodriguez B, Ben-Shlomo Y, Despr\u00e9s JP, Simons L, Barrett-Connor E, Bj\u00f6rkelund C, Notdurfter M, Kromhout D, Price J, Sutherland SE, Sundstr\u00f6m J, Kauhanen J, Gallacher J, Beulens JWJ, Dankner R, Cooper C, Giampaoli S, Deen JF, G\u00f3mez de la C\u00e1mara A, Kuller LH, Rosengren A, Svensson PJ, Nagel D, Crespo CJ, Brenner H, Albertorio-Diaz JR, Atkins R, Brunner EJ, Shipley M, Nj\u00f8lstad I, Lawlor DA, van der Schouw YT, Selmer RM, Trevisan M, Verschuren WMM, Greenland P, Wassertheil-Smoller S, Lowe GDO, Wood AM, Butterworth AS, Thompson SG, Danesh J, Di Angelantonio E, Meade T, Emerging Risk Factors Collaboration.", + "id": "32680743", + "doi": "https://doi.org/10.1016/j.jphys.2020.06.008", + "title": "Adaptation, self-motivation and support services are key to physical activity participation three to five years after major trauma: a qualitative study.", + "authorString": "Ekegren CL, Braaf S, Ameratunga S, Ponsford J, Nunn A, Cameron P, Lyons RA, Gabbe BJ.", "authorAffiliations": "", - "journalTitle": "JAMA cardiology", - "pubYear": "2019", - "date": "2019-02-01", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "Understanding the Causes of Disease", + "journalTitle": "Journal of physiotherapy", + "pubYear": "2020", + "date": "2020-07-14", + "isOpenAccess": "N", + "keywords": "Trauma; Recovery; Exercise; wounds and injuries; Sedentary Lifestyle", + "nationalPriorities": "", "healthCategories": "", - "abstract": "

Importance

It is uncertain to what extent established cardiovascular risk factors are associated with venous thromboembolism (VTE).

Objective

To estimate the associations of major cardiovascular risk factors with VTE, ie, deep vein thrombosis and pulmonary embolism.

Design, setting, and participants

This study included individual participant data mostly from essentially population-based cohort studies from the Emerging Risk Factors Collaboration (ERFC; 731\u202f728 participants; 75 cohorts; years of baseline surveys, February 1960 to June 2008; latest date of follow-up, December 2015) and the UK Biobank (421\u202f537 participants; years of baseline surveys, March 2006 to September 2010; latest date of follow-up, February 2016). Participants without cardiovascular disease at baseline were included. Data were analyzed from June 2017 to September 2018.

Exposures

A panel of several established cardiovascular risk factors.

Main outcomes and measures

Hazard ratios (HRs) per 1-SD higher usual risk factor levels (or presence/absence). Incident fatal outcomes in ERFC (VTE,\u20091041; coronary heart disease [CHD], 25\u202f131) and incident fatal/nonfatal outcomes in UK Biobank (VTE, 2321; CHD, 3385). Hazard ratios were adjusted for age, sex, smoking status, diabetes, and body mass index (BMI).

Results

Of the 731\u202f728 participants from the ERFC, 403\u202f396 (55.1%) were female, and the mean (SD) age at the time of the survey was 51.9 (9.0) years; of the 421\u202f537 participants from the UK Biobank, 233\u202f699 (55.4%) were female, and the mean (SD) age at the time of the survey was 56.4 (8.1) years. Risk factors for VTE included older age (ERFC: HR per decade, 2.67; 95% CI, 2.45-2.91; UK Biobank: HR, 1.81; 95% CI, 1.71-1.92), current smoking (ERFC: HR, 1.38; 95% CI, 1.20-1.58; UK Biobank: HR, 1.23; 95% CI, 1.08-1.40), and BMI (ERFC: HR per 1-SD higher BMI, 1.43; 95% CI, 1.35-1.50; UK Biobank: HR, 1.37; 95% CI, 1.32-1.41). For these factors, there were similar HRs for pulmonary embolism and deep vein thrombosis in UK Biobank (except adiposity was more strongly associated with pulmonary embolism) and similar HRs for unprovoked vs provoked VTE. Apart from adiposity, these risk factors were less strongly associated with VTE than CHD. There were inconsistent associations of VTEs with diabetes and blood pressure across ERFC and UK Biobank, and there was limited ability to study lipid and inflammation markers.

Conclusions and relevance

Older age, smoking, and adiposity were consistently associated with higher VTE risk.", + "abstract": "

Questions

What are the perceived long-term impacts of major trauma on physical activity participation over time? What factors influence physical activity participation in people recovering from major trauma?

Design

Longitudinal qualitative study.

Participants

Sixty-six people aged \u2265 16 years with non-neurological major trauma.

Methods

Participants were interviewed 3 years (n\u00a0= 66), 4 years (n\u00a0= 63) and 5 years (n\u00a0= 57) after their injury. A thematic analysis was performed.

Results

Despite wanting to be physically active, many participants experienced significant, long-term physical activity restriction after their injury, which persisted over time. Restrictions were often related to a fear of re-injury or of exacerbating pain and fatigue levels. These restrictions were a source of distress and frustration for many participants, given the perceived impacts on their social life, family roles and enjoyment of life. Participants were also concerned about weight gain, health decline and reduced physical fitness. Participants valued the support of insurers and specialised services in facilitating access to modified activities, such as clinical Pilates and hydrotherapy. Many participants also recognised the importance of adaptation, goal-setting, self-motivation and determination to be physically active despite limitations.

Conclusion

People recovering from major trauma experienced significant and persistent physical activity restriction after their injury. Given the high prevalence of activity restrictions, distress and health concerns that were reported, there is an urgent need to develop and evaluate support strategies to improve physical activity participation in this group.", "laySummary": "", - "urls": "pdf:https://pdxscholar.library.pdx.edu/cgi/viewcontent.cgi?article=1451&context=sph_facpub; doi:https://doi.org/10.1001/jamacardio.2018.4537; html:https://europepmc.org/articles/PMC6386140" + "urls": "doi:https://doi.org/10.1016/j.jphys.2020.06.008; doi:https://doi.org/10.1016/j.jphys.2020.06.008" }, { "id": "37647632", @@ -33659,23 +33676,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1182/blood.2023020118; html:https://europepmc.org/articles/PMC10733830" }, - { - "id": "32680743", - "doi": "https://doi.org/10.1016/j.jphys.2020.06.008", - "title": "Adaptation, self-motivation and support services are key to physical activity participation three to five years after major trauma: a qualitative study.", - "authorString": "Ekegren CL, Braaf S, Ameratunga S, Ponsford J, Nunn A, Cameron P, Lyons RA, Gabbe BJ.", - "authorAffiliations": "", - "journalTitle": "Journal of physiotherapy", - "pubYear": "2020", - "date": "2020-07-14", - "isOpenAccess": "N", - "keywords": "Trauma; Recovery; Exercise; wounds and injuries; Sedentary Lifestyle", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Questions

What are the perceived long-term impacts of major trauma on physical activity participation over time? What factors influence physical activity participation in people recovering from major trauma?

Design

Longitudinal qualitative study.

Participants

Sixty-six people aged \u2265 16 years with non-neurological major trauma.

Methods

Participants were interviewed 3 years (n\u00a0= 66), 4 years (n\u00a0= 63) and 5 years (n\u00a0= 57) after their injury. A thematic analysis was performed.

Results

Despite wanting to be physically active, many participants experienced significant, long-term physical activity restriction after their injury, which persisted over time. Restrictions were often related to a fear of re-injury or of exacerbating pain and fatigue levels. These restrictions were a source of distress and frustration for many participants, given the perceived impacts on their social life, family roles and enjoyment of life. Participants were also concerned about weight gain, health decline and reduced physical fitness. Participants valued the support of insurers and specialised services in facilitating access to modified activities, such as clinical Pilates and hydrotherapy. Many participants also recognised the importance of adaptation, goal-setting, self-motivation and determination to be physically active despite limitations.

Conclusion

People recovering from major trauma experienced significant and persistent physical activity restriction after their injury. Given the high prevalence of activity restrictions, distress and health concerns that were reported, there is an urgent need to develop and evaluate support strategies to improve physical activity participation in this group.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1016/j.jphys.2020.06.008; doi:https://doi.org/10.1016/j.jphys.2020.06.008" - }, { "id": "35849350", "doi": "https://doi.org/10.1093/nar/gkac612", @@ -33829,23 +33829,6 @@ "laySummary": "", "urls": "pdf:https://academic.oup.com/schizophreniabulletin/article-pdf/47/2/405/36620462/sbaa126.pdf; doi:https://doi.org/10.1093/schbul/sbaa126; html:https://europepmc.org/articles/PMC7965059; pdf:https://europepmc.org/articles/PMC7965059?pdf=render; doi:https://doi.org/10.1093/schbul/sbaa126" }, - { - "id": "33185016", - "doi": "https://doi.org/10.1002/art.41593", - "title": "Nonsteroidal Antiinflammatory Drugs and Susceptibility to COVID-19.", - "authorString": "Chandan JS, Zemedikun DT, Thayakaran R, Byne N, Dhalla S, Acosta-Mena D, Gokhale KM, Thomas T, Sainsbury C, Subramanian A, Cooper J, Anand A, Okoth KO, Wang J, Adderley NJ, Taverner T, Denniston AK, Lord J, Thomas GN, Buckley CD, Raza K, Bhala N, Nirantharakumar K, Haroon S.", - "authorAffiliations": "", - "journalTitle": "Arthritis & rheumatology (Hoboken, N.J.)", - "pubYear": "2021", - "date": "2021-05-01", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Objective

To identify whether active use of nonsteroidal antiinflammatory drugs (NSAIDs) increases susceptibility to developing suspected or confirmed coronavirus disease 2019 (COVID-19) compared to the use of other common analgesics.

Methods

We performed a propensity score-matched cohort study with active comparators, using a large UK primary care data set. The cohort consisted of adult patients age \u226518 years with osteoarthritis (OA) who were followed up from January 30 to July 31, 2020. Patients prescribed an NSAID (excluding topical preparations) were compared to those prescribed either co-codamol (paracetamol and codeine) or co-dydramol (paracetamol and dihydrocodeine). A total of 13,202 patients prescribed NSAIDs were identified, compared to 12,457 patients prescribed the comparator drugs. The primary outcome measure was the documentation of suspected or confirmed COVID-19, and the secondary outcome measure was all-cause mortality.

Results

During follow-up, the incidence rates of suspected/confirmed COVID-19 were 15.4 and 19.9 per 1,000 person-years in the NSAID-exposed group and comparator group, respectively. Adjusted hazard ratios for suspected or confirmed COVID-19 among the unmatched and propensity score-matched OA cohorts, using data from clinical consultations in primary care settings, were 0.82 (95% confidence interval [95% CI] 0.62-1.10) and 0.79 (95% CI 0.57-1.11), respectively, and adjusted hazard ratios for the risk of all-cause mortality were 0.97 (95% CI 0.75-1.27) and 0.85 (95% CI 0.61-1.20), respectively. There was no effect modification by age or sex.

Conclusion

No increase in the risk of suspected or confirmed COVID-19 or mortality was observed among patients with OA in a primary care setting who were prescribed NSAIDs as compared to those who received comparator drugs. These results are reassuring and suggest that in the absence of acute illness, NSAIDs can be safely prescribed during the ongoing pandemic.", - "laySummary": "", - "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/art.41593; doi:https://doi.org/10.1002/art.41593; html:https://europepmc.org/articles/PMC8252419; pdf:https://europepmc.org/articles/PMC8252419?pdf=render" - }, { "id": "31780306", "doi": "https://doi.org/10.1016/s2215-0366(19)30298-6", @@ -33863,6 +33846,23 @@ "laySummary": "", "urls": "html:https://eprints.keele.ac.uk/6650/1/Pharamcoepidemiology%20Lancet%20Psych%202019%20submitted%20version.docx; doi:https://doi.org/10.1016/S2215-0366(19)30298-6" }, + { + "id": "33185016", + "doi": "https://doi.org/10.1002/art.41593", + "title": "Nonsteroidal Antiinflammatory Drugs and Susceptibility to COVID-19.", + "authorString": "Chandan JS, Zemedikun DT, Thayakaran R, Byne N, Dhalla S, Acosta-Mena D, Gokhale KM, Thomas T, Sainsbury C, Subramanian A, Cooper J, Anand A, Okoth KO, Wang J, Adderley NJ, Taverner T, Denniston AK, Lord J, Thomas GN, Buckley CD, Raza K, Bhala N, Nirantharakumar K, Haroon S.", + "authorAffiliations": "", + "journalTitle": "Arthritis & rheumatology (Hoboken, N.J.)", + "pubYear": "2021", + "date": "2021-05-01", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Objective

To identify whether active use of nonsteroidal antiinflammatory drugs (NSAIDs) increases susceptibility to developing suspected or confirmed coronavirus disease 2019 (COVID-19) compared to the use of other common analgesics.

Methods

We performed a propensity score-matched cohort study with active comparators, using a large UK primary care data set. The cohort consisted of adult patients age \u226518 years with osteoarthritis (OA) who were followed up from January 30 to July 31, 2020. Patients prescribed an NSAID (excluding topical preparations) were compared to those prescribed either co-codamol (paracetamol and codeine) or co-dydramol (paracetamol and dihydrocodeine). A total of 13,202 patients prescribed NSAIDs were identified, compared to 12,457 patients prescribed the comparator drugs. The primary outcome measure was the documentation of suspected or confirmed COVID-19, and the secondary outcome measure was all-cause mortality.

Results

During follow-up, the incidence rates of suspected/confirmed COVID-19 were 15.4 and 19.9 per 1,000 person-years in the NSAID-exposed group and comparator group, respectively. Adjusted hazard ratios for suspected or confirmed COVID-19 among the unmatched and propensity score-matched OA cohorts, using data from clinical consultations in primary care settings, were 0.82 (95% confidence interval [95% CI] 0.62-1.10) and 0.79 (95% CI 0.57-1.11), respectively, and adjusted hazard ratios for the risk of all-cause mortality were 0.97 (95% CI 0.75-1.27) and 0.85 (95% CI 0.61-1.20), respectively. There was no effect modification by age or sex.

Conclusion

No increase in the risk of suspected or confirmed COVID-19 or mortality was observed among patients with OA in a primary care setting who were prescribed NSAIDs as compared to those who received comparator drugs. These results are reassuring and suggest that in the absence of acute illness, NSAIDs can be safely prescribed during the ongoing pandemic.", + "laySummary": "", + "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/art.41593; doi:https://doi.org/10.1002/art.41593; html:https://europepmc.org/articles/PMC8252419; pdf:https://europepmc.org/articles/PMC8252419?pdf=render" + }, { "id": "35068290", "doi": "https://doi.org/10.1080/09537104.2021.2003317", @@ -34237,23 +34237,6 @@ "laySummary": "", "urls": "pdf:https://kclpure.kcl.ac.uk/ws/files/177671246/Br_J_Dermatol_2022_Ramessur_Biomarkers_of_disease_progression_in_people_with_psoriasis_a_scoping_review.pdf; doi:https://doi.org/10.1111/bjd.21627; html:https://europepmc.org/articles/PMC9796834; pdf:https://europepmc.org/articles/PMC9796834?pdf=render" }, - { - "id": "37789377", - "doi": "https://doi.org/10.1186/s12943-023-01863-2", - "title": "Spatial transcriptomic analysis of virtual prostate biopsy reveals confounding effect of tissue heterogeneity on genomic signatures.", - "authorString": "Figiel S, Yin W, Doultsinos D, Erickson A, Poulose N, Singh R, Magnussen A, Anbarasan T, Teague R, He M, Lundeberg J, Loda M, Verrill C, Colling R, Gill PS, Bryant RJ, Hamdy FC, Woodcock DJ, Mills IG, Cussenot O, Lamb AD.", - "authorAffiliations": "", - "journalTitle": "Molecular cancer", - "pubYear": "2023", - "date": "2023-10-03", - "isOpenAccess": "Y", - "keywords": "prostate cancer; Virtual Biopsy; Spatial Transcriptomics; Prognostic Genetic Signatures", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Genetic signatures have added a molecular dimension to prognostics and therapeutic decision-making. However, tumour heterogeneity in prostate cancer and current sampling methods could confound accurate assessment. Based on previously published spatial transcriptomic data from multifocal prostate cancer, we created virtual biopsy models that mimic conventional biopsy placement and core size. We then analysed the gene expression of different prognostic signatures (OncotypeDx\u00ae, Decipher\u00ae, Prostadiag\u00ae) using a step-wise approach with increasing resolution from pseudo-bulk analysis of the whole biopsy, to differentiation by tissue subtype (benign, stroma, tumour), followed by distinct tumour grade and finally clonal resolution. The gene expression profile of virtual tumour biopsies revealed clear differences between grade groups and tumour clones, compared to a benign control, which were not reflected in bulk analyses. This suggests that bulk analyses of whole biopsies or tumour-only areas, as used in clinical practice, may provide an inaccurate assessment of gene profiles. The type of tissue, the grade of the tumour and the clonal composition all influence the gene expression in a biopsy. Clinical decision making based on biopsy genomics should be made with caution while we await more precise targeting and cost-effective spatial analyses.", - "laySummary": "", - "urls": "pdf:https://molecular-cancer.biomedcentral.com/counter/pdf/10.1186/s12943-023-01863-2; doi:https://doi.org/10.1186/s12943-023-01863-2; html:https://europepmc.org/articles/PMC10546768; pdf:https://europepmc.org/articles/PMC10546768?pdf=render" - }, { "id": "31588514", "doi": "https://doi.org/10.1093/ptj/pzz151", @@ -34271,6 +34254,23 @@ "laySummary": "", "urls": "pdf:https://academic.oup.com/ptj/article-pdf/100/2/332/32901113/pzz151.pdf; doi:https://doi.org/10.1093/ptj/pzz151" }, + { + "id": "37789377", + "doi": "https://doi.org/10.1186/s12943-023-01863-2", + "title": "Spatial transcriptomic analysis of virtual prostate biopsy reveals confounding effect of tissue heterogeneity on genomic signatures.", + "authorString": "Figiel S, Yin W, Doultsinos D, Erickson A, Poulose N, Singh R, Magnussen A, Anbarasan T, Teague R, He M, Lundeberg J, Loda M, Verrill C, Colling R, Gill PS, Bryant RJ, Hamdy FC, Woodcock DJ, Mills IG, Cussenot O, Lamb AD.", + "authorAffiliations": "", + "journalTitle": "Molecular cancer", + "pubYear": "2023", + "date": "2023-10-03", + "isOpenAccess": "Y", + "keywords": "prostate cancer; Virtual Biopsy; Spatial Transcriptomics; Prognostic Genetic Signatures", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Genetic signatures have added a molecular dimension to prognostics and therapeutic decision-making. However, tumour heterogeneity in prostate cancer and current sampling methods could confound accurate assessment. Based on previously published spatial transcriptomic data from multifocal prostate cancer, we created virtual biopsy models that mimic conventional biopsy placement and core size. We then analysed the gene expression of different prognostic signatures (OncotypeDx\u00ae, Decipher\u00ae, Prostadiag\u00ae) using a step-wise approach with increasing resolution from pseudo-bulk analysis of the whole biopsy, to differentiation by tissue subtype (benign, stroma, tumour), followed by distinct tumour grade and finally clonal resolution. The gene expression profile of virtual tumour biopsies revealed clear differences between grade groups and tumour clones, compared to a benign control, which were not reflected in bulk analyses. This suggests that bulk analyses of whole biopsies or tumour-only areas, as used in clinical practice, may provide an inaccurate assessment of gene profiles. The type of tissue, the grade of the tumour and the clonal composition all influence the gene expression in a biopsy. Clinical decision making based on biopsy genomics should be made with caution while we await more precise targeting and cost-effective spatial analyses.", + "laySummary": "", + "urls": "pdf:https://molecular-cancer.biomedcentral.com/counter/pdf/10.1186/s12943-023-01863-2; doi:https://doi.org/10.1186/s12943-023-01863-2; html:https://europepmc.org/articles/PMC10546768; pdf:https://europepmc.org/articles/PMC10546768?pdf=render" + }, { "id": "34173574", "doi": "https://doi.org/10.1016/j.puhip.2020.100039", @@ -34288,23 +34288,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.puhip.2020.100039; doi:https://doi.org/10.1016/j.puhip.2020.100039; html:https://europepmc.org/articles/PMC7486860; pdf:https://europepmc.org/articles/PMC7486860?pdf=render" }, - { - "id": "34767555", - "doi": "https://doi.org/10.1371/journal.pmed.1003832", - "title": "Educational and health outcomes of schoolchildren in local authority care in Scotland: A retrospective record linkage study.", - "authorString": "Fleming M, McLay JS, Clark D, King A, Mackay DF, Minnis H, Pell JP.", - "authorAffiliations": "", - "journalTitle": "PLoS medicine", - "pubYear": "2021", - "date": "2021-11-12", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Looked after children are defined as children who are in the care of their local authority. Previous studies have reported that looked after children have poorer mental and physical health, increased behavioural problems, and increased self-harm and mortality compared to peers. They also experience poorer educational outcomes, yet population-wide research into the latter is lacking, particularly in the United Kingdom. Education and health share a bidirectional relationship; therefore, it is important to dually investigate both outcomes. Our study aimed to compare educational and health outcomes for looked after children with peers, adjusting for sociodemographic, maternity, and comorbidity confounders.

Methods and findings

Linkage of 9 Scotland-wide databases, covering dispensed prescriptions, hospital admissions, maternity records, death certificates, annual pupil census, examinations, school absences/exclusions, unemployment, and looked after children provided retrospective data on 715,111 children attending Scottish schools between 2009 and 2012 (13,898 [1.9%] looked after). Compared to peers, 13,898 (1.9%) looked after children were more likely to be absent (adjusted incidence rate ratio [AIRR] 1.27, 95% confidence interval [CI] 1.24 to 1.30) and excluded (AIRR 4.09, 95% CI 3.86 to 4.33) from school, have special educational need (SEN; adjusted odds ratio [AOR] 3.48, 95% CI 3.35 to 3.62) and neurodevelopmental multimorbidity (AOR 2.45, 95% CI 2.34 to 2.57), achieve the lowest level of academic attainment (AOR 5.92, 95% CI 5.17 to 6.78), and be unemployed after leaving school (AOR 2.12, 95% CI 1.96 to 2.29). They were more likely to require treatment for epilepsy (AOR 1.50, 95% CI 1.27 to 1.78), attention deficit hyperactivity disorder (ADHD; AOR 3.01, 95% CI 2.76 to 3.27), and depression (AOR 1.90, 95% CI 1.62 to 2.22), be hospitalised overall (adjusted hazard ratio [AHR] 1.23, 95% CI 1.19 to 1.28) for injury (AHR 1.80, 95% CI 1.69 to 1.91) and self-harm (AHR 5.19, 95% CI 4.66 to 5.78), and die prematurely (AHR 3.21, 95% CI 2.16 to 4.77). Compared to children looked after at home, children looked after away from home had less absenteeism (AIRR 0.35, 95% CI 0.33 to 0.36), less exclusion (AIRR 0.63, 95% CI 0.56 to 0.71), less unemployment (AOR 0.53, 95% CI 0.46 to 0.62), and better attainment (AIRR 0.31, 95% CI 0.23 to 0.40). Therefore, among those in care, being cared for away from home appeared to be a protective factor resulting in better educational outcomes. The main limitations of this study were lack of data on local authority care preschool or before 2009, total time spent in care, and age of first contact with social care.

Conclusions

Looked after children had poorer health and educational outcomes than peers independent of increased neurodevelopmental conditions and SEN. Further work is required to understand whether poorer outcomes relate to reasons for entering care, including maltreatment and adverse childhood events, neurodevelopmental vulnerabilities, or characteristics of the care system.", - "laySummary": "", - "urls": "pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1003832&type=printable; doi:https://doi.org/10.1371/journal.pmed.1003832; html:https://europepmc.org/articles/PMC8589203; pdf:https://europepmc.org/articles/PMC8589203?pdf=render" - }, { "id": "31101093", "doi": "https://doi.org/10.1186/s12889-019-6888-9", @@ -34322,6 +34305,23 @@ "laySummary": "", "urls": "pdf:https://bmcpublichealth.biomedcentral.com/track/pdf/10.1186/s12889-019-6888-9; doi:https://doi.org/10.1186/s12889-019-6888-9; html:https://europepmc.org/articles/PMC6525436; pdf:https://europepmc.org/articles/PMC6525436?pdf=render" }, + { + "id": "34767555", + "doi": "https://doi.org/10.1371/journal.pmed.1003832", + "title": "Educational and health outcomes of schoolchildren in local authority care in Scotland: A retrospective record linkage study.", + "authorString": "Fleming M, McLay JS, Clark D, King A, Mackay DF, Minnis H, Pell JP.", + "authorAffiliations": "", + "journalTitle": "PLoS medicine", + "pubYear": "2021", + "date": "2021-11-12", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Looked after children are defined as children who are in the care of their local authority. Previous studies have reported that looked after children have poorer mental and physical health, increased behavioural problems, and increased self-harm and mortality compared to peers. They also experience poorer educational outcomes, yet population-wide research into the latter is lacking, particularly in the United Kingdom. Education and health share a bidirectional relationship; therefore, it is important to dually investigate both outcomes. Our study aimed to compare educational and health outcomes for looked after children with peers, adjusting for sociodemographic, maternity, and comorbidity confounders.

Methods and findings

Linkage of 9 Scotland-wide databases, covering dispensed prescriptions, hospital admissions, maternity records, death certificates, annual pupil census, examinations, school absences/exclusions, unemployment, and looked after children provided retrospective data on 715,111 children attending Scottish schools between 2009 and 2012 (13,898 [1.9%] looked after). Compared to peers, 13,898 (1.9%) looked after children were more likely to be absent (adjusted incidence rate ratio [AIRR] 1.27, 95% confidence interval [CI] 1.24 to 1.30) and excluded (AIRR 4.09, 95% CI 3.86 to 4.33) from school, have special educational need (SEN; adjusted odds ratio [AOR] 3.48, 95% CI 3.35 to 3.62) and neurodevelopmental multimorbidity (AOR 2.45, 95% CI 2.34 to 2.57), achieve the lowest level of academic attainment (AOR 5.92, 95% CI 5.17 to 6.78), and be unemployed after leaving school (AOR 2.12, 95% CI 1.96 to 2.29). They were more likely to require treatment for epilepsy (AOR 1.50, 95% CI 1.27 to 1.78), attention deficit hyperactivity disorder (ADHD; AOR 3.01, 95% CI 2.76 to 3.27), and depression (AOR 1.90, 95% CI 1.62 to 2.22), be hospitalised overall (adjusted hazard ratio [AHR] 1.23, 95% CI 1.19 to 1.28) for injury (AHR 1.80, 95% CI 1.69 to 1.91) and self-harm (AHR 5.19, 95% CI 4.66 to 5.78), and die prematurely (AHR 3.21, 95% CI 2.16 to 4.77). Compared to children looked after at home, children looked after away from home had less absenteeism (AIRR 0.35, 95% CI 0.33 to 0.36), less exclusion (AIRR 0.63, 95% CI 0.56 to 0.71), less unemployment (AOR 0.53, 95% CI 0.46 to 0.62), and better attainment (AIRR 0.31, 95% CI 0.23 to 0.40). Therefore, among those in care, being cared for away from home appeared to be a protective factor resulting in better educational outcomes. The main limitations of this study were lack of data on local authority care preschool or before 2009, total time spent in care, and age of first contact with social care.

Conclusions

Looked after children had poorer health and educational outcomes than peers independent of increased neurodevelopmental conditions and SEN. Further work is required to understand whether poorer outcomes relate to reasons for entering care, including maltreatment and adverse childhood events, neurodevelopmental vulnerabilities, or characteristics of the care system.", + "laySummary": "", + "urls": "pdf:https://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1003832&type=printable; doi:https://doi.org/10.1371/journal.pmed.1003832; html:https://europepmc.org/articles/PMC8589203; pdf:https://europepmc.org/articles/PMC8589203?pdf=render" + }, { "id": "35331425", "doi": "https://doi.org/10.1016/j.jacep.2021.09.001", @@ -34407,23 +34407,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.lana.2022.100335; doi:https://doi.org/10.1016/j.lana.2022.100335; html:https://europepmc.org/articles/PMC9381845; pdf:https://europepmc.org/articles/PMC9381845?pdf=render" }, - { - "id": "34091032", - "doi": "https://doi.org/10.1016/j.neuroimage.2021.118235", - "title": "Subspace-constrained approaches to low-rank fMRI acceleration.", - "authorString": "Mason HT, Graedel NN, Miller KL, Chiew M.", - "authorAffiliations": "", - "journalTitle": "NeuroImage", - "pubYear": "2021", - "date": "2021-06-03", - "isOpenAccess": "Y", - "keywords": "fMRI; Tikhonov regularization; Acceleration; temporal resolution; Low Rank; Temporal Smoothing; K-t Faster; Low Resolution Priors", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Acceleration methods in fMRI aim to reconstruct high fidelity images from under-sampled k-space, allowing fMRI datasets to achieve higher temporal resolution, reduced physiological noise aliasing, and increased statistical degrees of freedom. While low levels of acceleration are typically part of standard fMRI protocols through parallel imaging, there exists the potential for approaches that allow much greater acceleration. One such existing approach is k-t FASTER, which exploits the inherent low-rank nature of fMRI. In this paper, we present a reformulated version of k-t FASTER which includes additional L2 constraints within a low-rank framework. We evaluated the effect of three different constraints against existing low-rank approaches to fMRI reconstruction: Tikhonov constraints, low-resolution priors, and temporal subspace smoothness. The different approaches are separately tested for robustness to under-sampling and thermal noise levels, in both retrospectively and prospectively-undersampled finger-tapping task fMRI data. Reconstruction quality is evaluated by accurate reconstruction of low-rank subspaces and activation maps. The use of L2 constraints was found to achieve consistently improved results, producing high fidelity reconstructions of statistical parameter maps at higher acceleration factors and lower SNR values than existing methods, but at a cost of longer computation time. In particular, the Tikhonov constraint proved very robust across all tested datasets, and the temporal subspace smoothness constraint provided the best reconstruction scores in the prospectively-undersampled dataset. These results demonstrate that regularized low-rank reconstruction of fMRI data can recover functional information at high acceleration factors without the use of any model-based spatial constraints.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1016/j.neuroimage.2021.118235; doi:https://doi.org/10.1016/j.neuroimage.2021.118235; html:https://europepmc.org/articles/PMC7611820; pdf:https://europepmc.org/articles/PMC7611820?pdf=render" - }, { "id": "30382236", "doi": "https://doi.org/10.1038/s41433-018-0229-6", @@ -34441,6 +34424,23 @@ "laySummary": "Perrott et al. reviewed strengths and limitations of an eye (retinal) imagining method for diagnosis of a condition affecting the central part of the retina (the macula). This degenerative condition may result in loss of central vision in older adults. Perrott et al. concluded that diagnostic accuracy depends on both method and equipment. ", "urls": "pdf:https://www.nature.com/articles/s41433-018-0229-6.pdf; doi:https://doi.org/10.1038/s41433-018-0229-6; html:https://europepmc.org/articles/PMC6367454; pdf:https://europepmc.org/articles/PMC6367454?pdf=render; doi:https://doi.org/10.1038/s41433-018-0229-6" }, + { + "id": "34091032", + "doi": "https://doi.org/10.1016/j.neuroimage.2021.118235", + "title": "Subspace-constrained approaches to low-rank fMRI acceleration.", + "authorString": "Mason HT, Graedel NN, Miller KL, Chiew M.", + "authorAffiliations": "", + "journalTitle": "NeuroImage", + "pubYear": "2021", + "date": "2021-06-03", + "isOpenAccess": "Y", + "keywords": "fMRI; Tikhonov regularization; Acceleration; temporal resolution; Low Rank; Temporal Smoothing; K-t Faster; Low Resolution Priors", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Acceleration methods in fMRI aim to reconstruct high fidelity images from under-sampled k-space, allowing fMRI datasets to achieve higher temporal resolution, reduced physiological noise aliasing, and increased statistical degrees of freedom. While low levels of acceleration are typically part of standard fMRI protocols through parallel imaging, there exists the potential for approaches that allow much greater acceleration. One such existing approach is k-t FASTER, which exploits the inherent low-rank nature of fMRI. In this paper, we present a reformulated version of k-t FASTER which includes additional L2 constraints within a low-rank framework. We evaluated the effect of three different constraints against existing low-rank approaches to fMRI reconstruction: Tikhonov constraints, low-resolution priors, and temporal subspace smoothness. The different approaches are separately tested for robustness to under-sampling and thermal noise levels, in both retrospectively and prospectively-undersampled finger-tapping task fMRI data. Reconstruction quality is evaluated by accurate reconstruction of low-rank subspaces and activation maps. The use of L2 constraints was found to achieve consistently improved results, producing high fidelity reconstructions of statistical parameter maps at higher acceleration factors and lower SNR values than existing methods, but at a cost of longer computation time. In particular, the Tikhonov constraint proved very robust across all tested datasets, and the temporal subspace smoothness constraint provided the best reconstruction scores in the prospectively-undersampled dataset. These results demonstrate that regularized low-rank reconstruction of fMRI data can recover functional information at high acceleration factors without the use of any model-based spatial constraints.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1016/j.neuroimage.2021.118235; doi:https://doi.org/10.1016/j.neuroimage.2021.118235; html:https://europepmc.org/articles/PMC7611820; pdf:https://europepmc.org/articles/PMC7611820?pdf=render" + }, { "id": "37770476", "doi": "https://doi.org/10.1038/s41467-023-41249-y", @@ -34611,23 +34611,6 @@ "laySummary": "", "urls": "pdf:https://openaccess.city.ac.uk/id/eprint/24492/1/Wright%20Crabb%20et%20al%20Ophthalmology%202020.pdf; doi:https://doi.org/10.1016/j.ophtha.2020.03.029" }, - { - "id": "33782396", - "doi": "https://doi.org/10.1038/s41467-021-22213-0", - "title": "Implications of the school-household network structure on SARS-CoV-2 transmission under school reopening strategies in England.", - "authorString": "Munday JD, Sherratt K, Meakin S, Endo A, Pearson CAB, Hellewell J, Abbott S, Bosse NI, CMMID COVID-19 Working Group, Atkins KE, Wallinga J, Edmunds WJ, van Hoek AJ, Funk S.", - "authorAffiliations": "", - "journalTitle": "Nature communications", - "pubYear": "2021", - "date": "2021-03-29", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "In early 2020 many countries closed schools to mitigate the spread of SARS-CoV-2. Since then, governments have sought to relax the closures, engendering a need to understand associated risks. Using address records, we construct a network of schools in England connected through pupils who share households. We evaluate the risk of transmission between schools under different reopening scenarios. We show that whilst reopening select year-groups causes low risk of large-scale transmission, reopening secondary schools could result in outbreaks affecting up to 2.5 million households if unmitigated, highlighting the importance of careful monitoring and within-school infection control to avoid further school closures or other restrictions.", - "laySummary": "", - "urls": "pdf:https://www.nature.com/articles/s41467-021-22213-0.pdf; doi:https://doi.org/10.1038/s41467-021-22213-0; html:https://europepmc.org/articles/PMC8007691; pdf:https://europepmc.org/articles/PMC8007691?pdf=render" - }, { "id": "29780001", "doi": "https://doi.org/10.1016/s2352-3026(18)30053-x", @@ -34645,6 +34628,23 @@ "laySummary": "", "urls": "pdf:http://www.thelancet.com/article/S235230261830053X/pdf; doi:https://doi.org/10.1016/S2352-3026(18)30053-X; html:https://europepmc.org/articles/PMC6438177; pdf:https://europepmc.org/articles/PMC6438177?pdf=render; doi:https://doi.org/10.1016/s2352-3026(18)30053-x" }, + { + "id": "33782396", + "doi": "https://doi.org/10.1038/s41467-021-22213-0", + "title": "Implications of the school-household network structure on SARS-CoV-2 transmission under school reopening strategies in England.", + "authorString": "Munday JD, Sherratt K, Meakin S, Endo A, Pearson CAB, Hellewell J, Abbott S, Bosse NI, CMMID COVID-19 Working Group, Atkins KE, Wallinga J, Edmunds WJ, van Hoek AJ, Funk S.", + "authorAffiliations": "", + "journalTitle": "Nature communications", + "pubYear": "2021", + "date": "2021-03-29", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "In early 2020 many countries closed schools to mitigate the spread of SARS-CoV-2. Since then, governments have sought to relax the closures, engendering a need to understand associated risks. Using address records, we construct a network of schools in England connected through pupils who share households. We evaluate the risk of transmission between schools under different reopening scenarios. We show that whilst reopening select year-groups causes low risk of large-scale transmission, reopening secondary schools could result in outbreaks affecting up to 2.5 million households if unmitigated, highlighting the importance of careful monitoring and within-school infection control to avoid further school closures or other restrictions.", + "laySummary": "", + "urls": "pdf:https://www.nature.com/articles/s41467-021-22213-0.pdf; doi:https://doi.org/10.1038/s41467-021-22213-0; html:https://europepmc.org/articles/PMC8007691; pdf:https://europepmc.org/articles/PMC8007691?pdf=render" + }, { "id": "30351417", "doi": "https://doi.org/10.1093/bioinformatics/bty837", @@ -34679,23 +34679,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.injury.2019.12.016" }, - { - "id": "34708157", - "doi": "https://doi.org/10.12688/wellcomeopenres.16701.3", - "title": "Estimating the duration of seropositivity of human seasonal coronaviruses using seroprevalence studies.", - "authorString": "Rees EM, Waterlow NR, Centre for the Mathematical Modelling of Infectious Diseases COVID-19 Working Group, Lowe R, Kucharski AJ.", - "authorAffiliations": "", - "journalTitle": "Wellcome open research", - "pubYear": "2021", - "date": "2021-12-21", - "isOpenAccess": "Y", - "keywords": "Catalytic model; Seroprevalence; Waning Immunity; Seasonal Coronavirus", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Background: The duration of immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still uncertain, but it is of key clinical and epidemiological importance. Seasonal human coronaviruses (HCoV) have been circulating for longer and, therefore, may offer insights into the long-term dynamics of reinfection for such viruses. Methods: Combining historical seroprevalence data from five studies covering the four circulating HCoVs with an age-structured reverse catalytic model, we estimated the likely duration of seropositivity following seroconversion. Results: We estimated that antibody persistence lasted between 0.9 (95% Credible interval: 0.6 - 1.6) and 3.8 (95% CrI: 2.0 - 7.4) years. Furthermore, we found the force of infection in older children and adults (those over 8.5 [95% CrI: 7.5 - 9.9] years) to be higher compared with young children in the majority of studies. Conclusions: These estimates of endemic HCoV dynamics could provide an indication of the future long-term infection and reinfection patterns of SARS-CoV-2.", - "laySummary": "", - "urls": "doi:https://doi.org/10.12688/wellcomeopenres.16701.3; html:https://europepmc.org/articles/PMC8517721; pdf:https://europepmc.org/articles/PMC8517721?pdf=render" - }, { "id": "33550229", "doi": "https://doi.org/10.1136/bmjopen-2020-040167", @@ -34713,6 +34696,23 @@ "laySummary": "", "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/11/2/e040167.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-040167; html:https://europepmc.org/articles/PMC7925902; pdf:https://europepmc.org/articles/PMC7925902?pdf=render" }, + { + "id": "34708157", + "doi": "https://doi.org/10.12688/wellcomeopenres.16701.3", + "title": "Estimating the duration of seropositivity of human seasonal coronaviruses using seroprevalence studies.", + "authorString": "Rees EM, Waterlow NR, Centre for the Mathematical Modelling of Infectious Diseases COVID-19 Working Group, Lowe R, Kucharski AJ.", + "authorAffiliations": "", + "journalTitle": "Wellcome open research", + "pubYear": "2021", + "date": "2021-12-21", + "isOpenAccess": "Y", + "keywords": "Catalytic model; Seroprevalence; Waning Immunity; Seasonal Coronavirus", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Background: The duration of immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still uncertain, but it is of key clinical and epidemiological importance. Seasonal human coronaviruses (HCoV) have been circulating for longer and, therefore, may offer insights into the long-term dynamics of reinfection for such viruses. Methods: Combining historical seroprevalence data from five studies covering the four circulating HCoVs with an age-structured reverse catalytic model, we estimated the likely duration of seropositivity following seroconversion. Results: We estimated that antibody persistence lasted between 0.9 (95% Credible interval: 0.6 - 1.6) and 3.8 (95% CrI: 2.0 - 7.4) years. Furthermore, we found the force of infection in older children and adults (those over 8.5 [95% CrI: 7.5 - 9.9] years) to be higher compared with young children in the majority of studies. Conclusions: These estimates of endemic HCoV dynamics could provide an indication of the future long-term infection and reinfection patterns of SARS-CoV-2.", + "laySummary": "", + "urls": "doi:https://doi.org/10.12688/wellcomeopenres.16701.3; html:https://europepmc.org/articles/PMC8517721; pdf:https://europepmc.org/articles/PMC8517721?pdf=render" + }, { "id": "35507331", "doi": "https://doi.org/10.1002/art.42154", @@ -35036,23 +35036,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1111/bjd.20140" }, - { - "id": "35710247", - "doi": "https://doi.org/10.1136/bmjopen-2021-060280", - "title": "Structured follow-up pathway to support people after transient ischaemic attack and minor stroke (SUPPORT TIA): protocol for a feasibility study and process evaluation.", - "authorString": "Turner GM, Jones R, Collis P, Patel S, Jowett S, Tearne S, Foy R, Atkins L, Mant J, Calvert M.", - "authorAffiliations": "", - "journalTitle": "BMJ open", - "pubYear": "2022", - "date": "2022-06-16", - "isOpenAccess": "Y", - "keywords": "Qualitative Research; Rehabilitation Medicine; Stroke Medicine; Protocols & Guidelines; Organisation Of Health Services; Depression & Mood Disorders", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Introduction

People who experience transient ischaemic attack (TIA) and minor stroke have limited follow-up despite rapid specialist review in hospital. This means they often have unmet needs and feel abandoned following discharge. Care needs after TIA/minor stroke include information provision (diagnosis and stroke risk), stroke prevention (medication and lifestyle change) and holistic care (residual problems and return to work or usual activities). This protocol describes a feasibility study and process evaluation of an intervention to support people after TIA/minor stroke. The study aims to assess the feasibility and acceptability of (1) the intervention and (2) the trial procedures for a future randomised controlled trial of this intervention.

Methods and analysis

This is a multicentre, randomised (1:1) feasibility study with a mixed-methods process evaluation. Sixty participants will be recruited from TIA clinics or stroke wards at three hospital sites (England). Intervention arm participants will be offered a nurse or allied health professional-led follow-up appointment 4 weeks after TIA/minor stroke. The multifaceted intervention includes: a needs checklist, action plan, resources to support management of needs, a general practitioner letter and training to deliver the intervention. Control arm participants will receive usual care. Follow-up will be self-completed questionnaires (12 weeks and 24 weeks) and a clinic appointment (24 weeks). Follow-up questionnaires will measure anxiety, depression, fatigue, health related quality of life, self-efficacy and medication adherence. The clinic appointment will collect body mass index, blood pressure, cholesterol and medication. Assessment of feasibility and acceptability will include quantitative process variables (such as recruitment and questionnaire response rates), structured observations of study processes, and interviews with a subsample of participants and clinical staff.

Ethics and dissemination

Favourable ethical opinion was gained from the Wales Research Ethics Committee (REC) 1 (23 February 2021, REC reference: 21/WA/0036). Study results will be published in peer-reviewed journals and presented at conferences. A lay summary and dissemination strategy will be codesigned with consumers. The lay summary and journal publication will be distributed on social media.

Trial registration number

ISRCTN39864003.", - "laySummary": "", - "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/12/6/e060280.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-060280; html:https://europepmc.org/articles/PMC9207897; pdf:https://europepmc.org/articles/PMC9207897?pdf=render" - }, { "id": "33742045", "doi": "https://doi.org/10.1038/s41598-021-85354-8", @@ -35087,6 +35070,23 @@ "laySummary": "", "urls": "pdf:http://www.journal-of-hepatology.eu/article/S016882782030194X/pdf; doi:https://doi.org/10.1016/j.jhep.2020.03.032; html:https://europepmc.org/articles/PMC7372222; pdf:https://europepmc.org/articles/PMC7372222?pdf=render" }, + { + "id": "35710247", + "doi": "https://doi.org/10.1136/bmjopen-2021-060280", + "title": "Structured follow-up pathway to support people after transient ischaemic attack and minor stroke (SUPPORT TIA): protocol for a feasibility study and process evaluation.", + "authorString": "Turner GM, Jones R, Collis P, Patel S, Jowett S, Tearne S, Foy R, Atkins L, Mant J, Calvert M.", + "authorAffiliations": "", + "journalTitle": "BMJ open", + "pubYear": "2022", + "date": "2022-06-16", + "isOpenAccess": "Y", + "keywords": "Qualitative Research; Rehabilitation Medicine; Stroke Medicine; Protocols & Guidelines; Organisation Of Health Services; Depression & Mood Disorders", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Introduction

People who experience transient ischaemic attack (TIA) and minor stroke have limited follow-up despite rapid specialist review in hospital. This means they often have unmet needs and feel abandoned following discharge. Care needs after TIA/minor stroke include information provision (diagnosis and stroke risk), stroke prevention (medication and lifestyle change) and holistic care (residual problems and return to work or usual activities). This protocol describes a feasibility study and process evaluation of an intervention to support people after TIA/minor stroke. The study aims to assess the feasibility and acceptability of (1) the intervention and (2) the trial procedures for a future randomised controlled trial of this intervention.

Methods and analysis

This is a multicentre, randomised (1:1) feasibility study with a mixed-methods process evaluation. Sixty participants will be recruited from TIA clinics or stroke wards at three hospital sites (England). Intervention arm participants will be offered a nurse or allied health professional-led follow-up appointment 4 weeks after TIA/minor stroke. The multifaceted intervention includes: a needs checklist, action plan, resources to support management of needs, a general practitioner letter and training to deliver the intervention. Control arm participants will receive usual care. Follow-up will be self-completed questionnaires (12 weeks and 24 weeks) and a clinic appointment (24 weeks). Follow-up questionnaires will measure anxiety, depression, fatigue, health related quality of life, self-efficacy and medication adherence. The clinic appointment will collect body mass index, blood pressure, cholesterol and medication. Assessment of feasibility and acceptability will include quantitative process variables (such as recruitment and questionnaire response rates), structured observations of study processes, and interviews with a subsample of participants and clinical staff.

Ethics and dissemination

Favourable ethical opinion was gained from the Wales Research Ethics Committee (REC) 1 (23 February 2021, REC reference: 21/WA/0036). Study results will be published in peer-reviewed journals and presented at conferences. A lay summary and dissemination strategy will be codesigned with consumers. The lay summary and journal publication will be distributed on social media.

Trial registration number

ISRCTN39864003.", + "laySummary": "", + "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/12/6/e060280.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-060280; html:https://europepmc.org/articles/PMC9207897; pdf:https://europepmc.org/articles/PMC9207897?pdf=render" + }, { "id": "33480434", "doi": "https://doi.org/10.1093/pubmed/fdaa267", @@ -35291,23 +35291,6 @@ "laySummary": "", "urls": "pdf:https://link.springer.com/content/pdf/10.1007/s12471-019-1288-4.pdf; doi:https://doi.org/10.1007/s12471-019-1288-4; html:https://europepmc.org/articles/PMC6712144; pdf:https://europepmc.org/articles/PMC6712144?pdf=render" }, - { - "id": "36401199", - "doi": "https://doi.org/10.1186/s12888-022-04275-6", - "title": "Patient characteristics associated with retrospectively self-reported treatment outcomes following psychological therapy for anxiety or depressive disorders - a cohort of GLAD study participants.", - "authorString": "Rayner C, Coleman JRI, Skelton M, Armour C, Bradley J, Buckman JEJ, Davies MR, Hirsch CR, Hotopf M, H\u00fcbel C, Jones IR, Kalsi G, Kingston N, Krebs G, Lin Y, Monssen D, McIntosh AM, Mundy JR, Peel AJ, Rimes KA, Rogers HC, Smith DJ, Ter Kuile AR, Thompson KN, Veale D, Wingrove J, Walters JTR, Breen G, Eley TC.", - "authorAffiliations": "", - "journalTitle": "BMC psychiatry", - "pubYear": "2022", - "date": "2022-11-18", - "isOpenAccess": "Y", - "keywords": "Counselling; Cognitive Behavioral Therapy; Minimal Phenotyping", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Progress towards stratified care for anxiety and depression will require the identification of new predictors. We collected data on retrospectively self-reported therapeutic outcomes in adults who received psychological therapy in the UK in the past ten years. We aimed to replicate factors associated with traditional treatment outcome measures from the literature.

Methods

Participants were from the Genetic Links to Anxiety and Depression (GLAD) Study, a UK-based volunteer cohort study. We investigated associations between retrospectively self-reported outcomes following therapy, on a five-point scale (global rating of change; GRC) and a range of sociodemographic, clinical and therapy-related factors, using ordinal logistic regression models (n\u2009=\u20092890).

Results

Four factors were associated with therapy outcomes (adjusted odds ratios, OR). One sociodemographic factor, having university-level education, was associated with favourable outcomes (OR\u2009=\u20091.37, 95%CI: 1.18, 1.59). Two clinical factors, greater number of reported episodes of illness (OR\u2009=\u20090.95, 95%CI: 0.92, 0.97) and higher levels of personality disorder symptoms (OR\u2009=\u20090.89, 95%CI: 0.87, 0.91), were associated with less favourable outcomes. Finally, reported regular use of additional therapeutic activities was associated with favourable outcomes (OR\u2009=\u20091.39, 95%CI: 1.19, 1.63). There were no statistically significant differences between fully adjusted multivariable and unadjusted univariable odds ratios.

Conclusion

Therapy outcome data can be collected quickly and inexpensively using retrospectively self-reported measures in large observational cohorts. Retrospectively self-reported therapy outcomes were associated with four factors previously reported in the literature. Similar data collected in larger observational cohorts may enable detection of novel associations with therapy outcomes, to generate new hypotheses, which can be followed up in prospective studies.", - "laySummary": "", - "urls": "pdf:https://bmcpsychiatry.biomedcentral.com/counter/pdf/10.1186/s12888-022-04275-6; doi:https://doi.org/10.1186/s12888-022-04275-6; html:https://europepmc.org/articles/PMC9675224; pdf:https://europepmc.org/articles/PMC9675224?pdf=render" - }, { "id": "32479194", "doi": "https://doi.org/10.1161/circulationaha.120.045826", @@ -35326,21 +35309,21 @@ "urls": "pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCULATIONAHA.120.045826; doi:https://doi.org/10.1161/CIRCULATIONAHA.120.045826; html:https://europepmc.org/articles/PMC7614586; pdf:https://europepmc.org/articles/PMC7614586?pdf=render; doi:https://doi.org/10.1161/circulationaha.120.045826" }, { - "id": "35614427", - "doi": "https://doi.org/10.1186/s12889-022-13457-6", - "title": "The association between childhood hearing loss and self-reported peer victimisation, depressive symptoms, and self-harm: longitudinal analyses of a prospective, nationally representative cohort study.", - "authorString": "Butcher E, Cortina-Borja M, Dezateux C, Knowles R.", + "id": "36401199", + "doi": "https://doi.org/10.1186/s12888-022-04275-6", + "title": "Patient characteristics associated with retrospectively self-reported treatment outcomes following psychological therapy for anxiety or depressive disorders - a cohort of GLAD study participants.", + "authorString": "Rayner C, Coleman JRI, Skelton M, Armour C, Bradley J, Buckman JEJ, Davies MR, Hirsch CR, Hotopf M, H\u00fcbel C, Jones IR, Kalsi G, Kingston N, Krebs G, Lin Y, Monssen D, McIntosh AM, Mundy JR, Peel AJ, Rimes KA, Rogers HC, Smith DJ, Ter Kuile AR, Thompson KN, Veale D, Wingrove J, Walters JTR, Breen G, Eley TC.", "authorAffiliations": "", - "journalTitle": "BMC public health", + "journalTitle": "BMC psychiatry", "pubYear": "2022", - "date": "2022-05-25", + "date": "2022-11-18", "isOpenAccess": "Y", - "keywords": "Child; Hearing loss; Cohort studies; Mental health; Self-harm; Depressive Symptoms; Peer Victimisation", + "keywords": "Counselling; Cognitive Behavioral Therapy; Minimal Phenotyping", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Background

Childhood hearing loss (HL) predicts poor mental health and is associated with a higher risk of communication difficulties. The relationship of childhood HL with specific types of poor mental health (such as depressive symptoms or self-harm) and peer victimisation remains unclear.

Methods

We analysed data from the Millennium Cohort Study (MCS), a prospective observational cohort study of children living in the UK at age 9\u2009months and born between 2000 to 2002. Data were available on the children and their families at ages 9\u2009months, then at 3, 5, 7, 11, and 14\u2009years. Participants were 10,858 singleton children with self-reported data on peer victimisation, depressive symptoms, and self-harm at age 14\u2009years. Multivariable logistic regression models were fitted to estimate odds ratios (OR) for HL with peer victimisation, depressive symptoms, and self-harm. HL presence was examined in terms of any HL between ages 9\u2009months and 14\u2009years, as well as by HL trajectory type (defined by onset and persistence). Analyses were adjusted for potential sources of confounding, survey design, and attrition at age 14\u2009years. Interactions between sex and HL were examined in each model and multiple imputation procedures used to address missing data.

Results

Children with any HL had increased odds of depressive symptoms (OR: 1.32, 95% CI: 1.09-1.60), self-harm (1.41, 1.12-1.78) and, in girls only, peer victimisation (girls: 1.81, 1.29-2.55; boys: 1.05, 0.73-1.51), compared to those without HL. HL with later age at onset and persistence to age 14\u2009years was the only trajectory associated with all outcomes.

Conclusions

Childhood HL may predict peer victimisation (in girls), depressive symptoms, and self-harm. Further research is needed to identify HL trajectories and methods to facilitate good mental health in children with HL.", + "abstract": "

Background

Progress towards stratified care for anxiety and depression will require the identification of new predictors. We collected data on retrospectively self-reported therapeutic outcomes in adults who received psychological therapy in the UK in the past ten years. We aimed to replicate factors associated with traditional treatment outcome measures from the literature.

Methods

Participants were from the Genetic Links to Anxiety and Depression (GLAD) Study, a UK-based volunteer cohort study. We investigated associations between retrospectively self-reported outcomes following therapy, on a five-point scale (global rating of change; GRC) and a range of sociodemographic, clinical and therapy-related factors, using ordinal logistic regression models (n\u2009=\u20092890).

Results

Four factors were associated with therapy outcomes (adjusted odds ratios, OR). One sociodemographic factor, having university-level education, was associated with favourable outcomes (OR\u2009=\u20091.37, 95%CI: 1.18, 1.59). Two clinical factors, greater number of reported episodes of illness (OR\u2009=\u20090.95, 95%CI: 0.92, 0.97) and higher levels of personality disorder symptoms (OR\u2009=\u20090.89, 95%CI: 0.87, 0.91), were associated with less favourable outcomes. Finally, reported regular use of additional therapeutic activities was associated with favourable outcomes (OR\u2009=\u20091.39, 95%CI: 1.19, 1.63). There were no statistically significant differences between fully adjusted multivariable and unadjusted univariable odds ratios.

Conclusion

Therapy outcome data can be collected quickly and inexpensively using retrospectively self-reported measures in large observational cohorts. Retrospectively self-reported therapy outcomes were associated with four factors previously reported in the literature. Similar data collected in larger observational cohorts may enable detection of novel associations with therapy outcomes, to generate new hypotheses, which can be followed up in prospective studies.", "laySummary": "", - "urls": "pdf:https://bmcpublichealth.biomedcentral.com/counter/pdf/10.1186/s12889-022-13457-6; doi:https://doi.org/10.1186/s12889-022-13457-6; html:https://europepmc.org/articles/PMC9131522; pdf:https://europepmc.org/articles/PMC9131522?pdf=render" + "urls": "pdf:https://bmcpsychiatry.biomedcentral.com/counter/pdf/10.1186/s12888-022-04275-6; doi:https://doi.org/10.1186/s12888-022-04275-6; html:https://europepmc.org/articles/PMC9675224; pdf:https://europepmc.org/articles/PMC9675224?pdf=render" }, { "id": "30949070", @@ -35359,6 +35342,23 @@ "laySummary": "", "urls": "pdf:https://www.frontiersin.org/articles/10.3389/fpsyt.2019.00109/pdf; doi:https://doi.org/10.3389/fpsyt.2019.00109; html:https://europepmc.org/articles/PMC6436079; pdf:https://europepmc.org/articles/PMC6436079?pdf=render" }, + { + "id": "35614427", + "doi": "https://doi.org/10.1186/s12889-022-13457-6", + "title": "The association between childhood hearing loss and self-reported peer victimisation, depressive symptoms, and self-harm: longitudinal analyses of a prospective, nationally representative cohort study.", + "authorString": "Butcher E, Cortina-Borja M, Dezateux C, Knowles R.", + "authorAffiliations": "", + "journalTitle": "BMC public health", + "pubYear": "2022", + "date": "2022-05-25", + "isOpenAccess": "Y", + "keywords": "Child; Hearing loss; Cohort studies; Mental health; Self-harm; Depressive Symptoms; Peer Victimisation", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Childhood hearing loss (HL) predicts poor mental health and is associated with a higher risk of communication difficulties. The relationship of childhood HL with specific types of poor mental health (such as depressive symptoms or self-harm) and peer victimisation remains unclear.

Methods

We analysed data from the Millennium Cohort Study (MCS), a prospective observational cohort study of children living in the UK at age 9\u2009months and born between 2000 to 2002. Data were available on the children and their families at ages 9\u2009months, then at 3, 5, 7, 11, and 14\u2009years. Participants were 10,858 singleton children with self-reported data on peer victimisation, depressive symptoms, and self-harm at age 14\u2009years. Multivariable logistic regression models were fitted to estimate odds ratios (OR) for HL with peer victimisation, depressive symptoms, and self-harm. HL presence was examined in terms of any HL between ages 9\u2009months and 14\u2009years, as well as by HL trajectory type (defined by onset and persistence). Analyses were adjusted for potential sources of confounding, survey design, and attrition at age 14\u2009years. Interactions between sex and HL were examined in each model and multiple imputation procedures used to address missing data.

Results

Children with any HL had increased odds of depressive symptoms (OR: 1.32, 95% CI: 1.09-1.60), self-harm (1.41, 1.12-1.78) and, in girls only, peer victimisation (girls: 1.81, 1.29-2.55; boys: 1.05, 0.73-1.51), compared to those without HL. HL with later age at onset and persistence to age 14\u2009years was the only trajectory associated with all outcomes.

Conclusions

Childhood HL may predict peer victimisation (in girls), depressive symptoms, and self-harm. Further research is needed to identify HL trajectories and methods to facilitate good mental health in children with HL.", + "laySummary": "", + "urls": "pdf:https://bmcpublichealth.biomedcentral.com/counter/pdf/10.1186/s12889-022-13457-6; doi:https://doi.org/10.1186/s12889-022-13457-6; html:https://europepmc.org/articles/PMC9131522; pdf:https://europepmc.org/articles/PMC9131522?pdf=render" + }, { "id": "31040096", "doi": "https://doi.org/10.1016/s2352-4642(19)30114-2", @@ -35444,23 +35444,6 @@ "laySummary": "", "urls": "pdf:https://www.nature.com/articles/s41431-021-00835-8.pdf; doi:https://doi.org/10.1038/s41431-021-00835-8; html:https://europepmc.org/articles/PMC8440598; pdf:https://europepmc.org/articles/PMC8440598?pdf=render" }, - { - "id": "36706770", - "doi": "https://doi.org/10.1016/s2214-109x(23)00007-4", - "title": "Global investments in pandemic preparedness and COVID-19: development assistance and domestic spending on health between 1990 and 2026.", - "authorString": "Global Burden of Disease 2021 Health Financing Collaborator Network.", - "authorAffiliations": "", - "journalTitle": "The Lancet. Global health", - "pubYear": "2023", - "date": "2023-01-24", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

The COVID-19 pandemic highlighted gaps in health surveillance systems, disease prevention, and treatment globally. Among the many factors that might have led to these gaps is the issue of the financing of national health systems, especially in low-income and middle-income countries (LMICs), as well as a robust global system for pandemic preparedness. We aimed to provide a comparative assessment of global health spending at the onset of the pandemic; characterise the amount of development assistance for pandemic preparedness and response disbursed in the first 2 years of the COVID-19 pandemic; and examine expectations for future health spending and put into context the expected need for investment in pandemic preparedness.

Methods

In this analysis of global health spending between 1990 and 2021, and prediction from 2021 to 2026, we estimated four sources of health spending: development assistance for health (DAH), government spending, out-of-pocket spending, and prepaid private spending across 204 countries and territories. We used the Organisation for Economic Co-operation and Development (OECD)'s Creditor Reporting System (CRS) and the WHO Global Health Expenditure Database (GHED) to estimate spending. We estimated development assistance for general health, COVID-19 response, and pandemic preparedness and response using a keyword search. Health spending estimates were combined with estimates of resources needed for pandemic prevention and preparedness to analyse future health spending patterns, relative to need.

Findings

In 2019, at the onset of the COVID-19 pandemic, US$9\u00b72 trillion (95% uncertainty interval [UI] 9\u00b71-9\u00b73) was spent on health worldwide. We found great disparities in the amount of resources devoted to health, with high-income countries spending $7\u00b73 trillion (95% UI 7\u00b72-7\u00b74) in 2019; 293\u00b77 times the $24\u00b78 billion (95% UI 24\u00b73-25\u00b73) spent by low-income countries in 2019. That same year, $43\u00b71 billion in development assistance was provided to maintain or improve health. The pandemic led to an unprecedented increase in development assistance targeted towards health; in 2020 and 2021, $1\u00b78 billion in DAH contributions was provided towards pandemic preparedness in LMICs, and $37\u00b78 billion was provided for the health-related COVID-19 response. Although the support for pandemic preparedness is 12\u00b72% of the recommended target by the High-Level Independent Panel (HLIP), the support provided for the health-related COVID-19 response is 252\u00b72% of the recommended target. Additionally, projected spending estimates suggest that between 2022 and 2026, governments in 17 (95% UI 11-21) of the 137 LMICs will observe an increase in national government health spending equivalent to an addition of 1% of GDP, as recommended by the HLIP.

Interpretation

There was an unprecedented scale-up in DAH in 2020 and 2021. We have a unique opportunity at this time to sustain funding for crucial global health functions, including pandemic preparedness. However, historical patterns of underfunding of pandemic preparedness suggest that deliberate effort must be made to ensure funding is maintained.

Funding

Bill & Melinda Gates Foundation.", - "laySummary": "", - "urls": "pdf:http://www.thelancet.com/article/S2214109X23000074/pdf; doi:https://doi.org/10.1016/S2214-109X(23)00007-4; html:https://europepmc.org/articles/PMC9998276" - }, { "id": "32548911", "doi": "https://doi.org/10.1002/ehf2.12779", @@ -35478,6 +35461,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1002/ehf2.12779; doi:https://doi.org/10.1002/ehf2.12779; html:https://europepmc.org/articles/PMC7524089; pdf:https://europepmc.org/articles/PMC7524089?pdf=render" }, + { + "id": "36706770", + "doi": "https://doi.org/10.1016/s2214-109x(23)00007-4", + "title": "Global investments in pandemic preparedness and COVID-19: development assistance and domestic spending on health between 1990 and 2026.", + "authorString": "Global Burden of Disease 2021 Health Financing Collaborator Network.", + "authorAffiliations": "", + "journalTitle": "The Lancet. Global health", + "pubYear": "2023", + "date": "2023-01-24", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

The COVID-19 pandemic highlighted gaps in health surveillance systems, disease prevention, and treatment globally. Among the many factors that might have led to these gaps is the issue of the financing of national health systems, especially in low-income and middle-income countries (LMICs), as well as a robust global system for pandemic preparedness. We aimed to provide a comparative assessment of global health spending at the onset of the pandemic; characterise the amount of development assistance for pandemic preparedness and response disbursed in the first 2 years of the COVID-19 pandemic; and examine expectations for future health spending and put into context the expected need for investment in pandemic preparedness.

Methods

In this analysis of global health spending between 1990 and 2021, and prediction from 2021 to 2026, we estimated four sources of health spending: development assistance for health (DAH), government spending, out-of-pocket spending, and prepaid private spending across 204 countries and territories. We used the Organisation for Economic Co-operation and Development (OECD)'s Creditor Reporting System (CRS) and the WHO Global Health Expenditure Database (GHED) to estimate spending. We estimated development assistance for general health, COVID-19 response, and pandemic preparedness and response using a keyword search. Health spending estimates were combined with estimates of resources needed for pandemic prevention and preparedness to analyse future health spending patterns, relative to need.

Findings

In 2019, at the onset of the COVID-19 pandemic, US$9\u00b72 trillion (95% uncertainty interval [UI] 9\u00b71-9\u00b73) was spent on health worldwide. We found great disparities in the amount of resources devoted to health, with high-income countries spending $7\u00b73 trillion (95% UI 7\u00b72-7\u00b74) in 2019; 293\u00b77 times the $24\u00b78 billion (95% UI 24\u00b73-25\u00b73) spent by low-income countries in 2019. That same year, $43\u00b71 billion in development assistance was provided to maintain or improve health. The pandemic led to an unprecedented increase in development assistance targeted towards health; in 2020 and 2021, $1\u00b78 billion in DAH contributions was provided towards pandemic preparedness in LMICs, and $37\u00b78 billion was provided for the health-related COVID-19 response. Although the support for pandemic preparedness is 12\u00b72% of the recommended target by the High-Level Independent Panel (HLIP), the support provided for the health-related COVID-19 response is 252\u00b72% of the recommended target. Additionally, projected spending estimates suggest that between 2022 and 2026, governments in 17 (95% UI 11-21) of the 137 LMICs will observe an increase in national government health spending equivalent to an addition of 1% of GDP, as recommended by the HLIP.

Interpretation

There was an unprecedented scale-up in DAH in 2020 and 2021. We have a unique opportunity at this time to sustain funding for crucial global health functions, including pandemic preparedness. However, historical patterns of underfunding of pandemic preparedness suggest that deliberate effort must be made to ensure funding is maintained.

Funding

Bill & Melinda Gates Foundation.", + "laySummary": "", + "urls": "pdf:http://www.thelancet.com/article/S2214109X23000074/pdf; doi:https://doi.org/10.1016/S2214-109X(23)00007-4; html:https://europepmc.org/articles/PMC9998276" + }, { "id": "37128097", "doi": "https://doi.org/10.1038/s43016-020-0092-z", @@ -35750,23 +35750,6 @@ "laySummary": "", "urls": "pdf:https://www.frontiersin.org/articles/10.3389/fmed.2019.00048/pdf; doi:https://doi.org/10.3389/fmed.2019.00048; html:https://europepmc.org/articles/PMC6449432; pdf:https://europepmc.org/articles/PMC6449432?pdf=render" }, - { - "id": "36204496", - "doi": "https://doi.org/10.1177/23992026211048421", - "title": "Beyond trust: Amplifying unheard voices on concerns about harm resulting from health data-sharing.", - "authorString": "Mulrine S, Blell M, Murtagh M.", - "authorAffiliations": "", - "journalTitle": "Medicine access @ point of care", - "pubYear": "2021", - "date": "2021-01-01", - "isOpenAccess": "Y", - "keywords": "Data; Qualitative Methods; Data-sharing; Underrepresented Groups", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

The point of care in many health systems is increasingly a point of health data generation, data which may be shared and used in a variety of ways by a range of different actors.

Aim

We set out to gather data about the perspectives on health data-sharing of people living in North East England who have been underrepresented within other public engagement activities and who are marginalized in society.

Methods

Multi-site ethnographic fieldwork was carried out in the Teesside region of England over a 6-month period in 2019 as part of a large-scale health data innovation program called Connected Health Cities. Organizations working with marginalized groups were contacted to recruit staff, volunteers, and beneficiaries for participation in qualitative research. The data gathered were analyzed thematically and vignettes constructed to illustrate findings.

Results

Previous encounters with health and social care professionals and the broader socio-political contexts of people's lives shape the perspectives of people from marginalized groups about sharing of data from their health records. While many would welcome improved care, the risks to people with socially produced vulnerabilities must be appreciated by those advocating systems that share data for personalized medicine or other forms of data-driven care.

Conclusion

Forms of innovation in medicine which rely on greater data-sharing may present risks to groups and individuals with existing vulnerabilities, and advocates of these innovations should address the lack of trustworthiness of those receiving data before asking that people trust new systems to provide health benefits.", - "laySummary": "", - "urls": "pdf:https://journals.sagepub.com/doi/pdf/10.1177/23992026211048421; doi:https://doi.org/10.1177/23992026211048421; html:https://europepmc.org/articles/PMC9413596; pdf:https://europepmc.org/articles/PMC9413596?pdf=render" - }, { "id": "31358974", "doi": "https://doi.org/10.1038/s41562-019-0653-z", @@ -35784,6 +35767,23 @@ "laySummary": "", "urls": "pdf:https://boris.unibe.ch/174991/1/nihms-1649425.pdf; doi:https://doi.org/10.1038/s41562-019-0653-z; html:https://europepmc.org/articles/PMC7711277; pdf:https://europepmc.org/articles/PMC7711277?pdf=render; doi:https://doi.org/10.1038/s41562-019-0653-z" }, + { + "id": "36204496", + "doi": "https://doi.org/10.1177/23992026211048421", + "title": "Beyond trust: Amplifying unheard voices on concerns about harm resulting from health data-sharing.", + "authorString": "Mulrine S, Blell M, Murtagh M.", + "authorAffiliations": "", + "journalTitle": "Medicine access @ point of care", + "pubYear": "2021", + "date": "2021-01-01", + "isOpenAccess": "Y", + "keywords": "Data; Qualitative Methods; Data-sharing; Underrepresented Groups", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

The point of care in many health systems is increasingly a point of health data generation, data which may be shared and used in a variety of ways by a range of different actors.

Aim

We set out to gather data about the perspectives on health data-sharing of people living in North East England who have been underrepresented within other public engagement activities and who are marginalized in society.

Methods

Multi-site ethnographic fieldwork was carried out in the Teesside region of England over a 6-month period in 2019 as part of a large-scale health data innovation program called Connected Health Cities. Organizations working with marginalized groups were contacted to recruit staff, volunteers, and beneficiaries for participation in qualitative research. The data gathered were analyzed thematically and vignettes constructed to illustrate findings.

Results

Previous encounters with health and social care professionals and the broader socio-political contexts of people's lives shape the perspectives of people from marginalized groups about sharing of data from their health records. While many would welcome improved care, the risks to people with socially produced vulnerabilities must be appreciated by those advocating systems that share data for personalized medicine or other forms of data-driven care.

Conclusion

Forms of innovation in medicine which rely on greater data-sharing may present risks to groups and individuals with existing vulnerabilities, and advocates of these innovations should address the lack of trustworthiness of those receiving data before asking that people trust new systems to provide health benefits.", + "laySummary": "", + "urls": "pdf:https://journals.sagepub.com/doi/pdf/10.1177/23992026211048421; doi:https://doi.org/10.1177/23992026211048421; html:https://europepmc.org/articles/PMC9413596; pdf:https://europepmc.org/articles/PMC9413596?pdf=render" + }, { "id": "36208161", "doi": "https://doi.org/10.1093/eurheartj/ehac426", @@ -35818,23 +35818,6 @@ "laySummary": "", "urls": "pdf:https://www.mdpi.com/2075-4426/11/8/814/pdf?version=1629458822; doi:https://doi.org/10.3390/jpm11080814; html:https://europepmc.org/articles/PMC8399452; pdf:https://europepmc.org/articles/PMC8399452?pdf=render" }, - { - "id": "38701403", - "doi": "https://doi.org/10.1212/wnl.0000000000209388", - "title": "Patent Foramen Ovale Closure in Older Patients With Stroke: Patient Selection for Trial Feasibility.", - "authorString": "Wang AY, Rothwell PM, Nelson J, Saver JL, Kasner SE, Carroll J, Mas JL, Derumeaux G, Chatellier G, Furlan AJ, Herrmann HC, J\u00fcni P, Kim JS, Koethe B, Lee PH, Lefebvre B, Mattle HP, Meier B, Reisman M, Smalling RW, Sondergaard L, Song JK, Di Angelantonio E, DiTullio M, Elkind MSV, Homma S, Jaigobin C, Michel P, Mono ML, Nedeltchev K, Papetti F, Serena J, Weimar C, Li L, Mazzucco S, Silver LE, van Klaveren D, Thaler DE, Kent DM.", - "authorAffiliations": "", - "journalTitle": "Neurology", - "pubYear": "2024", - "date": "2024-05-03", - "isOpenAccess": "N", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background and objectives

Whether patent foramen ovale (PFO) closure benefits older patients with PFO and cryptogenic stroke is unknown because randomized controlled trials (RCTs) have predominantly enrolled patients younger than 60 years of age. Our objective was to estimate anticipated effects of PFO closure in older patients to predict the numbers needed to plan an RCT.

Methods

Effectiveness estimates are derived from major observational studies (Risk of Paradoxical Embolism [RoPE] Study and Oxford Vascular Study, together referred to as the \"RoPE-Ox\" database) and all 6 major RCTs (Systematic, Collaborative, PFO Closure Evaluation [SCOPE] Consortium). To estimate stroke recurrence risk, observed outcomes were calculated for patients older than 60 years in the age-inclusive observational databases (n = 549). To estimate the reduction in the rate of recurrent stroke associated with PFO closure vs medical therapy based on the RoPE score and the presence of high-risk PFO features, a Cox proportional hazards regression model was developed on the RCT data in the SCOPE database (n = 3,740). These estimates were used to calculate sample sizes required for a future RCT.

Results

Five-year risk of stroke recurrence using Kaplan-Meier estimates was 13.7 (95% CI 10.5-17.9) overall, 14.9% (95% CI 10.2-21.6) in those with high-risk PFO features. Predicted relative reduction in the event rate with PFO closure was 12.9% overall, 48.8% in those with a high-risk PFO feature. Using these estimates, enrolling all older patients with cryptogenic stroke and PFO would require much larger samples than those used for prior PFO closure trials, but selectively enrolling patients with high-risk PFO features would require totals of 630 patients for 90% power and 471 patients for 80% power, with an average of 5 years of follow-up.

Discussion

Based on our projections, anticipated effect sizes in older patients with high-risk features make a trial in these subjects feasible. With lengthening life expectancy in almost all regions of the world, the utility of PFO closure in older adults is increasingly important to explore.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1212/WNL.0000000000209388" - }, { "id": "34167318", "doi": "https://doi.org/10.1161/circulationaha.121.054302", @@ -35852,6 +35835,23 @@ "laySummary": "", "urls": "pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCULATIONAHA.121.054302; doi:https://doi.org/10.1161/CIRCULATIONAHA.121.054302; html:https://europepmc.org/articles/PMC8360674; pdf:https://europepmc.org/articles/PMC8360674?pdf=render" }, + { + "id": "38701403", + "doi": "https://doi.org/10.1212/wnl.0000000000209388", + "title": "Patent Foramen Ovale Closure in Older Patients With Stroke: Patient Selection for Trial Feasibility.", + "authorString": "Wang AY, Rothwell PM, Nelson J, Saver JL, Kasner SE, Carroll J, Mas JL, Derumeaux G, Chatellier G, Furlan AJ, Herrmann HC, J\u00fcni P, Kim JS, Koethe B, Lee PH, Lefebvre B, Mattle HP, Meier B, Reisman M, Smalling RW, Sondergaard L, Song JK, Di Angelantonio E, DiTullio M, Elkind MSV, Homma S, Jaigobin C, Michel P, Mono ML, Nedeltchev K, Papetti F, Serena J, Weimar C, Li L, Mazzucco S, Silver LE, van Klaveren D, Thaler DE, Kent DM.", + "authorAffiliations": "", + "journalTitle": "Neurology", + "pubYear": "2024", + "date": "2024-05-03", + "isOpenAccess": "N", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background and objectives

Whether patent foramen ovale (PFO) closure benefits older patients with PFO and cryptogenic stroke is unknown because randomized controlled trials (RCTs) have predominantly enrolled patients younger than 60 years of age. Our objective was to estimate anticipated effects of PFO closure in older patients to predict the numbers needed to plan an RCT.

Methods

Effectiveness estimates are derived from major observational studies (Risk of Paradoxical Embolism [RoPE] Study and Oxford Vascular Study, together referred to as the \"RoPE-Ox\" database) and all 6 major RCTs (Systematic, Collaborative, PFO Closure Evaluation [SCOPE] Consortium). To estimate stroke recurrence risk, observed outcomes were calculated for patients older than 60 years in the age-inclusive observational databases (n = 549). To estimate the reduction in the rate of recurrent stroke associated with PFO closure vs medical therapy based on the RoPE score and the presence of high-risk PFO features, a Cox proportional hazards regression model was developed on the RCT data in the SCOPE database (n = 3,740). These estimates were used to calculate sample sizes required for a future RCT.

Results

Five-year risk of stroke recurrence using Kaplan-Meier estimates was 13.7 (95% CI 10.5-17.9) overall, 14.9% (95% CI 10.2-21.6) in those with high-risk PFO features. Predicted relative reduction in the event rate with PFO closure was 12.9% overall, 48.8% in those with a high-risk PFO feature. Using these estimates, enrolling all older patients with cryptogenic stroke and PFO would require much larger samples than those used for prior PFO closure trials, but selectively enrolling patients with high-risk PFO features would require totals of 630 patients for 90% power and 471 patients for 80% power, with an average of 5 years of follow-up.

Discussion

Based on our projections, anticipated effect sizes in older patients with high-risk features make a trial in these subjects feasible. With lengthening life expectancy in almost all regions of the world, the utility of PFO closure in older adults is increasingly important to explore.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1212/WNL.0000000000209388" + }, { "id": "31204027", "doi": "https://doi.org/10.1016/j.injury.2019.06.012", @@ -36261,21 +36261,21 @@ "urls": "pdf:https://www.nature.com/articles/s41379-021-00953-0.pdf; doi:https://doi.org/10.1038/s41379-021-00953-0; html:https://europepmc.org/articles/PMC8964416; pdf:https://europepmc.org/articles/PMC8964416?pdf=render" }, { - "id": "38296292", - "doi": "https://doi.org/10.1136/bmjopen-2023-078135", - "title": "Risk factor associations for severe COVID-19, influenza and pneumonia in people with diabetes to inform future pandemic preparations: UK population-based cohort study.", - "authorString": "Hopkins R, Young KG, Thomas NJ, Godwin J, Raja D, Mateen BA, Challen RJ, Vollmer SJ, Shields BM, McGovern AP, Dennis JM.", + "id": "31021418", + "doi": "https://doi.org/10.1111/bjd.18046", + "title": "'It's like the bad guy in a movie who just doesn't die': a\u00a0qualitative exploration of young people's adaptation to\u00a0eczema and implications for self-care.", + "authorString": "Ghio D, Muller I, Greenwell K, Roberts A, McNiven A, Langan SM, Santer M.", "authorAffiliations": "", - "journalTitle": "BMJ open", - "pubYear": "2024", - "date": "2024-01-31", + "journalTitle": "The British journal of dermatology", + "pubYear": "2020", + "date": "2019-07-28", "isOpenAccess": "Y", - "keywords": "risk factors; Electronic Health Records; Diabetes & Endocrinology; Covid-19", + "keywords": "", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Objective

This study aimed to compare clinical and sociodemographic risk factors for severe COVID-19, influenza and pneumonia, in people with diabetes.

Design

Population-based cohort study.

Setting

UK primary care records (Clinical Practice Research Datalink) linked to mortality and hospital records.

Participants

Individuals with type 1 and type 2 diabetes (COVID-19 cohort: n=43\u2009033\u2009type 1 diabetes and n=584\u2009854\u2009type 2 diabetes, influenza and pneumonia cohort: n=42\u2009488\u2009type 1 diabetes and n=585\u2009289\u2009type 2 diabetes).

Primary and secondary outcome measures

COVID-19 hospitalisation from 1 February 2020 to 31 October 2020 (pre-COVID-19 vaccination roll-out), and influenza and pneumonia hospitalisation from 1 September 2016 to 31 May 2019 (pre-COVID-19 pandemic). Secondary outcomes were COVID-19 and pneumonia mortality. Associations between clinical and sociodemographic risk factors and each outcome were assessed using multivariable Cox proportional hazards models. In people with type 2 diabetes, we explored modifying effects of glycated haemoglobin (HbA1c) and body mass index (BMI) by age, sex and ethnicity.

Results

In type 2 diabetes, poor glycaemic control and severe obesity were consistently associated with increased risk of hospitalisation for COVID-19, influenza and pneumonia. The highest HbA1c and BMI-associated relative risks were observed in people aged under 70 years. Sociodemographic-associated risk differed markedly by respiratory infection, particularly for ethnicity. Compared with people of white ethnicity, black and south Asian groups had a greater risk of COVID-19 hospitalisation, but a lesser risk of pneumonia hospitalisation. Risk factor associations for type 1 diabetes and for type 2 diabetes mortality were broadly consistent with the primary analysis.

Conclusions

Clinical risk factors of high HbA1c and severe obesity are consistently associated with severe outcomes from COVID-19, influenza and pneumonia, especially in younger people. In contrast, associations with sociodemographic risk factors differed by type of respiratory infection. This emphasises that risk stratification should be specific to individual respiratory infections.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1136/bmjopen-2023-078135; html:https://europepmc.org/articles/PMC10831438; pdf:https://europepmc.org/articles/PMC10831438?pdf=render" + "abstract": "

Background

Eczema is a common childhood inflammatory skin condition, affecting more than one in five children. A popular perception is that children 'outgrow eczema', although epidemiological studies have shown that, for many, eczema follows a lifelong episodic course.

Objectives

To explore the perceptions of young people about the nature of their eczema and how these perceptions relate to their self-care and adapting to living with eczema.

Methods

This is a secondary inductive thematic analysis of interviews conducted for Healthtalk.org. In total 23 interviews with young people with eczema were included. Of the 23 participants, 17 were female and six male, ranging from 17 to 25 years old.

Results

Participants generally experienced eczema as an episodic long-term condition and reported a mismatch between information received about eczema and their experiences. The experience of eczema as long term and episodic had implications for self-care, challenging the process of identifying triggers of eczema flare-ups and evaluating the success of treatment regimens. Participants' experiences of eczema over time also had implications for adaptation and finding a balance between accepting eczema as long term and hoping it would go away. This linked to a gradual shift in treatment expectations from 'cure' to 'control' of eczema.

Conclusions

For young people who continue to experience eczema beyond childhood, a greater focus on self-care for a long-term condition may be helpful. Greater awareness of the impact of early messages around 'growing out of' eczema and provision of high-quality information may help patients to manage expectations and support adaptation to treatment regimens. What's already known about this topic? There is a common perception that people 'grow out of' eczema, but for many people eczema follows a lifelong episodic course. Qualitative work has shown that parents can find that being told their child will grow out of eczema is dismissive, and that they have difficulty with messages about 'control not cure' of eczema. It is unclear how young people perceive their eczema and the implications of this perception for their adaptation and self-care. What does this study add? The message that many people 'grow out of' eczema has a potentially detrimental effect for young people where the condition persists. This has implications for young people's perceptions of their eczema, their learning to self-care and how they adapt to living with eczema and eczema treatments. What are the clinical implications of this work? Clinicians need to promote awareness among young people that eczema is a long-term episodic condition in order to engage them with effective self-care. Young people transitioning to self-care need evidence-based information that is specific and relatable to them.", + "laySummary": " ", + "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/bjd.18046; doi:https://doi.org/10.1111/bjd.18046; html:https://europepmc.org/articles/PMC6972719; pdf:https://europepmc.org/articles/PMC6972719?pdf=render" }, { "id": "35211795", @@ -36295,38 +36295,21 @@ "urls": "pdf:https://link.springer.com/content/pdf/10.1007/s00467-022-05440-5.pdf; doi:https://doi.org/10.1007/s00467-022-05440-5; html:https://europepmc.org/articles/PMC9489583; pdf:https://europepmc.org/articles/PMC9489583?pdf=render" }, { - "id": "31021418", - "doi": "https://doi.org/10.1111/bjd.18046", - "title": "'It's like the bad guy in a movie who just doesn't die': a\u00a0qualitative exploration of young people's adaptation to\u00a0eczema and implications for self-care.", - "authorString": "Ghio D, Muller I, Greenwell K, Roberts A, McNiven A, Langan SM, Santer M.", - "authorAffiliations": "", - "journalTitle": "The British journal of dermatology", - "pubYear": "2020", - "date": "2019-07-28", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Eczema is a common childhood inflammatory skin condition, affecting more than one in five children. A popular perception is that children 'outgrow eczema', although epidemiological studies have shown that, for many, eczema follows a lifelong episodic course.

Objectives

To explore the perceptions of young people about the nature of their eczema and how these perceptions relate to their self-care and adapting to living with eczema.

Methods

This is a secondary inductive thematic analysis of interviews conducted for Healthtalk.org. In total 23 interviews with young people with eczema were included. Of the 23 participants, 17 were female and six male, ranging from 17 to 25 years old.

Results

Participants generally experienced eczema as an episodic long-term condition and reported a mismatch between information received about eczema and their experiences. The experience of eczema as long term and episodic had implications for self-care, challenging the process of identifying triggers of eczema flare-ups and evaluating the success of treatment regimens. Participants' experiences of eczema over time also had implications for adaptation and finding a balance between accepting eczema as long term and hoping it would go away. This linked to a gradual shift in treatment expectations from 'cure' to 'control' of eczema.

Conclusions

For young people who continue to experience eczema beyond childhood, a greater focus on self-care for a long-term condition may be helpful. Greater awareness of the impact of early messages around 'growing out of' eczema and provision of high-quality information may help patients to manage expectations and support adaptation to treatment regimens. What's already known about this topic? There is a common perception that people 'grow out of' eczema, but for many people eczema follows a lifelong episodic course. Qualitative work has shown that parents can find that being told their child will grow out of eczema is dismissive, and that they have difficulty with messages about 'control not cure' of eczema. It is unclear how young people perceive their eczema and the implications of this perception for their adaptation and self-care. What does this study add? The message that many people 'grow out of' eczema has a potentially detrimental effect for young people where the condition persists. This has implications for young people's perceptions of their eczema, their learning to self-care and how they adapt to living with eczema and eczema treatments. What are the clinical implications of this work? Clinicians need to promote awareness among young people that eczema is a long-term episodic condition in order to engage them with effective self-care. Young people transitioning to self-care need evidence-based information that is specific and relatable to them.", - "laySummary": " ", - "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/bjd.18046; doi:https://doi.org/10.1111/bjd.18046; html:https://europepmc.org/articles/PMC6972719; pdf:https://europepmc.org/articles/PMC6972719?pdf=render" - }, - { - "id": "37221222", - "doi": "https://doi.org/10.1038/s41397-023-00307-w", - "title": "SLCO1B1*5 is protective against non-senile cataracts in cohort prescribed statins: analysis in a British-South Asian cohort.", - "authorString": "Magavern EF, van Heel DA, Genes & Health Research Team, Smedley D, Caulfield MJ.", + "id": "38296292", + "doi": "https://doi.org/10.1136/bmjopen-2023-078135", + "title": "Risk factor associations for severe COVID-19, influenza and pneumonia in people with diabetes to inform future pandemic preparations: UK population-based cohort study.", + "authorString": "Hopkins R, Young KG, Thomas NJ, Godwin J, Raja D, Mateen BA, Challen RJ, Vollmer SJ, Shields BM, McGovern AP, Dennis JM.", "authorAffiliations": "", - "journalTitle": "The pharmacogenomics journal", - "pubYear": "2023", - "date": "2023-05-23", + "journalTitle": "BMJ open", + "pubYear": "2024", + "date": "2024-01-31", "isOpenAccess": "Y", - "keywords": "", + "keywords": "risk factors; Electronic Health Records; Diabetes & Endocrinology; Covid-19", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Background

Reported association between statin use and cataract risk is controversial. The SLCO1B1 gene encodes a transport protein responsible for statin clearance. The aim of this study was to investigate a possible association between the SLCO1B1*5 reduced function variant and cataract risk in statin users of South Asian ethnicity.

Methods

The Genes & Health cohort consists of British-Bangladeshi and British-Pakistani participants from East London, Manchester and Bradford, UK. SLCO1B1*5 genotype was assessed with the Illumina GSAMD-24v3-0-EA chip. Medication data from primary care health record linkage was used to compare those who had regularly used statins compared to those who had not. Multivariable logistic regression was used to test for association between statin use and cataracts, adjusting for population characteristics and potential confounders in 36,513 participants. Multivariable logistic regression was used to test association between SLCO1B1*5 heterozygotes or homozygotes and cataracts, in subgroups having been regularly prescribed statins versus not.

Results

Statins were prescribed to 35% (12,704) of participants (average age 41 years old, 45% male). Non-senile cataract was diagnosed in 5% (1686) of participants. An apparent association between statins and non-senile cataract (12% in statin users and 0.8% in non-statin users) was negated by inclusion of confounders. In those prescribed a statin, presence of the SLCO1B1*5 genotype was independently associated with a decreased risk of non-senile cataract (OR 0.7 (CI 0.5-0.9, p 0.007)).

Conclusions

Our findings suggest that there is no independent association between statin use and non-senile cataract risk after adjusting for confounders. Among statin users, the SLCO1B1*5 genotype is associated with a 30% risk reduction of non-senile cataracts. Stratification of on-drug cohorts by validated pharmacogenomic variants is a useful tool to support or repudiate adverse drug events in observational cohorts.", + "abstract": "

Objective

This study aimed to compare clinical and sociodemographic risk factors for severe COVID-19, influenza and pneumonia, in people with diabetes.

Design

Population-based cohort study.

Setting

UK primary care records (Clinical Practice Research Datalink) linked to mortality and hospital records.

Participants

Individuals with type 1 and type 2 diabetes (COVID-19 cohort: n=43\u2009033\u2009type 1 diabetes and n=584\u2009854\u2009type 2 diabetes, influenza and pneumonia cohort: n=42\u2009488\u2009type 1 diabetes and n=585\u2009289\u2009type 2 diabetes).

Primary and secondary outcome measures

COVID-19 hospitalisation from 1 February 2020 to 31 October 2020 (pre-COVID-19 vaccination roll-out), and influenza and pneumonia hospitalisation from 1 September 2016 to 31 May 2019 (pre-COVID-19 pandemic). Secondary outcomes were COVID-19 and pneumonia mortality. Associations between clinical and sociodemographic risk factors and each outcome were assessed using multivariable Cox proportional hazards models. In people with type 2 diabetes, we explored modifying effects of glycated haemoglobin (HbA1c) and body mass index (BMI) by age, sex and ethnicity.

Results

In type 2 diabetes, poor glycaemic control and severe obesity were consistently associated with increased risk of hospitalisation for COVID-19, influenza and pneumonia. The highest HbA1c and BMI-associated relative risks were observed in people aged under 70 years. Sociodemographic-associated risk differed markedly by respiratory infection, particularly for ethnicity. Compared with people of white ethnicity, black and south Asian groups had a greater risk of COVID-19 hospitalisation, but a lesser risk of pneumonia hospitalisation. Risk factor associations for type 1 diabetes and for type 2 diabetes mortality were broadly consistent with the primary analysis.

Conclusions

Clinical risk factors of high HbA1c and severe obesity are consistently associated with severe outcomes from COVID-19, influenza and pneumonia, especially in younger people. In contrast, associations with sociodemographic risk factors differed by type of respiratory infection. This emphasises that risk stratification should be specific to individual respiratory infections.", "laySummary": "", - "urls": "pdf:https://www.nature.com/articles/s41397-023-00307-w.pdf; doi:https://doi.org/10.1038/s41397-023-00307-w; html:https://europepmc.org/articles/PMC10506906; pdf:https://europepmc.org/articles/PMC10506906?pdf=render" + "urls": "doi:https://doi.org/10.1136/bmjopen-2023-078135; html:https://europepmc.org/articles/PMC10831438; pdf:https://europepmc.org/articles/PMC10831438?pdf=render" }, { "id": "31950891", @@ -36345,6 +36328,23 @@ "laySummary": "This study uses data from a mental healthcare provider to predict 3 things: 1) extended duration of stay in a hospital, 2) the likelihood of needing to be admitted to hospital again after discharge, and 3) likehood of needing 'high intesity service' (high cost services). The authors developed a natural language processing model (a computer system than aims to interpret text and draw out useful information) to review the text, diagnoses, medications and the patient symptoms to work out which patients would fall within those 3 categories. They conclude that their model could be used to improve services through predicting users who will require the most intense and costly care.", "urls": "pdf:https://www.cambridge.org/core/services/aop-cambridge-core/content/view/6EF9FC74DC5A744C9D841DD649992ABE/S2056472419000966a.pdf/div-class-title-predicting-high-cost-care-in-a-mental-health-setting-div.pdf; doi:https://doi.org/10.1192/bjo.2019.96; html:https://europepmc.org/articles/PMC7001466; pdf:https://europepmc.org/articles/PMC7001466?pdf=render" }, + { + "id": "37221222", + "doi": "https://doi.org/10.1038/s41397-023-00307-w", + "title": "SLCO1B1*5 is protective against non-senile cataracts in cohort prescribed statins: analysis in a British-South Asian cohort.", + "authorString": "Magavern EF, van Heel DA, Genes & Health Research Team, Smedley D, Caulfield MJ.", + "authorAffiliations": "", + "journalTitle": "The pharmacogenomics journal", + "pubYear": "2023", + "date": "2023-05-23", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Reported association between statin use and cataract risk is controversial. The SLCO1B1 gene encodes a transport protein responsible for statin clearance. The aim of this study was to investigate a possible association between the SLCO1B1*5 reduced function variant and cataract risk in statin users of South Asian ethnicity.

Methods

The Genes & Health cohort consists of British-Bangladeshi and British-Pakistani participants from East London, Manchester and Bradford, UK. SLCO1B1*5 genotype was assessed with the Illumina GSAMD-24v3-0-EA chip. Medication data from primary care health record linkage was used to compare those who had regularly used statins compared to those who had not. Multivariable logistic regression was used to test for association between statin use and cataracts, adjusting for population characteristics and potential confounders in 36,513 participants. Multivariable logistic regression was used to test association between SLCO1B1*5 heterozygotes or homozygotes and cataracts, in subgroups having been regularly prescribed statins versus not.

Results

Statins were prescribed to 35% (12,704) of participants (average age 41 years old, 45% male). Non-senile cataract was diagnosed in 5% (1686) of participants. An apparent association between statins and non-senile cataract (12% in statin users and 0.8% in non-statin users) was negated by inclusion of confounders. In those prescribed a statin, presence of the SLCO1B1*5 genotype was independently associated with a decreased risk of non-senile cataract (OR 0.7 (CI 0.5-0.9, p 0.007)).

Conclusions

Our findings suggest that there is no independent association between statin use and non-senile cataract risk after adjusting for confounders. Among statin users, the SLCO1B1*5 genotype is associated with a 30% risk reduction of non-senile cataracts. Stratification of on-drug cohorts by validated pharmacogenomic variants is a useful tool to support or repudiate adverse drug events in observational cohorts.", + "laySummary": "", + "urls": "pdf:https://www.nature.com/articles/s41397-023-00307-w.pdf; doi:https://doi.org/10.1038/s41397-023-00307-w; html:https://europepmc.org/articles/PMC10506906; pdf:https://europepmc.org/articles/PMC10506906?pdf=render" + }, { "id": "34937765", "doi": "https://doi.org/10.1136/injuryprev-2021-044309", @@ -36600,23 +36600,6 @@ "laySummary": "Inflammation is a risk factor for cardiovascular disease (CVD) and is linked with a higher risk of cancer. This study investigates the relationship between inflammation and risk of cancer in patients with stable CVD. The study reports that low-grade inflammation, is a risk factor for incident cancer, markedly lung cancer, in patients with stable CVD.", "urls": "pdf:https://academic.oup.com/eurheartj/article-pdf/40/48/3901/32523962/ehz587.pdf; doi:https://doi.org/10.1093/eurheartj/ehz587; html:https://europepmc.org/articles/PMC6925382; pdf:https://europepmc.org/articles/PMC6925382?pdf=render" }, - { - "id": "37918923", - "doi": "https://doi.org/10.1136/bmjopen-2023-072531", - "title": "Evaluation of variation in special educational needs provision and its impact on health and education using administrative records for England: umbrella protocol for a mixed-methods research programme.", - "authorString": "Zylbersztejn A, Lewis K, Nguyen V, Matthews J, Winterburn I, Karwatowska L, Barnes S, Lilliman M, Saxton J, Stone A, Boddy K, Downs J, Logan S, Rahi J, Black-Hawkins K, Dearden L, Ford T, Harron K, De Stavola B, Gilbert R.", - "authorAffiliations": "", - "journalTitle": "BMJ open", - "pubYear": "2023", - "date": "2023-11-02", - "isOpenAccess": "Y", - "keywords": "epidemiology; Public Health; Qualitative Research; Health Informatics; Statistics & Research Methods; Health Equity", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Introduction

One-third of children in England have special educational needs (SEN) provision recorded during their school career. The proportion of children with SEN provision varies between schools and demographic groups, which may reflect variation in need, inequitable provision and/or systemic factors. There is scant evidence on whether SEN provision improves health and education outcomes.

Methods

The Health Outcomes of young People in Education (HOPE) research programme uses administrative data from the Education and Child Health Insights from Linked Data-ECHILD-which contains data from all state schools, and contacts with National Health Service hospitals in England, to explore variation in SEN provision and its impact on health and education outcomes. This umbrella protocol sets out analyses across four work packages (WP). WP1 defined a range of 'health phenotypes', that is health conditions expected to need SEN provision in primary school. Next, we describe health and education outcomes (WP1) and individual, school-level and area-level factors affecting variation in SEN provision across different phenotypes (WP2). WP3 assesses the impact of SEN provision on health and education outcomes for specific health phenotypes using a range of causal inference methods to account for confounding factors and possible selection bias. In WP4 we review local policies and synthesise findings from surveys, interviews and focus groups of service users and providers to understand factors associated with variation in and experiences of identification, assessment and provision for SEN. Triangulation of findings on outcomes, variation and impact of SEN provision for different health phenotypes in ECHILD, with experiences of SEN provision will inform interpretation of findings for policy, practice and families and methods for future evaluation.

Ethics and dissemination

Research ethics committees have approved the use of the ECHILD database and, separately, the survey, interviews and focus groups of young people, parents and service providers. These stakeholders will contribute to the design, interpretation and communication of findings.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1136/bmjopen-2023-072531; html:https://europepmc.org/articles/PMC10626865; pdf:https://europepmc.org/articles/PMC10626865?pdf=render" - }, { "id": "35353173", "doi": "https://doi.org/10.1001/jamapsychiatry.2022.0407", @@ -36634,6 +36617,23 @@ "laySummary": "", "urls": "html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8968718; doi:https://doi.org/10.1001/jamapsychiatry.2022.0407; html:https://europepmc.org/articles/PMC8968718" }, + { + "id": "37918923", + "doi": "https://doi.org/10.1136/bmjopen-2023-072531", + "title": "Evaluation of variation in special educational needs provision and its impact on health and education using administrative records for England: umbrella protocol for a mixed-methods research programme.", + "authorString": "Zylbersztejn A, Lewis K, Nguyen V, Matthews J, Winterburn I, Karwatowska L, Barnes S, Lilliman M, Saxton J, Stone A, Boddy K, Downs J, Logan S, Rahi J, Black-Hawkins K, Dearden L, Ford T, Harron K, De Stavola B, Gilbert R.", + "authorAffiliations": "", + "journalTitle": "BMJ open", + "pubYear": "2023", + "date": "2023-11-02", + "isOpenAccess": "Y", + "keywords": "epidemiology; Public Health; Qualitative Research; Health Informatics; Statistics & Research Methods; Health Equity", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Introduction

One-third of children in England have special educational needs (SEN) provision recorded during their school career. The proportion of children with SEN provision varies between schools and demographic groups, which may reflect variation in need, inequitable provision and/or systemic factors. There is scant evidence on whether SEN provision improves health and education outcomes.

Methods

The Health Outcomes of young People in Education (HOPE) research programme uses administrative data from the Education and Child Health Insights from Linked Data-ECHILD-which contains data from all state schools, and contacts with National Health Service hospitals in England, to explore variation in SEN provision and its impact on health and education outcomes. This umbrella protocol sets out analyses across four work packages (WP). WP1 defined a range of 'health phenotypes', that is health conditions expected to need SEN provision in primary school. Next, we describe health and education outcomes (WP1) and individual, school-level and area-level factors affecting variation in SEN provision across different phenotypes (WP2). WP3 assesses the impact of SEN provision on health and education outcomes for specific health phenotypes using a range of causal inference methods to account for confounding factors and possible selection bias. In WP4 we review local policies and synthesise findings from surveys, interviews and focus groups of service users and providers to understand factors associated with variation in and experiences of identification, assessment and provision for SEN. Triangulation of findings on outcomes, variation and impact of SEN provision for different health phenotypes in ECHILD, with experiences of SEN provision will inform interpretation of findings for policy, practice and families and methods for future evaluation.

Ethics and dissemination

Research ethics committees have approved the use of the ECHILD database and, separately, the survey, interviews and focus groups of young people, parents and service providers. These stakeholders will contribute to the design, interpretation and communication of findings.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1136/bmjopen-2023-072531; html:https://europepmc.org/articles/PMC10626865; pdf:https://europepmc.org/articles/PMC10626865?pdf=render" + }, { "id": "37253531", "doi": "https://doi.org/10.1136/bmjgh-2022-009997", @@ -36736,23 +36736,6 @@ "laySummary": "", "urls": "pdf:https://www.ahajournals.org/doi/pdf/10.1161/STROKEAHA.120.029042; doi:https://doi.org/10.1161/STROKEAHA.120.029042; html:https://europepmc.org/articles/PMC7382539; pdf:https://europepmc.org/articles/PMC7382539?pdf=render" }, - { - "id": "35477868", - "doi": "https://doi.org/10.1136/bmjopen-2021-057579", - "title": "Public opinion on sharing data from health services for clinical and research purposes without explicit consent: an anonymous online survey in the UK.", - "authorString": "Jones LA, Nelder JR, Fryer JM, Alsop PH, Geary MR, Prince M, Cardinal RN.", - "authorAffiliations": "", - "journalTitle": "BMJ open", - "pubYear": "2022", - "date": "2022-04-27", - "isOpenAccess": "Y", - "keywords": "Information management; Mental health; Health Policy; Health Informatics", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Objectives

UK National Health Service/Health and Social Care (NHS/HSC) data are variably shared between healthcare organisations for direct care, and increasingly de-identified for research. Few large-scale studies have examined public opinion on sharing, including of mental health (MH) versus physical health (PH) data. We measured data sharing preferences.

Design/setting/interventions/outcomes

Pre-registered anonymous online survey, measuring expressed preferences, recruiting February to September 2020. Participants were randomised to one of three framing statements regarding MH versus PH data.

Participants

Open to all UK residents. Participants numbered 29 275; 40% had experienced an MH condition.

Results

Most (76%) supported identifiable data sharing for direct clinical care without explicit consent, but 20% opposed this. Preference for clinical/identifiable sharing decreased with geographical distance and was slightly less for MH than PH data, with small framing effects. Preference for research/de-identified data sharing without explicit consent showed the same small PH/MH and framing effects, plus greater preference for sharing structured data than de-identified free text. There was net support for research sharing to the NHS, academic institutions, and national research charities, net ambivalence about sharing to profit-making companies researching treatments, and net opposition to sharing to other companies (similar to sharing publicly). De-identified linkage to non-health data was generally supported, except to data held by private companies. We report demographic influences on preference. A majority (89%) supported a single NHS mechanism to choose uses of their data. Support for data sharing increased during COVID-19.

Conclusions

Support for healthcare data sharing for direct care without explicit consent is broad but not universal. There is net support for the sharing of de-identified data for research to the NHS, academia, and the charitable sector, but not the commercial sector. A single national NHS-hosted system for patients to control the use of their NHS data for clinical purposes and for research would have broad support.

Trial registration number

ISRCTN37444142.", - "laySummary": "", - "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/12/4/e057579.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-057579; html:https://europepmc.org/articles/PMC9058801; pdf:https://europepmc.org/articles/PMC9058801?pdf=render" - }, { "id": "31748235", "doi": "https://doi.org/10.1136/bmj.l6055", @@ -36770,6 +36753,23 @@ "laySummary": "Kaura et al. used a large database of about a quarter of a million patients who had toponin measurements and concluded that there was an association between positive troponin results and mortality regardless of age ", "urls": "pdf:https://www.bmj.com/content/bmj/367/bmj.l6055.full.pdf; doi:https://doi.org/10.1136/bmj.l6055; html:https://europepmc.org/articles/PMC6865859" }, + { + "id": "35477868", + "doi": "https://doi.org/10.1136/bmjopen-2021-057579", + "title": "Public opinion on sharing data from health services for clinical and research purposes without explicit consent: an anonymous online survey in the UK.", + "authorString": "Jones LA, Nelder JR, Fryer JM, Alsop PH, Geary MR, Prince M, Cardinal RN.", + "authorAffiliations": "", + "journalTitle": "BMJ open", + "pubYear": "2022", + "date": "2022-04-27", + "isOpenAccess": "Y", + "keywords": "Information management; Mental health; Health Policy; Health Informatics", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Objectives

UK National Health Service/Health and Social Care (NHS/HSC) data are variably shared between healthcare organisations for direct care, and increasingly de-identified for research. Few large-scale studies have examined public opinion on sharing, including of mental health (MH) versus physical health (PH) data. We measured data sharing preferences.

Design/setting/interventions/outcomes

Pre-registered anonymous online survey, measuring expressed preferences, recruiting February to September 2020. Participants were randomised to one of three framing statements regarding MH versus PH data.

Participants

Open to all UK residents. Participants numbered 29 275; 40% had experienced an MH condition.

Results

Most (76%) supported identifiable data sharing for direct clinical care without explicit consent, but 20% opposed this. Preference for clinical/identifiable sharing decreased with geographical distance and was slightly less for MH than PH data, with small framing effects. Preference for research/de-identified data sharing without explicit consent showed the same small PH/MH and framing effects, plus greater preference for sharing structured data than de-identified free text. There was net support for research sharing to the NHS, academic institutions, and national research charities, net ambivalence about sharing to profit-making companies researching treatments, and net opposition to sharing to other companies (similar to sharing publicly). De-identified linkage to non-health data was generally supported, except to data held by private companies. We report demographic influences on preference. A majority (89%) supported a single NHS mechanism to choose uses of their data. Support for data sharing increased during COVID-19.

Conclusions

Support for healthcare data sharing for direct care without explicit consent is broad but not universal. There is net support for the sharing of de-identified data for research to the NHS, academia, and the charitable sector, but not the commercial sector. A single national NHS-hosted system for patients to control the use of their NHS data for clinical purposes and for research would have broad support.

Trial registration number

ISRCTN37444142.", + "laySummary": "", + "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/12/4/e057579.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-057579; html:https://europepmc.org/articles/PMC9058801; pdf:https://europepmc.org/articles/PMC9058801?pdf=render" + }, { "id": "35386118", "doi": "https://doi.org/10.3389/fnagi.2022.840651", @@ -36804,23 +36804,6 @@ "laySummary": "", "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/11/7/e049611.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-049611; html:https://europepmc.org/articles/PMC8275361; pdf:https://europepmc.org/articles/PMC8275361?pdf=render" }, - { - "id": "33664493", - "doi": "https://doi.org/10.1038/s41591-021-01275-z", - "title": "The need for ethical guidance for the use of patient-reported outcomes in research and clinical practice.", - "authorString": "Cruz Rivera S, Mercieca-Bebber R, Aiyegbusi OL, Scott J, Hunn A, Fernandez C, Ives J, Ells C, Price G, Draper H, Calvert MJ.", - "authorAffiliations": "", - "journalTitle": "Nature medicine", - "pubYear": "2021", - "date": "2021-04-01", - "isOpenAccess": "N", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "", - "laySummary": "", - "urls": "pdf:https://www.nature.com/articles/s41591-021-01275-z.pdf; doi:https://doi.org/10.1038/s41591-021-01275-z" - }, { "id": "31675503", "doi": "https://doi.org/10.1016/j.cell.2019.10.004", @@ -36838,6 +36821,23 @@ "laySummary": "", "urls": "pdf:http://www.cell.com/article/S0092867419311201/pdf; doi:https://doi.org/10.1016/j.cell.2019.10.004; html:https://europepmc.org/articles/PMC7202134; pdf:https://europepmc.org/articles/PMC7202134?pdf=render; doi:https://doi.org/10.1016/j.cell.2019.10.004" }, + { + "id": "33664493", + "doi": "https://doi.org/10.1038/s41591-021-01275-z", + "title": "The need for ethical guidance for the use of patient-reported outcomes in research and clinical practice.", + "authorString": "Cruz Rivera S, Mercieca-Bebber R, Aiyegbusi OL, Scott J, Hunn A, Fernandez C, Ives J, Ells C, Price G, Draper H, Calvert MJ.", + "authorAffiliations": "", + "journalTitle": "Nature medicine", + "pubYear": "2021", + "date": "2021-04-01", + "isOpenAccess": "N", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "", + "laySummary": "", + "urls": "pdf:https://www.nature.com/articles/s41591-021-01275-z.pdf; doi:https://doi.org/10.1038/s41591-021-01275-z" + }, { "id": "36647047", "doi": "https://doi.org/10.1186/s12916-022-02722-5", @@ -37382,23 +37382,6 @@ "laySummary": "", "urls": "pdf:https://researchonline.lshtm.ac.uk/id/eprint/4660358/1/Global%20and%20national%20estimates%20of%20the%20number%20of%20healthcare%20workers%20at%20high%20risk%20of%20SARS-CoV-2%20infection.pdf; doi:https://doi.org/10.1016/j.jhin.2021.02.012; html:https://europepmc.org/articles/PMC7896121; pdf:https://europepmc.org/articles/PMC7896121?pdf=render" }, - { - "id": "38448586", - "doi": "https://doi.org/10.1038/s41586-024-07148-y", - "title": "Genome-wide characterization of circulating metabolic biomarkers.", - "authorString": "Karjalainen MK, Karthikeyan S, Oliver-Williams C, Sliz E, Allara E, Fung WT, Surendran P, Zhang W, Jousilahti P, Kristiansson K, Salomaa V, Goodwin M, Hughes DA, Boehnke M, Fernandes Silva L, Yin X, Mahajan A, Neville MJ, van Zuydam NR, de Mutsert R, Li-Gao R, Mook-Kanamori DO, Demirkan A, Liu J, Noordam R, Trompet S, Chen Z, Kartsonaki C, Li L, Lin K, Hagenbeek FA, Hottenga JJ, Pool R, Ikram MA, van Meurs J, Haller T, Milaneschi Y, K\u00e4h\u00f6nen M, Mishra PP, Joshi PK, Macdonald-Dunlop E, Mangino M, Zierer J, Acar IE, Hoyng CB, Lechanteur YTE, Franke L, Kurilshikov A, Zhernakova A, Beekman M, van den Akker EB, Kolcic I, Polasek O, Rudan I, Gieger C, Waldenberger M, Asselbergs FW, China Kadoorie Biobank Collaborative Group, Estonian Biobank Research Team, FinnGen, Hayward C, Fu J, den Hollander AI, Menni C, Spector TD, Wilson JF, Lehtim\u00e4ki T, Raitakari OT, Penninx BWJH, Esko T, Walters RG, Jukema JW, Sattar N, Ghanbari M, Willems van Dijk K, Karpe F, McCarthy MI, Laakso M, J\u00e4rvelin MR, Timpson NJ, Perola M, Kooner JS, Chambers JC, van Duijn C, Slagboom PE, Boomsma DI, Danesh J, Ala-Korpela M, Butterworth AS, Kettunen J.", - "authorAffiliations": "", - "journalTitle": "Nature", - "pubYear": "2024", - "date": "2024-03-06", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Genome-wide association analyses using high-throughput metabolomics platforms have led to novel insights into the biology of human metabolism1-7. This detailed knowledge of the genetic determinants of systemic metabolism has been pivotal for uncovering how genetic pathways influence biological mechanisms and complex diseases8-11. Here we present a genome-wide association study for 233 circulating metabolic traits quantified by nuclear magnetic resonance spectroscopy in up to 136,016 participants from 33 cohorts. We identify more than 400 independent loci and assign probable causal genes at two-thirds of these using manual curation of plausible biological candidates. We highlight the importance of sample and participant characteristics that can have significant effects on genetic associations. We use detailed metabolic profiling of lipoprotein- and lipid-associated variants to better characterize how known lipid loci and novel loci affect lipoprotein metabolism at a granular level. We demonstrate the translational utility of comprehensively phenotyped molecular data, characterizing the metabolic associations of intrahepatic cholestasis of pregnancy. Finally, we observe substantial genetic pleiotropy for multiple metabolic pathways and illustrate the importance of careful instrument selection in Mendelian randomization analysis, revealing a putative causal relationship between acetone and hypertension. Our publicly available results provide a foundational resource for the community to examine the role of metabolism across diverse diseases.", - "laySummary": "", - "urls": "pdf:https://www.nature.com/articles/s41586-024-07148-y.pdf; doi:https://doi.org/10.1038/s41586-024-07148-y; html:https://europepmc.org/articles/PMC10990933; pdf:https://europepmc.org/articles/PMC10990933?pdf=render" - }, { "id": "33430602", "doi": "https://doi.org/10.1161/circheartfailure.120.007022", @@ -37416,6 +37399,23 @@ "laySummary": "", "urls": "pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCHEARTFAILURE.120.007022; doi:https://doi.org/10.1161/CIRCHEARTFAILURE.120.007022; html:https://europepmc.org/articles/PMC7819533; pdf:https://europepmc.org/articles/PMC7819533?pdf=render" }, + { + "id": "38448586", + "doi": "https://doi.org/10.1038/s41586-024-07148-y", + "title": "Genome-wide characterization of circulating metabolic biomarkers.", + "authorString": "Karjalainen MK, Karthikeyan S, Oliver-Williams C, Sliz E, Allara E, Fung WT, Surendran P, Zhang W, Jousilahti P, Kristiansson K, Salomaa V, Goodwin M, Hughes DA, Boehnke M, Fernandes Silva L, Yin X, Mahajan A, Neville MJ, van Zuydam NR, de Mutsert R, Li-Gao R, Mook-Kanamori DO, Demirkan A, Liu J, Noordam R, Trompet S, Chen Z, Kartsonaki C, Li L, Lin K, Hagenbeek FA, Hottenga JJ, Pool R, Ikram MA, van Meurs J, Haller T, Milaneschi Y, K\u00e4h\u00f6nen M, Mishra PP, Joshi PK, Macdonald-Dunlop E, Mangino M, Zierer J, Acar IE, Hoyng CB, Lechanteur YTE, Franke L, Kurilshikov A, Zhernakova A, Beekman M, van den Akker EB, Kolcic I, Polasek O, Rudan I, Gieger C, Waldenberger M, Asselbergs FW, China Kadoorie Biobank Collaborative Group, Estonian Biobank Research Team, FinnGen, Hayward C, Fu J, den Hollander AI, Menni C, Spector TD, Wilson JF, Lehtim\u00e4ki T, Raitakari OT, Penninx BWJH, Esko T, Walters RG, Jukema JW, Sattar N, Ghanbari M, Willems van Dijk K, Karpe F, McCarthy MI, Laakso M, J\u00e4rvelin MR, Timpson NJ, Perola M, Kooner JS, Chambers JC, van Duijn C, Slagboom PE, Boomsma DI, Danesh J, Ala-Korpela M, Butterworth AS, Kettunen J.", + "authorAffiliations": "", + "journalTitle": "Nature", + "pubYear": "2024", + "date": "2024-03-06", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Genome-wide association analyses using high-throughput metabolomics platforms have led to novel insights into the biology of human metabolism1-7. This detailed knowledge of the genetic determinants of systemic metabolism has been pivotal for uncovering how genetic pathways influence biological mechanisms and complex diseases8-11. Here we present a genome-wide association study for 233 circulating metabolic traits quantified by nuclear magnetic resonance spectroscopy in up to 136,016 participants from 33 cohorts. We identify more than 400 independent loci and assign probable causal genes at two-thirds of these using manual curation of plausible biological candidates. We highlight the importance of sample and participant characteristics that can have significant effects on genetic associations. We use detailed metabolic profiling of lipoprotein- and lipid-associated variants to better characterize how known lipid loci and novel loci affect lipoprotein metabolism at a granular level. We demonstrate the translational utility of comprehensively phenotyped molecular data, characterizing the metabolic associations of intrahepatic cholestasis of pregnancy. Finally, we observe substantial genetic pleiotropy for multiple metabolic pathways and illustrate the importance of careful instrument selection in Mendelian randomization analysis, revealing a putative causal relationship between acetone and hypertension. Our publicly available results provide a foundational resource for the community to examine the role of metabolism across diverse diseases.", + "laySummary": "", + "urls": "pdf:https://www.nature.com/articles/s41586-024-07148-y.pdf; doi:https://doi.org/10.1038/s41586-024-07148-y; html:https://europepmc.org/articles/PMC10990933; pdf:https://europepmc.org/articles/PMC10990933?pdf=render" + }, { "id": "35605170", "doi": "https://doi.org/10.2196/37668", @@ -37603,23 +37603,6 @@ "laySummary": "", "urls": "pdf:https://www.ahajournals.org/doi/pdf/10.1161/JAHA.121.025935; doi:https://doi.org/10.1161/JAHA.121.025935; html:https://europepmc.org/articles/PMC9707839; pdf:https://europepmc.org/articles/PMC9707839?pdf=render" }, - { - "id": "34645462", - "doi": "https://doi.org/10.1186/s12974-021-02287-9", - "title": "T lymphocyte senescence is attenuated in Parkinson's disease.", - "authorString": "Kouli A, Jensen M, Papastavrou V, Scott KM, Kolenda C, Parker C, Solim IH, Camacho M, Martin-Ruiz C, Williams-Gray CH.", - "authorAffiliations": "", - "journalTitle": "Journal of neuroinflammation", - "pubYear": "2021", - "date": "2021-10-13", - "isOpenAccess": "Y", - "keywords": "T lymphocytes; Immunosenescence; Parkinson\u2019s Disease; Ageing Markers", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Immune involvement is well-described in Parkinson's disease (PD), including an adaptive T lymphocyte response. Given the increasing prevalence of Parkinson's disease in older age, age-related dysregulation of T lymphocytes may be relevant in this disorder, and we have previously observed changes in age-associated CD8+ T cell subsets in mid-stage PD. This study aimed to further characterise T cell immunosenescence in newly diagnosed PD patients, including shifts in CD4+ and CD8+ subpopulations, and changes in markers of cellular ageing in CD8+ T lymphocytes.

Methods

Peripheral blood mononuclear cells were extracted from the blood of 61 newly diagnosed PD patients and 63 age- and sex-matched controls. Flow cytometric analysis was used for immunophenotyping of CD8+ and CD4+ lymphocyte subsets, and analysis of recent thymic emigrant cells. Telomere length within\u00a0CD8+ T lymphocytes was assessed, as well as the expression of the telomerase reverse transcriptase enzyme (hTERT), and the cell-ageing markers p16INK4a and p21CIP1/Waf1.

Results

The number of CD8+ TEMRA T cells was found to be significantly reduced in PD patients compared to controls. The expression of p16INK4a in CD8+ lymphocytes was also lower in patients versus controls. Chronic latent CMV infection was associated with increased senescent CD8+ lymphocytes in healthy controls, but this shift was less apparent in PD patients.

Conclusions

Taken together, our data demonstrate a reduction in CD8+ T cell replicative senescence which is present at the earliest stages of Parkinson's disease.", - "laySummary": "", - "urls": "pdf:https://jneuroinflammation.biomedcentral.com/track/pdf/10.1186/s12974-021-02287-9; doi:https://doi.org/10.1186/s12974-021-02287-9; html:https://europepmc.org/articles/PMC8513368; pdf:https://europepmc.org/articles/PMC8513368?pdf=render" - }, { "id": "33777379", "doi": "https://doi.org/10.1093/ckj/sfaa045", @@ -37637,6 +37620,23 @@ "laySummary": "", "urls": "pdf:https://academic.oup.com/ckj/article-pdf/14/3/950/36670473/sfaa045.pdf; doi:https://doi.org/10.1093/ckj/sfaa045; html:https://europepmc.org/articles/PMC7986362; pdf:https://europepmc.org/articles/PMC7986362?pdf=render" }, + { + "id": "34645462", + "doi": "https://doi.org/10.1186/s12974-021-02287-9", + "title": "T lymphocyte senescence is attenuated in Parkinson's disease.", + "authorString": "Kouli A, Jensen M, Papastavrou V, Scott KM, Kolenda C, Parker C, Solim IH, Camacho M, Martin-Ruiz C, Williams-Gray CH.", + "authorAffiliations": "", + "journalTitle": "Journal of neuroinflammation", + "pubYear": "2021", + "date": "2021-10-13", + "isOpenAccess": "Y", + "keywords": "T lymphocytes; Immunosenescence; Parkinson\u2019s Disease; Ageing Markers", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Immune involvement is well-described in Parkinson's disease (PD), including an adaptive T lymphocyte response. Given the increasing prevalence of Parkinson's disease in older age, age-related dysregulation of T lymphocytes may be relevant in this disorder, and we have previously observed changes in age-associated CD8+ T cell subsets in mid-stage PD. This study aimed to further characterise T cell immunosenescence in newly diagnosed PD patients, including shifts in CD4+ and CD8+ subpopulations, and changes in markers of cellular ageing in CD8+ T lymphocytes.

Methods

Peripheral blood mononuclear cells were extracted from the blood of 61 newly diagnosed PD patients and 63 age- and sex-matched controls. Flow cytometric analysis was used for immunophenotyping of CD8+ and CD4+ lymphocyte subsets, and analysis of recent thymic emigrant cells. Telomere length within\u00a0CD8+ T lymphocytes was assessed, as well as the expression of the telomerase reverse transcriptase enzyme (hTERT), and the cell-ageing markers p16INK4a and p21CIP1/Waf1.

Results

The number of CD8+ TEMRA T cells was found to be significantly reduced in PD patients compared to controls. The expression of p16INK4a in CD8+ lymphocytes was also lower in patients versus controls. Chronic latent CMV infection was associated with increased senescent CD8+ lymphocytes in healthy controls, but this shift was less apparent in PD patients.

Conclusions

Taken together, our data demonstrate a reduction in CD8+ T cell replicative senescence which is present at the earliest stages of Parkinson's disease.", + "laySummary": "", + "urls": "pdf:https://jneuroinflammation.biomedcentral.com/track/pdf/10.1186/s12974-021-02287-9; doi:https://doi.org/10.1186/s12974-021-02287-9; html:https://europepmc.org/articles/PMC8513368; pdf:https://europepmc.org/articles/PMC8513368?pdf=render" + }, { "id": "36244350", "doi": "https://doi.org/10.1016/s2468-2667(22)00225-0", @@ -37943,23 +37943,6 @@ "laySummary": "", "urls": "pdf:http://www.thelancet.com/article/S0140673622011096/pdf; doi:https://doi.org/10.1016/S0140-6736(22)01109-6; html:https://europepmc.org/articles/PMC9333998; pdf:https://europepmc.org/articles/PMC9333998?pdf=render" }, - { - "id": "37188768", - "doi": "https://doi.org/10.1038/s42003-023-04836-9", - "title": "Fine-mapping of retinal vascular complexity loci identifies Notch regulation as a shared mechanism with myocardial infarction outcomes.", - "authorString": "Villaplana-Velasco A, Pigeyre M, Engelmann J, Rawlik K, Canela-Xandri O, Tochel C, Lona-Durazo F, Mookiah MRK, Doney A, Parra EJ, Trucco E, MacGillivray T, Rannikmae K, Tenesa A, Pairo-Castineira E, Bernabeu MO.", - "authorAffiliations": "", - "journalTitle": "Communications biology", - "pubYear": "2023", - "date": "2023-05-15", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "There is increasing evidence that the complexity of the retinal vasculature measured as fractal dimension, Df, might offer earlier insights into the progression of coronary artery disease (CAD) before traditional biomarkers can be detected. This association could be partly explained by a common genetic basis; however, the genetic component of Df is poorly understood. We present a genome-wide association study (GWAS) of 38,000 individuals with white British ancestry from the UK Biobank aimed to comprehensively study the genetic component of Df and analyse its relationship with CAD. We replicated 5 Df loci and found 4 additional loci with suggestive significance (P\u2009<\u20091e-05) to contribute to Df variation, which previously were reported in retinal tortuosity and complexity, hypertension, and CAD studies. Significant negative genetic correlation estimates support the inverse relationship between Df and CAD, and between Df and myocardial infarction (MI), one of CAD's fatal outcomes. Fine-mapping of Df loci revealed Notch signalling regulatory variants supporting a shared mechanism with MI outcomes. We developed a predictive model for MI incident cases, recorded over a 10-year period following clinical and ophthalmic evaluation, combining clinical information, Df, and a CAD polygenic risk score. Internal cross-validation demonstrated a considerable improvement in the area under the curve (AUC) of our predictive model (AUC\u2009=\u20090.770\u2009\u00b1\u20090.001) when comparing with an established risk model, SCORE, (AUC\u2009=\u20090.741\u2009\u00b1\u20090.002) and extensions thereof leveraging the PRS (AUC\u2009=\u20090.728\u2009\u00b1\u20090.001). This evidences that Df provides risk information beyond demographic, lifestyle, and genetic risk factors. Our findings shed new light on the genetic basis of Df, unveiling a common control with MI, and highlighting the benefits of its application in individualised MI risk prediction.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1038/s42003-023-04836-9; html:https://europepmc.org/articles/PMC10185685; pdf:https://europepmc.org/articles/PMC10185685?pdf=render" - }, { "id": "32546850", "doi": "https://doi.org/10.1038/s41598-020-66737-9", @@ -37977,6 +37960,23 @@ "laySummary": "", "urls": "pdf:https://www.nature.com/articles/s41598-020-66737-9.pdf; doi:https://doi.org/10.1038/s41598-020-66737-9; html:https://europepmc.org/articles/PMC7297971; pdf:https://europepmc.org/articles/PMC7297971?pdf=render" }, + { + "id": "37188768", + "doi": "https://doi.org/10.1038/s42003-023-04836-9", + "title": "Fine-mapping of retinal vascular complexity loci identifies Notch regulation as a shared mechanism with myocardial infarction outcomes.", + "authorString": "Villaplana-Velasco A, Pigeyre M, Engelmann J, Rawlik K, Canela-Xandri O, Tochel C, Lona-Durazo F, Mookiah MRK, Doney A, Parra EJ, Trucco E, MacGillivray T, Rannikmae K, Tenesa A, Pairo-Castineira E, Bernabeu MO.", + "authorAffiliations": "", + "journalTitle": "Communications biology", + "pubYear": "2023", + "date": "2023-05-15", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "There is increasing evidence that the complexity of the retinal vasculature measured as fractal dimension, Df, might offer earlier insights into the progression of coronary artery disease (CAD) before traditional biomarkers can be detected. This association could be partly explained by a common genetic basis; however, the genetic component of Df is poorly understood. We present a genome-wide association study (GWAS) of 38,000 individuals with white British ancestry from the UK Biobank aimed to comprehensively study the genetic component of Df and analyse its relationship with CAD. We replicated 5 Df loci and found 4 additional loci with suggestive significance (P\u2009<\u20091e-05) to contribute to Df variation, which previously were reported in retinal tortuosity and complexity, hypertension, and CAD studies. Significant negative genetic correlation estimates support the inverse relationship between Df and CAD, and between Df and myocardial infarction (MI), one of CAD's fatal outcomes. Fine-mapping of Df loci revealed Notch signalling regulatory variants supporting a shared mechanism with MI outcomes. We developed a predictive model for MI incident cases, recorded over a 10-year period following clinical and ophthalmic evaluation, combining clinical information, Df, and a CAD polygenic risk score. Internal cross-validation demonstrated a considerable improvement in the area under the curve (AUC) of our predictive model (AUC\u2009=\u20090.770\u2009\u00b1\u20090.001) when comparing with an established risk model, SCORE, (AUC\u2009=\u20090.741\u2009\u00b1\u20090.002) and extensions thereof leveraging the PRS (AUC\u2009=\u20090.728\u2009\u00b1\u20090.001). This evidences that Df provides risk information beyond demographic, lifestyle, and genetic risk factors. Our findings shed new light on the genetic basis of Df, unveiling a common control with MI, and highlighting the benefits of its application in individualised MI risk prediction.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1038/s42003-023-04836-9; html:https://europepmc.org/articles/PMC10185685; pdf:https://europepmc.org/articles/PMC10185685?pdf=render" + }, { "id": "37538507", "doi": "https://doi.org/10.1016/j.rpth.2023.100175", @@ -38470,23 +38470,6 @@ "laySummary": "", "urls": "pdf:https://www.nature.com/articles/s42003-020-0857-9.pdf; doi:https://doi.org/10.1038/s42003-020-0857-9; html:https://europepmc.org/articles/PMC7078216; pdf:https://europepmc.org/articles/PMC7078216?pdf=render" }, - { - "id": "33905495", - "doi": "https://doi.org/10.1093/nar/gkab291", - "title": "Endonuclease enrichment TAPS for cost-effective genome-wide base-resolution DNA methylation detection.", - "authorString": "Cheng J, Siejka-Zieli\u0144ska P, Liu Y, Chandran A, Kriaucionis S, Song CX.", - "authorAffiliations": "", - "journalTitle": "Nucleic acids research", - "pubYear": "2021", - "date": "2021-07-01", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Whole genome base-resolution methylome sequencing allows for the most comprehensive analysis of DNA methylation, however, the considerable sequencing cost often limits its applications. While reduced representation sequencing can be an affordable alternative, over 80% of CpGs in the genome are not covered. Building on our recently developed TET-assisted pyridine borane sequencing (TAPS) method, we here described endonuclease enrichment TAPS (eeTAPS), which utilizes dihydrouracil (DHU)-cleaving endonuclease digestion of TAPS-converted DNA to enrich methylated CpG sites (mCpGs). eeTAPS can accurately detect 87% of mCpGs in the mouse genome with a sequencing depth equivalent to 4\u00d7 whole genome sequencing. In comparison, reduced representation TAPS (rrTAPS) detected less than 4% of mCpGs with 2.5\u00d7 sequencing depth. Our results demonstrate eeTAPS to be a new strategy for cost-effective genome-wide methylation analysis at single-CpG resolution that can fill the gap between whole-genome and reduced representation sequencing.", - "laySummary": "", - "urls": "pdf:https://ora.ox.ac.uk/objects/uuid:3e48f9e0-d3c3-41ec-99ff-cc64d141d6cf/files/rcz30pt21m; doi:https://doi.org/10.1093/nar/gkab291; html:https://europepmc.org/articles/PMC8287915; pdf:https://europepmc.org/articles/PMC8287915?pdf=render" - }, { "id": "30681347", "doi": "https://doi.org/10.1161/circgen.118.002328", @@ -38504,6 +38487,23 @@ "laySummary": "", "urls": "pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCGEN.118.002328; doi:https://doi.org/10.1161/CIRCGEN.118.002328; html:https://europepmc.org/articles/PMC6380958; pdf:https://europepmc.org/articles/PMC6380958?pdf=render; doi:https://doi.org/10.1161/circgen.118.002328" }, + { + "id": "33905495", + "doi": "https://doi.org/10.1093/nar/gkab291", + "title": "Endonuclease enrichment TAPS for cost-effective genome-wide base-resolution DNA methylation detection.", + "authorString": "Cheng J, Siejka-Zieli\u0144ska P, Liu Y, Chandran A, Kriaucionis S, Song CX.", + "authorAffiliations": "", + "journalTitle": "Nucleic acids research", + "pubYear": "2021", + "date": "2021-07-01", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Whole genome base-resolution methylome sequencing allows for the most comprehensive analysis of DNA methylation, however, the considerable sequencing cost often limits its applications. While reduced representation sequencing can be an affordable alternative, over 80% of CpGs in the genome are not covered. Building on our recently developed TET-assisted pyridine borane sequencing (TAPS) method, we here described endonuclease enrichment TAPS (eeTAPS), which utilizes dihydrouracil (DHU)-cleaving endonuclease digestion of TAPS-converted DNA to enrich methylated CpG sites (mCpGs). eeTAPS can accurately detect 87% of mCpGs in the mouse genome with a sequencing depth equivalent to 4\u00d7 whole genome sequencing. In comparison, reduced representation TAPS (rrTAPS) detected less than 4% of mCpGs with 2.5\u00d7 sequencing depth. Our results demonstrate eeTAPS to be a new strategy for cost-effective genome-wide methylation analysis at single-CpG resolution that can fill the gap between whole-genome and reduced representation sequencing.", + "laySummary": "", + "urls": "pdf:https://ora.ox.ac.uk/objects/uuid:3e48f9e0-d3c3-41ec-99ff-cc64d141d6cf/files/rcz30pt21m; doi:https://doi.org/10.1093/nar/gkab291; html:https://europepmc.org/articles/PMC8287915; pdf:https://europepmc.org/articles/PMC8287915?pdf=render" + }, { "id": "35103486", "doi": "https://doi.org/10.1128/msystems.01132-21", @@ -38555,23 +38555,6 @@ "laySummary": "", "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/12/4/e056541.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-056541; html:https://europepmc.org/articles/PMC9058769; pdf:https://europepmc.org/articles/PMC9058769?pdf=render" }, - { - "id": "37247330", - "doi": "https://doi.org/10.1093/eurheartj/ehad260", - "title": "SCORE2-Diabetes: 10-year cardiovascular risk estimation in type 2 diabetes in Europe.", - "authorString": "SCORE2-Diabetes Working Group and the ESC Cardiovascular Risk Collaboration.", - "authorAffiliations": "", - "journalTitle": "European heart journal", - "pubYear": "2023", - "date": "2023-07-01", - "isOpenAccess": "Y", - "keywords": "Cardiovascular diseases; Prediction model; Diabetes", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Aims

To develop and validate a recalibrated prediction model (SCORE2-Diabetes) to estimate the 10-year risk of cardiovascular disease (CVD) in individuals with type 2 diabetes in Europe.

Methods and results

SCORE2-Diabetes was developed by extending SCORE2 algorithms using individual-participant data from four large-scale datasets comprising 229 460 participants (43 706 CVD events) with type 2 diabetes and without previous CVD. Sex-specific competing risk-adjusted models were used including conventional risk factors (i.e. age, smoking, systolic blood pressure, total, and HDL-cholesterol), as well as diabetes-related variables (i.e. age at diabetes diagnosis, glycated haemoglobin [HbA1c] and creatinine-based estimated glomerular filtration rate [eGFR]). Models were recalibrated to CVD incidence in four European risk regions. External validation included 217 036 further individuals (38 602 CVD events), and showed good discrimination, and improvement over SCORE2 (C-index change from 0.009 to 0.031). Regional calibration was satisfactory. SCORE2-Diabetes risk predictions varied several-fold, depending on individuals' levels of diabetes-related factors. For example, in the moderate-risk region, the estimated 10-year CVD risk was 11% for a 60-year-old man, non-smoker, with type 2 diabetes, average conventional risk factors, HbA1c of 50 mmol/mol, eGFR of 90 mL/min/1.73 m2, and age at diabetes diagnosis of 60 years. By contrast, the estimated risk was 17% in a similar man, with HbA1c of 70 mmol/mol, eGFR of 60 mL/min/1.73 m2, and age at diabetes diagnosis of 50 years. For a woman with the same characteristics, the risk was 8% and 13%, respectively.

Conclusion

SCORE2-Diabetes, a new algorithm developed, calibrated, and validated to predict 10-year risk of CVD in individuals with type 2 diabetes, enhances identification of individuals at higher risk of developing CVD across Europe.", - "laySummary": "", - "urls": "pdf:https://academic.oup.com/eurheartj/advance-article-pdf/doi/10.1093/eurheartj/ehad260/50482240/ehad260.pdf; doi:https://doi.org/10.1093/eurheartj/ehad260; html:https://europepmc.org/articles/PMC10361012; pdf:https://europepmc.org/articles/PMC10361012?pdf=render" - }, { "id": "31794059", "doi": "https://doi.org/10.1111/bjd.18778", @@ -38589,6 +38572,23 @@ "laySummary": "", "urls": "pdf:https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/bjd.18778; doi:https://doi.org/10.1111/bjd.18778; html:https://europepmc.org/articles/PMC7496176; pdf:https://europepmc.org/articles/PMC7496176?pdf=render" }, + { + "id": "37247330", + "doi": "https://doi.org/10.1093/eurheartj/ehad260", + "title": "SCORE2-Diabetes: 10-year cardiovascular risk estimation in type 2 diabetes in Europe.", + "authorString": "SCORE2-Diabetes Working Group and the ESC Cardiovascular Risk Collaboration.", + "authorAffiliations": "", + "journalTitle": "European heart journal", + "pubYear": "2023", + "date": "2023-07-01", + "isOpenAccess": "Y", + "keywords": "Cardiovascular diseases; Prediction model; Diabetes", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Aims

To develop and validate a recalibrated prediction model (SCORE2-Diabetes) to estimate the 10-year risk of cardiovascular disease (CVD) in individuals with type 2 diabetes in Europe.

Methods and results

SCORE2-Diabetes was developed by extending SCORE2 algorithms using individual-participant data from four large-scale datasets comprising 229 460 participants (43 706 CVD events) with type 2 diabetes and without previous CVD. Sex-specific competing risk-adjusted models were used including conventional risk factors (i.e. age, smoking, systolic blood pressure, total, and HDL-cholesterol), as well as diabetes-related variables (i.e. age at diabetes diagnosis, glycated haemoglobin [HbA1c] and creatinine-based estimated glomerular filtration rate [eGFR]). Models were recalibrated to CVD incidence in four European risk regions. External validation included 217 036 further individuals (38 602 CVD events), and showed good discrimination, and improvement over SCORE2 (C-index change from 0.009 to 0.031). Regional calibration was satisfactory. SCORE2-Diabetes risk predictions varied several-fold, depending on individuals' levels of diabetes-related factors. For example, in the moderate-risk region, the estimated 10-year CVD risk was 11% for a 60-year-old man, non-smoker, with type 2 diabetes, average conventional risk factors, HbA1c of 50 mmol/mol, eGFR of 90 mL/min/1.73 m2, and age at diabetes diagnosis of 60 years. By contrast, the estimated risk was 17% in a similar man, with HbA1c of 70 mmol/mol, eGFR of 60 mL/min/1.73 m2, and age at diabetes diagnosis of 50 years. For a woman with the same characteristics, the risk was 8% and 13%, respectively.

Conclusion

SCORE2-Diabetes, a new algorithm developed, calibrated, and validated to predict 10-year risk of CVD in individuals with type 2 diabetes, enhances identification of individuals at higher risk of developing CVD across Europe.", + "laySummary": "", + "urls": "pdf:https://academic.oup.com/eurheartj/advance-article-pdf/doi/10.1093/eurheartj/ehad260/50482240/ehad260.pdf; doi:https://doi.org/10.1093/eurheartj/ehad260; html:https://europepmc.org/articles/PMC10361012; pdf:https://europepmc.org/articles/PMC10361012?pdf=render" + }, { "id": "34321180", "doi": "https://doi.org/10.1016/j.aucc.2021.05.013", @@ -39082,23 +39082,6 @@ "laySummary": "", "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/12/5/e059258.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-059258; html:https://europepmc.org/articles/PMC9083394; pdf:https://europepmc.org/articles/PMC9083394?pdf=render" }, - { - "id": "36568709", - "doi": "https://doi.org/10.1136/bmjmed-2022-000215", - "title": "Burden and treatment of chronic obstructive pulmonary disease among people using illicit opioids: matched cohort study in England.", - "authorString": "Lewer D, Cox S, Hurst JR, Padmanathan P, Petersen I, Quint JK.", - "authorAffiliations": "", - "journalTitle": "BMJ medicine", - "pubYear": "2022", - "date": "2022-09-28", - "isOpenAccess": "Y", - "keywords": "Substance-related disorders; Pulmonary disease, chronic obstructive; epidemiology; Health Services; Primary Health Care; Healthcare Disparities", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Objective

To understand the burden of chronic obstructive pulmonary disease among people who use illicit opioids such as heroin, and evaluate inequalities in treatment.

Design

Cohort study.

Setting

Patients registered at primary care practices in England.

Participants

106\u2009789 patients in the Clinical Practice Research Datalink with illicit opioid use recorded between 2001 and 2018, and a subcohort of 3903 patients with a diagnosis of chronic obstructive pulmonary disease. For both cohorts, the study sampled a comparison group with no history of illicit opioids that was matched by age, sex, and general practice.

Main outcome measures

In the base cohort: diagnosis of chronic obstructive pulmonary disease and death due to the disease. In the subcohort: five treatments (influenza vaccine, pneumococcal vaccine, pulmonary rehabilitation, bronchodilators or corticosteroids, and smoking cessation support) and exacerbations requiring hospital admission.

Results

680 of 106 789 participants died due to chronic obstructive pulmonary disease, representing 5.1% of all cause deaths. Illicit opioid use was associated with 14.59 times (95% confidence interval 12.28 to 17.33) the risk of death related to chronic obstructive pulmonary disease, and 5.89 times (5.62 to 6.18) the risk of a diagnosis of the disease. Among patients with a new diagnosis, comorbid illicit opioid use was associated with current smoking, underweight, worse lung function, and more severe breathlessness. After adjusting for these differences, illicit opioids were associated with 1.96 times (1.82 to 2.12) times the risk of exacerbations requiring hospital admission, but not associated with a substantially different probability of the five treatments.

Conclusions

Death due to chronic obstructive pulmonary disease is about 15 times more common among people who use illicit opioids than the general population. This inequality does not appear to be explained by differences in treatment, but late diagnosis of the disease among people who use illicit opioids might contribute.", - "laySummary": "", - "urls": "pdf:https://bmjmedicine.bmj.com/content/bmjmed/1/1/e000215.full.pdf; doi:https://doi.org/10.1136/bmjmed-2022-000215; html:https://europepmc.org/articles/PMC9770021; pdf:https://europepmc.org/articles/PMC9770021?pdf=render" - }, { "id": "35296488", "doi": "https://doi.org/10.1136/bmjopen-2021-058552", @@ -39116,6 +39099,23 @@ "laySummary": "", "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/12/3/e058552.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-058552; html:https://europepmc.org/articles/PMC8928293; pdf:https://europepmc.org/articles/PMC8928293?pdf=render" }, + { + "id": "36568709", + "doi": "https://doi.org/10.1136/bmjmed-2022-000215", + "title": "Burden and treatment of chronic obstructive pulmonary disease among people using illicit opioids: matched cohort study in England.", + "authorString": "Lewer D, Cox S, Hurst JR, Padmanathan P, Petersen I, Quint JK.", + "authorAffiliations": "", + "journalTitle": "BMJ medicine", + "pubYear": "2022", + "date": "2022-09-28", + "isOpenAccess": "Y", + "keywords": "Substance-related disorders; Pulmonary disease, chronic obstructive; epidemiology; Health Services; Primary Health Care; Healthcare Disparities", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Objective

To understand the burden of chronic obstructive pulmonary disease among people who use illicit opioids such as heroin, and evaluate inequalities in treatment.

Design

Cohort study.

Setting

Patients registered at primary care practices in England.

Participants

106\u2009789 patients in the Clinical Practice Research Datalink with illicit opioid use recorded between 2001 and 2018, and a subcohort of 3903 patients with a diagnosis of chronic obstructive pulmonary disease. For both cohorts, the study sampled a comparison group with no history of illicit opioids that was matched by age, sex, and general practice.

Main outcome measures

In the base cohort: diagnosis of chronic obstructive pulmonary disease and death due to the disease. In the subcohort: five treatments (influenza vaccine, pneumococcal vaccine, pulmonary rehabilitation, bronchodilators or corticosteroids, and smoking cessation support) and exacerbations requiring hospital admission.

Results

680 of 106 789 participants died due to chronic obstructive pulmonary disease, representing 5.1% of all cause deaths. Illicit opioid use was associated with 14.59 times (95% confidence interval 12.28 to 17.33) the risk of death related to chronic obstructive pulmonary disease, and 5.89 times (5.62 to 6.18) the risk of a diagnosis of the disease. Among patients with a new diagnosis, comorbid illicit opioid use was associated with current smoking, underweight, worse lung function, and more severe breathlessness. After adjusting for these differences, illicit opioids were associated with 1.96 times (1.82 to 2.12) times the risk of exacerbations requiring hospital admission, but not associated with a substantially different probability of the five treatments.

Conclusions

Death due to chronic obstructive pulmonary disease is about 15 times more common among people who use illicit opioids than the general population. This inequality does not appear to be explained by differences in treatment, but late diagnosis of the disease among people who use illicit opioids might contribute.", + "laySummary": "", + "urls": "pdf:https://bmjmedicine.bmj.com/content/bmjmed/1/1/e000215.full.pdf; doi:https://doi.org/10.1136/bmjmed-2022-000215; html:https://europepmc.org/articles/PMC9770021; pdf:https://europepmc.org/articles/PMC9770021?pdf=render" + }, { "id": "36434067", "doi": "https://doi.org/10.1038/s42003-022-04252-5", @@ -39218,23 +39218,6 @@ "laySummary": "", "urls": "pdf:https://www.tandfonline.com/doi/pdf/10.1080/19490976.2022.2038863?needAccess=true; doi:https://doi.org/10.1080/19490976.2022.2038863; html:https://europepmc.org/articles/PMC8865277; pdf:https://europepmc.org/articles/PMC8865277?pdf=render" }, - { - "id": "38508198", - "doi": "https://doi.org/10.1016/j.xgen.2024.100523", - "title": "Integrative polygenic risk score improves the prediction accuracy of complex traits and diseases.", - "authorString": "Truong B, Hull LE, Ruan Y, Huang QQ, Hornsby W, Martin H, van Heel DA, Wang Y, Martin AR, Lee SH, Natarajan P.", - "authorAffiliations": "", - "journalTitle": "Cell genomics", - "pubYear": "2024", - "date": "2024-03-19", - "isOpenAccess": "Y", - "keywords": "Combination; Clinical Utility; South Asian; Integrative; Prs; Cross Ancestry", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Polygenic risk scores (PRSs) are an emerging tool to predict the clinical phenotypes and outcomes of individuals. We propose PRSmix, a framework that leverages the PRS corpus of a target trait to improve prediction accuracy, and PRSmix+, which incorporates genetically correlated traits to better capture the human genetic architecture for 47 and 32 diseases/traits in European and South Asian ancestries, respectively. PRSmix demonstrated a mean prediction accuracy improvement of 1.20-fold (95% confidence interval [CI], [1.10; 1.3]; p\u00a0= 9.17\u00a0\u00d7\u00a010-5) and 1.19-fold (95% CI, [1.11; 1.27]; p\u00a0= 1.92\u00a0\u00d7\u00a010-6), and PRSmix+ improved the prediction accuracy by 1.72-fold (95% CI, [1.40; 2.04]; p\u00a0= 7.58\u00a0\u00d7\u00a010-6) and 1.42-fold (95% CI, [1.25; 1.59]; p\u00a0= 8.01\u00a0\u00d7\u00a010-7) in European and South Asian ancestries, respectively. Compared to the previously cross-trait-combination methods with scores from pre-defined correlated traits, we demonstrated that our method improved prediction accuracy for coronary artery disease up to 3.27-fold (95% CI, [2.1; 4.44]; p value after false discovery rate (FDR) correction\u00a0= 2.6\u00a0\u00d7\u00a010-4). Our method provides a comprehensive framework to benchmark and leverage the combined power of PRS for maximal performance in a desired target population.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1016/j.xgen.2024.100523; html:https://europepmc.org/articles/PMC11019356; pdf:https://europepmc.org/articles/PMC11019356?pdf=render" - }, { "id": "34240696", "doi": "https://doi.org/10.2807/1560-7917.es.2021.26.27.2000004", @@ -39286,6 +39269,23 @@ "laySummary": "", "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/11/6/e046450.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-046450; html:https://europepmc.org/articles/PMC8246365; pdf:https://europepmc.org/articles/PMC8246365?pdf=render" }, + { + "id": "38508198", + "doi": "https://doi.org/10.1016/j.xgen.2024.100523", + "title": "Integrative polygenic risk score improves the prediction accuracy of complex traits and diseases.", + "authorString": "Truong B, Hull LE, Ruan Y, Huang QQ, Hornsby W, Martin H, van Heel DA, Wang Y, Martin AR, Lee SH, Natarajan P.", + "authorAffiliations": "", + "journalTitle": "Cell genomics", + "pubYear": "2024", + "date": "2024-03-19", + "isOpenAccess": "Y", + "keywords": "Combination; Clinical Utility; South Asian; Integrative; Prs; Cross Ancestry", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Polygenic risk scores (PRSs) are an emerging tool to predict the clinical phenotypes and outcomes of individuals. We propose PRSmix, a framework that leverages the PRS corpus of a target trait to improve prediction accuracy, and PRSmix+, which incorporates genetically correlated traits to better capture the human genetic architecture for 47 and 32 diseases/traits in European and South Asian ancestries, respectively. PRSmix demonstrated a mean prediction accuracy improvement of 1.20-fold (95% confidence interval [CI], [1.10; 1.3]; p\u00a0= 9.17\u00a0\u00d7\u00a010-5) and 1.19-fold (95% CI, [1.11; 1.27]; p\u00a0= 1.92\u00a0\u00d7\u00a010-6), and PRSmix+ improved the prediction accuracy by 1.72-fold (95% CI, [1.40; 2.04]; p\u00a0= 7.58\u00a0\u00d7\u00a010-6) and 1.42-fold (95% CI, [1.25; 1.59]; p\u00a0= 8.01\u00a0\u00d7\u00a010-7) in European and South Asian ancestries, respectively. Compared to the previously cross-trait-combination methods with scores from pre-defined correlated traits, we demonstrated that our method improved prediction accuracy for coronary artery disease up to 3.27-fold (95% CI, [2.1; 4.44]; p value after false discovery rate (FDR) correction\u00a0= 2.6\u00a0\u00d7\u00a010-4). Our method provides a comprehensive framework to benchmark and leverage the combined power of PRS for maximal performance in a desired target population.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1016/j.xgen.2024.100523; html:https://europepmc.org/articles/PMC11019356; pdf:https://europepmc.org/articles/PMC11019356?pdf=render" + }, { "id": "32724858", "doi": "https://doi.org/10.1136/bmjophth-2020-000481", @@ -39422,23 +39422,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1099/mgen.0.000393; doi:https://doi.org/10.1099/mgen.0.000393; html:https://europepmc.org/articles/PMC7478626; pdf:https://europepmc.org/articles/PMC7478626?pdf=render" }, - { - "id": "36029521", - "doi": "https://doi.org/10.1093/ije/dyac171", - "title": "Cohort Profile: The United Kingdom Research study into Ethnicity and COVID-19 outcomes in Healthcare workers (UK-REACH).", - "authorString": "Bryant L, Free RC, Woolf K, Melbourne C, Guyatt AL, John C, Gupta A, Gray LJ, Nellums L, Martin CA, McManus IC, Garwood C, Modhawdia V, Carr S, Wain LV, Tobin MD, Khunti K, Akubakar I, Pareek M, UK-REACH Collaborative Group+.", - "authorAffiliations": "", - "journalTitle": "International journal of epidemiology", - "pubYear": "2023", - "date": "2023-02-01", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "", - "laySummary": "", - "urls": "pdf:https://academic.oup.com/ije/article-pdf/52/1/e38/49127215/dyac171.pdf; doi:https://doi.org/10.1093/ije/dyac171; html:https://europepmc.org/articles/PMC9452183; pdf:https://europepmc.org/articles/PMC9452183?pdf=render" - }, { "id": "31171806", "doi": "https://doi.org/10.1038/s41598-019-44907-8", @@ -39456,6 +39439,23 @@ "laySummary": "", "urls": "pdf:https://www.nature.com/articles/s41598-019-44907-8.pdf; doi:https://doi.org/10.1038/s41598-019-44907-8; html:https://europepmc.org/articles/PMC6554413; pdf:https://europepmc.org/articles/PMC6554413?pdf=render" }, + { + "id": "36029521", + "doi": "https://doi.org/10.1093/ije/dyac171", + "title": "Cohort Profile: The United Kingdom Research study into Ethnicity and COVID-19 outcomes in Healthcare workers (UK-REACH).", + "authorString": "Bryant L, Free RC, Woolf K, Melbourne C, Guyatt AL, John C, Gupta A, Gray LJ, Nellums L, Martin CA, McManus IC, Garwood C, Modhawdia V, Carr S, Wain LV, Tobin MD, Khunti K, Akubakar I, Pareek M, UK-REACH Collaborative Group+.", + "authorAffiliations": "", + "journalTitle": "International journal of epidemiology", + "pubYear": "2023", + "date": "2023-02-01", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "", + "laySummary": "", + "urls": "pdf:https://academic.oup.com/ije/article-pdf/52/1/e38/49127215/dyac171.pdf; doi:https://doi.org/10.1093/ije/dyac171; html:https://europepmc.org/articles/PMC9452183; pdf:https://europepmc.org/articles/PMC9452183?pdf=render" + }, { "id": "35587468", "doi": "https://doi.org/10.1371/journal.pmed.1003981", @@ -39541,23 +39541,6 @@ "laySummary": "", "urls": "pdf:https://bmcmedethics.biomedcentral.com/counter/pdf/10.1186/s12910-022-00875-9; doi:https://doi.org/10.1186/s12910-022-00875-9; html:https://europepmc.org/articles/PMC9756740; pdf:https://europepmc.org/articles/PMC9756740?pdf=render" }, - { - "id": "36522333", - "doi": "https://doi.org/10.1038/s41467-022-35454-4", - "title": "Multi-omics identify falling LRRC15 as a COVID-19 severity marker and persistent pro-thrombotic signals in convalescence.", - "authorString": "Gisby JS, Buang NB, Papadaki A, Clarke CL, Malik TH, Medjeral-Thomas N, Pinheiro D, Mortimer PM, Lewis S, Sandhu E, McAdoo SP, Prendecki MF, Willicombe M, Pickering MC, Botto M, Thomas DC, Peters JE.", - "authorAffiliations": "", - "journalTitle": "Nature communications", - "pubYear": "2022", - "date": "2022-12-15", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Patients with end-stage kidney disease (ESKD) are at high risk of severe COVID-19. Here, we perform longitudinal blood sampling of ESKD haemodialysis patients with COVID-19, collecting samples pre-infection, serially during infection, and after clinical recovery. Using plasma proteomics, and RNA-sequencing and flow cytometry of immune cells, we identify transcriptomic and proteomic signatures of COVID-19 severity, and find distinct temporal molecular profiles in patients with severe disease. Supervised learning reveals that the plasma proteome is a superior indicator of clinical severity than the PBMC transcriptome. We show that a decreasing trajectory of plasma LRRC15, a proposed co-receptor for SARS-CoV-2, is associated with a more severe clinical course. We observe that two months after the acute infection, patients still display dysregulated gene expression related to vascular, platelet and coagulation pathways, including PF4 (platelet factor 4), which may explain the prolonged thrombotic risk following COVID-19.", - "laySummary": "", - "urls": "pdf:https://www.nature.com/articles/s41467-022-35454-4.pdf; doi:https://doi.org/10.1038/s41467-022-35454-4; html:https://europepmc.org/articles/PMC9753891; pdf:https://europepmc.org/articles/PMC9753891?pdf=render" - }, { "id": "34490590", "doi": "https://doi.org/10.1007/s40256-021-00496-4", @@ -39576,21 +39559,21 @@ "urls": "pdf:https://pure.rug.nl/ws/files/223545267/Cost_Effectiveness_of_a_CYP2C19_Genotype_Guided_Strategy_in_Patients_with_Acute_Myocardial_Infarction_Results_from_the_POPular_Genetics_Trial.pdf; doi:https://doi.org/10.1007/s40256-021-00496-4" }, { - "id": "37132645", - "doi": "https://doi.org/10.1017/s0033291721002257", - "title": "Life expectancy, mortality risks and cause of death in patients with serious mental illness in South East London: a comparison between 2008-2012 and 2013-2017.", - "authorString": "Chang CK, Chesney E, Teng WN, Hollandt S, Pritchard M, Shetty H, Stewart R, McGuire P, Patel R.", + "id": "36522333", + "doi": "https://doi.org/10.1038/s41467-022-35454-4", + "title": "Multi-omics identify falling LRRC15 as a COVID-19 severity marker and persistent pro-thrombotic signals in convalescence.", + "authorString": "Gisby JS, Buang NB, Papadaki A, Clarke CL, Malik TH, Medjeral-Thomas N, Pinheiro D, Mortimer PM, Lewis S, Sandhu E, McAdoo SP, Prendecki MF, Willicombe M, Pickering MC, Botto M, Thomas DC, Peters JE.", "authorAffiliations": "", - "journalTitle": "Psychological medicine", - "pubYear": "2023", - "date": "2021-09-07", + "journalTitle": "Nature communications", + "pubYear": "2022", + "date": "2022-12-15", "isOpenAccess": "Y", - "keywords": "Mortality; Schizophrenia; Life expectancy; Cause of death; Bipolar disorder; Standardised Mortality Ratio", + "keywords": "", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Background

People with serious mental illness (SMI) have a significantly shorter life expectancy than the general population. This study investigates whether the mortality rate in this group has changed over the last decade.

Methods

Using Clinical Record Interactive Search software, we extracted data from a large electronic database of patients in South East London. All patients with schizophrenia, schizoaffective disorder or bipolar disorder from 2008 to 2012 and/or 2013 to 2017 were included. Estimates of life expectancy at birth, standardised mortality ratios and causes of death were obtained for each cohort according to diagnosis and gender. Comparisons were made between cohorts and with the general population using data obtained from the UK Office of National Statistics.

Results

In total, 26 005 patients were included. In men, life expectancy was greater in 2013-2017 (64.9 years; 95% CI 63.6-66.3) than in 2008-2012 (63.2 years; 95% CI 61.5-64.9). Similarly, in women, life expectancy was greater in 2013-2017 (69.1 years; 95% CI 67.5-70.7) than in 2008-2012 (68.1 years; 95% CI 66.2-69.9). The difference with general population life expectancy fell by 0.9 years between cohorts in men, and 0.5 years in women. In the 2013-2017 cohorts, cancer accounted for a similar proportion of deaths as cardiovascular disease.

Conclusions

Relative to the general population, life expectancy for people with SMI is still much worse, though it appears to be improving. The increased cancer-related mortality suggests that physical health monitoring should consider including cancer as well.", + "abstract": "Patients with end-stage kidney disease (ESKD) are at high risk of severe COVID-19. Here, we perform longitudinal blood sampling of ESKD haemodialysis patients with COVID-19, collecting samples pre-infection, serially during infection, and after clinical recovery. Using plasma proteomics, and RNA-sequencing and flow cytometry of immune cells, we identify transcriptomic and proteomic signatures of COVID-19 severity, and find distinct temporal molecular profiles in patients with severe disease. Supervised learning reveals that the plasma proteome is a superior indicator of clinical severity than the PBMC transcriptome. We show that a decreasing trajectory of plasma LRRC15, a proposed co-receptor for SARS-CoV-2, is associated with a more severe clinical course. We observe that two months after the acute infection, patients still display dysregulated gene expression related to vascular, platelet and coagulation pathways, including PF4 (platelet factor 4), which may explain the prolonged thrombotic risk following COVID-19.", "laySummary": "", - "urls": "pdf:https://www.cambridge.org/core/services/aop-cambridge-core/content/view/F28CB69D452C5EFDAFF77D0FE59FC094/S0033291721002257a.pdf/div-class-title-life-expectancy-mortality-risks-and-cause-of-death-in-patients-with-serious-mental-illness-in-south-east-london-a-comparison-between-2008-2012-and-2013-2017-div.pdf; doi:https://doi.org/10.1017/S0033291721002257; html:https://europepmc.org/articles/PMC9975985; pdf:https://europepmc.org/articles/PMC9975985?pdf=render" + "urls": "pdf:https://www.nature.com/articles/s41467-022-35454-4.pdf; doi:https://doi.org/10.1038/s41467-022-35454-4; html:https://europepmc.org/articles/PMC9753891; pdf:https://europepmc.org/articles/PMC9753891?pdf=render" }, { "id": "33199917", @@ -39610,21 +39593,21 @@ "urls": "pdf:https://europepmc.org/articles/pmc7116530?pdf=render; doi:https://doi.org/10.1038/s41588-020-00725-7; html:https://europepmc.org/articles/PMC7116530; pdf:https://europepmc.org/articles/PMC7116530?pdf=render; doi:https://doi.org/10.1038/s41588-020-00725-7" }, { - "id": "38783292", - "doi": "https://doi.org/10.1186/s12939-024-02198-0", - "title": "Discrimination, disadvantage and disempowerment during COVID-19: a qualitative intrasectional analysis of the lived experiences of an ethnically diverse healthcare workforce in the United Kingdom.", - "authorString": "Gogoi M, Qureshi I, Chaloner J, Al-Oraibi A, Reilly H, Wobi F, Agbonmwandolor JO, Ekezie W, Hassan O, Lal Z, Kapilashrami A, Nellums L, Pareek M, UK-REACH Study Collaborative Group Members.", + "id": "37132645", + "doi": "https://doi.org/10.1017/s0033291721002257", + "title": "Life expectancy, mortality risks and cause of death in patients with serious mental illness in South East London: a comparison between 2008-2012 and 2013-2017.", + "authorString": "Chang CK, Chesney E, Teng WN, Hollandt S, Pritchard M, Shetty H, Stewart R, McGuire P, Patel R.", "authorAffiliations": "", - "journalTitle": "International journal for equity in health", - "pubYear": "2024", - "date": "2024-05-23", + "journalTitle": "Psychological medicine", + "pubYear": "2023", + "date": "2021-09-07", "isOpenAccess": "Y", - "keywords": "Discrimination; Healthcare Workers; Disadvantage; Disempowerment; Covid-19 Pandemic; Intersectionality; Intrasectionalism", + "keywords": "Mortality; Schizophrenia; Life expectancy; Cause of death; Bipolar disorder; Standardised Mortality Ratio", "nationalPriorities": "", "healthCategories": "", - "abstract": "

Background

Healthcare workers (HCWs) in the United Kingdom (UK) have faced many challenges during the COVID-19 pandemic, some of these arising out of their social positions. Existing literature explicating these challenges (e.g., lack of appropriate PPE, redeployment, understaffing) have highlighted inequities in how these have been experienced by HCWs based on ethnicity, gender or, job role. In this paper, we move a step ahead and examine how the intersection of these social positions have impacted HCWs' experiences of challenges during the pandemic.

Methods

We collected qualitative data, using interviews and focus groups, from 164 HCWs from different ethnicities, gender, job roles, migration statuses, and regions in the United Kingdom (UK) between December 2020 and July 2021. Interviews and focus groups were conducted online or by telephone, and recorded with participants' permission. Recordings were transcribed and a hybrid thematic analytical approach integrating inductive data-driven codes with deductive ones informed by an intersectional framework was adopted to analyse the transcripts.

Results

Thematic analysis of transcripts identified disempowerment, disadvantage and, discrimination as the three main themes around which HCWs' experiences of challenges were centred, based on their intersecting identities (e.g., ethnicity gender, and/or migration status). Our analysis also acknowledges that disadvantages faced by HCWs were linked to systemic and structural factors at the micro, meso and macro ecosystemic levels. This merging of analysis which is grounded in intersectionality and considers the ecosystemic levels has been termed as 'intrasectionalism'.

Discussion

Our research demonstrates how an intrasectional lens can help better understand how different forms of mutually reinforcing inequities exist at all levels within the healthcare workforce and how these impact HCWs from certain backgrounds who face greater disadvantage, discrimination and disempowerment, particularly during times of crisis like the COVID-19 pandemic.", + "abstract": "

Background

People with serious mental illness (SMI) have a significantly shorter life expectancy than the general population. This study investigates whether the mortality rate in this group has changed over the last decade.

Methods

Using Clinical Record Interactive Search software, we extracted data from a large electronic database of patients in South East London. All patients with schizophrenia, schizoaffective disorder or bipolar disorder from 2008 to 2012 and/or 2013 to 2017 were included. Estimates of life expectancy at birth, standardised mortality ratios and causes of death were obtained for each cohort according to diagnosis and gender. Comparisons were made between cohorts and with the general population using data obtained from the UK Office of National Statistics.

Results

In total, 26 005 patients were included. In men, life expectancy was greater in 2013-2017 (64.9 years; 95% CI 63.6-66.3) than in 2008-2012 (63.2 years; 95% CI 61.5-64.9). Similarly, in women, life expectancy was greater in 2013-2017 (69.1 years; 95% CI 67.5-70.7) than in 2008-2012 (68.1 years; 95% CI 66.2-69.9). The difference with general population life expectancy fell by 0.9 years between cohorts in men, and 0.5 years in women. In the 2013-2017 cohorts, cancer accounted for a similar proportion of deaths as cardiovascular disease.

Conclusions

Relative to the general population, life expectancy for people with SMI is still much worse, though it appears to be improving. The increased cancer-related mortality suggests that physical health monitoring should consider including cancer as well.", "laySummary": "", - "urls": "pdf:https://equityhealthj.biomedcentral.com/counter/pdf/10.1186/s12939-024-02198-0; doi:https://doi.org/10.1186/s12939-024-02198-0; html:https://europepmc.org/articles/PMC11118759; pdf:https://europepmc.org/articles/PMC11118759?pdf=render" + "urls": "pdf:https://www.cambridge.org/core/services/aop-cambridge-core/content/view/F28CB69D452C5EFDAFF77D0FE59FC094/S0033291721002257a.pdf/div-class-title-life-expectancy-mortality-risks-and-cause-of-death-in-patients-with-serious-mental-illness-in-south-east-london-a-comparison-between-2008-2012-and-2013-2017-div.pdf; doi:https://doi.org/10.1017/S0033291721002257; html:https://europepmc.org/articles/PMC9975985; pdf:https://europepmc.org/articles/PMC9975985?pdf=render" }, { "id": "32127008", @@ -39643,6 +39626,23 @@ "laySummary": "", "urls": "pdf:https://genomebiology.biomedcentral.com/track/pdf/10.1186/s13059-020-01969-6; doi:https://doi.org/10.1186/s13059-020-01969-6; html:https://europepmc.org/articles/PMC7053107; pdf:https://europepmc.org/articles/PMC7053107?pdf=render" }, + { + "id": "38783292", + "doi": "https://doi.org/10.1186/s12939-024-02198-0", + "title": "Discrimination, disadvantage and disempowerment during COVID-19: a qualitative intrasectional analysis of the lived experiences of an ethnically diverse healthcare workforce in the United Kingdom.", + "authorString": "Gogoi M, Qureshi I, Chaloner J, Al-Oraibi A, Reilly H, Wobi F, Agbonmwandolor JO, Ekezie W, Hassan O, Lal Z, Kapilashrami A, Nellums L, Pareek M, UK-REACH Study Collaborative Group Members.", + "authorAffiliations": "", + "journalTitle": "International journal for equity in health", + "pubYear": "2024", + "date": "2024-05-23", + "isOpenAccess": "Y", + "keywords": "Discrimination; Healthcare Workers; Disadvantage; Disempowerment; Covid-19 Pandemic; Intersectionality; Intrasectionalism", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Healthcare workers (HCWs) in the United Kingdom (UK) have faced many challenges during the COVID-19 pandemic, some of these arising out of their social positions. Existing literature explicating these challenges (e.g., lack of appropriate PPE, redeployment, understaffing) have highlighted inequities in how these have been experienced by HCWs based on ethnicity, gender or, job role. In this paper, we move a step ahead and examine how the intersection of these social positions have impacted HCWs' experiences of challenges during the pandemic.

Methods

We collected qualitative data, using interviews and focus groups, from 164 HCWs from different ethnicities, gender, job roles, migration statuses, and regions in the United Kingdom (UK) between December 2020 and July 2021. Interviews and focus groups were conducted online or by telephone, and recorded with participants' permission. Recordings were transcribed and a hybrid thematic analytical approach integrating inductive data-driven codes with deductive ones informed by an intersectional framework was adopted to analyse the transcripts.

Results

Thematic analysis of transcripts identified disempowerment, disadvantage and, discrimination as the three main themes around which HCWs' experiences of challenges were centred, based on their intersecting identities (e.g., ethnicity gender, and/or migration status). Our analysis also acknowledges that disadvantages faced by HCWs were linked to systemic and structural factors at the micro, meso and macro ecosystemic levels. This merging of analysis which is grounded in intersectionality and considers the ecosystemic levels has been termed as 'intrasectionalism'.

Discussion

Our research demonstrates how an intrasectional lens can help better understand how different forms of mutually reinforcing inequities exist at all levels within the healthcare workforce and how these impact HCWs from certain backgrounds who face greater disadvantage, discrimination and disempowerment, particularly during times of crisis like the COVID-19 pandemic.", + "laySummary": "", + "urls": "pdf:https://equityhealthj.biomedcentral.com/counter/pdf/10.1186/s12939-024-02198-0; doi:https://doi.org/10.1186/s12939-024-02198-0; html:https://europepmc.org/articles/PMC11118759; pdf:https://europepmc.org/articles/PMC11118759?pdf=render" + }, { "id": "33075408", "doi": "https://doi.org/10.1016/j.jaci.2020.10.007", @@ -39677,23 +39677,6 @@ "laySummary": "", "urls": "pdf:http://www.thelancet.com/article/S0140673622005323/pdf; doi:https://doi.org/10.1016/S0140-6736(22)00532-3; html:https://europepmc.org/articles/PMC9168805" }, - { - "id": "37263751", - "doi": "https://doi.org/10.1183/13993003.01667-2022", - "title": "Genome-wide association study of chronic sputum production implicates loci involved in mucus production and infection.", - "authorString": "Packer RJ, Shrine N, Hall R, Melbourne CA, Thompson R, Williams AT, Paynton ML, Guyatt AL, Allen RJ, Lee PH, John C, Campbell A, Hayward C, de Vries M, Vonk JM, Davitte J, Hessel E, Michalovich D, Betts JC, Sayers I, Yeo A, Hall IP, Tobin MD, Wain LV.", - "authorAffiliations": "", - "journalTitle": "The European respiratory journal", - "pubYear": "2023", - "date": "2023-06-15", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Chronic sputum production impacts on quality of life and is a feature of many respiratory diseases. Identification of the genetic variants associated with chronic sputum production in a disease agnostic sample could improve understanding of its causes and identify new molecular targets for treatment.

Methods

We conducted a genome-wide association study (GWAS) of chronic sputum production in UK Biobank. Signals meeting genome-wide significance (p<5\u00d710-8) were investigated in additional independent studies, were fine-mapped and putative causal genes identified by gene expression analysis. GWASs of respiratory traits were interrogated to identify whether the signals were driven by existing respiratory disease among the cases and variants were further investigated for wider pleiotropic effects using phenome-wide association studies (PheWASs).

Results

From a GWAS of 9714 cases and 48\u2009471 controls, we identified six novel genome-wide significant signals for chronic sputum production including signals in the human leukocyte antigen (HLA) locus, chromosome 11 mucin locus (containing MUC2, MUC5AC and MUC5B) and FUT2 locus. The four common variant associations were supported by independent studies with a combined sample size of up to 2203 cases and 17\u2009627 controls. The mucin locus signal had previously been reported for association with moderate-to-severe asthma. The HLA signal was fine-mapped to an amino acid change of threonine to arginine (frequency 36.8%) in HLA-DRB1 (HLA-DRB1*03:147). The signal near FUT2 was associated with expression of several genes including FUT2, for which the direction of effect was tissue dependent. Our PheWAS identified a wide range of associations including blood cell traits, liver biomarkers, infections, gastrointestinal and thyroid-associated diseases, and respiratory disease.

Conclusions

Novel signals at the FUT2 and mucin loci suggest that mucin fucosylation may be a driver of chronic sputum production even in the absence of diagnosed respiratory disease and provide genetic support for this pathway as a target for therapeutic intervention.", - "laySummary": "", - "urls": "pdf:https://erj.ersjournals.com/content/erj/61/6/2201667.full.pdf; doi:https://doi.org/10.1183/13993003.01667-2022; html:https://europepmc.org/articles/PMC10284065; pdf:https://europepmc.org/articles/PMC10284065?pdf=render" - }, { "id": "32423943", "doi": "https://doi.org/10.1136/bmjopen-2020-038974", @@ -39711,6 +39694,23 @@ "laySummary": "", "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/10/5/e038974.full.pdf; doi:https://doi.org/10.1136/bmjopen-2020-038974; html:https://europepmc.org/articles/PMC7239532; pdf:https://europepmc.org/articles/PMC7239532?pdf=render" }, + { + "id": "37263751", + "doi": "https://doi.org/10.1183/13993003.01667-2022", + "title": "Genome-wide association study of chronic sputum production implicates loci involved in mucus production and infection.", + "authorString": "Packer RJ, Shrine N, Hall R, Melbourne CA, Thompson R, Williams AT, Paynton ML, Guyatt AL, Allen RJ, Lee PH, John C, Campbell A, Hayward C, de Vries M, Vonk JM, Davitte J, Hessel E, Michalovich D, Betts JC, Sayers I, Yeo A, Hall IP, Tobin MD, Wain LV.", + "authorAffiliations": "", + "journalTitle": "The European respiratory journal", + "pubYear": "2023", + "date": "2023-06-15", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Chronic sputum production impacts on quality of life and is a feature of many respiratory diseases. Identification of the genetic variants associated with chronic sputum production in a disease agnostic sample could improve understanding of its causes and identify new molecular targets for treatment.

Methods

We conducted a genome-wide association study (GWAS) of chronic sputum production in UK Biobank. Signals meeting genome-wide significance (p<5\u00d710-8) were investigated in additional independent studies, were fine-mapped and putative causal genes identified by gene expression analysis. GWASs of respiratory traits were interrogated to identify whether the signals were driven by existing respiratory disease among the cases and variants were further investigated for wider pleiotropic effects using phenome-wide association studies (PheWASs).

Results

From a GWAS of 9714 cases and 48\u2009471 controls, we identified six novel genome-wide significant signals for chronic sputum production including signals in the human leukocyte antigen (HLA) locus, chromosome 11 mucin locus (containing MUC2, MUC5AC and MUC5B) and FUT2 locus. The four common variant associations were supported by independent studies with a combined sample size of up to 2203 cases and 17\u2009627 controls. The mucin locus signal had previously been reported for association with moderate-to-severe asthma. The HLA signal was fine-mapped to an amino acid change of threonine to arginine (frequency 36.8%) in HLA-DRB1 (HLA-DRB1*03:147). The signal near FUT2 was associated with expression of several genes including FUT2, for which the direction of effect was tissue dependent. Our PheWAS identified a wide range of associations including blood cell traits, liver biomarkers, infections, gastrointestinal and thyroid-associated diseases, and respiratory disease.

Conclusions

Novel signals at the FUT2 and mucin loci suggest that mucin fucosylation may be a driver of chronic sputum production even in the absence of diagnosed respiratory disease and provide genetic support for this pathway as a target for therapeutic intervention.", + "laySummary": "", + "urls": "pdf:https://erj.ersjournals.com/content/erj/61/6/2201667.full.pdf; doi:https://doi.org/10.1183/13993003.01667-2022; html:https://europepmc.org/articles/PMC10284065; pdf:https://europepmc.org/articles/PMC10284065?pdf=render" + }, { "id": "31844048", "doi": "https://doi.org/10.1038/s41467-019-13585-5", @@ -39915,23 +39915,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.nicl.2022.103253; doi:https://doi.org/10.1016/j.nicl.2022.103253; html:https://europepmc.org/articles/PMC9639388; pdf:https://europepmc.org/articles/PMC9639388?pdf=render" }, - { - "id": "36895957", - "doi": "https://doi.org/10.1093/braincomms/fcad037", - "title": "Investigating genotype-phenotype relationship of extreme neuropathic pain disorders in a UK national cohort.", - "authorString": "Themistocleous AC, Baskozos G, Blesneac I, Comini M, Megy K, Chong S, Deevi SVV, Ginsberg L, Gosal D, Hadden RDM, Horvath R, Mahdi-Rogers M, Manzur A, Mapeta R, Marshall A, Matthews E, McCarthy MI, Reilly MM, Renton T, Rice ASC, Vale TA, van Zuydam N, Walker SM, Woods CG, Bennett DLH.", - "authorAffiliations": "", - "journalTitle": "Brain communications", - "pubYear": "2023", - "date": "2023-02-20", - "isOpenAccess": "Y", - "keywords": "Sodium channels; Neuropathic pain; Peripheral Neuropathy; Whole Genome Sequencing", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "The aims of our study were to use whole genome sequencing in a cross-sectional cohort of patients to identify new variants in genes implicated in neuropathic pain, to determine the prevalence of known pathogenic variants and to understand the relationship between pathogenic variants and clinical presentation. Patients with extreme neuropathic pain phenotypes (both sensory loss and gain) were recruited from secondary care clinics in the UK and underwent whole genome sequencing as part of the National Institute for Health and Care Research Bioresource Rare Diseases project. A multidisciplinary team assessed the pathogenicity of rare variants in genes previously known to cause neuropathic pain disorders and exploratory analysis of research candidate genes was completed. Association testing for genes carrying rare variants was completed using the gene-wise approach of the combined burden and variance-component test SKAT-O. Patch clamp analysis was performed on transfected HEK293T cells for research candidate variants of genes encoding ion channels. The results include the following: (i) Medically actionable variants were found in 12% of study participants (205 recruited), including known pathogenic variants: SCN9A(ENST00000409672.1): c.2544T>C, p.Ile848Thr that causes inherited erythromelalgia, and SPTLC1(ENST00000262554.2):c.340T>G, p.Cys133Tr variant that causes hereditary sensory neuropathy type-1. (ii) Clinically relevant variants were most common in voltage-gated sodium channels (Nav). (iii) SCN9A(ENST00000409672.1):c.554G>A, pArg185His variant was more common in non-freezing cold injury participants than controls and causes a gain of function of NaV1.7 after cooling (the environmental trigger for non-freezing cold injury). (iv) Rare variant association testing showed a significant difference in distribution for genes NGF, KIF1A, SCN8A, TRPM8, KIF1A, TRPA1 and the regulatory regions of genes SCN11A, FLVCR1, KIF1A and SCN9A between European participants with neuropathic pain and controls. (v) The TRPA1(ENST00000262209.4):c.515C>T, p.Ala172Val variant identified in participants with episodic somatic pain disorder demonstrated gain-of-channel function to agonist stimulation. Whole genome sequencing identified clinically relevant variants in over 10% of participants with extreme neuropathic pain phenotypes. The majority of these variants were found in ion channels. Combining genetic analysis with functional validation can lead to a better understanding as to how rare variants in ion channels lead to sensory neuron hyper-excitability, and how cold, as an environmental trigger, interacts with the gain-of-function NaV1.7 p.Arg185His variant. Our findings highlight the role of ion channel variants in the pathogenesis of extreme neuropathic pain disorders, likely mediated through changes in sensory neuron excitability and interaction with environmental triggers.", - "laySummary": "", - "urls": "pdf:https://academic.oup.com/braincomms/article-pdf/5/2/fcad037/49446967/fcad037.pdf; doi:https://doi.org/10.1093/braincomms/fcad037; html:https://europepmc.org/articles/PMC9991512; pdf:https://europepmc.org/articles/PMC9991512?pdf=render" - }, { "id": "35131700", "doi": "https://doi.org/10.1016/j.media.2022.102366", @@ -39949,6 +39932,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.media.2022.102366; doi:https://doi.org/10.1016/j.media.2022.102366; html:https://europepmc.org/articles/PMC8907871; pdf:https://europepmc.org/articles/PMC8907871?pdf=render" }, + { + "id": "36895957", + "doi": "https://doi.org/10.1093/braincomms/fcad037", + "title": "Investigating genotype-phenotype relationship of extreme neuropathic pain disorders in a UK national cohort.", + "authorString": "Themistocleous AC, Baskozos G, Blesneac I, Comini M, Megy K, Chong S, Deevi SVV, Ginsberg L, Gosal D, Hadden RDM, Horvath R, Mahdi-Rogers M, Manzur A, Mapeta R, Marshall A, Matthews E, McCarthy MI, Reilly MM, Renton T, Rice ASC, Vale TA, van Zuydam N, Walker SM, Woods CG, Bennett DLH.", + "authorAffiliations": "", + "journalTitle": "Brain communications", + "pubYear": "2023", + "date": "2023-02-20", + "isOpenAccess": "Y", + "keywords": "Sodium channels; Neuropathic pain; Peripheral Neuropathy; Whole Genome Sequencing", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "The aims of our study were to use whole genome sequencing in a cross-sectional cohort of patients to identify new variants in genes implicated in neuropathic pain, to determine the prevalence of known pathogenic variants and to understand the relationship between pathogenic variants and clinical presentation. Patients with extreme neuropathic pain phenotypes (both sensory loss and gain) were recruited from secondary care clinics in the UK and underwent whole genome sequencing as part of the National Institute for Health and Care Research Bioresource Rare Diseases project. A multidisciplinary team assessed the pathogenicity of rare variants in genes previously known to cause neuropathic pain disorders and exploratory analysis of research candidate genes was completed. Association testing for genes carrying rare variants was completed using the gene-wise approach of the combined burden and variance-component test SKAT-O. Patch clamp analysis was performed on transfected HEK293T cells for research candidate variants of genes encoding ion channels. The results include the following: (i) Medically actionable variants were found in 12% of study participants (205 recruited), including known pathogenic variants: SCN9A(ENST00000409672.1): c.2544T>C, p.Ile848Thr that causes inherited erythromelalgia, and SPTLC1(ENST00000262554.2):c.340T>G, p.Cys133Tr variant that causes hereditary sensory neuropathy type-1. (ii) Clinically relevant variants were most common in voltage-gated sodium channels (Nav). (iii) SCN9A(ENST00000409672.1):c.554G>A, pArg185His variant was more common in non-freezing cold injury participants than controls and causes a gain of function of NaV1.7 after cooling (the environmental trigger for non-freezing cold injury). (iv) Rare variant association testing showed a significant difference in distribution for genes NGF, KIF1A, SCN8A, TRPM8, KIF1A, TRPA1 and the regulatory regions of genes SCN11A, FLVCR1, KIF1A and SCN9A between European participants with neuropathic pain and controls. (v) The TRPA1(ENST00000262209.4):c.515C>T, p.Ala172Val variant identified in participants with episodic somatic pain disorder demonstrated gain-of-channel function to agonist stimulation. Whole genome sequencing identified clinically relevant variants in over 10% of participants with extreme neuropathic pain phenotypes. The majority of these variants were found in ion channels. Combining genetic analysis with functional validation can lead to a better understanding as to how rare variants in ion channels lead to sensory neuron hyper-excitability, and how cold, as an environmental trigger, interacts with the gain-of-function NaV1.7 p.Arg185His variant. Our findings highlight the role of ion channel variants in the pathogenesis of extreme neuropathic pain disorders, likely mediated through changes in sensory neuron excitability and interaction with environmental triggers.", + "laySummary": "", + "urls": "pdf:https://academic.oup.com/braincomms/article-pdf/5/2/fcad037/49446967/fcad037.pdf; doi:https://doi.org/10.1093/braincomms/fcad037; html:https://europepmc.org/articles/PMC9991512; pdf:https://europepmc.org/articles/PMC9991512?pdf=render" + }, { "id": "31922447", "doi": "https://doi.org/10.1177/0141076819890551", @@ -40085,23 +40085,6 @@ "laySummary": "", "urls": "pdf:https://www.bmj.com/content/bmj/368/bmj.l6927.full.pdf; doi:https://doi.org/10.1136/bmj.l6927" }, - { - "id": "35347521", - "doi": "https://doi.org/10.1007/s11136-022-03119-w", - "title": "Knowledge translation concerns for the CONSORT-PRO extension reporting guidance: a review of reviews.", - "authorString": "Mercieca-Bebber R, Aiyegbusi OL, King MT, Brundage M, Snyder C, Calvert M.", - "authorAffiliations": "", - "journalTitle": "Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation", - "pubYear": "2022", - "date": "2022-03-26", - "isOpenAccess": "Y", - "keywords": "Quality of life; research methodology; Reporting; Patient-reported Outcomes; Research Waste; Consort-pro", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "This review of reviews aimed to appraise the use of the CONSORT-PRO Extension as an evaluation tool for assessing the reporting of patient-reported outcome (PROs) in publications, and to describe the reporting of PRO research across reviews. We also outlined how variation in such evaluations impacts knowledge translation and may lead to potential misuse of the CONSORT-PRO Extension. We systematically searched Medline, Pubmed and CINAHL from 2013 to 2025 March 2021 for reviews of the completeness of reporting of PRO endpoints according to CONSORT-PRO criteria. Two reviewers extracted details of each review, the percentage of included studies that addressed each CONSORT-PRO item, and key recommendations from each review. Fourteen reviews met inclusion criteria, and only six of these used the full CONSORT-PRO checklist with minimal justified modifications. The remaining eight studies made significant or unjustified adjustments to the CONSORT-PRO Extension. Review studies also varied in how they scored multi-component CONSORT-PRO items. CONSORT-PRO items were often unreported in trial reports, and certain CONSORT-PRO items were reported less often than others. The reporting of statistical approaches to dealing with missing PRO data were poor in RCTs included in all 14 review articles. Studies reviewing PRO publications often omitted recommended CONSORT-PRO items from their evaluations, which may cause confusion among readers regarding how best to report their PRO research according to the CONSORT-PRO extension. Many trials published since CONSORT-PRO's release did not report recommended CONSORT-PRO items, which may lead to misinterpretation and consequently to research waste.", - "laySummary": "", - "urls": "pdf:https://link.springer.com/content/pdf/10.1007/s11136-022-03119-w.pdf; doi:https://doi.org/10.1007/s11136-022-03119-w; html:https://europepmc.org/articles/PMC9470606; pdf:https://europepmc.org/articles/PMC9470606?pdf=render" - }, { "id": "31112426", "doi": "https://doi.org/10.1161/circgen.118.002436", @@ -40119,6 +40102,23 @@ "laySummary": "", "urls": "pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCGEN.118.002436; doi:https://doi.org/10.1161/CIRCGEN.118.002436" }, + { + "id": "35347521", + "doi": "https://doi.org/10.1007/s11136-022-03119-w", + "title": "Knowledge translation concerns for the CONSORT-PRO extension reporting guidance: a review of reviews.", + "authorString": "Mercieca-Bebber R, Aiyegbusi OL, King MT, Brundage M, Snyder C, Calvert M.", + "authorAffiliations": "", + "journalTitle": "Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation", + "pubYear": "2022", + "date": "2022-03-26", + "isOpenAccess": "Y", + "keywords": "Quality of life; research methodology; Reporting; Patient-reported Outcomes; Research Waste; Consort-pro", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "This review of reviews aimed to appraise the use of the CONSORT-PRO Extension as an evaluation tool for assessing the reporting of patient-reported outcome (PROs) in publications, and to describe the reporting of PRO research across reviews. We also outlined how variation in such evaluations impacts knowledge translation and may lead to potential misuse of the CONSORT-PRO Extension. We systematically searched Medline, Pubmed and CINAHL from 2013 to 2025 March 2021 for reviews of the completeness of reporting of PRO endpoints according to CONSORT-PRO criteria. Two reviewers extracted details of each review, the percentage of included studies that addressed each CONSORT-PRO item, and key recommendations from each review. Fourteen reviews met inclusion criteria, and only six of these used the full CONSORT-PRO checklist with minimal justified modifications. The remaining eight studies made significant or unjustified adjustments to the CONSORT-PRO Extension. Review studies also varied in how they scored multi-component CONSORT-PRO items. CONSORT-PRO items were often unreported in trial reports, and certain CONSORT-PRO items were reported less often than others. The reporting of statistical approaches to dealing with missing PRO data were poor in RCTs included in all 14 review articles. Studies reviewing PRO publications often omitted recommended CONSORT-PRO items from their evaluations, which may cause confusion among readers regarding how best to report their PRO research according to the CONSORT-PRO extension. Many trials published since CONSORT-PRO's release did not report recommended CONSORT-PRO items, which may lead to misinterpretation and consequently to research waste.", + "laySummary": "", + "urls": "pdf:https://link.springer.com/content/pdf/10.1007/s11136-022-03119-w.pdf; doi:https://doi.org/10.1007/s11136-022-03119-w; html:https://europepmc.org/articles/PMC9470606; pdf:https://europepmc.org/articles/PMC9470606?pdf=render" + }, { "id": "33248277", "doi": "https://doi.org/10.1016/j.jclinepi.2020.11.014", @@ -40170,23 +40170,6 @@ "laySummary": "", "urls": "pdf:https://fn.bmj.com/content/fetalneonatal/early/2023/01/30/archdischild-2022-324548.full.pdf; doi:https://doi.org/10.1136/archdischild-2022-324548; html:https://europepmc.org/articles/PMC10314049; pdf:https://europepmc.org/articles/PMC10314049?pdf=render" }, - { - "id": "37601966", - "doi": "https://doi.org/10.1016/j.xgen.2023.100361", - "title": "Genotyping and population characteristics of the China Kadoorie Biobank.", - "authorString": "Walters RG, Millwood IY, Lin K, Schmidt Valle D, McDonnell P, Hacker A, Avery D, Edris A, Fry H, Cai N, Kretzschmar WW, Ansari MA, Lyons PA, Collins R, Donnelly P, Hill M, Peto R, Shen H, Jin X, Nie C, Xu X, Guo Y, Yu C, Lv J, Clarke RJ, Li L, Chen Z, China Kadoorie Biobank Collaborative Group.", - "authorAffiliations": "", - "journalTitle": "Cell genomics", - "pubYear": "2023", - "date": "2023-07-20", - "isOpenAccess": "Y", - "keywords": "Genetics; Genetic epidemiology; Genotyping; complex disease; Gwas; Genetic Association Studies; Biobank; Omics; Prospective; Cardiovascular Health", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "The China Kadoorie Biobank (CKB) is a population-based prospective cohort of >512,000 adults recruited from 2004 to 2008 from 10 geographically diverse regions across China. Detailed data from questionnaires and physical measurements were collected at baseline, with additional measurements at three resurveys involving \u223c5% of surviving participants. Analyses of genome-wide genotyping, for >100,000 participants using\u00a0custom-designed Axiom arrays, reveal extensive relatedness, recent consanguinity, and signatures reflecting large-scale population movements from recent Chinese history. Systematic genome-wide association studies of incident disease, captured through electronic linkage to death and disease registries and to the national health insurance system, replicate established disease loci and identify 14 novel disease associations. Together with studies of candidate drug targets and disease risk factors and contributions to international genetics consortia, these demonstrate the breadth, depth, and quality of the CKB data. Ongoing high-throughput omics assays of collected biosamples and planned whole-genome sequencing will further enhance the scientific value of this biobank.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1016/j.xgen.2023.100361; doi:https://doi.org/10.1016/j.xgen.2023.100361; html:https://europepmc.org/articles/PMC10435379; pdf:https://europepmc.org/articles/PMC10435379?pdf=render" - }, { "id": "32435697", "doi": "https://doi.org/10.1038/s41746-020-0267-x", @@ -40204,6 +40187,23 @@ "laySummary": "", "urls": "pdf:https://www.nature.com/articles/s41746-020-0267-x.pdf; doi:https://doi.org/10.1038/s41746-020-0267-x; html:https://europepmc.org/articles/PMC7224173; pdf:https://europepmc.org/articles/PMC7224173?pdf=render" }, + { + "id": "37601966", + "doi": "https://doi.org/10.1016/j.xgen.2023.100361", + "title": "Genotyping and population characteristics of the China Kadoorie Biobank.", + "authorString": "Walters RG, Millwood IY, Lin K, Schmidt Valle D, McDonnell P, Hacker A, Avery D, Edris A, Fry H, Cai N, Kretzschmar WW, Ansari MA, Lyons PA, Collins R, Donnelly P, Hill M, Peto R, Shen H, Jin X, Nie C, Xu X, Guo Y, Yu C, Lv J, Clarke RJ, Li L, Chen Z, China Kadoorie Biobank Collaborative Group.", + "authorAffiliations": "", + "journalTitle": "Cell genomics", + "pubYear": "2023", + "date": "2023-07-20", + "isOpenAccess": "Y", + "keywords": "Genetics; Genetic epidemiology; Genotyping; complex disease; Gwas; Genetic Association Studies; Biobank; Omics; Prospective; Cardiovascular Health", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "The China Kadoorie Biobank (CKB) is a population-based prospective cohort of >512,000 adults recruited from 2004 to 2008 from 10 geographically diverse regions across China. Detailed data from questionnaires and physical measurements were collected at baseline, with additional measurements at three resurveys involving \u223c5% of surviving participants. Analyses of genome-wide genotyping, for >100,000 participants using\u00a0custom-designed Axiom arrays, reveal extensive relatedness, recent consanguinity, and signatures reflecting large-scale population movements from recent Chinese history. Systematic genome-wide association studies of incident disease, captured through electronic linkage to death and disease registries and to the national health insurance system, replicate established disease loci and identify 14 novel disease associations. Together with studies of candidate drug targets and disease risk factors and contributions to international genetics consortia, these demonstrate the breadth, depth, and quality of the CKB data. Ongoing high-throughput omics assays of collected biosamples and planned whole-genome sequencing will further enhance the scientific value of this biobank.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1016/j.xgen.2023.100361; doi:https://doi.org/10.1016/j.xgen.2023.100361; html:https://europepmc.org/articles/PMC10435379; pdf:https://europepmc.org/articles/PMC10435379?pdf=render" + }, { "id": "35189842", "doi": "https://doi.org/10.1186/s12888-022-03753-1", @@ -40272,23 +40272,6 @@ "laySummary": "", "urls": "pdf:https://neurologyopen.bmj.com/content/bmjno/3/1/e000133.full.pdf; doi:https://doi.org/10.1136/bmjno-2021-000133; html:https://europepmc.org/articles/PMC8183200; pdf:https://europepmc.org/articles/PMC8183200?pdf=render" }, - { - "id": "35876478", - "doi": "https://doi.org/10.3201/eid2808.211787", - "title": "Lack of Evidence for Ribavirin Treatment of Lassa Fever in Systematic Review of Published and Unpublished Studies1.", - "authorString": "Cheng HY, French CE, Salam AP, Dawson S, McAleenan A, McGuinness LA, Savovi\u0107 J, Horby PW, Sterne JAC.", - "authorAffiliations": "", - "journalTitle": "Emerging infectious diseases", - "pubYear": "2022", - "date": "2022-08-01", - "isOpenAccess": "Y", - "keywords": "Viruses; Bias; Ribavirin; Systematic review; Observational Study; Lassa Fever", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Ribavirin has been used widely to treat Lassa fever in West Africa since the 1980s. However, few studies have systematically appraised the evidence for its use. We conducted a systematic review of published and unpublished literature retrieved from electronic databases and gray literature from inception to March 8, 2022. We identified 13 studies of the comparative effectiveness of ribavirin versus no ribavirin treatment on mortality outcomes, including unpublished data from a study in Sierra Leone provided through a US Freedom of Information Act request. Although ribavirin was associated with decreased mortality rates, results of these studies were at critical or serious risk for bias when appraised using the ROBINS-I tool. Important risks for bias related to lack of control for confounders, immortal time bias, and missing outcome data. Robust evidence supporting the use of ribavirin in Lassa fever is lacking. Well-conducted clinical trials to elucidate the effectiveness of ribavirin for Lassa fever are needed.", - "laySummary": "", - "urls": "pdf:https://wwwnc.cdc.gov/eid/article/28/8/pdfs/21-1787.pdf; doi:https://doi.org/10.3201/eid2808.211787; html:https://europepmc.org/articles/PMC9328902; pdf:https://europepmc.org/articles/PMC9328902?pdf=render" - }, { "id": "31160290", "doi": "https://doi.org/10.1128/aac.00400-19", @@ -40306,6 +40289,23 @@ "laySummary": "", "urls": "pdf:https://aac.asm.org/content/aac/63/8/e00400-19.full.pdf; doi:https://doi.org/10.1128/AAC.00400-19; html:https://europepmc.org/articles/PMC6658746; pdf:https://europepmc.org/articles/PMC6658746?pdf=render; doi:https://doi.org/10.1128/aac.00400-19" }, + { + "id": "35876478", + "doi": "https://doi.org/10.3201/eid2808.211787", + "title": "Lack of Evidence for Ribavirin Treatment of Lassa Fever in Systematic Review of Published and Unpublished Studies1.", + "authorString": "Cheng HY, French CE, Salam AP, Dawson S, McAleenan A, McGuinness LA, Savovi\u0107 J, Horby PW, Sterne JAC.", + "authorAffiliations": "", + "journalTitle": "Emerging infectious diseases", + "pubYear": "2022", + "date": "2022-08-01", + "isOpenAccess": "Y", + "keywords": "Viruses; Bias; Ribavirin; Systematic review; Observational Study; Lassa Fever", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Ribavirin has been used widely to treat Lassa fever in West Africa since the 1980s. However, few studies have systematically appraised the evidence for its use. We conducted a systematic review of published and unpublished literature retrieved from electronic databases and gray literature from inception to March 8, 2022. We identified 13 studies of the comparative effectiveness of ribavirin versus no ribavirin treatment on mortality outcomes, including unpublished data from a study in Sierra Leone provided through a US Freedom of Information Act request. Although ribavirin was associated with decreased mortality rates, results of these studies were at critical or serious risk for bias when appraised using the ROBINS-I tool. Important risks for bias related to lack of control for confounders, immortal time bias, and missing outcome data. Robust evidence supporting the use of ribavirin in Lassa fever is lacking. Well-conducted clinical trials to elucidate the effectiveness of ribavirin for Lassa fever are needed.", + "laySummary": "", + "urls": "pdf:https://wwwnc.cdc.gov/eid/article/28/8/pdfs/21-1787.pdf; doi:https://doi.org/10.3201/eid2808.211787; html:https://europepmc.org/articles/PMC9328902; pdf:https://europepmc.org/articles/PMC9328902?pdf=render" + }, { "id": "38432242", "doi": "https://doi.org/10.1016/s2352-3026(24)00030-9", @@ -40459,23 +40459,6 @@ "laySummary": "", "urls": "pdf:https://www.science.org/cms/asset/e974db95-138d-4a9f-aa91-2f8f6c705f36/pap.pdf; doi:https://doi.org/10.1126/science.abf9648; html:https://europepmc.org/articles/PMC8139426; pdf:https://europepmc.org/articles/PMC8139426?pdf=render" }, - { - "id": "37393924", - "doi": "https://doi.org/10.1016/s0140-6736(23)00860-7", - "title": "The unfinished agenda of communicable diseases among children and adolescents before the COVID-19 pandemic, 1990-2019: a systematic analysis of the Global Burden of Disease Study 2019.", - "authorString": "GBD 2019 Child and Adolescent Communicable Disease Collaborators.", - "authorAffiliations": "", - "journalTitle": "Lancet (London, England)", - "pubYear": "2023", - "date": "2023-06-29", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Communicable disease control has long been a focus of global health policy. There have been substantial reductions in the burden and mortality of communicable diseases among children younger than 5 years, but we know less about this burden in older children and adolescents, and it is unclear whether current programmes and policies remain aligned with targets for intervention. This knowledge is especially important for policy and programmes in the context of the COVID-19 pandemic. We aimed to use the Global Burden of Disease (GBD) Study 2019 to systematically characterise the burden of communicable diseases across childhood and adolescence.

Methods

In this systematic analysis of the GBD study from 1990 to 2019, all communicable diseases and their manifestations as modelled within GBD 2019 were included, categorised as 16 subgroups of common diseases or presentations. Data were reported for absolute count, prevalence, and incidence across measures of cause-specific mortality (deaths and years of life lost), disability (years lived with disability [YLDs]), and disease burden (disability-adjusted life-years [DALYs]) for children and adolescents aged 0-24 years. Data were reported across the Socio-demographic Index (SDI) and across time (1990-2019), and for 204 countries and territories. For HIV, we reported the mortality-to-incidence ratio (MIR) as a measure of health system performance.

Findings

In 2019, there were 3\u00b70 million deaths and 30\u00b70 million years of healthy life lost to disability (as measured by YLDs), corresponding to 288\u00b74 million DALYs from communicable diseases among children and adolescents globally (57\u00b73% of total communicable disease burden across all ages). Over time, there has been a shift in communicable disease burden from young children to older children and adolescents (largely driven by the considerable reductions in children younger than 5 years and slower progress elsewhere), although children younger than 5 years still accounted for most of the communicable disease burden in 2019. Disease burden and mortality were predominantly in low-SDI settings, with high and high-middle SDI settings also having an appreciable burden of communicable disease morbidity (4\u00b70 million YLDs in 2019 alone). Three cause groups (enteric infections, lower-respiratory-tract infections, and malaria) accounted for 59\u00b78% of the global communicable disease burden in children and adolescents, with tuberculosis and HIV both emerging as important causes during adolescence. HIV was the only cause for which disease burden increased over time, particularly in children and adolescents older than 5 years, and especially in females. Excess MIRs for HIV were observed for males aged 15-19 years in low-SDI settings.

Interpretation

Our analysis supports continued policy focus on enteric infections and lower-respiratory-tract infections, with orientation to children younger than 5 years in settings of low socioeconomic development. However, efforts should also be targeted to other conditions, particularly HIV, given its increased burden in older children and adolescents. Older children and adolescents also experience a large burden of communicable disease, further highlighting the need for efforts to extend beyond the first 5 years of life. Our analysis also identified substantial morbidity caused by communicable diseases affecting child and adolescent health across the world.

Funding

The Australian National Health and Medical Research Council Centre for Research Excellence for Driving Investment in Global Adolescent Health and the Bill & Melinda Gates Foundation.", - "laySummary": "", - "urls": "pdf:http://www.thelancet.com/article/S0140673623008607/pdf; doi:https://doi.org/10.1016/S0140-6736(23)00860-7; html:https://europepmc.org/articles/PMC10375221; pdf:https://europepmc.org/articles/PMC10375221?pdf=render" - }, { "id": "34446501", "doi": "https://doi.org/10.1136/bmjopen-2021-052629", @@ -40493,6 +40476,23 @@ "laySummary": "", "urls": "pdf:https://bmjopen.bmj.com/content/bmjopen/11/8/e052629.full.pdf; doi:https://doi.org/10.1136/bmjopen-2021-052629; html:https://europepmc.org/articles/PMC8395280; pdf:https://europepmc.org/articles/PMC8395280?pdf=render" }, + { + "id": "37393924", + "doi": "https://doi.org/10.1016/s0140-6736(23)00860-7", + "title": "The unfinished agenda of communicable diseases among children and adolescents before the COVID-19 pandemic, 1990-2019: a systematic analysis of the Global Burden of Disease Study 2019.", + "authorString": "GBD 2019 Child and Adolescent Communicable Disease Collaborators.", + "authorAffiliations": "", + "journalTitle": "Lancet (London, England)", + "pubYear": "2023", + "date": "2023-06-29", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Communicable disease control has long been a focus of global health policy. There have been substantial reductions in the burden and mortality of communicable diseases among children younger than 5 years, but we know less about this burden in older children and adolescents, and it is unclear whether current programmes and policies remain aligned with targets for intervention. This knowledge is especially important for policy and programmes in the context of the COVID-19 pandemic. We aimed to use the Global Burden of Disease (GBD) Study 2019 to systematically characterise the burden of communicable diseases across childhood and adolescence.

Methods

In this systematic analysis of the GBD study from 1990 to 2019, all communicable diseases and their manifestations as modelled within GBD 2019 were included, categorised as 16 subgroups of common diseases or presentations. Data were reported for absolute count, prevalence, and incidence across measures of cause-specific mortality (deaths and years of life lost), disability (years lived with disability [YLDs]), and disease burden (disability-adjusted life-years [DALYs]) for children and adolescents aged 0-24 years. Data were reported across the Socio-demographic Index (SDI) and across time (1990-2019), and for 204 countries and territories. For HIV, we reported the mortality-to-incidence ratio (MIR) as a measure of health system performance.

Findings

In 2019, there were 3\u00b70 million deaths and 30\u00b70 million years of healthy life lost to disability (as measured by YLDs), corresponding to 288\u00b74 million DALYs from communicable diseases among children and adolescents globally (57\u00b73% of total communicable disease burden across all ages). Over time, there has been a shift in communicable disease burden from young children to older children and adolescents (largely driven by the considerable reductions in children younger than 5 years and slower progress elsewhere), although children younger than 5 years still accounted for most of the communicable disease burden in 2019. Disease burden and mortality were predominantly in low-SDI settings, with high and high-middle SDI settings also having an appreciable burden of communicable disease morbidity (4\u00b70 million YLDs in 2019 alone). Three cause groups (enteric infections, lower-respiratory-tract infections, and malaria) accounted for 59\u00b78% of the global communicable disease burden in children and adolescents, with tuberculosis and HIV both emerging as important causes during adolescence. HIV was the only cause for which disease burden increased over time, particularly in children and adolescents older than 5 years, and especially in females. Excess MIRs for HIV were observed for males aged 15-19 years in low-SDI settings.

Interpretation

Our analysis supports continued policy focus on enteric infections and lower-respiratory-tract infections, with orientation to children younger than 5 years in settings of low socioeconomic development. However, efforts should also be targeted to other conditions, particularly HIV, given its increased burden in older children and adolescents. Older children and adolescents also experience a large burden of communicable disease, further highlighting the need for efforts to extend beyond the first 5 years of life. Our analysis also identified substantial morbidity caused by communicable diseases affecting child and adolescent health across the world.

Funding

The Australian National Health and Medical Research Council Centre for Research Excellence for Driving Investment in Global Adolescent Health and the Bill & Melinda Gates Foundation.", + "laySummary": "", + "urls": "pdf:http://www.thelancet.com/article/S0140673623008607/pdf; doi:https://doi.org/10.1016/S0140-6736(23)00860-7; html:https://europepmc.org/articles/PMC10375221; pdf:https://europepmc.org/articles/PMC10375221?pdf=render" + }, { "id": "31995663", "doi": "https://doi.org/10.1111/cts.12725", @@ -40765,23 +40765,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.12688/wellcomeopenres.17403.2; html:https://europepmc.org/articles/PMC9951545; pdf:https://europepmc.org/articles/PMC9951545?pdf=render" }, - { - "id": "33208942", - "doi": "https://doi.org/10.1038/s41586-020-2927-z", - "title": "Host ANP32A mediates the assembly of the influenza virus replicase.", - "authorString": "Carrique L, Fan H, Walker AP, Keown JR, Sharps J, Staller E, Barclay WS, Fodor E, Grimes JM.", - "authorAffiliations": "", - "journalTitle": "Nature", - "pubYear": "2020", - "date": "2020-11-18", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Aquatic birds represent a vast reservoir from which new pandemic influenza A viruses can emerge1. Influenza viruses contain a negative-sense segmented RNA genome that is transcribed and replicated by the viral heterotrimeric RNA polymerase (FluPol) in the context of viral ribonucleoprotein complexes2,3. RNA polymerases of avian influenza A viruses (FluPolA) replicate viral RNA inefficiently in human cells because of species-specific differences in acidic nuclear phosphoprotein 32 (ANP32), a family of essential host proteins for FluPol activity4. Host-adaptive mutations, particularly a glutamic-acid-to-lysine mutation at amino acid residue 627 (E627K) in the 627 domain of the PB2 subunit, enable avian FluPolA to overcome this restriction and efficiently replicate viral RNA in the presence of human ANP32 proteins. However, the molecular mechanisms of genome replication and the interplay with ANP32 proteins remain largely unknown. Here we report cryo-electron microscopy structures of influenza C virus polymerase (FluPolC) in complex with human and chicken ANP32A. In both structures, two FluPolC molecules form an asymmetric dimer bridged by the N-terminal leucine-rich repeat domain of ANP32A. The C-terminal low-complexity acidic region of ANP32A inserts between the two juxtaposed PB2 627 domains of the asymmetric FluPolA dimer, suggesting a mechanism for how the adaptive PB2(E627K) mutation enables the replication of viral RNA in mammalian hosts. We propose that this complex represents a replication platform for the viral RNA genome, in which one of the FluPol molecules acts as a replicase while the other initiates the assembly of the nascent replication product into a viral ribonucleoprotein complex.", - "laySummary": "", - "urls": "pdf:https://www.nature.com/articles/s41586-020-2927-z.pdf; doi:https://doi.org/10.1038/s41586-020-2927-z; html:https://europepmc.org/articles/PMC7116770; pdf:https://europepmc.org/articles/PMC7116770?pdf=render" - }, { "id": "31978332", "doi": "https://doi.org/10.1016/j.ajhg.2020.01.003", @@ -40799,6 +40782,23 @@ "laySummary": " ", "urls": "pdf:http://www.cell.com/article/S0002929720300033/pdf; doi:https://doi.org/10.1016/j.ajhg.2020.01.003; html:https://europepmc.org/articles/PMC7010967; pdf:https://europepmc.org/articles/PMC7010967?pdf=render" }, + { + "id": "33208942", + "doi": "https://doi.org/10.1038/s41586-020-2927-z", + "title": "Host ANP32A mediates the assembly of the influenza virus replicase.", + "authorString": "Carrique L, Fan H, Walker AP, Keown JR, Sharps J, Staller E, Barclay WS, Fodor E, Grimes JM.", + "authorAffiliations": "", + "journalTitle": "Nature", + "pubYear": "2020", + "date": "2020-11-18", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Aquatic birds represent a vast reservoir from which new pandemic influenza A viruses can emerge1. Influenza viruses contain a negative-sense segmented RNA genome that is transcribed and replicated by the viral heterotrimeric RNA polymerase (FluPol) in the context of viral ribonucleoprotein complexes2,3. RNA polymerases of avian influenza A viruses (FluPolA) replicate viral RNA inefficiently in human cells because of species-specific differences in acidic nuclear phosphoprotein 32 (ANP32), a family of essential host proteins for FluPol activity4. Host-adaptive mutations, particularly a glutamic-acid-to-lysine mutation at amino acid residue 627 (E627K) in the 627 domain of the PB2 subunit, enable avian FluPolA to overcome this restriction and efficiently replicate viral RNA in the presence of human ANP32 proteins. However, the molecular mechanisms of genome replication and the interplay with ANP32 proteins remain largely unknown. Here we report cryo-electron microscopy structures of influenza C virus polymerase (FluPolC) in complex with human and chicken ANP32A. In both structures, two FluPolC molecules form an asymmetric dimer bridged by the N-terminal leucine-rich repeat domain of ANP32A. The C-terminal low-complexity acidic region of ANP32A inserts between the two juxtaposed PB2 627 domains of the asymmetric FluPolA dimer, suggesting a mechanism for how the adaptive PB2(E627K) mutation enables the replication of viral RNA in mammalian hosts. We propose that this complex represents a replication platform for the viral RNA genome, in which one of the FluPol molecules acts as a replicase while the other initiates the assembly of the nascent replication product into a viral ribonucleoprotein complex.", + "laySummary": "", + "urls": "pdf:https://www.nature.com/articles/s41586-020-2927-z.pdf; doi:https://doi.org/10.1038/s41586-020-2927-z; html:https://europepmc.org/articles/PMC7116770; pdf:https://europepmc.org/articles/PMC7116770?pdf=render" + }, { "id": "34319235", "doi": "https://doi.org/10.2196/28873", @@ -41207,23 +41207,6 @@ "laySummary": "", "urls": "pdf:http://www.cell.com/article/S1074761322000462/pdf; doi:https://doi.org/10.1016/j.immuni.2022.01.017; html:https://europepmc.org/articles/PMC8789571; pdf:https://europepmc.org/articles/PMC8789571?pdf=render" }, - { - "id": "34812717", - "doi": "https://doi.org/10.1099/mgen.0.000700", - "title": "Antimicrobial resistance determinants are associated with Staphylococcus aureus bacteraemia and adaptation to the healthcare environment: a bacterial genome-wide association study.", - "authorString": "Young BC, Wu CH, Charlesworth J, Earle S, Price JR, Gordon NC, Cole K, Dunn L, Liu E, Oakley S, Godwin H, Fung R, Miller R, Knox K, Votintseva A, Quan TP, Tilley R, Scarborough M, Crook DW, Peto TE, Walker AS, Llewelyn MJ, Wilson DJ.", - "authorAffiliations": "", - "journalTitle": "Microbial genomics", - "pubYear": "2021", - "date": "2021-11-01", - "isOpenAccess": "Y", - "keywords": "Nosocomial infection; Bacterial Pathogens; Bacteraemia; Microbial Genomics; Microbial Epidemiology", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Staphylococcus aureus is a major bacterial pathogen in humans, and a dominant cause of severe bloodstream infections. Globally, antimicrobial resistance (AMR) in S. aureus remains challenging. While human risk factors for infection have been defined, contradictory evidence exists for the role of bacterial genomic variation in S. aureus disease. To investigate the contribution of bacterial lineage and genomic variation to the development of bloodstream infection, we undertook a genome-wide association study comparing bacteria from 1017 individuals with bacteraemia to 984 adults with asymptomatic S. aureus nasal carriage. Within 984 carriage isolates, we also compared healthcare-associated (HA) carriage with community-associated (CA) carriage. All major global lineages were represented in both bacteraemia and carriage, with no evidence for different infection rates. However, kmers tagging trimethoprim resistance-conferring mutation F99Y in dfrB were significantly associated with bacteraemia-vs-carriage (P=10-8.9-10-9.3). Pooling variation within genes, bacteraemia-vs-carriage was associated with the presence of mecA (HMP=10-5.3) as well as the presence of SCCmec (HMP=10-4.4). Among S. aureus carriers, no lineages were associated with HA-vs-CA carriage. However, we found a novel signal of HA-vs-CA carriage in the foldase protein prsA, where kmers representing conserved sequence allele were associated with CA carriage (P=10-7.1-10-19.4), while in gyrA, a ciprofloxacin resistance-conferring mutation, L84S, was associated with HA carriage (P=10-7.2). In an extensive study of S. aureus bacteraemia and nasal carriage in the UK, we found strong evidence that all S. aureus lineages are equally capable of causing bloodstream infection, and of being carried in the healthcare environment. Genomic variation in the foldase protein prsA is a novel genomic marker of healthcare origin in S. aureus but was not associated with bacteraemia. AMR determinants were associated with both bacteraemia and healthcare-associated carriage, suggesting that AMR increases the propensity not only to survive in healthcare environments, but also to cause invasive disease.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1099/mgen.0.000700; doi:https://doi.org/10.1099/mgen.0.000700; html:https://europepmc.org/articles/PMC8743558; pdf:https://europepmc.org/articles/PMC8743558?pdf=render" - }, { "id": "31951611", "doi": "https://doi.org/10.1371/journal.pbio.3000586", @@ -41241,6 +41224,23 @@ "laySummary": " ", "urls": "pdf:https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3000586&type=printable; doi:https://doi.org/10.1371/journal.pbio.3000586; html:https://europepmc.org/articles/PMC6992231; pdf:https://europepmc.org/articles/PMC6992231?pdf=render" }, + { + "id": "34812717", + "doi": "https://doi.org/10.1099/mgen.0.000700", + "title": "Antimicrobial resistance determinants are associated with Staphylococcus aureus bacteraemia and adaptation to the healthcare environment: a bacterial genome-wide association study.", + "authorString": "Young BC, Wu CH, Charlesworth J, Earle S, Price JR, Gordon NC, Cole K, Dunn L, Liu E, Oakley S, Godwin H, Fung R, Miller R, Knox K, Votintseva A, Quan TP, Tilley R, Scarborough M, Crook DW, Peto TE, Walker AS, Llewelyn MJ, Wilson DJ.", + "authorAffiliations": "", + "journalTitle": "Microbial genomics", + "pubYear": "2021", + "date": "2021-11-01", + "isOpenAccess": "Y", + "keywords": "Nosocomial infection; Bacterial Pathogens; Bacteraemia; Microbial Genomics; Microbial Epidemiology", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Staphylococcus aureus is a major bacterial pathogen in humans, and a dominant cause of severe bloodstream infections. Globally, antimicrobial resistance (AMR) in S. aureus remains challenging. While human risk factors for infection have been defined, contradictory evidence exists for the role of bacterial genomic variation in S. aureus disease. To investigate the contribution of bacterial lineage and genomic variation to the development of bloodstream infection, we undertook a genome-wide association study comparing bacteria from 1017 individuals with bacteraemia to 984 adults with asymptomatic S. aureus nasal carriage. Within 984 carriage isolates, we also compared healthcare-associated (HA) carriage with community-associated (CA) carriage. All major global lineages were represented in both bacteraemia and carriage, with no evidence for different infection rates. However, kmers tagging trimethoprim resistance-conferring mutation F99Y in dfrB were significantly associated with bacteraemia-vs-carriage (P=10-8.9-10-9.3). Pooling variation within genes, bacteraemia-vs-carriage was associated with the presence of mecA (HMP=10-5.3) as well as the presence of SCCmec (HMP=10-4.4). Among S. aureus carriers, no lineages were associated with HA-vs-CA carriage. However, we found a novel signal of HA-vs-CA carriage in the foldase protein prsA, where kmers representing conserved sequence allele were associated with CA carriage (P=10-7.1-10-19.4), while in gyrA, a ciprofloxacin resistance-conferring mutation, L84S, was associated with HA carriage (P=10-7.2). In an extensive study of S. aureus bacteraemia and nasal carriage in the UK, we found strong evidence that all S. aureus lineages are equally capable of causing bloodstream infection, and of being carried in the healthcare environment. Genomic variation in the foldase protein prsA is a novel genomic marker of healthcare origin in S. aureus but was not associated with bacteraemia. AMR determinants were associated with both bacteraemia and healthcare-associated carriage, suggesting that AMR increases the propensity not only to survive in healthcare environments, but also to cause invasive disease.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1099/mgen.0.000700; doi:https://doi.org/10.1099/mgen.0.000700; html:https://europepmc.org/articles/PMC8743558; pdf:https://europepmc.org/articles/PMC8743558?pdf=render" + }, { "id": "37810217", "doi": "https://doi.org/10.1016/j.isci.2023.107795", @@ -42040,23 +42040,6 @@ "laySummary": "", "urls": "doi:https://doi.org/10.1016/j.jadr.2021.100201; doi:https://doi.org/10.1016/j.jadr.2021.100201; html:https://europepmc.org/articles/PMC8689407" }, - { - "id": "34820659", - "doi": "https://doi.org/10.1016/j.xgen.2021.100028", - "title": "The Data Use Ontology to streamline responsible access to human biomedical datasets.", - "authorString": "Lawson J, Cabili MN, Kerry G, Boughtwood T, Thorogood A, Alper P, Bowers SR, Boyles RR, Brookes AJ, Brush M, Burdett T, Clissold H, Donnelly S, Dyke SOM, Freeberg MA, Haendel MA, Hata C, Holub P, Jeanson F, Jene A, Kawashima M, Kawashima S, Konopko M, Kyomugisha I, Li H, Linden M, Rodriguez LL, Morita M, Mulder N, Muller J, Nagaie S, Nasir J, Ogishima S, Ota Wang V, Paglione LD, Pandya RN, Parkinson H, Philippakis AA, Prasser F, Rambla J, Reinold K, Rushton GA, Saltzman A, Saunders G, Sofia HJ, Spalding JD, Swertz MA, Tulchinsky I, van Enckevort EJ, Varma S, Voisin C, Yamamoto N, Yamasaki C, Zass L, Guidry Auvil JM, Nyr\u00f6nen TH, Courtot M.", - "authorAffiliations": "", - "journalTitle": "Cell genomics", - "pubYear": "2021", - "date": "2021-11-10", - "isOpenAccess": "Y", - "keywords": "Standard; Consent; Ontology; Data Access; Fair; Secondary Data Use; Ga4gh; Data Restrictions; Controlled Access; Automated Data Access", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Human biomedical datasets that are critical for research and clinical studies to benefit human health also often contain sensitive or potentially identifying information of individual participants. Thus, care must be taken when they are processed and made available to comply with ethical and regulatory frameworks and informed consent data conditions. To enable and streamline data access for these biomedical datasets, the Global Alliance for Genomics and Health (GA4GH) Data Use and Researcher Identities (DURI) work stream developed and approved the Data Use Ontology (DUO) standard. DUO is a hierarchical vocabulary of human and machine-readable data use terms that consistently and unambiguously represents a dataset's allowable data uses. DUO has been implemented by major international stakeholders such as the Broad and Sanger Institutes and is currently used in annotation of over 200,000 datasets worldwide. Using DUO in data management and access facilitates researchers' discovery and access of relevant datasets. DUO annotations increase\u00a0the FAIRness of datasets and support data linkages using common data use profiles when integrating the data for secondary analyses. DUO is implemented in the Web Ontology Language (OWL) and, to increase community awareness and engagement, hosted in an open, centralized GitHub repository. DUO, together with the GA4GH Passport standard, offers a new, efficient, and streamlined data authorization and access framework that has enabled increased sharing of biomedical datasets worldwide.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1016/j.xgen.2021.100028; doi:https://doi.org/10.1016/j.xgen.2021.100028; html:https://europepmc.org/articles/PMC8591903; pdf:https://europepmc.org/articles/PMC8591903?pdf=render" - }, { "id": "33887342", "doi": "https://doi.org/10.1016/j.ijcard.2021.04.029", @@ -42074,6 +42057,23 @@ "laySummary": "", "urls": "pdf:https://pure.rug.nl/ws/files/200111410/1_s2.0_S0167527321006653_main.pdf; doi:https://doi.org/10.1016/j.ijcard.2021.04.029" }, + { + "id": "34820659", + "doi": "https://doi.org/10.1016/j.xgen.2021.100028", + "title": "The Data Use Ontology to streamline responsible access to human biomedical datasets.", + "authorString": "Lawson J, Cabili MN, Kerry G, Boughtwood T, Thorogood A, Alper P, Bowers SR, Boyles RR, Brookes AJ, Brush M, Burdett T, Clissold H, Donnelly S, Dyke SOM, Freeberg MA, Haendel MA, Hata C, Holub P, Jeanson F, Jene A, Kawashima M, Kawashima S, Konopko M, Kyomugisha I, Li H, Linden M, Rodriguez LL, Morita M, Mulder N, Muller J, Nagaie S, Nasir J, Ogishima S, Ota Wang V, Paglione LD, Pandya RN, Parkinson H, Philippakis AA, Prasser F, Rambla J, Reinold K, Rushton GA, Saltzman A, Saunders G, Sofia HJ, Spalding JD, Swertz MA, Tulchinsky I, van Enckevort EJ, Varma S, Voisin C, Yamamoto N, Yamasaki C, Zass L, Guidry Auvil JM, Nyr\u00f6nen TH, Courtot M.", + "authorAffiliations": "", + "journalTitle": "Cell genomics", + "pubYear": "2021", + "date": "2021-11-10", + "isOpenAccess": "Y", + "keywords": "Standard; Consent; Ontology; Data Access; Fair; Secondary Data Use; Ga4gh; Data Restrictions; Controlled Access; Automated Data Access", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Human biomedical datasets that are critical for research and clinical studies to benefit human health also often contain sensitive or potentially identifying information of individual participants. Thus, care must be taken when they are processed and made available to comply with ethical and regulatory frameworks and informed consent data conditions. To enable and streamline data access for these biomedical datasets, the Global Alliance for Genomics and Health (GA4GH) Data Use and Researcher Identities (DURI) work stream developed and approved the Data Use Ontology (DUO) standard. DUO is a hierarchical vocabulary of human and machine-readable data use terms that consistently and unambiguously represents a dataset's allowable data uses. DUO has been implemented by major international stakeholders such as the Broad and Sanger Institutes and is currently used in annotation of over 200,000 datasets worldwide. Using DUO in data management and access facilitates researchers' discovery and access of relevant datasets. DUO annotations increase\u00a0the FAIRness of datasets and support data linkages using common data use profiles when integrating the data for secondary analyses. DUO is implemented in the Web Ontology Language (OWL) and, to increase community awareness and engagement, hosted in an open, centralized GitHub repository. DUO, together with the GA4GH Passport standard, offers a new, efficient, and streamlined data authorization and access framework that has enabled increased sharing of biomedical datasets worldwide.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1016/j.xgen.2021.100028; doi:https://doi.org/10.1016/j.xgen.2021.100028; html:https://europepmc.org/articles/PMC8591903; pdf:https://europepmc.org/articles/PMC8591903?pdf=render" + }, { "id": "31730918", "doi": "https://doi.org/10.1016/j.jclinepi.2019.11.006", @@ -42516,23 +42516,6 @@ "laySummary": "", "urls": "pdf:https://academic.oup.com/jnci/article-pdf/114/5/740/43623241/djac011.pdf; doi:https://doi.org/10.1093/jnci/djac011; html:https://europepmc.org/articles/PMC9086764; pdf:https://europepmc.org/articles/PMC9086764?pdf=render" }, - { - "id": "36240095", - "doi": "https://doi.org/10.1212/wnl.0000000000201006", - "title": "Contribution of Common Genetic Variants to Risk of Early-Onset Ischemic Stroke.", - "authorString": "Jaworek T, Xu H, Gaynor BJ, Cole JW, Rannikmae K, Stanne TM, Tomppo L, Abedi V, Amouyel P, Armstrong ND, Attia J, Bell S, Benavente OR, Boncoraglio GB, Butterworth A, Cervical Artery Dissections and Ischemic Stroke Patients (CADSIP) Consortium, Carcel-Marquez J, Chen Z, Chong M, Cruchaga C, Cushman M, Danesh J, Debette S, Duggan DJ, Durda JP, Engstrom G, Enzinger C, Faul JD, Fecteau NS, Fernandez-Cadenas I, Gieger C, Giese AK, Grewal RP, Grittner U, Havulinna AS, Heitsch L, Hochberg MC, Holliday E, Hu J, Hu J, Ilinca A, INVENT Consortium, Irvin MR, Jackson RD, Jacob MA, Rabionet R, Jimenez-Conde J, Johnson JA, Kamatani Y, Kardia SLR, Koido M, Kubo M, Lange L, Lee JM, Lemmens R, Levi CR, Li J, Li L, Lin K, Lopez H, Luke S, Maguire J, McArdle PF, McDonough CW, Meschia JF, Metso T, M\u00fcller-Nurasyid M, O'Connor TD, O'Donnell M, Peddareddygari LR, Pera J, Perry JA, Peters A, Putaala J, Ray D, Rexrode K, Ribases M, Rosand J, Rothwell PM, Rundek T, Ryan KA, Sacco RL, Salomaa V, Sanchez-Mora C, Schmidt R, Sharma P, Slowik A, Smith JA, Smith NL, Wassertheil-Smoller S, S\u00f6derholm M, Stine OC, Strbian D, Sudlow CLM, Tatlisumak T, Terao C, Thijs V, Torres-Aguila NP, Tr\u00e9gou\u00ebt DA, Tuladhar AM, Veldink JH, Walters RG, Weir DR, Woo D, Worrall BB, Hong CC, Ross OA, Zand R, Leeuw FE, Lindgren AG, Pare G, Anderson CD, Markus HS, Jern C, Malik R, Dichgans M, Mitchell BD, Kittner SJ, Early Onset Stroke Genetics Consortium of the International Stroke Genetics Consortium (ISGC).", - "authorAffiliations": "", - "journalTitle": "Neurology", - "pubYear": "2022", - "date": "2022-10-17", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background and objectives

Current genome-wide association studies of ischemic stroke have focused primarily on late-onset disease. As a complement to these studies, we sought to identify the contribution of common genetic variants to risk of early-onset ischemic stroke.

Methods

We performed a meta-analysis of genome-wide association studies of early-onset stroke (EOS), ages 18-59 years, using individual-level data or summary statistics in 16,730 cases and 599,237 nonstroke controls obtained across 48 different studies. We further compared effect sizes at associated loci between EOS and late-onset stroke (LOS) and compared polygenic risk scores (PRS) for venous thromboembolism (VTE) between EOS and LOS.

Results

We observed genome-wide significant associations of EOS with 2 variants in ABO, a known stroke locus. These variants tag blood subgroups O1 and A1, and the effect sizes of both variants were significantly larger in EOS compared with LOS. The odds ratio (OR) for rs529565, tagging O1, was 0.88 (95% confidence interval [CI]: 0.85-0.91) in EOS vs 0.96 (95% CI: 0.92-1.00) in LOS, and the OR for rs635634, tagging A1, was 1.16 (1.11-1.21) for EOS vs 1.05 (0.99-1.11) in LOS; p-values for interaction = 0.001 and 0.005, respectively. Using PRSs, we observed that greater genetic risk for VTE, another prothrombotic condition, was more strongly associated with EOS compared with LOS (p = 0.008).

Discussion

The ABO locus, genetically predicted blood group A, and higher genetic propensity for venous thrombosis are more strongly associated with EOS than with LOS, supporting a stronger role of prothrombotic factors in EOS.", - "laySummary": "", - "urls": "pdf:https://n.neurology.org/content/neurology/99/16/e1738.full.pdf; doi:https://doi.org/10.1212/WNL.0000000000201006; html:https://europepmc.org/articles/PMC9620803; pdf:https://europepmc.org/articles/PMC9620803?pdf=render" - }, { "id": "31488387", "doi": "https://doi.org/10.1016/s2214-109x(19)30318-3", @@ -42567,6 +42550,23 @@ "laySummary": "", "urls": "pdf:https://europepmc.org/articles/pmc6726478?pdf=render; doi:https://doi.org/10.1038/s41588-019-0483-y; html:https://europepmc.org/articles/PMC6726478; pdf:https://europepmc.org/articles/PMC6726478?pdf=render" }, + { + "id": "36240095", + "doi": "https://doi.org/10.1212/wnl.0000000000201006", + "title": "Contribution of Common Genetic Variants to Risk of Early-Onset Ischemic Stroke.", + "authorString": "Jaworek T, Xu H, Gaynor BJ, Cole JW, Rannikmae K, Stanne TM, Tomppo L, Abedi V, Amouyel P, Armstrong ND, Attia J, Bell S, Benavente OR, Boncoraglio GB, Butterworth A, Cervical Artery Dissections and Ischemic Stroke Patients (CADSIP) Consortium, Carcel-Marquez J, Chen Z, Chong M, Cruchaga C, Cushman M, Danesh J, Debette S, Duggan DJ, Durda JP, Engstrom G, Enzinger C, Faul JD, Fecteau NS, Fernandez-Cadenas I, Gieger C, Giese AK, Grewal RP, Grittner U, Havulinna AS, Heitsch L, Hochberg MC, Holliday E, Hu J, Hu J, Ilinca A, INVENT Consortium, Irvin MR, Jackson RD, Jacob MA, Rabionet R, Jimenez-Conde J, Johnson JA, Kamatani Y, Kardia SLR, Koido M, Kubo M, Lange L, Lee JM, Lemmens R, Levi CR, Li J, Li L, Lin K, Lopez H, Luke S, Maguire J, McArdle PF, McDonough CW, Meschia JF, Metso T, M\u00fcller-Nurasyid M, O'Connor TD, O'Donnell M, Peddareddygari LR, Pera J, Perry JA, Peters A, Putaala J, Ray D, Rexrode K, Ribases M, Rosand J, Rothwell PM, Rundek T, Ryan KA, Sacco RL, Salomaa V, Sanchez-Mora C, Schmidt R, Sharma P, Slowik A, Smith JA, Smith NL, Wassertheil-Smoller S, S\u00f6derholm M, Stine OC, Strbian D, Sudlow CLM, Tatlisumak T, Terao C, Thijs V, Torres-Aguila NP, Tr\u00e9gou\u00ebt DA, Tuladhar AM, Veldink JH, Walters RG, Weir DR, Woo D, Worrall BB, Hong CC, Ross OA, Zand R, Leeuw FE, Lindgren AG, Pare G, Anderson CD, Markus HS, Jern C, Malik R, Dichgans M, Mitchell BD, Kittner SJ, Early Onset Stroke Genetics Consortium of the International Stroke Genetics Consortium (ISGC).", + "authorAffiliations": "", + "journalTitle": "Neurology", + "pubYear": "2022", + "date": "2022-10-17", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background and objectives

Current genome-wide association studies of ischemic stroke have focused primarily on late-onset disease. As a complement to these studies, we sought to identify the contribution of common genetic variants to risk of early-onset ischemic stroke.

Methods

We performed a meta-analysis of genome-wide association studies of early-onset stroke (EOS), ages 18-59 years, using individual-level data or summary statistics in 16,730 cases and 599,237 nonstroke controls obtained across 48 different studies. We further compared effect sizes at associated loci between EOS and late-onset stroke (LOS) and compared polygenic risk scores (PRS) for venous thromboembolism (VTE) between EOS and LOS.

Results

We observed genome-wide significant associations of EOS with 2 variants in ABO, a known stroke locus. These variants tag blood subgroups O1 and A1, and the effect sizes of both variants were significantly larger in EOS compared with LOS. The odds ratio (OR) for rs529565, tagging O1, was 0.88 (95% confidence interval [CI]: 0.85-0.91) in EOS vs 0.96 (95% CI: 0.92-1.00) in LOS, and the OR for rs635634, tagging A1, was 1.16 (1.11-1.21) for EOS vs 1.05 (0.99-1.11) in LOS; p-values for interaction = 0.001 and 0.005, respectively. Using PRSs, we observed that greater genetic risk for VTE, another prothrombotic condition, was more strongly associated with EOS compared with LOS (p = 0.008).

Discussion

The ABO locus, genetically predicted blood group A, and higher genetic propensity for venous thrombosis are more strongly associated with EOS than with LOS, supporting a stronger role of prothrombotic factors in EOS.", + "laySummary": "", + "urls": "pdf:https://n.neurology.org/content/neurology/99/16/e1738.full.pdf; doi:https://doi.org/10.1212/WNL.0000000000201006; html:https://europepmc.org/articles/PMC9620803; pdf:https://europepmc.org/articles/PMC9620803?pdf=render" + }, { "id": "33444330", "doi": "https://doi.org/10.1371/journal.pmed.1003498", @@ -42601,23 +42601,6 @@ "laySummary": "", "urls": "pdf:https://cardiab.biomedcentral.com/track/pdf/10.1186/s12933-020-01130-4; doi:https://doi.org/10.1186/s12933-020-01130-4; html:https://europepmc.org/articles/PMC7520021; pdf:https://europepmc.org/articles/PMC7520021?pdf=render" }, - { - "id": "38428419", - "doi": "https://doi.org/10.1016/j.xgen.2024.100511", - "title": "Genomic evolution shapes prostate cancer disease type.", - "authorString": "Woodcock DJ, Sahli A, Teslo R, Bhandari V, Gruber AJ, Ziubroniewicz A, Gundem G, Xu Y, Butler A, Anokian E, Pope BJ, Jung CH, Tarabichi M, Dentro SC, Farmery JHR, CRUK ICGC Prostate Group, Van Loo P, Warren AY, Gnanapragasam V, Hamdy FC, Bova GS, Foster CS, Neal DE, Lu YJ, Kote-Jarai Z, Fraser M, Bristow RG, Boutros PC, Costello AJ, Corcoran NM, Hovens CM, Massie CE, Lynch AG, Brewer DS, Eeles RA, Cooper CS, Wedge DC.", - "authorAffiliations": "", - "journalTitle": "Cell genomics", - "pubYear": "2024", - "date": "2024-02-29", - "isOpenAccess": "Y", - "keywords": "prostate cancer; Ordering; Cancer Evolution; Ar Binding; Evotype Model; Evotypes", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "The development of cancer is an evolutionary process involving the sequential acquisition of genetic alterations that disrupt normal biological processes, enabling tumor cells to rapidly proliferate and eventually invade and metastasize to other tissues. We investigated the genomic evolution of prostate cancer through the application of three separate classification methods, each designed to investigate a different aspect of tumor evolution. Integrating the results revealed the existence of two distinct types of prostate cancer that arise from divergent evolutionary trajectories, designated as the Canonical and Alternative evolutionary disease types. We therefore propose the evotype model for prostate cancer evolution wherein Alternative-evotype tumors diverge from those of the Canonical-evotype through the stochastic accumulation of genetic alterations associated with disruptions to androgen receptor DNA binding. Our model unifies many previous molecular observations, providing a powerful new framework to investigate prostate cancer disease progression.", - "laySummary": "", - "urls": "doi:https://doi.org/10.1016/j.xgen.2024.100511; html:https://europepmc.org/articles/PMC10943594; pdf:https://europepmc.org/articles/PMC10943594?pdf=render" - }, { "id": "33442528", "doi": "https://doi.org/10.1140/epjds/s13688-020-00257-4", @@ -42635,6 +42618,23 @@ "laySummary": "", "urls": "pdf:https://epjdatascience.springeropen.com/track/pdf/10.1140/epjds/s13688-020-00257-4; doi:https://doi.org/10.1140/epjds/s13688-020-00257-4; html:https://europepmc.org/articles/PMC7790778; pdf:https://europepmc.org/articles/PMC7790778?pdf=render" }, + { + "id": "38428419", + "doi": "https://doi.org/10.1016/j.xgen.2024.100511", + "title": "Genomic evolution shapes prostate cancer disease type.", + "authorString": "Woodcock DJ, Sahli A, Teslo R, Bhandari V, Gruber AJ, Ziubroniewicz A, Gundem G, Xu Y, Butler A, Anokian E, Pope BJ, Jung CH, Tarabichi M, Dentro SC, Farmery JHR, CRUK ICGC Prostate Group, Van Loo P, Warren AY, Gnanapragasam V, Hamdy FC, Bova GS, Foster CS, Neal DE, Lu YJ, Kote-Jarai Z, Fraser M, Bristow RG, Boutros PC, Costello AJ, Corcoran NM, Hovens CM, Massie CE, Lynch AG, Brewer DS, Eeles RA, Cooper CS, Wedge DC.", + "authorAffiliations": "", + "journalTitle": "Cell genomics", + "pubYear": "2024", + "date": "2024-02-29", + "isOpenAccess": "Y", + "keywords": "prostate cancer; Ordering; Cancer Evolution; Ar Binding; Evotype Model; Evotypes", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "The development of cancer is an evolutionary process involving the sequential acquisition of genetic alterations that disrupt normal biological processes, enabling tumor cells to rapidly proliferate and eventually invade and metastasize to other tissues. We investigated the genomic evolution of prostate cancer through the application of three separate classification methods, each designed to investigate a different aspect of tumor evolution. Integrating the results revealed the existence of two distinct types of prostate cancer that arise from divergent evolutionary trajectories, designated as the Canonical and Alternative evolutionary disease types. We therefore propose the evotype model for prostate cancer evolution wherein Alternative-evotype tumors diverge from those of the Canonical-evotype through the stochastic accumulation of genetic alterations associated with disruptions to androgen receptor DNA binding. Our model unifies many previous molecular observations, providing a powerful new framework to investigate prostate cancer disease progression.", + "laySummary": "", + "urls": "doi:https://doi.org/10.1016/j.xgen.2024.100511; html:https://europepmc.org/articles/PMC10943594; pdf:https://europepmc.org/articles/PMC10943594?pdf=render" + }, { "id": "32956399", "doi": "https://doi.org/10.1371/journal.pmed.1003336", @@ -43910,23 +43910,6 @@ "laySummary": "", "urls": "pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-021-02193-0; doi:https://doi.org/10.1186/s12916-021-02193-0; html:https://europepmc.org/articles/PMC8750876; pdf:https://europepmc.org/articles/PMC8750876?pdf=render" }, - { - "id": "38373851", - "doi": "https://doi.org/10.3399/bjgp.2023.0198", - "title": "Long-term cardiovascular risks and the impact of statin treatment on socioeconomic inequalities: a microsimulation model.", - "authorString": "Wu R, Williams C, Zhou J, Schlackow I, Emberson J, Reith C, Keech A, Robson J, Armitage J, Gray A, Simes J, Baigent C, Mihaylova B, CTT Collaboration secretariat, Armitage J, Baigent C, Barnes E, Blackwell L, Collins R, Davies K, Emberson J, Fulcher J, Halls H, Herrington WG, Holland L, Keech A, Kirby A, Mihaylova B, O'Connell R, Preiss D, Reith C, Simes J, Wilson K, CTT Collaboration trialists: A to Z trial (phase Z), Blazing M, Braunwald E, Lemos J, Murphy S, Pedersen TR, Pfeffer M, White H, Wiviott S, AFCAPS/TEXCAPS (AirForce/Texas Coronary Atherosclerosis Prevention Study), Clearfield M, Downs JR, Gotto A, Weis S, ALERT (Assessment of Lescol in Renal Transplantation), Fellstr\u00f6m B, Holdaas H, Jardine A, Pedersen TR, ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial), Gordon D, Davis B, Furberg C, Grimm R, Pressel S, Probstfield JL, Rahman M, Simpson L, ALLIANCE (Aggressive Lipid-Lowering Initiation Abates New Cardiac Events), Koren M, ASCOT (Anglo-Scandinavian Cardiac Outcomes Trial), Dahl\u00f6f B, Gupta A, Poulter N, Sever P, Wedel H, ASPEN (Atorvastatin Study for the Prevention of Coronary Heart Disease Endpoints in Non-Insulin Dependent Diabetes Mellitus), Knopp RH, AURORA (A study to evaluate the Use of Rosuvastatin in subjects On Regular haemodialysis: an Assessment of survival and cardiovascular events), Cobbe S, Fellstr\u00f6m B, Holdaas H, Jardine A, Schmieder R, Zannad F, CARDS (Collaborative Atorvastatin Diabetes Study), Betteridge DJ, Colhoun HM, Durrington PN, Fuller J, Hitman GA, Neil A, CARE (Cholesterol And Recurrent Events Study), Braunwald E, Davis B, Hawkins CM, Moy\u00e9 L, Pfeffer M, Sacks F, CORONA (Controlled Rosuvastatin Multinational Trial in Heart Failure), Kjekshus J, Wedel H, Wikstrand J, 4D (Die Deutsche Diabetes Dialyse Studie), Wanner C, Krane V, GISSI (Gruppo Italiano per lo Studio della Sopravvivenza nell\u2019Infarto miocardico) Heart Failure and Prevention trials, Franzosi MG, Latini R, Lucci D, Maggioni A, Marchioli R, Nicolis EB, Tavazzi L, Tognoni G, HOPE-3, Bosch J, Lonn E, Yusuf S, HPS (Heart Protection Study), Armitage J, Bowman L, Collins R, Keech A, Landray M, Parish S, Peto R, Sleight P, IDEAL (Incremental Decrease in Endpoints through Aggressive Lipid-lowering), Kastelein JJ, Pedersen TR, JUPITER (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin), Glynn R, Gotto A, Kastelein JJ, Koenig W, MacFadyen J, Ridker PM, LIPID (Long-term Intervention with Pravastatin in Ischaemic Disease), Keech A, MacMahon S, Marschner I, Tonkin A, Shaw J, Simes J, White H, LIPS (Lescol Intervention Prevention Study), Serruys PW, Post-CABG (Post-Coronary Artery Bypass Graft Study), Knatterud G, PROSPER (Prospective Study of Pravastatin in the Elderly at Risk), Blauw GJ, Cobbe S, Ford I, Macfarlane P, Packard C, Sattar N, Shepherd J, Trompet S, PROVE-IT (Pravastatin or Atorvastatin Evaluation and Infection Therapy), Braunwald E, Cannon CP, Murphy S, SEARCH (Study of Effectiveness of Additional Reductions in Cholesterol and Homocysteine), Collins R, Armitage J, Bowman L, Bulbulia R, Haynes R, Parish S, Peto R, Sleight P, SPARCL (Stroke Prevention by Aggressive Reduction in Cholesterol Levels), Amarenco P, Welch KM, 4S (Scandinavian Simvastatin Survival Study), Kjekshus J, Pedersen TR, Wilhelmsen L, TNT (Treating to New Targets), Barter P, Gotto A, LaRosa J, Kastelein JJ, Shepherd J, WOSCOPS (West of Scotland Coronary Prevention Study), Cobbe S, Ford I, Kean S, Macfarlane P, Packard C, Roberston M, Sattar N, Shepherd J, Young R, Other CTT Collaboration members, Arashi H, Clarke R, Flather M, Goto S, Goldbourt U, Hopewell J, Hovingh GK, Kitas G, Newman C, Sabatine MS, Schwartz GG, Smeeth L, Tobert J, Varigos J, Yamamguchi J.", - "authorAffiliations": "", - "journalTitle": "The British journal of general practice : the journal of the Royal College of General Practitioners", - "pubYear": "2024", - "date": "2024-02-19", - "isOpenAccess": "Y", - "keywords": "Cardiovascular disease; Socioeconomic status; Quality-adjusted Life Years; Inequality; Markov Microsimulation Model; Individual Patient Characteristics", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

UK cardiovascular disease (CVD) incidence and mortality have declined in recent decades but socioeconomic inequalities persist.

Aim

To present a new CVD model, and project health outcomes and the impact of guideline-recommended statin treatment across quintiles of socioeconomic deprivation in the UK.

Design and setting

A lifetime microsimulation model was developed using 117 896 participants in 16 statin trials, 501 854 UK Biobank (UKB) participants, and quality-of-life data from national health surveys.

Method

A CVD microsimulation model was developed using risk equations for myocardial infarction, stroke, coronary revascularisation, cancer, and vascular and non-vascular death, estimated using trial data. The authors calibrated and further developed this model in the UKB cohort, including further characteristics and a diabetes risk equation, and validated the model in UKB and Whitehall II cohorts. The model was used to predict CVD incidence, life expectancy, quality-adjusted life years (QALYs), and the impact of UK guideline-recommended statin treatment across socioeconomic deprivation quintiles.

Results

Age, sex, socioeconomic deprivation, smoking, hypertension, diabetes, and cardiovascular events were key CVD risk determinants. Model-predicted event rates corresponded well to observed rates across participant categories. The model projected strong gradients in remaining life expectancy, with 4-5-year (5-8 QALYs) gaps between the least and most socioeconomically deprived quintiles. Guideline-recommended statin treatment was projected to increase QALYs, with larger gains in quintiles of higher deprivation.

Conclusion

The study demonstrated the potential of guideline-recommended statin treatment to reduce socioeconomic inequalities. This CVD model is a novel resource for individualised long-term projections of health outcomes of CVD treatments.", - "laySummary": "", - "urls": "doi:https://doi.org/10.3399/BJGP.2023.0198; html:https://europepmc.org/articles/PMC10904120; pdf:https://europepmc.org/articles/PMC10904120?pdf=render" - }, { "id": "32134384", "doi": "https://doi.org/10.7554/elife.52677", @@ -43944,6 +43927,23 @@ "laySummary": "", "urls": "doi:https://doi.org/10.7554/elife.52677; doi:https://doi.org/10.7554/eLife.52677; html:https://europepmc.org/articles/PMC7162660; pdf:https://europepmc.org/articles/PMC7162660?pdf=render" }, + { + "id": "38373851", + "doi": "https://doi.org/10.3399/bjgp.2023.0198", + "title": "Long-term cardiovascular risks and the impact of statin treatment on socioeconomic inequalities: a microsimulation model.", + "authorString": "Wu R, Williams C, Zhou J, Schlackow I, Emberson J, Reith C, Keech A, Robson J, Armitage J, Gray A, Simes J, Baigent C, Mihaylova B, CTT Collaboration secretariat, Armitage J, Baigent C, Barnes E, Blackwell L, Collins R, Davies K, Emberson J, Fulcher J, Halls H, Herrington WG, Holland L, Keech A, Kirby A, Mihaylova B, O'Connell R, Preiss D, Reith C, Simes J, Wilson K, CTT Collaboration trialists: A to Z trial (phase Z), Blazing M, Braunwald E, Lemos J, Murphy S, Pedersen TR, Pfeffer M, White H, Wiviott S, AFCAPS/TEXCAPS (AirForce/Texas Coronary Atherosclerosis Prevention Study), Clearfield M, Downs JR, Gotto A, Weis S, ALERT (Assessment of Lescol in Renal Transplantation), Fellstr\u00f6m B, Holdaas H, Jardine A, Pedersen TR, ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial), Gordon D, Davis B, Furberg C, Grimm R, Pressel S, Probstfield JL, Rahman M, Simpson L, ALLIANCE (Aggressive Lipid-Lowering Initiation Abates New Cardiac Events), Koren M, ASCOT (Anglo-Scandinavian Cardiac Outcomes Trial), Dahl\u00f6f B, Gupta A, Poulter N, Sever P, Wedel H, ASPEN (Atorvastatin Study for the Prevention of Coronary Heart Disease Endpoints in Non-Insulin Dependent Diabetes Mellitus), Knopp RH, AURORA (A study to evaluate the Use of Rosuvastatin in subjects On Regular haemodialysis: an Assessment of survival and cardiovascular events), Cobbe S, Fellstr\u00f6m B, Holdaas H, Jardine A, Schmieder R, Zannad F, CARDS (Collaborative Atorvastatin Diabetes Study), Betteridge DJ, Colhoun HM, Durrington PN, Fuller J, Hitman GA, Neil A, CARE (Cholesterol And Recurrent Events Study), Braunwald E, Davis B, Hawkins CM, Moy\u00e9 L, Pfeffer M, Sacks F, CORONA (Controlled Rosuvastatin Multinational Trial in Heart Failure), Kjekshus J, Wedel H, Wikstrand J, 4D (Die Deutsche Diabetes Dialyse Studie), Wanner C, Krane V, GISSI (Gruppo Italiano per lo Studio della Sopravvivenza nell\u2019Infarto miocardico) Heart Failure and Prevention trials, Franzosi MG, Latini R, Lucci D, Maggioni A, Marchioli R, Nicolis EB, Tavazzi L, Tognoni G, HOPE-3, Bosch J, Lonn E, Yusuf S, HPS (Heart Protection Study), Armitage J, Bowman L, Collins R, Keech A, Landray M, Parish S, Peto R, Sleight P, IDEAL (Incremental Decrease in Endpoints through Aggressive Lipid-lowering), Kastelein JJ, Pedersen TR, JUPITER (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin), Glynn R, Gotto A, Kastelein JJ, Koenig W, MacFadyen J, Ridker PM, LIPID (Long-term Intervention with Pravastatin in Ischaemic Disease), Keech A, MacMahon S, Marschner I, Tonkin A, Shaw J, Simes J, White H, LIPS (Lescol Intervention Prevention Study), Serruys PW, Post-CABG (Post-Coronary Artery Bypass Graft Study), Knatterud G, PROSPER (Prospective Study of Pravastatin in the Elderly at Risk), Blauw GJ, Cobbe S, Ford I, Macfarlane P, Packard C, Sattar N, Shepherd J, Trompet S, PROVE-IT (Pravastatin or Atorvastatin Evaluation and Infection Therapy), Braunwald E, Cannon CP, Murphy S, SEARCH (Study of Effectiveness of Additional Reductions in Cholesterol and Homocysteine), Collins R, Armitage J, Bowman L, Bulbulia R, Haynes R, Parish S, Peto R, Sleight P, SPARCL (Stroke Prevention by Aggressive Reduction in Cholesterol Levels), Amarenco P, Welch KM, 4S (Scandinavian Simvastatin Survival Study), Kjekshus J, Pedersen TR, Wilhelmsen L, TNT (Treating to New Targets), Barter P, Gotto A, LaRosa J, Kastelein JJ, Shepherd J, WOSCOPS (West of Scotland Coronary Prevention Study), Cobbe S, Ford I, Kean S, Macfarlane P, Packard C, Roberston M, Sattar N, Shepherd J, Young R, Other CTT Collaboration members, Arashi H, Clarke R, Flather M, Goto S, Goldbourt U, Hopewell J, Hovingh GK, Kitas G, Newman C, Sabatine MS, Schwartz GG, Smeeth L, Tobert J, Varigos J, Yamamguchi J.", + "authorAffiliations": "", + "journalTitle": "The British journal of general practice : the journal of the Royal College of General Practitioners", + "pubYear": "2024", + "date": "2024-02-19", + "isOpenAccess": "Y", + "keywords": "Cardiovascular disease; Socioeconomic status; Quality-adjusted Life Years; Inequality; Markov Microsimulation Model; Individual Patient Characteristics", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

UK cardiovascular disease (CVD) incidence and mortality have declined in recent decades but socioeconomic inequalities persist.

Aim

To present a new CVD model, and project health outcomes and the impact of guideline-recommended statin treatment across quintiles of socioeconomic deprivation in the UK.

Design and setting

A lifetime microsimulation model was developed using 117 896 participants in 16 statin trials, 501 854 UK Biobank (UKB) participants, and quality-of-life data from national health surveys.

Method

A CVD microsimulation model was developed using risk equations for myocardial infarction, stroke, coronary revascularisation, cancer, and vascular and non-vascular death, estimated using trial data. The authors calibrated and further developed this model in the UKB cohort, including further characteristics and a diabetes risk equation, and validated the model in UKB and Whitehall II cohorts. The model was used to predict CVD incidence, life expectancy, quality-adjusted life years (QALYs), and the impact of UK guideline-recommended statin treatment across socioeconomic deprivation quintiles.

Results

Age, sex, socioeconomic deprivation, smoking, hypertension, diabetes, and cardiovascular events were key CVD risk determinants. Model-predicted event rates corresponded well to observed rates across participant categories. The model projected strong gradients in remaining life expectancy, with 4-5-year (5-8 QALYs) gaps between the least and most socioeconomically deprived quintiles. Guideline-recommended statin treatment was projected to increase QALYs, with larger gains in quintiles of higher deprivation.

Conclusion

The study demonstrated the potential of guideline-recommended statin treatment to reduce socioeconomic inequalities. This CVD model is a novel resource for individualised long-term projections of health outcomes of CVD treatments.", + "laySummary": "", + "urls": "doi:https://doi.org/10.3399/BJGP.2023.0198; html:https://europepmc.org/articles/PMC10904120; pdf:https://europepmc.org/articles/PMC10904120?pdf=render" + }, { "id": "30941398", "doi": "https://doi.org/10.1093/aje/kwz090", @@ -44131,23 +44131,6 @@ "laySummary": "", "urls": "pdf:https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-020-01712-9; doi:https://doi.org/10.1186/s12916-020-01712-9; html:https://europepmc.org/articles/PMC7437104; pdf:https://europepmc.org/articles/PMC7437104?pdf=render" }, - { - "id": "37880365", - "doi": "https://doi.org/10.1038/s41586-023-06630-3", - "title": "Normative spatiotemporal fetal brain maturation with satisfactory development at 2 years.", - "authorString": "Namburete AIL, Papie\u017c BW, Fernandes M, Wyburd MK, Hesse LS, Moser FA, Ismail LC, Gunier RB, Squier W, Ohuma EO, Carvalho M, Jaffer Y, Gravett M, Wu Q, Lambert A, Winsey A, Restrepo-M\u00e9ndez MC, Bertino E, Purwar M, Barros FC, Stein A, Noble JA, Moln\u00e1r Z, Jenkinson M, Bhutta ZA, Papageorghiou AT, Villar J, Kennedy SH.", - "authorAffiliations": "", - "journalTitle": "Nature", - "pubYear": "2023", - "date": "2023-10-25", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "Maturation of the human fetal brain should follow precisely scheduled structural growth and folding of the cerebral cortex for optimal postnatal function1. We present a normative digital atlas of fetal brain maturation based on a prospective international cohort of healthy pregnant women2, selected using World Health Organization recommendations for growth standards3. Their fetuses were accurately dated in the first trimester, with satisfactory growth and neurodevelopment from early pregnancy to 2\u2009years of age4,5. The atlas was produced using 1,059 optimal quality, three-dimensional ultrasound brain volumes from 899 of the fetuses and an automated analysis pipeline6-8. The atlas corresponds structurally to published magnetic resonance images9, but with finer anatomical details in deep grey matter. The between-study site variability represented less than 8.0% of the total variance of all brain measures, supporting pooling data from the eight study sites to produce patterns of normative maturation. We have thereby generated an average representation of each cerebral hemisphere between 14 and 31\u2009weeks' gestation with quantification of intracranial volume variability and growth patterns. Emergent asymmetries were detectable from as early as 14\u2009weeks, with peak asymmetries in regions associated with language development and functional lateralization between 20 and 26\u2009weeks' gestation. These patterns were validated in 1,487 three-dimensional brain volumes from 1,295 different fetuses in the same cohort. We provide a unique spatiotemporal benchmark of fetal brain maturation from a large cohort with normative postnatal growth and neurodevelopment.", - "laySummary": "", - "urls": "pdf:https://www.nature.com/articles/s41586-023-06630-3.pdf; doi:https://doi.org/10.1038/s41586-023-06630-3; html:https://europepmc.org/articles/PMC10620088; pdf:https://europepmc.org/articles/PMC10620088?pdf=render" - }, { "id": "34098341", "doi": "https://doi.org/10.1016/j.ebiom.2021.103414", @@ -44165,6 +44148,23 @@ "laySummary": "", "urls": "pdf:https://research-information.bris.ac.uk/files/280339070/1_s2.0_S2352396421002073_main.pdf; doi:https://doi.org/10.1016/j.ebiom.2021.103414; html:https://europepmc.org/articles/PMC8176919; pdf:https://europepmc.org/articles/PMC8176919?pdf=render" }, + { + "id": "37880365", + "doi": "https://doi.org/10.1038/s41586-023-06630-3", + "title": "Normative spatiotemporal fetal brain maturation with satisfactory development at 2 years.", + "authorString": "Namburete AIL, Papie\u017c BW, Fernandes M, Wyburd MK, Hesse LS, Moser FA, Ismail LC, Gunier RB, Squier W, Ohuma EO, Carvalho M, Jaffer Y, Gravett M, Wu Q, Lambert A, Winsey A, Restrepo-M\u00e9ndez MC, Bertino E, Purwar M, Barros FC, Stein A, Noble JA, Moln\u00e1r Z, Jenkinson M, Bhutta ZA, Papageorghiou AT, Villar J, Kennedy SH.", + "authorAffiliations": "", + "journalTitle": "Nature", + "pubYear": "2023", + "date": "2023-10-25", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "Maturation of the human fetal brain should follow precisely scheduled structural growth and folding of the cerebral cortex for optimal postnatal function1. We present a normative digital atlas of fetal brain maturation based on a prospective international cohort of healthy pregnant women2, selected using World Health Organization recommendations for growth standards3. Their fetuses were accurately dated in the first trimester, with satisfactory growth and neurodevelopment from early pregnancy to 2\u2009years of age4,5. The atlas was produced using 1,059 optimal quality, three-dimensional ultrasound brain volumes from 899 of the fetuses and an automated analysis pipeline6-8. The atlas corresponds structurally to published magnetic resonance images9, but with finer anatomical details in deep grey matter. The between-study site variability represented less than 8.0% of the total variance of all brain measures, supporting pooling data from the eight study sites to produce patterns of normative maturation. We have thereby generated an average representation of each cerebral hemisphere between 14 and 31\u2009weeks' gestation with quantification of intracranial volume variability and growth patterns. Emergent asymmetries were detectable from as early as 14\u2009weeks, with peak asymmetries in regions associated with language development and functional lateralization between 20 and 26\u2009weeks' gestation. These patterns were validated in 1,487 three-dimensional brain volumes from 1,295 different fetuses in the same cohort. We provide a unique spatiotemporal benchmark of fetal brain maturation from a large cohort with normative postnatal growth and neurodevelopment.", + "laySummary": "", + "urls": "pdf:https://www.nature.com/articles/s41586-023-06630-3.pdf; doi:https://doi.org/10.1038/s41586-023-06630-3; html:https://europepmc.org/articles/PMC10620088; pdf:https://europepmc.org/articles/PMC10620088?pdf=render" + }, { "id": "34051920", "doi": "https://doi.org/10.1016/s2468-2667(21)00065-7", @@ -44352,23 +44352,6 @@ "laySummary": "", "urls": "pdf:https://www.nature.com/articles/s41467-021-22752-6.pdf; doi:https://doi.org/10.1038/s41467-021-22752-6; html:https://europepmc.org/articles/PMC8121846; pdf:https://europepmc.org/articles/PMC8121846?pdf=render" }, - { - "id": "35387486", - "doi": "https://doi.org/10.1161/circulationaha.121.057888", - "title": "Genetic Landscape of the ACE2 Coronavirus Receptor.", - "authorString": "Yang Z, Macdonald-Dunlop E, Chen J, Zhai R, Li T, Richmond A, Klari\u0107 L, Pirastu N, Ning Z, Zheng C, Wang Y, Huang T, He Y, Guo H, Ying K, Gustafsson S, Prins B, Ramisch A, Dermitzakis ET, Png G, Eriksson N, Haessler J, Hu X, Zanetti D, Boutin T, Hwang SJ, Wheeler E, Pietzner M, Raffield LM, Kalnapenkis A, Peters JE, Vi\u00f1uela A, Gilly A, Elmst\u00e5hl S, Dedoussis G, Petrie JR, Pola\u0161ek O, Folkersen L, Chen Y, Yao C, V\u00f5sa U, Pairo-Castineira E, Clohisey S, Bretherick AD, Rawlik K, GenOMICC Consortium\u2020, IMI-DIRECT Consortium\u2020, Esko T, Enroth S, Johansson \u00c5, Gyllensten U, Langenberg C, Levy D, Hayward C, Assimes TL, Kooperberg C, Manichaikul AW, Siegbahn A, Wallentin L, Lind L, Zeggini E, Schwenk JM, Butterworth AS, Micha\u00eblsson K, Pawitan Y, Joshi PK, Baillie JK, M\u00e4larstig A, Reiner AP, Wilson JF, Shen X.", - "authorAffiliations": "", - "journalTitle": "Circulation", - "pubYear": "2022", - "date": "2022-04-07", - "isOpenAccess": "Y", - "keywords": "Cardiovascular diseases; Angiotensin-converting Enzyme 2; Genome-wide Association Study; Covid-19; Sars-cov-2", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

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

Methods

We have conducted the largest genome-wide association meta-analysis of plasma ACE2 levels in >28\u2009000 individuals of the SCALLOP Consortium (Systematic and Combined Analysis of Olink Proteins). We summarize the cross-sectional epidemiological correlates of circulating ACE2. Using the summary statistics-based high-definition likelihood method, we estimate relevant genetic correlations with cardiometabolic phenotypes, COVID-19, and other human complex traits and diseases. We perform causal inference of soluble ACE2 on vascular disease outcomes and COVID-19 severity using mendelian randomization. We also perform in silico functional analysis by integrating with other types of omics data.

Results

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

Conclusions

Human plasma ACE2 shares a genetic basis with cardiovascular disease, COVID-19, and other related diseases. The genetic architecture of the ACE2 protein is mapped, providing a useful resource for further biological and clinical studies on this coronavirus receptor.", - "laySummary": "", - "urls": "pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCULATIONAHA.121.057888; doi:https://doi.org/10.1161/CIRCULATIONAHA.121.057888; html:https://europepmc.org/articles/PMC9047645; pdf:https://europepmc.org/articles/PMC9047645?pdf=render" - }, { "id": "30498058", "doi": "https://doi.org/10.1136/archdischild-2018-315866", @@ -44386,6 +44369,23 @@ "laySummary": "This study looked at whether there is a link between gestational length of a child (the length of time of pregnancy) and the likelihood of permanent hearing impairment. The authors looked at data from over 19000 children from a study called the Millenium Cohort Study. They found that shorter gestational length did not increase the likelihood of childhood permanent hearting impairment. However, they found that children who had neonatal illness (illness in the immediate days after birth), if they were Bangladeshi or Pakistani in ethnicity, or if they were born to younger mothers.", "urls": "pdf:https://adc.bmj.com/content/archdischild/105/2/187.full.pdf; doi:https://doi.org/10.1136/archdischild-2018-315866; html:https://europepmc.org/articles/PMC7025723; pdf:https://europepmc.org/articles/PMC7025723?pdf=render" }, + { + "id": "35387486", + "doi": "https://doi.org/10.1161/circulationaha.121.057888", + "title": "Genetic Landscape of the ACE2 Coronavirus Receptor.", + "authorString": "Yang Z, Macdonald-Dunlop E, Chen J, Zhai R, Li T, Richmond A, Klari\u0107 L, Pirastu N, Ning Z, Zheng C, Wang Y, Huang T, He Y, Guo H, Ying K, Gustafsson S, Prins B, Ramisch A, Dermitzakis ET, Png G, Eriksson N, Haessler J, Hu X, Zanetti D, Boutin T, Hwang SJ, Wheeler E, Pietzner M, Raffield LM, Kalnapenkis A, Peters JE, Vi\u00f1uela A, Gilly A, Elmst\u00e5hl S, Dedoussis G, Petrie JR, Pola\u0161ek O, Folkersen L, Chen Y, Yao C, V\u00f5sa U, Pairo-Castineira E, Clohisey S, Bretherick AD, Rawlik K, GenOMICC Consortium\u2020, IMI-DIRECT Consortium\u2020, Esko T, Enroth S, Johansson \u00c5, Gyllensten U, Langenberg C, Levy D, Hayward C, Assimes TL, Kooperberg C, Manichaikul AW, Siegbahn A, Wallentin L, Lind L, Zeggini E, Schwenk JM, Butterworth AS, Micha\u00eblsson K, Pawitan Y, Joshi PK, Baillie JK, M\u00e4larstig A, Reiner AP, Wilson JF, Shen X.", + "authorAffiliations": "", + "journalTitle": "Circulation", + "pubYear": "2022", + "date": "2022-04-07", + "isOpenAccess": "Y", + "keywords": "Cardiovascular diseases; Angiotensin-converting Enzyme 2; Genome-wide Association Study; Covid-19; Sars-cov-2", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

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

Methods

We have conducted the largest genome-wide association meta-analysis of plasma ACE2 levels in >28\u2009000 individuals of the SCALLOP Consortium (Systematic and Combined Analysis of Olink Proteins). We summarize the cross-sectional epidemiological correlates of circulating ACE2. Using the summary statistics-based high-definition likelihood method, we estimate relevant genetic correlations with cardiometabolic phenotypes, COVID-19, and other human complex traits and diseases. We perform causal inference of soluble ACE2 on vascular disease outcomes and COVID-19 severity using mendelian randomization. We also perform in silico functional analysis by integrating with other types of omics data.

Results

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

Conclusions

Human plasma ACE2 shares a genetic basis with cardiovascular disease, COVID-19, and other related diseases. The genetic architecture of the ACE2 protein is mapped, providing a useful resource for further biological and clinical studies on this coronavirus receptor.", + "laySummary": "", + "urls": "pdf:https://www.ahajournals.org/doi/pdf/10.1161/CIRCULATIONAHA.121.057888; doi:https://doi.org/10.1161/CIRCULATIONAHA.121.057888; html:https://europepmc.org/articles/PMC9047645; pdf:https://europepmc.org/articles/PMC9047645?pdf=render" + }, { "id": "34516908", "doi": "https://doi.org/10.1126/sciadv.abh0534", @@ -44726,23 +44726,6 @@ "laySummary": "", "urls": "pdf:http://www.cell.com/article/S0002929721001348/pdf; doi:https://doi.org/10.1016/j.ajhg.2021.04.003; html:https://europepmc.org/articles/PMC8206199; pdf:https://europepmc.org/articles/PMC8206199?pdf=render; doi:https://doi.org/10.1016/j.ajhg.2021.04.003" }, - { - "id": "38554713", - "doi": "https://doi.org/10.1016/s2213-8587(24)00040-8", - "title": "Effects of statin therapy on diagnoses of new-onset diabetes and worsening glycaemia in large-scale randomised blinded statin trials: an individual participant data meta-analysis.", - "authorString": "Cholesterol Treatment Trialists\u2019 (CTT) Collaboration. Electronic address: ctt@ndph.ox.ac.uk, Cholesterol Treatment Trialists\u2019 (CTT) Collaboration.", - "authorAffiliations": "", - "journalTitle": "The lancet. Diabetes & endocrinology", - "pubYear": "2024", - "date": "2024-03-27", - "isOpenAccess": "Y", - "keywords": "", - "nationalPriorities": "", - "healthCategories": "", - "abstract": "

Background

Previous meta-analyses of summary data from randomised controlled trials have shown that statin therapy increases the risk of diabetes, but less is known about the size or timing of this effect, or who is at greatest risk. We aimed to address these gaps in knowledge through analysis of individual participant data from large, long-term, randomised, double-blind trials of statin therapy.

Methods

We conducted a meta-analysis of individual participant data from randomised controlled trials of statin therapy that participated in the CTT Collaboration. All double-blind randomised controlled trials of statin therapy of at least 2 years' scheduled duration and with at least 1000 participants were eligible for inclusion in this meta-analysis. All recorded diabetes-related adverse events, treatments, and measures of glycaemia were sought from eligible trials. Meta-analyses assessed the effects of allocation to statin therapy on new-onset diabetes (defined by diabetes-related adverse events, use of new glucose-lowering medications, glucose concentrations, or HbA1c values) and on worsening glycaemia in people with diabetes (defined by complications of glucose control, increased use of glucose-lowering medication, or HbA1c increase of \u22650\u00b75%). Standard inverse-variance-weighted meta-analyses of the effects on these outcomes were conducted according to a prespecified protocol.

Findings

Of the trials participating in the CTT Collaboration, 19 trials compared statin versus placebo (123\u2009940 participants, 25\u2009701 [21%] with diabetes; median follow-up of 4\u00b73 years), and four trials compared more versus less intensive statin therapy (30\u2009724 participants, 5340 [17%] with diabetes, median follow-up of 4\u00b79 years). Compared with placebo, allocation to low-intensity or moderate-intensity statin therapy resulted in a 10% proportional increase in new-onset diabetes (2420 of 39\u2009179 participants assigned to receive a statin [1\u00b73% per year] vs 2214 of 39\u2009266 participants assigned to receive placebo [1\u00b72% per year]; rate ratio [RR] 1\u00b710, 95% CI 1\u00b704-1\u00b716), and allocation to high-intensity statin therapy resulted in a 36% proportional increase (1221 of 9935 participants assigned to receive a statin [4\u00b78% per year] vs 905 of 9859 participants assigned to receive placebo [3\u00b75% per year]; 1\u00b736, 1\u00b725-1\u00b748). For each trial, the rate of new-onset diabetes among participants allocated to receive placebo depended mostly on the proportion of participants who had at least one follow-up HbA1c measurement; this proportion was much higher in the high-intensity than the low-intensity or moderate-intensity trials. Consequently, the main determinant of the magnitude of the absolute excesses in the two types of trial was the extent of HbA1c measurement rather than the proportional increase in risk associated with statin therapy. In participants without baseline diabetes, mean glucose increased by 0\u00b704 mmol/L with both low-intensity or moderate-intensity (95% CI 0\u00b703-0\u00b705) and high-intensity statins (0\u00b702-0\u00b706), and mean HbA1c increased by 0\u00b706% (0\u00b700-0\u00b712) with low-intensity or moderate-intensity statins and 0\u00b708% (0\u00b707-0\u00b709) with high-intensity statins. Among those with a baseline measure of glycaemia, approximately 62% of new-onset diabetes cases were among participants who were already in the top quarter of the baseline distribution. The relative effects of statin therapy on new-onset diabetes were similar among different types of participants and over time. Among participants with baseline diabetes, the RRs for worsening glycaemia were 1\u00b710 (1\u00b706-1\u00b714) for low-intensity or moderate-intensity statin therapy and 1\u00b724 (1\u00b706-1\u00b744) for high-intensity statin therapy compared with placebo.

Interpretation

Statins cause a moderate dose-dependent increase in new diagnoses of diabetes that is consistent with a small upwards shift in glycaemia, with the majority of new diagnoses of diabetes occurring in people with baseline glycaemic markers that are close to the diagnostic threshold for diabetes. Importantly, however, any theoretical adverse effects of statins on cardiovascular risk that might arise from these small increases in glycaemia (or, indeed, from any other mechanism) are already accounted for in the overall reduction in cardiovascular risk that is seen with statin therapy in these trials. These findings should further inform clinical guidelines regarding clinical management of people taking statin therapy.

Funding

British Heart Foundation, UK Medical Research Council, and Australian National Health and Medical Research Council.", - "laySummary": "", - "urls": "pdf:http://www.thelancet.com/article/S2213858724000408/pdf; doi:https://doi.org/10.1016/S2213-8587(24)00040-8; html:https://europepmc.org/articles/PMC7615958; pdf:https://europepmc.org/articles/PMC7615958?pdf=render" - }, { "id": "34087097", "doi": "https://doi.org/10.1016/s2352-3018(21)00051-5", @@ -44760,6 +44743,23 @@ "laySummary": "", "urls": "pdf:https://digital.library.adelaide.edu.au/dspace/bitstream/2440/131776/2/hdl_131776.pdf; doi:https://doi.org/10.1016/S2352-3018(21)00051-5; html:https://europepmc.org/articles/PMC8187986" }, + { + "id": "38554713", + "doi": "https://doi.org/10.1016/s2213-8587(24)00040-8", + "title": "Effects of statin therapy on diagnoses of new-onset diabetes and worsening glycaemia in large-scale randomised blinded statin trials: an individual participant data meta-analysis.", + "authorString": "Cholesterol Treatment Trialists\u2019 (CTT) Collaboration. Electronic address: ctt@ndph.ox.ac.uk, Cholesterol Treatment Trialists\u2019 (CTT) Collaboration.", + "authorAffiliations": "", + "journalTitle": "The lancet. Diabetes & endocrinology", + "pubYear": "2024", + "date": "2024-03-27", + "isOpenAccess": "Y", + "keywords": "", + "nationalPriorities": "", + "healthCategories": "", + "abstract": "

Background

Previous meta-analyses of summary data from randomised controlled trials have shown that statin therapy increases the risk of diabetes, but less is known about the size or timing of this effect, or who is at greatest risk. We aimed to address these gaps in knowledge through analysis of individual participant data from large, long-term, randomised, double-blind trials of statin therapy.

Methods

We conducted a meta-analysis of individual participant data from randomised controlled trials of statin therapy that participated in the CTT Collaboration. All double-blind randomised controlled trials of statin therapy of at least 2 years' scheduled duration and with at least 1000 participants were eligible for inclusion in this meta-analysis. All recorded diabetes-related adverse events, treatments, and measures of glycaemia were sought from eligible trials. Meta-analyses assessed the effects of allocation to statin therapy on new-onset diabetes (defined by diabetes-related adverse events, use of new glucose-lowering medications, glucose concentrations, or HbA1c values) and on worsening glycaemia in people with diabetes (defined by complications of glucose control, increased use of glucose-lowering medication, or HbA1c increase of \u22650\u00b75%). Standard inverse-variance-weighted meta-analyses of the effects on these outcomes were conducted according to a prespecified protocol.

Findings

Of the trials participating in the CTT Collaboration, 19 trials compared statin versus placebo (123\u2009940 participants, 25\u2009701 [21%] with diabetes; median follow-up of 4\u00b73 years), and four trials compared more versus less intensive statin therapy (30\u2009724 participants, 5340 [17%] with diabetes, median follow-up of 4\u00b79 years). Compared with placebo, allocation to low-intensity or moderate-intensity statin therapy resulted in a 10% proportional increase in new-onset diabetes (2420 of 39\u2009179 participants assigned to receive a statin [1\u00b73% per year] vs 2214 of 39\u2009266 participants assigned to receive placebo [1\u00b72% per year]; rate ratio [RR] 1\u00b710, 95% CI 1\u00b704-1\u00b716), and allocation to high-intensity statin therapy resulted in a 36% proportional increase (1221 of 9935 participants assigned to receive a statin [4\u00b78% per year] vs 905 of 9859 participants assigned to receive placebo [3\u00b75% per year]; 1\u00b736, 1\u00b725-1\u00b748). For each trial, the rate of new-onset diabetes among participants allocated to receive placebo depended mostly on the proportion of participants who had at least one follow-up HbA1c measurement; this proportion was much higher in the high-intensity than the low-intensity or moderate-intensity trials. Consequently, the main determinant of the magnitude of the absolute excesses in the two types of trial was the extent of HbA1c measurement rather than the proportional increase in risk associated with statin therapy. In participants without baseline diabetes, mean glucose increased by 0\u00b704 mmol/L with both low-intensity or moderate-intensity (95% CI 0\u00b703-0\u00b705) and high-intensity statins (0\u00b702-0\u00b706), and mean HbA1c increased by 0\u00b706% (0\u00b700-0\u00b712) with low-intensity or moderate-intensity statins and 0\u00b708% (0\u00b707-0\u00b709) with high-intensity statins. Among those with a baseline measure of glycaemia, approximately 62% of new-onset diabetes cases were among participants who were already in the top quarter of the baseline distribution. The relative effects of statin therapy on new-onset diabetes were similar among different types of participants and over time. Among participants with baseline diabetes, the RRs for worsening glycaemia were 1\u00b710 (1\u00b706-1\u00b714) for low-intensity or moderate-intensity statin therapy and 1\u00b724 (1\u00b706-1\u00b744) for high-intensity statin therapy compared with placebo.

Interpretation

Statins cause a moderate dose-dependent increase in new diagnoses of diabetes that is consistent with a small upwards shift in glycaemia, with the majority of new diagnoses of diabetes occurring in people with baseline glycaemic markers that are close to the diagnostic threshold for diabetes. Importantly, however, any theoretical adverse effects of statins on cardiovascular risk that might arise from these small increases in glycaemia (or, indeed, from any other mechanism) are already accounted for in the overall reduction in cardiovascular risk that is seen with statin therapy in these trials. These findings should further inform clinical guidelines regarding clinical management of people taking statin therapy.

Funding

British Heart Foundation, UK Medical Research Council, and Australian National Health and Medical Research Council.", + "laySummary": "", + "urls": "pdf:http://www.thelancet.com/article/S2213858724000408/pdf; doi:https://doi.org/10.1016/S2213-8587(24)00040-8; html:https://europepmc.org/articles/PMC7615958; pdf:https://europepmc.org/articles/PMC7615958?pdf=render" + }, { "id": "34228774", "doi": "https://doi.org/10.1001/jama.2021.11330",